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.

Mast Cell Activation Syndrome and Excipients

Mast Cell Activation Syndrome and Excipients

Mast cell activation syndrome (MCAS) is a complex disease that I’ve previously written about at length. It’s a multi-faceted condition that can often be frustrating and difficult to manage for both the patient and the provider.

Mast cells are immune cells that function to help your body get rid of what they deem to be harmful compounds. In the presence of a harmful substance, the mast cells release mediators such as histamine, leukotrienes and prostaglandins which help your body to expel the invader.

However, in certain individuals, mast cells can be oversensitive and release large amounts of mediators in response to certain triggers. These include heat, cold, sunlight, certain medications, and certain foods, among other things. These reactions can cause a cascade of symptoms of varying severity, up to and including anaphylactic shock.

Treatment for MCAS involves identification and strict avoidance of your triggers, along with medication therapy and lifestyle changes. Medications that may help with the management of MCAS include H1 and H2 histamine blockers.

However, sometimes these changes alone aren’t enough to help you completely manage your MCAS. You may also struggle to identify what triggers your MCAS reactions.

MCAS is considered ‘idiopathic’ when triggers can’t be identified. If you’re struggling with idiopathic MCAS, this article will be of interest to you.

Common drugs known to trigger MCAS

  • Vancomycin is an antibiotic often used in C. Difficile treatment, which is known to cause ‘Red Man Syndrome’.
  • Morphine and other opiates, with fentanyl and Dilaudid being the opiates that are the most easily tolerated.
  • Aspirin and non-steroidal anti-inflammatories (NSIADS), like Motrin and Advil, are only sometimes a problem as in certain people they can actually act as mast cell inhibitors.
  • Angiotensin converting enzyme inhibitors, known as ACE inhibitors, are drugs used to treat hypertension and can increase bradykinin levels, which in turn activates mast cells.
  • Beta-blockers are used to treat hypertension, anxiety and tachycardia and lower the threshold for mast cell activation, interfering with the efficacy of epinephrine if this is needed for anaphylaxis. A glucagon pen can be used as an alternative if beta-blockers are necessary to treat other conditions.
  • Some local anesthetics, such as benzocaine, procaine, tetracaine, and chloroprocaine, can trigger mast cell activation, although lidocaine is usually well tolerated.
  • Some muscle relaxants like atracurium and succinylcholine can act as triggers, but vecuronium and pancuronium are usually well tolerated.

One relatively recent development in the treatment and management of MCAS involves considering drug and supplement excipients or inactive ingredients, rather than the actual drug itself. Drug formulations vary significantly between brands and there’s mounting evidence to suggest that many people with MCAS may have reactions to certain excipients found in their medications and/or supplements. The same drug or supplement made by different manufactures with different dyes, excipients, or fillers may provoke very different reactions in patients with MCAS. The active drug itself may not be the issue, but the excipients, dyes, and fillers may be the culprit.

In this article, you’ll learn:

  • What excipients are
  • How they can trigger mast cell responses
  • Some of the most common harmful excipients
  • How to tell if you’re having a reaction to an excipient
  • How to identify and avoid excipients that may worsen your MCAS

What are excipients?

Excipients are inactive ingredients found in over-the-counter and prescription medications, as well as in vaccines. These ingredients play a number of different roles in the proper delivery of the active ingredient to the body and many of these roles are absolutely necessary to facilitate the efficacy of the drug. (1)

In fact, most drugs are made mostly of excipients and the active ingredients represent only a small percentage of the drug by weight.

According to Dr. Jill Schofield of the Center for Multisystem Disease, excipients “are supposed to be ‘inert’ and ‘safe,’ but they may cause problematic reactivity in MCAS patients, including anaphylaxis.” (2)

Unfortunately, many excipients pose a risk of reactivity in people with MCAS, so it’s important to fully consider the impact of not only the active ingredients of a drug, but also its inactive ingredients when starting a new medication.

Types of excipients

There are over a thousand known drug excipients and the list grows almost daily, as researchers continue to develop new drugs and drug delivery systems.

Here are some of the main categories of excipients and their role in medications, according to Dr. Schofield:

  • Lubricants: These prevent pills from sticking together in storage, examples being silica and magnesium stearate
  • Binders and fillers: These provide volume to pills and bind ingredients together. Binders and fillers include cellulose and polyethylene glycol.
  • Coatings: These protect pills from damage, make them easier to swallow, and may provide ‘time-release’ or ‘extended-release’ function, examples being shellac and gelatin.
  • Dyes: As you’d expect, these alter the color of medications. Dyes used include FD&C red #5 and FD&C blue #2.
  • Flavourings: These alter the taste of the drug to mask bad-tasting ingredients and improve acceptance of the medication, especially in the case of children. Flavouring examples include sucralose and xylitol.
  • Preservatives:Substances such ascitric acid and retinol palmitate improve the shelf life of medications.

This is just a small sampling of some commonly used excipients. Not only are there hundreds more individual excipients, there are also many more categories of excipients that play different roles in medications. If you have had a previous reaction to a vaccine for unknown reasons and wish to be receive a specific vaccine in the future you may wish to consult this chart and consider having a sensitivity test run on you for the VACCINE INGREDIENTS. 

How can excipients affect MCAS?

Dr. Schofield describes people with MCAS as “canaries in the coal mine.” If you’re unfamiliar with this turn of phrase, it refers to the canaries that were carried by miners deep into mines when they worked. If there were toxic levels of gases present in the mine, the canary would die well before the miners, serving as warning that they needed to get out of the mine.

People with MCAS, like the canaries in the coal mine, are profoundly more sensitive to the chemicals they’re exposed to than other people. Unfortunately, this means that many people with MCAS experience reactivity to one or more drug excipients. These reactions can manifest in the following ways:

  • Fatigue
  • Malaise
  • Gastrointestinal upset, such as abdominal pain, nausea, vomiting, or diarrhea
  • Skin rashes
  • Itchy skin
  • Hives
  • Headache
  • Anxiety
  • Flushing
  • Anaphylaxis
  • Headaches
  • Insomnia

However, this isn’t a complete list of symptoms of excipient reactivity. MCAS is such a complex and individualized disease and symptoms can differ vastly from person to person.

If you’ve been diagnosed with MCAS and have removed your known triggers but are still experiencing symptoms, it may be time to investigate drug and supplement excipients and how they may be affecting you.

What are some of the common harmful excipients?

Some of the most common excipients that people with MCAS are reactive to include alcohol, dyes, and povidone. In fact, according to Dr. Schofield, dyes and alcohol are a great starting point for determining excipient reactivity in MCAS patients, primarily because so many people are reactive to them.

Povidone

Povidone is an extremely common excipient, used as an ingredient in hundreds of drugs. (3) It’s a polymer that’s added to drugs to help disperse the active ingredient evenly throughout a liquid or powder solution. It’s also used as a binder and to help drugs in pill form disintegrate properly. It’s water-soluble, so it’s commonly used in liquid drug solutions as well as in tablets or capsules.

It’s an ingredient in betadine, an antiseptic iodine solution that’s used to prep the skin before medical procedures. According to Lawrence B. Afrin, M.D., if you’ve previously been diagnosed with a betadine allergy, it’s highly likely that you’re actually sensitive to povidone. (4) You see, iodine is absolutely vital for proper body functioning so it’s illogical, and emerging research suggests it’s impossible, to be allergic to iodine (5). Because the only ingredients in iodine solutions like betadine are often water, iodine, and povidone, and it’s highly unlikely that you are allergic to water or iodine, this leaves povidone as the likely culprit.

Dyes

Dyes are ubiquitous in medications, a very common MCAS trigger, and unfortunately serve no purpose beyond an aesthetic one.

Although you may find that you’re only sensitive to one or two dyes, it’s often best to avoid all FD&C dyes when possible. Ferric oxide red and yellow may be better tolerated by people with MCAS, according to Dr. Schofield.

You should note that even white tablets may contain dyes, so you’ll need to check the ingredient list for confirmation.Many drugs have dye-free formulations or, in the case of drugs in capsule form, you can discard the capsule. This is often the only portion of the drug containing the dye and you can then simply take the powder inside.

Alcohol

According to Dr. Schofield, alcohols are an extremely common trigger. They’re commonly added to liquid medications, IV medications, or topical medications, which are applied directly to the skin.

Alcohol has some antiseptic qualities, which is why it’s used to disinfect the skin prior to medical procedures, along with being used as the active ingredient in most hand sanitizers. It’s also used as a solvent, to help suspend the active ingredient evenly throughout a drug, and as a preservative, to extend the shelf life of a drug.

Luckily, tablet or capsule forms of alcohol-containing liquid or IV medications are often alcohol-free. This makes them a potential alternative that wouldn’t cause reactivity.

Although these are some of the most common excipients that MCAS sufferers may react to, theoretically you could have a reaction to any of the hundreds of excipients that are used in medications today. This is why an understanding of how to identify an excipient reaction is of the utmost importance for people with MCAS that suspect they have excipient triggers.

Adhesives

Many adhesives are based in glycerin, which is corn-derived. If people react to corn, they may have problems with standard adhesives. Standard tegaderm adhesive wound dressings may be replaced with Opsite 3000 and the IV 3000 line of adhesive products.

Another product is DuoDerm Extra Thin CGF Dressing. If adhesives can’t be used and a patient needs an IV line, this can be wrapped with guaze, on top of which tape is then fastened. All IV bags should be DEHO free to reduce the risks of mast cells reactions

How to tell if you’re reacting to an excipient

There are several ways to tell if you’re reacting to an excipient in a drug, according to Dr. Schofield.


First and foremost, you should suspect excipient reactivity if you have an unexpected reaction to a drug that you previously tolerated well. In this case, some questions you can ask are:

  • Did you get this from a different pharmacy than usual?
  • Is this drug from a different manufacturer than the one that was well tolerated?
  • Was there a risk for environmental contamination when this drug was compounded?

Next, you should suspect an excipient reaction if you have different reactions to two different medications that are in the same class of drug. For example, loratadine and fexofenadine are two over-the-counter antihistamines that function in similar ways to help manage allergies. If you react differently to these drugs, it may be because one contains an excipient that you’re reacting to.

Additionally, if you experience side effects that aren’t typical for a drug, these side effects may actually be a result of reactivity to one of the excipients in that particular formulation of the drug.

You should also consider an excipient reaction if you react to a drug or supplement within the first few doses of taking a new pill. 

Finally, if you’ve been diagnosed with multiple drug allergies or intolerances, you should strongly suspect excipient reactivity. Particularly if you’ve been diagnosed with an iodine or betadine allergy, this is a strong indicator that you may actually be sensitive to povidone. This is an excipient that’s commonly added to iodine solutions along with a variety of other medications, including those as seemingly harmless as over-the-counter pain medications.

Identifying and avoiding harmful excipients

Identification of excipients to which you’re sensitive will require collaboration between you, your physician, and your pharmacist.

According to Dr. Schofield, once you’re able to identify an excipient that you react to, it should be added to your allergy list. However, you shouldn’t add the medication in which it was found to that list, as it’s likely you’re only sensitive to the specific excipient and not the medication itself.

Luckily, due to the availability of different brands and formulations of drugs, it’s often easier than you expect to find a formulation of your needed medication that doesn’t contain any of your excipient triggers.

However, you’ll need to thoroughly review the ingredient list of all medications you’re prescribed, or purchased over-the-counter, to see if they include any excipients that you’re sensitive to. Dr. Schofield recommends using DailyMed, a service of the U.S. National Library of Medicine that provides detailed information about medication ingredients, including excipients.

You may need to get creative in your avoidance of your excipient triggers. For example, if the tablet form of a medication contains an excipient you’re sensitive to, check to see if there’s a capsule, liquid, or IV form that would be okay for you.

As I already mentioned, if you’re sensitive to dyes, you can often just discard the capsule that contains the dye and still use the powder inside the capsule. You can sprinkle it on top of yogurt or mix it into a drink.

If you find that you’re profoundly sensitive to a certain excipient, you may need to have your medications especially compounded in a ‘clean room’ that poses minimal risk for cross-contamination with your triggers. Your local compounding pharmacist should be intimately involved with the challenges of MCAS and the potential risks of excipient reactivity. Sourcing of the pure powder ingredient in a medication may be necessary. Compounding pharmacies should be accredited with their parent organization, the Pharmacy Compounding Accreditation Board (PCAB).Established in 2007 by eight of the nation’s leading pharmacy organizations, PCAB offers the most comprehensive compliance solution in the industry. This includes the combining, mixing, or altering of drug ingredients to create a medication pursuant to a prescription order for an individually identified patient.

In Canada, most of the compounding pharmacies will use microcrystalline cellulose, known as Avicel, as a filler. This compound is derived from wood pulp and contains strings of glucose molecules strung together. It’s commonly used a texturizer, an anti-caking agent, a fat substitute, an emulsifier, an extender, and a bulking agent in food production.The most common form is used in vitamin supplements or tablets or as an alternative binder in compounding medications. Some people may also not tolerate gelatin capsules and are given vegicaps as a substitute. These are composed of hypromellose, short for hydroxypropyl mMethylcellulose (HPMC), a substance that’s prepared from cellulose, which is the main polysaccharide and constituent of wood and all plant structures.

Additionally, excipients aren’t only found in medications. If you’re sensitive to an excipient, you’ll also need to check foods, supplements, cleaning products, cosmetics, and body care products to see if they contain any of your excipient triggers.

Please reach out to me or my team if you need help managing your MCAS or identifying potential triggers or excipient reactivity. My team is extremely experienced with the management of MCAS, and we can help you formulate a plan to identify your potential triggers and remove them so that you can have some relief.

References:

  1. Abrantes CG, Duarte D, Reis CP. An Overview of Pharmaceutical Excipients: Safe or Not Safe? J Pharm Sci. 2016;105(7):2019‐2026. doi:10.1016/j.xphs.2016.03.019 Abstract: https://pubmed.ncbi.nlm.nih.gov/27262205/
  2. Schofield J. The Problem of Excipient Reactivity in MCAS Patients. Lecture from The Center for Multisystem Disease, n.d.
  3. National Center for Biotechnology Information. PubChem Database. Povidone, CID=131751496, https://pubchem.ncbi.nlm.nih.gov/compound/povidone (accessed on May 31, 2020)
  4. Afrin LB. Re: [MASTerMinds] Precautions for Oral Surgeons doing Wisdom tooth extractions in CCI patients? #cci #mcas #dental. Email communication from MASTerMinds listserv. 2020 May 8.
  5. Dewachter P, Mouton-Faivre C. Allergie aux médicaments et aliments iodés : la séquence allergénique n’est pas l’iode [Allergy to iodinated drugs and to foods rich in iodine: Iodine is not the allergenic determinant]. Presse Med. 2015;44(11):1136‐1145. doi:10.1016/j.lpm.2014.12.008

How a Multi-Level Approach to Medicine Can Augment a Cancer Patient’s Treatment

How a Multi-Level Approach to Medicine Can Augment a Cancer Patient’s Treatment

Contrary to mainstream rhetoric, the treatment and prevention of cancer in patients is much more layered than a simple diagnosis and chemo, for example. Things such as past trauma, mold exposure, allergies, and metal toxicity exposure can truly impact how one recovers and even how one reacts to chemo. 

Watch the full video as Dr. Hoffman dives into some of the complexities of a multi-level approach to treatment of cancer in patients. 

Watch the Video

How a Multi-Level Approach to Medicine Can Augment a Cancer Patient’s Treatment

Reference Links

Transcript

Hi everybody. I received an email today from a colleague who is posting his case history on a cancer patient. He detailed the specific oncology issues that had arisen, his approach, and what he believed to be the correct treatment. I was thinking as I was reading this report from an integrative medicine physician about how far integrated medicine, medicine that incorporates many different layers and levels and dimensions of a personal experience, has come. This patient was managed impeccably by her oncologists. Insights were derived from post oncology or peri oncology type issues. When I read through the presentation of my colleague, I was struck by how we can bring so many more diagnostic and therapeutic features to the patient’s experience. When we consider the layers and levels that any individual person brings to the consultation, the history given by my colleague on this patient just touched on a few issues and could have been further expanded upon. I’d like to expand upon the history to provide a road map of how the seven levels, or the seven stages, to health and transformation can be incorporated when thinking of strictly biologically-based medicine.

In his history, he mentioned that this patient had breast cancer. She was treated with chemo and radiation and developed side effects. He went on to mention a few things, such as that she was sensitive, that she had experienced early developmental trauma, that she was a poet and artist, and that she had post chemo fatigue. He also happened to mention that she had a supportive framework, a loving husband, and was very involved in her own patient advocacy. In addition to everything else that he was bringing to the table, he wanted to treat her mast cell activation syndrome. He was looking for further triggers as to why she was still fatigued and anxious, things such as mold exposures or possible Lyme disease. 

In looking through this history, things came to my mind. Whenever there’s a history of early trauma, you have to look upstream to ancestral Inheritance. We know now that individuals carry the experiences of their forefathers. This is well researched and well studied and is now being incorporated into clinical medicine. Whatever the ancestors, particularly the mother, father, and grandparents had emotionally experienced gets epigenetically transferred into the proteomics and metabolomics. This is the cellular expression of that patient’s life that can’t be ignored. Secondly, when a person is born into a dramatic scenario, when they have interrupted bonds between them and their mothers, particularly their mothers in the first ten, twenty even thirty years, there’s a price that’s paid. Particularly if the patient isn’t entrained with the mother’s right prefrontal cortex in an empathic entrainment, one sense of self that inhibits early anxiety and stress or fear doesn’t develop a robust mechanism or the ability to inhibit should anxiety and stressful events arise in the future. So in early developmental trauma, when the child’s developing brain doesn’t entrain with the mother’s development, the mother’s external prefrontal cortex and just a side note, the mother may not have a very robust right prefrontal cortex either, but the child pays a price. They pay a price of potentially a fragile sense of self or even a very undeveloped sense of self and an inability to self regulate.

This is very obviously seen when you do NeuroQuant MRIs or qEEGs. You can see these fingerprints on the qEEG and on the NeuroQuant MRI in the form of increased amygdala size and increased thalamus size. The evidence is there. On a qEEG you can see heightened amplitude of the beta brainwaves, what’s called the anterior cingulate area, and you can see diminished alpha brain waves. You can see these fingerprints of biographical data on biomedical equipment. It’s important to know that. So if somebody has cancer and he’s had a very bad chemo experience with many symptoms post chemo, one does look upstream to any possible inherited trauma from the ancestral realm. One looks at early developmental trauma because all of these get affected through what’s called the HPA axis, the hypothalamic pituitary adrenal axis, in the form of a heightened stress response. The height and stress response can create permeability of gut membranes, mitochondrial membranes, and blood-brain barrier membranes, leading to a flood of potential autoimmune disease and/or inflammatory compounds. So it’s important to take that particular history to look at the brain through a NeuroQuant MRI and to look at the qEEG to see if there are any fingerprints and then therapeutically to assist that individual in self-regulation through various techniques, whether they be inside therapy, m-wave training, vehicle tone stimulators. I always recommend that people get an insight into the underlying dynamics, not just downregulate the biochemical or physiological pathway. 

When there’s early trauma and when there’s early developmental trauma we usually suggest family constellation therapy insight or family constellation workshop to look at the unconscious dynamics of that inheritance. For early developmental trauma, again we use family constellation therapy but sometimes we have to be more advanced. In those cases instead of doing a technique like DNRS, which just downregulates the expression of the anxiety that’s being felt, you need to do more advanced psychological techniques like ISDP. This looks at the defenses the individual developed as a child who wasn’t safe in their environment. They’ve developed the provisional self in order to cope with the slings and arrows of modern life, or just their early life.  So you’ve got to look at the family system that’s inherited, look at early developmental trauma, and the defenses that were developed by that person. Then you’ve got to look at the ego strength and structure of that individual to see if they have a robust sense of self. This determines if they can cope with sometimes what’s required of them to get their physiology and their health back online.

So with oncology and cancer, yes we can give chemo, we do radiation. We do those plus all the natural therapies but if you don’t look further upstream to all these potential mediators that keep a person somewhat off kilter, you don’t complete your healing interrogation and your diagnostic interrogation. So it’s very important to shine your light upstream to look at these potential inherited issues. We know from clinical experience that when you heal at a deeper level, the downstream metabolites and the downstream effects are profound. The body tends to express those consequences of the new images and the new insights and the new narratives in a more cohesive fashion. We say in this work that nobody truly heals until they have a new image or a new narrative or a new story to tell about their past and their present. This is vitally true to understand people who present with extreme complex multi-system illness. It’s never only at level two,which is the physical level. You can do all the most sophisticated functional medicine workups, you can give them every supplement in the book, you can send them to wherever you want to detoxify, or you can do bioidentical hormone therapy. But it doesn’t land in a robust place if that sense of self is fragile, if the ability to self-regulate is poor, if the defenses of the individual are too fortified and won’t allow you in. If a child has had an early experience that keeps them from trusting parental figures, do you think they’re going to trust medical authorities? Unlikely since we’re just external representations of parental figures. No healing occurs without a deep sense of trust. This is deeply profound. I’ve been called out over the years for not taking this seriously and developing an empathic trusting relationship with the patient because if that’s not established you might as well give up the rest of it. It’s not going to occur. Patients will resist your efforts to help them if there’s not an empathic relatedness between you and them whereby you understand their dynamics, you understand the fortifications of the psyche that prevent healing from occurring, and you relate subtly to what they’re asking you to do. Sometimes it takes time to establish a therapeutic alliance and a trusting relationship. If you bulldoze your way in and try to tell somebody what to do who has high resistance, something called projection of will, which means they’re asking you to fix them without any advocacy of their own, you’re in a precarious position and success is very limited.

So in this particular case I was struck by the fact that:

A) she had early trauma 

B) she had heightened anxiety

C) she had post chemo fatigue

And the whole world of post chemo fatigue of course has lots to do with mitochondrial dysfunction. In traditional medicine we’re not taught anything about mitochondrial dysfunction unless it’s a genetically inherited mitochondrial disease. Even in functional medicine you know mitochondrial dysfunction is paid lip service and people are given you know coenzyme q10, carnitine, lipoic acid, vitamin C, magnesium, and so on. But through the work of Robert Naviaux and the cell danger response we know that the mitochondria also need to be approached with a certain elegance, a certain sophistication, a certain patience because you can’t coax a mitochondria back to health by just throwing everything in the kitchen sink at it, hoping it’s going to recover. You have to understand the timelines and the movement through what they call the cell danger response, where there’s an inflammatory response and the mitochondria shut down

to protect the host. Then there’s moving through a healing response, which takes time. Our bone marrow turns over every four months and the mitochondria too have their own timeline, their own seasons so to speak. If you’re interested in the subject I’d suggest you read anything by Robert Naviaux. 

So this patient needed chemo, she had post radiation, post chemo fatigue, she was highly anxious, and wasn’t sleeping but she also had resources and she had some insight into her case. With these issues in mind it’s always important to expand our diagnostic and therapeutic base and try and bring everything to the table, to assist that person moving through their present symptomatology of anxiety fatigue and gut issues. This particular individual had gut issues. You have to do a full functional medicine workup with food sensitivities, gut permeability, hormonal HPA axis assessment, and methylation micelle detoxification. That’s just a given, a basement workup. I was struck by how far we’ve come in the understanding of illness and the fact that illness isn’t something that just requires a therapeutic drug. That concept of n squared, d squared, name of disease, name of drug, is so far advanced. We’ve come so far over the last thirty years in this understanding. Unfortunately the healthcare systems that exist are still very mechanistically based, disease based, which is fine. But when it comes to a true transformative healing experience, all layers, all levels, and interpersonal relatedness with trust are now available to us. It behooves us as therapists and medical personnel and healers if you wish to use that word. We have to do our own work and we have to know how to navigate the nuances and subtleties and levels and layers of a person’s experience and how to read the hidden signs. How to access unconscious dynamics and how to make conscious that which is being asked to be made conscious. Symptoms are often in a person’s life in order to bring to consciousness that which is hidden. It’s been said before that all sickness is homesickness. Even though this could be considered a sort of glib metaphor, especially when somebody’s suffering severely.  It’s been my experience that if you really lean into that possibility, the full potential of the person’s self-expression can be realized through a sensitive, insightful and broad palette of diagnostic and therapeutic insights. So these were my musings on a Sunday afternoon and I just wanted to share those with you. Thank You.

A Discussion About Mold and Mold Exposure with Dr. Bruce Hoffman

A Discussion About Mold and Mold Exposure with Dr. Bruce Hoffman

We discuss how mold and mold exposure can be a trigger for Chronic Inflammatory Response Syndrome (CIRS), and Mast Cell Activation Syndrome (MCAS). We discuss ways to investigate and determine if you have been exposed to mold and what you should do if you suspect mold exposure is affecting your overall health.

To learn more about mold treatment, prevention, and recommendations, visit the Mold Illness section of our Hoffman Centre website.

Watch the Video

A Discussion About Mold and Mold Exposure with Dr. Bruce Hoffman

Reference Links

Transcript

I wanted to talk a bit about mold and mold exposure as a potential cause for chronic ill health. Mold is ubiquitous and, without question, many people are suffering from the effects of mold. Mold triggers Mast Cell Activation Syndrome (MCAS), and many people are suffering from that, which is why I feel that it has to be part of a differential diagnosis for chronic ill health.  

It’s shocking how many people have mold exposure as a trigger and as an ongoing mediator, keeping them in an inflamed state resulting in Chronic Inflammatory Response Syndrome or CIRS. There is a 34-page article on my website describing the diagnosis and treatment of mold illness or CIRS.  

I would recommend the following steps to people who feel they have mold exposure.

Do the CIRS questionnaire found on page 9 of the aforementioned article. You can see if you fulfill the criteria for the potential diagnosis of mold illness. Some of those symptoms are not just for mold illness. Some are more psychiatric based questions that can arise from mold. So, the questionnaire itself isn’t enough but it’s a good start. If you have more than eight symptoms in more than six of the subtypes on the questionnaire, consider mold as a potential differential diagnosis.

The second thing you can do is a visual contrast test. This too can be googled. Dr. Shoemaker’s website has access to a computerized VCS test. Take the test and if you fail it, consider mold as a potential illness or reason for feeling unwell.

Then, of course, the most important consideration is exposure. If you know that you’ve got a basement full of mold or your bathroom or your bedroom has mold on the windows from condensation, you have to consider that in your differential.

Not everybody gets sick from mold. Some people simply get allergy type symptoms,  but some people get true inflammatory response illness (CIRS). It’s been estimated that only 25% of people will have significant illness from mold. However, in my experience it’s more than that. People often downplay how important mold and the mycotoxins produced by mold are in influencing your health. 

So, what is important? Your exposure and your history. Is what you are exposed to visible mold? If it’s not visible, it could be hidden and so you often have to do your own homework and call in a mold inspector to look for the potential sources of mold. So, what can you do to potentially identify a problem? Look up at your pot lights. Is there a brown ring around your pot lights? Do you have buckled baseboards? Do you have black mold on your window frames? Is there mold in the grout in your shower? Do you have a front-end loading washing machine that smells musty? Does your house smell musty? Is there any potential mold in your air-conditioning system? Do you have a food composter in your kitchen? Because a lot of mold grows there. If you aren’t sure, it’s important that you call in a mold inspector, someone who will do a visual inspection and is armed with specific tools such as an infrared camera. Someone who is able to actually measure the dryness or wetness of drywall and put a small hole through drywall if you suspect mold or moisture behind the wall. The inspector will begin the examination of your home in the attic, looking at the insulation and at the condensation potential. Is your upstairs attic vented? A lot of the homes that we built in the Calgary building boom in 2009-2010, including my own by the way, didn’t have venting.  Condensation and wetness were ubiquitous and many people didn’t discover the mold until many years later, so get a good visual inspection. Find somebody to come in and inspect from the attic to the basement, someone who goes inside and outside and looks in multiple areas. If you go online, you’ll see how to do a visual inspection and a lot of it you can do yourself.   

Then you want somebody to do what’s called an ERMI test, which is a mold spore count. You want to do it either through a vacuum collecting dust from carpets or a swiffer cloth collecting dust off the floors. We recommend living rooms and bedrooms first. Some people do it in the basements although it’s not often recommended because a lot of basements are moldy. In my personal experience it’s important to know if your basement is moldy because through your furnace you’ll be pulling in mold through the furnace and pushing it throughout the house. Molds have also traveled from the basement through convection currents when your home heats up and so if the basement is a source, you want to know exactly how bad it is.  

Once you’ve done the visual inspection, once you’ve done ERMI testing looking for mold spores, once you’ve found mold (or not), the next step in the diagnosis is to do what we call the cytokine testing. Those aren’t done in Canadian labs, so we have to send them out. We call them the Shoemaker panel and we measure things like C4a, TGF Beta-1, MMP-9, VEGF, MSH and we do a nasal swab for something called MARCoNS, a coagulase negative staph. Basically, it’s a staph that lives in your nasal passages. It doesn’t produce overt nasal symptoms but can have significant cognitive effects and mitochondrial effects on your symptoms. So, we do those inflammatory markers.  

Recent advances have been very controversial regarding the use of urinary mycotoxin testing. In the original workup by Dr. Shoemaker didn’t believe that urea mycotoxin testing had any role to play in the diagnosis of mold illness. He has personally moved on to transcriptomic testing for definitive diagnosis but many other clinicians do urine mycotoxin testing to determine if there are any toxic mycotoxins of mold in the urine.  This is used quite extensively by the breakaway group that doesn’t adhere strictly to the Shoemaker protocol. There are two schools, which are the Shoemaker purists and then the group that has broken away. Like any good movement, there are always two camps, we can’t get away from that. Support and challenge exists throughout nature, exists throughout medicine, exists throughout clinical diagnosis and treatment.   

So, if you have a symptom profile that was suggested by the questionnaire, if you have a positive VCS test, if you have any signs of mold in your home, if the testing for mold spores in your home is positive, if your urine mycotoxin tests are positive and your Shoemaker labs are very positive, it’s highly likely that mold is playing a role in your illness. You need to find a practitioner who knows how to treat it. The treatment is extensive, requires lots of steps, and has to be followed in a specific sequence otherwise you can overload the detox pathways and get into increased symptom expression and feeling worse, not better.

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A Discussion About Lyme Disease with Dr. Bruce Hoffman

A Discussion About Lyme Disease with Dr. Bruce Hoffman

The diagnosis and care of a patient with Lyme Disease is multifaceted and can be approached from more than one angle. It likely goes without saying that mainstream medicine is taking a much different approach than those in the functional and integrative space. 

In this video, I discuss the importance of looking at the larger history of said patient and how lab testing plays a role in proper diagnosis of Lyme Disease. 

If you are looking for answers regarding your situation, please contact our office today for more information. 

Watch the Video

A Discussion About Lyme Disease, with Dr. Bruce Hoffman

Reference Links

https://hoffmancentre.com/podcast-understanding-symptoms-and-treating-the-whole-person/

Transcript

Good afternoon everybody. I just finished an interview with the CBC (Canadian Broadcasting Corporation) and they wanted to talk about Lyme disease in Canada. We had a good, 20-minute chat that will probably be aired on some CBC broadcast in the fall. 

I was struck by one of the issues that often arises in my practice when I’m asked to treat complex multi-system, multi-symptom patients. They often come in and say, “I’ve got Lyme disease can you help me?” or “I’ve seen five doctors, naturopaths, et cetera, but I’m not better”.  

One of the biggest frustrations has been people believing that there’s one single trigger for their presentation of symptoms. They have one or two positive antibodies on their lab test, are told that’s a positive Lyme marker, and then are told by their medical provider that they should be on a full treatment program. I think that it’s medical malpractice to jump into the diagnosis and treatment of Lyme disease without a considered approach. 

We do know that there are two schools of thought in the standard of Lyme diagnosis. There are the traditional infectious disease specialists, who have very strict criteria for the diagnosis of Lyme disease, rightfully or wrongfully. Then there is a more broad approach to the understanding, diagnosis, and treatment of Lyme disease, which is purported and put forth by a group called ILADS, to which I happen to belong. 

The two schools of thought do not see eye to eye and that continual friction places the patient in the middle, trying to work out what is the best approach. 

Often patients get a diagnosis of Lyme disease from a provider they’ve seen based on the US test. They then get sent by their family doctor to an infectious disease specialist who reads them the riot act and lets them know that the tests are recording too many false positives, that they are irrelevant, that the lab is just trying to make money, or that the labs aren’t standardized. This battle goes back and forth, causes frustration for everyone, and the poor patient sits in the middle, trying to make sense of it all. 

Our aim is to talk about the differences between the two approaches, address the specifics as to why one group is vehemently certain of their position and the other group contests that position and has their own set of criteria for diagnosing and treating, which, based on the data, can’t be invalidated and has to be taken into account.

So here’s my take on patients who believe Lyme may be a trigger without a thorough health history. Lyme disease and co-infections are based on a very thorough clinical history.

I’m not going to go into the specifics of that clinical history, but the doctor or healthcare professional interviewing you must spend a lot of time taking a very specific history as to what symptoms you’re presenting and how you came to this diagnosis.

Just walking in with a positive lab test, whether it be US based or even Canadian based, isn’t good enough. Although with the Canadian test, if it’s positive, there’s a strong likelihood that Lyme disease is playing a role.

The Canadian test has very strict criteria for false positives and negatives, so if you have a positive test in the Canadian lab, it’s very likely that Lyme is an issue. So, I suggest that your practitioner takes a very thorough history and starts to use certain criteria to make the diagnosis.

One, is there history of a visit to an endemic area? Secondly, is there a history of tick bites?  Third, is there history of rashes? The problem is that many times, in fact most times, that history isn’t obtained. But if the history is there, that guides you in a certain direction. Those questions must be asked. Then a full list of symptoms must be taken, to try and differentiate whether your symptoms are specific to Lyme and related co-infections or whether they cross over with other conflicting or added potential causes for illness.

For instance, we know that in Lyme disease patients, after the first thirty days, the disease is characterized particularly in the later stages by migratory polyarthritis, which is joint pain or muscle pain that goes from joint to joint or muscle to muscle. These sorts of symptoms are very diagnostic. There are other things that cause this, but in the context of exposure to tick-borne illness, if those symptoms exist, you want to dig deeper.   

So migratory polyarthritis or muscle pain, those are very big symptoms for Lyme disease. Now for the co-infections, you want to ask very specific things. Do you have night sweats? Do you have day sweats? These occurrences are very specific for Babesia symptomatology. Do you have shortness of breath or “air hunger”? Do your symptoms come and go? Are there a lot of emotionally based symptoms, particularly anxiety as this has been associated with Babesia. You want to ask these very specific things.

Bartonella tends to be more peripheral so you tend to get a lot of pain syndromes such as Neuritis, which is pain in the peripheral nerves. Painful soles of the feet, particularly when you get out of bed in the morning. This is why the history is so important.

Lyme disease is now considered to be a clinical diagnosis based on history and physical examination, not based on a positive lab test. Why? Because you do get false positives and depending on which tests you run, the interpretation of results is highly complex. Unfortunately, due to cost we have the Canadian tests, which are elementary and introductory at best. 

Infectious disease specialists will say that they’re good enough, however, I disagree. When you want to look further and beyond you do have to look at more advanced testing which is, unfortunately, cost prohibitive. Most people can’t afford what’s really needed. I do try and get as many tests as I can across the spectrum of different testing types, including B-cell antibody testing, T-cell testing, PCR testing, plasma testing, and FISH testing. The more tests you can get, and the more that you correlate those tests with the clinical diagnosis in the symptom profile picture, the more you can hone in on the diagnosis of potential Lyme disease.

In Canada, Lyme disease is rising at a very alarming rate due to the migration of ticks and songbirds to the North. There was a study done showing that there are 32 million South American ticks brought north by South American birds every year. That’s a pretty alarming statistic. We know that songbirds are migrating to the North due to global warming and spreading their tick-borne load further and further North, hence the rise in tick-borne illness in Canada.

So, be cautious. Don’t jump to a diagnosis of Lyme disease because you have a positive test. Make sure that you have a very thorough history taken and make sure that the person who’s interviewing you has experience in the diagnosis and in interpreting lab data. The more lab data you have, the better.

Don’t rush ahead and treat yourself for Lyme disease without due caution. It can lead you into the wrong direction and make your immune system and your gut microbiome quite compromised if you treat inappropriately with some of the drugs out there that are available. Just a word of caution. This was covered in a podcast that you can listen to here.