Are High Oxalate Levels Harming Your Health?

Are High Oxalate Levels Harming Your Health?

You’re encouraged to eat a healthy diet, so you make sure you get your seven-a-day portions of goodness, often blending vegetables and fruits into a green juice drink. Yet despite all your healthy eating, you continue to feel diffuse pain, are fatigued, and generally spaced out. Or maybe you experience other symptoms, such as terrible aching in your joints, painful bladder conditions, or feel as if you’re always suffering from some variety of gum disease. Perhaps you’ve been given a mysterious diagnosis of fibromyalgia, a meaningless name that’s used to describe people who have muscles that hurt, or have sleep and fatigue issues, along with other symptoms resulting from diffuse inflammation of undetermined origin.

Unfortunately, a high vegetable or specific carbohydrate diet, while frequently touted as being healthy, may be making your chronic condition worse. Certain vegetables and fruits contain oxalates, which are naturally occurring compounds that comprise part of their natural defense system. Oxalates are believed to create bitter tastes that prevent them from being eaten by animals in the wild. Oxalates are found in large quantities in a plant’s roots and leaves, the part of the plant that’s essential for it to survive. For many people, a plant-based, vegetarian type, high-oxalate diet isn’t a cause for concern, but it can seriously exacerbate kidney stones, digestive issues, mineral absorption, and diffuse unexplained symptoms for those that experience oxalate sensitivity. We also produce small amounts of oxalates ourselves within our cell’s mitochondria, as part of the Krebs cycle. Some individuals with genetic polymorphisms will produce larger amounts of oxalates endogenously that the body is unable to clear, which result in subsequent health issues.

However, it is possible to break free from the effects of oxalate on the body, be tested for high oxalate levels, and treat the condition with the correct diet and with supplements.

What is oxalate?

Oxalate is a fascinating compound that your body commonly absorbs as a result of the consumption of plant-based food. Oxalate is a very simple compound that comprises two carbon and four oxygen atoms, along with two negative charges that seek out positively charged molecules, such as minerals, that are necessary for metabolism. Oxalate prefers calcium to other minerals but also searches for and binds other toxic metals and minerals, (the list appears below). Certain plants create oxalate as a tool to store calcium deposits. This is similar to how vertebrates use bone to store and sequester calcium that can be used later. Oxalates also create insoluble crystals that absorb light, which is essential for photosynthesis. These crystals can be the source of severe pain, acting almost like tiny razor blades or shards of glass on susceptible tissue like mucosal membranes. Oxalates even deter animals from grazing on their leaves, creating pain and toxicity when the animals eat these in large quantities.

Your body also creates oxalate when breaking down vitamin C. In this case, oxalate is a toxic end product that needs to be removed from your body as waste. Humans are unable to digest oxalate, so if your health is optimal, it’s processed from your body via the gut. Specifically, your gut microbiome digests the oxalates. The ‘good’ bacteria in your gut produce enzymes, which work to disintegrate oxalate. The remaining waste products are then removed from the body within your stool. 

When fat maldigestion occurs due to lowered bile production, our dietary fats aren’t emulsified and broken up, resulting in these fats binding to dietary minerals that are excreted in the stool, along with the fats. When this process occurs, the uptake of dietary oxalates by our gut is significantly increased.

Oxalate can also act as an antinutrient as it binds to trace minerals and nutrients, preventing your body from absorbing the mineral. 

Oxalate can bind to: 

  • Calcium
  • Magnesium
  • Manganese
  • Zinc
  • Aluminum
  • Cobalt
  • Mercury

High oxalate levels in the body can thus lead to malnutrition, but they’re also the leading culprits behind the formation of kidney stones, as oxalate prefers to bind to calcium. In fact, 80 percent of all kidney stones are caused by calcium oxalate. Your body can only flush out the calcium oxalate, not destroy it, so your gut acts as an extrarenal pathway to transfer this into your kidneys then into your urine. Unfortunately, as these crystals build up in the kidneys or bladder, they bind together, creating painful kidney stones that are difficult to pass. However, only about one percent of people with high levels of oxalates will go on to develop calcium oxalate kidney stones. In some cases, these oxalate crystals are extremely small, almost nanoparticle in size, binding to sulfate receptors in your body and undetected by normal medical imaging techniques. Connective tissue, fascia, and joints are very high in sulfate receptors and therefore the oxalates can bind to these tissues, causing joint or soft tissue tendon or muscle pain.

You may think that the easiest way to solve this issue would be to stop eating food that contains calcium. Unfortunately, reducing your calcium intake is unlikely to ‘fix’ the kidney stones or prevent your body from holding on to oxalate. Eating sufficient calcium creates the insoluble form of calcium oxalate, which is passed through your bowel and bladder. If your body doesn’t receive enough calcium, the oxalate becomes soluble and is then easily passed into the bloodstream. This means the oxalate circulates through your body, which is unable to remove it all.

If you have a gastrointestinal condition, such as leaky gut, inflammatory bowel disease (IBS), or Crohn’s disease, you may also be unknowingly dealing with high levels of oxalate. While kidney stones are a severe indicator of excess oxalate, there are other, and often more insidious, symptoms to watch for.

What do high oxalate symptoms look like?

Oxalate sensitivity or high levels of oxalate in the body don’t always manifest similarly between patients. If you have an oxalate issue, it may develop in a part of the body you least suspect, particularly if you also struggle with intestinal permeability or what’s commonly known as leaky gut. This is a disorder in which your intestinal barrier is altered, resulting in your gut wall becoming unable to adequately filter the gut’s contents. Harmful particles slip through the wall and into your bloodstream. If oxalate slips through, this can lead to consequences in the rest of your body.

High oxalate symptoms may include:

There may also be symptoms commonly associated with urinary tract infections or UTI, including pain during urination, pelvic pain, and the need to urinate frequently. Symptoms related to multiple sclerosis may also occur, including fatigue, pain, numbness and tingling, brain fog, and muscle weakness.

Some of these symptoms may have been misdiagnosed at some point along your health journey, as oxalate levels aren’t usually examined during routine tests. However, it’s clear that oxalate sensitivity can have a severe impact on your health and the way you live your life.

What health conditions are associated with high oxalate levels?

1. Oxalate arthritis. With this condition crystals collect inside the synovial fluid of knee, hip, wrist, and shoulder joints. Normally, this fluid keeps your joints lubricated while acting as a shock absorber, protecting your cartilage from wear and tear and filtering nutrients into the joint. A build-up of oxalate results in swelling, joint pain, and lack of movement of the joint.

2. Vulvodynia/interstitial cystitis and benign prostatic hypertrophy (BPH). Both these conditions cause chronic pain in the vulva, which can be unbearable for female patients that are afflicted. Vulvodynia is a misunderstood disease, which was linked to oxalate by the late Dr. Clive C. Solomons. He identified that high levels of oxalate can irritate the epithelium of the vulva and cause pain if there was prior trauma in the area. Oxalate aggravates a pre-existing condition, but also irritates the glycosaminoglycan layer in the bladder.

3. Cystic fibrosis. In cases of cystic fibrosis(CF), high levels of calcium oxalate in the urine of patients with the condition indicate a fat malabsorption issue within the gut. In patients with CF, oxalate is unable to bind with calcium. Instead, the oxalate binds with sodium and other minerals and is able to travel around the body via the bloodstream.

4. COPD. Oxalate has been found in the bronchoalveolar lavage fluid and breath of patients with chronic obstructive pulmonary disease (COPD). This indicates that a build-up of oxalate around the lungs can trigger inflammation in the surrounding tissues, with resultant pulmonary fibrosis.

5. Fibromyalgia. As oxalate can travel throughout the body through the bloodstream, it seems highly likely that the extreme aches and pains experienced by fibromyalgia patients may be due to high concentrations of oxalate. In the United Kingdom, Dr. Clare Morrison improved her fibromyalgia by means of a low-oxalate diet and encourages fibromyalgia patients to follow her example.

6. Hashimotos thyroiditis. This is a common cause of hypothyroidism. The symptoms of thyroid disorders can be exacerbated by an inflammatory response to the build-up of oxalate crystals in the thyroid. Hashimoto’s thyroiditis has been associated with high oxalates.

7. ADD. Many children with attention deficit disorder (ADD) require a higher supplement of magnesium in order to reduce their condition’s symptoms. High levels of oxalate can impede magnesium absorption, so there may be a link between extreme ADD behavior and oxalates.

8. Autistic spectrum disorders. Studies have indicated that children with autistic spectrum disorders have high levels of oxalates in their urine. Reduction in oxalate intake through changes in diet can often improve autistic symptoms.

9. Inflammatory bowel disease. The role played by oxalates in the gut also needs to be considered. There’s a connection between the health of the digestive system and where and how oxalate travels around and out of the body. High oxalate levels have also been linked with several gastrointestinal conditions, including  Crohn’s disease and inflammatory bowel disease, and intestinal permeability or leaky gut, which leads to greatly increased levels of absorbed oxalates.

10. Antibiotics. High levels of antibiotic use can also lead to imbalanced gut microbiome, with resulting oxalate issues. When your gut microbiome isn’t functioning at full capacity,oxalobacter formigenes is unable to metabolize oxalate, causing a build-up of crystals. This can often occur after taking a course of antibiotics, which can kill off your ‘good’ bacteria. Probiotics are often recommended as a defense against recurring kidney stones.

11. Intestinal permeability. In the case of leaky gut, when your intestinal permeability is damaged, your gut wall is unable to be as discerning as it once was, resulting in larger molecules, food debris, and toxins entering the bloodstream. Oxalate is also able to slip through the gaps in the gut lining, bypassing important safeguards and becoming more mobile throughout your body.

12. Mold toxicity. Mold toxicity or chronic inflammatory response syndrome (CIRS) is covered in my essay here. Aspergillus mold species will produce oxalates during their fermentation process. In fact, if I discover high levels of oxalates in a patient’s urine samples, I always look for mold species first and then treat mold as an initial step.

13. Anemia. Oxalates can bind to iron and subsequently lead to chronic anemia. The most common cause of unexplained anemia in women is the loss of menstrual blood due to heavy periods, but high oxalates may be something else to consider regarding unexplained iron or ferritin deficiency with anemia, low hemoglobin, or low hematocrit. If patients begin excreting oxalates bound to iron, they may discover that their urine is rust-colored due to the iron/oxalate deposits. 

14. Mitochondrial disorders and chronic fatigue syndrome. In these conditions, oxalates can destroy mitochondrial membranes and lead to vitamin B1 and antioxidant deficiencies.

15. Eye conditions. Cataracts, styes, and blepharitis are all eye conditions that may also be linked to oxalates.

16. Heavy metals. These are similarly associated with oxalates, as high levels may act as a binder, holding on to metals such as mercury. 

17. Other conditions. A variety of medical conditions in the literature associated with high oxalate levels include diverticulitis, breast cancer, sarcoidosis, osteopenia, osteoporosis, vertigo, endometriosis, and uterine fibroids. 

Resources

https://www.ncbi.nlm.nih.gov/pubmed/27002809

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300851/

https://www.ncbi.nlm.nih.gov/pubmed/28624518

https://www.ncbi.nlm.nih.gov/pubmed/24384768

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192488/

https://www.greatplainslaboratory.com/articles-1/2015/11/13/the-green-smoothie-health-fad-this-road-to-health-hell-is-paved-with-toxic-oxalate-crystals

https://www.ncbi.nlm.nih.gov/pubmed/18264917

https://www.ncbi.nlm.nih.gov/pubmed/18060273

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710657/

https://www.ncbi.nlm.nih.gov/pubmed/1816400

https://www.ncbi.nlm.nih.gov/pubmed/9322615

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2589049/

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https://www.ncbi.nlm.nih.gov/pubmed/17526194

http://www.pulsetoday.co.uk/views/off-duty/could-a-low-oxalate-diet-reduce-the-symptoms-of-fibromyalgia/14635294.article

https://www.ncbi.nlm.nih.gov/pubmed/2435146

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2396938/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300857/

Podcast: Practicing the Medical Arts

Practicing the Medical Arts

Full Transcript

Yoshino:

Hey everyone, welcome back to Artist Decoded. This is your host, Yoshino. And, this is yet another Mind/Wave episode. These episodes have been transforming over the course of time, but mainly my intention for these episodes is that I want to explore various modes of thinking. And, I want to hopefully give people an access point to create positive mental health routines. I’m a firm believer in conscious decision-making and in creating a solid foundation for self-reflection, self-care, and self-growth. Creating good habits in all aspects of life is extremely important, which takes a conscious effort to do so. I personally work out about 12 times per week, so that’s twice a day with one day off. I lift weights in the morning and do calisthenics in the morning, and do my cardiovascular activities such as walking, running, and cycling before sunset. I also know from personal experience that good habits, both physically and mentally, have to be developed slowly and over time.

This can be holistically compared to creating a solid foundation for a career in the arts, or just simply having an artistic practice because not everyone necessarily needs to have a career in the arts. But either way, this takes a conscious, consistent, and concerted effort to continue your craft. Which can be likened to anything in life, including developing positive mental health practices, which leads me to my guest for today, Dr. Bruce Hoffman, who is the founder of the Hoffman Centre for Integrative and Functional Medicine.

So let me tell you a bit about Dr. Hoffman. Dr. Bruce Hoffman did not choose the medical arts as a vocation. Originally, he wanted to be a writer and poet. His interest in health and healing developed later in life after a long and winding road of self-discovery, life experience and learning. He only applied to medical school so he could complete a residency in psychiatry and subsequently study Jungian analysis to understand the human condition and behavior. As life would have it, his destiny took him on a different journey. He never did formally pursue a psychiatry residency or Jungian analytic training, but his love for art, poetry, and psychology remains.

Dr. Hoffman was born and educated in South Africa and obtained his medical degree from the University of Cape Town. After two years of compulsory military training, his distaste for the local regime convinced him to immigrate to Canada in 1986, where he pursued family medical practice in rural Saskatchewan, Canada. Once ensconced in the practice of family medicine, he quickly realized that his interests in medicine were broader than just drugs and surgery. The allopathic medical practice was limited to treating symptoms and illnesses, but failed short in restoring the patient’s health entirely. Bruce embarked on a journey to understand what constitutes the human experience. What are the triggers and mediators that perpetuate human suffering? He wanted to assist his patients not only to be free of disease, but to realize their maximum potential.

Well, I hope you all enjoy this podcast episode. There’s a lot of rich information here, so stay tuned for that. But before we begin, please go to our iTunes page, leave us a review. It helps reviewers just like yourself to hear about the podcast. We’re also now on YouTube. There are a lot of new videos and content from past episodes up there. So, check us out over there and be sure to tune into our no wave cinema conversations on Clubhouse. The next conversation will be with me and Justin Dasher Hopkins. We’ll be talking about the classic 1964 Hiroshi Tasha Guevara film, Woman and the Dunes. We will be having this conversation on Wednesday, April 7th at 6:00 PM Pacific Standard Time. So definitely go check it out and listen to us over there. Maybe even contribute to the conversation as well. So anyways, without further ado, here’s my conversation with Dr. Bruce Hoffman. Hope you enjoy it.

Dr. Hoffman, thank you so much for taking the time to do this. And the main reason why I want to bring you on is to talk about good mental health practices and as Maslow would put it to hopefully reach self-actualization. And I think it’s really important for people in general, to be honest with themselves about every single aspect in their life, to live a holistic practice. And I was wondering if you can speak about your early pursuits for wanting to become a writer and poet and how that eventually led you down a path of studying traditional medicine.

Dr. Bruce Hoffman:

Sure. I was brought up in apartheid, South Africa. And initially in quite a conservative traditional home. But at a young age, when my parents got divorced at around age 10, my mother drifted off into more creative endeavors and found herself hanging out with Keith Anderson, who was a head of a circus, also an artist, a set designer with the opera company and the director of the opera company. And so, I found myself hanging out with Keith and his group of merry pranksters, if you will, because they were circus people, artists, creatives, and opera participants. And I found myself as a trapeze artist in a circus that traveled around South Africa, hanging out with these rather unique individuals, clowns, dwarfs, transvestites, just a crazy band of merry pranksters, which at a young age in conservative South Africa was completely unheard of.

So, I was exposed to alternative lifestyles from a young age. But then when my father got wind of this, he sent me off to an all-male boarding school, a thousand miles from home. And when I got to this all-male boarding school, they took one look at me and said; Hoffman, we’re going to knock you back into shape. So, then I was forced into this narrow, masculine boarding school mentality, and I was horrified it was like the worst thing that ever happened. But the school was an outward-bound school based on the boarding school that Prince Charles went to Gordonstoun and Prince Phillip went to. Just based on those same principles, go out into the mountains and find yourself. But after a couple of years of being at a boarding school, I had a school teacher by the name of Roger Loveday. And Roger was a devotee of a guru called Ramana Maharshi. He exposed me to the teachings from India and particularly the subset of Hinduism called  Advaita or non-dual Vedanta. And also at the same time, I got exposed to the writings of Jung; Memories, Dreams, and Reflections- his autobiography had a huge impact on me. And what ended up happening was I had a satori experience.

One day, Roger was speaking to me outside the school, outside the classroom, after he’d given a big dissertation on the bible and Christianity. After I was very cynically inclined at that time. I said to him; Roger, you don’t believe in all of those myths, do you? And he said to me, “of course I do”. And in that moment when he said, of course I do, I had a sudden awakening. I went into the state called non-dual state or satori. And, that’s where all space-time sort of, linear time disappears and you see behind the curtain, so to speak. You see the appearance of reality through the quantum lens, which is, there’s no time, there’s no future, there’s no danger, there’s no fear of death. Everything just dissolves into this oneness and where everything’s light. Which is well-documented in all the literature, many people have had these experiences. But that then set the stage for further exploration of these principles and these studies. I just continued to be inspired by the fact that there was a reality behind the reality that the rest of the world was operating on.

And then my mother applied for me to go to medical school, unbeknownst to me. Why, because she had a friend who had a friend who could get a scholarship for medical school, for somebody from the particular part of the country that I came from. So, she applied and I was actually up in Johannesburg building sets, scenery for a play with Keith Anderson and his group. I got a phone call and my mother said; Oh, by the way, you got into medical school. And I said, what? What’s medicine, I’m go to do what? She said, no, you got to go study medicine. I said, are you out of your mind? I want to go and study literature. Anyway, I ended up going to med school and not knowing what I was doing there. It is quite a peculiar experience. But while I was in medical school, I happened to go and stay on a remote farm up on the mountain. And there were a group of people around that area who were very influenced by the beat poets, Kerouac,  Ginsberg, et cetera. And I started to read them with great sort of joy. And, and then I ended up in my second year of med school, going to San Francisco and started to hang out with Gregory Corso and a lot of the other beat poets. And that was another inspiration for me.

I just got involved in creative endeavors, integrating Jung and Eastern thoughts and philosophies, and then finished my medical training, ended up in rural Saskatchewan as a family practitioner and really loved being a doctor, when I actually discovered what being a doctor was, because I had no clue. But then after a period of a year or two, I realize that this whole N2D2, name of disease, name of drug method of practicing was ridiculous. Even though it serves a function. And then I came across the writings and the videotapes of a medical writer and thinker called Larry Dossey. Larry Dossey had explored the interface between Eastern philosophies and Western medicine. I’ve written quite extensively about it. And, I watched his video and I was like completely moved. I realized that; Hey, I can bring back everything I learned in my youth that I thought I had to leave behind forever into the integration of this kind of medical practice. I flew down, met Larry Dossey, at a conference, had dinner with him. Very inspired, and then started off with that. To eat, discover, and study anything I could across the whole spectrum of medicine. Healing and the healing arts, including anything that could help an individual live at their maximum potential.

People enter into the medical office. I’m sitting in my medical office. I’ve just seen patients this morning and they come in with symptoms of depression, mold illness, Lyme disease, mast cell activation syndrome, a whole host of chronic fatigue or whatever. Then you start to work with a bigger lens are really entry points into a much greater dialogue and a much greater roadmap that you need to bring to the table in order to assist the person through this transformation of illness to wellness. People think they have a disease in which they label, and they think that’s where it begins and ends. But in the system I use and the method I’ve employed, and I’m proud to say that some of the success I have is that I employ a much larger roadmap. It was a much larger set of tools and hence have written about this new curriculum that’s necessary in order to interface with complex patients who can’t just be mechanistically reduced to a diagnosis. It’s actually absurd when you start to think of it. We’re just not trained to think with a different paradigm. We’re very mechanistic in our thought process, but there’s a lot more mystery that goes on into diagnostics and treatment.

What happened after that was that I started to study Chinese medicine, Ayurvedic medicine, homeopathy and German biological medicine, and the the sub-disciplines. And, happened to spend number of years with Deepak Chopra and David Simon. And when I discovered Ayurvedic medicine, they had an explanation of the different layers and levels of what they consider to be human reality, which is stepped down from soul to spirit, to mind, to emotion, to energy, to physicality, to outer world, out there, the expanded universe.

And I started to use that diagnostic model to think of human behavior and illness. And now I’ve incorporated that and expanded that and happened to also, at the time, meet up with a German doctor who’s still alive and still very active, Dietrich Klinghardt. He had also thought of these things and integrated some of these systems into his roadmap. And then I just expanded the roadmap. And now I use the Seven Levels of Diagnosis and Treatment TM across all layers and levels. And when a person enters my room, I use western diagnosis and their symptomatology as an entry point into a much wider dialogue and a much wider diagnostic and therapeutic potential roadmap. So that’s how I work nowadays.

Yoshino:

In terms of just like a, I want to say like a global scale, but I guess, you know, some of the pitfalls for allopathic medicine and the way that it’s practiced in a Western context, like what are some of the things that you’ve observed that needs to change within that context? And how do you think that you implement it in your particular practice?

Dr. Bruce Hoffman:

Well, being a trained western MD, I have the fortunate privilege of being able to look at disease through that lens. And the pitfalls are that the Western diagnosis implies that an organ system gets diseased, then you must find a pharmacology or a therapy or a surgical treatment for that. That is often the case, as we know. Sometimes when you got pneumonia, you want to get intravenous antibiotics, nothing wrong with that. But now we have a whole new paradigm upon us of complex multi-system multi-symptom disease presentations. And that model, that DSM- 10 classification of organ systems and pharmacological interventions is hopelessly inadequate to address those complexities. And it’s quite uncanny really when you start to work with complex patients as to how often western medicine gets it entirely wrong. And it’s only because their tool bag is so limited, it’s this perception that human beings are these mechanistic beings that, a little biochemical particles, that disease just falls out of the sky. And then you got to find a drug to kind of turn down the symptom.

Yoshino:

Do you think that that’s more of a systemic issue or what do you think the actual issue there is?

Dr. Bruce Hoffman:

Well, we think of human beings as being physical bodies, mechanistic bodies. So, it’s the paradigm, it’s the lens through which human beings are observed. That becomes a limiting factor. And we think diseases just fall out of the sky. There’s no antecedents, mediators, and triggers over the inflammatory disease process that is constellated. And we now know generationally, people exhibit, as you spoken with Mark Wolynn, people can come and present with disease processes that the initial triggers have been three generations before they were even born. And that epigenetic transfer of data is real. It’s studied at all the major universities. So that isn’t taken into account in the mechanistic model and the drug-based model. 5 minutes, 10 minutes, what diagnosis, what symptom cluster, what drug, boom. And in America is even worse because your insurance companies control what goes through the gates. And it’s ridiculous. I mean, it’s silly. It’s not how it works.

Yoshino:

Yeah. I think in America, it’s more capitalized, but that’s just part of the whole system. So pharmacologically, it could be traced from that. And also like the way that the educational system is structured as well.

Dr. Bruce Hoffman:

Yeah. It’s a disease-based model, it’s a mechanistic model. And the only therapeutic input that’s of any use is pharmacologically based, and the gateway to that is controlled by the drug industry and the drug lobbyists. It’s very bizarre how it’s all got set up. It’s very peculiar really. Because it’s not real. The human body is the final resting place of every incoming influence. And every top-down influence. The hidden and the obvious. And the body is the final kind of resting place of an individual for all of those influences. And if you don’t start looking at the toxicological logical input of a very diseased planet, the genetics of the individual, which can either detoxify or not that process. And then the influences of the energy body, because we basically, our DNA emits light, which then stands as a standing wave around us, either coherent or incoherently and is highly affected by electromagnetic fields. If you don’t take those things into account, and then the emotional influences we bring up from early childhood, we know from all the literature that children that have been either suffered from abuse trauma, or neglect trauma. Neglect trauma being often more damaging than abuse trauma. They have an infinite amount of increased disease processes later on in life. So, the environmental body, the physical body, the structural body, dentistry, chiropractic, if you don’t take all of those moving parts into play.

Like today, this morning, I saw a woman with a headache, but she had a bite misalignment. She had an overbite, with TMJ issues, had root canals, implants, and had a swollen back of the throat, which we call a Mallampati grade four with sleep apnea. I’m not trained about dentistry as a medical practitioner. I wouldn’t even look in the mouth as a doctor, but its obvious that her dentistry was playing a huge role in her headache presentation. I would just find a drug to treat the headache if I’m using my western practice.

So, the structural piece, then the energetic piece, and then the emotional piece, and then the ego development of the individual. The first half of life, ego structure, which takes us out into the world to become something that drives the first half of life. If we don’t know the internal dialogue of that person, the defenses they develop in order to stay safe, the thoughts that they have, the beliefs that they carry, the value systems, the hierarchy of values that they have. If you sitting in front of a patient and you don’t know their hierarchy of values, you can’t treat them because if their health is a fourth on their value system and running their businesses is the first on their value system, guess what? You have chaos in your low value systems, and you have order, you run your business well, but you’re going to delegate your health to your wife. And you’re not going to show up for all that’s required for you to transform your life. So, if you don’t know the hierarchy of values of people, you can’t really effectively relate to them where they are. Because they will come in and say, they want to feel better. But when you examine their hierarchy of values, it’s fourth on their value list. And unless they raise it, they’re not going to achieve any ends.

Yoshino:

Yeah. I think that’s really important to bring up because, even in that ICI presentation that you were giving, you were talking about how traditional allopathic approaches not taking into account different states of consciousness. And, you know, you could speak obviously more about this than I can, but I’m curious, how would you diagnose someone that doesn’t really take their health into consideration, but is more focused on maybe their business and work and value that as like something that is more important?

Dr. Bruce Hoffman

Oh, I take a history and I have a questionnaire. One of my set of questions, in my 70-page questionnaire, is determining your hierarchy of values. And I ask the question; how do you spend your time, your money, your attention, what you talk about, what you’re surrounded by? And if somebody says, well, I get up at six in the morning, I go to work. I talk business all day. I come home along the cell phone, I’m doing business deals and I’m surrounded by financial books and I watch business TV. It’s pretty obvious where their hierarchy of values is. Well, you got to “rob Peter to pay Paul”. If you want to get your hypertension under control, and  your diabetes under control, how much time are you going to devote to exercise, diet, meditation, sleep, et cetera? And they go, I’ll do my best. I’ll do my best, usually means not much.

Unless you’re inspired to have health as a high value, you have to be motivated from the outside, not inspired from the inside. Motivation lasts six weeks and then you give up, you can’t sustain somebody else’s value system to motivate you if it’s not inside of you.

Yoshino:

Yeah. It’s kind of like that traditional saying, you can lead the horse to water, but ask to take a sip. Maybe sometimes a much bigger sip. So going back to non-duality and speaking of…

Dr. Bruce Hoffman:

Hey, can I just say something? Sorry Yoshino, can I just say something quick just before we leave that subject. Mahatma Gandhi said that the problem with Western medicine is it works. You know, he said that. If you’ve got heartburn, you take a PPI, you take Pepcid, it goes away, nothing to do with what you ate before, how much you drank, blah, blah, blah. So people just take a whole bunch of suppressing drugs and they get on with their life, which is fine. But if you want, if you value health and wellbeing, you want to do a lot to get where you want to be. There’s this whole new group of younger people who are called bio-hackers, who make it their life’s work to study all that it takes to sustain a healthy cell membrane and a healthy internal milieu of the mitochondria. And a brain functioning and sexuality and libido, and they just devote the whole life to enhancing that. And that’s a full-time job. So, there’s is a gradation of what you can expect from a patient from just take a few supplements, to really devote your life, to turning your life around from a health perspective.

Yoshino:

But going back to the non-duality approach, how do you at the Hoffman Centre integrate that into the practice of educating people that are your patients, and then also integrating those more nuanced approaches with allopathic approaches and Western medicine?

Dr. Bruce Hoffman:

Well, the non-duality concept can’t be taught as you know, it’s either happens or it doesn’t happen. You either wake up to non-duality or you don’t. And it’s one of those strange events that other people experience or don’t experience. That’s when you start to see reality from behind, you see it with what they call One Mind. There’s no dual mind, there’s no you and me. We are just part of the same consciousness. Everything is consciousness, and that can’t be taught. Many gurus have set for decades on their stools, talking about the fact that the very thing you seek is preventing you from finding it. So, the very seeking prevents it, it just happens. But that’s a non-dual, that’s Level Seven in my model. But then there’s the other levels which I integrate in my model of assisting people achieve maximum potential within the realms of the dual life. The non-dual part is it can’t be imparted. It happens or not.

Yoshino:

Can you break down your seven-step method, essentially? I’m curious what exactly is in each part of the system.

Dr. Bruce Hoffman:

So, the Ayurvedic or Vedantic breakdown of human reality is we arise from Brahman. The one mind, the unified field, which we call spirit. You won’t be able to see this and I’m not going to attempt, but I sort of broken it down like this. Spirit, soul, intellect, emotion, electromagnetic, physical, extended (bodies). And on each of those stages, each of those layers of an individual’s reality, there’s definitely experiences, anatomical, designations, sciences related, diagnostics and therapeutics. So that’s the system I use. If you look at my website, I believe there’s a chart there, or that ISEAI lecture. That’s a system I practically use in order to assist people and get better. But they all enter through the physical, they come with a diagnosis and their symptomatology. And then I look at all the environmental influences, the biochemical imbalances, the genetics, the structure, the brain, I do, I have a brain treatment center. So, we’re always looking at brain function. And the electromagnetic, heart rate variability, et cetera. And I take a history of early developmental trauma. And then I look at ego structures and defenses and if need be, I send them for psychometric assessments. And then for the soul piece, for the family soul, I use a genogram and do Mark Wolynn’ s work or Bert Hellinger’s work, family constellation work. And for the individual soul, do dreamwork and Jungian type approaches.

So at each layer, there’s different ways of perceiving and experiencing human reality. And so, in a two-hour consult, you’re doing your best to sort of take as much in as you can to get to know that person and where the major blocks are. So even if they come in with Lyme disease, sometimes it’s a question of inherited family trauma, that’s really running the show. Or sometimes it’s due to a traumatic brain injury and they need brainwork. Sometimes it’s all layers, all levels. So having done this for a long time I sort of getting get better and better making the diagnostic and therapeutic recommendations.

Yoshino:

Can you talk a bit about your success stories with this process? I like to understand that a bit.

Dr. Bruce Hoffman

Well, all cases in the end sort of blur into one. But you know, there’s endless amount of patients that present with, say a diagnosis of Lyme disease or mast cell activation syndrome, who believe that that’s the only reason why they are sick. But when they start to explore all the other potential diagnostic possibilities, they all of a sudden realize that that was truly a teleological entry point into a much larger dialogue with themselves. And then they start to explore the whole of their lives and they start to make the necessary adjustments. I’ve got case histories in my upcoming book. I can’t pull one right now because this sort of endless variety of different presentations that I see on a daily basis. I mean, it’s just one little thing today. I saw somebody just very recently who was in her thirties, failed marriage, young child, no direction in life, presents with depression.

Her diagnosis is depression, on antidepressants. And could I help her with her depression and poor self-esteem. Upon further inquiry I found out that she’s moving back home with her parents at the age of 38. And she was very ashamed by all of that. At 38, I don’t know what I’m doing. I’m going back home. What a tragedy. And the man she just divorced, was castigating her for being hopeless, no good, et cetera, et cetera. But when you take a deep inquiry, you see that this soul has had interrupted bonds with her mother at a young age. Mother was separated from her for six weeks. She had a very poor diet. When she went to her mother in teens with developing puberty, her mother was offline, and didn’t see her. She never felt seen. And then she had the series of events, sexual abuse, medication and drug abuse, and then never really found her calling.

So, subsequently turns out that going home to mother and father at age 38 was an opportunity to actually reconnect and heal the interrupted bonds that she’d never been seen in heard for in the first half of her life. So instead of being castigated and feeling so ashamed, she now sees this as an opportunity to reconnect with her mother and father in a truly humble way where the parents, carry the greater weight, and she’s the child. And she can go back and start to integrate her life with her mother’s life and her grandmother’s life, both of whom were artists. She was a makeup artist, but always thought that her makeup career had nothing to do with art. But when it was reframed that she was disconnected from the feminine lineage and her makeup artistry was a continuation of that lineage, she all of a sudden blossomed into the realization that she was part of that maternal lineage and she need not be ashamed of it.

And even though she’d put the makeup artistry aside because of her child and she has to take care of the child because the hours were wrong, she realized she could always pick it up again, and she could step into that female lineage. And she did have a calling. She thought she didn’t, all of a sudden, she knew her whole calling was still on that feminine lineage. Her mother had had a transformation and had said to her; “darling, I realize I didn’t see you when you were younger. I apologize for that”. And all of a sudden, she had this entry into this greater feminine lineage that she could not use so she can pass on to her daughter. So, the daughter doesn’t feel as strained and shameful, et cetera, et cetera. So, yes, she’s depressed. She’s depressed because he’s in an existential crisis of not knowing. She was floundering in life, but she had all this opportunity that’s presenting itself. If she just turned the switches and started to see how it was all part of a grand design that was going to help her realign with her life calling. So, it just gets reframed in a new context and all of a sudden, the life force opens back up.

Yoshino:

Yeah. So, can you speak about the neurological significance of reframing, perceived negative events in one’s life and then transforming them into something positive in one’s mind?

Dr. Bruce Hoffman:

Well, the way I was introduced to, it’s a combination of neuro-linguistic programming and Jungian psychotherapy done cognitively, strangely enough, was through the work of a person by the name of John Demartini. And being exposed to his work, I was able to see how the perceptions that we take into life are often not real. And he uses this teaching tool. He says, look, basically in the quantum world it’s all light. Light gets broken down or dumbed down into matter. Matter is both equal positron and electrons, it’s got both sides. Our lower mind, which always seeks pleasure. One side is always excluding the other side. We always looking for dopamine and trying to avoid pain. And he says, the lower mind can see both sides simultaneously, but you can train your mind to see the integration of both sides to any event, if you just train it. It’s a cognitive restructuring of your mental processes. So, I learned how to do that. I learnt his methodology of how to re-perceive reality through non-dual, if you will, both sides, eyes. So, any event in the future, which looks disastrous, you start asking yourself, where is the upside to this so-called disastrous event? Anything you judge very negatively, like if you judge somebody with very negative trait, you’ll find out where you have the trait, how that trait serves, how that person’s negative trait is benefiting you. It’s not just something that should be a thorn in your side. And how, when you being challenged by a so-called person, who’s is sort of challenging you, where are you being supported? The universe is constantly in this flux of support and challenge, positrons and electrons, which is the basic nature of the quantum reality.

If you can train your higher mind to collapse the world into its opposites, as quickly as possible, you can stay poised in what John calls love. And love to him is just a synthesis of all opposites, where you see both sides simultaneously. And there’s no judgment or no lowering yourself into black and white unipolar perception. So, I try and assist patients like “you going home to mom, this is the most terrible thing at 38, but what is the soul wanting of you? “What is being asked of you? And once I took a history after, she came in saying that this is a horrible thing. She felt so ashamed. She left, she couldn’t wait to go home to see her mother to reconnect because it was reframed. She just saw how it had served her soul’s experience. It was necessary to go home, to receive the love of the mother in a new light, because she had had interrupted bonds all her life with mother. Her mother was ready. She had to be ready. She had to shift the perception from negative, to not positive, but just as opposite. As soon as reframed, boom, I’m going home. Thank God.

Yoshino:

No. Yeah, definitely. I mean, that’s a beautiful story, but I think, especially in the metaphorical sense, you know, when you think of a situation such as a purgatory situation, you can even think about it in certain ways, in a biblical context or in many different stories of purgatory. But we sometimes put ourselves in that purgatory by not seeing the positive association that could be taken out of that negative or what we perceive, quote, unquote, “as that negative lesson of the past”. And if there was something negative that happened the past, if I could say, Oh, that actually helped build my character for who I am today. And then constantly frame it in that context, you can find those lessons. But all those lessons are always there screaming at you to essentially, show themselves in a way that can benefit you. This is at least from my observations.

Dr. Bruce Hoffman:

Yeah. I have the firm belief that every experience that you have, whether it’s positive or negative is serving the projection, the evolution of your life experience. You sort of born over here; you die over there. The acorn does become the oak tree. The acorn needs the wind, the sun, the stresses and support of the environment to become who it’s meant to be. And, I’ve no doubt in my existence, your voids, the things you find most missing, the things you judge the most negatively actually become your highest values. In the end, you look back and I have the unfortunate and fortunate privilege of being in my second half of life. So, when you’re more soul based than ego-based not that you, without ego, not saying that, but you’re more trying to integrate the parts of you that you left behind in your pursuit and the drives of the first half of life when you’re driven. Adler drives, Freud’s drives, that you’re driven to become something in the first half of life.

And then in the second half of life, you try and pick up the pieces of the parts you left behind. And you try and reintegrate your authentic, innate self. And, in that process, you realize everything that ever happened to you was in service of your soul. There was never a mistake. You never were out of purpose for your soul’s trajectory. Nothing ever occurred to you that wasn’t in service of yourself. You have no regrets. And there’s nothing to forgive because everything was in service. Forgiveness is a ridiculous concept because it’s implying that, that one was given to you was wrong. And now you must forgive them. No, everything’s in service. Thank you for giving me that experience. Forgiveness implies I’m bigger than you. What you did to me, you were wrong, I’m right. And now I’m going to forgive you. How dare you, you know. Say, yes, thank you for giving me that experience. It’s always in service of our soul.

Yoshino:

So, speaking specifically about that forgiveness and you speak so passionately about it, but you know, if someone is suffering from some sort of shame or guilt, what sort of questions would you prompt to them to be able to have them question that shame and guilt and where that comes from. I’m curious about that.

Dr. Bruce Hoffman:

So, guilt is the perception, that in the past you’ve done something that’s caused others more pain than pleasure. So, the only question you need to ask is where do you think that experience that you gave that individual, where did it serve them? How did they perhaps benefit from that experience? Could you please look in the seven areas of their life? We have spiritual, which is our calling. We have relationships, social friends, we have health and beauty. We have careers, we have making money. And we have intellectual, mental development. If you feel guilty by some act you’ve done, it’s incumbent upon you to ask; where do you think that person benefited in those areas of their life that served their evolution? Keeping in mind that everything serves, everything is in evolution of the soul’s progression. So where might it have served them? Not where did it damage them? We know that there’s both sides. Yes, it was maybe painful to them, but how did it serve their evolution in the end? And if you ask those questions, which of the seven areas did they benefit, you could find? Some people because of pain, you’ve caused them, branch out and start to develop. They read, they go to courses, they connect with their family because they sort of destitute and in pain that they have to reach out to whoever they can. So, they start forming relationships back with strange family members. They form new friendships. They go online, they go to self-help, they go to retreats. They build careers around the adversity that you caused them. So, at the end of the day, you’ve got to ask the right questions of individuals.

Nobody suffers without gaining. If it doesn’t exist, the universe is not one sided. It doesn’t work that way. Which brings into question the whole victim mentality of “I’m a victim”. No, I’m not, this can provoke a whole outlandish backlash that victims will be up in arms but if you look through the lens of moral and ethics, yes, there’s victims and perpetrators. I’m not questioning that. But if you look through the eyes of the soul, there’s a balance there that’s evolutionary. And, if you look through the right lens, you can see an evolutionary projection. It’s just how I tend to see the world.

Yoshino:

No, that’s great. And I think that it’s interesting because of your background in more traditional western forms of medicine. And also, how you combined the western perspectives and also these eastern perspectives. Or what would be deemed as western and eastern. And, you’re able to eloquently, within practice, like what you do at the Hoffman Centre within practice, to be able to mold these things. And even on your bio, you said writing and poetry, which led you to the medical arts. I think that’s very important because that is what you do. Cause you’re essentially utilizing all of your experiences, your own personal pursuits, such as your pursuit of literature and poetry. And letting that inform you in a way to ask the right questions of your patients. But at the same time to ask the right questions of yourself.

Dr. Bruce Hoffman:

It’s so important Yoshino that you know to stay in an inquiring mode, a student mode. And once you have the privilege of having lived longer is you start to see patterns and trends. You’ll see an individual present with anxiety and OCD and anorexia and so forth and so on, and like a young woman in her thirties. And then you’ll see this archetypal trend that exists that she’s addicted to perfection. And she’s following the value system of a patriarchy, which is inculcated. And she’s introjected somebody else’s value system, like an overbearing father and wants it to achieve. And you see these archetypal trends emerging in your practice. And that’s based on reading, is based on literature, is based on knowing. In the ancient Greek temples, once you’ve gone through, this is in my lecture, the outer healing and the inner healing, you are then sent out into the theater where you watch Greek tragedies, which were archetypal or depictions of life. And you see these trends occurring. You see these people in certain stages. If you don’t know the stage of life the person’s in. Your first half of life patients, very different from second half of life patients. They’re not the same. They’re different flavor, different. You approach them differently. You got to be sensitive to the stage of life. And if I wouldn’t have known that. If I hadn’t been exposed to all these different paradigms of insights.

Yoshino:

Uh, I’m curious. You were speaking of liking essentially, or interested in Jungian philosophy, but also have you read a lot of Joseph Campbell? I’m sure you have.

Dr. Bruce Hoffman

Well, when I first got interested in Jungian work, Joseph Campbell was very popular. He had that PBS series, I think, in the 90’s…

Yoshino:

Power of Myth. Is that right?

Dr. Bruce Hoffman

I don’t know how old you are, Yoshino. Hahaha

Speaker 5:

No, I’m 34.

Dr. Bruce Hoffman:

You probably were. But, Joseph Campbell did the Power of Myth. It was everywhere on PBS. And we watched that series. I’ve got all the videos. We have all the VHS videos of that. I still have that.

Yoshino:

I know I’ve seen them.

Dr. Bruce Hoffman:

I still got them in my library right there. And I read his books and yes, very moved, very beautiful. He was a big influence.

Yoshino:

No, I was just curious, because you were talking about seeing certain patterns and archetypes.

Dr. Bruce Hoffman:

You do see them; you see them over and over again. It’s quite uncanny when you tune to those archetypes. And, you can see when a person is presenting with symptomatology, when it’s got nothing to do with the western diagnosis. When it’s actually a calling from the soul to wake up to a deeper transformation, that’s being asked of them. And you just get used to knowing how to have that dialogue with people and when to watch out for signs and symptoms. And know that, oh, the Lyme disease is not Lyme disease. It’s the fact that they are misaligned with, they haven’t integrated an aspect of themselves, which is calling to be integrated. They’re still living out the first half of life, dictates, which need to be given up at some stage. You can’t,  a 70 year old man in a Ferrari, that’s diagnostic. It’s just is.

Yoshino:

Yeah. I mean, I’m sure you can see many examples of that from either people that are also in your working profession or there’s so many examples of that. And, just someone having a Ferrari at any point of life, you just have to ask, like, what is the reason for that? You know, and also you can only drive one car at a time. They can’t drive two at a time, at least not from what I understand.

Dr. Bruce Hoffman:

Yeah, there’s all those clues, the history taking is filled with clues. And you just got to be sensitive to them and hopefully tuned in as much as you’re able to. And so that requires a whole new curriculum for the healers of the future. It has to be rewritten. The curriculum must be rewritten. Not to say that MDs must become healers. I disagree. Doctors should stay doctors. Stay with all that. Stay with a mechanized symptom-organ system- method medicine. Be very good at it, be the best at it. And leave them alone. Don’t ask them to become healers. Let’s have a new curriculum for healers. People are called into a different way of interrelating with their patients. And let’s have that curriculum outlined. And let’s co-exist with each other in equal exchange, which doesn’t happen. Doctors have this peculiar arrogance that what they’re not up on, they down on. And so, anything that doesn’t fit into that model, they tend to dismiss, which is unfortunate.

Yoshino:

Makes sense. I mean, it’s essentially breaking up the paradigm that if you believed in this certain way of life being educated by the system. And it creates a certain type of way that you think about the world and your perception of your space in it, essentially.

Dr. Bruce Hoffman:

Absolutely.

Yoshino:

I have one more question for you because I don’t want to take too much of your time and I appreciate you for taking the time to be on the podcast, but what sort of advice do you have for artists and creatives?

Dr. Bruce Hoffman:

Wow. I spoke to you before we got on,  that my great love is art. Now in the last 10 years, I rediscovered this huge passion, interests, and I was deeply moved by art and still to this day. Before I answer the question, I was estranged, I was South African living in Canada, and I felt deeply homesick. But as soon as I started to buy South African art with its imagery and symbology, I could bring it over and have it in Canada, I settled down, I had living symbols of my African heritage with me, and there was no such need to go back home. So, I mean, artists generally are tuned in, at a deeper dimension and they bring forth symbolic messages and are able to translate archetypal stories, like poets. When they tuned in and the higher their skill, both intuitive and skill, the deeper the symbolism, the deeper the impact on that, because we all resonate at some level with archetypal symbolism. It hits us like a break when it’s true. And it speaks to us.

So advice, I’m in awe of artists. I mean, those surrealists’ artists like Leonora Carrington. Oh, my goodness. I mean, what were they bringing forth? And what’s really going on. I’m fascinated. I believe some of their outer lives are maybe quite chaotic, but they sort of balanced it with this inner rock of their own unconscious that just pours through them. So, I think it’s an equal balance between outer neuroses, if you will. Then in a solidity and what a beautiful exchange, what a beautiful gift to humanity.

Yoshino:

Well, I mean that’s a sound observation. It sounds like you have a very deep love for and appreciation for the arts and what the arts can provide for humanity.

Dr. Bruce Hoffman

Yeah. Poetry. I mean, Mary Oliver, The Wild Geese. Oh man. When it speaks, it speaks and you just fall over into ecstasy. It’s so archetypally resonant. It’s just makes life meaningful. Provides meaning. It’s a beauty. Beauty and meaning.

Yoshino:

I agree. I agree.

Dr. Bruce Hoffman:

Have you ever seen that movie? The Great Beauty?

Yoshino:

I haven’t, no. When did that come out?

Dr. Bruce Hoffman:

Oh, it’s by that French (incorrect- Italian) director, Paolo Sorrentino. It’s about a man who gets to be in the 60s and nothing inspires him anymore. And so this whole movie is about him visiting sights and sounds. And is in Rome, all this opulence and decadence and nothing excites him. And he’s just like desperate. Until he realizes that at some stage he was moved by a great beauty. It happened to be in the form of a woman he loved. But all of a sudden, he just wakes up to some things that he’s left far behind. And he wakes up into another phase of his life, realizing how many years he’d lived in this outer world without connecting to his true inspiration. It’s a beautiful movie. Wow.

Yoshino:

You know, what that reminds me of,  have you seen Citizen Kane recently?

Dr. Bruce Hoffman:

You know, I saw it once and I read it. I’d read how perfect a movie it was. And when I watched it, I thought, what are they talking about? But after 10 minutes, I watched each frame and I immediately got the majesty and the marvelous sort of symmetry and exactness of the whole development of that movie. And I’ve got why it’s one of the greatest movies of all time. I just could see it just so obvious actually, you know, Jungian.

Yoshino:

Definitely. Well, I just bring that movie up because what you’re talking about specifically at the end of the film. I don’t think I need to say like spoiler alert because this film came out in, I think 1945 or 43, but at the end of the film he just keeps on saying rosebud. And then you find out what that symbolized to him. And so, I think, he does all these things throughout his life to attain power, to attain wealth, but then this was it, I believe it’s a sled when he was a child carried so much meaning and symbolism to him. And it’s just interesting how there’s that consciousness shift. So it just kind of sounded similar to the film that you were telling me about.

Dr. Bruce Hoffman

Well, now I’m going to watch both movies back-to-back and then keep that in mind to see the connections. Well, we live our lives through symbols and meaning in the end, the outer world is just a playground for meaning and symbol.

Yoshino:

It’s interesting. Just to leave you with this, but yeah. I’ve been meaning to crack open Jung the Book of Symbols. Is that what it’s called? I have it downstairs and I need to spend some time, cracking that open. But anyways, thanks so much for doing this and taking the time. I appreciate you for doing this.

Dr. Bruce Hoffman

Yeah, absolutely lovely. I’m going to look at your podcast and see what else you’ve done. That it is inspired me through your connection to the artists and artistry.

Speaker 2:

Yeah. You might like some of the artists, you know? All right, Bruce. Well, thank you very much. I appreciate it.

Dr. Bruce Hoffman:

Thanks for the talk. I appreciate the talk. Thank you.

The Cell Danger Response: Restoring Cellular Health with Phospholipids and Bioactive Lipids

The Cell Danger Response: Restoring Cellular Health with Phospholipids and Bioactive Lipids

Dr. Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine, and today is no exception. I am delighted to be with a very longtime colleague, Dr. Bruce Hoffman. We’ve got an exciting sort of depth conversation planned for you today. Let me actually spell out why it’s going to be a deep conversation just listening to his extensive training will suggest where we’re going.

So Dr. Hoffman is a Calgary, Canada-based integrative and functional medicine doctor. He is the director of the Hoffman Centre for Integrative Medicine, also The Brain Center of Alberta, specializing in complex medical conditions. He was born in South Africa and obtained his medical degree from the University of Cape Town. He’s got a master’s in nutrition. He’s a certified functional medicine practitioner through the Institute for Functional Medicine.

He’s board certified with a fellowship in anti-aging and regenerative medicine. He’s trained in the Shoemaker Mold protocol. He’s a certified Ayurvedic practitioner. He’s trained in Bredesen ReCODE brain treatment, in the MAPS autism training. He’s a certified family constellation therapy specialist. He’s trained in ILADS for Lyme and co-infections.

He’s also a contributing author to the recent paper, which is available. In fact, we’ll link to it on our show notes, from Dr. Afrin’s group titled Diagnosis of Mast Cell Activation Syndrome: a Global Consensus-2. So mast cell activation is something that he’s also focused on. I actually also want to bring to your attention more, just kind of the rich depth. I mean, clearly, Bruce, you’re a lifelong learner, but I think you’ve really kind of taken these things in. I just want to give you a little more of his background.

He’s trained in Chinese medicine, and homeopathy, and German biological medicine. You almost went to get board certified in psychiatry. You wanted to be a Jungian analyst. I found that really interesting, Dr. Hoffman, in your history. And so you bring that to your work now with patients. So you did some of that training, even though you didn’t move into psychiatry, but you did some of that training. You worked with Jon Kabat-Zinn, with Deepak Chopra, with Dr. Klinghardt, with Ken Wilber.

I mean, first of all, welcome to New Frontiers.

Dr. Bruce Hoffman: Thank you, Kara.

Dr. Kara Fitzgerald: And what haven’t you done?

Dr. Bruce Hoffman: It sounds like I don’t have a life.

Dr. Kara Fitzgerald: It’s extraordinary, I want to spell it out. I know that you’re just doing this amazing work with your patients, and you’re fusing this intense training that you’ve undergone, and that you continue to experience into what you described as the Seven Stages of Health and Transformation. So it’s not like you do a weekend course and then the books go away, or the PDFs are put away.

I mean, you’re actually working with these tools and making them into something your own. And it’s called the Seven Stages of Health and Transformation. And I know that you’re working with very complex patients in Canada, and actually beyond Canada. I know people are drawn to your work from all over the place. And so, I want you to talk about the seven stages, and what your approach is to these complex patients that are coming to see you.

Dr. Bruce Hoffman: Yeah, sure. When I was a young teenager, I was exposed to a schoolteacher in South Africa who was very different. And he took us out of our sort of South African apartheid, white, privileged background and sort of threw us into … threw me in particular into an alternative universe whereby I was exposed to the world of psychotherapy, psychoanalysis and eastern thought.

And I had, at a very young age, an experience which they call satori, which is this sense of seeing space-time as a continuous whole and not seeing cause and effect as being linear. And it was a sort of … Many people have these. They are sort of called awakening experiences or high experiences. And that just sort of catapulted me into a different way of looking at things, and then initiated in me a curiosity about all aspects of the human psyche and human development and human potential.

And originally, I sort of got interested in Jungian psychoanalysis and wanted to become an analyst and went to med school only to become an analyst. And I was actually accepted into the psychiatric residency, but actually didn’t go through with it. I worked for two years in psychiatry in the military. I had to go to compulsory military training. But I didn’t actually do my residency.

And I do feel quite privileged in the sense that by not taking that particular route, I was able to keep expanding across all layers and levels of experience. And what I found was when I ended up just being a family doctor in rural Saskatchewan, and seeing the limitations of drug-based, which Majid Ali beautifully named it N2D2 medicine, name of disease, name of drug.

Once you start to see the limitations, and then you start to look at the potential of human achievement and what they can aspire to, one sort of moves out of just treating disease to trying to get your patients to look at optimal potential of their entire existence. And so, what I do now through the seven stage model is view pathology, or the so-called disease states or complex symptomatology, as this entry point into a dialogue with a patient.

But I’m also looking at other aspects of the psyche and the experiences to see what it is that their soul, if you will, is asking to come through. What is it that they’re trying to achieve? Symptoms to me are etiological. They’re sort of pointing towards hidden subjects that need to be brought to the surface. I never see symptoms as linear. I always think of them as what is the body attempting to do by throwing out these particular imbalances?

And with that approach, and using my early exposure to Ayurveda and Advaita, which is a system of Hindu philosophy that I was exposed to by the schoolteacher, and I was able to build a model called the Seven Stages of Health and Transformation, which looks at the human experience as being divided, which is a silly term, because there is no division. But it’s conceptually divided into these layers and levels of experience.

The first level being the outer world, the external environment. And that’s sort of level one in this conceptual field. And from that, we draw everything to do with what’s going on in the chemosphere, outside of ourselves, the toxicology and the infectious load. And we look at that from etiological point of view. That’s level one.

Level two is the physical structure, which is made up of biochemistry and structural aspects. And that is what we do in both traditional medicine and in functional medicine, and in all the structural modalities like chiropractic, and bodywork, et cetera. And then level three is to do with the brain, the peripheral, and the autonomic nervous system, and its electrical effects on physiology and biochemistry. And then what are the manmade EMFs effects on that.

And then level four is to do with the emotional body. And as we know, that many people have these adverse childhood experiences, which then get laid down neurologically in the brain as specific defects particularly in right frontal lobe development, and activation of the amygdala, and the fight-flight response with down regulation of the vagal nerve. And because I have this brain treatment center, you can diagnostically look at this and treat it accordingly.

And then level five is to do with ego development, how people negotiate the slings and arrows of this … The world is a tough place. We’re sort of always somewhat vigilant against the next thing that’s going to arise. And so, we develop in the first half of life a very different set of strategies from in the second half of life in terms of how we develop our ego, which is our sense of how we negotiate the world and our belief systems, our values and our defenses.

People grow up with a way of orientating themselves, but they also remain highly defended to those things which are most traumatic. And depending on early childhood experiences, defenses can be highly helpful or healthy, you could say. But they can also be highly pathological when people suppress anything that comes close to an early experience of trauma, and the so-called PTSD response.

So level five is everything to do with the ego and how it negotiates its way in the world. And the first 30 years are all about ego development and they’re characterized by certain drives, drives of the libido, drives of full power, drives to know oneself. And all the great psychoanalysts of the 19th century were very … They had great insight into these mechanisms.

But they’re now used therapeutically in a system called ISTDP, where psychologists look at different structures that people bring to the therapeutic encounter and work one on one with them in transference and countertransference to try and get behind that which they’re defending against and which is asking to be brought forward. So that level is very important.

And then level six is that what we call the soul. This is the most authentic part of who you are, the most instinctual part of who you are, which never really comes to any sort of conscious assertion until the second half of life, I would say. Carl Jung, the great psychoanalyst wouldn’t look at patients before the age of 40. He said they’ve taken up two drives. There’s no conscious awareness of their deepest self to work with. And so he wouldn’t work with anybody under the age of 40, which is rather strange, but it’s true.

Dr. Kara Fitzgerald: It’s very interesting in this anti-aging obsession that we have, isn’t it? I mean, clearly, there’s some wisdom, but keep going.

Dr. Bruce Hoffman: Yeah. So, in our personal, when we’re born and we’re born into our experiences, very often when you’re not seen by your parents adequately, and being seen by parent, you don’t have to be perfectly seen but a good parent who will always support and challenge a child accordingly. But if there’s any neglect or abuse and neglect-trauma appears to be even more traumatic to a child, an abuse trauma.

The child will develop a provisional self, an adaptive self to go out into the world in order to achieve what it’s meant to achieve. But the authentic self, the instinctual self will often go underground and then be hidden by these defenses and this comes up. I can’t tell you how many people present to me in sort of midlife … Midlife being anywhere from 35 to 55. It starts at somewhat of a younger age when entropy starts to set in.

And they are being driven to ask deeper questions of themselves and to reclaim those parts of themselves, which they know instinctively, they left behind in their pursuit of safety and being seen. So their provisional selves go out, achieve something in the outer world, but there’s something crippled and something quite damaged, or well preserved. Some innocence, well preserved, but it’s hidden from sight.

And people in midlife generally kind of know that. And they want to often go back and retrieve those hidden parts of themselves that they know are manifesting as symptoms, but they have no conscious connection with them. So part of the work I do is trying to find out what … I don’t ask this question out loud, but I’m asking it while I’m interfacing with a patient is, what are these symptoms telling me, and what does the soul want?

What is the innate wisdom and innate creativity of this patient that needs to be brought to the forefront? And that’s the fundamental question that sits there while I’m looking at all the functional medicine, toxicology, biochemistry, hormones, mitochondria. I’m always having these conversations in my head, what does the soul want? What is being asked of this person? What do they need to manifest in order to bring parts of themselves back home?

And that is the second half of life quest really, how do you gain your creative, instinctual self. And not only that, but there’s also another hidden part and that’s a hidden part of your family system. Family systems carry secrets and carry hidden entanglements that often manifest themselves epigenetically and get expressed through biochemistry as symptoms.

And I’ve done some marvelous work with, or I haven’t. But I’ve partnered with Mark Wolynn, who is an exceptionally gifted functional family constellation practitioner. And we looked at, once a year, we used to do a workshop where we looked at the symptoms of patients who came to my clinic and try to link them to any inner entanglements or the family system two to three generations before the patient is even born.

And it’s extraordinary what entanglements you find and what dynamics you find, which can manifest as symptomatology in the patient. And this research is very well established now to all the major universities, that there’s an epigenetic chapter of trauma through the generations. And then lastly, is spirit. The level seven is the spiritual body. And that’s the part of ourselves that’s transcendent to any ego-based space-time demands. And that’s where you surrender to some intelligence greater than yourself and just sort of stay open to that potential. And that’s sort of the whole realm of what we call the one mind beyond space-time.

So I use that model. So when patients present, I’m just trying to sense, they come … One of the great tragedies that I find, or one of the great challenges, not tragedies so much as challenges, is that when you become well versed in functional medicine, people will present and they’ll write in their entry forms. You ask them, “Why are you here?” And they’ll say, “Well, I’ve got mast cell,” Lyme or mold, and whatever.

And they will sort of have reduced their entire symptomatology to what they believe to be a lab test or a symptom that they’re experiencing. And it’s never the case. It’s never the case. Those are just inquiries as an entry points into a much deeper dialogue, in my experience. And so, I’m always curious. Yes, you may have a trigger called Lyme or a trigger mold and mast cells have gone awry. Yes, that’s true.

But really, what’s the deeper reality that we need to sort of work with? And sometimes I get to it, and sometimes I don’t. Sometimes I just treat mast cell, and Lyme, and mold and be done with it. But other times, not. Yeah, sorry?

Dr. Kara Fitzgerald: I mean, what an extraordinary entry into our conversation, thanks for all of that. I mean, it’s amazing. And I can just tell that you are sitting with all of these levels. And I think that, in functional medicine, they talk about gathering before the patient encounter.

Dr. Bruce Hoffman: Yes, that’s right.

Dr. Kara Fitzgerald: And I can hear that you’re gathering at all of those levels, which creates a possibility in the encounter. It’s been extraordinary. So is this written? Have you written about this? Have you-

Dr. Bruce Hoffman: Yeah, I’ve written. I’ve got podcasts with transcripts, and I’ve written a book, which unfortunately, sits on my laptop.

Dr. Kara Fitzgerald: You can link to it on our show notes then. I’m kidding. But it’s powerful. And, well, we’ll bug you about it so that we can link to what you’ve got available in our show notes. It’s an expansion on functional medicine principles in a very important way. So that was one question. And then the other thought that I was having and you started to touch on is, so the presentation, this phenotypic presentation of mast cell activation, or Lyme, and it’s true that our patients will come to us with pretty rigid ideas on this, and what it means.

And as you said, either you move beyond it or you don’t, and you address it and life goes on. But you alluded to in the beginning of your unpacking the seven stages, you alluded to sort of these as having information in and of themselves, like what kind of a … Is there kind of a personality type or somebody who comes with a certain type of a family constellation structure that might be more vulnerable to Lyme and co-infection or might be more vulnerable to autism or MCAS? And can you speak to that?

Dr. Bruce Hoffman: Well, the interplay is complex as you know, from genetics to diet, to sleep, to rest, to toxicology. And to ever increasingly, obviously, to early developmental experiences. I can’t emphasize how profound those experiences play on auto-expression of biochemistry. It’s unbelievable.

Dr. Kara Fitzgerald: I want to just say as an aside that I am with you on that. I mean, we’ve just published a study in looking at DNA methylation, so looking at the epigenome. And one of the things that’s just stopped me in my tracks is this idea of biological embedding, which is exactly what you’re talking about, where the signatures of the psychic experience are laid down on the genome.

Dr. Bruce Hoffman: It’s quite extraordinary. And if people come and they see me, say for mast cell, and then they find themselves doing acute EEG, and the NeuroQuant MRI, and doing neuropsych questionnaires and they go, “Why are you doing all this? I’ve got mast cell.” Well, mast cell is the expression of your, mitochondria undergo the cell danger response. They released ATP, ATP caused the granulation of the mast cell, and the release of a thousand mediators.

So yes, you had mast cell activation syndrome, but what’s underlying, what are all the triggers in functional medicine, the antecedents, mediators and triggers that provoked this mast cell to go crazy? The brain is the interface between one’s epigenetic and early developmental experiences, and one’s outer experiences. The brain is the interface, and if you look at acute EEG, and even a NeuroQuant MRI, you can read biographies of those. They’re so alarmingly informative.

And so, I look at a body-based stress assessment. I look at heart rate variability, as we all do. But then I look at acute EEG, and I look at this sort of juxtaposition of the delta-theta-beta-alpha brainwaves, and you can really see imprints of early developmental trauma. And you can see people who are stuck in fight/flight responses, people who stuck in Porges’ polyvagal, dorsal vagal responses.

You can see it right there in the biochemistry and the physiology. And you know that that person, say, who’s stuck in Porges’ dorsal vagal shutdown response, that’s a whole different patient and somebody who just got a few allergies. You’re dealing with a whole different kettle of fish there. And you can’t just jump right in and just do your normal functional medicine and try a few supplements … It’s a whole another experience, which you have to be sensitized as a practitioner to those layers and levels of complexity. And I use these tools to interpret it.

If you look at it and do a NeuroQuant MRI, you can see the amygdala hypertrophy at like 97 percentile. It’s like twice the size of the standard, the paired match group. You can see amygdala hypertrophy. You can see the thalamus hypertrophy, and the thalamus is rich in mast cells. You can see white matter being decreased, and so forth and so on. You can see all sorts of fingerprints of these complex triggers that can create symptomatology in these complex patients.

Dr. Kara Fitzgerald: Absolutely. It’s just extraordinary. So somebody comes in a typical allergy, seasonal allergy, maybe they’re bad, and so you’ll just treat them accordingly and get them balanced, but it’s relatively straightforward. But you’ve got somebody else also coming in and sneezy, allergic, et cetera, et cetera, but you diagnose this amygdala imbalance. I mean, you go down this whole different direction. Just roughly describe your entry into treatment with these two, with similar phenotypic but very different underlying causes.

Dr. Bruce Hoffman: Well, first of all, I don’t see patients anymore with just simple allergies. I wish I did. But those, I would just treat with H1 or H2 blockers, and Quercetin and vitamin C like all of us know how to do. But people with complex illness who have these multiple layers and levels of imbalances, I throw quite a large diagnostic net. I mean, I do a lot of tests. I’m criticized for it because of costs. But I also know myself well enough to know that without it, I’m going to be just another practitioner along the long chain of practitioners who took a little swipe at something and didn’t get much done, and didn’t look at the complex interface of all the different parameters.

So I do throw a large diagnostic net and do ask for the tests we know so well. Food sensitivities, gut microbiome, histamine levels, zonulin, DAO. I do all the mast cell mediator markers. I do all the ION panels and things like levels in methylation. I do all of that. I look at toxicology.

But I also do quite a lot with the brain, heart rate variability, autonomic nervous system functioning, and often refer for psychometric assessment to look for psychiatric diagnosis, whether they’d be cluster B personality disorders or whether they’d just be mood disorders. So I refer out for those. And I gather all this data. I also refer a lot to dentists and chiropractors particularly NUCCA chiropractors, visceral manipulation therapists.

We do a lot of diagnostics and trying to gather an insight into what hierarchically will be the entry point into this person’s therapeutic experience. I left out the most important, which is I look, apart from food and gut, which of course trumps most things. We look at the mitochondrial functioning and we look at the fatty acids because as you know, the mitochondria, the canaries in the coal mine, and they’re the first thing to sense any danger whether the danger is perceived or real, chemical or imagined.

And we have this credible capacity now through the IGL test in Germany to look at mitochondrial functioning and through BodyBio or the Kennedy Krieger fatty acid test to look at fatty acids. And those are the two tools that have trumped everything else in my practice.

Dr. Kara Fitzgerald: Wow, what is that? Tell me just briefly what the IGL is and then we can link to the … And the Kennedy Krieger and we’ll link to both.

Dr. Bruce Hoffman: So before this test came along, we in functional medicine would look at mitochondrial dysfunction, all we really had was a cheek swab. We had the organic acid test, but now we’ve got this ability to look into about 300 lab parameters that tell us the following: A, mitochondrial numbers, if they’re normal or if they are low in number. And mitochondrion, as you know, when they’re low in number, they must be undergoing some form of autophagy or cell death which ties into Naviaux’s cell danger response theory, that when we’re under threat, perceived or real, mitochondria start to self-destruct and release their ATP extracellularly, that then sends off a whole inflammatory cascade that oxidizes lipid peroxide, cell membranes and leads to this innate immune activation, mast cell activation, et cetera, et cetera.

Dr. Kara Fitzgerald: What’s the specimen? What’s the specimen for that test, sorry?

Dr. Bruce Hoffman: Blood. It’s a blood test.

Dr. Kara Fitzgerald: Both are blood tests, okay.

Dr. Bruce Hoffman: Yeah. So, it goes off and then they measure ATP production. They measure percentage of ATP that’s blocked. They measure cell free DNA. I mean, DNA that’s outside the cell shouldn’t be there.

Dr. Kara Fitzgerald: Where it shouldn’t be here.

Dr. Bruce Hoffman: They look at DNA adducts, toxins sitting on the DNA interfering with protein expression, interfering with the DNA expression of all the factors that go to make up messenger RNA and enzymes, et cetera, et cetera. It looks at phospholipid production. Phospholipids, phosphatidylcholine genome, most potent of all the cellular membrane ingredients.

It measures phosphatidylethanolamine, the phospholipid on the inner membrane which transfers electrons and the electron transport chain. It looks at outer phosphatidylcholine. It looks at cardiolipin synthase enzymes to see if they are making cardiolipin which is part of the inner membrane. It looks at whether you have what your amount of cardiolipin is so you’re looking at your phospholipids content.

It also looks at mold markers, markers for fungal metabolites. It looks at microtoxin metabolites. It looks at superoxide dismutase level. It looks at occupation of cell membranes. It looks at glutathione peroxidase, glutathione transferase. It looks at cell membrane voltage, incredibly helpful. When you’re looking at membrane voltage below 170 millivolts, it’s like 150.

And you’re looking at intracellular calcium excess or magnesium-potassium deficiencies. It looks at methylthionine levels. It’s incredible insight into toxicology and mitochondrial homeostasis. And from that, combined with the Kennedy Krieger fatty acid panel, which looks at your polyunsaturated omega 3, omega 6 levels, and it looks at renegade in very long chain fats and it looks to see if you’re myelinating adequately, et cetera, et cetera.

You can really transform a person’s biochemistry into something that ships them from this so-called cell-doubt, cell-danger response into a healthy response. And it takes an average four to six months of hard-work. But if you address the mental, the mind-body, the defense, the psyche and the biochemistry and toxicology in a hierarchical manner, and sometimes you got to stop biochemical work and you got to go work psychologically or even spiritually sometimes.

But if you start working with complex patients in this way, you’ll very soon know when to stop by a chemical work and to work at another level. If you’re sitting behind a desk and the patient is in front of you, and you’ve done beautiful biochemical work and you know that your work is impeccable and the patient is still sick, you know you’ve addressed the wrong level and it’s time to look at another level.

Dr. Kara Fitzgerald: I would imagine that you’re not … I mean, you said hierarchical, and I think that is true. But you’re doing it concurrently as well. I mean, you must be.

Dr. Bruce Hoffman: You always are. You always do it concurrently, but you learn to sense when it’s time to address, say, amygdala overactivity and vagal nerve shutdown as opposed to doing intravenous lipids and butyrate. Sometimes you’re doing all these beautiful biochemical interventions repeating the nutrition, food, gut and hormones and the patient stays resistant and/or hyperreactive.

And then you know they got an overactive amygdala and/or underactive vagal nerve. And so, you’ve got to shift focus and go down a different path. And just having done this for a long time, I’m sure you have experiences. You get to know when you probably are working at the wrong level.

Dr. Kara Fitzgerald: Yes, it does. This is such a simple thing, but in my residency, we don’t do IV therapy in my clinic here in Connecticut. We mostly do telemedicine these days. But in my residency, back when you and I used to talk, that was also in a clinic setting as well. And just that IV experience, I thought about it because I know you’re doing IV. We set up the environment to bring the energy down and so, even for those individuals who don’t want to hear it, that there’s a psychological component to their presentation.

There’s sort of backdoor ways to enter into that healing relationship or that healing, meeting the needs for healing in that space even when patients don’t want it.

Dr. Bruce Hoffman: It’s such a dance that goes on in this complex relationship between the so-called healer and the one who’s coming for your help. That if you’re not cognizant of the complexities that may arise, one can attempt to impose therapeutics onto a patient when the psyche is not intending to cooperate. It has no intent to allow that vulnerability.

And if you don’t know sort of the trauma of that person, the defenses, the fragility, the resistances, you can often rarely get into a difficult therapeutic encounter. And so it behooves us as healers, whatever the word may be, to stay very conscious of our own projections and our own inabilities and our own blind spots when we’re interfacing with patients.

And yes, they may have amygdala upregulation. They may be fragile and highly resistant. But does that mean that we get rid of them and say, I can’t help you anymore? Does that mean that we have to dig deeper into our consciousness to try and meet them where they are. And if we can unlock the door that’s previously been not open to them, we can assist in unlocking that door, there’s an incredible flood of therapeutic material and healing material that gets unleashed.

So I don’t like to do neuro biofeedback and amygdala training. If the psyche of that patient isn’t receptive to it, so it-

Dr. Kara Fitzgerald: Absolutely.

Dr. Bruce Hoffman: … a lot of conversation and a lot of negotiation sometimes around some of these issues. And people can remain hyper reactive and highly fragile and resistant. And that behooves us to just stay with that patient if we can until something shifts in the psyche and so often it does. Often it does.

Dr. Kara Fitzgerald: Yes, that been my experience as well that when they don’t achieve what they came to me to achieve or they get through some but not all, then perhaps they are open to a broader inquiry. I want to just ask, so I want to talk about, I want to get to your interventions. I know people will be very interested in how you’re addressing some of the mitochondrial issues that you’re seeing. But I just wanted to ask in your time and practice …

I mean, your practice now is self-selecting for challenging cases because you’ve been doing this for a long time and you’re just recognized as an expert, but are you also seeing sort of uptick in these kind of complex patient presentations?

Dr. Bruce Hoffman: It’s all I see now and sometimes, I wish it wasn’t.

Dr. Kara Fitzgerald: Right, I want to go back to insulin resistance case there.

Dr. Bruce Hoffman: Hormone replacement therapy, sure. But I am excited by the challenge. As you know, there’s no rest. I’m in my 60s and I don’t think I’ve studied more now. I mean, when I was a young medical student, that is nothing. This is boot camp all over again. You better stay ahead of all the research and all the latest series and all the latest issues that come across us.

But yes, am I seeing more complex cases? Absolutely.

Dr. Kara Fitzgerald: And there’s a change though, would you just say there’s sort of a change in the challenge of cases? I mean again, just going back to when you and I talked a lot, SIBO might be a challenging case. But those days seem …

Dr. Bruce Hoffman: SIBO is like one of 24 things that need to be looked at. As we’ve expanded our diagnostic possibilities and as new researchers have come up, Afrin and his mast cell activation syndrome along with the other writers and the other researchers, that’s thrown a huge level of insight into a certain presentation that we didn’t have 10 years ago. So, we have that and Naviaux’s mitochondrial cell danger response, unbelievable what that’s done to our consciousness as practitioners.

It just opened up … Now, before when we did functional medicine training, we learned about food, gut, hormones and nutrition. But now, that’s a subset within a subset of complexity. And that stuff, we have to know backwards, otherwise, we can’t get to anywhere. But what else do you bring to the table? And now, we’ve got to bring in all these other things, all these other factors into the healing relationship.

And it is far more complex. There are a lot more sicker people. And they are still looking for N2D2 solution. Even the ones who are educated, they will come and say, “I’ve got mold, Lyme, as I said in the beginning, and can you treat it?” I say, “Sure. But is that what you really have, or is that just what’s showing up as a presenting feature?” People come with false positive antibodies on Lyme test, and they say, “I got Lyme.” “Oh, it’s three on the Armin Lyme EliSpot. Is that really Lyme disease? Is that a false positive?”

And so you got to know all these subtleties. You got to constantly be in touch with the researchers and the lab directors and you got to listen to all the experts in our fields. You got to shine the light of the single aspect. And you got to know how to incorporate that clinically in patient because patients are smart now. They come with all their research.

Dr. Kara Fitzgerald: Yeah, they are.

Dr. Bruce Hoffman: And they know stuff and sometimes, it’s misguided. Sometimes, it’s spot on and they intuitively can often sort of guide a path that is previously hidden from you. They were often uncovered and helped shine a light down a certain pathway. People are smart.

Dr. Kara Fitzgerald: I want to talk a little bit about your approach. I mean we could look at mast cell activation or I mean, the mitochondria. The conversation I think is pretty provocative and one that’s interesting. I mean, are there core biochemical imbalances that you’re looking for?

Dr. Bruce Hoffman: Absolutely, yeah.

Dr. Kara Fitzgerald: Can you just talk about some of these? Let’s pull together somebody with mitochondrial dysfunction, like I want to just kind of pull together how you’re going to address it and maybe what you’re looking for in laboratory and other tools of evidence and then how you’re actually addressing it clinically?

Dr. Bruce Hoffman: Yeah. When people present their history, two, three-hour history, you do your biochemical workup. Take a very extensive dietary history. Usually get dental workup, get sleep studies, NeuroQuant MRIs, brain studies, et cetera. And once you have those in front of you, what do you do first of all? The first thing I do is always look, I use my traditional medical insight and I look at straightforward pathology.

Free T3 is low and the TSH is high, B12 is low. I’d look at straight biochemistry and I never bypass it. I pay very close attention to traditional medicine’s biochemical imbalances, and look at nutrition in great detail. And it behooves us now with all these complex illnesses to know all those approaches to nutrition that are out there whether it’d be GAPS or paleo autoimmune low histamine, et cetera, et cetera.

So, I look at traditional biochemistry. I look at nutrition and then I use nutritionist chef health coach, Justine Stenger, on our staff to take a dietary history and start to introduce a dietary approach which is commensurate with their presentation. And most of the time, it’s a paleo autoimmune low histamine diet, sometimes low FODMAPs, sometimes low oxalate. But generally, I find getting people off some of those major foods that are inflammatory and getting onto paleo autoimmune low histamine diet quietens the microbiome to an extent that we can begin to repair.

So, traditional biochemistry, nutrition, dietary approaches and then start to look at all the things that most functional medicine doctors look at. The food sensitivities, status of a gut, nutritional levels, macro and micronutrients, antioxidants, toxicology, heavy metals, chemicals, mold, fungi, mast cell activation in great detail, and look at hormone levels.

And I look at hormones in three distinct compartments. I don’t just look blood levels. I look at blood, saliva and urine all on the same day to look at the different compartments of how hormones are attached to transport proteins, how they show up at the cell surface and how they get metabolized through the methylation pathways. I’ll look at all three to start with.

And then I look at infectious agents, and I tend to do quite extensive infectious disease workups, both B cell and T cell assessments. I find if you just do T cell, do ELISpots, it’s not enough. And if you don’t do B cell, you often get very confused and go down the wrong pathways.

Dr. Kara Fitzgerald: What tests are you using? Tell me what tests are you using?

Dr. Bruce Hoffman: I’m using the ArminLabs. I do the ELISpot, and I use IGeneX. I do the IGeneX ImmunoBlots and I do the co-infection panels. I use Galaxy labs for the Bartonella. And I do also use MDL labs for some of the other infections, Garth Nicholson’s lab. Those labs are usually used to look at infectious load. And then, so once I had that diagnostic roadmap, and then therapeutically as I said, I’d correct any traditional metabolic imbalances, thyroid, hormone, whatever.

Dr. Kara Fitzgerald: So, you’ll start … So, you’ve got diet. And then you’re going to start them on some thyroid if they need it, some magnesium, some B12, et cetera. So, you’ll do those foundational first step?

Dr. Bruce Hoffman: Yes. And often if there’s great dysregulation in the qEEGs and/or in the stress assessments, and/or in the MoCA cognitive assessment or the CNS vital signs or TOVA, I’ll often start them in neurobiofeedback. I’ll start them on biofeedback programs and start them on neuromodulation techniques using different devices that we use from traditional feedback to Vielight to photomodulation. We’ll use different techniques.

So I often start those concurrent with food and traditional interventions whether it’d be hormones or nutrition. And if the toxic burden is extremely high, I never go ahead and start to detoxify them day one. And I never treat infections in the beginning. Even though Naviaux is very clear that unless you get rid of the threat, you’re not going to change the cell danger response.

So, I usually start out by using oral and intravenous lipid therapy or membrane therapy to try and provoke a mitochondria backing to more of a healing response. And I found that profoundly influential and help in patient outcomes.

Dr. Kara Fitzgerald: What is that?

Dr. Bruce Hoffman: I do a power drink or a membrane stabilizing shake, if you will, where we put into a blender phosphatidylcholine from BodyBio. BodyBio is the only phospholipid I use because of its very high phosphatidylcholine content, which doesn’t break down in the gut. And it contains the phosphatidylethanolamine. It contains all the subfractionations of phospholipids.

So, I use BodyBio phospholipids and BodyBio balanced oils, usually the 6:3 ratio and 4:1 ratio. You put that in the shake along with minerals and electrolytes and then any other ingredient that has shown up in the test that could be instrumental at restoring some homeostatic imbalance. So for instance, if they have low aminos on the ION panel, we use amino acids. If they have low glutathione, we use liquid glutathione as well as oral glutathione as well as oral NAC, all the standard things we learn as functional medicine doctors.

We put in tons of Resveratrol if we can. People tolerate it. And we use usually half a cup or quarter cup of blueberries. We found most people don’t seem to react adversely to blueberries. And then learning from Dr. Kharrazian, we chop up … On a Sunday, I advise patients to go and get every vegetable they like provided it’s not histaminic or oxalates or something on their testing shows they shouldn’t. Organic, chop it up, put it into the freezer. Every day in your shake, you take a couple of tablespoons or half a cup and you put that into the shake with the phospholipids.

And then that becomes a liposomal polyphenolic compound that then crosses the blood brain barrier and exhibits this antioxidant effect intracellularly. So, that’s been a gamechanger for my practice along with intravenous therapies. I start with very, very low dose phospholipids, sometimes vitamins and minerals just to provide the micronutrients for the enzyme systems, sometimes with intravenous amino acids.

But generally, I move over slowly but surely into phosphatidylcholine and glutathione intravenously, not to provoke a massive detoxification response but to try and repair cell membranes. Cell membrane repair is better done with oral phosphatidylcholine, but the IV phosphatidylcholine conjointly with the oral not only helps the cell membrane repair but it also starts to gently sweep adducts off the toxins that are sitting on the DNA of the mitochondria.

But it’s not aggressive. It’s very gentle. Later on, we start to use butyrate and other short-chain fatty acids to further the removal of adducts in toxins.

Dr. Kara Fitzgerald: How are you introducing those?

Dr. Bruce Hoffman: Intravenously and orally. I use them quite a lot. I use oral butyrate and IV butyrate quite a lot.

Dr. Kara Fitzgerald: What’s the oral butyrate? I mean, it’s kind of smelly, but in a capsule like in an enteric-coated capsule? What do you-

Dr. Bruce Hoffman: You can get different kinds. There’s the cal-mag butyrate. There’s the sodium butyrate. There’s sodium potassium butyrate. So, you got to look at the electrolyte balance of the patient and then introduce the specific butyrate formulation that is going to be most helpful for that person’s biochemistry.

So, if they’ve got intracellular calcium deficiency, you’re going to use the calcium one. If they have POTS syndrome … By the way, that’s one of the greatest. One thing I learned 10, 15 years ago was to make sure every patient does the 10-minute, cheap, lying standing test. If you misdiagnosed POTS, that patient is never going to get better.

And I know you’re familiar with it but I do suggest that any young or new practitioner, just get yourself an Omron blood pressure cuff. Every patient that comes in your door, lie them down, do their blood pressure and their pulse after they’ve laid down for a minute or two. Stand them up one minute, three minutes, five minutes, 10 minutes, look at their blood pressure and pulse and look for drops in systolic blood pressures and look at rises in pulse rates.

And those patients don’t perfuse the mitochondria or the brain and they won’t improve until you get increased perfusion to their cellular structures into their brains. They just won’t. You have to treat that first.

Dr. Kara Fitzgerald: And are you addressing it with this protocol?

Dr. Bruce Hoffman: I address that with the standard POTS approaches with increased fluids with salt, a lot of salt, two to three teaspoons of salt. Salt sticks compression stockings and I liberally use Florinef and Midodrin and other medications. And it’s a gamechanger. It’s absolutely a gamechanger in certain patients.

And many people are misdiagnosed. There’s a combination of sort of different … You can get orthostatic hypertension. You can get postural orthostatic tachycardia syndrome, and you can just get pure tachycardias. And they’re different and if I need to differentiate, I send them to cardiologists.

And we have one particular one in our city who does tilt table testing. He’s written lots of papers, very experienced. And so we refer to him to sort of introduce further medications if need be. And patients always know about the triad of dysautonomia and mast cell and gastric motility issues. Many patients present with mast cell activation, POTS, and Ehlers-Danlos syndrome with dysautonomias and gastric motility issues. And they’re called triad or pentad patients as per Afrin’s group.

Dr. Kara Fitzgerald: Why are we seeing more of these people?

Dr. Bruce Hoffman: I think the stresses imposed upon our modern society are overwhelming our defenses. We just become extremely vulnerable to this incoming toxic load. We’re not genetically resilient enough to withstand this onslaught, whether it’d be electromagnetic fields or chemicals or foods. Even the fact that we could open the fridge five times a day, eat what we want, I mean that’s a stressor on our system, it’s unbelievable.

We’ve got out of sync with our innate biorhythms and there’s been a huge movement in the functional medicine community through biodiversity and regenerative agriculture. And we’re paying lip service to this need, but I don’t know. I think our DNA and I think microbiomes will eventually adjust to these incoming onslaughts. I don’t think we’ll be extinguished. It always appears that stresses on the system create greater resilience down the line and barring a sort of huge six apocalypse. I think we will become more resilient as we sort of evolve through this toxic phase that we’re going through.

But right now, I think we’re very vulnerable and we are under a lot of stress, under a lot of toxic load.

Dr. Kara Fitzgerald: Well, we’re kind of heading towards the end of the podcast. This is to clinicians, and so this is going to create a lot of interests in your approach to care. I guess I have two questions. One is, where do people learn more about this model that you’re working from? This sounds so powerful, and I certainly appreciate you’re casting a very wide net and people are coming to you because of that and so forth.

But as you described such a careful start to the journey … By the way, we’re going to try to piece together that shake recipe. That was so awesome. We’ll put it on the show notes, people. It’s just the most sophisticated shake yet, so I want to see if we can pull that together and put something on the show notes.

But I mean you must be seeing some pretty good outcome just after this evaluation and you’re pushing the ship from the shore. I mean you must be seeing some good change. And if not, I’m sure you’re just really going back to rethinking.

Dr. Bruce Hoffman: I don’t have a research assistant in my office, so it’s hard to know outcomes. One believes that one’s practice is achieving remarkable outcomes, but I think unless you have a statistician in there, a hardcore research, we’ll never really know. But what I’ve noticed … By the way, a lecture I did is on my website. I lectured to the ICI Conference and it’s on my website. We are doing one and a half hour synopsis of the seven stages.

Dr. Kara Fitzgerald: Okay, perfect.

Dr. Bruce Hoffman: I think it’s the most insightful sort of snapshot of the levels and layers and complexity that’s possible. So, the outcomes we have from what I can tell, because one never really knows the drop-off rate. I don’t think it’s very large. When patients present with complex illness and you do your due diligence and you throw the net far and wide and the patients can keep up with it, and many patients can because they’re so educated and so driven, they’re so sick and tired of seeing hundreds of people and not getting any better.

And you’re looking at your data and you’re looking at mitochondrial function and fatty acids function and ION panels and things and you do repeat them from time to time. It has been my experience that within six months on average, on average, the test itself reverts from highly problematic to restored function, the IGL test. You will see mitochondrial numbers go from low to normal. You will see phosphatidylcholine go from extremely low to normal. You will see glutathione levels come back. You will see microbial toxins disappear. You will see mercury, lead, cadmium, glyphosate levels disappear.

But concurrent with that, the patient will tell you, “I feel completely different.” And we keep objective, we do different score systems. But I use the old MSQ from IFM. And patient’s levels drop from 180 to 20 once you start working from the mitochondria outwards into the whole complexity of the mind-body and familial inherited system. If you start using a broad map and you just don’t run down too many rabbit holes, and you keep your head above you and you just work it through. And if you hit the blank wall, you just ask more questions. You don’t give up.

Somewhere along in that experience, the patients, they feel better, their symptoms improve and they move through that cell danger 1, 2, 3, into the cell danger 3 response, the healing response. And they feel amazing. We have a large amount of patients who do experience that once they’d gone through their process, but we always preface it with, “Look, this is only as successful as the amount of effort you put in. If you stay passive, there’s nothing we can do. You have to be a cooperative partner in this experience. If you have side effects, you don’t throw baby out with the bathwater. You come to the table. We find out what happened, and you work through this process. And if you can’t, you get yourself somebody, an advocate, who can help you.”

In that sort of dynamic and with the staff, the great staff I have and the support systems and the ability to rerun lab tests from time to time, I would hazard a guess that the majority of our patients get better, the majority. I wish I had the statistic to tell you, but I don’t.

Dr. Kara Fitzgerald: Maybe now is the time to get a PhD student in your practice. It would be really nice to gather. I know you’ve been at this for a long time. It’d be nice to maybe get some data.

Dr. Bruce Hoffman: I think I should, yeah.

Dr. Kara Fitzgerald: Yeah, get a student, that good PhD work. Well, Dr. Hoffman. It was just really lovely to connect with you and talk about this. Folks, we will gather as much as we can for the show notes and link over to the site to some of the content that he’s referencing. And if you think of anything else, just let us know. Thanks for joining me today, for this really nice dive into what you’re doing.

Dr. Bruce Hoffman: Thanks, Kara, and nice to speak to you again after all these years.

Dr. Kara Fitzgerald: Right, absolutely. And hopefully, I’ll see you in person at AIC, not this year but next year.

Dr. Bruce Hoffman: Yeah, maybe, who knows? I quite enjoyed this sort of remote telemedicine, teleconference …

Dr. Kara Fitzgerald:  Thank you kindly, for your time. Much appreciated.

The podcast was originally posted on Dr. Kara Fitzgerald’s website here.

Chronic Inflammatory Response Syndrome (CIRS) Evaluation and Treatment

Chronic Inflammatory Response Syndrome (CIRS) Evaluation and Treatment

Introduction

When a patient presents to a doctor with many symptoms, has seen many doctors, and has not improved despite many attempts by the most well meaning practitioners, both traditional and alternative/integrative/functional, it is time to consider whether a diagnosis of CIRS may be playing a role in his presentation. However, this decision can be complex. Unless a specific roadmap is followed and a process of deductive reasoning applied to a differential diagnosis, one may find oneself in a quagmire of conflicting information.

What will follow in this essay is a step by step map for health care practitioners to follow in the process of deductive reasoning in the consideration of whether CIRS may be underlying the patient’s presentation. Unless a practitioner follows an evidence-based protocol of carefully developed steps as outlined by Dr Shoemaker and others, one may be tempted to omit or skip specific steps in the diagnostic process thereby reaching conclusions that are not in keeping with the published research. Thus, it is vital to follow the steps exactly so to support or refute the evidence.

Health care practitioners must precede a diagnostic workup for CIRS with the normal workup one employs for chronically ill patients: present history, presenting symptoms, past history, family history, medications, allergies, supplements, surgeries, dental history, toxin exposure, review of systems. A cognitive and mood history is also essential. As a certified functional medicine practitioner, I am most interested in the timeline of illness presentation, as well as any antecedents, mediators, and triggers that may fall outside of the CIRS presentation.

However, if the patient’s symptom clusters point towards a possible diagnosis of CIRS, the diagnosis of CIRS must be included in the differential diagnosis.  It is then incumbent upon the practitioner to enquire as to whether or not there have been any exposures to the possible agents and/or biotoxins that are responsible for initiating this potential diagnosis and if so, to then follow the rest of the diagnostic criteria to establish the diagnosis.  

Questions to ask patients who have been exposed to water damaged buildings include: Do you/did you live in a building with obvious mold visible? Has your home ever been flooded?  Is there any obvious water intrusion? Do you smell musty odors? Does your home have condensation on the windows? Are there any water stains around your light fixtures in the ceilings? Did you feel worse after you moved homes, school, and work place? Has conventional air quality testing revealed mold spores present?

Further questioning includes: Have you had a tick bite, EM rash, severe flu-like illness that persisted after visiting Lyme endemic areas? Have you been exposed or swam in a body of water with an algae bloom? Have you ever been in waters/estuaries where sudden fish kills were reported through direct contact or inhalation of aerosolized or volatized toxins? Have you eaten reef fish and felt ill soon afterwards? Have you ever had a spider bite (brown recluse spider)?

Background Information prior to engaging in the diagnostic criteria

Immune System

The immune system is composed of two major subdivisions: the innate or nonspecific and the adaptive or specific immune system (found only in vertebrates). We are born with innate immune responses intact; we develop adaptive immune systems after birth.

The innate immune system is the body’s primary defense mechanism against invading antigens: the adaptive immune system is summonsed by the innate immune system as a second line of defense provided there are no HLA genetic defects in the individual (74% of the population).

26 % (1 in 4) of the population has an aberrant HLA system that leads to upregulation of the innate immune system with an inability to adequately notify and summons the adaptive immune system.

This defective setup informs the basic underlying issue with CIRS; an aberrant upregulation of the innate immune system due to biotoxin inducing triggers, with a defective adaptive immune response to these inflammatory signals

Innate System

  • Acts almost immediately to infection, the adaptive takes longer to respond
  • Is not specific to a particular antigen and reacts the same way to a variety of infectious agents and inflammagens.
  • Recognizes toxins with pattern recognition receptors
  • Does not provide long-lasting immunity to the host
  • Communicates with the adaptive immune system via macrophages/monocytes and dendritic cells as antigen-presenting cells, the first responders of the innate immune system
  • Recruits immune cells to the site of infection via the use of cytokines and TGF beta-1
  • Activates the complement cascade system to assist in removing antigens
  • Presents toxins to the adaptive immune system naïve lymphocytes called T cells, the lead cells of the adaptive immune system. These inflammatory molecules do not have a specific target and they do not remove biotoxins. Trichothecenes, the biotoxins released from Stachybotrys and Fusarium mold species can slow the maturation rate of dendritic cells, [1] resulting in defective antigen presentation to the adaptive immune system

Both aspects of the immune system have cellular and humoral components.


[1] Hymery N, Sibiril Y, Parent-Massin D. In vitro effects of trichothecenes on human dendritic cells. Toxicol In Vitro. 2006 Sep; 20 (6): 899-909. PMID: 16517116

Adaptive System

  • Provides long term immunity by creating immunological memory after the initial exposure to a specific pathogen or biotoxin
  • Adaptive immunity involves the destruction of foreign pathogens and presentation of their peptide remains to T cells to begin process of antibody production by B cells, and NK cells and cytotoxic T cells. [1]  The T cells teach the B cells to recognize and respond to invading toxins so that, in the future, if re-exposed, antibodies produced by the B cells can mount an appropriate antibody response  
  • In biotoxin illness, due to specific genetic HLA susceptibilities, the adaptive system cannot see the biotoxins presented to them by the innate system and thus cannot produce antibodies to neutralize them. The toxin isn’t recognized as foreign. [2] These toxins have a unique structure called “ionophores” that prevent them being metabolized or excreted. The innate immune system continues to create inflammatory cytokines, leading to dysregulation of multiple systems and thus the CIRS diagnosis 
  • Patients with CIRS have dysfunction of T reg cells which are converted into pathogenic T lymphocytes via the inflammatory cytokine TGF beta-1
  • B cells, the cells of TH 2 immunity, tend to fight infections and inflammagens outside of the cell and produce antibodies
  • T cells, the cells of TH 1 immunity, tend to fight infections and inflammagens within the cell and produce transfer factors. Transfer factors are made in a similar fashion to B cells antibodies [3]

[1] Ryan J, Shoemaker R. Transcriptomic signatures in whole blood of patients who acquire a chronic inflammatory response syndrome (CIRS) following an exposure to the marine toxin ciguatoxin. BMC Medical Genomics 2015 8:15

[2] Shoemaker R. Mold Warriors . Otter Bay Books Baltimore pg. 63

[3] Rappaport S. The Evaluation and Treatment of Chronic Inflammatory Response Syndrome. Pg 16

Case Definition of CIRS

Chronic Inflammatory Response Syndrome (CIRS) is a syndrome which was originally described and expanded upon by Dr Ritchie Shoemaker in the late 90s. To date, there are over 1700 scientific articles on this condition. 

CIRS is defined as a multi-symptom, multisystem illness caused by exposure to biotoxins or neurotoxins derived from a biological source. [1]  It is associated with a well-defined set of abnormal biochemical disorders and test results in genetically susceptible individuals.

In a 2013 paper, CIRS was described as a chronic, progressive, multi-system, multi-symptom syndrome characterized by exposure to biotoxins, HLA genetic predisposition, altered innate and adaptive immunity, peripheral hypoperfusion at multiple sites and multiple hypothalamic-pituitary-end organ dysregulations. [2] This inflammatory dysregulation can affect every organ in the body and if left untreated, can become debilitating. Diagnosis begins with a history of symptoms suggestive of CIRS plus a history of exposure to a known trigger. Once these criteria are established, a set of specific diagnostic biomarkers is undertaken to establish the diagnosis. 

Biotoxins are extremely small, fat soluble molecules capable of going from cell to cell through membranes without being carried directly in the blood stream rendering them impossible to find in the blood stream. Biotoxins can enter through inhalation, direct contact with contaminated water, ingestion, tick bites and spider bites. These biotoxins, in genetically susceptible people whose immune system (antibodies) do not recognize and tag them, lead to chronic inflammation and long lasting chronic illness. Biotoxins bind to certain surface receptors, particularly those on white blood cells (macrophages, monocytes and dendritic cells) called antigen presenting cells.

Pattern recognition receptors (PRRs) are a primitive part of the immune system. They are proteins expressed by cells of the innate immune system to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with cell components that are released during cell damage or death. The microbe-specific molecules that are recognized by a given PRR are called pathogen-associated molecular patterns (PAMPs) and include bacterial carbohydrates (such as lipopolysaccharide or LPS, mannose), nucleic acids (such as bacterial or viral DNA or RNA), bacterial peptides (flagellin,


[1] Shoemaker RC, House D, Ryan J, Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health, 2013;5 (3): 396-401

[2] Shoemaker R.C. Ryan JC Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health 5 (3), 396-401

microtubule elongation factors), peptidoglycans and lipoteichoic acids (from Gram-positive bacteria), N-formylmethioninelipoproteins and fungal glucans, mannans, and chitin.

Endogenous stress signals are called damage-associated molecular patterns (DAMPs) and include uric acid and extracellular ATP, among many other compounds.[1]

This binding releases specific amounts of inflammatory molecules, cytokines, complement and TGF beta-1- the innate immune system activation sequence. This inflammation is not specific and cannot remove the biotoxins but result in persistent inflammation and a syndrome now known as CIRS.

Unlike bacterial or viral pathogens, which can be identified in blood work, biotoxins cannot be identified by routine blood tests and therefore one needs to rely on identifying them via the damage they inflict on the immune system, neuropeptide hormones and end-organ hormone systems.

Keith Berndtson MD, describes the structure of biotoxins in his Chronic Inflammatory Response Syndrome essay.[2] For example, cell membranes depend on ion channels to transport potassium, sodium and calcium ions in and out of cells. Biotoxins show the structural forms of amphipathic ionophores, creating ion channels that disrupt cell electrodynamics and hence the battery-like charge, rendering the cell incapable of performing its energy producing functions derived from the ion pumps. They also behave as “rogue” ion channels.

Biotoxins have both water and fat-soluble capacities. Biotoxins nestle on the inner fat-soluble membrane of cells, thus showing a predilection for fatty tissue like the brain, nervous tissue and the autonomic nervous system. Thus, they disrupt cell function without destroying the cell; as opposed to pore-forming toxins which create large holes in cell membranes, which are enough to kill the cell itself.

Cell-signaling is disrupted inside the cell by the disruption in the ion movement. The cell then triggers a defensive response by activating genes that code for inflammatory cytokines, on top of the already overworked innate immune system driven by CIRS. Elevated TGF beta-1 is a sign that the body is over revving from both an innate and an adaptive immune system T cell response.

CIRS biotoxins are first and foremost neurotoxins due to the fatty acid predilection with the brain being a common site, especially if there is porous blood-brain barrier.  Cardiovascular and GI sites are also common organ sites due to the rich nervous innervation and the fact that these biotoxins reside intracellularly in the fatty acid membrane, not accessible in the blood stream. They are difficult to dislodge particularly when the adaptive immune system is not adequately working.

Originally, the case definition criteria included Tier One and Tier Two criteria. All tier-one criteria had to be met and three of the six tier- two criteria had to be met to confirm the condition. As research progressed and deeper insights were gained, Dr Shoemaker updated his case definition in 2006 by including Tier-Three criteria which described the response to successful treatment.

 In 2008, the Government Accountability Office (GAO) issued their case definition, which was largely reliant on the published work of Dr. Shoemaker. It is the definition commonly used today. Dr. Scott McMahon at the 2016 Surviving Mold Conference at Irving, California, recommended that the GAO case definition be used in clinical practice.


[1] https://en.wikipedia.org/wiki/Pattern_recognition_receptor

[2] Berndtson K. Chronic Inflammatory Response Syndrome, 2013

TIER ONE CRITERIA – all three must be met

1. Exposure

The patient must have a story of an exposure to a biotoxin causing illness.

Mold – water damaged buildings (due to faulty construction, defects in ventilation, condensation issues, high humidity, leaky pipes, poor basement designs, flat roofs without adequate ventilation, fake stucco, faulty appliances, poorly ventilated bathrooms, front end loading washing machines) host microbial growth (bacteria, fungi, mycobacteria and actinomycetes) and produce over 30 different toxins and inflammagens (including mannans, beta glucans, hemolysins and proteinases). Toxic metabolic fragments and cell wall fragments from these filamentous molds are the major source of these biotoxins.

Mold is a specific biotoxin producing component of many water damaged buildings. In 2011, the National Institute for Occupational Safety and Health reported that 50 % of buildings have sustained water damage. Indoor fungi such as Stachybotrys, Aspergillus, Acremonium, Penicillium and Chaetomium have been implicated.

The Center for Disease Control (CDC) agrees with these findings, stating in a paper published after Hurricane Katrina and Rita in New Orleans, “Mold, endotoxins and fungal glucans were detected in the environment after Hurricanes Katrina and Rita in New Orleans at concentrations that have been previously associated with health effects.” [1]  Among the sources of biotoxins that can produce CIRS, biotoxins from molds known to grow in water damaged buildings (WDB) account for some 80% of the CIRS-related illness burden.[2]

Lyme disease- Borrelia burgdorferi infections produce a biotoxin (Bbtox1). [3]A history of a tick-bite, an EM rash, followed by a flu-like illness and the use of suitable testing (Elisa plus confirmatory Western Blot) is required to make the diagnosis. Lyme disease and post Lyme treatment syndrome remains a highly contentious area of investigation. Dr Shoemaker’s research showed that up to 21 % of the population is genetically Lyme susceptible, more likely to develop post-Lyme syndrome and less responsive to antibiotics for Lyme disease. They will be more likely to have an upregulated, persistent, inflammatory immune response due to the circulating neurotoxins, in spite of the bacteria being adequately killed by antibiotics.

A 2010 paper showed that Borrelia antigens may bind to pattern recognition receptors of the innate immune system and result in decreased CD 38 and thus decreased dendritic cell activation.[4]  Individuals thus have genetically determined defective protective antibody production and upregulated innate immune systems; they fail to respond to antibiotics, the definition of post-treatment Lyme syndrome (PTLS).


[1] Rao C, Brown C, et al. Applied and Environmental Micro 2007; 73 (5); 1630-1634

[2] Berndtson K. Chronic Inflammatory Response Syndrome. 2013. Pg 3

[3] Cartwright MJ, Martin SE, Donta ST. A novel neurotoxin (Bbtox1) of Borrelia burgdorferi. Meeting of the American Society for Microbiology. 1999 May: Chicago.

[4] Hartiala P, Hytonen J, et al. TLR2 utilization of Borrelia does not induce p38 and IFN-beta autocrine loop-dependent expression of CD38, resulting in poor migration and weak IL-12 secretion of dendritic cells. Journal of Immunology 2010 May 2015;184 (10): 5732 -42.

Invertebrate species producing neurotoxins including dinoflagellates (ciguatera and red tide), Pfiesteria (PEAS), and cyanobacteria- (freshwater blue-green algae Cylindrospermopsis and Microcystis – a genus of freshwater cyanobacteria) exposure. Ciguatera fish poisoning is the most common marine toxin poisoning worldwide with an estimated 50,000-500,000 cases annually. [1] Ciguatoxins are dinoflagellates of the genus Gambierdiscus found in numerous (over 400) reef fish such as barracuda, grouper and snapper with larger and older fish higher up the fish chain being the most toxic.

Poisonous spiders like Brown Recluse and Mediterranean Recluse spiders.


[1] Ryan J, Shoemaker R. Transcriptomic signatures in whole blood of patients who acquire a chronic inflammatory response syndrome (CIRS) following an exposure to the marine toxin ciguatoxin. BMC Medical Genomics 2015 8:15

2. Other Diseases

are ruled out via a thorough differential diagnosis workup. Patients with CIRS are often misdiagnosed as having depression, anxiety, PTSD, somatization, Alzheimer’s, Parkinsonism, allergy, ADD/ADHD, fibromyalgia and Chronic Fatigue Syndrome. If treated for these underlying conditions, it will make no difference to their underlying CIRS diagnosis. [1]


[1] Ryan J, Shoemaker RC, RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal polypeptide (VIP)shows a shift in metabolic state and innate immune fluctuations that coincide with healing. Medical Research Archives Vol 4 Issue 7 2016.

3. Symptoms

  1. must be allied with the clinical picture as outlined by Dr. Shoemaker in numerous publications.  

Symptoms associated with CIRS (37 in number) are grouped into 8 organ system categories. Symptoms in at least 4 out of the 8 organ system categories (below) are considered diagnostic.

 The symptoms categories are listed in the table below:

  1. General fatigue and weakness
  2. Muscles – aches, cramps (claw-like cramping of hands and feet), joint pains, morning stiffness, ice-pick pains
  3. General – headache, frequent urination and increased thirst, night sweats, static electricity or shocks, appetite swings.
  4. Eyes – light sensitivity, red eyes, blurred vision, tearing
  5. Respiratory – sinus congestion, cough, shortness of breath
  6. Gastrointestinal – abdominal pain, diarrhoea
  7. Neurological – numbness, tingling, metallic taste, vertigo, temperature regulation, dizziness, tics, atypical seizures, fine motor skill problems
  8. Cognitive – memory loss, concentration difficulties, confusion, learning difficulties, difficulty finding words, disorientation, mood swings, anxiety, panic

These 8 categories are further organized in a questionnaire (below) into 13 symptom clusters. Each cluster has between 1-5 symptoms. The clusters were selected by statisticians in order to maximize predictive capabilities.  A patient presenting with at least 1 symptom in at least 6 of the 13 clusters for more than two weeks, needs to be considered as having the CIRS diagnosis and should have a thorough diagnostic workup. In adults, if symptoms are present in at least 8 symptom clusters, this is considered consistent with biotoxin illness. In children, if symptoms are in 6 symptom clusters, these results are considered positive.

Clinical questionnaire chart

Signs

Signs were not included in the Three Tier categories.

There are many possible clues on physical examination as to the possibility of a CIRS diagnosis:

  1. Red eyes
  2. Tremor – resting.
  3. Cool hands and feet
  4. Discolored hands and feet
  5. Pallor
  6. Weakness in the shoulder extensor muscles
  7. Decreased muscle strength in the arms and forearms
  8. Grip strength and shrugging of shoulders against resistance
  9. Hyper flexibility – Flexibility is tested
  10. A full examination of all systems is to be done, including thyroid, cardiac and respiratory systems[1]

[1] Shoemaker R. Biotoxin Illness Treatment Protocol Pg. 1

TIER TWO CRITERIA – at least three of the following six criteria must be met

1. Abnormal Visual Contrast Sensitivity (VCS)   

http://www.survivingmold.com/store1/online-screening-test

  • In 1997, Dr. Shoemaker and Ken Hudnell published a study demonstrating that patients with exposure to biotoxins showed abnormal VCS results consistent with biotoxin illness. The visual contrast test measures the neurologic function of the optic nerve from the retina to the cortex by measuring the least amount (threshold) of luminescence difference between adjacent areas (contrast) necessary for an observer to detect a visual pattern.
  • The test measures contrast sensitivity for five sizes (spatial frequencies) of light, gray and dark bar patterns (sinusoidal gratings). The VCS eliminates near, far, color, motion and peripheral vision variables.
  • There are spatial frequencies measured amongst healthy individuals which is the curve formed by the highest level of contrast the patient will see, versus the CIRS patients who will have lower contrast sensitivities and their curves will fall below the healthy control line. Higher contrast sensitivity is better.
  • In the presence of biotoxin illness, visual contrast sensitivity decreases. Only rows C and D count for scoring pass or fail. One must see 7 in each eye on C and 6 in each eye on D.  Rows D and C show improvement with clearing of biotoxins. With an intensification reaction to cholestyramine, there will be a fall in column E followed by a fall in column D. [1] A fail in 1 eye and not the other eye, still constitutes a fail.
  • VCS appears to be an early, persistent, highly sensitive, inexpensive and easily measured indicator for biotoxin illness.[2] Only 8 % of people with CIRS will have a normal VCS. Thus, 92 % of people with biotoxin illness will fail the VCS. However, 98 % of patients who fail the VCS test and who have 8 of the symptom clusters will have biotoxin illness.
  • A few people will pass the VCS but still show signs, symptoms, and inflammatory markers suggestive of biotoxin illness such as artists and professional baseball players with extra keen vision. [3] Occupational exposure to solvents, hydrocarbons and petrochemicals can cause a person to fail the VCS test but not have biotoxin illness. This phenomenon is rare.

For accuracy, the following conditions need to be met:

  1. Visual acuity must be better than 20:50.
  2. Patients must wear their corrective eyewear
  3. Lighting must be sufficient
  4. Patients must sit 14 inches away from the screen for visual acuity, 18 inches for contrast sensitivity.[4]

If a patient either passes or fails the VCS test and there is still a high index of suspicion for biotoxin illness based on a history of exposure, symptom cluster analysis and/or signs on physical examination, it is still advisable to proceed with HLA and inflammatory biomarker testing.


[1] Shoemaker R. State of the Art answers to 500 Mold Questions Question 212.

[2] Shoemaker R, Hudnell K. Possible Estuary-Associated Syndrome: Symptoms, Vision and Treatment Environmental Health Perspectives Vol 109. No5 May 2001.

[3] Shoemaker, 2011, June 27, DVD.

[4] Shoemaker R., Letter to St Barnard Parish, 2/22/2006. pg. 8

VCS test results

2. Human Leukocyte Antigen (HLA) Genetic Testing

  • Approximately 24 % of the USA population have HLA gene types that make them susceptible to biotoxin illness i.e.- they do not have the genetic capability to clear biotoxins. The susceptible population makes up 95 % of the CIRS patients. The remaining 5% of CIRS patients do not have this genetic susceptibility. Approximately 76 % of the population is not susceptible to CIRS.
  • HLA refers to the Human Leukocyte Antigen genes on chromosome 6. HLA’s are found on the surface of nearly every cell in the human body. They provide instructions for making a group of related proteins known as the HLA complex which helps the immune system distinguish between the body’s own proteins and proteins made by foreign invaders such as bacteria, viruses, and fungi. This gene encodes for proteins that present foreign antigens to immune cells for removal. The HLA DR test determines ones susceptibility to CIRS plus many other diseases. [1]
  • These HLA DR/DQ encoded proteins are found on antigen presenting cells such as macrophages, B cells and dendritic cells and they present foreign cells from outside the cell to naive T lymphocytes. The T lymphocytes eliminate the antigen and transfer to B lymphocytes the ability to identify the antigen for removal. The structures of the HLA DR molecules are critical to the initial peptide/antigen recognition. The alleles most important for chronic illness expression include DRB1, DQ, DRB3, DRB4, and DRB5.
  • Just as we inherit one red blood cell type from our parent, we also inherit white cell types from our parents. However, the proteins inherited are not just one or two as in red cell proteins; they are many more combinations of proteins into groups resulting in over 50 different HLA types. The chart below will demonstrate which haplotypes are associated with which biotoxin illness susceptibility
  • The following haplotypes are associated with these different biotoxin illnesses.
  • Multi-susceptible:  4/3/53; 11/3/52B; 12/3/52B; 14/5/52B
  • Mold specific: 7/2/53; 7/3/53; 13/6/52A, B or C; 17/2/52A; 18/4/52A
  • Borrelia specific: 15/6/51; 16/5/51
  • Dinoflagellate specific: 4/7/53; 4/8/53
  • MARCoNS susceptible: 11/7/52B
  • MSH low: 1/5
  • Mold- low risk: 7/9/53; 12/7/52B; 9/9/53

[1] Shoemaker RC. Johanning E. Sick Building Syndrome in Water-damaged Buildings: Bioaerosols, Fungi, Bacteria, Mycotoxins and Human Health, pp 66-77, 2005

HLA-DR Patterns

SusceptibilityDRB1DQDRB3DRB4DRB5
Multi-susceptible43 53 
Unable to clear an/all toxins from system11 or 12352B  
 14552B  
Mold72 or 3 53 
Unable to recognize or clear mold toxins13652 A, B, C  
 17252A  
 18*452A  
Chronic Lyme-post Lyme syndrome156  51
Unable to clear Lyme toxins165  51
Dinoflagellates47 or 8 53 
MARCoNS immune system lacks ability to recognize and attack methicillin resistant staph infections11752B  
Low MSH15   

Clinical Observation

  • 4-3-53 – has 12 subtypes DRB1- 0401, -0402 and -0404 are the worst, 3% incidence, the worst RA, malaria, autoimmune hepatitis. Have the highest C4a and TGF beta-1. 0401 is the worst.
  • 11/12-3-52B – 1% incidence, tall, hypermobile, long arm span, good athletes. With free/unbound TGF β-1, they get “sicker quicker” upon exposure.
  • 17-2-52 A,B,C and 7-2-53 haplotypes associated with celiac disease
  • If a Lyme patient does not have the Lyme or multi-susceptible haplotypes there is a higher chance that he will respond to antibiotics alone. 
  • If the patient is not better with antibiotics and he has one of these haplotypes, he will need a biotoxin pathway approach. Taking antibiotics for prolonged periods alone will not fix these patients.
  • Low risk mold HLA types are: 7-9-53; 12-7-52B; 9-9-53;
  • No recognized significance types are: 8-3,4,6. 1-5,6,8

3. Matrix Metallopeptidase 9 (MMP-9) 

Lab Results

Normal range: 85-332 ng/ml; 28.14-109.89 nmol/l

A prechilled SST tube is essential to use. Following the lab draw, the specimen should be immediately centrifuged and frozen. This step will prevent the release of MMP9 from the white blood cells into the blood specimen which can double or triple at room temperature in as little as 30 minutes. Use LabCorp.

  • MMP-9 is an enzyme activated by macrophages inducing inflammatory cytokines of the innate immune system that destroys the basement membrane of endothelial cells. This provides a barrier between the blood and tissue
  • With high MMP-9, as when the immune system is chronically stimulated, the basement membrane is porous, allowing inflammatory compounds/chemokines to penetrate tissues such as muscles, joints, brain, lungs, peripheral and autonomic nervous system.[1]
  • High MMP-9 will increase blood-brain barrier permeability. [2]

[1] Shoemaker RC. Defining Sick Building Syndrome in adults and children in a case -control series as a biotoxin-associated illness: American Journal of Tropical Hygiene and Health; 2005;73 (6):228

[2] Candelario-Jalil E, Thompson J, Taheri S, Grossetete M, et al. Matrix metalloproteinases are associated with increased blood-brain barrier opening in vascular cognitive impairment. Stroke. 2011 Mar 31.

  • MMP-9 can contribute to the destruction of connective tissue as seen in arthritis, atherosclerosis and cardiomyopathy.
  • MMP-9 increases lipoprotein a and oxidized LDL
  • MMP-9 correlates with high toxic load, total cytokine load, reflect disease progression, exposure, Herxheimer reaction (with TNF). It is a great marker for hidden cytokine production.
  • Increased in head injury
  • Patient may feel worse with CSM if they have high MMP9.

4. ACTH/Cortisol

Lab Results

Normal Range:

 ACTH:  8-37 pg./ml; 1.76-8.14 pmol/l

 Cortisol: A.M. 4.3-22.4 ug/dl; 3.07-15.99 umol/l

                        P.M. 3.1-16.7 ug/dl; 2.21-11.92 umol/l

Absolute or relative ACTH dysregulations may be seen:

  1. Absolute high: ACTH > 45 or cortisol > 21
  2. Absolute low: ACTH <5 or cortisol <4
  3. Relative:  ACTH was < 10 when cortisol was < 7- two-tiered test
  4. Relative: ACTH was > 15 when cortisol was > 16 –  two-tiered test
  • ACTH and cortisol are hypothalamic-pituitary-end organ dysregulation markers.  ACTH and cortisol measure hypothalamic regulation of the adrenal glands. ACTH is released with the breakdown of POMC. It stimulates the adrenals to release cortisol, a stress hormone.
  • Cortisol release raises blood sugar. Levels are higher in the morning and lower at night. Cortisol levels begin to increase at approx. 6 am in an individual with normal circadian rhythms (i.e. not a shift worker).
  • Cortisol is said to “boot us up – mentally and physically” in the morning.  If higher during the night, this may result in insomnia.
  • When stressed either physiologically or mentally, both cortisol and DHEA rise in tandem. We may adjust to long term stress with higher than average levels of both DHEA and cortisol. However, over time, levels of DHEA may start to decline, followed by cortisol levels. We may also have dysregulated day and night levels of cortisol with low daytime and high night time levels. Daytime fatigue and nighttime insomnia with awakening issues can result. 
  • The normal response of ACTH to cortisol is that if cortisol levels fall, ACTH levels should rise.
  • Both of these may be elevated in the beginning stages of CIRS but later both may be decreased.
  • Having low ACTH in relationship to cortisol is often a common pattern seen in CIRS.
  • Cortisol regulation is lost in 50 % of people with low MSH
  • Early in the CIRS diagnosis, as MSH falls, high ACTH is not associated with many symptoms
  • As ACTH falls, there is a marked rise in symptoms
  • People who are quite ill can have low ACTH and low cortisol levels.  
  • Treating CIRS through the different stages may correct these abnormalities.
  • Adrenal support through lifestyle and/or supplementation may also be needed. This approach, however, is not part of the Shoemaker protocol.

5. Antidiuretic Hormone (ADH) and Osmolality

Lab Results

Normal range:  ADH: 1- 13.3 pg./ml; 0.9 – 12.28pmol/l;

                           Osmolality: 280-300 mOsm/kg.

High serum osmolality – High ADH = normal

Low serum osmolality – Low ADH = normal

High serum osmolality with low ADH = abnormal. Consider treatment with Desmopressin

Absolute or relative ADH dysregulations may be seen:

  1. Absolute high: ADH > 13 or osmolality > 300
  2. Absolute low: ADH <5 or osmolality <275
  3. Relative:  ADH was < 2.2 when osmolality was 292-300 –  two-tiered test
  4. Relative: ADH was > 4 when osmolality was 275-278 –  two-tiered test
  • ADH and osmolality are hypothalamic-pituitary-end organ dysregulation markers
  • Dr. Shoemaker published data showing that up to 80 % of patients with CIRS have dysregulated ADH/osmolality levels.
  • If mold is remediated, biotoxins are bound with CSM, the VCS improves and MARCoNS is eradicated, low ADH will normalize in many cases on its own. Some patients will still require treatment.
  • ADH is a marker of disrupted MSH function. Reduced hypothalamic output of ADH in response to increased osmolarity is associated with reduced VEGF production in response to low microcirculatory oxygen levels. Low ADH is also associated with autistic behaviour and social avoidance behaviour in CIRS patients. [1] [2] 
  • The hypothalamus contains cells called osmoreceptors that respond to serum osmolality.
  • When the serum osmolality is high (body fluids/blood concentrated due to dehydration), the osmoreceptors shrink and release antidiuretic hormone from the posterior pituitary where it is stored. ADH is a 9-amino acid peptide. ADH binds to receptors on cells in the collecting ducts in the kidneys and reabsorbs water. Thus, cells become rehydrated and ADH levels fall.
  • When serum osmolality falls (overhydrated, more water in the blood), the osmoreceptors swell and block ADH release from the posterior pituitary. ADH levels drop and free water is lost in the kidneys.
  • In CIRS patients there is a dysregulation of this mechanism. Most commonly ADH levels are low (they may however be high) and osmolality levels are high (dehydrated); however, they may be low). What is apparent is that the ADH levels and the osmolality levels do not appear to be synchronous with each other as they should be in a healthy non-CIRS patient.

[1] Berndston K. Chronic Inflammatory Response Syndrome pg.  15

[2] Tansey KE, Hill MJ, Cochrane LE, Gill M, et al. Functionality of promotor microsatellites of arginine vasopressor 1A (AVPR1A): implications for autism. Molecular Autism. 2011 Mar 31;2(1):3

  • Patients with CIRS often have increased thirst and increased urination. They are also susceptible to electric shocks from touching door handles. This happening is due to the fact that as salt levels rise in blood due to the dehydration, salt is released onto the skin, through the sweat glands and creates a battery-like effect that increases the electrostatic shock potential. Chloride levels may be higher than cystic fibrosis patients in some cases.
  • Dehydration may also produce migraine like headaches.[1]
  • ADH also affects VIP and MSH levels in the suprachiasmatic nucleus of the hypothalamus. Without these three hormones, the hypothalamic regulation is significantly affected. Patients with low MSH will most often have low levels of ADH.
  • Treatment is to use DDAVP.

[1] Shoemaker R. Biotoxin Illness Treatment Protocol pg. 6

6. Melanocyte Stimulating Hormone (MSH)

Lab Results

Normal Range:  35-81 pg/ml; 206-478.7 pmol/. Run through LabCorp:

  • MSH is one of the most critically supressed neuroregulatory peptide hormones in the dysregulation seen in CIRS patients.
  • MSH is decreased in more than 95 % of patients with CIRS.
  • One of most potent anti-inflammatory compounds in the body; it regulates the innate immune system.
  • Inflammatory cytokines bind to leptin receptors, usually activating MSH and beta endorphins.  MSH would then control leptin. In biotoxin illness, cytokines block leptin receptors, MSH is not made, disrupting nerves, hormones and immune function.
  • MSH is controlled by leptin in the pituitary gland; pro-opiomelanocortin (POMC) is split into three components- alpha-MSH, or adrenocorticotrophin (ACTH) and beta-endorphin. 
  • MSH functions include: melatonin production, immune surveillance of mucous membranes intestinal permeability, nasal pathogen protection), regulates ADH and VIP, reduces inflammation, controls cytokine release in skin and gut, prevents Candida infections, controls pain through endorphin release
  • When abnormal, the result is problems with sleep, pain, gut symptoms, fluid dysregulation due to ADH with increased thirst and increased urination, cortisol dysregulation, fatigue, nasal colonization with MARCoNS, stress management problems, reduced sex hormones.
  • Due to leptin issues, weight gain which does not respond to more exercise and less eating, can be a problem.
  • Low MSH causes dysregulation of T reg cells leading to inflammation and autoimmune disorders
  • MSH has been shown to regulate the inflammatory cytokines (TNF and nitric oxide) found in inflammatory bowel disease.[1]
  • Low MSH associated with anti-gliadin positivity.

Important: Markers of hypothalamic illness include high leptin and osmolality, low MSH, low ADH, ACTH and/or VIP.


[1] Rajora N, alpha MSH Modulates Inflammatory Bowel Disease Peptides Vol 18 Issue 3 pg. 381-385.

TIER THREE CRITERIA

These criteria were based on the 2010 Consensus Report as written by Dr Shoemaker and his research committee. [1]  These criteria are evaluated after treatment has begun and are the final validation of the diagnosis of CIRS.

Improvement in the following areas is required to validate the CIRS diagnosis.

  1. Symptoms and VCS improve with treatment; and
  2. Lab markers (leptin, MMP 9) return to normal levels.

[1] Shoemaker RC, Mark L and McMahon S, Research Committee Report on Diagnosis and Treatment of Chronic Inflammatory Response Syndrome Caused by Exposure to the Interior Environment of Water-Damaged Buildings. Mold Research Committee, Pocomoke 2010

SUMMARY OF THE THREE TIERS CRITERIA FOR DIAGNOSIS OF CIRS:

  • Thus, in summary, with these Shoemaker criteria in mind, three of the Tier-Two criteria in addition to all of the Tier- One criteria must be met to make the preliminary diagnosis of CIRS.
  • Once the diagnosis is made, there are other proteomic, genomic and imaging studies which can be done in order to establish the diagnosis and assist in the treatment protocol.
  • One of the most striking features of the CIRS diagnosis is the absence of the anti-inflammatory neuropeptides vasoactive intestinal peptide (VIP) and melanocyte stimulating hormone (MSH), with the concurrent master immune regulator TGF beta-1 being abnormally increased.[1]
  • Patients should present with at least four out of the eight objective serum markers found in CIRS – TGFB1, VIP, MSH, MMP9, C4a, VEGF, ACTH/cortisol and ADH/osmolality.

[1] Shoemaker R.C. Ryan JC Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health 5 (3), 396-401

Government Accountability Office (GAO) 2008 Case Definition

The GAO issued its case definition in 2008 which became the standard for case definition. The GAO definition focuses exclusively on CIRS from water-damaged buildings and not from other initiating triggers. 

  1. Patient exposed to WDB -verified by presence of musty smells, visible mold or mycological testing.
  2. Multiple symptoms from multiple systems similar to Dr Shoemakers published research.
  3. Lab abnormalities similar to Dr Shoemaker’s lab abnormalities.
  4. Improvement with therapy similar to those found in peer-reviewed published research.

Challenges with CIRS Case Definition

One of the challenges of the CIRS case definition is that it takes more than one visit to confirm the diagnosis, patients need to have labs, need to take their medications, and thus the diagnosis cannot be made on the first visit.

Further Diagnostic Tests

If a patient has a positive exposure history, more than 6 symptom clusters, a positive VCS test, and fulfills the diagnositc criteria of the first 2 tiers, then further confirmatory lab testing must be done to confirm or diprove the CIRS diagnosis.

The following chart gives a visual representation of the biotoxin pathway with some of the lab markers being represented.

Biotoxin pathway

FURTHER BIOMARKERS/IMAGING/TESTS ASSESSED IN CIRS:

  • ERMI            
  • MARCoNS
  • Antigliadin antibodies
  • Androgens
  • Leptin
  • C3a
  • C4a- run through Quest
  • VEGF
  • TGFbeta-1
  • VIP
  • Von Willebrands
  • CD4+CD25+
  • Anti-cardiolipin antibodies
  • PAI-1
  • Pulmonary Function Tests
  • VO2 Max
  • Stress Echocardiogram
  • Neuroquant
  • Genomics

PHYSICIAN ORDER SHEET

Physician order sheet
Physician order sheet

ENVIRONMENTAL RELATIVE MOLDINESS INDEX (ERMI)

  • If water damaged buildings/mold is suspected, an ERMI is essential.
  • Mold illness and CIRS arise from any indoor environment that is damaged by water intrusion. Until recently, there had been no standardized objective methods available to quantify the indoor air mold burden.[1]  Air sampling has come under much criticism due to the fact that it samples air for just a few minutes in time, does not separate all the toxigenic molds into the correct genera, and does not take into account Wallemia. Stachybotrys can often be missed as it is not an airborne mold, being heavy in nature and existing mostly on the ground. Not all molds are toxic to humans and not all “mold is mold.”
  • Dr. Stephen Vesper and his team at the Microbial Exposure Laboratories of the EPA in Cincinnati pioneered the use of Mold Specific Quantitative Polymerase Chain Reaction (MSQPCR), and its application called the Environmental Relative Mold Index (ERMI).[2]  ERMI is an objective, standardized DNA-based method that will identify and quantify molds. ERMI does not measure the DNA of all fungi, but those that carry the highest implications for the relative mold burden in water damaged buildings.
  • There are currently three labs that offer the ERMI test: EMSL Analytical www.emsl.com, Mycometrics www.mycometrics.com and EMLab P&K www.emlab.com. Mycometrics is the most accurate according to Dr Shoemaker and provides both a Swiffer cloth method of detection and offers the HERTSMI-2 score. 
  • The ERMI classifies 36 species of mold into 26 species or clusters associated with WDB (Group 1) and 10 common species/clusters not associated with WDB (Group 2) and commonly found outside.[3]  The number calculated as the ERMI is the sum of the logs of the concentrations of the DNA of the different species. The mold index (ERMI) is the difference between Group 1 and Group 2. The ERMI was calibrated to the specific measurements (3 feet by 6 feet) in the living room and bedroom for 5 minutes and all the national standards reflect measurements from these areas only. Measuring mold in the basement only is not recommended as a first line measurement for these reasons. 

Computerized ERMI values are graphed from the lowest to the highest (see figure below). The ERMI value is typically between -10 (lowest mold levels) and 20 (highest relative mold levels). An


[1] Lin K-T, Shoemaker R.C. Inside Air Quality Filtration News Vol 26, No 3, pg. 32, 2007.

[2] Ibid

[3] Ibid

ERMI above 5 is in the top 75 % of homes for relative mold burden. An ERMI of -4 and below is on the lowest 25 % of homes in the US. 

Mycometrics LLC Report

As Dr. Shoemaker and Dr. Lin point out, the ERMI is a mold index, not a health index.

  • If the ERMI is low and there are people living in the home with positive symptoms for CIRS, that is, exceeding the cut-off criteria, and/or failing the VCS test, the ERMI should be repeated in different areas of the house. An ERMI does not exclude the value of a thorough top to toe visual inspection by a mold indoor specialist.
  • If you are not ill, an ERMI will help determine if your home is safe for visitors who have the mold susceptible gene and who are known to have health effects from moldy buildings
  • If the ERMI is low and no one is ill, one’s sense of security increases. Doing an ERMI is very helpful before one considers buying a new home. 
  • Elevated ERMI test result have been shown to have a positive correlation with lab abnormalities associated with CIRS, symptoms of CIRS, neurotoxicological studies, measurements of abnormal brain metabolites and symptoms of cognitive decline including brain fog, memory deficits and poor executive cognitive functioning. [1] Dr. Shoemaker writes that the high levels of mold translate in genetically susceptible patients into inflammation that reduces blood flow in particular parts of the brain so that it does not work efficiently. Furthermore, if a person is adequately treated but returns to a home with an ERMI above 2, he relapses.
  • In general, an ERMI value greater than 2 is considered unsafe for CIRS patients if the MSH is less than 35 and the C4a is less than 20,000. If the MSH is less than 35 and C4a is greater than 20,000, the ERMI score needs to less than -1.

[1] Ibid

HEALTH EFFECTS ROSTER OF TYPE SPECIFIC FORMERS OF MYCOTOXINS AND INFLAMMAGENS – HERTSMI-2

  • A secondary result can be calculated called a HERTSMI-2. This scoring system is application of the DNA testing shown on ERMI test results.  The new roster is designed to help patients previously sickened by water-damaged buildings and genetically predisposed understand if a given building is safe for occupancy. The roster is based on the results of 738 ERMI consecutive test results with 592 that were over 2 and 146 under 2.
  • This uses values of five specific molds-  Aspergillus penicilloides, Aspergillus versicolor, Chaetomium globosum, Stachybotrys chartarum and Wallemia sebi – from group 1 on ERMI based on 2 criteria:
  • Representative of varied water saturations (60-80%; 80-90%; 90-100%); and
  • Relative risk for enrichment is WDB compared to non-WDB is at least 10.

               A specific scale is used to grade the counts of each of the five species as and added up. 

             10 points are awarded for:

  • Aspergillus penicilloides                >500 spore E/mg
  • Aspergillus versicolor                      >500 spore E/mg
  • Chaetomium globosum                 >125 spore E/mg
  • Stachybotrys chartarum                >125 spore E/mg
  • Wallemia sebi                                    >2500 spore E/mg

             6 points are awarded for    

  • A. penicilloides or A. versicolor   >100
  • Chaetomium or Stachybotrys     >25
  • Wallemia                                             >500

              4 points awarded for   

  • A. penicilloides or A versicolor    >10
  • Chaetomium or Stachybotrys     >5
  • Wallemia   sebi                                  >100

*Any score over 15 is too dangerous for previously sickened patients to occupy.
*Any score under 11 has been safe to date.

* Some individuals may need a HERTSMI-2 score of <8 to not relapse

*Any score 11-15 is borderline. The building must be treated before safety can be assessed. 

Fungal ID/Sample IDSpore E./mg
Aspergillus flavus/oryzaeND
Aspergillus fumigatusND
Aspergillus nigerND
Aspergillus ochraceus<1
Aspergillus penicillioides13
Aspergillus restrictus*<1
Aspergillus sclerotiorumND
Aspergillus sydowiiND
Aspergillus unguis<1
Aspergillus versicolor190
Aureobasidium pullulans140
Chaetomium globosumND
Cladosporium sphaerospermum<1
Eurotium (Asp.) amstelodami9
Paecilomyces variotii<1
Penicillium brevicompactum45
Penicillium corylophilum1
Penicillium crustosum*10
Penicillium purpurogenum<1
Penicillium spinulosum*ND
Penicillium variabile<1
Scopulariopsis brevicaulis/fuscaND
Scopulariopsis chartarum13
Stachybotrys chartarum<1
Trichoderma viride*<1
Wallemia sebi230
Sum of the Logs (Group I):12.61
Acremonium strictum1
Alternaria alternata19
Aspergillus ustusND
Cladosporium cladosporioides 1130
Cladosporium cladosporioides 26
Cladosporium herbarum 63510
Epicoccum nigrum93
Mucor amphibiorum*1
Penicillium chrysogenum26
Rhizopus stolonifer<1
Sum of the Logs (Group II):10.26
ERMI (Group I – Group II):2.35

MULTIPLE ANTIBIOTIC RESISTANCE COAGULASE-NEGATIVE STAPH (MARCoNS)

Lab Test: API-Staph culture

Resistance to two or more distinct classes of antibiotics plus the presence of a biofilm.

  • MARCoNS plus biofilms is identified by a nasopharyngeal culture. Thrives in deep aerobic spaces of nasal cavity.
  • Must use API Staph Isolate to get biofilm forming coagulase negative Staph. This is not a routine nasal culture technique that is only cultured for two days at Quest or LabCorp.
  • Biofilms are slimy polysaccharide matrixes that surround the bacteria, acting as a protective barrier protecting bacteria from the immune system.
  • Dr Shoemaker observed in 1998 that in MSH deficient patients, over 80 % had MARCoNS in the nasopharynx and in MSH normal patients, less than 1 % were positive for MARCoNS. 
  • MARCoNS will result in MSH deficiency.
  • MARCoNS release endotoxin A and B which cleave MSH, rendering it ineffective and thus leading to immune dysregulation.
  • MARCoNS release hemolysins, which disrupt red blood cells and endothelial cell membranes increasing inflammation, coagulation risk, and anti-phospholipid abnormalities.
  •  Low MSH impairs its ability to coordinate dendritic cell responses within gut and respiratory mucous membrane compartments. [1]
  • With low MSH, multiple neuro-immune pathways are impacted leading to dysregulation in ACTH, cortisol, androgens, ADH and osmolality, melatonin (sleep disturbances), endorphins (pain issues.)   In addition, cytokines are stimulated.
  • MSH acts as a guard immune modulator on the skin and mucous membranes and kills fungi and coagulase negative staphylococci. With normal MSH, MARCoNS will not survive. [2]
  • Inadequate treatment of MARCoNS will reduce the efficiency of CSM therapy possibly because of MARCoNS continued effect on MSH.
  • Low MSH patients rarely get better until MARCoNS is treated. Hard to raise MSH with MARCoNS present.
  • With MARCoNS, thick biofilms are made which prevent antibiotics and natural immune function from dealing with the offending organisms.
  • MARCoNS colonization produces no symptoms but dysregulates MSH.
  • MARCoNS can also be isolated from dental cavitations.
  • MARCoNS with low MSH patients have a differential genomic profile than negative MARCoNS patients and low MSH. [3]
  • MARCoNS not to be confused with other coagulase -negative staphylococci that are not antibiotic resistant.

[1] Catania A, Caterina L, Sordi A, et al., The melanocortin system in control of inflammation. The Scientific World Journal 2010; 10:1840-1853.

[2] Shoemaker R. Katz BEG DVD 2013

[3] Shoemaker R. Katz 2013 BEG DVD

Microbiology Dx report
Microbiology Dx report

ANTIGLIADIN- ANTIBODIES (AGA)

Lab results

AGA normal range:  0-19 U

  • Low MSH results in T reg dysregulation, leading to inflammation and possibly autoimmunity
  • Serum IgA and IgG antigliadin antibodies (AGA) are antibodies against gliadin, the protein found in wheat, barley and rye. Some oats is cross-contaminated with gliadin but does not, in and of itself, contain gliadin.
  • AGA is not specific for celiac disease, but it does indicate an inflammatory response to gluten
  • I tend to do the HLA DQ2/DQ8 genes and serum tissue transglutaminase (TTG-IGA) levels to exclude celiac disease.
  • Over 58 % of children with CIRS have elevated AGA levels according to Dr. Shoemaker.

ANDROGEN DEFICIENCY

Lab Results

Normal Range:  DHEA and testosterone: Various ranges for age and gender

  • Abnormal androgens are due to an upregulated aromatase enzyme.
  • Testosterone is often dysregulated and DHEA may be low.
  • Using testosterone is contraindicated in these patients.
  • Due to low VIP and inflammation, testosterone is more rapidly converted into estrogen resulting in high estrogen and low testosterone.
  • One may use DHEA.
  • VIP nasal spray corrects aromatase activity.

LEPTIN

Lab results: LabCorp

Normal ranges: 0.5-13.8 ng/ml; in men

                            1.1-27.7 ng/ml; in women

  • Leptin is a hormone that controls how fat stores fatty acids. If the leptin receptors are disrupted, high levels of leptin will be seen.
  • Leptin regulates the pro-opiomelanocortin (POMC) pathway, thus MSH pathways that also control ADH.
  • Low leptin levels contribute to low MSH, ADH, VIP and ACTH.
  • Leptin outside the brain binds to immune cells and increases inflammatory cytokines. [1]
  • If leptin is high, fatty acids are stored in fat, resulting in weight gain.
  • Leptin is not considered a major marker in the CIRS workup.  
  • Markers of hypothalamic illness include high leptin and osmolality, low MSH, low ADH, ACTH and/or VIP.

[1] Bjorbaek C, Kahn BB. Leptin signaling in the central nervous system and periphery. Recent Progress in Hormone Research. 2004; 59: 305-31. PMID: 14749508

C3a

Lab results: Quest

Normal ranges: 55-486 ng/ml;  

  • C3a generated when C4a and C2a are made by activating MASP-2; splitting C4 and C2 creates C4b and C2a thereby activating C3
  • C3a is only activated when the innate immune system is presented with a bacterial cell membrane.
  • If elevated, tick -borne illness must be excluded or diagnosed.
  • Increased C3a can cause anaphylaxis through an upregulated immune response resulting in vasoconstriction, capillary hypoperfusion, increased vascular permeability and WBC release of oxidants, leukotrienes and enzymes.[1]
  • C3a will usually be low unless there is Lyme- usually more acute in nature.
  • C3a elevates within 12 hours of a tick-bite
  • If HLA is Lyme susceptible pattern – 15-6-51; 16-5-51, most likely will need longer than 3 weeks of antibiotics and CIRS can be a distinct possibility.
  • Will need Cholestyramine to remove the biotoxins if inflammatory CIRS markers and positive VCS present.
  • May need statin therapy if C3a persists after antibiotic therapy.

[1] Shoemaker R Biotoxin Illness Treatment Protocol pg. 8

C4a

Lab Results: Quest

Normal Range:  0-2830 ng/ml;

  • If levels are very high, this could be due to delays in shipping, sample not frozen quickly enough or the specimen thawed in transit.
  • C4a is an innate immune system biomarker. If high, it usually means that the innate immune system is in overdrive to PAMPS (pathogen -associated molecular patterns) and that a biotoxin burden is present.
  • Usually results in capillary hypoperfusion of the CNS.
  • C4a is a split product of the mannose binding lectin pathways of the complement system of the innate immune system and predicts the severity of CIRS.
  • C4a has been associated with elevated levels of mannin-binding lectin serine protease 2 (MASP2) in patients with chronic fatigue syndrome.[1]
  • C4a helps the antibodies and phagocytic cells remove infections and toxins from the body.

[1] Sorensen B, Jones JF, Vernon SD, Rajeevan MS. Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. Molecular Medicine 2009 Jan-Feb; 15 (1-2): 34-42

  • Complement proteins circulate as inactive precursors but when split into active components they amplify the immune response of the membrane attack complex (MAC).[1] MAC kills the outer layer of cells causing cell death.
  • Both C3a and C4a are anaphylatoxins which cause smooth muscle release, can activate mast cells, increase histamine, increase basophils, increase vascular permeability, cause capillary hypoperfusion with resultant cellular hypoxia resulting in reduced mitochondrial function, increase lactate production from glycolysis,  and can increase cognitive dysfunction (memory loss, concentration, word finding difficulties, disorientation, confusion, difficulty integrating new information.) as well as fatigue. [2]
  • Brain fog caused by increased lactate and suppression of the glutamate/glutamine ratio. -increased inhibition versus excitation.
    • When C4a with anaphylatoxin activity stimulates the degranulation of mast cells, vascular permeability ensues, dermatographia can exist on the skin and smooth muscle contractions occur.
    • C4a can causes high lactate levels >1.29 and low glutamate/glutamine ratio <2.19 on MR spectroscopy.
    • If C4a levels are above 20,000 with low MSH levels the individual cannot be in a home with an ERMI above -1.
    • Cognitive functions improve when C4a drops.
    • C4a can be elevated in Lyme disease and SLE.

[1] Rapaport S. Evaluation and Treatment of CIRS pg. 7

[2] Ogata RT, Rosa PA, Zepf NE. Sequence of the gene for murine complement component C4a. The Journal of Biological Chemistry, 1989; 264( 28): 16565-72.

VEGF

Lab results: LabCorp and Quest

Normal Ranges: 31-86 pg./ml

  • VEGF is a marker of capillary hypoperfusion. A low level of skeletal muscle VEGF is associated with decreased muscle endurance.[1]
  • Treat VEGF if less than 31. If high, say 105, it means the innate immune is activated, but does not give the cause.
  • VEGF is high in renal failure and Bartonella infections. [2]
  • Inflammatory cytokines bind to endothelial receptors, which release “glues”- adhesion and integrins.  These hold the white cells together and narrow the capillaries creating hypoxia. This is sensed by regulatory cells which produce a gene controller hypoxia inducible factor (HIF), which produces VEGF.  
  • VEGF is a growth factor which stimulates blood vessel growth in response to HIF and dilates blood vessels in healthy people.

[1] Olfert IM, Howlett RA, Tang K, Dalton ND et al. Muscle specific VEGF deficiency greatly reduces exercise endurance in mice. Journal of Physiology 2009 Apr 15; 587:1755-1767

[2] Kempf VAVolkmann BSchaller MSander CAAlitalo KRiess TAutenrieth IB. Evidence of a leading role for VEGF in Bartonella henselae-induced endothelial cell proliferations. Cell Microbiol. 2001 Sep;3(9):623-32.

  • In biotoxin patients, inflammation and cytokines suppress VEGF, creating persistent capillary hypoperfusion.
  • This result in fatigue, cognitive fallout, muscle aching, and poor recovery from exercise due to anaerobic mitochondrial metabolism.
  • Usually glycolysis and protein are used for energy, taking several days to replenish glycogen.
  • In lactic acid metabolism, due to low VEGF, one obtains only 2 ATP for every glucose molecule, instead of 36 ATP as is normally the case.
  • Early in CIRS, VEGF can be increased, signifying that the body is trying to compensate for low oxygen delivery to tissues.

TRANSFORMING GROWTH FACTOR BETA-1 (TGF beta-1)

Lab results: LabCorp and Quest

Must be double spun plasma with Cambridge to make sure all plasma platelet contamination is gone. Not serum. If result is greater than 40,000, the specimen is likely mishandled.

Normal range:   < 2380 pg/ml; =normal

> 5000 = symptoms appear

                                > 10,000 = restrictive lung disease, tremor, cognitive issues, joint problems may occur

  • TGF beta-1 is a protein that causes cells to change and usually results in innate-adaptive immune system dysregulation. It can either produce or suppress inflammation.
  • It must be addressed vigorously as it represents widespread tissue involvement, most common in people with highly susceptible 11-3-52B and 4-3-53 HLA haplotypes. Limiting mold exposure is crucial to down regulate this biomarker.
  • Elevated levels usually indicate that the body is trying hard to down regulate an overactive T cell adaptive immune system as in allergy (asthma) and autoimmunity (multiple sclerosis) as well as an overactive innate system (CIRS)- both caused by biotoxins in the HLA susceptible host.
  • TGF-beta-1 has a dual function in the innate immune system. If elevated it indicates an overactive immune system and it a key marker of the CIRS severity.
  • If stays high, it can indicate the person is having a difficult time recovering.
  • It helps control the growth and differentiation of cells, cell motility and cell death. In utero, it helps form new blood vessels, regulates muscle and body fat development and wound healing. 
  • It is an inflammatory regulatory cytokine which affects autoimmunity through differential gene activation. It can damage T reg cells CD4+CD2++, which regulate TH1 (autoimmunity), TH2 (allergy), TH17 cells. It converts CD4+CD25++ T reg cells into pathologic T cells, thus activating TH17 (autoimmune system) driven inflammation. Together, TH-17 and T-regulatory cells are responsible for preventing autoimmunity. TGF beta-1 can thus activate or reduce autoimmunity.
  • In the treatment, one must increase the low T reg cells (cellular immunity) and lower TGFB, thus improving humoral immunity.
  • If T reg cells are low <4.66 %, TGF beta will be high > 2,380.
  • VIP will raise T Reg cells (CD4, CD25).
  • TGF beta-1 can cause tissue remodeling in the liver, heart, central nervous system and the kidney.
  • If TGF beta-1 levels are >10,000, this may result in pulmonary remodeling and interstitial, restrictive lung disease (shortness of breath and asthma like symptoms), pulmonary
  • hypertension (where endothelial cells become thick fibroblasts and result in acquired pulmonary hypertension). Pulmonary stress testing can determine VO2 max and pulmonary function testing can look for signs of restrictive lung disease. Stress echocardiogram to estimate pulmonary arterial pressure (the measurement of the tricuspid jet and right atrial pressure) can also be done and which will measure further pulmonary cell transformation
  • High TGF beta-1 associated with joint inflammation
  • High TGF-B-1 may result in neurological diseases (MS), seizures, tremor, Parkinson’s, Autoimmune diseases (lupus, RA, dermatomyositis, ulcerative colitis, positive ANCA, ACLA, scleroderma), learning disabilities, vocal polyps and nasal polyps  and cognitive symptoms.
  • High TGF beta-1 can be seen in HIV, cancer and connective tissue disorders
  • High TGF beta-1, along with low MSH can contribute to GI dysfunction which improves when immune markers are normalized.
  • CD4+CD25++ blood levels = T reg cells. If low, the TGFbeta-1 would expect to be high.
  • VIP will cause T reg cells to increase, but re-exposure to biotoxins will cause them to drop.
  • TGF beta-2 will cause hair loss with increased catagen hair. Growing hair follicles are anagen, rest-phase hair is telogen but dying hair follicles are catagen due to TGF β-1.[1]

[1]Hibino T1Nishiyama T. Role of TGF-beta2 in the human hair cycle  J Dermatol Sci. 2004 Jun;35(1):9-18.

VASOACTIVE INTESTINAL POLYPEPTIDE (VIP)

Lab Results: Quest

Normal range:   23-63 pg/ml

  • No accurate test for VIP at the moment.
  • VIP is a 28-amino acid regulatory neuropeptide, neuro-immune modulator which downregulates cytokine levels with interactions with other peptides: MSH and Vasopressin.
  • It has hypothalamic receptors; it regulates blood flow and distribution.
  • Low levels are associated with capillary hypoperfusion and abnormal pulmonary artery pressure at rest or in response to exercise. [1]
  • It is also made in the nerve endings, gut and pancreas.
  • It can have a positive effect on the entire Biotoxin Pathway.
  • Like MSH, it regulates peripheral cytokine responses and inflammation throughout the body.
  • Low levels found in 98 % of CIRS patients and in less than 10 % of controls.
  • VIP helps reduce pulmonary artery hypertension. If pulmonary artery pressure raised with tricuspid valve regurgitation, one can have shortness of breath, especially with exercise. VIP will help reduce post exertional fatigue and shortness of breath
  • Helps with MCS, releases endorphins, reduces sicker-quicker phenomenon, downregulates MASP2- the enzyme that stimulates cleavage of C4-C4a; the key to reducing “quicker/sicker” phenomenon.
  • VIP induces smooth muscle relaxation in the intestinal tract stimulating water secretion into bile and pancreatic fluid; it can reduce stomach acid and absorption of nutrients from the GI tract. Diarrhea can result.  

[1] Berndtson K. Chronic Inflammatory Response Syndrome. Overview, Diagnosis, and Treatment. Pg.7

  • Restores hormone levels, Vit D 3 levels, decreases aromatase upregulation caused by cytokines thereby restoring estrogen and testosterone levels, corrects ADH/osmolality.
  • Helps restore energy in chronically fatigued patients.
  • Enhances IL-10 production
  • Increases CD4+/CD25+ T reg cells, restoring their numbers and thereby regulated TH 17 autoimmune response. If used appropriately, it will suppress overly active inflammation and will regulate dendritic cells, the cells that mediate between the innate and adaptive immune systems.  Inhibits TGF beta-1. Down regulates cytokines and thus is a down-regulator of inflammation
  • Restores circadian rhythm.
  • It helps treat genomic dysregulation caused by CIRS.
  • VIP assists in treating the brain abnormalities found in NeuroQuant esp. caudate nuclei atrophy.
  • Upregulates VEGF esp. if not responded to Actos or Fish oil 1 spray – alternating nostrils 4 times per day.
  • Dr. Shoemaker published a study in 2013 on VIP used on CIRS-WDB patients which demonstrated the following: [1]
    • refractory symptoms reduced to control levels
    • corrected inflammatory biomarkers -C4a, TGF beta-1, VEGF and MMP 9 and reduced levels to controls
    • raised VIP and MSH, corrected estradiol, testosterone and Vit D levels,
    • corrected T-reg levels,
    • retuned PASP during exercise to normal
    • enhanced quality of life in 100% of patients in the study
  • Dr. Shoemaker found that 100 % of over 500 patients with multiple chemical sensitivities were found to have low VIP.
  • In order to use VIP, need to be out of a moldy building (ERMI less than 2), have a normal VCS and be MARCoNS free.

[1] Shoemaker RC, House D, Ryan J. Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health, 2013; 5 (3) 396-401

CD4+ CD25+

  • No commercial test is currently availablealthough select centres may do the test under special circumstances. 

VON WILLEBRANDS PROFILE

Lab results: Quest

  • Factor VIII activity, von Willebrand Factor antigen, Ristocetin Cofactor, von Willebrand Factor Collagen Binding Assay, von Willebrand Antigen) –as well as coagulase study- PT, PTT, PT/INR –  esp. if history of bleeding with exposure to WDB.
  • Patients with levels of Factor VIII, von Willebrand’ s antigen or Ristocetin associated cofactor either <50 or >150 IU are classified as abnormal for von Willebrand’ s antigen.
  • Blood will be thinner and bleeding will result.
  • Acquired von Willebrand syndrome can be the result of increased C4a resulting in increased bleeding tendencies. Water damaged building avoidance is the first step in treatment as well as using DDAVP.

ANTI-CARDIOLIPIN ANTIBODIES

  • Marker of autoimmunity.

PAI-1

  • A marker of increased blood coagulation.

PULMONARY FUNCTION TESTS

Unusual shortness of breath with post exertional fatigue warrants a workup for pulmonary function and possibly acquired pulmonary hypertension.

  • In CIRS, pulmonary function tests may show a restrictive pattern rather than an obstructive pattern of respiratory difficulties. If restrictive test is shown, proceed to VO2 max.  

VO2 MAX

  • VO2 max testing done on a treadmill may show abnormally low VO2 max, often lower than 20. This reflects capillary hypoperfusion and post exertional fatigue and malaise. High cytokine levels can first raise and then lower VEGF leading to chronic tissue hypoxia. CIRS patients have a lower threshold for hypoxia as a result.
  • Exercise is very helpful for these patients but they must stay below their anaerobic threshold.  If they stay below their anaerobic threshold, glycogen store depletion is prevented. This is determined by performing a cardiopulmonary stress treadmill test.
  • VO2 max > 35 = normal
  • VO2 max < 20 = CIRS patients 
  • VO2 max 12-15 = Stage IV Cardiac failure

STRESS ECHOCARDIOGRAM

This is to be pursued in the patient with unusual shortness of breath, asthma like symptoms and excessive post-exertional fatigue/poor exercise tolerance.

  • A stress echocardiogram will non-invasively measure the tricuspid jet and the right atrial pressure, thus estimating pulmonary arterial pressure (PA) response to exercise.
  • Normally the pulmonary pressure drops with exercise, allowing for increased oxygenation.
  • In CIRS patients, the PA pressure may increase, resulting in reduced oxygen absorbed into blood during exercise and thus poor exercise tolerance
  • A high pressure at rest may be seen, esp. if TGF beta-1 is high and T-reg cells are low. Th-17, induced by high TGF beta-1 will convert T reg cells to pathogenic T cells.
  • Avoid mold, use losartan and use VIP to correct this abnormality.

NEUROQUANT

A Neuroquant MRI is a software addition to an MRI and assists in determining if there are any changes in brain volume and structure according to specific quantifiable determinants in 11 different brain regions.

 Patients with CIRS due to mold exposure have a specific pattern of abnormalities as compared to controls:[1]

  • Forebrain parenchyma increased
  • Cortical gray increased

[1] Shoemaker R, D House R, Ryan J, Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings,” Center for Research on Biotoxin Associated Illness, Pocomoke

  • Hippocampus increased – although not included in the criteria
  • Caudate decreased – reversible through use of VIP according to Dr. Shoemaker’s clinical experience
  • Pallidum increased

Patients with CIRS due to Lyme neuroborreliosis have the following pattern:[1]

  • Small forebrain parenchyma
  • Small putamen
  • Large thalamus – (isolated post gray matter change)
  • Large cerebellum

Neuroquant also assists in the detection of other nuclei that can be atrophied and is helpful when looking at brain atrophy in dementia Alzheimer’s disease.

In Dr. Shoemaker’s research, no confirmed case of CIRS had less than 5 points and no controls had 3 or more points. One needs to take the average of the two sides to determine the points awarded.


[1] Ibid

 Black = Mold  Red = Lyme1 point2 points
Forebrain>31.9>32.5
Cortical Gray>16.3>17.0
Caudate<0.255<0.235
Pallidum>0.07>0.08
Putamen<0.345<0.335
Right thalamus>0.58>0.60
 AtrophyHypertrophy
Forebrain<29.00>31.9
Cortical Gray<13.50>16.3
Hippocampus<0.255>0.31
Amygdala<0.10>0.14
Caudate<0.255>0.30
Putamen<0.345>0.375
Pallidum<0.055>0.07
Thalamus<0.495>0.58
Cerebellum<3.50>4.55

GENOMICS

www.survivingmold.com/store1/progene-dx

  • PAX genomics allows for measurement of mRNA and miRNA in serum samples so as to assess metabolic patterns of cellular function based on RNA transcription patterns. [1]

A 2016 paper by Dr Shoemaker and James Ryan set out the underlying genomic abnormalities found in white blood cells that can result in someone suffering from a CIRS diagnosis leading to


[1] Berndston K.

  • chronic inflammation. [1] 14 patients who had failed the normal CIRS protocol were investigated genomically while using VIP.
  • This new RNA sequencing focuses on the abnormal gene expression found in the white blood cells of CIRS patients. Several key immune regulators were found to be differentially expressed over the course of the investigation including CD244, CD3D, CD48, CD 52, granzymes, defensins, and the Ikaros family of lymphoid transcription factors.
  • Two families of genes upregulated in CIRS are alpha defensins (these are antimicrobial peptides which keep bacteria in bodies from spreading by using mucosal layer coating inside the gut, airways or nasal passages) and granzymes (these are cytotoxic proteases found elevated in patients with autoimmune disease and infections). [2] These were downregulated with VIP.
  • The Ikaros family of five different zinc finger transcription factors may indicate a decline in lymphocyte proliferation after treatment with VIP.
  • In addition to these down regulated innate immune functions, there was a significant metabolic shift with a downregulation of ribosomal and mitochondrial gene expression possibly indicating a quietening of the overall upregulated immune response. [3] 
  • Patient reporting of CIRS symptoms decreased from a mean of 12.9 to a 3.3 over the duration of the therapy. TGF beta-1 and C4a were significantly lower after VIP therapy. MMP9 was lower post VIP but not significantly and VEGF was unchanged.
  • In addition, ribosomal genes as well as nuclear encoded mitochondria genes were shown to be down regulated after treatment with VIP and this coincided with the abatement of symptoms.  This argues the return to normal function of ribosomal and mitochondrial gene expression.
  • It is a great advance in the treatment of CIRS that both pre- and post-genomic expression patterns can be measured. Added to the measurement of proteomic expression and Neuroquant evaluation pre- and post treatment, the genomic insights add much additional value to quantifying the patients return to normal functioning.
  • Diagrams per Jimmy Ryan presentation at 2016 Surviving Mold conference Irvine, California.

[1] Ryan J, Shoemaker RC, RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal polypeptide (VIP)shows a shift in metabolic state and innate immune fluctuations that coincide with healing. Medical Research Archives Vol 4 Issue 7 2016.

[2] www.survivingmold.com

[3] Ibid.

Before VIP
After VIP
Mitochondrial proteins pre-vip
Mitochondrial proteins post-vip

OTHER LAB TESTS DONE IN CIRS

  • These lab tests are done to rule out other possible illnesses.
  • CBC, Metabolic panel, Lipid panel, C-reactive protein, ESR, ANA, ENA, Thyroid studies with thyroid antibodies, sex hormones (estradiol, progesterone), pregnenolone, cardiolipin antibodies, PTT, Prothrombin time, Thrombin time, d-Dimer, IgE, Immunoglobin panel, protein electrophoresis.
  • If autoimmunity is suspected, check anti-gliadin antibodies, (due to low MSH and dysregulation of T reg cells) anticardiolipin antibodies, lupus anticoagulant, phospholipid.
  • If mast cell activation syndrome is suspected, consider doing serum histamine, serum tryptase, urinary prostaglandin D2, enolase.

Treatment Steps

Stepwise treatment protocol for CIRS

Dr. Shoemaker’s Surviving Mold Protocol involves a number of specific steps:

It must be kept in mind that CIRS is an inflammatory upregulation of the innate immune system and is thus an immune disorder occurring in genetically susceptible individuals. It will not therefore just respond to removal of the initial triggers. The particular triggers do need to be taken into account, but so does the immune dysregulation, the inflammatory markers, the neurohormonal abnormalities, potential autoimmune dysregulation as well as possible coagulation disorders.  

  1. Removal from exposure – monitor home or WDB with ERMI or HERTS-MI-2 testing
  2. Removal of biotoxins with either cholestyramine or Welchol – monitor with VCS
  3. Treat MARCoNS with BEG spray or EDTA- Check API-Staph nasal culture
  4. Begin a gluten free diet if anti-gliadin antibodies present
  5. Correct abnormal androgens – use DHEA-S if indicated
  6. Correction of elevated MMP-9
  7. Correction of low VEGF
  8. Correction of elevated C3a
  9. Correction of elevated C4a
  10. Reduce elevated TGF-beta-1
  11. Treat low VIP
  12. Recheck labs and VCS

STEP 1: REMOVAL FROM EXPOSURE

  • This is the most important step in the treatment process if a diagnosis of CIRS has been established. Attempt to determine the source of the biotoxin exposure; was it from Borrelia spirochete, dinoflagellate food poisoning or ciguatera. A person may be exposed to one or more of these toxins. If the source is identified, every effort must be made to remove the individual from the source of exposure.
  • If water damaged building is the issue and as up to 50 % of all USA homes have some form of water damage, mold exposure and all the corresponding inflammagens are the most frequent source of biotoxin illness. An ERMI test must be done and a visual inspection must be undertaken by a qualified mold/indoor air specialist. The article Inside Indoor Air Quality by Dr. Ritchie Shoemaker and Dr.  King-Teh Lin is a helpful resource.
  • If an ERMI test is positive with a reading >2, the building or home is considered unsafe for occupation with the CIRS diagnosis.  
  • Once a building has been declared unfit for occupation due to the visual inspection and the patient fulfilling the CIRS diagnosis, a sick patient should most often have to be removed from the building and a mold remediation team is called in.
  • One of the challenges for CIRS patients is what to do with belongings as they often have to be removed (clothing, furniture that cannot be adequately wiped down, contents esp. paper and cloth products and personal effects). All porous material should be removed and taken out of the house and discarded. Non-porous items need to be thoroughly and professionally cleaned.
Diagram: Written permission granted by Dr Lynese Lawson
Diagram: Written permission granted by Dr Lynese Lawson
  • Finding someone who can adequately undertake the remediation is often a major problem. An organized approach to the problem is vital but often is not able to be initiated due to the cognitive difficulties many people face with the CIRS diagnosis.
  • Small brief exposures must be avoided due to “sicker, quicker” phenomenon.
  • Patients that I see are given a list of companies that can assist them in their assessment and remediation process. HEPA filters (IQ air and Blue Sense Air filters) are used which can remove particles smaller than 0.3 microns in size. Air purifiers such as the Air Oasis are also used.
  • It is important that remediation efforts are continued until ERMI levels are down to safe levels – ERMI less than 2 or = 2 in patients with MSH <35; ERMI to < or = to – 1 if MSH <35 and C4a >20,000 with HERTSMI-2 < 11.
  • Post remediation testing should occur 3-5 weeks after remediation. One can place black or green garbage bags and collect new dust.

STEP 2: REMOVE TOXINS AND INFLAMMAGENS

Biotoxins must be removed from the body, particularly in a patient with the genetic predisposition to biotoxin illness. These patients cannot recognize the biotoxins and need help in doing so.

Cholestyramine (CSM), a bile acid sequestrant, has a quaternary cation structure that binds negatively charged ionophore biotoxins which possess an anion dipole. The biotoxins are excreted in bile and removed from the body while bound to the CSM, through the GI tract. This excretion prevents enterohepatic recirculation of the biotoxins. A handout should be given and consent obtained.

CSM can also bind industrial chemicals

  • CSM must be taken on an empty stomach away from meals and medications and/or supplements. 
  • Many people start with ¼ teaspoon a day. Take ½ hour before meals and 1 hour after meals, drugs or supplements.
  • Drink 6 –  8 oz. of water with the dose.
  • Juice is often a better mix for this very chalky tasting medication.
  • Side effects include heartburn, GERD, belching, bloating, nausea, bad tastes and/or constipation.
  • Welchol is a second option, although not as effective. There is said to be a 4:1 differential in terms of efficiency for biotoxin removal. CSM has 4 times as many electrically active sites. However, Welchol may be better tolerated but longer to change lab tests in the right direction.
  • These two binding agents are to be taken until the patient either passes the VCS test and/or eradicate MARCoNS.
  • Some patients combine the two meds: CSM twice per day – morning and bedtime and Welchol – lunch and dinner. Avoid the CSM with aspartame additives.
  • Chemically sensitive patients and patients with GI issues and/or food allergies, do better on Welchol.
  • If problems with toxin release or treatment reactions, start with Actos 15-45mg a day, or EPA 2.4 gms DHA 1.8gms for 5 days, then add cholestyramine again.
  • If Leptin <7 use omega 3s.
  • Watch fat-soluble vitamins A, D, E, K as CSM can bind these.
  • Welchol 625- work up to 2 caps three times per day.
  • CSM dosing: 4 -9 grams four times a day. Mix with 6 oz. water or juice. 30 mins before food. Followed by 4-6 oz. water.  
  • Paed. <120 lbs. or less than 18 years old.  Use 60 mg/kg/dose TID with 6 oz. water 30 mins before food.
  • Use Welchol 625 bid (1 tab) if out and about and exposed to mold.
  •  If re-exposed- use Welchol or CSM for 3 days.
  •  Works within a week.
  • Treat constipation with magnesium oxide or citrate powders. Can use 70 % sorbitol (Miralax).
  • Recheck VCS one month after starting treatment and then with each step.
  • When VCS normalized, switch to Welchol 625 mg twice daily if person is out a lot.
  • If at home mostly, no meds used.
  • If treatment fails, consider continued exposure, non-compliance or MARCoNS not adequately treated.   

STEP 3: ERADICATE MARCoNS

If positive for MARCoNS on API-Staph culture and if associated with a biofilm, eradication is important.

BEG spray:

  • Start one month after using CSM
  • Comprised of Bactroban, EDTA, and Gentamycin.
  • Blow nose first.
  • Use for 30 days 2 sprays each nostril 3 times per day in adults, 1 spray alternative nostril in children- seldom need to use
  • The patient may feel worse after starting treatment due to “die-off”.
  • Use low amylose diet, high dose fish oil and Actos if this occurs.
  • Repeat nasal culture to see if eradicated.
  • If symptoms worse after starting, it may imply re-exposure; VCS row D and E will fall and MMP9 will go up
  • If still positive after treatment, consider pet dog as source of reservoir, re-exposure to mold, or a partner with low MSH and MARCoNS
  • Rifampin has been used in the past at 600 mg per day with adults or 10-20 mg/kg/day in children. Start the rifampin the same day as the BEG spray to discourage resistance
  • Rifampin is known to induce multiple enzymes responsible for drug metabolism including cytochrome P450 (CYP)1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and some glucuronidation pathways. In addition, it has been reported to induce the activity of several drug transporters, such as the organic anion transporter and P-glycoprotein.[1] Need to quite careful with anticoagulants and pain medications (may reduce their efficiency).
  • Recent MARCoNS resistance to multiple antibiotics has emerged due to what Dr Shoemaker believes to be the overuse of -azole antifungals.
  • This step is essential if VIP is going to be successful.
  • If symptoms worsen after 1 month, check for re-exposure, recheck VCS and MMP9 levels.
  • If patient better, stop BEG spray, recheck API- Staph nasal culture and VCS.

[1] http://www.pharmacytimes.com/publications/issue/2011/april2011/druginteractions-0411

STEP 4: ELIMINATE GLUTEN IN AGA POSITIVE PATIENTS

  • If positive for AGA, it is imperative they are completely gluten free for at least 3 months.
  • This will reduce GI sources of inflammation
  • The no-amylose diet prescribed during CSM treatment is already gluten free, thus no gluten continues for an additional 3 months assuming that that the VCS corrected.
  • No amylose diet involves eliminating:
  • Grains- wheat, rice, barley, oats, rye – corn appears to be okay as has a natural inhibitor of amylase- no sugar added.  
  • Fruits-all fruit allowed except bananas. Can use fresh fruit juice.
  • Vegetables – all okay except root vegetables grown below the ground (potatoes, yams, radishes, carrots, beets). Garlic and onions are okay.
  • Other foods –  glucose, dextrose, sucrose, maltodextrin, low-fat corn syrup, cereal, chocolate, fast food, soft drinks, commercial fruit juices. Lactose (milk), artificial sweeteners, spices and condiments, diet soft drinks and caffeine drinks are allowed
  • Many patients will have many other possible food issues including but not limited to IgE allergies, IgG sensitivities, oxalate issues, salicylate issues, FODMAPS issues, SIBO issues, high histamine issues etc. These issues are not part of the Shoemaker protocol but need to be taken into account when addressing and treating chronic GI issues. 
  • If AGA is negative after 3 months, reintroduce gluten and keep monitoring for GI symptoms.
  • If patient feels better off gluten, and/or AGA returns as positive, stay off gluten for life.
  • If a patient is known to have celiac disease, it is imperative he follows a strict gluten free diet for life. [1]

[1] Shoemaker RC. Surviving Mold: Life in the Era of Dangerous Buildings. Otter Bay Books. Baltimore 2010.

STEP 5: CORRECT ANDROGENS: DHEA/Testosterone/Androgens and Cortisol

Treatment:

  • DHEA – 25 -75 mg a day- men. 5-25 mg a day -women
  • HCG injections 125 250 mg twice weekly. This raises LH. Not part of Shoemaker protocol
  • VIP nasal spray 4 times per day for 30 days- can stabilize aromatase and rebalance androgens
  • Measure DHEA before treatment and monitor estradiol levels- at least every 3 months
  • Resist using testosterone replacement
  • Do not use aromatase inhibitors with a low-MSH patient<35, this will cause significant deterioration.

STEP 6: CORRECT ADH/OSMOLALITY

Treatment: Desmopressin Acetate (DDAVP)

  • Use DDAVP when osmolality is high>295
  • Use 0.2 mg every other night to verify tolerance and absence of side effects especially if weight gain. Initial correction of ADH can lead to edema and rapid weight gain due to fluid retention.
  • After 5 doses – check serum osmolality, ADH and electrolytes verifying normal sodium and not too low.
  • If symptoms persist, especially on “off days”, use 0.2 mg daily.
  • Check electrolytes and osmolality after 10 days.
  • Some people (especially those with POTS) may need to be on drug daily for indeterminate basis.
  • Some may need it twice daily.
  • ADH abnormalities usually normalizes over time.
  • This treatment may also correct von Willebrand syndrome and help reduce MMP9 (and C4a) levels. Von Willebrands patients need to carry DDAVP to stop nasal hemorrhage.
  • One needs to taper DDAVP when endpoint of normal ADH for a given osmolality is reached. 
  • Children need to use 1-4 sprays based on weight and age.
  • If odd symptoms occur while on treatment, stop treatment and check electrolytes and serum osmolality.
  • Taurine can cause polyuria and Lithium can cause ADH resistance.
  • Symptoms addressed include polyuria, polydipsia, orthostatic hypotension, recurrent headaches and static shocking.

STEP 7: CORRECT ELEVATED MMP-9

Treatment: Actos and/or EPA/DHA Fish oil

  • The goal of therapy is to upregulate PPAR-gamma production and reduce MMP-9 expression.
  • Lowers TNF, leptin, MMP9, PAI-1, and raises low VEGF.
  • If low leptin-less than 7 or less than 18 years, can’t use Actos.
  • If leptin less than 7, use high dose fish oil: EPA 2.4 mg, DHA 1.8 mg daily.
  • If high or normal leptin, use Actos- low carb/amylose, high protein diet.
  • Actos 45 mg once daily for 30 days.
  • If get swollen and hypoglycemic have to stop.
  • Watch kidney function and blood sugar.
  • Actos is also implicated in bladder cancer with long term use.
  • Takes longer to work but is effective.
  • Recheck labs after 30 days.
  • High MMP-9 patients may get worse when starting CSM with Herxheimer reactions.  
  • Herxheimer reaction defined as- symptoms gotten worse, new symptoms arise, reactivation of old symptoms.
  • With an increase in MMP-9 there is worsening in row E of the VCS test.
  • Trental, progesterone, curcumin, glutamine, glutathione and phosphatidyl choline have been anecdotally shown to lower MMP-9- not part of Shoemaker protocol.

Step 8: CORRECT VEGF – Correction of Hypoperfusion

  • The previous steps may have improved VEGF.
  • If not improved, exercise is added to the protocol to increase low VEGF.
  • Graded exercise below anaerobic threshold 7 days per week is recommended.
  • Patients are asked to start very slowly but may end up exercising to a maximum of 45 minutes
  • Suitable routine eventually may include 15 minutes of cardio, 15 minutes of weights, 15 minutes of abdominal exercises.
  • Corrects low VEGF.
  • Procrit and VIP can increase VO2 max.

Step 9: CORRECT ELEVATED C3a

  • Statins show reduction in T cell activation, macrophage infiltration and vascular wall infiltration.
  • Statins inhibit an enzyme HMG-COA reductase that controls the rate of cholesterol production.
  • Must be used with Coenzyme Q10 (CoQ10) – needed by mitochondria to make ATP.
  • Coenzyme Q10 levels can be measured in the serum.
  • Start Coenzyme Q10 150-300 mg for 10 days.
  • Then start statins – Zocor 80 mg day, Pravastatin, Atorvastin, Fluvastin, Rosuvastatin and Lovastatin may all be used.
  • Statins metabolized by Cytochrome P450 3A4.
  • Drugs that inhibit CYT 3A4= Sporonox, Ketoconazole, Erythromycin, Clarithromycin, HIV protease inhibitors, Nefazodone, gemfibrozil, Biaxin, Ketek and Posaconazole.  
  • No large quantities of grapefruit juice.
  • With Lovastatin, do not exceed 20 mg dose if on danazol, diltiazem or verapamil.
  • Monitor liver function, renal function and creatine.
  • May increase cognitive symptoms and raise blood sugars.

Step 10: CORRECT ELEVATED C4a

  • Reduce C4a with erythropoietin (Procrit) 8,000 units twice weekly (Mon and Thurs) for 5-8 doses with baby aspirin. 40,000 units per vial.
  • Higher doses once per week not effective due to short half-life of 1.5 days.
  • Erythropoietin causes tissue remodeling and repair.
  • Informed consent must be signed as there is a black box warning.
  • Most practitioners now use VIP instead of Procrit.  
  • Monitor CBC, iron studies, blood pressure, D-dimer.
  • Use baby aspirin when using Procrit.
  • Check levels of C4a, TGF beta-1, T reg cells and VEGF before each dose to ensure efficiency of treatment.
  • Ensure no polycythemia occurs thus increase risk for thrombus formation.
  • Keep track of symptoms to see if improvement- breathing easier, increased mental clarity.  
  • High C4a can cause decreased cognitive function due to hypoperfusion.
  • Treating C4a can improve cognitive deficits- memory, concentration, word finding, assimilation of new knowledge, confusion, disorientation.
  • Can use VIP 4 sprays a day if cannot use Procrit.
  • High C4a can cause hypoperfusion and increased brain swelling as seen on Neuroquant. Will see high lactate (>1.29) in frontal lobes and hippocampus and low glutamate/glutamine ratio (<2.19). These findings result in cognitive dysfunction and brain fog.
  • Assess cognitive function: if abnormal, do MRI spectroscopy.
  • If MRI abnormal showing low glutamate/glutamine ratio (capillary hypoperfusion) – then use Procrit. [1]
  • Recheck MRI spectroscopy after Procrit = normal G:G, normal lactate and improvement in 6 areas of cognitive functions.

[1] Shoemaker R. Biotoxin Illness Treatment Protocol pg. 10.

Step 11: REDUCE ELEVATED TGF beta -1

  • Every effort must be made to reduce this biomarker as it represents widespread tissue involvement.[1]
  • Losartan can prevent TH17 conversion of T reg cells and thus correct TGF beta-1 levels.
  • Losartan/Cozaar 12.5 mg bid, up to 25-50mg a day.
  • Child dosage is 0.6-0.7 mg/kg/day bid.  
  • VIP also lowers TGF-b1.
  • Use 4 sprays VIP a day if can’t use Cozaar due to low b.p. Patient must meet VIP criteria.  
  • If CD4+CD25++ T reg cells <4.66% and TGF beta -1 >2,380 and blood pressure normal.
  • Treat with Cozaar 25 mg daily- start with 12.5 mg.
  • Increase to 25 mg bid if necessary.
  • Monitor TGFB monthly and blood pressure daily.
  • Transfer Factor may also reduce TGF beta-1. This is not part of the Shoemaker protocol.

[1] Berndston K. pg. 14 

STEP 12: REPLACE LOW VIP

  • If patients have cleared a number of the Dr. Shoemaker biomarkers (see below) but still have signs of capillary hypoperfusion with fatigue, unusual shortness of breath with exertion and post-exertion malaise, a trial of VIP may be the most effective treatment so far in the treatment protocol.
  • Neuroquant findings will also determine suitability of use
  • Patients must be given a VIP handout before treatment.
  • VIP is dispensed in a brown bottle, must be refrigerated in upright position. It can last for 90 days if stored properly.
  • If deficient in VIP, the final step can provide significant relief.
  • Most people will have at least 75% of their symptoms relieved before starting VIP providing all the preceding steps have been done successfully.
  • All prior steps need to be fulfilled prior to use of VIP:
  • MARCoNS must be eradicated
  • VCS must be normal
  • Lipase must be normal
  • No significant exposure can be tolerated- home must have an ERMI of less or equal to 2 or Health Effects Roster Type Species Mycotoxin and Inflammagen test (HERTSMI-2) must be less than or equal to 10
  • Once decision made to use VIP the following steps need to be taken:
  • Patients must be in the office
  • Pre -VIP administration labs: VIP, MSH (this may be one of the last hormones to correct and may need VIP), TGF-beta-1, C4A, VEGF, MMP-9, CD4+/CD25++, Vit D-25-OH, estradiol, total testosterone and lipase should also be measured
  • Baseline stress echo to measure tricuspid regurgitation/ pulmonary artery systolic pressure (PASP) – verify it does not rise over 8 mm during exercise.
  • CIRS patients will often have over 8 mm Hg elevation of PASP- this can result in palpitations and dyspnea not responsive to asthma medication.[1]
  • After bloods are drawn, test spray one dose 50 mcg in one nostril.
  • Patient observed for any symptom improvement.
  • Vital signs (b. p. pulse) followed every 5 minutes for 3 separate occasions. Look for rash.
  • Watch for improvements in shortness of breath, reduced joint pain and improved cognition.
  • Post-VIP 15 minutes, redraw TF beta-1 and C4a levels. If there is a twofold increase, hidden mold may be present.
  • Patient leaves office if they tolerate the second dose.
  • Dosing thereafter is 1 spray 50 mcg 4 times per day for 30 days.
  • Redo stress echo and blood pressure after 30 days. Redo lipase, C4a,TGF beta-1, VCS.
  • Dosage can be increased to 8 sprays or reduced to less than 4 sprays per day. 
  • One needs to watch for pancreatitis and increased lipase levels. Lipase needs to be checked monthly and any signs of abdominal pain need to be noted.
  • If lipase rises, VIP needs to be stopped.
  • One must check for gallbladder issues if lipase remains elevated.
  • If TGF-beta-1 and VCS are stable, lipase is normal and symptoms are improving, VIP can continue for 30 days tapering to twice daily and then discontinued.
  • Check at 6 months when off VIP: lipase, VCS and stress echo for any changes to PASP.
  • Can use VIP for up to 4 years without adverse effects.
  • Patients with MCS and chronic fatigue syndrome may improve over time. CFS patients will have low VIP.
  • Can use Cialis 20 mg 3 times per week if VIP low and poor response to exercise.
  • VIP will increase CD4 + CD25 + FoxP3 and reduce shortness of breath and cognitive problems.
  • However, reduced joint stiffness may be seen in as little as 10 minutes as it causes immediate endorphin release.
  • Improved exercise tolerance will occur as well as overall all symptoms will improve.
  • Tight clenched hands can open and patients able to take a deeper breath on VIP.
  • Immediate pain relief is a huge relief for most patients.
  • Cognitive issues respond more slowly.

[1] Shoemaker R. Biotoxin Illness Treatment Protocol pg. 12.

Re-exposure Protocol

The phrase used by Dr Shoemaker is that patients previously exposed who are re-exposed will become “sicker-quicker” due to the immediate upregulation of immunological markers.

The following steps to be used if re-exposed:

  1. Treat with CSM or Welchol immediately. A VCS is an excellent idea to monitor biotoxin exposure. Measure key labs:  C4a, leptin, MMP-9, TGF beta-1, VEGF, von Willebrands (if bleeding).
  2. Patient to move to safe environment immediately the issue is discovered.
  3. Stay off binders and other meds if patient’s labs and VCS stable

Re-exposure Trial

If it is needed to prove that a certain building is unsafe for occupation, the following protocol can be followed: SEQUENTIAL activation of innate immune elements (SAIIE)

  • After CSM use has ended, draw the following labs: C4a, TGF beta-1, MMP9, leptin, VEGF and CD4+CD25+
  • Stop all treatment meds- CSM and Welchol.
  • Stay away from building for 3 days
  • Document symptoms having been away from the building for 3 days. Do VCS and do same labs as above.
  • Return to the suspicious building for 8 hours on no meds. Record symptoms and redo above labs
  • Return to building for a second 8 hours on the second day. Record symptoms and redraw same labs
  • Return for the 3rd day, document symptoms and obtain labs.
  • Restart medications. Record symptom scores, and VCS. Labs get scored by office.

   VIII Sequential Activation of Innate Immune Elements (SAIIE)[1]


[1] http://www.tequestafamilypractice.com/articles/CIRS_Overview.htm#SAIIE

BASELINEDAY 1DAY 2DAY 3
VCSDeceasingDecreasingDecreasing
C4aIncreasingIncreasingIncreasing
VEGFIncreasingDecreasing (2 to TGF β-1)Decreasing
LeptinStableIncreasingIncreasing
MMP9StableSpikesIncreasing
vWF Factor VIIIDecreasingIncreasingNormalizes
vWF RistocetinNormalDecreasingDecreasing/may bleed on day 3
CD4+CD25+DecreasingDecreasingDecreasing
Compare to baselineC4a, VEGFLeptin, MMP9MMP9, CD’s, VEGF, & symptoms

Scoring the SAIIE;

  • Compare the C4a on day 1 to baseline
    • Compare Leptin on day 2 to baseline
    • Compare MMP9 as average of day 2 and 3 to baseline
    • Compare VEGF to baseline; rise on day 1, fall by day 3
    • Compare symptoms day 3 to baseline.
    • Add the values

 SAIIE Scores;

  • 5 for 100%; 4 for 80%, 3 for 70%, 2 for 60%, and 1 for 50%
    • Controls mean is 6.3
    • Cases mean is 17.9
    • TGF β-1 rapidly changes
    • CD4+CD25+; it drops rapidly.

 What is SAIIE really showing?

  1. Looking at the progression of innate immune responses- extremely sensitive C4a and TGF β-1
    1. Gene activation following receptor resistance (leptin)
    1. Bottom line; this is absolute proof of causation.
    1. A/B/B’/A/B research design.
      1. A Person at baseline
      1. B Intervention fixes them
      1. B’ Stop medicine
      1. A Re-expose
      1. B Intervention fixes them again

   This is demonstrative of:

  1. Pattern recognition; antigen presentation gone awry
    1. Inflammatory responses not controlled, neuropeptides are depleted
    1. Innate immune abnormalities become chronic as a host-response syndrome

Summary

Patients who present with a CIRS diagnosis, at present, have an enormous amount of information to ingest and, on occasion, significant skepticism to overcome. Skepticism usually rises when the patient returns to the primary care provider or specialist, to discuss the diagnostic and therapeutic path that may have been outlined. There is a common saying in life, “what you are not up on, you are usually down on.” Nowhere is this more evident than in the world of medicine. It is not uncommon for medical doctors to dismiss outright any information that is not part of their consensual reality. Even if one is not trained in this area of emerging medicine, it still requires a deep commitment to study the literature, learn the diagnostic and therapeutic criteria for CIRS and apply them to complex multi-symptom, multi system patients who fit the CIRS diagnosis.

At present, the CIRS diagnosis may be dismissed, diminished, misdiagnosed or misunderstood. It may take some time before the full scope and implications of this diagnosis make its way into clinical practice and hence consensual reality. In the meantime, it is incumbent upon practitioners of the CIRS protocol to continue learning the emerging science, particularly the role of genomics in the diagnosis and treatment protocol.

Adequate standards of remediation are another problem many patients frequently encounter. Too often I have heard of patients phoning a mold specialist who does not perform an adequate attic to basement visual inspection of the house but instead does an air sample and proclaims that the home is “mold free.”

Thanks to the recent Consensus Statement on the investigation and remediation of water-damaged buildings in case of CIRS-WD, [1] specific guidelines now exist for patients, practitioners, and indoor air practitioners to follow in cases of those patients with a known CIRS diagnosis.

It will take some time before critical mass is reached and this diagnosis and treatment protocol makes its way into everyday clinical practice. Having worked with the Dr. Shoemaker protocol for over five years, it has been my experience that if a patient is correctly diagnosed and follows the protocol exactly as it has been set out, the possibilities in their returning to good, if not excellent health, are directly proportional to the effort he applies to strictly following the diagnostic and treatment criteria. It is certainly a rewarding moment to witness patient’s symptom scores fall away as he makes progress with the protocol. The protocol does not produce overnight miracles, but at each step of the way, gains are made as the patient’s lives slowly return to normal. It is a wonderful experience to be a part of this transformation.


[1] Schwartz L, Weatherman G, Schrantz M, Spates W, Charlton J, Berndtson K, Shoemaker R. Indoor Environmental Professional Panel of Surviving Mold – Consensus Statement

How Does Time Restricted Eating and Intermittent Fasting Work? Part II

How Does Time Restricted Eating and Intermittent Fasting Work? Part II

Intermittent fasting or IF is a practice involving alternating fasting time and/or calorie restriction with periods of feeding that has proven cellular benefits, metabolic gains and remission or reversal for a variety of symptoms and disease states. Time restricted eating is compressing an eating window to a specific number of hours each day. An example of this would be eating all the day’s food within a 6–8-hour window. 

With the prevalence of obesity and chronic disease impacting our healthspan and quality of life, implementing the practices of intermittent fasting or time restricted eating may prove to be an important lifestyle tool for maintaining health and vitality as we age.

In Part One of this series, I went into detail about how intermittent fasting and time restricted eating works along with the long list of health benefits that have been linked to these lifestyle tools. In today’s article, Part Two takes a more practical view regarding the different ways to structure intermittent fasting and time restricted eating. We will also cover some of the most common questions about the safety and details of these two lifestyle practices. This will essentially be a guide to intermittent fasting and time restricted eating for beginners and experienced fasters alike.

This article covers the following topics:

  • How to intermittent fast
  • Does intermittent fasting work?
  • Intermittent fasting times
  • How to do time restricted eating
  • Is intermittent fasting and time restricted eating safe?
  • Are these two practices different for men and women?
  • Can you drink coffee or tea?
  • Does intermittent fasting and time restricted eating promote weight loss?
  • Can a ketogenic diet be combined with intermittent fasting and time restricted eating?

By the end of this article, you’ll know if intermittent fasting and time restricted eating are for you and how to get started.

Time restricted eating meal plan hours – 16:8, 18:6, and 20:4

There are many ways to implement a time restricted eating and/or intermittent fasting plan. Let’s look at some of the most popular schedules for time restricted eating and intermittent fasting.

Type of time restricted eating or intermittent fastingExplanationSample scheduleWhat to eat in your windowTips
Time restricted feeding (TRF)Fast for 16 hours overnight and condense meals into an 8-hour windowFinish dinner by 8 pm then fast until 12 pm the next dayRegular dietMay be practiced daily or a few times per week
Time restricted feeding 18:6 (TRF)Fast for 18 hours overnight and condense meals into a 6-hour eating windowFinish dinner by 6 pm and fast until 12 pm the next dayRegular dietMay be practiced daily or a few times per week
Time restricted feeding 20:4 (TRF)Fast for 20 hours overnight and condense meals into a 4-hour eating windowFinish dinner by 6 pm and fast until 2 pm the next dayRegular dietMay be challenging to meet nutrient needs if practiced daily
One Meal A Day (OMAD)Eat only one meal per day and fast for 23 hoursEat between 12 pm and 1pm each dayRegular dietMay be challenging to meet nutrient needs if practiced daily 
Alternate Day Fasting (ADF)24-hour fast every other dayFor example Monday – Fast Tuesday – Eat Wednesday – Fast Thursday – Eat  Regular dietSafe for several months, long-term challenges (1)
5:2 fasting (periodic fasting)24-hour fast 2 days per weekMonday, Tuesday – Eat Wednesday – Fast Thursday, Friday – Eat Saturday – Fast Sunday – EatRegular diet 
Fasting-Mimicking Diet (FMD)5 days of plant-based dietMay be practiced monthly for between 3 and 6 monthsPlant-based diet of 800 to 1000 calories per dayFood available through Prolon or Whole Food FMD program, available through the Hoffman Centre

With so many options, it may be challenging to determine how to start time restricted feeding or intermittent fasting. For example, do you just dive in or do you ease into it more slowly? I recommend starting with either time restricted feeding (TRF) or with the fasting-mimicking diet. (FMD). With that experience, you can then work with your provider or myself to determine if you’d benefit from other practices.

TRF may begin with a simple 12:12 schedule, meaning that you begin fasting overnight and then eat your regular diet within a twelve-hour eating window. For many people this isn’t that much different from their typical pattern, although they may have to be aware of any tendencies for late night snacking. A fast from 8 pm until breakfast at 8 am the following day is a good schedule to start with. Once you have this under your belt, you can expand your fasting window, in increments if needed, to a fourteen-hour fast with a ten-hour eating window. You can then potentially lengthen this to include a fast of sixteen hours or longer.

The fasting-mimicking diet (FMD) is a five-day program, typically practiced once per month for between three and six months, and then one time every 3-4 months as a maintenance program. During the five day fast, you follow a plant-based, calorie-restricted diet. The diet is derived from plant sources like vegetables, nuts, seeds, and fruit. The diet relies on plant foods for protein, olives, coconut and nuts and seeds for healthy fats. The diet constituents are carefully chosen by a nutritional expert. There is a commercially available program involving packaged constituents called ProLon.

With calories restricted to approximately between 750 and 1100 per day, with day one containing the most calories. This represents a réduction in calories of around 50 to 60 percent, this diet is designed to mimic molecular and cellular fasting while increasing patient compliance. The stomach sees food, while the cells see fasting. (2, 3)

The fasting mimicking diet has been clinically studied as a therapy for a variety of conditions including autoimmunity, breast cancer, and metabolic disease such as heart disease and diabetes. Extensive studies in mice have been completed, along with a few human clinical trials.

In the most recent randomized controlled trial from 2021, obese women received either a five-day fasting mimicking diet or their typical diet with a calorie deficit of 500 calories each day. This particular study didn’t indicate a difference in weight between the two groups, but the women following the fasting-mimicking plan showed reduced insulin resistance and improved appetite regulating hormones, along with preserved muscle mass and metabolic rate. (4)

At the Hoffman Centre, Justine leads a whole food fasting-mimicking program which I’ve personally undertaken three times and seen the dramatic results. An additional benefit to this structure is the group dialogue component and support provided throughout the process.

Learn more about this program here

It’s important to note that many fasting trends such as juice fasting don’t have the same benefits and may even have risks. Prolonged fasting of more than two days without food may contribute to electrolyte imbalances, dizziness, exhaustion, and other symptoms, making compliance quite challenging. Both time restricted feeding and the fasting-mimicking diet offer the benefits of fasting with intermittent fasting rules that are easy to follow.

Frequently asked questions

Let’s dive into some of the most common questions that I’m asked about intermittent fasting and time restricted eating, who it’s recommended for and who it’s not recommended for, along with some details to help you feel more confident moving forward.

Are intermittent fasting and time restricted eating safe?

Intermittent fasting and time restricted eating are safe and effective practices for many people. However, it’s important to work with your doctor, especially if you have a medical condition or take any medications. A doctor should look at your medical history, complete a physical exam, and review any laboratory testing. Please however note that your doctor may not be that familiar with these approaches to nutrition nor know the science behind it. Be sure that you are practicing the most well informed kind of patient advocacy and be prepared to educate you doctor on the subject .

While intermittent fasting and time restricted eating might be beneficial in a variety of medical cases, as explained in Part One, there are many cases in which intermittent fasting and time restricted eating are not indicated including:

  • Pregnancy and lactation
  • Anorexia, underweight, or chronic malnutrition
  • Type 1 diabetes or insulin-dependent Type 2 diabetes (as insulin requirements may plummet dramatically requiring a lowering of insulin dosing)
  • Recent stroke or heart attack
  • Pulmonary embolism or deep vein thrombosis
  • Cardiac instability or atrial fibrillation
  • Advanced kidney disease
  • Advanced liver disease
  • Advanced heart disease
  • Porphyria, MCAD
  • Inability to discontinue medications
  • Inability to obtain adequate rest while fasting
  • Active growth, such as with children or adolescents
  • Current fever, cough, or signs of an active infection (5)

Alternatively, if you’re working on any of the following imbalances or disease states, it may be worth discussing intermittent fasting and time restricted eating with your personal doctor or with myself.

  • Excess weight or obesity
  • Elevated cholesterol
  • Elevated blood pressure
  • Cardiovascular disease
  • Metabolic syndrome or type 2 diabetes
  • Lymphoma and other cancers
  • Digestive imbalance, including SIBO
  • Autoimmune disease
  • Dependency or toxicity

Fasting side effects may include fatigue, weakness, headache, dry mouth, menstrual irregularity, memory impairment, muscle pain, constipation, sugar cravings, and brain fog. Be sure to stay well hydrated and avoid strenuous exercise or extreme environments while fasting. Fasting is the ideal time for rest.

Is intermittent fasting and time restricted eating different for men and women?

While much of the initial intermittent fasting research has been conducted on animals and human men, we’re starting to learn more about the unique needs of women when it comes to fasting. Whereas men have similar hormonal patterns from day to day, women’s hormones fluctuate on a monthly cycle and then decline through perimenopause and menopause. You can learn more in my article on hormone replacement therapy.

Women seem to be more sensitive to over-fasting and restricting their food intake too much, too often. They might see imbalances in stress hormones, thyroid hormones, and sex hormones. In extreme cases, too much fasting may lead to amenorrhea or the loss of a woman’s period, especially when percentage body fat drops below a certain percentage. When it comes to intermittent fasting for women, it’s important to note that more fasting isn’t always better. A less-is-more-approach often applies.

And while each woman is different, it’s challenging to provide advice for fasting in women on a worldwide basis. For example, some women with autoimmune disease do very well with implementing intermittent fasting practices, while others might do more poorly. Remember that fasting is a stressor on the body and this can be a good stressor that leads to autophagy, detoxification, and cellular rejuvenation. Yet if the system is already stressed, fasting can sometimes be the straw that breaks the camel’s back. Often, if a woman is exhausted, overwhelmed, and feeling burnt out this isn’t the time to add even more stress.

In a study of obese women, intermittent fasting combined with calorie restriction was shown to reduce weight over a ten-week period. (6) However, many restrictive methods work in the short-term and we may need to learn more about the long-term results of fasting for women.

In another study comparing men and women in a forty-eight-hour fast, it was noted that women tend to accumulate triglycerides in their muscles, while men accumulate these in their livers, although other physiological aspects during the fast were similar. (7) We certainly need more research to further establish the differences related to long-term fasting practices and the different types of intermittent fasting between men and women regarding the potential benefits fasting.

As always with functional medicine, a personalized approach is best. As discussed above, I recommend starting with gentle time restricted feeding or with the fasting-mimicking diet.

Can I drink coffee or tea during fasting hours?

This question about hot drinks usually leads to hot debate! Whether you can drink coffee while intermittent fasting may depend on what works best for you as an individual.

Experts in the fasting field recommend “complete abstinence from all substances except pure water.” (5) Biological fasting is the absence of anything that triggers nutrient-sensing pathways. (3) This certainly means no protein, carbohydrates, or fats, but most likely no vitamins, minerals, or plant compounds either.

While black coffee or tea, doesn’t contain any calories, it does contain caffeine, which can influence the hormones cortisol and insulin. It also contains phytonutrients, the antioxidant compounds that are absorbed and which rely on digestion and metabolism.

So, what can you drink during intermittent fasting? If you want to be a purist, stick to only water during your fasting window then enjoy coffee or tea with your first meal of the day or at any time within your eating window.

After that, you can experiment with plain coffee or tea within your fasting window and see whether it improves, or deters from, your results. Coffee or tea with added fat, such as bulletproof coffee, should be enjoyed during the eating window.

Does intermittent fasting and time restricted eating help with weight loss?

Weight loss is difficult and traditional strategies are largely based on reducing calories and increasing exercise. However, these strategies, especially extreme versions, typically only produce short-term results. Many factors contribute to weight, including hormones, sleep, stress, nutrient levels, toxin exposure, mindset, and so much more. Simply looking at calories doesn’t always address the situation and a short-lived fast may only result in a Band-Aid effect. Yet for some, even a quick boost in hope and confidence that the body can lose stubborn weight can be a catalyst for deeper change. That’s why discussing how to use fasting with a trained professional is key.

Using intermittent fasting and time restricted eating for weight loss might be a solution, or just part of the weight solution, especially for someone who spends the majority of their time in the fed state. Fasting might provide the metabolic balance that will address some of the underlying physiology contributing to weight gain, such as inflammation, elevated insulin, and oxidative stress.

In a review of different types of intermittent fasting, IF produced similar weight loss results to those derived from caloric restriction. 5:2 fasting was similar to restricting daily calories in nine out of eleven studies. In addition, the majority of the weight loss occurred in the first three months before weight hit a plateau and results were similar with different distributions of macronutrients. Time restricted feeding and caloric restriction also seemed similar as far as weight was concerned. (8)

In a long-term study that compared alternate day fasting or ADF with daily calorie restriction in obese adults, weight loss after one year was 6 percent in the ADF group compared to 5.3 percent in the calorie restriction group, so there wasn’t a huge difference. (9)

When examining human studies involving individuals with diabetes, those practicing time restricted feeding as opposed to consuming six small meals per day lost more weight. The studies also showed more results with intermittent fasting in terms of decreasing A1C and blood glucose, which are markers of diabetes, compared to a common recommendation of eating frequent small meals. (10)

The definitive answer to this question regarding the intermittent fasting weight loss diet may not be clear in the science. However, I’ve seen it used successfully in my practice for patients who are good candidates, along with other functional medicine interventions.

Does intermittent fasting and time restricted eating work while following a ketogenic diet?

Ketogenic diets, time restricted eating, and intermittent fasting are often discussed as going hand in hand. Keto, which is an abbreviation for the ketogenic diet, is a high fat, low carbohydrate eating pattern that in its own way mimics the fasting state through the restriction of dietary glucose. The ketogenic diet, time restricted eating, and intermittent fasting all have the potential to increase ketones in the blood that can be used as fuel by the cells instead of them employing glucose. The ketogenic diet combined with time restricted eating and intermittent fasting may also have similar benefits related to a treatment approach to chronic and metabolic diseases.

To answer the question, yes, intermittent fasting and time restricted eating can be combined with a ketogenic diet. Those following a ketogenic diet that are in a state of ketosis, where the body is efficient at turning fat into ketones and using them as fuel, may have a better experience with fasting and fewer negative side effects. Similarly, those with an existing fasting practice might have an easier time transitioning to a ketogenic diet because their metabolism is already primed to use ketones.

So, while intermittent fasting or time restricted eating combined with a keto diet may certainly be an important dietary approach for some people healing from chronic disease or working to promote longevity, it may be too restrictive for others. This is another reason why working with an experienced practitioner can be so helpful. You can dial in your nutrition plan and then have support adjusting, and even expanding, the diet over time.

We all want to remain healthy and high-functioning as we get older, but it’s about more than living a long time. It’s about improving our quality of life. Intermittent fasting is meant to mimic the balance between feast and famine that humans have always experienced throughout history. Regular feasting is a relatively recent development and this excess time in the fed state may deter us from experiencing all of the important health and longevity benefits that come from fasting. The best part about intermittent fasting is that it makes fasting simple, gentle, and fit into modern life.

To learn more about working with me individually or to join our next group fasting-mimicking diet, please contact my office.

References:

  1. Stekovic S, Hofer SJ, Tripolt N, et al. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans [published correction appears in Cell Metab. 2020 Apr 7;31(4):878-881]. Cell Metab. 2019;30(3):462-476.e6.
  2. Di Francesco, A., Di Germanio, C., Bernier, M., de Cabo, R. A time to fast. Science. 2018;362(6416),770-775.
  3. Hong, K. Intermittent Fasting and Fasting Mimicking: Clinical Applications. Presentation. University of Southern California.
  4. Sadeghian M, Hosseini SA, Zare Javid A, Ahmadi Angali K, Mashkournia A. Effect of Fasting-Mimicking Diet or Continuous Energy Restriction on Weight Loss, Body Composition, and Appetite-Regulating Hormones Among Metabolically Healthy Women with Obesity: a Randomized Controlled, Parallel Trial [published online ahead of print, 2021 Jan 9]. Obes Surg. 2021;10.1007/s11695-020-05202-y.
  5. Goldhamer, A. Can Fasting Save Your life. TrueNorth Health Center.
  6. Klempel MC, Kroeger CM, Bhutani S, Trepanowski JF, Varady KA. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr J. 2012;11:98. Published 2012 Nov 21.
  7. Browning JD, Baxter J, Satapati S, Burgess SC. The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men. J Lipid Res. 2012;53(3):577-586.
  8. Rynders CA, Thomas EA, Zaman A, Pan Z, Catenacci VA, Melanson EL. Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Nutrients. 2019;11(10):2442. Published 2019 Oct 14.
  9. Trepanowski JF, Kroeger CM, Barnosky A, et al. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Intern Med. 2017;177(7):930-938. doi:10.1001/jamainternmed.2017.0936
  10. Muñoz-Hernández L, Márquez-López Z, Mehta R, Aguilar-Salinas CA. Intermittent Fasting as Part of the Management for T2DM: from Animal Models to Human Clinical Studies. Curr Diab Rep. 2020;20(4):13. Published 2020 Mar 12.

How Does Time Restricted Eating and Intermittent Fasting Work? Part I

How Does Time Restricted Eating and Intermittent Fasting Work? Part I

If you’re interested in living a healthier lifestyle, you’ve probably heard of time restricted eating, or intermittent fasting and the success stories associated with incorporating these practices into your life. Despite living longer these days, the healthspan of many Americans is actually cut short as the average person spends seventeen of their final years living in poor health. This is due to chronic diseases such as diabetes, heart disease, cancer, and Alzheimer’s. In fact, 80 percent of older adults have at least one chronic condition, which is primarily related to their lifestyle.

What if time restricted eating or intermittent fasting could be a solution, one of the tools in the kit, to help combat the underlying factors that contribute to such diseases? Is time restricted eating and intermittent fasting simply a diet trend? Or is there a substantial and credible scientific basis to warrant its therapeutic use?

In this two-part series, we’ll explore these questions, and more.

In Part One we’ll examine the nature of time restricted eating and intermittent fasting, how it works, and the health benefits of both practices.

Part Two will cover methods of fasting and time restricted eating, along with answers to the most commonly asked questions regarding this popular practice.

What are time restricted eating and intermittent fasting?

Time restricted eating, (TRF) and intermittent fasting, also referred to as IF, are often treated as if they are one and the same, but there are actually some major differences between the two.

Time restricted eating involves simply alternating periods of eating with periods of fasting. With TRF, all of your eating is compressed into a 1 -12 hour feeding window. Most hours of the waking day, you’ll spend in a feeding state—say from 8:00 am to 4:00 pm. The other hours, you don’t consume any calories, although you are allowed calorie-less drinks, like water, sparkling water, decaffeinated tea and black coffee. Some people, (known as OMAD’s), eat only one meal a day (OMAD) and fast for 23 hours. 

The term intermittent fasting can be confusing and inaccurate. The term ruffles some researchers feathers because there are many different forms of fasting or restriction. It’s important to distinguish between them. The other problem with the term intermittent fasting is the flexibility around the term “fasting.” Most studies on various intermittent fasting schedules allow up to 700 calories per day on fasting days, while others don’t allow any calories. I want to be very particular about the definitions because I think different forms of fasting and different types of restriction may have different physiologic effects, and by lumping all forms of fasting together, we may dilute such insights.

Intermittent fasting includes the fasting-mimicking diet or FMD, where your intake is restricted to between 750 and 1050 calories (approximately) per day for a five-day period out of the month. This has been shown to mimic some of the physiological benefits of water fasting.

In addition, intermittent fasting also includes alternate day fasting or ADF. With this type of fasting a regular diet is followed for one day followed by a day of fasting. Another option is 5:2, which involves five days of regular eating followed by two fasting days in one week. With each of these methods, the fasting days can feature either a water fast or a calorie-reduced diet.

In contrast, a long-term or prolonged fast is considered more than two days and up to several weeks without food.

As you can see, there are several versions of intermittent fasting in which individuals can engage and that have been explored with scientific research. I’ll cover these in more detail when we discuss an intermittent fasting schedule and how to implement it in Part Two of this series.

How intermittent fasting works

If we take a look back in time to more ancestral or hunter-gatherer ways of eating, feasting was always balanced with famine. There were naturally times of the year when food was abundant and times of the year when food was scarce. The human body has the ability to adapt and thrive in both cases.

With the onset of our modern agricultural system, most of us in the developed world no longer have natural periods of fasting and life is a perpetual feast. We have access to whatever food we desire, grown anywhere in the world, every day. It’s no wonder that rates of obesity are the highest they’ve ever been, leading to inflammation and chronic disease. These days the body’s systems never have an opportunity to rest and reset.

So how exactly does intermittent fasting work? To answer this question, we need to go behind the scenes and into the cell to understand what’s happening on the cellular level, in both the fed state and the fasting state.

When we eat a meal, the body’s system is dedicated to processing food, which places the cell in growth mode. Insulin levels are higher, signaling the cell to grow. More specifically, insulin signals mTOR, meaning mammalian target of rapamycin, which instructs the cell to grow and divide. mTOR also decreases autophagy, the process of cellular recycling, that’s predominant during fasting and important for regular repair and maintenance of the cell. (1)

Autophagy naturally declines with age and decreased autophagy is related to neurodegenerative disease, cardiomyopathy, cancer, metabolic syndrome, suppressed immunity, and signs of aging. Boosting autophagy by means of intermittent fasting methods may help to slow or reverse these changes.

In the fasting state AMPK, or 5’ AMP-activated protein kinase, slows down mTOR. This causes fat breakdown and works to activate autophagy, allowing the body to run on its own stored fuel in the form of fat. AMPK also cleans up and repairs parts of the cell that don’t work, an important process that contributes to healthy aging and preventing diseases such as cancer. (1)

In addition, fasting, intermittent fasting, and calorie restriction down regulates IGF-1, or insulin-like growth factor-1. IGF-1 signaling is important for protein synthesis, as well as blood sugar regulation and growth. Later in life, increased IGF-1 can accelerate the aging process and decreasing it, through methods such as IF or time restricted eating, may increase longevity. Studies in mice indicate that employing different types of intermittent fasting can result in an increased lifespan. (1)

When food is scarce, the body conserves energy by downregulating or decreasing both mTOR and IGF-1, which increases stress resilience and protection on the cellular level. In fact, this can be considered inner rejuvenation, which reduces inflammation and increases autophagy. The results include increased stem cell regeneration and improved immunity, especially during fasts lasting more than a few days or by means of fasting-mimicking. (1)

Decreasing IGF-1 also decreases cellular senescence, in which the cell loses its ability to divide, as measured by telomere length. This process of cellular senescence is caused by underlying factors that produce oxidative stress, changes in the epigenetic gene expression, metabolic dysfunction, and mitochondrial dysfunction and the process is considered irreversible. However, decreasing IGF-1 or mTOR increases sirtuins, via the antiaging molecule NAD+, autophagy, and enables DNA repair. (1)

When the body is in a fed state, cells are highly acetylated so that genes are turned on. This helps cells to survive and proliferate. When these genes are on, the ones that are more related to fat metabolism, stress resistance, and cellular repair are turned down. (1)

This is what happens metabolically throughout a longer fast or a fast-mimicking diet over the course of five days.

  • 12 hours: The body transitions from primarily using glucose as fuel to increasing ketones as the preferred fuel for cells, including cells in the brain. (2) This causes an increase in BDNF, or brain-derived neurotropic factor, which allows for increased brain plasticity and neurogenesis. (1)
  • 18 hours: Ketone levels continue to rise. More ketones lead to a decreased need for glucose and insulin, along with more BDNF.
  • 24 hours: Cells increase autophagy, allowing for recycling and the breakdown of old or broken cellular components. (3)
  • 48 hours: Growth hormone (GH) is five times higher than normal, helping to preserve lean muscle mass, reduce fat, and is important for longevity. (4)
  • 54-72 hours: Insulin sensitivity increases and new stem cells and immune cells form. (5)

In summary, on the cellular level, fasting results in the following:

  • Decreased mTOR
  • Reduced IGF-1
  • Increased AMPK
  • Increased autophagy
  • Greater NAD+ and sirtuins
  • Increased ketones
  • Increased BDNF
  • Increased GH
  • Reduced levels of insulin and blood glucose
  • Decreased cellular senescence
  • Increased fat metabolism
  • Improved resistance to cellular stress
  • Reduced inflammation

Our bodies still need both the fed and fasting state, but in our modern culture the balance strongly favors always being fed. Intentional fasting may be a way to add greater balance to the system by allowing for these natural cellular processes that primarily happen in the fasted state.

Health Benefits of Intermittent Fasting and Time Restrictive Eating

Now that we’ve covered the science of fasting and time restricted eating, the question I’m often asked is whether these practices work in regard to health and longevity. This is an exciting area of study, using a wide variety of animal models, along with increasing numbers of studies in humans, in order to decipher the potential benefits of intermittent fasting and implementing time restricted eating.

Research has indicated a number of positive clinical benefits related to intermittent fasting and time restricted eating

  • Weight loss
  • Changes in body composition/fat loss
  • Improved insulin sensitivity or decreased insulin resistance
  • Reduced oxidative stress
  • Increased cellular autophagy
  • Stem cell regeneration
  • Optimized neurogenesis
  • Enhanced parasympathetic nervous system response
  • Improved gut motility, which is important for conditions like SIBO
  • Reduced heart rate
  • Reduced blood pressure
  • Improved lipid/cholesterol balance
  • Improved cognitive function
  • Improved detoxification
  • Improved physical performance
  • Improved sleep patterns
  • Improved immunity (1,6,7)

Taken together, all these clinical benefits translate into important applications related to longevity and chronic disease reversal. Intermittent fasting results are clearly beneficial for a variety of disease states and populations, including those with cardiovascular disease, diabetes, obesity, dementia, cancer, depression, and a number of other conditions. (6,7)

Intermittent fasting addresses the metabolic root causes that contribute to disease over time. IF and time restricted eating may be an important lifestyle tool, along with diet, physical activity, and stress reduction, that brings health more into balance.

In Part Two of this series on intermittent fasting, we explore the specifics of the different types of intermittent fasting, along with how to implement an intermittent fasting schedule. We’ll then cover some frequently asked questions on the topic and provide details and guidance to get you started.

If you’re looking for more personalized guidance, or are interested in our whole food fasting-mimicking program available through Justine Stenger and the Hoffman Centre for Integrative and Functional Medicine, please contact us for more information.

References:

  1. Hong, K. Intermittent Fasting and Fasting Mimicking: Science and Molecular Mechanisms. Presentation. University of Southern California.
  2. Anton SD, Moehl K, Donahoo WT, et al. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring). 2018;26(2):254-268.
  3. Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton JL, Kiosses WB. Short-term fasting induces profound neuronal autophagy. Autophagy. 2010;6(6):702-710.
  4. Hartman ML, Veldhuis JD, Johnson ML, et al. Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men. J Clin Endocrinol Metab. 1992;74(4):757-765.
  5. Klein S, Sakurai Y, Romijn JA, Carroll RM. Progressive alterations in lipid and glucose metabolism during short-term fasting in young adult men. Am J Physiol. 1993;265(5 Pt 1):E801-E806.
  6. Hong, K. Intermittent Fasting and Fasting Mimicking: Clinical Applications. Presentation. University of Southern California.
  7. Goldhamer, A. Can Fasting Save Your life. TrueNorth Health Center.
  8. Rynders CA, Thomas EA, Zaman A, Pan Z, Catenacci VA, Melanson EL. Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Nutrients. 2019;11(10):2442. Published 2019 Oct 14.

Patient Questions – HRT and Weight Gain

hormone replacement therapy weight gain

Question 

I’m an active baby boomer who tries to stay in good shape. I walk a lot, go to aerobics twice a week, inline skate in summer, and curl twice a week in the winter. I try to eat healthy food but I’m finding it nearly impossible to lose that excess fat around my waist. My question is, does taking hormonal drugs, such as Premarin and Prometrium, have any effect on trying to lose weight? I’ve tried several times to get completely off the drugs and although I’m only taking half my original dosage, I can’t bear the hot flashes and night sweats without the drugs. I personally believe that I’d be better off without the drugs but I don’t know if it would then be any easier to lose the abdominal fat.

Thank you,
Cathy 

Answer 

Dear Cathy,

Your letter has raised a number of very pertinent questions that every woman that’s approaching menopause should be aware of. 

First of all, we know that the negative conclusions reached by the Women’s Health Initiative study¹ led to 50 percent of women being removed from or voluntarily stopping their hormone replacement therapy. The negative findings were suggestive of an increased risk of heart disease, strokes, breast cancer, and dementia.

However, in later reviews and critiques of the study, many researchers have reversed some of their earlier conclusions. Please see my blog post on this subject, entitled Risks of Hormone Replacement Therapy in Women. The researchers suggest that women become informed regarding the many helpful benefits of hormone replacement therapy, not just about the symptomatic treatment of hot flushes and night sweats. In the journal Fertility and Sterility in December 2005, the authors critiqued the study design and proposed two major reasons why the original authors of the study reached the conclusions that they did². The authors criticized the use of continuous combined estrogen/progestin or estrogen alone as a standard regime to an aging female population with little previous hormonal treatment, who because of their age were naturally predisposed to cardiovascular and cerebrovascular disease. The authors also criticized the use of continuous synthetic progestin or Provera, which is known to have significant side effects and has been linked to increasing rates of breast cancer. There are now over a hundred published studies indicating that estrogen can be safely prescribed to women with a history of breast cancer. The hormone estrogen when prescribed alone, rather than in combination with the synthetic progestin Provera, hasn’t been found to be harmful in any study to date. The hormone combination Prempro was to blame and more specifically, the synthetic progestin, Provera. 

Due to the premature termination of hormone replacement therapy, many women are being exposed to increased risks of osteoporosis and hip fractures, colon cancer, and increased risks of heart disease, strokes, and breast cancer. In the field of anti-aging medicine, we’ve been warning patients of the detrimental effects of synthetic hormones and have strongly suggested that women use bioidentical hormones instead. Restoring one’s hormones to youthful levels seems highly appropriate and is supported by scientific literature. It’s strongly encouraged that you begin to use hormones as soon as possible after menopause. You should also check with your doctor that you have no personal or family history risk factors for hormone replacement therapy before beginning your regime.   

Cathy, bearing this in mind I’d strongly suggest that you continue your hormone replacement therapy, but switch to bioidentical hormones and be sure to reach therapeutic levels. If your doctor prescribes hormones to merely relieve hot flushes and night sweats, and doesn’t reach therapeutic levels with your hormones, you’ll not be protected against the deterioration of your bones, brain, and cardiovascular system. In addition, your risk of colon cancer will increase. 

With regards to the weight issue, it’s well established that Provera, which is synthetic progesterone, can lead to significant weight gain. Sometimes physicians use synthetic progestin in cancer patients suffering from severe wasting to increase their appetite and reverse a condition known as cachexia³. I suggest that you switch to bioidentical progesterone and see if this makes any difference. Prometrium is a reasonable choice but I prefer sublingual slow-release progesterone, which is available from compounding pharmacies. 

I suggest that you also check your levels of estradiol. If the level’s too high, this may lead to weight gain. The suggested level is between 186-367 pmol/l. I also suggest that you have your blood level taken approximately twenty-four hours after your last estrogen dose, if you’re taking oral estradiol. This will reflect the ‘steady state’ level in your bloodstream. If you’re taking transdermal estrogen cream, you’ll need to do a saliva hormone test to measure estradiol, estriol, and estrone levels to more accurately reflect your levels at the surface of your cell’s receptors. Blood levels of estrogen do not reflect levels of estrogen when given in a transdermal form, a mistake made by many practitioners new to the prescribing bioidentical hormones. You’ll also need to test your urinary metabolites of estradiol to ascertain if you’re making the less harmful metabolites of estradiol, which is known as 2-hydroxyestradiol, as opposed to the potentially more harmful metabolites of estradiol known as 4-hydroxy and 16-hydroxyestradiol.

In a study published by the Oregon Health and Science University, scientists observed a group of forty-six pre- and post-menopausal women. The scientists reached the conclusion that the drop in estrogen levels commonly associated with menopause is linked to an increase in the stress hormone cortisol. This hormone is strongly linked to an increase in abdominal obesity. It was determined that if the women received therapeutic levels of estrogen, cortisol levels decreased and there was a reduction in visceral fat.

In addition, as we age, we lose muscle mass and there’s a corresponding decline in the metabolic rate. As a result, many perimenopausal and menopausal women who continue to eat the same amount of food that they did when they were younger find that with decreasing energy expenditure, they gain weight that’s difficult to lose. Find out if the gym or health clinic closest to you has a bioimpedance machine that can measure your percentage of muscle mass and ask them to track it over time. We routinely measure such biometrics at every visit when patients complain of weight gain or loss. 

Most weight gain during perimenopause and menopause is usually secondary to an increase in appetite. It’s well known that all hormones can significantly increase a person’s appetite. If there’s been rapid weight gain, this is usually due to fluid retention and brief use of a diuretic may be helpful. If your weight gain is gradual, it’s most likely due to an increase in appetite. 

It’s established that hormones have no caloric value. In fact, in a study in 1999⁴, the authors concluded that not only does hormone replacement therapy prevent weight gain, it also favours weight loss by significantly increasing the breakdown of fat after three months of treatment. It also positively influences the insulin/blood sugar response, plasma cholesterol, and energy expenditure.  

In another study published in 2004⁵, the authors determined that hormone replacement therapy in postmenopausal women, along with testosterone replacement therapy in older men, appeared to reduce the degree of central obesity. 

So Cathy, in conclusion I suggest the following:

  • Continue your hormone replacement therapy, but find a doctor who knows how to prescribe bioidentical hormones in therapeutic doses. 
  • Eat a low glycemic paleo autoimmune type diet with a decrease in the total daily dose of calories consumed.
  • Increase the amount of hot, spicy, bitter foods that you consume, as it has been shown in studies of Ayurvedic medicine that these tastes increase one’s metabolism. 
  • Concurrently, decrease your consumption of sweet, sour, and salty foods as these tastes have been shown to increase weight gain. 
  • Exercise five days a week with an exercise regime that includes significant muscle strengthening with large muscle groups, such as those in the legs, to increase your metabolic rate. 
  • Be sure to get a good night’s sleep as this naturally increases your levels of growth hormone, which has also been linked to weight reduction. 

If you’re interested in learning more about how hormone replacement therapy can affect or is affecting your health, then please don’t hesitate to read the other posts on the Hoffman Centre blog or contact my office to set up an appointment.

Resources:

¹JAMA. 2002;288(3) 321-333

²Fert Steril. 2005 Dec; 84 (6): 1589 -601

³Sem Oncol 1991: 18:35-42

⁴Maturitas 1999 Aug 16; 32(3);147 -53

⁵Obesity Review 2004 Nov; 5 (4);197 -216

Risks of Hormone Replacement Therapy in Women

Risks of Hormone Replacement Therapy in Women

Does Estrogen and Progesterone HRT Increase Breast Cancer?

Hormone replacement therapy, or HRT, for peri or postmenopausal women is one of the most satisfying treatments that we, as ‘anti-aging’ doctors, are able to prescribe. We all have high numbers of very satisfied women who let us know that since the prescribing of HRT, they ‘got their lives back.’ I can attest to this as I have post-graduate training in HRT, being board-certified and having a Fellowship in HRT therapies with the American Academy of Anti-Aging Medicine (A4M).

However, getting to this place of being able to help women through the hormonal transitions of life using natural and bioidentical options has been a long time coming. Many were turned away from a large early study from the Women’s Health Initiative that warned of the dangers of synthetic hormones, and unfortunately this fear continues to permeate much of the conversation around using HRT. 

In this article, I’m going to walk you through the history of HRT, along with the studies that came after that first Women’s Health Initiative trial that clarified many of our questions regarding HRT, so that it can be used safely and effectively to improve the quality of life for so many women. 

Keep reading to learn more about HRT – Is it our enemy or our friend? 

This article will cover: 

  • Hormone replacement therapy for women,
  • Health risks of hormone replacement therapy,
  • Estrogen HRT breast cancer risk,
  • The history of HRT,
  • Findings of observational studies and randomized controlled trials,
  • Benefits of estrogen and progesterone HRT,
  • Conclusions about hormone replacement therapy and breast cancer, 
  • And where medicine is moving in terms of HRT.

Hormone replacement therapy for women

When discussing HRT for women in their perimenopausal or post-menopausal years, we are mostly talking about estrogen and progesterone hormone replacement therapy, the two main sex hormones involved in a woman’s sense of well-being.

As estrogen and progesterone levels fluctuate and eventually decline through the perimenopausal years and then reach the very low levels during menopause, many women experience uncomfortable symptoms and a loss of the wellness and protection that these hormones provide. Replacing these hormones often does wonders for how a woman feels, looks and enjoys her life. 

Estrogen is known to protect against depression, mood disorders, insomnia, loss of memory and cognition, dementia, colon cancer, reduction in bone fractures, dry vaginal tissue, wrinkles, and loss of teeth. Estrogen also contributes to the prevention of urogenital atrophy, the improvement of lipid metabolism and increasing libido. Overall, estrogen improves wellbeing and general symptoms of malaise. 

The benefits of progesterone include improved sleep, reduced anxiety, and protection against breast cancer, coronary artery disease, and osteoporosis.  

Risks of hormone replacement therapy – The WHI study

Does HRT increase the risk of breast cancer? Does HRT cause cancer? What about increase strokes, heart disease, and blood clots? What are the risks of hormone replacement therapy? 

These are the most common questions I get from women when discussing HRT. 

The reason for their concern is still firmly etched in everyone’s mind from when the conclusions of the Women’s Health Initiative (WHI) study were published in 2002. This showed that women on HRT had increased rates of breast cancer of 34 percent, strokes of 37 percent, blood clots and pulmonary emboli of 24 percent, and heart disease of 27 percent. When these figures were published, there was a huge media frenzy highlighting HRT risks, patients were immediately taken off HRT, and all research into this type of therapy was seriously curtailed. 

Since that time, there’s been considerable research, some carried out by the same WHI group, that actually refutes aspects of these findings and also examines some of the pitfalls and perils of the original WHI publication. However, none of the same fanfare and publicity has been given to these new findings. Many patients and doctors are still influenced by the 2002 guidelines initiated after this trial was first published.  

Keep in mind that when we prescribe HRT for women in the postmenopausal years, the hormones that we use include, but are not limited to, estrogen, progesterone, testosterone, DHEA, pregnenolone, thyroid, oxytocin, hydrocortisone, and melatonin. However, the WHI study was concerned with oral Premarin, a synthetic, non-bioidentical estrogen made from horse urine, along with oral Progestin, which is also a synthetic progestin rather than bioidentical progesterone HRT. The elucidation of these distinctions is vital to understanding these results, as we’ll explore later. 

HRT and breast cancer

With breast cancer incidences, it’s well established in oncology that anti-estrogen approaches to breast cancer, such as oophorectomy (removal of one or both ovaries), tamoxifen (a medication that blocks estrogen), or aromatase inhibitors (medication that blocks the conversion of testosterone to estrogen), are all beneficial for breast cancer response, survival, and even prevention. 

So, if these anti-estrogenic approaches are beneficial, by inference estrogen must be carcinogenic. However, as mentioned above, with recent updated publications on breast cancer and hormone replacement therapy, the results reflect that this may not be the case. 

In fact, recent data suggests the exact opposite: Estrogen-based hormone replacement therapy appears to reduce breast cancer and all-cause mortality rates

How can this be? Let’s explore this conundrum and the history of breast cancer and HRT. 

Here are the results from some historical studies outlining forty years of research on this very question, with some surprisingly new observations that will require our serious attention. 

The history of HRT

The relationship between hormones and breast cancer dates back to the late nineteenth century. At that time a George Beatson, a British surgeon, was the first to postulate an association between the hormonal action of the ovaries and the proliferation of breast cells, first discovering the relationship in lactating sheep. He wondered if removing the ovaries, that produce estrogen and progesterone, could be a treatment for breast cancer. He tested his theory in June of 1895.

A thirty-three-year-old woman had noticed a small lump on her left breast while she was breast-feeding her first child. This lump became larger after the birth of her second baby. A large tumor was successfully removed from her breast, but the cancer was already far advanced. She was referred to Dr. Beatson who removed both her ovaries. He reported the case to the Edinburgh Medico-Chirurgical Society and published details in the Lancet in July 1896. The woman survived for nearly four years before dying of recurrent disease. Thus, the removal of the ovaries as therapy for breast cancer was born and continues in present day. What’s so interesting is this discovery was made thirty years before estrogens were identified. 

But, Dr. Beatson didn’t know what the full function of the ovaries was. In the 1920s, researchers Edgar Allen and Edward A. Doisy from St. Louis University identified, extracted, and characterized the molecule of estrogen from a pig’s ovarian follicle. This was a major scientific breakthrough and explained the success of oophorectomy. Once estrogen was isolated from the ovaries and an oophorectomy induced a positive breast cancer response, it implied that estrogen is most likely breast carcinogenic. 

Indeed, when anti-estrogens such as tamoxifen and aromatase inhibitors were subsequently developed in the 1970s and 1980s, with tamoxifen as the best example of a dedicated, specialized antiestrogen, a positive response rate of between 20 and 50 percent was seen in stage IV breast cancer. In the 1980s, when aromatase inhibitors were used, a 25 to 30 percent reduction of breast cancer mortality was noted and a reduction in new breast cancer incidence was determined to be between 30 and 40 percent.  

Estrogen HRT has been used since the 1940s, became popular in the 1960s then gained a very high level of popularity in the 1990s. It was primarily used to reduce hot flashes, the classic sign of menopause. Yet, in the very beginning their use was also tied to the issues of femininity and sexuality, very well described by Masters and Johnson in the early 1970s. After the seventies, more science emerged within HRT research, confirming that the therapy improved energy, reduced the incidence of bone loss and bone fractures, reduced cholesterol, and had many potential benefits for the cardiovascular system and the risk for heart attacks.

Observational studies

There are approximately fifty-nine observational studies summarized by the Oxford Group on the question of HRT and breast cancer mortality over the past forty years. These studies show an increase in breast cancer mortality with HRT, ranging from 30 to 80 percent, meaning that HRT increases the risk by a considerable amount. Let’s dive more into what this means and the limitations of this type of study. 

In observational studies, participants aren’t randomly assigned to a treatment or a control group. Instead, they’re simply observed over time to see whether a particular treatment or intervention helped, harmed, or did nothing. The results are then compared to a similar group that received a placebo or no treatment at all. In the HRT studies, women selected themselves to receive treatment. After twenty years, the researchers would eventually follow up and study these self-selected HRT users against the general population of non-HRT users in a non-randomized fashion.

The benefit of observational studies is that they’re less expensive, can be done more quickly, and can include a broader range of patients. They’re often used when a randomized trial would be impossible or unethical.

The Collaborative Group on Hormonal Factors in Breast Cancer, in Oxford in the UK, the leading authorities recognized in this particular field of epidemiological studies, summarized the observational studies of the previous thirty years of research and published their findings in the Lancet Journal in September 2019, using the comparative analysis of users against non-users. They showed that taking Premarin or progestins had double or a 208 percent increase in the risk of breast cancer. 

With estrogen alone, for women after hysterectomy, the risk is lower but incidence is still increased by almost a third or 33 percent. Progestin is used along with estrogen in women who still have a uterus to prevent the risk of endometrial cancer, since estrogen alone stimulates the growth of the endometrial lining. 

When looking at mortality rates or death cases with estrogen alone HRT versus non-users, there was a 35 percent increase in mortality. For estrogen plus progestin, there was an almost 64 percent increase in breast cancer mortality. This is the present understanding of the HRT outcomes, when you examine observational non-randomized studies, as reported by the Oxford overview group. 

Indeed, from these studies it appears that the incidence and mortality of breast cancer associated with HRT was definitely increased and thus by deduction, estrogen is undoubtedly breast carcinogenic. This information, understandably, would raise caution in a woman looking for symptom relief and anti-aging benefits in menopause. Luckily, there is more to the story. 

Limitations of observational studies

Other researchers have looked into the issue of potential flaws in these studies, particularly when new studies have shown that estrogen use alone has shown a reduced incidence of breast cancer, with many added benefits of estrogen HRT. Dr. Ragaz’s group has raised the issue that in non-randomized studies like the Oxford overview, with self-selection of HRT users, a potential bias could be created in that women with high-risk of breast cancer were selected. One bias was that more affluent women take HRT. Therefore, the question arises regarding the link between affluence and breast cancer risk.

Affluence and higher socio-economic status have been associated in many studies with an increased risk of breast cancer. 

Affluent women have:

  • More carbohydrate-rich diets 
  • Higher body mass index
  • Less physical activity
  • Reproductive factors that are substantially different from non-affluent women, such as lower parity, less breastfeeding, and later age pregnancy
  • More frequent breast examinations and mammograms 

There’s plenty of data indicating that all these particular factors are very much linked with higher breast cancer rates.

What’s most important is that randomization is essential when attempting to analyze breast cancer risk in HRT users. Researchers must use a sampling of women from all socioeconomic groups in order to equivalize as many variables as possible.

Randomized studies

Randomized controlled trials (RCTs) are considered the gold standard and an ideal method when it comes to medical research.  In an RCT, women are randomly assigned to receive hormones, or any other treatment being studied, or a placebo. If the study is double-blinded, neither the patient nor the investigators know which patient is taking what. 

The start of large randomized HRT trials began with the WHI studies. The Women’s Health Initiative (WHI) was established in the 1990s under the leadership of Bernadine Healy, the first female director of the National Institute of Health. In 1992, the WHI project conducted a series of four randomized trials examining issues of women’s health, two of which were aimed at the HRT issue. 

The Women’s Health Initiative is the most active epidemiological group in USA. Unfortunately, soon after the beginning of these WHI studies, Bernadine Healy died of brain tumors resulting from glioblastoma. She sadly never saw the result of her initiative. 

The biggest randomized study to date was initiated by the WHI and called Trial 1. In routine randomized studies the numbers usually amount to a few hundred, but in this study group there were 16,000, a huge amount by routine standards.  

In the WHI Trial 1, 16,608 women with an intact uterus were randomised to Arm 1 using estrogen (Premarin) plus a progestin (Provera). Arm 2 received a placebo only. This was the first study looking at both estrogen and progestin and showed a 44 percent increase in breast cancer mortality.  

The WHI Trial 1 was terminated prematurely and the results published in JAMA 2002. As mentioned earlier, there was a substantial media frenzy. The media and television networks were full of the data and publicity was aggressive and prolific. This study showed an almost 27 percent increase in heart attacks, 34 percent increase in breast cancer, 37 percent increase in strokes, and a 24 percent increase in pulmonary emboli or blood clots in the lungs. There were some benefits, as quality of life markedly improved and bone fractures were reduced quite significantly. The interpretation by the lead investigators of the WHI Trail 1 dramatically changed guidelines for HRT. 

  • HRT was to be used for the shortest time only 
  • HRT should only to be administered for the treatment of postmenopausal symptoms 
  • The risks of HRT far outweighed the benefits
  • The risks of coronary heart disease and breast cancer far exceeded the benefits of osteoporosis prevention and a decrease in colon cancer

With HRT discredited as a therapy, sales dropped by 50 percent in one month and all the major clinical organizations, such as the American Association of Clinical Endocrinologists (AACE), the American College of Obstetricians and Gynecologists (ACOG), and the North American Menopause Society (NAMS) recommended only using HRT for a very short time and solely for the control of menopausal symptoms. 

With regards to the cardiovascular risk factors, some of the initial criticisms of the study declared that most of the women studied were much older and already had significant baseline coronary artery disease. In addition, they were given oral estrogen which is known, particularly in the first year of taking it, to increase clotting factors in the liver. 

Soon after the WHI Trial 1 findings were made public, Dr. Lobo published the findings from four large randomized trials in Family Practice News in 2003. These showed that that the risk of cardiovascular diseases is extremely low in healthy women in early menopause and that the results of the WHI didn’t apply to younger women between fifty and sixty years of age who initiate HRT around menopause. 

There was overwhelming evidence that the anti-atherosclerotic effect of HRT depends on the time of initiation and that early initiation is protective. The Nurses’ Health Study (NHS), which has produced the most data for observational studies for risk factors for major chronic disease causation in women, didn’t find any association between coronary artery disease (CAD) and HRT. It was hypothesised that once CAD is established, HRT has no protective or beneficial effect, but estrogen given to menopausal women significantly retards progression of CAD by its positive effects on lipids and endothelial functioning, which is related to the inner lining of blood vessels. However, oral estrogen given to women over sixty with CAD may make the condition worse. 

WHI Trial 2 – Positive results for HRT

A second study by WHI, called Trial 2, using estrogen hormone replacement therapy alone, showed astounding results, but in the other direction. 

In the WHI Trial 2, 10,739 women, after hysterectomy, were randomized to estrogen against placebo. Arm 1 used estrogen-based HRT alone, while Arm 2 was a placebo only.

In 2004, the first publication of the WHI Trial 2was released regarding the estrogen-alone arm, which has continued onwards until the present. These results were from women under the age of sixty. 

The WHI Trial 2 mostly indicated benefits, including a 40 percent reduction in breast cancer mortality! Remember, in WHI 1 there was an increase in breast cancer, but here we have a 40 percent reduction in breast cancer mortality with the use of estrogen HRT alone. It’s very important to note in this case that progestin wasn’t used. 

Furthermore, there was a 25 percent reduction of diabetes, a 26 percent reduction of Alzheimer’s dementia mortality, a 55 percent reduction in myocardial infarction among patients between fifty and fifty-nine years old, a 21 percent reduction in all-cause mortality, and a 32 percent reduction in bone fractures with an 80 percent improvement in quality-of-life benefits. This is remarkable and the findings are very different from the WHI Trial 1 results. 

However, unlike the WHI Trial 1, which according to these publications had revealed mostly remarkable benefits, there was no publicity. There wasn’t a single article or television report. Not a thing. From 2004 to 2020, the WHI has updated this study, with the same benefits being shown, but they’ve entirely suppressed their own publicity. Consequently, nobody knows much about these outcomes. 

Does HRT cause cancer? – What I tell my patients about the risks

So, when patients inevitably ask me if HRT therapy is safe or inform me that their doctor has told them to stop using HRT because it isn’t safe, I immediately know that they aren’t aware of the WHI Trial 2 studies, which have refuted the majority of the WHI Trial 1 findings. 

These findings are completely opposite to the WHI Trial 1 studies, which incorporated estrogen and progestin. A further WHI Trail 2 study published by Stefanick et al in 2006 showed a reduction in the estrogen-alone HRT group, the breast cancer incidence reduced by between 20 and 43 percent. However, nobody has heard about these outcomes. There was no publicity at all. As a result, the consensual opinion of patients and the majority of health practitioners continue to be based on the WHI Trail 1 findings.   

With continuation of the WHI Trial 2, published by Andersen et al in Lancet Oncology 2012, showed the persistence of benefit with estrogen alone. There was a 23 percent reduction in breast cancer incidence with a 63 percent reduction in breast cancer mortality and a 38 percent reduction in all-cause mortality with estrogen alone. This is unbelievable. 

Almost twenty years later, the WHI Trial 2 continues to publish data. An updated study, published by Manson J. et al in JAMA 2017 showed a 45 percent mortality reduction with estrogen alone and the 2020 Chlebowski R. et al JAMA 2020 publication showed mortality for breast cancer reduced by 40 percent. 

Please note that the conclusions from the WHI Trial 2 findings from all studies from 2004 to date show a very statistically significant 40 percent breast cancer mortality reduction with estrogen.  

Benefits of Estrogen

So here we have to ask how is it possible that estrogen, which for decades has been linked to breast cancer, provides benefits? 

There’s some evidence for the biological impact of estrogen on breast cancer cells. Research by Dr. Joseph Ragaz’s group has shown the following:

  • Estrogen reduces apoptosis 
  • An increase or improved stem cell differentiation with lower invasiveness of breast cancer cells means that the breast cancer becomes less aggressive
  • Estrogen also influences insulin growth factors in a positive way  

As far back as 2010, Dr. Ragaz’s group presented the potentially very important concept of estrogen duality, which shows that exogenous estrogen in HRT is protective, whereas endogenous estrogen made by the body proliferates the breast cancer cells. We know that exogenous estrogen in HRT is protective as the WHI Trial 2 data above attests. 

We also know that because of the endogenous estrogen, we can remove the ovaries and administer anti-estrogens such as tamoxifen, with these being aimed against endogenous estrogen. These studies show that suppression of endogenous estrogen is breast cancer beneficial. Therefore, endogenous estrogen stimulates and remains carcinogenic. 

The message is that now there’s clear evidence of exogenous estrogen emerging as a potent, powerful anti-estrogen to the endogenous estrogen. This is basically the information that needs to be published, publicised, and the message spread amongst the lay and medical communities. 

What about progesterone?

The other question is why there’s so much difference between the two trials. The evidence very clearly appears to be centered on the issue of the synthetic progestins used. It’s been known for some time and there’s adequate evidence to show that the progestin/Provera used is actually carcinogenic and inflammatory and can erase the benefit of estrogen. 

In Trial 1 with estrogen and Provera, the incidence of breast cancer mortality was increased by 44 percent. In the WHI Trial 2, with no progesterone but estrogen alone, there was a 45 percent reduction in breast cancer mortality. However, the new generation of bioidentical progesterone, including Prometrium and compounded bioidentical progesterone rather than progestin, don’t appear to be as harmful to breast cancer. That’s a very important concept as most patients and many doctors equate the two, meaning progestins such as Provera and bioidentical progesterone, as being the same. 

Progesterone was isolated and produced in the 1930s and so named because it’s the hormone that supports pregnancy and is pro-gestation. Today, the word progesterone is often misleadingly applied to many different forms of this hormone, rather than the natural progesterone that the body produces. Prometrium is the most common bioidentical micronized form of progesterone used in North America. 

In contrast, progestins are synthetic compounds, not bioidentical to what your body produces. The most frequently prescribed synthetic progestin in North America is called methoxy progesterone acetate (MPA), which has the trade name Provera. Prempro is a combination of synthetic estrogen and synthetic progestin and was the one used in the WHI Trial 1. 

Progestins are known to adversely affect mood, fatigue, edema, anxiety, bloating, depression, breast swelling, and reduce HDL levels. Progesterone is devoid of these side effects, unless given in amounts above what’s normal for the body. 

All this to say that the form of HRT really matters and bioidentical is the most beneficial with the least risk. 

Estrogen and all-cause mortality 

Estrogen has an impact on all-cause mortality, referring to the health of women and the cause of death for all other conditions other than breast cancer, and is decreased considerably in those who take estrogen-only HRT. 

Dr. Ragaz and his group obtained data from the WHI and transformed the numbers into crude, absolute numbers of deaths that could be avoided each year by women taking estrogen-only HRT. Their final aim was to influence the HRT prescribing guidelines, because the current HRT guidelines haven’t yet taken into consideration the updated data or results since 2004, which have been explained above.

In the 2017 overview from Mason’s WHI Trial 2 publication, breast cancer mortality reduction was 45 percent, Alzheimer dementia mortality reduction was 26 percent, and all-cause mortality reduction was 21 percent. This includes every other cause of death, other than dementia and breast cancer. They took the annualized mortality rates for these three conditions, applied the reduction in deaths from them as published in the WHI Trial 2 and came up with the following figures. The results were stunning! 

Every year in the United States, with the use of estrogen-only HRT, there would be 9,292 fewer breast cancer deaths, 18,966 fewer Alzheimer’s dementia deaths, and 21,750 fewer deaths from other causes, such as diabetes, bone fractures, or from cardiac factors. In total, the lower mortality rates amounted to 50,008 fewer deaths from all causes every year by using estrogen-only HRT. 

The evidence is clear that we see an unexpected numerical HRT benefit with avoidance or breast cancer cases, Alzheimer’s dementia, and all-cause mortality. 

Moving forward with anti-aging medicine

Dr. Ragaz’s recommendation is to adopt and implement HRT, without synthetic progestins, to the current medical guidelines in order to pass on the benefit to millions of women. This means that hundreds or even thousands of deaths could be avoided worldwide. In the USA alone, 50,000 deaths could be prevented and many more women could be saved if these recommendations are adopted worldwide.  

In summary, the absence of randomization in the previous observational studies highlights the fact that these studies were methodologically flawed and the conclusions they reached have to be viewed from this perspective. Secondly, because of the carcinogenicity of progestin/Provera included in the randomized WHI Trial No 1, this trial’s conclusion can’t be applied to modern prescribing of HRT, which excludes progestin/Provera in favour of bioidentical progesterone. 

As a result, the estrogen-alone based HRT evaluated in the WHI Trial 2constitutes the new gold standard. This is a basic constituent for present HRT regimens to be recommended in new guidelines, with the new generation of progesterone, which aren’t carcinogenic, to be applied for most women approaching menopause.

There’s hope that breast cancer prevention is possible and that estrogen will likely play a larger role.  If you’d like to explore if HRT is a good fit for you, please contact my office to schedule a consultation.

Heal Your Chronic Illness and Take Your Life Back

Heal Your Chronic Illness and Take Your Life Back

Mary Vallarta:

Hey everybody. Welcome back to the virtual summit. I’m your host, Mary Vallarta.  As you know, we are here to talk about healing your chronic illness and taking back your life.  Basically how to balance your mind, body, and spirit to restore your health and vitality.

Mary Vallarta:

Today I have Dr. Bruce Hoffman and I am super excited to chat with him. Before I get into the questions, let me tell you a bit about who he is. Dr. Hoffman is board certified in anti-aging medicine, has a master’s degree in clinical nutrition, and is a certified Functional Medicine practitioner. In addition to his clinical training, Dr. Hoffman has studied with many of the leading mind, body, and spiritual healers of our times, including Deepak Chopra, Osho, Ramesh Balsekar, and John Kabat-Zinn. He has shared the stage with Deepak Chopra and Dr. John Demartini, and he continues to spread his inspiring vision of healing and wellness with audiences and patients around the world. Once ensconced in the practice of family medicine, he quickly realized that his interests in medicine were broader than just drugs and surgery. The allopathic medical practice was limited to treating symptoms and illnesses but fell short of restoring the patient’s health entirely. So Dr. Hoffman embarked on a journey to understand what constitutes the human experience and what the triggers and mediators are that perpetuate human suffering.  He wanted to do this not only to help patients be free of disease but to realize their maximum potential.  Dr. Hoffman welcome. That is quite a resume.

Dr. Bruce Hoffman:

Nice to be here.  I’m looking forward to this conversation and seeing what we can come up with.

Mary Vallarta:

Me too. I’ve been looking forward to this conversation. I’m super energized to be speaking with you. Let’s get into it.  Dr. Hoffman, I love how you’ve combined the strengths of Western medicine with the mindful and spirit-centered approach of Eastern medicine. As your bio states, you didn’t actually start out this way. You were practicing Family Medicine. What pushed you to go into the path of functional and integrative medicine that takes mind, body, and spirit into account?

Dr. Bruce Hoffman:

Well, the part leading to where I am now is quite interesting in that when I was a young boy in my teenage years, I went to boarding school and I had a teacher there. My teacher was very interested in not only Western psychology, particularly the work of Carl Jung but also very interested in Eastern mythology and religions, particularly the work of a subset of the Vedantic Hindu medicine called Advaita. Advaita takes the point of view that there is no “there out there”. Everything springs from one source. So there is just one mind, one consciousness, and there is no separation. It’s a very specific way of looking at reality. Many of the quantum physicists who came onto the scene at the turn of the century had a very similar point of view. When they dissolved matter into light, they said, all light is continuous. There is no separation

Dr. Bruce Hoffman:

So this ancient, theological concept, was being married with Western physics. My teacher, Roger, I just hung out with him and we explored all these things and so I became very interested. When I was about 15 years of age, I had what they call a Satori experience, where I directly experienced this One Mind, One Reality. It descends upon you, and you just know that to be true. Before too long, you descend back into your dualistic past, present and future, gain and loss reality and the awareness is lost.  I still remember that. Then I had a second experience like that in my thirties. So having had two experiences of One Mind, One Reality. It sort of cemented, in my body based understanding, that was behind all systems of appearance.

Dr. Bruce Hoffman:

Nonetheless, I continued my high school education. My mother applied for me to go to med school. I had no idea. I find myself in med school. I wanted to be a poet, go hang out with all the beat poets in San Francisco, but my mother thought I should have a more formal education. So she applied for med school and I found myself in med school. Actually, after six years of medical training, I became a Family Physician and fell in love with it. I actually loved what I did. I ended up in Saskatchewan, Canada, practicing Family Medicine. When I got to Canada practicing Family Medicine, it was very apparent that that system of medicine is very limited in terms of what you can offer. We call it the N2 / D2 system of medicine. Name of disease, name of drug. That’s about it.

Dr. Bruce Hoffman:

But what happened was then I also came across a video by Dr. Larry Dossey, one of the great thinkers of the last 50 years in the field of integrative medicine. I watched Larry Dossey sort of draw out this long explanation as to how he combined East and West into his medical practice and his thought process. That triggered another huge explosion of interest and reignited my childhood experiences with my high school teacher and Advaita and psychology. All of a sudden this whole roadmap just opened up and I thought, this is a very interesting possibility. So I then just started learning as much as I could about the human experience. I became a student of as much as I could possibly absorb across all spectrums of human reality from toxicology to illumination. I started to develop a roadmap and with different teachers and different experiences and different ways of seeing and being exposed to different systems of information.  I did Ayurvedic training and they talk about different bodies, different systems of the body.  I spent time with a very well-known doctor from Germany who lives in Seattle by the name of Dr. Dietrich Klinghardt.  I spent years studying with Deepak Chopra and David Simon, et cetera, et cetera. And I just started to develop a roadmap for looking at the human condition from traditional medicine, then expanding it a bit to Functional Medicine and then moving to the brain and then to the emotions, then to the mental field, then to the soul and then to the spirit, which is beyond all confines to space/time. So I developed this roadmap of experiences at each level, diagnosis at each level, potential treatments at each level, because many people will want to go to an acupuncturist, which is at level three in this energy model, but they really should be seeing an oncologist or they’ll go to an oncologist where they really should be doing trauma work.

Dr. Bruce Hoffman:

I tried to sort out all these different possibilities across all layers and levels and help teach/write a new curriculum, really for doctors or healers. Not really doctors. MDs should keep doing what they do. They do it well. Every patient that sits in front of me says well, why doesn’t my doctor know this.  Well,  because it wasn’t his interest and he didn’t train to know this. So give it up. Don’t even ask the question, don’t waste your time. We need a new curriculum for a new expansive model. That’s been my life calling, my life passion, and to which I’m still a student. I mean, I study more now than I did when I was young. I just keep expanding the knowledge base.

Mary Vallarta:

I think that’s what makes your work so fascinating to me. You have sort of like a 360-degree view since you’ve been on the MD side, the family medicine side, and then you’re now continuing to learn more about the Eastern methodologies. So you’re kind of taking everything and putting it all together to make these roadmaps that you’re talking about.

Dr. Bruce Hoffman:

It’s not just Eastern, Mary,  it’s all systems of knowledge, you know, from phenomenology to theology, to psychology East to West, to up and down, it’s all layers, all levels. It’s not only Eastern insights. Some of it is Eastern, but it’s not only Eastern insights.

Mary Vallarta:

I see. Interesting. So integrating all that together is very fascinating and it gives you more of a well-rounded perspective. As you mentioned, MDs aren’t trained to have that type of approach. That’s why there’s a time and place where that’s going to be appropriate. There’s also another time and place where something else might be more appropriate for a patient. So I think that’s important to note. There is a lot of research coming to light on the important role that food plays on one’s ability to prevent disease and sometimes also reverse or heal. As you pointed out, there are such things called trauma. You’ll recommend people see some trauma specialists or stress. What are your thoughts on having more emphasis or focus on things like mindset, changing internal narratives, and healing emotional trauma when it comes to healing?

Dr. Bruce Hoffman:

One of the great challenges of working with patients is when they present with complex multi-system illness, which is the only kind of patient I see these days, they are still very in that diagnostic mindset of “what do I have”? Usually singular, what one thing do I have? Is it mold or Lyme or Mast Cell or whatever? Then they start to think diagnostically and therapeutically in an allopathic way. When you start to have a broad spectrum of understanding the human condition, and you start to understand all the antecedents, mediators, and triggers that eventually ended up in biology and pathology/disease, you can’t stop yourself from taking a far more comprehensive history. So the healer of the future can commit both acts of commission, as well as acts of omission. It’s not what he knows, but it’s also what he doesn’t know.

Dr. Bruce Hoffman:

So if you’re sitting in front of a patient and they are presenting  with symptomatology at this moment in space-time, it behooves you to ask every single possible trigger that may have led up to that presentation. It’s our Western understanding and consensual reality that diseases kind of fall out of the sky. It’s like, Oh, I’ve got rheumatoid arthritis. Then you can go to the doctor and get an immune modulator, or you can go to a naturopath and get an herb, but it’s still that singular mindset. When we look at patients from a more complex model, we have to start looking at not only diagnosis from a Western perspective, because you need to know that, that it’s an inflammatory and immune system-based disease based on autoimmunity, which has its links in leaky gut, et cetera, et cetera, and the genetic predisposition.

Dr. Bruce Hoffman:

You’ve got to know that, but you’ve also got to understand how people arrive at a point in time with a diagnosis. You know, people, they inherit epigenetically the traumas of their forefathers. So if you don’t ask a history of their forefathers and the ancestors you are missing out on a piece. Then they get born into a family system, and whether or not they were adequately seen by the mothers in the first 10 years and by their fathers in the second 10 years and peers, and by the loved ones in the third decade, they don’t adequately myelinate the three different brains that grow up, the reptilian, limbic and adult brains. So if they are not self-regulated by external parental figures, they don’t learn to self-regulate themselves and they have a fragile personality structure very often.

Mary Vallarta:

So how do you help them uncover all of this information?

Dr. Bruce Hoffman:

You’ve got to take a very thorough history. I take a two and a half to three-hour history and ask all of these questions.

Dr. Bruce Hoffman:

Then those experiences, your epigenetic transfer, ancestral trauma, early childhood experiences that all gets then translated into your perception of reality, your internal dialogue, your thoughts, your value systems, your beliefs, and your defenses. So many people stay highly defended from feelings that arose in the first 30 years of life because they are too painful. So they’re defended and they are traumatized. That then translates into electrical messages in the brain, which you can read on a qEEG. I have a brain treatment center, which reads qEEGs. You can see hallmarks of early trauma on the brain. You’ll see the one brainwave, the [1] beta brainwave highly red, highly amplified. That then gets turned into chemical signals. That then starts to interact with your phospholipid cell membranes, which you can measure, which then turn on receptors, which then turn on genes, which then turn on proteins, which then turn on all the biochemistry that runs your life.

Dr. Bruce Hoffman:

So you have this whole cascade of possible antecedents that can set you up for what’s happening at this moment with so-called symptomatology or disease expression, but it’s not just rheumatoid arthritis. It’s way back in the ancestry, trickling all the way down to physiology. And then you have the environment coming in. That plays havoc with your, your detox pathways and sitting on DNA. Sitting as adducts on your DNA and mitochondria affecting their expression of lipids and proteins. So if you don’t ask all these questions, you’ve got a limited roadmap and you got a couple of tools in your toolbox. You’ve got to have a very broad toolbox, and that’s why education becomes important. We have to educate healthcare providers of the future to broaden their toolbox. Not only to broaden their toolbox but also to broaden their self-understanding as well.

Dr. Bruce Hoffman:

If a healer approaches a patient with a hero type approach, I’m all-knowing, and you’re all sick. They also perpetuate a very lopsided point of view. The patient’s well side doesn’t get activated. They don’t activate the healthy part of who they are. They identify with the disease, the doctor as the hero is going to fix them. That’s a very lopsided relationship. Often patients sort of, in order to survive that lopsidedness, they just don’t activate their intent to do what is required for them to activate the healer within. The healing archetype within. Without activating that there’s no outcome.

Mary Vallarta:

Right. So would you say your approach is also about giving power back to the patient? Like letting them realize that they have a big role to play in their healing?

Dr. Bruce Hoffman:

We try to. Some people are highly defended.  People have value systems, a hierarchy of values. People will say that their health is a high value. They come to you to treat their health or help them treat their health. When you start to take a history, you’ll find out, particularly with men, by the way, this is like a big male thing. Their highest value is their career, making money, health is secondary. They often delegate their health to the loved ones, their spouses, or somebody else. They don’t really want to rob Peter, their career-making money, to pay Paul, to invest in their health. So they don’t raise health up as a value. Unless patients are prepared to raise health up as a value and become a participant in their own healing experience, they remain passive and they have what we call “projection of will”.

Dr. Bruce Hoffman:

They project their will to heal onto you. If you rise up in the healing archetype “I’m all-knowing, I’m going to fix you”, you start working harder than the patient. It’s a very lopsided relationship, almost doomed to fail. So you’ve got to try and enter into their system and sort of feel where they are in their own evolution.  Is health a high-value? How healthy is their ego strength? Is it fragile? How much projection of will do they have? Do they have outer resources to assist them or are they without resources? Do they have personality disorders? Do they have what it takes to take on such an extensive journey? And, of course, finances.  Most of this isn’t funded by healthcare systems and nor should it be because it would bankrupt most of them.

Mary Vallarta:

Right. Also, one of the most important questions for them to know the answer to is why do they want to heal? Why do they want to get better?

Dr. Bruce Hoffman:

On the first page of my 70-page questionnaire is “Why are you here, How can we help you, What is it you want to achieve?” and how committed are you to making the changes necessary? It’s interesting when it comes back 50% or 75% committed. Immediately I say we have to have this conversation first and find out what that’s about. Because if people haven’t been seen by their parents, if they haven’t been supported and challenged in a healthy, supportive, challenging way, which is how love evolves and how you develop a concept of self. You only develop a good concept of self, good ego strength if you are both supported and challenged by your parents, not just supported. If they don’t have a healthy sense of self, they can’t take on what is being required of them to sort of move through this experience. They just don’t have the resources to do so.

Mary Vallarta:

Right. That’s very true.

Dr. Bruce Hoffman:

You have to find out where they are with that, you know, and where is health in their value system. You really have to ask that question before you launch into “tell me about your disease”. You have to find out who this person is sitting in front of you and where they are at in their hierarchy of values as to doing what it takes to get better. You know, there are many possibilities for healing. The first possibility is just treating disease. Get this symptom out of me. I want to do it quickly without money and without me being involved, just give me a pill. Mahatma Gandhi said the tragedy of modern medicine is that it works. There’s that possibility. Then the other possibility is they see symptoms as teleological. Those symptoms are actually asking them to enter into their own life, to try and find out why they are this way in space-time. Then they see mind, body connections.  That the way that they construct reality may influence the systems they put in place to support them and the way they perceive things and what they eat, it all plays a role. So they become more conscious of their own advocacy. That’s the second possibility. The third possibility for healing are those people who do not only want to be free of disease, which is sometimes not possible, you’ve always got some symptomatology and, but they want to live at the highest maximum potential. To do that, they have to go through a lot of personal development and personal growth to know their value systems, to know how inspired they are. To find out what wakes them up every morning. Are they called from above by some spiritual purpose or do they just get out of bed and just sort of see what happens?

Mary Vallarta:

Right.  So that brings us back to the why.  Let’s talk more about maximum potential, because I know that’s a big part of your work. Can you describe what maximum potential is?

Dr. Bruce Hoffman:

Well, when a person wakes up in the morning inspired by what they do, that’s living at your maximum potential. They are living at their maximum potential. It’s a vision of what they are here to do on this planet while they’re in a body. In psychology, it was called a daemonic calling. Your inner constellated self calls you from above to become who you’re meant to be. So you’re just inspired to do what you do, and you know what you are meant to do and you throw all your life force into that outcome.

Mary Vallarta:

Which is basically their higher purpose.

Dr. Bruce Hoffman:

Their highest value, their highest purpose. They don’t need to be motivated to get out of bed. They get out of bed and just do what they do. They stay up very late at night trying to manifest it. Their life force is invested in it. There’s that old image that I love, if you will go to a university and you stand outside and you look at the different levels of a university, the undergraduate student’s lights go out at four o’clock, the postgraduate at six o’clock, the doctoral students at 10 o’clock and the Nobel prizewinner’s their lights get switched off at one o’clock in the morning. They are just called into the daemonic calling. They just know who they are and what they meant to do.

Mary Vallarta:

…and that’s what pushes them, yes.

Dr. Bruce Hoffman:

But that’s only the third possibility. The fourth possibility of healing is when you know that you are part of a connected whole. You don’t identify with your body, your emotions, your mind. You identify with that aspect of you that is beyond all of that.  Your deepest self, your soul, which is sort of linked to this one mind, this eternal consciousness. You know you’re not your body, you’re not your mind, you’re not your thoughts, but instead, you’re part of this continuous oneness and you stay connected to that in that field of consciousness that is that. I’ve had patients die, fully healed, connected to that aspect of themselves. They just know who they are. They know they are not their bodies, they’re not their minds,  they’re not their thoughts, they’re not their actions. They are beyond that.

Mary Vallarta:

That reminds me of the concept of  Satva  in Ayurveda.

Dr. Bruce Hoffman:

It’s called Brahmi in the Vedantic model.

Mary Vallarta:

Oh, nice. I’m just getting into more Vedic studies. I’m in Ayurveda right now, which I’m really loving. That’s really what inspired my own healing journey.

Dr. Bruce Hoffman:

I took my model from Ayurveda because I studied it for years and went to India and did an internship there.

Mary Vallarta:

That’s my dream. I want to go to India and study it one day.

Dr. Bruce Hoffman:

But they have these koshas, these bodies. I took that model and added a few and I made the seven stages to health and transformation model based on Ayurvedic and Vedantic scriptures.

Mary Vallarta:

Oh, got it. So what are those seven stages? Can you share them with us?

Dr. Bruce Hoffman:

Yes. Spirit, soul, mind, emotion, energy, physiology and structure, environment.

Mary Vallarta:

Okay. Interesting.

Dr. Bruce Hoffman:

Yeah. They are based on the five koshas from the Vedantic philosophy, the five bodies, the five layers.

Mary Vallarta:

So obviously when your patients are working with you, I can only imagine some of them get challenged. Right? Some of them might get frustrated during this whole process. So how do you go about helping them and supporting them push through or be comfortable with feeling this discomfort? Cause a lot of times people run away from discomfort.

Dr. Bruce Hoffman:

Again, it’s incumbent upon me if I’m doing a reasonable job, not to impose my model on them, but just ask what they want.

Mary Vallarta:

Ok, going back to that.

Dr. Bruce Hoffman:

Some people just want to not have asthma.  They’re not interested in seven levels of healing. I respect that. Then I pull out all my functional medicine, toxicology tricks, and just treat asthma.  Treat triggers of asthma such as mold and food sensitivities and Mast Cell blockade and mitochondrial resuscitation. I do all my functional medicine things. Other people come to me and say, I’ve been sick my whole life and they give you 50 symptoms. And you know, immediately that that person probably has not had the most advantageous experience from either ancestrally or from birth. Almost definitely you can tell that. The adverse childhood experiences studies show that people who’ve had adverse childhood experiences had three to four times increased health disadvantages as they mature.

Dr. Bruce Hoffman:

So you know when people tell you they’ve been sick for as long as they remember. You immediately go into early childhood trauma history and it’s always there. You can always tell. Interrupted bonds with their mothers. They have merged with mothers. They were sent off to boarding schools at young ages. They go to intensive care units and incubators and the mother has problems with the father so the mother takes her eyes off the child and doesn’t myelinate the child’s sense of self. Then mother’s offline. Then they have stillbirths and miscarriages and they’re all there in the history almost every time in a complex illness patient.

Mary Vallarta:

Hmm. So basically you meet them where they’re at.

Dr. Bruce Hoffman:

Yes, I tend to meet them where they’re at. You try and work out each level.  At level one what’s going on? Is it food? Is it mold? You do your normal medicine. Then you ask deeper questions. Are some of these symptoms teleological? Are these symptoms bringing patients to you because they have to heal a part of themselves that they never integrated in their evolution? For instance, I had a patient with MS whose father was a very famous sports coach and she never felt seen by her father, always neglected. She had a superego that is highly punitive, and she didn’t feel ever seen. So she was constantly beating herself up and attempting/strivinh to become more than she could possibly be. She tried and tried and tried, but dad was always coaching the team.

Dr. Bruce Hoffman:

Then the dad, when she was 18 or 19  I believe, her father got fired from the team. The next day she developed MS. The next day. That symptom was saying, dad, you were never there to take care of me. Now, look at me, I’m sick. He rose to the occasion. When he was fired, he was at home and he could be with his daughter. It was set up that way, that the symptoms drew that complexity together for it to be resolved. When she got that installed that she used that to use that in healing. It was very powerful. I have many, many cases and stories like that, where symptoms guide people to heal a part of themselves they’ve left behind.

Mary Vallarta:

Right. That is fascinating.

Dr. Bruce Hoffman:

Symptoms don’t fall out of the sky.  They have intent. In my experience.

Mary Vallarta:

Yeah. I think that the more I speak to all of the experts that I’ve talked to so far, the more I’m realizing that symptoms are really an opportunity for people to get to know themselves on a deeper level.

Dr. Bruce Hoffman:

I did a workshop with Mark Wolynn who is one of the great family constellations authors and workshop leaders out there. Once a year, we’ll do a workshop on illness and your family system and early developmental trauma. Almost to the person, we can link the rising of symptoms to events in the lifespan that needed to be resolved and healed. Once we linked them and made them conscious and gave them the homework to do, there was a vast new release of healing potential because you don’t heal until you have a new internal dialogue, a new story, a new narrative. If you have the old narrative, you create the same biochemistry. People with a new narrative, they have a new insight. It releases a potent internal life force that then constellates the biochemical pathways downstream to advocate healing.

Dr. Bruce Hoffman:

So we would do this workshop. Mark was a master at family constellations. Patients would sit next to him, and we would ask what their problem is and they’d say thyroiditis or leaky gut or Mast Cell, mold, whatever.  Then you’d say, well, tell me about your mother. Tell me about your father. Tell me about your grandparents and your siblings. Then he’d put up people in this constellation and worked with them energetically as to what was going on in the system and how their symptoms correlated with the dynamics of the system, the entanglements of the system. They could see how their symptoms didn’t just arise from nowhere. They were contingent upon some of these entanglements that needed to be healed. Once they saw what they hadn’t perceived before because children will often tell themselves a story that’s not true.

Dr. Bruce Hoffman:

They’ll say their mother was mean and angry, but their mother lost two children before they were born. The mother got very little from her mother. The mother was always bothered about the father who is out doing something or other. So the mother just had a little bit to give and unless the child sees that, and sees the mother through new eyes, the judgment of the mother will be there.  A person is half their mother, half their father. If they start judging half of themselves, guess what? They’re not open to the healing force, which is their whole self.  So everybody ultimately has to realign with their parental mothers and fathers. If you don’t say yes to your mother and father, your healing is going to be limited, no matter what you’ve experienced.

Mary Vallarta:

Because it’s pushing yourself away. They’re half of you like you mentioned.

Dr. Bruce Hoffman:

That’s the setup for auto-immunity by the way.

Mary Vallarta:

Oh yeah, because you’re rejecting yourself and autoimmune, right? Oh my God, that is powerful. I don’t even know what to say right now, but it shows how important it is to really understand yourself, but also understand your parents.  Also understanding your grandparents because your grandparents affected your parents’ psyche. It affected how your parents treated you.

Dr. Bruce Hoffman:

No question. 100%. There’s a one-to-one correlation.

Mary Vallarta:

So Dr. Hoffman, switching gears here a little bit because I’m also quite interested in anti-aging medicine, but I don’t know too much about it. Could you tell us a little bit about what that is?

Dr. Bruce Hoffman:

It’s a myth.  I’ve trained in it but there is no anti-aging medicine. It’s a nice sort of slogan for slowing down the process of aging. Okay. We all age. You’ve got the hormones of youth and you’ve got these drives.  In the first 30 years, you can do no wrong. You just push yourself through everything. Then entropy sets in and you start to sort of come apart slowly but surely.

Mary Vallarta:

You’re noticing it now.

Dr. Bruce Hoffman:

No question. The wrinkles and the skin sags.

Mary Vallarta:

The low back pain

Dr. Bruce Hoffman:

Then you get the inflammatory diseases of aging. Then you get separated into either heart disease or cancer or one of those things. They are all driven by genetics and environment and lifestyle and mind/ body.  The more inflamed you are by your lifestyle, the more unresolved you are with multiple triggers, the more interleukin six and tumor necrosis factor and all the inflammatory signalings are flying around, destroying your mitochondria, which then reduce your ATP, which then reduce your life force. So what we do in anti-aging medicine is try and slow down that trajectory before all is lost.

Mary Vallarta:

Yeah. There’s no way that you can stop yourself from aging. It’s just really about how to stop those symptoms of aging or delay them, right?

Dr. Bruce Hoffman:

Modify it so that your entropy isn’t like this.  Then you drop dead one day because your gene pools run out,  it’s time.

Mary Vallarta:

Yeah. It reminds me of my grandmother. She died, but she didn’t really die of any disease or illness. I think it was just because she was older and her body was just tired.

Dr. Bruce Hoffman:

The genes give up.  Everything ends.

Mary Vallarta:

Yeah. So share some of the most important things you’ve learned from your spiritual teachers. You’ve named a lot of big names, in your bio, like Deepak Chopra and Osho.

Dr. Bruce Hoffman:

So, here’s the answer. You probably won’t want this one.

Mary Vallarta:

Give us the real answer, not what you think we want to hear.

Dr. Bruce Hoffman:

People who’ve had difficult upbringings, who’ve had some complexity in their early developmental years, will often go to find spiritual teachers to take the part of the good parent that they feel they didn’t get. So whenever I have patients come in who have spiritual teachers and gurus, I’m very suspicious. Having had very many spiritual teachers and gurus myself. Having been to India three times and sat on many mountain tops meditating. So that’s the first insight that I really want to emphasize. It’s not wrong. It’s just when people don’t heal with their individual mothers and fathers, they’ll find a great mother and father that will look upon them benignly.

Dr. Bruce Hoffman:

You’ll find a lot of the great spiritual teachers who went to Burma and Thailand and India in the seventies, all of the Western students of spirituality. There are a lot of them. Jon Kabat-Zinn is one of them, Jack Kornfield is another. They all went and meditated for 15, 20 years, put on red robes and then came out of the forest, went back into cities of America, started to see people and all of a sudden realized, hold on a second, we are just performing spiritual bypass. These people have got messed up lives and they all went and became psychologists.  They all needed to heal the early traumas that people were trying to bypass to develop spiritual awakening. So that’s one of the greatest insights I’ve seen over the years. It’s not that spiritual teachers can’t provide some insight, but I always get a little uneasy when I see a guru sitting on a big white pedestal.  Then there are all of these devotees.  And I’ve done that for decades.  I’m judging myself.

Dr. Bruce Hoffman:

Then I just always ask, what is it about this experience that was being bypassed? What is it that they are trying to gain? What, what layer and level is still unfulfilled in their evolution? That’s what my curiosity is because an awakening experience into Satori is a sort of a brief exposure where you go beyond mind/ body and you actually know that everything is unified. There is no past/present/future. There’s nothing to fear and you’re sort of eternal,  immortal and you’re never born and you never die. That is what happens when you awaken.  But to sit in front of a guru to try and get that experience, I’m not sure that’s the best use of your time.

Mary Vallarta:

Yeah. I think it’s just an illustration of how you’re still searching for answers outside of you.

Dr. Bruce Hoffman:

That’s what Advaita says.  The essence of Advaita, which I learned at 15 was the very act of seeking prevents you from being who you are because you are that. So what are you seeking? You are already that thing.

Mary Vallarta:

What are you seeking? Exactly. I get that. That is really good advice when you think about it.  The answers are not out there. They are in here.

Dr. Bruce Hoffman:

Carl Jung said the urge to be whole is evolutionary. You can’t avoid it. Dianne Connelly said all sickness is homesickness. You try to come home to the most integrated aspect of who you are.  You can’t just go and sit with a guru.

Mary Vallarta:

That won’t give you the answers.

Dr. Bruce Hoffman:

It’s fun, and it’s very pleasant for a time. And I’ve done it for a long time, but you still got to go down the chakras and work your way through them. Early developmental trauma.  All of that stuff. You’ve got to heal that stuff.

Mary Vallarta:

If anything, it’s sort of a way where someone could continue resisting actually looking at themselves, getting to know themselves by sitting with a guru, and not ever advancing to internal examination.

Dr. Bruce Hoffman:

Perfect, perfect example you just gave.  It really does, in many cases, exemplify and exaggerate, the very pathology that’s brought them to the guru in the first place, which is resistance and projection. By sitting in front of the guru they are refusing to face the very thing that they need to face, which is themselves and their defenses.

Mary Vallarta:

Yes. Fascinating. So aside from sitting or seeing your patients, one-on-one Dr. Hoffman, you also actually have online programs and courses that people can take. Can you tell us a bit about what those are?

Dr. Bruce Hoffman:

Well, it’s funny, I used to do weekend workshops and all sorts of things. Then I condensed it all into a Friday afternoon lecture, a one-hour lecture for my new patients. Then the one-hour lecture became seven hours. I felt sorry for my patients. So then I took that lecture and made it into a book. So that book and those videos are available.

Mary Vallarta:

Nice.

Dr. Bruce Hoffman:

Yeah. So if you want to learn Seven Stages to Health and Transformation, I have a video and I have a PowerPoint explanation of it all, but I no longer lecture to that degree. I’m going back and starting to do lectures on different topics like Alzheimer’s disease and Mast Cell Activation and mold exposure and various aspects of mind-body healing. Those are in development. Most of the time now I’m helping other practitioners. Guiding them through this new curriculum of Seven Stages to Health and Transformation where not only do they learn new skills, but they learn about themselves.

Dr. Bruce Hoffman:

They have to stay congruent, they have to be present in that experience. I forgot to mention as part of my explanation, I went off at a tangent, that patients who don’t have good relationships with their parents have low trust. If they have medical PTSD or trauma from the medical system, that gets projected on you as a healer because all medical systems are very patriarchal and you are a parental figure. So if you’re sitting in front of a patient and there’s no trust established, there’s nothing you can do. So you have to ask that question first. You know I’m trying to teach people, other practitioners, how to be present with patients before they get more tools in their toolbox and go into courses and learn things.

Mary Vallarta:

That is so important.

Dr. Bruce Hoffman:

How to develop trust with a patient. Sometimes you can’t, they’re too traumatized and you try your best, but it’s just not possible.

Mary Vallarta:

But that just shows the role that each person plays. The role that the practitioner plays and also the role that the patient plays. If either one of them is not invested, it’s not going to yield the highest potential outcome.

Dr. Bruce Hoffman:

It won’t. Some people are too traumatized with too much mental health illness that they just can’t do what it takes to show up in that experience. Then you just have to admit that it’s not going to work out. You have to learn who is sitting in front of you. Also, know yourself through your own Myers – Briggs typology, through your own Ayurvedic typology,  you have to know if you’re Vata, Pitta, Kapha. Is that patient Vata, Pitta, Kapha because the Vata patient is not going to do what the Kapha patient does. They are an entirely different person.

Mary Vallarta:

Yeah. And then honoring and accepting that type of person and not projecting another type of person in that chair.

Dr. Bruce Hoffman:

If I’m a Pitta practitioner in my hero archetype and I know everything, I’m going to tell you what to do. And the Vatta patient walks in and is very sort of inspired for like three days and then they lose interest. If you impose your value system and your Ayurvedic typology or dosha onto them, and you don’t resonate and know how to treat Vata patients, you will lose them and you’ll feel frustrated.  Like a Kapha patient, they always show up, they never do what you asked them to do, or they do very little, but they’re always very loyal.

Mary Vallarta:

Very loyal. And we’re talking about Kapha, Vatta, Pitta. Those are the different dosha constitutions, that we talk about in Ayurveda.

Dr. Bruce Hoffman:

Then the Pitta patient, if you’re not the best in the city, they’ll leave you and go find the best.

Mary Vallarta:

They are looking for the facts. They’re like the fact-finder.

Dr. Bruce Hoffman:

You’re not sharp enough and don’t have the best office and are always on time….

Mary Vallarta:

You gotta check all the boxes for the Pitta patients.

Dr. Bruce Hoffman:

But as a practitioner, you’ve got to know who’s coming in the door because you’ve got to adjust the way you interact with them.  Knowing your Myers-Briggs typology as well, thinking people are not the same as feeling people. You’ve got to know that.

Mary Vallarta:

That’s very true. It’s sort of like detective work that you have to do when you work with your patients. Well, Dr. Hoffman, I can talk to you for hours. There are so many different questions that I can keep asking you, but for the sake of this particular interview, I’d like to ask if there’s anything else, one thing that you can leave us with here today that you didn’t get a chance to cover.

Dr. Bruce Hoffman:

In regards to talking to well people? Or people with complex illnesses? Or could you give you more direction?

Mary Vallarta:

Yeah. Well, the title of the summit is Healing Your Chronic Illness and Taking Your Life Back, meaning taking control of your health, right? Being the person and seeing the power that you have to own your life, to own your health. And so what would be the last thing that you’d want to leave us with here today?

Dr. Bruce Hoffman:

I think what’s most important is that people have to understand that if they present with chronic ill health or chronic complex illness, they have to try and find a practitioner who has a broad range of experience with multiple tools in their toolbox. They can’t just do one stool test and hope to heal. That’s number one.

Number two, they have to become their own patient advocates. If they are not invested in advocacy, there is very little that you can do.

Number three, they can’t project all the will to heal on the practitioner. They have to take some of that responsibility themselves.

Number four, they have to raise health up as a value. If the health isn’t one of the first or second values, it will default to number four or five, wherever you have your highest value, you will have your most order. Wherever you  have your lowest value you will have your most chaos. If health truly isn’t your highest value, be honest with yourself. Then look at it and say in the future, I will make it my high-value but right now I want to keep working and eating poorly and making money because that’s where my highest value is. Not wrong or right.  Just be honest and truthful and know your value system.

Mary Vallarta:

Wow. That is a great way to end the discussion. I feel like you beautifully summarized our conversation and added new thoughts to it. So I appreciate that. I will go ahead and make sure that I link Dr. Hoffman’s website, where some of his writings and programs are, so you all can take a look. I’ll also include that in the post-summit email. Dr. Hoffman, you’re also on social media. So what is your handle where people can find you and possibly connect with you there?

Dr. Bruce Hoffman:

So Instagram. My staff said, “make sure you say this at the end”.

So Instagram is www.instagram.com/drbrucehoffman/

Facebook is www.facebook.com/TheHoffmanCentreforIntegrativeMedicine/

and then the website is www.hoffmancentre.com.

I also have a brain treatment center, www.braintreatmentcentreofalberta.com I think those are all the handles.

Mary Vallarta:

Yeah. I mean, there are more.  Do you have a Tik Tok? Do you have a Twitter?

Dr. Bruce Hoffman:

Yeah. Yeah. Yesterday my Twitter account was activated by an assistant. I have no clue.

Mary Vallarta:

There you go. Well, Dr. Hoffman is on Instagram, so you can catch him there. I think that everyone’s on Instagram. So find him on IG. You should see the links in the handles below. Look at his website. There are a lot of resources there where you can get started if you are interested in everything that we’ve talked about. As Dr. Hoffman said, be truthful to yourself and meet yourself where you are. Stop, resisting, and meet yourself where you are, because that is an integral part of starting and continuing the healing journey.

Dr. Bruce Hoffman:

Also, the outer aspects of healing often in complex illness have to be congruent with inner healing too. You can’t just take a potion or herb. It’s much more complex than that. You’ve got to take a full system approach. There is a lecture being posted on my website soon on YouTube, where I give a 1 ½ hour lecture on the Seven Stages of Healing which will summarize some of the things we’ve mentioned.

Mary Vallarta:

Ooh, yes. I’m gonna watch that for sure. Okay. Thank you so much for joining us today. Hope you got a lot out of this.  Dr. Hoffman, you are amazing. Thank you for speaking with me.

Dr. Bruce Hoffman:

Yeah. It was nice talking with you.

Health Benefits of NAD+ Supplements

Health Benefits of NAD+ Supplements

NAD+ is a molecule that’s found in every cell of your body that plays many key roles in energy production, health, and longevity. Exciting research has uncovered why NAD+ is so essential and has led to many clinical applications, addressing everything from the signs and symptoms of aging to treating and preventing chronic disease.

In this article, you’ll learn more about:

  • What NAD supplement is
  • The two forms of NAD, namely NAD+ and NADH
  • The role NAD+ plays in health and disease
  • Why increasing levels of NAD+ is important
  • What sirtuins are and how they require NAD+
  • The role sirtuins and NAD+ play in vascular aging
  • Health conditions that benefit from increasing NAD+
  • The three ways the body produces NAD+
  • Natural ways to increase NAD+ levels in the body

What is NAD+?

A fair amount of attention has been given to NAD+, particularly for its ability to slow down the effects of aging. NAD+ stands for nicotinamide adenine dinucleotide and it’s used as a coenzyme in many molecular processes that keep your cells and body alive. A coenzyme is like an enzyme helper or assistant and needs to be available for the reaction to take place.

Adequate intracellular NAD+ levels don’t just prevent hastening of cellular aging. They also help to prevent the visible signs of aging that become apparent on the skin. The use of NAD treatment for addiction relies on the speedy delivery of NAD IV therapy and there are numerous NAD+ addiction clinics operational in the United States.

The NAD+ molecule is found in every cell in the body, enabling the conversion of food we eat into energy and chemical products that the body needs to sustain itself. This is very important, since the health and function of every cell relies on this tiny molecule.

NAD+ also plays a critical role with enzymes that regulate gene expression involved in the repair of damaged DNA. Through these pathways, NAD+ influences a variety of processes involved in every cell in your body, improving mitochondrial efficiency, enhancing cell viability, down-regulating inflammation, increasing the antioxidant capacity of cells and tissues, and activating SIRT1, a sirtuin enzyme that plays a role in longevity.

NAD+ and NADH are two different forms of the same molecule, picking up and dropping off electrons. This energy exchange of electrons is what allows the Krebs cycle and electron transport chain to produce ATP, the energy currency in humans. When it picks up an electron, this is NADH, while without the electron it is known as NAD+.

The role of NAD+ in health and disease

Several of these critical roles have already been mentioned, but let’s take a closer look at some of the life-sustaining benefits of NAD+ .

NAD+ is a cofactor for hundreds of enzymatic reactions, such as chromosomal stability and DNA repair. DNA damage is linked to deteriorating chronic health problems, as recently discussed by Robert Naviaux and his theory of the Cell Danger Response.

NAD+ also plays a vital role in energy production, in the Krebs cycle conversion of macronutrients including protein, fats and carbohydrates, and micronutrients such as vitamins and minerals, to ATP. This is the energy molecule that’s crucial to the running of all the body’s essential functions.

In addition, NAD+ is also a cofactor for hundreds of similar enzymatic reactions that are involved in:

  • Immune cell signaling and immune strengthening
  • Decreasing inflammation
  • Decreasing oxidative stress and ‘rusting’ of cells
  • Telomere production, with longevity enhanced by longer telomeres
  • Neurotransmitter production
  • A healthy circadian rhythm and sleep cycle
  • Increased activity of sirtuins, which play a role in longevity (see more on this below)
  • Prevention of blood vessel damage that reduces the risk of heart disease
  • Healthy aging

The importance of increasing levels of NAD+

NAD+ plays a central role in every one of the body’s functions. We simply can’t do without it. In addition, if we boost its levels, we can further optimise cell functions and energy outcome. Unfortunately, as we age levels of NAD+ decline, leading to signs and symptoms of aging.

Low levels of NAD+ are associated with:

  • Accelerated aging
  • Increased sunburn and skin cancer
  • Decreased cellular antioxidants
  • Decreased metabolism along with thyroid hormones
  • Harmed immune function
  • Increased inflammation
  • Impaired brain function
  • Hypoxia (low levels of oxygen) intracellularly

When NAD+ levels are higher and more robust, we see the following:

  • Improved mitochondrial health
  • Improved cellular metabolism and energy production
  • Improved production of sirtuins
  • More NAD anti-aging benefits
  • Improved DNA repair and recovery
  • Increased immunity, with NAD+ stimulating CD38 that’s present on T-cell immune cells, effectively boosting the immune response
  • Stimulation of CD38 activity increasing oxytocin, a hormone associated with social intimacy and bonding
  • Increased autophagy or cellular recycling
  • Increased redox potential, with more antioxidant action protecting cells
  • Improved insulin sensitivity, decreasing the risk of metabolic syndrome and diabetes
  • Improved protection of brain cells from oxidative stress, rescuing neuronal loss and improving myelination
  • Improved skin health by boosting levels of collagen, keratin, elastin, and hyaluronic acid, a compound found in many skin rejuvenating creams
  • Increased stem cells
  • Improved exercise performance

NAD+ provides these benefits through several key mechanisms, including:

  • Promoting AMPK activity, an enzyme that improves metabolism and helps protect against obesity and diabetes.
  • Modulating p53, a tumor suppressor gene that repairs damaged DNA and protects against cancer initiation
  • Inhibiting NF-kB or nuclear factor-kappa B, a protein that induces the chronic inflammation tied to many diseases and premature aging
  • Inhibiting mTOR, a molecular complex whose abnormal activation contributes to many chronic diseases of aging

Sirtuins and NAD

Sirtuin is an acronym for ‘silent information regulator’. This refers to any family of enzymes, made up of proteins, that occur in all living organisms. They’re thought to regulate a wide array of cellular processes such as cellular aging, apoptosis, and stress resistance in more complex organisms. It’s been demonstrated that increasing sirtuin activity leads to longer life and reduction in age-related loss of function. It also protects against DNA damage. NAD levels decline with aging, which also results in reduced sirtuin activity. Boosting NAD+ helps to ramp up this activity.

Seven sirtuins have been identified and play different roles in the body.

  • Sirtuin 1 (SIRT1) repairs DNA and vascular tissue and is highly dependent on NAD+ levels
  • Sirtuin 2 (SIRT2) reduces body fat and oxidative stress
  • Sirtuin 3 (SIRT3) influences longevity
  • Sirtuin 4 (SIRT4) can repress tumors and autophagy
  • Sirtuin 5 (SIRT5) reduces fatty acids in the liver and oxidative stress
  • Sirtuin 6 (SIRT6) regulates blood sugar and decreases insulin resistance
  • Sirtuin 7 (SIRT7) benefits the heart

NAD+, sirtuins, and vascular aging

As we age, our small blood vessels die off. This compromises blood flow and the oxygenation of organs and tissues that are fed by these small vessels. Vascular aging is responsible for a constellation of disorders, such as cardiac and neurological conditions, muscle loss, impaired wound healing, and overall frailty.

Dr. David Sinclair, a researcher at the Department of Genetics at Harvard Medical School and a co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School, has discovered a way to reverse vascular aging by boosting the presence of naturally occurring molecules in the body that augment the physiological response to exercise. He states that, “The approach stimulates blood vessel growth and boosts stamina endurance in mice and sets the stage for therapies in humans to address the spectrum of diseases that arise from vascular aging.”

Dr. Sinclair’s study revealed that NAD+ and SIRT1 enable the conversation between endothelial cells in the walls of blood vessels and muscles, but specifically the cells in young mouse muscles, activating SIRT1 signaling generating new capillaries that supply oxygen and nutrients to tissues and organs. Conversely, the study demonstrated that as NAD+/SIRT1 activity diminished over time so did blood flow, which left muscle tissue deprived of nutrients and starved of oxygen.

Dr. Sinclair gave an NAD supplement, as an NAD+ precursor, for two months to a group of mice that were twenty months old, roughly equivalent to seventy in human years, to test its effect on SIRT1 signaling. The treatment worked and restored the number of blood capillaries and capillary density to those seen in younger mice. Blood flow to the muscles also increased and was more significantly higher than blood supply to the muscle seen in mice of the same age that didn’t receive the NAD+ precursor.

The most striking effect emerged in the aging mice’s ability to exercise. These animals showed a 56 to 80 percent greater exercise capacity when compared to that of untreated mice. It was concluded that this observation underscored the notion that age plays a critical role in the crosstalk between blood vessels and muscles. This points to a loss of NAD+ and SIRT1 as the reason behind the reduction in exercise effectiveness after middle age. The researchers believe that their findings might pave the way to therapeutic advances that might be able to help the millions of older people for whom regular physical activity is no longer an option.

“Even if you’re an athlete you eventually decline,” Sinclair says. “But there is another category of people – what about those who are in a wheelchair or those with otherwise reduced mobility?”

Dr. Sinclair’s mouse study suggests that NAD+ may support exercise performance in humans. In a study involving elderly men, supplementation with an NAD+ precursor resulted in improved exercise performance. The men had an 8 percent improvement in peak isometric muscle torque, which is a measure of muscle force, and a 15 percent improvement in lessening of fatigue associated with exercise.

Health conditions that benefit from increased NAD+

Considering what we’ve explored regarding NAD+ energy production in every cell and the importance of this molecule in all aspects of health and longevity, it’s no surprise that NAD+ may benefit a number of health conditions, including chronic disease. Conditions that may benefit from increased levels of NAD+ in the cells include:

  • Addiction
  • Allergies
  • Neurological deficits
  • Depression
  • Brain injury
  • Cholesterol metabolism issues
  • Cancer
  • Chronic fatigue syndrome
  • Fibromyalgia
  • Irritable bowel syndrome (IBS)
  • Diabesity spectrum, including obesity, metabolic syndrome, and Type 2 diabetes
  • Systemic inflammation
  • Lyme disease
  • Malabsorption syndromes
  • Parkinson’s disease
  • Alzheimer’s disease
  • Huntington’s disease
  • ALS
  • PTSD
  • Autism spectrum
  • Small bowel overgrowth syndrome (SIBO)
  • Cardiovascular disease
  • Multiple sclerosis
  • Hearing loss
  • Renal disease

NAD+ pathways of production

There are three major pathways that our body employs to synthesize in NAD+. Influencing and activating these pathways are a way to increase NAD+ within the cells of the body.

The first pathway is the de nova synthesis from the amino acid tryptophan from food protein sources, which also intersects with vitamin B3. This is the long way round.

The second is a salvage pathway, used by the supplement company PRICERA, that our body uses daily to recycle nicotinamide (NAM) according to circadian rhythms. This is the dominant and most robust path for any NAD+ synthesis.

The third pathway is specialized for nicotinamide riboside (NR) reactivation. NR is a shunt product in NAD+ synthesis.

The supplement company claims that PRICERA is the only available compound that utilizes the naturally dominant pathway to generate NAD+ efficiently and robustly. This product is said to improve the tissue distribution of NAD+, maintain and enhance mitochondrial health and creation, and plays a key role in calorie restriction for increased lifespan and exercise response. PRICERA is also said to prevent neurodegeneration and reduce age-related cognitive decline. In addition, it’s claimed that PRICERA increases ATP and maintains antioxidant levels including glutathione, which generally becomes depleted with higher energy requirements or when we’re under stress.

PRICERA differs from other NAD precursor products in that it includes D-ribose, a known source of energy for the mitochondria in the heart, brain, and muscles. Other NAD precursor products need ATP to prime the pathway. However, since PRICERA spares the body’s own energy, one of its key applications may be to serve individuals with compromised mitochondrial function. This can actually hamper performance under oxidative stress.

How To Raise NAD+ Naturally

Fasting, calorie restriction, exercise, and NAD boosters increase the intracellular levels of NAD+, activate SIRT1, and have other physiological benefits. There are a number of ways to boost your NAD+ levels naturally through lifestyle change, diet, and supplementation.

When we exercise, we use up NAD+ and replenish it rapidly. As a result exercise can help us to build up our reserves.

When we burn fat for energy instead of carbohydrates, we preserve adequate levels of NAD+ and increase levels of NAD+ in the brain. This reduces DNA damage in the hippocampus, which is the location of memory storage. Ketosis is achieved by following a ketogenic diet. In addition, ketosis might be enhanced for part of the day through practices such as intermittent fasting, fasting mimicking, or periodic longer fasts. Calorie restriction and intermittent fasting will also increase NAD+ levels.

Vitamin B3 or niacin supplements, along with foods rich in vitamin B3, such as green vegetables, chicken, portabella mushrooms, rice, nuts, tuna, although you need to be careful of mercury, will benefit the body’s NAD+ production. Niacin is believed to act as a building block for NAD+ levels. Lycopene-rich foods, such as tomatoes, also help to prevent NAD+ depletion.

You can take a NAD+ supplement orally or apply it to your skin. When taking an oral preparation you have to take a precursor molecule, as NAD+ will break down in your gut without being absorbed. Nicotinamide riboside (NR) is this type of NAD+ precursor.

NAD IV may be an option for individuals with certain conditions such as addiction, who have access to this type of therapy. NAD+ bypasses the gut and is delivered directly to the bloodstream, where it can enter cells.

NAD repletion strategies, such as those outlined above, have shown therapeutic potential as a means to restore a healthy metabolism and physiological function. Many health conditions are multifactorial and require a root cause approach. Bearing in mind the robust and expanding research on NAD+ I’m often considering NAD+ depletion as a factor in patient’s cases, working with them to restore these pathways and reap all of the physiological and anti-aging benefits.

To work together one-on-one, please contact my office for an appointment.