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
  • 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.

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.

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.

Inflammatory Bowel Disease – Crohn’s Disease and Ulcerative Colitis, Part 1

Inflammatory Bowel Disease – Crohn’s Disease and Ulcerative Colitis

In anticipation of the upcoming Crohn’s and Colitis Summit, I want to share more about inflammatory bowel disease, Crohn’s disease, and ulcerative colitis. This two-part series will be a deep-dive into the root cause of inflammatory bowel disease, along with a comprehensive look at lifestyle changes and functional therapies that may provide relief. This free summit, hosted by Ravi Jandhyala and Mallika Allu of Gut Heal Protocol, will be held September 21st-27th. I will be speaking at the summit, and I encourage you to sign up if you or a loved one has Crohn’s disease or ulcerative colitis.

Inflammatory bowel disease (IBD) comprises a number of different medical conditions. The most significant of these are Crohn’s disease (CD) and ulcerative colitis (UC). These are chronic, immunologically mediated diseases with periods of relapse and remission, in addition to marked variations in mucosal inflammation from near normal in remission to severe ulceration in relapse.

UC affects only the colon with superficial inflammation, whereas CD affects the entire gastrointestinal tract and leads to transmural inflammation, strictures, fistulas, and abscess formation. 

The etiology of IBD is complex, but intricate dynamic interactions between the intestinal microbiome, host genetics, and external environmental factors all play an interrelated role in the development of IBD and its subsequent outcomes. 

The key mechanisms underlying the pathogenesis of these diseases are a genetically susceptible host exposed to external environmental factors, affecting gut microbiome and commensal flora. This results in a dysregulated immune response to different aspects of the gut microflora and increased intestinal permeability.

In this article, you will learn:

  • The etiology (root causes) of IBD, CD, and UC,
  • How the intestinal microbiome and your body’s immune response lead to IBD,
  • And the risk factors that may make you more susceptible to developing CD or UC, or having more severe flare-ups.

In Part 2, I will discuss our current strategies for diagnosing and treating CD and UC.

What causes IBD?


The health of the intestinal microbiome plays a key role in the pathogenesis of CD and UC. In particular, this is related to dysbiosis and reduced diversity of the gut microbiome. It also relates to protective bacteria subpopulations, such as Firmicutes, and an increased representation of potentially pathogenic bacteria, such as enteroinvasive Escherichia coli in subsets of ileal CD. In these conditions, species richness decreases, although some species seem to overgrow and increase in number. 

Both CD and UC are defined by an abnormal immune response, in which the immune system mistakes benign or beneficial cells and bacteria for harmful foreign substances. When this happens, the immune system, through a process known as molecular mimicry, can damage the gastrointestinal tract and produce symptoms of IBD.  UC is primarily a T-helper 2 (Th2) immune cell response, while CD is primarily T-helper 1 (Th1) cell mediated. 

Starting at birth, the cumulative effects of different environmental exposures, combined with a predetermined genetic susceptibility, is thought to cause IBD. It appears that continuous exposure to the collective effect of dynamic environmental factors, referred to as ‘exposome’ by Christopher Wild, affects the incidence of IBD.  Infancy and early childhood influence the formation of the immune system, whereas adult exposures to environmental factors alter established pathways.

Western lifestyles also seem to play a role, indicated by higher number of cases of IBD in Europe and the USA. The condition affects 1.5 million US citizens and 2.2 million people in Europe. There has been a significant increase in the last five years that’s consistent across several distinct ethnic groups and geographic locations. This increase parallels the Westernization or industrialization of an area’s lifestyle

Immigrants moving from low risk to high risk areas tend to assume the qualities of the high-risk areas within a generation or two. In their new location, the risks are much higher than in their low-risk country of origin. There has also been an increase in the number of cases in developing countries in Asia, Eastern Europe, and Northern Africa, as their lifestyles and living environments change. Onset of IBD in young adulthood is characterized by a relapsing and remitting course with frequent hospitalizations or surgery.

  1. Is irritable bowel syndrome a type of IBD?

Irritable Bowel Syndrome (IBS) is considered non-inflammatory and a syndrome, or a group of symptoms, rather than a specific disease. Symptoms of IBS typically include chronic abdominal pain, diarrhea, constipation, or alternating bouts of both of these. People with IBS are also more likely to have other functional disorders such as fibromyalgia and chronic fatigue syndrome (CFS). IBS doesn’t produce the destructive inflammation found in IBD, so it may be considered a less serious condition. However, it can still cause chronic discomfort and affect quality of life. Research suggests that IBS can be caused by stress and the manner in which the brain and gut interact.

Risk factors of IBD


Well known risk factors for IBD include:

  1. Cigarette smoking: reduced risk of UC, increased risk of CD
  2. Appendectomy: reduced risk 
  3. Western diet: increased risk
  4. Stress: increased risk 
  5. Depression: increased risk 
  6. Low vitamin D levels: increased risk
  7. Estrogen replacement therapy: increased risk of UC
  8. Left-handedness: increased risk
  9. Mycobacterium paratuberculosis infection: increased risk of CD

Breast-feeding, appendectomy, and smoking, surprisingly, are all associated with reduced risk of UC. 

The effects of some of the risk factors outlined above appear to differ between CD and UC. Despite shared genetic and immunologic mechanisms, distinct pathways of pathogenesis exist.

There’s a substantial body of research that’s available regarding risk factors, but limited evidence for the treatment of these environmental triggers to modify disease outcomes or prevent relapse. There have only been a few controlled clinical trials for modification of risk factors resulting in an improvement in patient outcomes.

Risk loci, or specific gene locations within your chromosomes that appear to alter IBD risk, highlight several key pathways in pathogenesis. These include the following:

  • Innate immunity
  • Adaptive immune responses
  • Abnormal glycosaminoglycan (GAG) content of the mucosa
  • Maintenance of intestinal barrier function with increased intestinal permeability
  • Pathogen sensing 
  • Endoplasmic reticulum stress
  • Response to oxidative stress
  • Decreased oxidation of short chain fatty acids  
  • Increased inflammatory mediators 
  • Increased sulfide production
  • Decreased methylation
  1. Genetics

Everyone is born with a certain genetic susceptibility to IBD. Following exposure to a Western lifestyle, diet, and certain environmental triggers, a specific threshold is reached and IBD may develop. This explains the low concordance rate in twins, suggesting that genetic influence, while important, is only one piece of the IBD puzzle. The exposome, or the total coherent effect of all environmental factors from birth to death, plays the determining role.  

A positive family history of IBD is the most important risk factor for the development of the condition. Whole genome scans have found susceptibility genes for UC on chromosomes 1 and 4. A concordance rate of 19 percent for UC and 50 percent for CD in monozygotic twins has also been established. 

Genetics have shown 204 distinct genetic risk loci for IBD, with the majority of risk alleles being shared between both diseases. However, 37 CD-specific and 27 UC-specific loci have been identified. Known loci account for only a third of the risk for either disease. 

  1. Childhood exposures

Breast-feeding appears to confer a protective effect on both UC (1.8-fold) and CD (2.2-fold), in keeping with known protective effects for other immune-mediated diseases such as eczema and asthma, allergic rhinitis, and type 1 diabetes. This is thought to be due to protective maternal antibodies and the induction of immune tolerance to specific food antigens and gut microbes.

Antibiotic exposure is associated with an increased risk of adult and pediatric-onset IBD. Exposure during infancy or early childhood is associated with the greatest increase in risk. Use of antibiotics between the ages of five and sixteen, through the effect on the microbiome, appears to increase the incidence 1.6-fold. If antibiotics are used in the first year of life, the risk of CD increases 5.3-fold. 

The strongest risk increase is linked to the use of broad-spectrum penicillin (3.1-fold), pen V (2.9-fold), then cephalosporin (1.9-fold).

It’s been hypothesized that by altering the gut microbiome composition, pathogenic bacteria colonize while the normal process of tolerance, which is crucial for immune development, is disrupted. This leads to an aberrant response of the host immune system to its microflora.

On the other hand, early childhood Helicobacter pylori infection is associated with a decreased risk of CD of 1.7-fold and UC of 1.3-fold. H. pylori increases Fox-3, the transcription factor of T-regulatory cells, which down-regulates the inflammatory response. 

  1. Hygiene

A high hygiene level increases the risk of IBD. Living in an urban environment increases risk by 1.2-fold.

Having a smaller number of siblings increases risk 2.6-fold. The more siblings you have, the lower your risk for IBD.

Sharing a bedroom decreases risk of UC by 2.1-fold and CD by 2.3-fold, while a hot water tap in the home increases the risk of CD by 5-fold.

Animal contact decreases risk of UC and CD, with similar effects seen regarding asthma and eczema.

The implication is that the more hygiene measures employed, the fewer helminths (worms and parasites) you’re exposed to, and therefore less induction of dendritic cells maturation and ability to drive the T-cell immune system occurs. This results in decreased protection against autoimmunity. 

In simpler terms, “germophobes” may be at an increased risk of developing IBD.

  1. Autism

There have been several reports of a link between autism spectrum disorder (ASD) and chronic gastrointestinal (GI) symptoms. Endoscopy trials have demonstrated a higher prevalence of nonspecific colitis, lymphoid hyperplasia, and focally enhanced gastritis in people with ASD compared with controls. Postulated mechanisms include aberrant immune responses to some dietary proteins, abnormal intestinal permeability, and unfavourable gut microflora. 

Wakefield et al conducted one of the earliest studies investigating gastrointestinal anomalies in autistic children in 1998. In this study, twelve children with regressive developmental disorders, nine of whom were autistic, were all reported to have abnormal colonoscopies. The most consistent finding was lymphoid nodular hyperplasia (LNH), which was present in nine of the twelve children. This mild to moderate colitis was deemed nonspecific on the basis of not fulfilling criteria for either Crohn’s disease or ulcerative colitis.

Criticism regarding the ‘normalcy’ of LNH in children prompted Wakefield, et al. to perform ileocolonoscopies in 60 children with regressive developmental disorders and compare them with 37 developmentally normal controls. In this trial, ileal LNH was present in 93 percent of affected children in comparison to 14.3 percent of controls (P<0.001). Chronic colitis was detected in 88% of affected children compared with 4.5% of controls. 

Torrente et al. compared the gastric biopsies of 25 autistic children with those of ten normal controls, ten CD patients, and ten children with H. pylori infection. Eleven of the 25 autistic children had a focally enhanced gastritis, while two had mild diffuse gastritis. Immunohistochemistry results demonstrated the pattern of lymphocyte infiltration was most similar to Crohn’s disease, with the exception of a striking predominance of CD8-positive over CD4-positive cells and a marked increase in intra-epithelial lymphocytes. Another highly specific finding among autistic children was a dense, sub-epithelial basement membrane immunoglobulin G deposition, which was absent in the other subgroups.

ASD patients and their caregivers often report improvement in the patient’s condition after following elimination diets. Improvements occur not only in the GI symptoms, but also in behavioural and cognitive problems such as hyperactivity, communication skills, and attentiveness. Interestingly, 36% of children with ASD have a history of cow’s milk and/or soy protein intolerance in infancy. In addition, while studies haven’t indicated an increased incidence of Celiac disease in these individuals, parents have often reported an improvement in their child’s behavioural disturbances when following a gluten-free diet. These benefits haven’t been seen consistently in randomized trials, although a Cochrane review did report a significant reduction in autistic traits on a gluten-free, casein-free diet.

One hypothesis is that ASD may be accompanied by aberrant innate immune responses to dietary proteins, leading to GI inflammation and aggravation of behavioural problems. One study, measuring pro-inflammatory cytokines in response to common dietary proteins, showed a greater than two standard deviations (SD) excess in tumour necrosis factor-alpha and interferon-gamma production in response to gluten and cow’s milk protein among ASD children, when compared with controls. 

A subsequent study confirmed a higher prevalence of elevated tumour necrosis factor-alpha and interleukin-12 production with beta-lactoglobin and alpha-lactoglobin, but not casein, in autistic children and children with non-allergic food hypersensitivity, compared with normal controls. 

Another theory suggests that abnormal intestinal permeability in children with ASD causes them to absorb fragments of incompletely broken-down peptides such as gluten or casein, which cross the blood-brain barrier and act as endogenous opioids. 

The gut microflora has also been targeted as a potential player. There have been anecdotal reports of the onset of autism following broad-spectrum antibiotics, suggesting that disruption of the indigenous flora may lead to colonization by neurotoxin-producing bacteria. Autistic children have been shown to have higher counts and more species of Clostridia than controls matched by age or gender. A small prospective trial demonstrated a significant but transient improvement in autistic features following a course of vancomycin (antibiotic) therapy, with relapses presumed to occur because of persistent spores that proliferate upon discontinuing the medication.

  1. Yeast

The ratios of yeasts in the gut, such as Saccharomyces cerevisiae and Candida albicans, may be significantly altered by IBD. Normally, yeasts and fungi account for less than 0.1% of the total microbiota population. However, there is often a decreased population of S. cerevisiae and increased populations of C. albicans and other Candida yeasts in the guts of people with IBD.

Antibiotic use can result in fungal overgrowth, especially of the Candida yeasts, which may then compete with the bacteria in the gut for survival and growth. This fungal overgrowth can make the host more susceptible to mold illness, paving the way for an immune response that may invoke chronic inflammation, autoimmunity, or IBD.

It appears also that certain components of the cell walls of fungi can trigger immune responses, which may add to the overall exposomeXI.

  1. Gut microbiome

Recent studies have highlighted the association between the gut microbiome and the pathogenesis of IBD. 

Reduced biodiversity of the gut microbiome is apparent even at the onset of diagnosis, before treatment is initiated. CD, especially ileal CD, has been associated with increased frequency of pathogenic bacteria such as enteroinvasive E. coli. There can also be a reduction in the frequency of anti-inflammatory bacterial subgroups, particularly Faecalibacterium prausnitzii. Giving strains of this specific bacteria has resulted in improved outcomes and amelioration of colitis in animal models.

By the time someone reaches adulthood, the immune system has matured and lifestyle factors become more apparent as choices are increased. Adult exposures seem to be involved in changing the already developed immune system. Several environmental factors have been identified as playing a role in IBD development independent of stage of life, previous development of acute bacterial gastroenteritis, geographical location, and vitamin D. 

Bacterial gastroenteritis as a result of Clostridium difficile, Campylobacter, and/or Salmonella infections can increase risk of IBD. The risk of developing IBD increases significantly after bacterial gastroenteritis, especially within the first year. The largest effect is seen with CD, for which there is a 2.9-fold increase, rather than the 2.1-fold for UC. This may be explained by the increase in interleukin-6 (IL6), blockage of T-reg cells, and the activation of self-reactive T-cells, leading to a chronic inflammatory response.

  1. Mycobacterium avium infection

M. avium subspecies paratuberculosis (MAP) infection rates are higher in CD, although a causative link hasn’t been established. Meta-analysis has shown a 7-fold increase in CD in MAP infections, but the timing of this infection couldn’t be ascertained to be a cause of CD and is perhaps merely a bystander. 

  1. Tap water

Drinking tap water lowers the risk of CD 2-fold. It’s been proposed that this might be due to harmless microorganisms triggering regulatory T-cells.  

  1. Flying

Individuals have an increased risk of disease flare following high-altitude flights or after travelling more than 2,000 metres above sea level. Mild hypoxia leads to an increase in IL6 and C-reactive protein (CRP), which are markers of inflammation.

  1. Obesity

An American cohort study showed a 2.5-fold increase in CD in obese women with a body mass index (BMI) greater than 30 kg/m2. 

  1. Smoking 

Smoking confers a 2-fold increase in risk of CD, which is somewhat lessened when stopping smoking, although the pathogenic mechanism remains unknown. 

Smoking is associated with a more aggressive form of CD, more surgery, and an earlier risk of recurrence and re-operation following a bowel resection. Stopping smoking prior to the diagnosis can result in a reduced likelihood of progressing to complicated disease behaviour or the need for surgery. Smoking cessation is also associated with a reduced rate of relapse regarding CD.

With UC, current but not former smokers appear to have some protection, with half the risk of UC in current smokers compared to individuals that have never smoked. Smoking confers a 1.7-fold reduction in risk for UC. 

For former smokers, the risk for both UC and for CD increases by the same amount.

For patients with UC, smoking leads to a more benign disease course with fewer flares, a reduced need for steroids, and lower colectomy rates. Smoking cessation increases the risk, with the effect lasting for up to ten years after quitting smoking. This suggests that smoking only defers the development of UC. Quitting smoking is also associated with flare-ups.

Passive, or second-hand, smoking has a weaker beneficial effect. The mechanism of this different effect between CD and UC is unknown, but is thought to be influenced by the constituents of cigarette smoke having different effects on oxidative stress in mononuclear cells.

Smoking is known to affect the immune system through both cellular and humeral pathways by transforming the synthesis of pro-inflammatory cytokines, altering gut permeability, reducing smooth muscle tone and contractility due to nitrous oxide, and effecting changes in the gut microflora. 

There’s also an interaction between smoking and genetic variants in the CYP2A6/EGLN 2 locus and glutathione transferase enzymes (GSTP1) and risk of CD and UC. Snips in these genes showed significantly different outcomes. 

  1. Appendectomy

There are divergent effects between UC and CD following appendectomy.

When performed before the age of twenty, there’s an increased risk of UC with no effect or only a slightly increased risk of CD. The mechanisms remain unclear, and appendectomy may result in intestinal microbiome alteration with a protective effect on UC. The microbiome composition in the appendix also appears to confer protective effects against UC

  1. Diet 

The role of diet has been problematic to determine. This is due to difficulty in tracking it through the course of a lifetime, different recall between controls and cases, and potential restrictions on diet choices pre-diagnosis based on the nature of the disease. 

Increased fibre of approximately 24 grams was associated with a significant reduction in risk of CD but not UC.   This was related to fruit fibre and not that of vegetables, including cruciferous ones. No association was found between fibre from cereals, whole grains, or legumes. 

Fibre may confer epithelial integrity and reduce translocation of potentially pathogenic bacteria such as enterovirus E. Coli, which may play a role in CD. Fibre activates the aryl hydrocarbon receptor (AhR) expressed in intestinal lymphocytes, which offers protection against environmental antigens.  

A diet high in long-chain n-3 polyunsaturated fatty acids (PUFA) was associated with a reduced risk of UC. CD had no modifiable fat intake risk factors for CD. One large study found omega-3 supplements had no beneficial effects, while a high intake of animal protein revealed a potential association with IBD. Sugar and a high-carbohydrate diet are associated with an increased risk of IBD, while fruits and vegetables seem to have a protective effect.

Alteration of diet can trigger flares in many different types of disease. High fat diets result in expansion of specific bacterial subpopulations that are associated with a pro-inflammatory response, particularly diets high in meats, as well as polyunsaturated omega-6 fats (like those found in industrial seed oils such as soybean oil, corn oil, and canola oil).XVI Elemental diets show improved outcomes in CD, whereas partial and complete enteral nutrition show effects superior to placebo but lower than steroids. 

Elimination diets, such as the specific carbohydrate diet, lectin-free diet, autoimmune paleo, and Whole30, are of particular interest as well, but there is still a lack of strong evidence regarding their efficacy for IBD treatment.

Childhood diet and antibiotic exposure is an important determinant of microbiome composition. Breastfeeding appears to reduce UC risk, but it doesn’t appear that formula-feeding necessarily increases UC risk. Researchers have found that the gut microbiome of both breastfed and formula-fed children changes significantly after the introduction of foods. Therefore, the first foods a child receives (other than breastmilk or formula), and the foods they eat throughout their early childhood, may profoundly affect their gut microbiota composition and affect their IBD risk level.

  1. Glyphosate

Glyphosate is the world’s most widely produced herbicide. It’s the primary toxic chemical in Roundup™ and many other herbicides. As a broad-spectrum herbicide, glyphosate is present in more than 700 different products and used in industries such as agriculture and forestry, and even in the home. 

Glyphosate was introduced in the 1970s to kill weeds by targeting the enzymes that produce the amino acids tyrosine, tryptophan, and phenylalanine. However, the enzymes of many bacteria are susceptible to inhibition by this chemical, so it can also alter the gut flora of many animals. 

Usage of glyphosate significantly increased after the introduction of genetically modified (GMO), glyphosate-resistant crops that grow well despite the presence of this chemical in the soil. In addition, the toxicity of the surfactant polyoxyethyleneamine (POEA), which is commonly mixed with glyphosate, is greater than the toxicity of glyphosate alone. 

In addition, Enlist Duo™, a herbicide product containing a 2,4-dichlorophenoxyacetic acid (2,4-D) salt and glyphosate, was approved for use in Canada and the United States in 2014. This was for use on GMO soybeans and maize, both of which were designed to be resistant to both 2,4-D and glyphosate. 2,4-D has many toxic effects of its own. 

Research has shown that glyphosate disrupts the microbiome in the intestine, causing a decrease in the ratio of beneficial to harmful bacteria. Highly pathogenic bacteria such as Salmonella entritidis, Salmonella gallinarum, Salmonella typhimurium, Clostridium perfringens, and Clostridium botulinum are highly resistant to glyphosate. Unfortunately, however, most beneficial bacteria such as Enterococcus faecalis, Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis, and Lactobacillus ssp. were found to be moderately to highly susceptible. 

The relationship between the microbiome of the intestine and overall human health is still unclear.

 However, current research indicates that disruption of the microbiome could lead to conditions such as metabolic disorder, diabetes, depression, autism, cardiovascular disease, and autoimmune diseases such as IBD. 

  1. Celiac disease, IBD, and the glyphosate connection

Researchers have found that people with Celiac disease are about 10 times as likely as a control group to have IBD. Conversely, the prevalence of Celiac disease in IBD appears to be comparable with that indicated in controls.

Celiac disease, and more generally, gluten intolerance, is a growing problem worldwide. It’s particularly serious in North America and Europe, where an estimated 5% of the population now suffers from this condition. It’s a multi-factorial disease associated with numerous nutritional deficiencies, as well as reproductive issues and an increased risk of thyroid disease, kidney failure, and cancer. 

It has been proposed by researchers Samsel and Seneff that glyphosate is the most important causal factor in this epidemic. Fish exposed to glyphosate develop digestive problems that are reminiscent of Celiac disease. The condition is associated with imbalances in gut bacteria that can be fully explained by the known effects of glyphosate on these particular types of bacteria. 

Characteristics of celiac disease point to impairment in many cytochrome P450 (CYP450) enzymes, which are involved with detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A, and maintaining bile acid production and sulfate supplies to the gut. Glyphosate is known to inhibit CYP450 enzymes. 

Deficiencies in iron, cobalt, molybdenum, copper, and other rare metals associated with Celiac disease can also be attributed to glyphosate’s strong ability to chelate these elements. Deficiencies in tryptophan, tyrosine, methionine, and selenomethionine associated with Celiac disease also match glyphosate’s known depletion of these amino acids. 

Celiac disease patients have an increased risk of developing non-Hodgkin’s lymphoma, which has also been implicated in glyphosate exposure. Reproductive issues associated with Celiac disease, such as infertility, miscarriages, and birth defects, can similarly be linked to glyphosate. 

Glyphosate residues in wheat and other crops have been increasing recently due to the growing practice of crop desiccation just prior to the harvest. The practice of ‘ripening’ sugar cane with glyphosate may also explain the recent surge in cases of kidney failure among agricultural workers in Central America. 

  1. Mast Cell Activation Syndrome (MCAS)

As early as 1980, Dvorak and colleagues reported that mast cells were markedly increased in the ileum of patients with CD. In 1990, Nolte et al. showed the same findings in patients with UC. There were increased numbers of mast cells with associated degranulation products of histamine and tryptase, along with associated increases in cytokines and leukotrienes IL-16. TNF-alpha and substance P have also been found in the mucosa of patients with IBD, particularly when stained with the CD 117 stain. 

According to the latest literature research conducted by Dr. Lawrence Afrin, one of the key researchers in MCAS, mast cells release at least 1,000 mediators of inflammation. This includes, but isn’t limited, to histamine, proteoglycans (heparin and chondroitin sulfate), proteases (tryptase, chymase and carboxypeptidase), eicosanoids, and platelet activating factor (PAF).

Activation of mast cells leads to the release of the eicosanoid arachidonic acid from the phospholipids on the cell membrane. This 20-carbon fatty acid is then rapidly oxidised, along either the cyclooxygenase pathway to form prostaglandin D2 (PGD2) or the lipoxygenase pathway to form leukotriene C4 (LTC4). Histamine triggers the histamine H1 receptor and tryptase, the protease-activated receptor 2 (PAR2).

Therapies aimed at down-regulation of mast cell activity may be important in the treatment of IBD. 

Mast cell cytokines constitute a third category in that they may be both preformed and newly synthesized. These include IL-4, IL-5, IL-6 and TNF-alpha in the nasal mucosa and bronchi, as well as IL-1B, IL-3, IL-8, IL-9, IL-10, IL-13, IL-16, IL-18, IL-25, granulocyte -macrophage colony stimulating factor (GM-CSF), and stem cell factor macrophage chemotactic peptide (MCP)-1, MCP-3, and MCP-4. 

Many factors are known to activate mast cells, and their activation is a crucial step involving pathophysiological changes. These factors include antigens, anti-IgE, substance P, VIP, C5a, C3a, somatostatin, morphine, very low-density lipoprotein, stem cell factor, tryptase, and eosinophil cationic protein, all of which are known to activate mast cells. 

It should be noted that mechanisms of mast cell activation differ with different classes of triggers.

  1. Nutrient deficiencies 

UC patients were found to have lower levels of vitamin A, vitamin E, and carotenoids than those in  controls. This implies that certain nutrient deficiencies may either play a role in the development of UC, or, conversely, are a complication of UC. 

  1. Vitamin D

Vitamin D intake is inversely associated with UC risk, meaning that higher vitamin D intake is linked to a lower UC risk.  Additionally, higher blood levels of vitamin D are associated with reduced risk of CD.

 Patients who increased their blood vitamin D levels had a 1.9-fold protective effect for CD, but not for UC. They also had a lower risk of surgery compared to those who remained vitamin D deficient. Low vitamin D levels are also associated with a higher rate of colon cancer and C. difficile infections.

Vitamin D administration may reduce the risk of IBD relapses. Vitamin D is also known to play a role in the regulation of the innate immune system by activating the TH1 lymphocytes and monocytes. This causes the inflammatory response to be down-regulated. 

  1. Weather and latitude

Incidence of IBD is higher in northern latitudes where people have reduced exposure to ultraviolet (UV) light. The Women’s Health Initiative (WHI) study noted a lower risk for both UC and CD in women in southern latitudes (1.6-fold for UC) compared to those at higher latitudes. Living in southern latitudes appears to be protective, likely due to increased UV light and subsequently higher vitamin D levels.

Warm summers have a protective effect for UC and possibly for CD as well. This is also the case for other inflammatory diseases such as multiple sclerosis (MS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). This is thought to be due to an increase in microbial diversity, which in turn confers benefit.

  1. Psychological behaviours

IBD has long been associated with neuroticism, dependency, anxiety, and perfectionism. Recent well-designed studies have confirmed that adverse life events, chronic stress, and depression increase the likelihood of relapse in patients with quiescent (dormant) IBD.

The evolving science of psychoneuroimmunology has outlined the mechanisms by which the nervous system can affect immune function at both the systemic and gut mucosal levels. These mechanisms are thought to be due to changes in the hypothalamic-pituitary-adrenal (HPA) axis and alterations in the bacterial mucosal barrier. These occur via mucosal mast cells and mediators, such as corticotrophin releasing factor (CRF). 

To maintain homeostasis, a living organism must constantly adapt at a mental, emotional, molecular, cellular, physiological, and environmental level. Stress is defined as a threat to an organism’s homeostasis. The function of the stress response is to maintain homeostasis through behavioural and biological or physiological adaptations. The stress response involves the complex integration between a series of interconnected regions within the brain. These are the hypothalamus, the amygdala, and the hippocampus. This hub receives inputs from viscera and somatic afferents and from higher cortical structures, including the internal dialogue and mental perceptions of the patient. This in turn, affects the neuroendocrine stress response via two interconnected effector pathways, namely the HPA axis and the autonomic nervous system (ANS).  

Stress stimulates the release of CRF from the hypothalamus, causing the release of adrenocorticotrophic hormone (ACTH) from the anterior pituitary. This in turn causes the release of cortisol from the adrenal cortex. Stress also activates the descending neural pathways from the hypothalamus to pontomedullary nuclei, which control the autonomic nervous system response. Stimulation of the sympathetic nervous system (fight/flight) causes the release of adrenaline and noradrenaline from the adrenal medulla. This is in addition to supplying the entire gut directly. The parasympathetic vagus nerve and sacral nerves provide parasympathetic input to the upper gut and to the distal colon and rectum. 

The gut has its own nervous supply called the enteric nervous system (ENS), which is innervated by both sympathetic and parasympathetic fibres. This network has been termed the gut-brain axis. The ENS contains 100 million neurons and regulates the motility, the exocrine and endocrine functions, and the microcirculation of the gut. These axes (HPA, ANS, ENS) can then interact directly with the immune system. Psychoneuroimmunology is the study of how behavioural factors and CNS function can influence the immune system, and hence inflammation, at both systemic and local tissue levels.

Nerve fibres of the ANS form close effector junctions with lymphocytes and macrophages in lymph glands, bone marrow, the thymus, the spleen, and mucosa associated lymph tissue. These nerve fibres also release a number of chemicals called neurotransmitters, such as catecholamines, vasoactive intestinal peptides, angiotensin II, neurotensin, somatostatin, and substance P. These are capable of affecting lymphocytes, macrophages, neutrophils, and other inflammatory cells at the neuro-immune cell junction. Lymphocytes and other inflammatory cells also carry receptors for the hormones and neuropeptides of the HPA axis, such as growth hormone, ACTH, corticosteroids, and CRF. 

At high concentrations, cortisol has an immunosuppressive effect, increasing the release of anti-inflammatory proteins and IL-10. Transcription of inflammatory signalling molecules such as IL-6, IL-1, and TNF-α are reduced through transcription factors AP-1 and nuclear factor kappa beta. At lower doses, cortisol has an immune stimulating effect.

Similarly, adrenaline and noradrenaline have mixed effects at different doses on immunity and inflammation. Adrenaline causes an increase in serum IL-6, an increase in lipopolysaccharide (LPS) induced IL-8 and IL-10, and an increase in cytotoxic (cell-killing) T-cells and natural killer (NK) cells.

Chronic sustained stress due to adverse life events, such as bereavement, divorce, and depression, have been shown to reduce the numbers of cluster of differentiation 8 (CD8, a glycoprotein) lymphocytes, NK cells, and macrophages in the blood. However, in addition to immunosuppression, chronic stress with reduced heart rate variability, which is a sign of increased sympathetic tone, has been shown to increase inflammation, showing raised CRP.  

Acute stress causes stimulation of the sympathetic nervous system with a rise in adrenaline and noradrenaline, followed a little later by a rise in cortisol. This leads to an acute episode of immune enhancement with an increase in inflammatory cytokines that are known to be associated with flares of IBD. This includes a rise in cytotoxic CD8 T lymphocytes and NK cells and an increase in their cytolytic activity, in addition to platelet activation and thrombin generation, producing effects of microcirculation ischemia causing thrombosis and microinfarction. This effect is lowered with beta blockers rather than aspirin, suggesting that a stress response or sympathetic activation is at the root of it. 

Psycho-social stressors have long been associated with triggers. Recent and remote stress is associated with an increased incidence of IBD, with recent stress being more significant. When questioned, patients indicated that stress was the trigger for 70% of their flares. Depression feelings were associated with a 2.4-fold increased risk of CD, but not UC. Depression, anxiety, and stress are also associated with increased rates of relapse and surgery for IBD.

The inflammatory response to stress through elevation of IL-6 levels can be changed in mice by administrating antibiotics, suggesting antibiotics exerts their effects through changes in the gut microbiota.

Using medications to treat these conditions appears to have variable effects. People referred for therapy following increased stress due to the diagnosis have reduced rates of relapse, outpatient attendance, and use of steroids or other medications for IBD. 

In summary, stress can play a significant role in immune system dysfunction leading to an inflammatory response, which may trigger new-onset IBD or a flare of existing disease.

  1. Sleep

Both increased and reduced amounts of sleep have been associated with negative health outcomes. Reduced sleep quality was associated with an increased risk of relapse at six months post-remission in CD, supporting an association between poor sleep and gut inflammation. Sleep disturbances in IBD may lead to a 2-fold increase of disease flare. Sleep deprivation also leads to activation of the immune cascade.

  1. Nonsteroidal anti-inflammatory drugs

The use of nonsteroidal anti-inflammatory drugs (NSAIDS) for fifteen days per month increases the risk of UC 1.9-fold and CD 1.6-fold. These figures are increased by greater weekly dosage, and a higher frequency or longer duration of use. NSAIDS lead to inhibition of cyclooxygenase (COX), resulting in a decrease in protective prostaglandins in the gut mucosa, increasing gut permeability. 

  1. Oral contraceptives

Current use of oral contraceptives (OCP) leads to 1.3-fold increased risk of UC. The risk of developing CD with current use of OCP is increased by 1.5-fold. 

  1. Post -menopausal HRT

Post menopausal HRT increases the risk of UC by 1.7-fold, but not CD. It’s been proposed that estrogen modulates gut inflammation by acting on estrogen receptors that are found on gastrointestinal epithelial and immune cells. 

UC is a Th2 mediated illness, and estrogen promotes Th2 cytokines. The same holds true for other Th2 mediated diseases, such as RA and SLE. However, this is not the case with CD, which is a Th1 mediated illness. 

A prospective cohort study (the Women’s Health Study) followed 108,844 postmenopausal American women, with a median age of 54, without a prior history of CD or UC in 1976. The risk of UC appeared to increase with longer duration of hormone use and decrease depending on the time since discontinuation. There was no difference in risk according to the type of hormone therapy used, such as estrogen as opposed to estrogen and progestin. No association was noted between the current use of hormones and the risk of CD. The effect of hormones on the risk of UC and CD was also not modified by age, BMI, or smoking.

  1. Ambient air pollution

On the whole, air pollution exposure wasn’t associated with the incidence of IBD. However, residential exposure to sulfur dioxide and nitrous dioxide gases found in industrialized regions may increase the risk of early-onset UC and CD respectively. 

Living in regions with high sulfur dioxide emissions before the age of 25 increases the chances of UC 2-fold. A high nitrogen dioxide exposure before the age of 23 increases the chance of CD 2.3-fold. Total pollutant emissions correlate significantly with an increased risk of hospitalization in established IBD. Pollutants may also be absorbed and incite the inflammatory process that’s characteristic of IBD.

  1. Physical activity

Researchers have found that women engaging in active physical activity have a 44% reduction in CD risk compared with sedentary women. Physical activity was not associated with risk of UC.

The absolute risk of UC and CD among women in the highest fifth of physical activity levels was at just 8 and 6 events per 100,000 person years. This compares to 11 and 16 events per 100,000 person years among women in the lowest fifth of physical activity. 

Age, smoking, BMI, and cohort didn’t significantly modify the association between physical activity and the risk of UC or CD in these findings. The pathway appears to be mediated through the autophagy (clearing out or recycling of damaged cells) pathway or cell senescence (cell aging).

Summary

There’s a rich body of research showing potential environmental risk factors for the development of IBD. However, there aren’t many high-quality studies showing that environmental changes may have a large effect on disease outcomes. For a large number of possible environmental factors, meta-analyses are not yet available.

Many novel factors are identified by large cohort or case-control studies, but are yet to be reproduced by and validated by independent research groups. Consequently, the level of evidence is somewhat low and caution should be exercised when drawing firm conclusions or making recommendations.

However, individuals with a genetic susceptibility can be cognisant of environmental factors and do their best to lower or delay their genetic expression, as their exposure threshold may not be reached. Being aware of which environmental factors are involved in developmental phases as well as along the course of the disease to increase flares and development of complications, gives the treating physician and patient as advocate the opportunity to make the necessary adjustments along the patient’s timeline.

 This has the effect of lowering the risk of disease expression with a more personalized treatment plan.

In Part 2, I will be reviewing the lab tests that are used to diagnose CD and UC, along with lifestyle changes and treatment options that are often successfully employed in IBD care.

In the meantime, I encourage you to join me at the Crohn’s & Colitis Summit from September 21st-27th, or to contact my office if you are seeking functional and integrative care for your IBD. 

Podcast: Understanding Symptoms and Treating the Whole Person

Looking at Lyme

I was recently interviewed by Sarah Cormode for an episode of Looking at Lyme, an educational podcast created by the Canadian Lyme Disease Foundation, where I highlight the importance of taking an in-depth patient history to understand and document symptoms.

I also discuss several approaches to treating Lyme disease and explain why such a variety of symptoms amongst patients with Lyme disease exists.

Take a listen below.

Diagnosis of Mast Cell Activation Syndrome – A Global Consensus 2

Diagnosis of Mast Cell Activation Syndrome - A Global Consensus

Please take a look at this newly published peer-reviewed article by Dr. Lawrence Afrin of which I was a co-author, on the revised criteria for the diagnosis of mast cell activation syndrome (MCAS):

Diagnosis of mast cell activation syndrome: a global “consensus-2”

One of the most common difficulties patients seem to face after they have been to our clinic and given a diagnosis of mast cell activation syndrome is when they return to their GP’s or specialists with a description of this syndrome. Traditional medicine is well-schooled in the diagnosis of systemic mastocytosis, a condition characterized by an increased number of mast cells as opposed to MCAS which is a diagnosis arrived at due to the increased activity of mast cells (and not an increase in the actual numbers).

Systemic mastocytosis is most often diagnosed by using a biomarker called tryptase, whereas the diagnosis of MCAS has much broader diagnostic criteria as this article will outline.

For a much more in-depth description of MCAS, please see my treatment page and the following articles:

  1. Treating Mast Cell Activation Syndrome (MCAS)
  2. Mast Cell Activation Syndrome: When You Immune System Runs Rampant
  3. Natural Treatments For Mast Cell Activation Syndrome
  4. Your Ultimate Guide to the Low-Histamine Diet

COVID-19 Testing: What You Need To Know

As I learn more about COVID-19 and share that information with you, my community, I’m increasingly asked about testing. Time is moving on and it’s clear that one of the limitations regarding the management of this global pandemic has been testing, or more specifically the lack of testing. There are still so many questions about how widespread SARS-CoV-2 (the virus that causes COVID-19 disease) is here in Alberta, Canada, and across the globe. We know that many people carry and spread the virus without showing any symptoms or just display very mild ones, but how many people are we talking about? 

As we enter the next phase of pandemic management, as people begin to enter communities again, testing will play a key role.1 It’s incredibly important to know who’s been exposed as well as who hasn’t and therefore may still be at risk. More widespread testing will help to keep those most vulnerable, including those with pre-existing conditions safe. 

While there’s undoubtedly still a lot to learn, in this article I’ll distill for you what I know and believe, as of now. I’ll cover:

  • Some background on testing, including understanding the timeline of COVID-19 infections
  • Types of testing, including viral RNA and antibody 
  • What test results mean
  • Test accuracy
  • Next steps for testing

Background on testing: The viral timeline 

To understand testing it’s helpful to understand the timeline of COVID-19 infection. This image was compiled by the Institute for Functional Medicine and provides a helpful visual.2 It’s important to note that this timeline is based on the data that has been collected so far, and some of it hasn’t been peer-reviewed and published yet. 

As you can see, the first thing that can be detected after exposure and with the onset of symptoms is the virus itself. This is depicted by the red and purple lines in the graph. 

After the initial infection, the body begins to mount an immune response and develop antibodies. This is depicted by the orange, blue, and green lines. 

Most of the testing that’s been done so far, mainly in hospitals, has been conducted when people are symptomatic. It’s also important to note that the time between when someone’s exposed to the virus and when they begin showing symptoms is widely variable. Some will show symptoms two days later and others may not show symptoms for three weeks. Others will show no symptoms at all, or only mild ones, yet still be spreading the virus during the first couple weeks of infection.

Time Course for testing after Exposure to SARS-CoV-2
Source:  https://p.widencdn.net/n3trkt/IFM_Sars_Graph_v3

Types of testing

There are two main types of testing, namely viral and antibody. Both have their place in the timeline of events. 

The Viral RNA tests look for an active viral infection. They test for the presence of RNA (ribonucleic acid) from SARS-CoV-2. The test will be positive for someone with a current or very recent infection.3 This test can be undertaken using several methods of collection.

  • Nasopharyngeal swab – This goes into the nose about three or four inches. 
  • Oropharyngeal swab – This down the throat and is similar to a test for strep throat. 
  • Sputum – This is the thick mucus produced by the lungs during an infection. If this can be collected from a person’s coughing, it can be tested. 
  • Saliva – Saliva collection for this test works best after a cough.
  • Stool – Viral RNA can be detected in the stool after an infection.4

A positive test result doesn’t necessarily mean that you’re contagious and are ‘shedding’ the virus. In order to verify that, we’d need to culture your sample in a laboratory. However, there are issues with safety and containing the virus in a laboratory setting, so this type of testing is mostly only done in a research environment at the moment. 

Therefore, we’ll assume that a positive test means you’re contagious and that you need to quarantine for two weeks in order to protect others. It also means that you should watch for symptoms and seek medical care if needed. You can read about treatment options, including herbs and nutrients, here. Tracking positive testing is also important from a public health perspective, in order to trace the spread of the virus.  

Viral RNA testing is going to be most accurate around four to six days after symptoms appear, since this is the peak of the viral RNA production.4 If you wait too long to be tested, you might get a negative Viral RNA test, even though you were infected. This is why this testing has a high false negative rate. You need to get the timing right. If you have a negative test, but a known exposure, you’ll still need to take precautions and may need to be tested again. 

The second type of test that’s helpful is an antibody test. This is a blood test that studies your immune response to the viral exposure. Essentially, it’s looking to determine if you were exposed to SARS-CoV-2 in the past and may be particularly helpful for mild or asymptomatic cases.5 The best time to take the test is about seven days after symptoms resolve or a minimum of fifteen to twenty-one days after exposure. 

There are two main antibodies that current testing is looking at.

  • IgM – This non-specific antibody is produced as the immune system is figuring out exactly what it’s dealing with. If you look at the chart above, you’ll see that IgM rises and then fades away as more specific antibodies (IgG) are produced. 
  • IgG – This more specific antibody takes a little time to develop and then stays high for a period of time.6

This pattern that we’re seeing with SARS-CoV-2 antibodies is typical of what we see with other viruses. 

A positive test suggests that you’ve been infected and that your body mounted an immune response to the infection, whether you had severe symptoms, mild ones, or no symptoms at all. Timing matters here as well. If you test IgG antibodies too early, you might miss them because they take some time, possibly around three weeks, to develop. False positive tests are also possible as some of the tests are detecting previous exposures to other coronaviruses, such as the ones that cause the common cold.4

A negative test might mean that you still need to take precautions to prevent exposure, especially if you’re at higher risk for severe COVID-19. Because of the timeline, it’s important to note that a negative antibody test does not rule out current infection. 

As you can see, the testing is quite nuanced, which is why connecting with your healthcare team for guidance is so important. 

Understanding test accuracy

Naturally, we want a test to be accurate, to be both sensitive and specific. This will limit false positive and false negative results. 

When it comes to accuracy, sensitivity refers to how likely a test is to pick up a positive result in those that have definitely been infected, known as true positives. It’s those that have been exposed to the virus that test positive. Specificity refers to individuals that haven’t been infected by the virus that test negative, which are referred to as true negatives.7. In a perfect world we always want a test to be 100 percent sensitive and 100 percent specific, but this isn’t the case when it comes to coronavirus testing. It can also be similar for many other antibody tests. The poor test results for Lyme disease detection are a good example of this.

We’ve already seen that there are cases of false positives and negatives based on timing and other factors. For example, with a viral RNA test, the nose swab can be really unpleasant so it’s possible that an error can occur as a result of not going deep enough to collect the appropriate sample. Alternatively, there might be low sensitivity because the test picks up antibodies to another coronavirus that are connected to a previous coronavirus infection.4

You might also hear the terms positive predictive value (PPV) and negative predictive value (NPV) in discussion regarding test accuracy. These take into account sensitivity and specificity in terms of the infection rates in a specific population.7 Of course, we need more testing to determine what rates are in each area. This article in Scientific American provides a useful guideline to the testing.

If I have the antibodies, am I immune? 

A conservative answer to this question is that we don’t know for sure. Because this virus is new, we don’t know if everyone that’s exposed develops antibodies, if those antibodies truly mean immunity, and if so for how long.4

However, it’s likely that this virus acts like other viruses that we know more about. For example, for a coronavirus that causes a common cold, you get the cold, develop antibodies, and those antibodies protect you for a while. For something more severe than a cold, such as chicken pox, you can develop immunity for a lifetime. 

You may have heard stories of those that tested positive, negative, and then tested positive again sometime later. However, this is more likely to be an issue with testing methods and timing more than a case of the immune system not creating immunity.  

That being said, I do think that having positive antibodies will be a tool that’s used to help open society up and allow individuals to return to daily life with more confidence.  

Should I get tested?

While I do think that widespread testing is important for both the individual and society, the availability of testing is still quite limited. 

There are many laboratories working to address the issues of access. These include functional testing laboratories, that are frequently used by myself and my colleagues, which are now coming to the market with tests. I have some colleagues that prefer one test over another and others that are waiting for the testing to become more accurate before widely applying it to their patient population. Another factor is that testing through private laboratories is quite expensive. At some point the cost will come down and testing will become more widely available. 

In Canada, we only have access to the provincial laboratory services, whereby they’ll perform PCR testing and antibody testing provided the correct criteria are met. If a private test is requested, we’re able to use certain US-based laboratories. Diagnostic Solutions Laboratory ships their COVID test kits to Canada. They have three test options, which are nasal swab, antibody and stool. 

A German laboratory called Euroimmun AG introduced a test with 100 percent specificity, thus eliminating the chance of a false positive. It’s been approved in the USA. A full list of all the tests approved for diagnostic purposes in all countries is included here at the Center for Health Security website. The Mayo Clinic has also launched an antibody assay with a specificity of 99.3 percent when tested against normal serum. Approximately three percent of serum is IgG positive less than seven days post-symptom onset, 35 percent are IgG positive in samples collected between eight and fourteen days after symptom onset, and 100 percent are IgG positive after fourteen days of symptom onset.

We’ve learned a lot so far about SARS-CoV-2 and COVID-19, but still have plenty that we need to understand. I’ll be keeping a pulse on the new research as it becomes available and will continue these important discussions with my colleagues in order to keep you updated regarding the very latest information. My understanding of this virus is that it’s evolving day by day and although testing is relatively new, it’s still extremely important. 

As we navigate this next wave of outbreak management, testing will be key in order to understand who has active infections, who’s already been exposed, and who may still be at risk. Testing will help us to understand how the virus is spreading, answer important questions about immunity, and ultimately to save lives. My sense is that until the antibody testing can approach a specificity that’s close to 100 percent, it may be worthwhile to wait it out.  

Please don’t hesitate to reach out for support as needed. My team and I are always here for you during this challenging time. 

References: 

  1. Patel R, Babady E, Theel ES, et al. Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS-CoV-2/COVID-19. mBio. 2020;11(2):e00722-20. Published 2020 Mar 26. Full text: https://mbio.asm.org/content/11/2/e00722-20 
  2. The Institute for Functional Medicine. The Functional Medicine Approach to COVID-19: Primer on SARS-CoV-2 Testing. https://www.ifm.org/news-insights/functional-medicine-approach-covid-19-primer-sars-cov-2-testing/ 
  3. Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019 [published online ahead of print, 2020 Apr 1]. Nature. 2020;10.1038/s41586-020-2196-x. Abstract: https://pubmed.ncbi.nlm.nih.gov/32235945
  4. The Institute for Functional Medicine. The Functional Medicine Approach to COVID-19: Primer on SARS-CoV-2 Testing Webinar. Hosted by Dr. Patrick Hanaway with Dr. Helen Messier. April 28, 2020. 
  5. Guo L, Ren L, Yang S, et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19) [published online ahead of print, 2020 Mar 21]. Clin Infect Dis. 2020;ciaa310. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184472/ 
  6. He-wei Jiang, Yang Li, Hai-nan Zhang, Wei Wang, Dong Men, Xiao Yang, Huan Qi, Jie Zhou, Sheng-ce Tao. Global profiling of SARS-CoV-2 specific IgG/ IgM responses of convalescents using a proteome microarray. Preprint article: https://www.medrxiv.org/content/10.1101/2020.03.20.20039495v1 
  7. Abdul Ghaaliq Lalkhen, MB ChB FRCA, Anthony McCluskey, BSc MB ChB FRCA, Clinical tests: sensitivity and specificity, Continuing Education in Anaesthesia Critical Care & Pain, Volume 8, Issue 6, December 2008, Pages 221–223, Full text: https://academic.oup.com/bjaed/article/8/6/221/406440