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. Please note this summit has already taken place.

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 contact my office if you are seeking functional and integrative care for your IBD. 

Podcast: Looking at Lyme: 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 Lyme disease 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.

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.

People with Lyme disease have a lot of different symptoms, the bacteria attacks the body in so many different ways. Sometimes it attacks the brain, the heart, the joints, you name it. Today I'm looking at Lyme, we're going to dive into functional medicine, we'll look at the body from a holistic perspective and meet a doctor who treats the whole body and the mind.

Getting treated early for acute Lyme disease is critical. Some people find the attach ticks and others might get a bull's eye rash. But that's not always the case. And without these telltale signs, people might not get diagnosed. The longer that you have the disease, the worse it gets, and the harder it is to treat. That's when we need to go to the doctor. So, let's do that. There are very few medical doctors with the expertise of Dr. Bruce Hoffman. He practices functional medicine, and we'll get him to tell us more about that. We reached him at his Calgary clinic. Good morning, Dr. Hoffman.

Good morning to you.

What's the first thing that you look for in a patient who potentially has Lyme disease?

Your patients present to a doctor's office with many symptoms and many complex, interlocking possible what we call in medicine, differential diagnosis. So, they present with a whole host of symptoms. And it's the task of the doctor taking the history to try and work out what may or may not be Lyme disease. And sometimes patients come in with some Lyme test and say they definitively have Lyme disease, or they have positive biomarkers for Lyme disease on some of the tests they've done. But when a closer history is taken, that may not be the case. So, there's quite a lot to really sift through when you're trying to differentiate whether somebody has Lyme disease or not. The most important thing is the symptomatology. You want to take a very definitive history. In my clinic, we use different types of questionnaires to try and determine whether or not Lyme may be a diagnosis. And we also then start to take a very specific history about whether they visited endemic areas, which is somewhat a moot point because Lyme disease is somewhat, you know, it's specific, it's everywhere. If they visit an endemic area, if they've been bitten by a tick, if they've had the rash, which is very uncommon, by the way. But we start to ask the history of exposure, history of tick bite, history of rashes and in a symptom history, looking over the variable symptoms that present with Lyme disease and/or co-infections that come along with Lyme disease. A lot of questions need to be asked, and you've got to sift through them and try and determine if Lyme disease is the primary presenting feature or are there any other coexisting disorders that interlock, like mold exposure, or heavy metal toxicity or food sensitivities? And there's many of them that may interlock with a symptom presentation. So, there's a lot to ask.

Yeah, it sounds like getting that patient history is just so critical. 

History is everything. You know, you've got to take a good history. You can’t have a patient walk in and say I've got Lyme disease, and I go, okay, let's treat you. No, no, you have to stop and really ask very specific questions.

And it also sounds like you mentioned that most of your patients don't ever remember having a tick attached or getting a rash.

You know, the majority don't. I do have a number of patients who went to college in northeast in the United States, and they were out in the fields and in the forests, have a history of tick bite and rash exposure. But I would say that's probably 5% of my population. My patient population, it's very low.

Guess when we spend time in the outdoors, if we check for ticks and do a tick check and actually found one attached, we have something to at least document or same with a rash. If you found one, it'd be a good idea to get a photo of that to share with your doctor.

Absolutely. It would be lovely if we had that cookie cutter you know, clear cut, walked in the woods, got a tick, notices for within three days a high fever, headache, and then the Lyme disease rash. That's so seldom.

It's never that that clear? Is it?

Never. I wish it was easier.

So how critical is it then for people to get diagnosed and treated early?

Oh, if they've been exposed and there's definitely a tick bite. And the symptomatology of high fever, sore neck, chills and joints. If that occurs, you get them on antibiotics while waiting for lab data or getting the tick, if it's discovered, sent off to the lab for analysis. Definitely, I’ll put them on treatment right away. And there's different standards of Lyme disease treatment, depending on which school of thought you belong to. Some schools of thought say, you just need like a brief dose of doxycycline. And others say at least four to six weeks of treatment. It depends on your approach.

Do you have a preference?

Longer term antibiotics, definitely not a short term

Yeah, that was certainly my experience, I had about 10 days of antibiotics, and then all of my symptoms came back afterwards.

Absolutely. If patients have an acute exposure, and they have symptomatology, we do have a baseline laboratory test. And then we repeat it four to eight weeks later to see if there's any rising titers. And we send the tick off for analysis. I usually cover them with antibiotics for at least six weeks. 

Wow. That's great to hear. And so, what is functional medicine?

Well, functional medicine is this emergent system of approaching a patient from a very different point of view. Like my medical training is what we, I don't mean to be derogatory, but it's called the N2D2 method of diagnosis and treatment; name the disease, name the drug. You know, that's how we learned in medical school, we just look at differential diagnoses, what disease or symptom cluster does this person have, and what drug can I pull out to help them. That's the specific training, highly relevant, nothing wrong with it. But now we have this emerging cohort of patients who have this chronic multi system, multi symptom disease profiles, with many interlocking issues. And that model doesn't work. And I tend to see and many people who are outside of the so-called traditional healthcare system tend to see that cohort of patients. Functional medicine attempts to take an upstream history back to what we call antecedents, mediators, and triggers. We go and look upstream to see, first of all, what's your symptom profile now? But, when did you start to feel unwell? One of the most relevant questions I ask a patient is; when did you last feel well, and then you want to take it from there, backwards and forwards. So functional medicine looks backwards as to the timeline, or the potential triggers and inherited factors which may play a role, the triggers what may have triggered the illness, and then what we call mediators, what may be keeping that symptom cluster alive. In conjunction with that we look at, not so much as pathology and disease laboratory tests, but we look at functional laboratory tests. How is the biochemistry and the metabolomics? How are they functioning? Are they optimized? Or are they deficient within a spectrum? Traditional Medicine has a reference range of, you know, negative or positive. Functional medicine optimizes function based on individual susceptibility and genetics. It's a very elegant form of practicing medicine within chemical principles. Just old school sort of, you know, when did you last feel well; what happened and what may have been playing a role. No longer looking at single factors, instead, looking at multiple causative factors as to what keeps this patient still symptomatic. And I can tell you, from my experience, that there is never one reason why a person is not feeling well. There's usually a whole myriad and host of issues from poor sleep, poor diet, early childhood trauma, dental issues, food and gut sensitivities. It is complex, long list of what made you unwell. 

Yeah, absolutely. Why do the symptoms vary so much from one patient to the other?

You mean with Lyme disease specifically?

Yes. with Lyme disease specifically?

Well, while it depends on a whole host of factors, it depends on the individual immune response of the person, the total toxic load, the infectious load, the expression of the Lyme disease spirochaete, with or without co infections, the metabolic and nutritional strength of the individual, the immune competencies, the presence of natural killer cell functions, whether they can suppress the immune response. The fact that Lyme disease goes from different forms; the cellular form to an intracellular form, to a cystic form to a biofilm form then it comes and goes depending on your immune surveillance. There's a lot of reasons why somebody has waxing and waning of symptoms and feels variations in their symptom profile.

Is it possible for someone to have Lyme but not have any symptoms?

You can have positive laboratory testing for Lyme and be asymptomatic. Absolutely, absolutely. But you don't see those people because they feel good.

Yeah, definitely. Do symptoms flare and go dormant normally for some of your patients?

They do. They wax and wane depending on stressors, diet, travel and multiple factors affect the expression of symptomatology. Treatment or no treatment. Some treatments exacerbate the symptomatology quite dramatically. They get what they call the Jarisch Herxheimer reaction (JHR) where you put in a treatment and the patient's symptoms just go through the roof. And so, there's all these variations as to why people wax and wane and get increased symptoms at times. But yeah, we certainly have people with, with no symptoms, who have positive laboratory tests as well.

Dr. Hoffman, are you seeing a larger increase in the number of patients that you suspect to have Lyme disease and other co infections?

Absolutely. Yeah. As you know that the Lyme disease diagnosis is highly controversial, depending on which school of thought you belong to. Whether you belong to the sort of infectious disease society, the infectious disease group of medicine, or whether you follow the ILADS criteria for the diagnosis and treatment. Those are these two different schools of thought. Now you know, even with that, there's been a tremendous uptake in the Lyme disease diagnosis and co-infections due to global warming. The migration of songbirds further north and the spread of ticks deeper into the north because of global warming. It's been estimated, one study showed that the songbird flight path from South America to North America brought up to 32 million tick species. In the yearly migration just northwards from South America. So, there's a there's a huge increase in the diagnosis. For sure.

Yeah, especially for anyone who's living along any kind of migratory bird path.

Absolutely. Yeah, absolutely. And there’s this great Canadian researcher, John Scott, showing us published papers on this issue.

Yes, hopefully, we'll get him on a future podcast as well. I'd love to hear more about his research

Absolutely. Yeah.

So I was fortunate to go to the ILADS conference last year in Boston, and I learned about mast cell activation. And I was just wondering if you could tell me a little bit about that disorder.

Well, Mast Cell Activation Syndrome (MCAS) is a relatively new diagnosis. It's been around for a while. Dr. Lawrence Afrin is one of the leaders in the diagnosis and treatment. He's just recently published, which I co-authored, a criteria for the diagnosis. And the reason why that has been important is because previously at medical school, we learned about systemic mastocytosis, which is an increase in the number of mast cells that create disease processes. But mast cell activation syndrome is an increase in activity without an increase in number. And there are different criteria for the diagnosis. Mast cell activation syndrome is a very, very important concept to keep in mind when seeing patients with chronic systemic illness because you'll see it a lot. I see it a lot. Mast cells or white cells act as vigilante cells to try and protect you from incoming stressors. Whatever they may be, whether it's mental, chemical, environmental, infections or food, they spew out at least 1000, not 200 as one's thought, but more than 1000 mediators of inflammation. One of them is histamines. Everybody knows the histamine is a sort of allergy hive reaction. There are many other mediators of inflammation. People with mast cell activation syndrome have this heightened inflammatory response to ongoing day to day environmental exposures and present with a multitude of symptoms in multiple organ systems. And they travel from doctor to doctor you know, they go to the allergist and the rheumatologist and to the neurologists, but nobody ties the systemic nature of this condition together. So, it's important again to take a thorough history and elicit whether somebody may be presenting with mast cell activation syndrome. Now, interestingly, mold exposures and Lyme disease trigger mast cell activation syndrome. So you often get a cross mapping of symptomatology.

Well, what would be your best advice for someone who suspects that they might have Lyme disease?

Well, it's a very tricky one. Because here's my experience. People often want to believe in a one diagnosis - one treatment approach when they present with complex illness. And it's really doesn't do them any favors to adopt that attitude. Yes, you may have a classic exposure and symptom profile, no question about that. But when you've got chronic illness, and chronic multi system, multi symptom exposures, and you go into a Lyme test with a naturopath or an MD, they send it to the states or even they send it to the Canadian Winnipeg group. And you come back with a positive test, it doesn't mean that the reason for your symptom profile is Lyme. Lyme may be the trigger, but you may have a whole host of underlying issues that are playing a role in your symptom profile. And one of the great tragedies that I see in my practice is people who come to see me, they've got a positive Lyme test and they've been treated for Lyme. But it's really not the key diagnosis, there are 70 other underlying factors that are far more relevant than that positive laboratory test. So, in response to your question is just be extremely discriminatory, when you jump to the diagnosis of Lyme disease as causing your symptoms, it may not be that. It may be there, you may have a positive test. But it doesn't mean that Lyme disease is at the root of it. It may be that it is. But you can't just take a positive test and treat it as if that's it. And I see that 90-95% of the time. They just go get treated for Lyme, but it's not really Lyme that's causing a symptom profile. Sometimes it is, of course it is, but you've got to discriminate.

So it's that combination of diagnostic testing and patient history,

History, history, history. If you're not taking a two-hour history with your patient, a timeline from conception to present, plus even intergenerational issues because we know that you inherit epigenetically family trauma. It is very well studied and well researched. Now, if you're not taking a thorough history, and following the timeline and symptom presentation of that patient, at least a two-hour history, you can't really discriminate on a history basis, whether this patient is suffering from one illness or 15 possible comorbid conditions. You have to take that history, then you back it up with laboratory data. The more laboratory data, the better, which unfortunately and again, with our healthcare system, that sort of privilege and that sort of luxury of a two-hour interview with extensive lab data. It doesn't exist. You have to go outside the healthcare system to get that service, you know, which is a tragedy, but it's the truth.

I couldn't agree more. Thank you so much for your time, Dr. Hoffman.

Thank you so much.

My key takeaway from that conversation was just how important it is that a doctor gets a full patient history. I know that in my case, I had a lot of symptoms and it was really confusing to understand what was going on in my body. That wraps up another podcast. Thank you so much for listening. Stay safe in the outdoors.

Lecture: 11th Annual CHNC, Mild Cognitive Impairment

Since 2000, deaths from heart disease have decreased by 14%, while deaths from Alzheimer’s disease have increased by 89%. Alzheimer’s disease is the third-leading cause of death in the USA. There is a major distinction between just memory loss and a wider range of cognitive abilities and decline.

In this lecture, Dr. Hoffman discusses how to differentiate between mild symptoms of cognitive decline versus those of advancing Alzheimer’s dementia. Only 5% of all incidents of Alzheimer’s disease are considered genetic in origin; the rest are caused by lifestyle factors over which we can exert significant control.

Dr. Hoffman also talks about the different subtypes of Alzheimer’s disease, many of the 150 potential risk factors for their development and the lifestyle, nutritional, hormonal and medication interventions that can make a marked difference in patient outcomes.

Mild Cognitive Impairment 11th Annual CHNC Part 1

Dr Bruce Hoffman

Mild Cognitive Impairment 11th Annual CHNC Part 2

Dr Bruce Hoffman

Transcript

Dr. Bruce Hoffman:

And so, I look at the broader model, the seven levels of healing, I look upstream, I look at the family system. Epigenetically, you don’t escape the fate of your forefathers. Whatever fate your forefathers went through, you don’t escape it, you epigenetically manifest their experiences and if they have unresolved experiences, traumas, murders, deaths, you do not escape the effects. It has been studied extensively, many studies now, mainstream research, this is not esoteric research, with children that have been born since the world trade centres went down- higher incidence of PTSD even though they weren’t there. These events were just epigenetically transmitted.  

We know through cognitive behavior therapy that if you don’t change the way you interpret reality, you can release a whole storm of inflammatory and toxic neurochemistry which then influences your cellular expression of micro RNA, which then influences metabolic cellular outcomes; so your very thoughts, every single thought you think, 60,000 thoughts a day depending on how you bias those thoughts, determines physiological outcomes. That’s what CBT is all about. Those of you know about CBT- (cognitive behavioral therapy) – is all about changing the way you interpret reality, based on a new world view or interpretation. We have a saying in this work that we don’t heal until we actually have a new image, a new way of interpretation, a new way of looking at the world, a new story. Also, we don’t heal until we align ourselves in an accepting if not loving way with our mothers and fathers, and our ancestors. Those of you who hate your mothers and fathers. Those of you who cut off from your mothers and fathers. Those of you who judge your mothers and fathers for not having given you enough. You need to maybe open that up and look a bit closer because you are half your mother and you are half your father. How are you going to heal and cut off half your lifeforce? You can’t do it.  I tell my kids, when they need new partners, I say to them, here’s your screening tool, the one question to ask the person in front of you to whom you are potentially attracted to, “how are you with your mother and father”? Just ask the question. If they tell you that they hate their mother and father, and that they never want to see them again, run like hell. It’s not going to go well. And I tell you that’s a very reliable indicator for how people are in the world. So we use a much larger, larger model to view and interpret people’s health.

Just by way of some definitions. Dementia is when cognition fails, but Alzheimer’s is characterized by particular findings that you find in the brain. The tangles, and the amyloid plaque that defines Alzheimer’s and although it starts with memory loss, it very soon ends up in the inability to formulate language, and then socialize, and then eventually end up in the with the reptilian brain expression where you barely function. You can eat, you can sleep, but your whole orientation to the world outside of you is shut down. 

There are different types of dementia. Alzheimer’s is the most common, but there are other types. Neurologists are extraordinarily good diagnosticians. So, if anybody has a dementing process, or cognitive decline, you really do want to see your neurologist because they have the ability to really discern the subtleties of different types of dementia, and what differentiates Alzheimer’s disease from other forms of dementia. As I said there is the APOE4 gene- if you have the APOE  3/3 gene, you have a 9% risk of Alzheimer’s. If you have the 3/4 gene you have a 30% three times increased risk, and if you have the 4/4 gene you have a 50-90% risk potential for developing Alzheimer’s disease as you age if you don’t do something to change the inputs. There is a website https://www.apoe4.info/wp/ for carriers of these genes because the people who run this website are aware now of how profound this gene is. This website is dedicated to informing individuals with the gene and what can be done to down-regulate the potentially negative outcomes of disease expression. 

I’m going to skip some of the basics because I know I’m going to run out of time but here’s the hallmark of Alzheimer’s, these tau tangles which are in the neurofibrillary and the amyloid plaque. This creates an inflammatory response which shuts down neuronal synaptic communication, which kills neurons so as your synapses die from these tangles, neurons die. Your brain atrophies and dementia can ensue, and if you had to look at what in at the most minute level- what’s really going on in Alzheimer’s disease. It has everything to do with the interplay between trophic factors and blastic factors, growth factors and destructive factors that influence one particular protein called the amyloid precursor protein. This is where amyloid plaque comes from, it comes from this protein. It’s a subset of it and you have what are called molecular scissors, or proteases that come along and they snip through this amyloid precursor protein. If it makes one snip, you get the anti-Alzheimer’s outcome. If it makes four snips, you get the pro Alzheimer’s outcome, so the entire Bredesen protocol is everything to do with how you influence these molecular scissors to favorably produce the two pieces of amyloid precursor protein, as opposed to the four. That’s what it is, what you can do to drive support for neurons, as opposed to destruction of neurons by influencing these molecular switches. That’s it at the molecular level anyway. 

So, we don’t go progress straight to Alzheimer’s disease. Before Alzheimer’s occurs, there’s a subjective cognitive decline that can occur, for people 10-15 years before where people may say “I’m just off my game, I’m not as smart as I used to be now.” Normal aging produces this, our brains slow down but if you are going down the dementing routes- if you’re going down the Alzheimer’s route, you may start in a preclinical way. Some of your tests may be already positive before you actually pick it up. It’s subjective decline. Then you actually start to get mild cognitive decline where you actually objectively starting to register negatively with specific testing. I can’t tell you how many people come to my office who are running corporations, CEOs, with mild cognitive decline. Their biochemistry, their markers of cognition, they fail, but they’re still operational but they’ve got objective signs of decline. After that is when you lose tasks of daily living and you start to go down the dementing path. There is a difference between dementia and normal aging with statements like “I forgot my keys.” People with just normal aging usually remember where they parked. They can retrace their movements and realize, “Ah that’s where I left them.” So, these are some differences, but it’s a bit of a fuzzy line in the beginning. As I said those of you on the right side of your biological drives when your brains speed is still travelling at 300 milliseconds. You still got a good brain speed, so you’re not so concerned about this but I’m personally on the other side of that curve and I’m very concerned about things like this. That’s why I started the brain treatment centre, not only to help patients. I had a selfish interest; I want to keep my brain moving at 300 milliseconds for as long as I can. Okay so this is the difference. Everything has to do with brain speed. Our brains move at 300 milliseconds per second. After age 20, and every decade thereafter, 10 milliseconds are lost just through normal aging. That’s profound, you know when your brain speed slows down you literally slow down. When your brain slows down, neurons and synapses die and there may be a bad outcome if you don’t do something about it. There’s a separation, a gap, between thinking a thought and executing the thought, by doing. 

There’s many reasons why people’s brains slow down or are exacerbated by lifestyle issues that don’t lead to necessarily dementing Alzheimer’s illness. The aging is the number one cause of brain slowing down but then you may have strokes and stress. People also drink far too much, it’s a neurotoxin they get addicted to. Certain things, prescription medications, can have profound effects. I mean you have no idea how many statins are given out like candy. Some of them cross the blood-brain barrier and shut down cholesterol metabolism. Cholesterol is a building block of brain neurons and myelin. You have got to think before people start taking these drugs. Some people come into the office and we suggest they go through something called the Cognoscopy. Everybody at age 50 gets a free colonoscopy, free under health care. Now, in terms of the future, start spreading the word, ask you friends, ask your parents, mom have you undergone a cognoscopy? A cognoscopy is a brain evaluation. Now your mother will say no because it doesn’t exist in the healthcare system. We can plant the seed; we can start thinking about it. It will happen because as I said in the beginning, try living one day without a functional brain. You know, it’s awful.

At the clinic we do questionnaires. Any of you recognize this MoCA (Montreal Cognitive Assessment)? You recognize it? Do you remember Donald Trump 2 months ago flashed this test and said “I’m brilliant, I’m a genius.” No, I’m serious he did pass the most elementary of cognition testing called the MoCA- and this is a five-minute test. He got 30 out of 30 apparently, but people with dementia they fail it. If you know anybody with a score less than 19, you’re on the wrong side of your MoCA. Your MoCA score for the average Alzheimer’s patient is around 16, 16.2. If the score is 19 to 22 those people with dementia will, if they can’t you now- they can’t take care of the daily tasks of living.  That’s a serious pattern. People with a mild cognitive impairment they have a MoCA score between 22 to 25. People who passed had a score of 26 or up. If you want to be in that range, I suggest that you get your brains assessed even if you do this online. It takes five minutes. We also have at our center the computerized CNS vital signs tool which is a computerized measurement of cognition. With this slide you can see this is one of our Alzheimer’s patients. They can’t perform the tasks of executive functioning which the frontal lobe performs. What we take for granted they completely failed as opposed to somebody with a relatively normal executive functioning. You see how the brain atrophies and the brain atrophy starts in this part of the brain called the medial temporal cortex; that’s the hippocampus. The hippocampus is where we lay down new memories. It has limited capacity but we lay down our new memories in the hippocampus and as the dementing process spreads, it reduces the hippocampal neurogenesis and the nerves start to die but then it’s spread throughout the brain and this is a typical brain with Alzheimer’s. It really is shrunk, it’s quite remarkable, when you see it on MRI and there’s many imaging techniques which are used, MRIs, FDG-PET scans, amyloid PET scans, there’s all kinds of diagnostic tests. We’ve recently introduced in Canada software called the NeuroQuant MRI and this has to be privately ordered. You can’t get this from healthcare, I’ve asked, they won’t do it. But this NeuroQuant MRI actually measures objectively the size of each different area of your brain and compares you to a normative database of particularly the hippocampus and the frontal cortex. These are the two parts that go first, they shrink and we can objectively measure and compare these to other people’s brains. A normal MRI doesn’t do this. Here you can see the hippocampus is reduced. We also do QEEGs, and we can see the brain slowing down, that’s a slowed brainwave that we measure through a QEEG. 

Then we get to Dr. Bresden’s six subtypes of Alzheimer’s disease. Here we really have to understand the different six subtypes to learn how to work them up and how to treat them. If we don’t understand them according to this model, we can’t treat themand so the subtypes are: 

A) Inflammation. Here inflammation is at the root cause of the Alzheimer’s expression, Here, all these inflammatory markers get expressed in APOE4 subtypes. Inflammation is the most important risk factor for that subtype. Here you can see the hippocampus atrophied. We then have to seek out all the causes of that inflammation and all of you know the following triggers very well. Food, gut health, leaky gut, this is at the basis of this inflammatory subtype. We look at the causes of leaky gut, these are all lifestyle issues and we can actually measure how leaky your gut is and how leaky your brain is. You can actually measure now with specific labs the leakiness of your barrier functions and you can measure gut ecology and look at inflammatory factors. You can measure and look at zonulin – the protein that causes leakiness and histamine that makes it worse and then you can actually measure the protein in the lipopolysaccharide coating of bacteria that leak across the gut and cause bacterial endotoxemia and an inflammatory response. These are called LPS lipopolysaccharides. This is the root of many inflammatory brain disorders. Look at all the diseases that get expressed when lipopolysaccharides get expressed.

Then you look at food sensitivities. There are many different ways to look at food sensitivities. Many people come and see me and they have done one IgG test. That’s not it, you have to look at different immunological pathways to look at food expression. One test at our local private lab for IgG foods is not how you work up food sensitivity. You must learn about the other methodologies because they are extremely relevant. One may be positive may be negative in the next test. We also do a whole ton of work around gluten. Gluten as you know, nobody processes gluten well, even if you have or don’t have celiac disease. Even if you have or don’t have gluten sensitivity, nobody has the enzymes to break down the gluten molecule. Nobody. Dr. Fasano the great gluten researcher has said this for 10 years. You get a leaky gut from gluten, now those of you without the bad genes can repair it within hours. But every time you have gluten, you have a leaky gut- quick repair- ok. We measure the gluten molecule in all of its subsets with specialized labs and we measure antibodies to cross-reactive foods. Gluten cross-reacts with different foods. How many of you like coffee? How many of you like coffee and are gluten sensitive? How many of you knew (instant) coffee performs molecular mimicry and ignites the same pathways as gluten may? Just a thought. A particularly horrible thought. And then we can measure antibodies to specific tissue. We can measure antibodies against all of our organs and particularly we can actually measure immune systems attacking of core neurological structures, synapses, tubulins, myelin. You can see how under attack your brain is when you start doing these tests. 

Dentistry. How many of you lump dentistry and health together? How many of you lump dentistry and medicine together? It’s a separated discipline in present ways it is practiced. We can’t work up an Alzheimer’s patient without doing an extensive dental work-up. I do a panorex x-ray and a 3D cone beam CT, looking for periodontal disease, root canals, mercury fillings, dissimilar metals, implants, cavitations. There’s a whole slew of potential toxicity existing in the mouth. Multiple studies show the link between periodontal disease and the risk of Alzheimer’s disease. We do peridontal workups.

B). The second subtype is the glycotoxic, the type that causes too much sugar. Sugar as you all know is a potent, potent toxin. It should be a classified substance. 300 years ago, it was sought after like cocaine is today, people would seek it out because they knew how it made you feel- temporarily. Our bodies can’t cope with more than 15 grams of sugar a day. What is in one  sugar soda contain -4200 grams of sugar (not diet). We can’t cope with this huge input of sugar, I mean I know you know formulas but this is the second subtype that causes neurological causes, dementing processes.

C) And then we get the atrophic type, the atrophic type is the type that as the brain ages, it loses neurotropic support, vitamin D, zinc, estrogen, testosterone, pregnenolone, DHEA, all of it gets withdrawn as we age. If there’s one thing in my practice that I enjoy the most, is to see a postmenopausal woman who’s not dementing but she has cognitive decline, go back onto bioidentical hormones and they are so happy. Three months later they come in and the first thing they’ll say, I can’t believe it, I’ve got my brain back. Why? Estrogen is a neurotropic, neuroblastic hormone. It improves synaptic connections and improves dopamine; it changes cognition dramatically. This is the second type. 

D) The third subtype is the subtype that is toxic. This is a subtype of Alzheimer’s, it’s a different presentation of Alzheimer’s. It’s usually in younger people, it’s not so much influenced by the APOE4 gene and they usually present with a lot of frontal lobe symptoms as opposed to the typical hippocampal memory loss. But they do get- the first sign of somebody who’s got a toxic sort of brain is somebody who can’t multitask anymore. They used to do five things and now they can’t, they just have to delegate and that’s one of the first symptoms and we have a whole new world of work being done by Ritchie Shoemaker and others on the chronic inflammatory response syndrome. This is where the innate immune system is upregulated due to mold and Lyme and it causes this very specific profile of inflammation through the innate immune system which affects the brain and effects all the neuro peptides in the brain which regulate leaky gut which regulate hormones which regulate oxygen delivery to mitochondria. This is a whole subset of work that’s going on not in mainstream medicine, you won’t see it, you won’t find it, it’s not there but it’s in the research literature and we do certain things in our clinic to try and find out. We do questionnaires of that particular type, type three chronic inflammatory response. We look at the visual contrast test to see if people fail this test and we do spore counts and mold counts in their homes. Then we look at metals, heavy metals is a big cause and pesticides and air pollution and Lyme disease. How many people will have heard about Lyme disease epidemic, it doesn’t exist in Alberta right? Yeah. My entire day- do day-to-day, week-to-week- is made up by mold and Lyme, toxic people. They travel, they get it from other sources and we believe now the literature’s quite clear that Lyme disease may be transmitted by other factors, and there’s literature here in Calgary by Maureen Middleveen, that it may be sexually transmitted as well. This hasn’t been published in peer-reviewed journals but the literature is out there making those suggestions. With Lyme disease we find the pathogen inside the brains of people with Alzheimer’s disease. We find herpes simplex 1, the good old cold sore as a big cause. There is also a link between pesticides and Alzheimer’s. Glyphosate. How many of you eat organic food? Even organic food is riddled with glyphosate because of cross-contamination. It’s everywhere. Glyphosate is highly toxic to many core organs. It causes gut permeability; it shuts down neuronal pathways. 

E) Then the vascular subtype is with people with hypertension and atherosclerosis which decreases oxygen supply to the brain causing Alzheimer’s decline. 

F) And then we get the traumatic subtyppe; the brain injured people; I mean look at these statistics. Not all head trauma patients will develop Alzheimer’s, but there is 2.3 times increase incidence in mild or moderate traumatic brain injury. 4.5 increase in severe brain trauma. There are no studies linking mild brain injury to Alzheimer’s disease, but three or more concussions -a fivefold higher incidence for memory loss and cognitive impairment.

I’m out of time. Well there’s a whole slew of lab tests you can do to sort of think through this problem. You won’t get it under health care, you won’t get it from your family doctor, in fact you’ll get dismissed so it’s up to you to educate yourself. Dr. Bredesen’s book The End of Alzheimer’s is fabulous, I suggest you read it and you start working through your own cognoscopies, how you can work yourself up to see if you’re at risk and then therapeutically there’s at least 36 things you can do to down regulate cognitive decline and/or Alzheimer’s of which- guess what’s number one? Nutrition. 

One last word, ketogenic diets seems to trump every other diet when to comes to changing brain outcomes. Combine that with good sleep, exercise, stress reduction, you’ve got the four pillars of turning down mild cognitive decline of potential dementia, and then you can look at all the other factors with influence outcomes and just teach yourself because nobody out there is going to teach it to you and you definitely won’t get it from your medical doctors. So thank you very much. Thank you.

Judith Cobb:

Thank you, Dr. Hoffman, that was amazing. If you have questions please come and use the mic, we have about 8 minutes for questions, and at 9:30 you might get cut off right in the middle because we’ll be live streaming with Toronto, so questions?

Question:

Just a quick one, I know vitamin D is a really controversial item right now and is limited in information especially with auto-immunity, so what do you recommend for dosing, food versus supplements in the grocery list this summer?

Dr. Bruce Hoffman:

So, those are the  foods that contain vitamin D, this is how you can calculate your vitamin D needs, but I can tell you it’s not that accurate. Every Calgarian that I’ve ever seen who’s not on vitamin D supplements is vitamin D deficient, everyone. But you can’t tell them how much to take because everybody has a variation in the amount they need, depending on A) The VDR gene receptors which is from the 23andme gene test. because the people with a VDR plus plus gene need a lot more vitamin D. The state of the small intestines is where you absorb vitamin D and many people have very disrupted small intestines, and they have SIBO and small bowel SIFO with fungal overgrowth and they don’t absorb the D vitamin and you need the D vitamin and you need a lot of oil. In fact, Vit D – this is a fat-soluble vitamin. I can’t tell you how many people are fatty acid deficient, the majority of people by far. Everybody’s taking omega-3s, that’s epidemic right now, everybody comes in taking fish oil- fish oil isn’t it. It’s got benefits but you need your omega-3, your sixes, your nines, your mono and saturate fats; your saturates in order to absorb vitamin D and vitamin A and vitamin E which are fat soluble. So, to answer that question is complex but patients hate me, they always ask me questions and I say “I’m not sure, it’s complex”, they go “give me an answer”. Then I will do a ten minute explanation, and they go “oh I see”. So that’s the kind of complexity that this requires to answer that question.

Question:

For people in our industry, it’s really hard for us to help with stuff like this especially now that Alberta does not test vitamin D, so how do you recommend we help people that do come to us with these issues when we can’t convince them to their doctor to get tested for this?

Dr. Bruce Hoffman:

So, it’s a great question. First of all, you can get vitamin D tested just so you know, there’s a trick. Yes, the trick you got to have a friendly GP who’s going to lie and say you’ve got celiac disease or malabsorption syndrome or osteoporosis. They need to sign a form, if they sign the form you can get it done, but I can tell you from my experience, none of them will, but if you have a good relationship with them and you can prove to them that there’s a need, they will do it for you. If you put a circle where it shouldn’t be and you don’t cross the box where it should be, you’ll be rejected. It’s that weird, that’s firstly. Secondly you can get vitamin D from private labs so people have to spend out of pocket. 

This notion of having Canadian healthcare pay for your functional medicine and wellbeing, please give it up, it’s not going to happen. You have to have health as an extremely high value and you have to invest in your health with your own after-tax dollars because they won’t let you deduct it in order to maximize your health outcomes. Please don’t think that Alberta health care is going to do this for you and I don’t think they should by the way. People always feel almost shattered when I say that. The disease based system,  we already pay exorbitant taxes to fund the free health care and they do a good job of you know, when we have a heart attack and go to the emergency and we get 5-star treatment and intensive care. Don’t try and muddy the waters asking that system which treats tertiary disease, to start doing preventative medicine overnight. I think it will creep in overtime but if you want them to do functional medicine and preventive medicine and start to fund what you do your taxes will be 95%. It can’t happen, so please be responsible, get rid of an adolescent fantasy that health care should take care of all this, it won’t and I don’t think it can afford to. You have to have health as a high value, you have to invest in yourself, you have to educate yourself,  you have to become your own patient advocate and you have to do what it takes to get you where you need to go.

Question:

Hello, outside of MRIs, EEGs, CAT scans and others in our regular system, how do you feel about the spec imaging, neurospec imaging?

Dr. Bruce Hoffman:

Neurospec imaging? It’s not- it’s generalized but it’s not specific. You can see signs and symptoms, you can see certain images like you know the ring of fire, Daniel Amen’s. It’s not specific but it is done. PET scans, more accurate and some of the more advanced PET scans are more accurate. Neurospec is sort of a secondary test, I wouldn’t use it as a primary test unless you got free access.

Question:

Hi, I just saw on a slide that you said with inflammation it had to do with Pitta and Ayurveda and what the relationship was there?

Dr. Bruce Hoffman:

Are you familiar with the Ayurveda? So, I evaded talking about doshas- doshas are constellations of elements, vata is air and space, pitta is fire. What is inflammation? Fire, too much fire.

Question:

So, someone with Pitta is more susceptible to Alzheimer’s?

Dr. Bruce Hoffman:

I don’t know if that’s statistically true, but theoretically of the subtype one, inflammation, I would say, I would posit a guess, I don’t think studies have been done- now Bredesen knows a bit about Ayurveda.  I was astonished that he did, so I would think they may be something to that, there may be literature on that  that but I can’t say for sure, but it makes sense. Pita is the hardest to treat by the way. 

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Podcast: Mast Cell Activation Syndrome With Dr Bruce Hoffman

I was recently interviewed for The Dr. Hedberg Show, where we spoke about mast cell activation syndrome and how exactly the condition is diagnosed. In this podcast, we reviewed the similarities that exist among certain conditions (fatigue, brain fog, and GERD to name a few) and how they may be indicative of mast cell activation syndrome.

 

Dr. Hedberg: Well, welcome everyone to “Functional Medicine Research.” I’m Dr. Hedberg. And I’m really looking forward to today’s conversation with Dr. Bruce Hoffman. He’s a board-certified physician, and he has a Fellowship in Anti-Aging Medicine, as well as a Master’s Degree in Clinical Nutrition. He’s a certified functional medicine practitioner. And, one of the really interesting things about him is that, in addition to his clinical training, he studied with many of the leading mind-body and spiritual healers of our time. People like Deepak Chopra, Paul Lowe, Osho, Ramesh Balsekar, and one of my favorites, Jon Kabat-Zinn.

So, Dr. Hoffman, you shared the stage with Dr. Deepak Chopra and Dr. John Demartini. And he continues to spread his inspiring vision of healing and wellness with audiences and patients around the world. So, Dr. Hoffman, welcome to the show.

Dr. Hoffman: Thanks very much, Nikolas. I’m glad to be here. Thank you.

Dr. Hedberg: Great. So I’m really looking forward to this discussion on mast cell activation syndrome. It’s something I haven’t seen a lot of in my practice. I have heard a number of lectures on this and read quite a bit about it. And it seems to be an area of your expertise. So why don’t we jump right in and just talk about what mast cell activation is, and how is this condition diagnosed?

Dr. Hoffman: Sure. I first got interested in mast cell activation syndrome when I started to work with a cancer patient advocate by the name of Dr. Mark Renneker out of San Francisco. And he alerted me to the connection between cancer and mast cell activation syndrome, particularly in gynecological cancers. And then put me in touch with Dr. Lawrence Afrin, who leads one of the major sort of advocacy groups for mast cell activation syndrome as opposed to systemic mastocytosis, which I’ll explain in a bit.

And so, I’ve been for the last three to four years working with Dr. Lawrence Afrin’s group and learning to understand the implications of mast cell activation syndrome in most of the patients that we see. Which are chronic multisystem, multisymptom patients who, as you know, have been everywhere and remain frustrated with the one disease, one drug paradigm that we learned at medical school. So, what I learned over time was how to separate between two specific conditions, one called systemic mastocytosis and the other called mast cell activation syndrome.

Mast CellBut before I begin with that, I’d like to say that mast cells are part of, they’re produced in our bone marrow, and they’re part of our immune system. And they make up a very small percentage of it. And they act as defense structures against incoming invading pathogens. So, anything that comes into our environment or into our biome, mast cells are often at the first line of defense. And they were actually discovered a long time ago, 1878, I believe, by Paul Ehrlich. And he called them mast cells because they were fat and puffy.

And the word mast in Greek means breast or the German means masticate. So, this is how the name mast cell got generated. Just for your North American readers, I say mast, and most people don’t know what I’m saying. So, it is mast in North America. People often don’t know mast cells, what I’m saying.

So, these were originally discovered by Paul Ehrlich when he developed specific staining for them. And since then, they sort of lingered on in the literature. They were linked early on to cancer, but that sort of faded out of the picture until it was resuscitated by some Italian researchers who now are doing massive amounts of work on mast cell activation syndrome and cancers. And then it really sort of resurfaced in the 1990s and didn’t really gather steam until about 2007, when two, you know, researchers and clinicians put together sort of a consensus statement on what constitutes MCAS.

There are two different schools of thought and they do tend to conflict with each other in terms of the diagnostic criteria. But basically, mast cells being part of the immune system, and regulating many of the incoming so-called antigens or toxins tend to be distributed in almost all tissues, but nowhere quite as much as on mucosal surfaces: so eyes, mouth, skin, GI tract, bladder, etc. They’re also found in other tissues, you know, lungs and heart tissues, and brain, many mast cells are activated in the brain.

And so, when they get triggered, they do tend to release many, many mediators of inflammation. And it was estimated that there were over 200 mediators of inflammation that get released by these mast cells. But Dr. Afrin in a very recent post, as of last night, said that he’s now changing his opinion that he believes there are over 1,000 mediators released by mast cells. All these inflammatory mediators like histamine, like proteases, prostaglandins, leukotrienes, all these inflammatory mediators that then set up this multisystem, inflammatory response, which can confuse diagnosticians particularly if you have been trained in single organ, you know, specialties.

So that leads to the sort of difficulty with the diagnosis as people present with many different symptoms. And unless you have an understanding of mast cell activation syndrome, and a method of sort of sifting through the multiple systems they can present, you can often get very confused and misled. So, the recent, you know, people speaking about mast cell activation syndrome is an attempt to bring some coherence to this somewhat disorganized field. And hence, establishing criteria for the diagnosis, lab tests, and then treatment protocols. So now it’s coming into its own and I think you’re going to hear a lot about it in the years to come.

Dr. Hedberg: Mm-hmm, so we’re talking about illnesses that may be so-called mystery illnesses, and multifactorial presentations like gut issues, skin, brain, and things like that. Can you just let everyone know some of the overlap that you see in various conditions in your practice that would specifically indicate mast cell activation syndrome?

Dr. Hoffman: Yeah. So, mast cells, when they release the inflammatory mediators, can present locally or systemically. So, a local condition would be something like hives, urticaria, or interstitial cystitis. Or it can be systemically like people can present with cognitive symptoms. So, they’ll have fatigue and brain fog, and associated GI symptoms, like GERD. GERD is a potentially very big diagnostic category for mast cell activation syndrome or, you know, the irritable bowel syndrome. Even the autoimmune diseases of Crohn’s disease and ulcerative colitis have been linked to mast cell activation syndrome.

Asthma is another one. Asthma, you know, if you analyze all the triggers of an asthma response, and you identify them, like, for instance, mold, allergy or mold inflammation, which are two different criteria, and you remove the trigger and downregulate the mast cell activation potential, I can’t tell you how many cases of asthma have been absolutely shut down when you treat the mast cell activation. It’s very rewarding. The same goes for GERD, the same goes for irritable bowel syndrome. The same goes for anxiety and cognitive decline. When you target the triggers and downregulate the mast cell activation, it’s very rewarding to treat these patients, and they’re very grateful. Angioedema, another one, canker sores another one, there’s many, many symptoms in all the organs that can present with this syndrome.

Afrin has written a chapter in a book. The book is called “Mast Cells,” the editor is David Murray. The chapter is chapter…I think it’s chapter 6, and it’s called Presentation, Diagnosis and Management of Mast Cell Activation Syndrome. And at the back, he gives a long, long list of every organ that can be affected from ophthalmic, to lymphatic, to pulmonary, to cardiovascular, and just goes through all the systems. Even fibromyalgia, even osteoporosis, headache, all the mood disorders, dysmenorrhea, endometriosis, many of the hematological conditions, the immunological conditions. There’s a huge long list of different organ systems that can be affected that present as isolated diagnoses to specialists, but often they miss the overriding pathophysiological basis to the condition.

And our training as MDs makes us very aware of what is called systemic mastocytosis, which is when the mast cell from a clonal perspective within the bone marrow becomes amplified. There’s actually a mutation of the KIT gene. And the mast cells become very high in numbers. So, there’s increased numbers of mast cells, which is systemic mastocytosis, which is very different from mast cell activation syndrome, which is an abnormal reaction of the mast cells, not an increased number.

So, I can’t tell you how many patients come back to me after having got the diagnosis of mast cell activation syndrome by myself with the criteria I use, go to the specialties, go to the hematologist, go to the gastroenterologist, or pulmonologist, who then does a serum tryptase and even sometimes go as far as do a bone marrow biopsy, and then come back and say, “Oh, that diagnosis is incorrect, he doesn’t or she doesn’t have systemic mastocytosis.” Systemic mastocytosis is a very rare condition, I’ve never seen one in my life. But I see almost twice a day, mast cell activation syndrome. Dr. Afrin believes that probably about 30% of the population gets affected to some degree or the other.

Dr. Hedberg: And are there any theories at this point about why mast cells become so overactive in an individual’s body. Any good research out there on that?

Dr. Hoffman: Well, there’s lots of speculation. And the most common hypothesis is that we do live in a much more sort of, you know…we’re inundated, so to speak, with multiple stressors far more than our capacity to withstand them. Our immune system, it just gets triggered because of multiple stressors. And there are many triggers for mast cell activation. Poor sleep. Stress is one of the biggest triggers. Food, I mean, food is incredible in its ability to trigger the mast cells that are in the mucosal surfaces of the mouth through to the anus.

So, we believe that our ability to…..we can no longer withstand the onslaught of our ongoing multiple stressors, whether they be environmental, emotional, nutritional. We just are in this constant state of over reactivity if you’re genetically predisposed. Now, Dr. Afrin doesn’t believe it’s necessarily a genetic condition that is transmitted through the germline. But he believes there are mutations in some of the mast cell production. And Dr. Molderings, who’s published a lot of papers with Dr. Afrin, has done a lot of research on the so-called KIT mutation, not in the bone marrow, but within the mast cells themselves, and has shown that they are these sporadic and spontaneous mutations that occur. Why those occur? I can’t say. I don’t know the answer to that. Yeah.

LAB TESTS

Lab Tests

Dr. Hedberg: So, there’s a number of functional medicine practitioners listening to this, so let’s just talk a little bit about lab tests, and some of the ones that you’re using and the ones that are beneficial. Obviously, CBC might be beneficial with elevated eosinophils, basophil, or possibly those are normal, histamine testing and things like that. What are some of the top tests you’re doing in your practice to identify this?

Dr. Hoffman: So yes, we do all the normal standard CBC and electrolytes, and liver function, etc., but those don’t usually yield what you’re looking for. And one of the challenges is that the lab testing positive results fluctuate depending on whether the symptoms are being expressed or not.

So, the first thing is you want to try and catch a person in a flare. Well, that’s difficult you know. So that’s the first challenge. And many of these tests need to be repeated over and over again until you get what Dr. Afrin likes to identify as two positive lab tests, which I’ll explain in a second. The second challenge is that you have to process a lot of these labs on ice. You have to have a refrigerated centrifuge to get accurate results. And it took me two years to get a refrigerated centrifuge. And as soon as I was able to, the positive rate of my lab has skyrocketed. Many of these lab specimens are very poorly handled. And, you know, they sit around for days and you’ll get these false positives for sure, false negatives, I mean. Sorry.

And also, a lot of the mast cell activation syndrome people or patients, they don’t always cause these abnormalities in the lab tests. Positive lab work is only obtained around 20% of the time. So, it’s quite frustrating, you know. But if you want to get lab work tests, I use sort of the minor and the major criteria. There are 10 major lab tests that we do. And then depending on the budget, we do the top 5 or 10, if we can.

And the tests that I recommend are plasma histamine, has to be chilled. And you should catch a person who’s in a flare. If they’re not in a flare, it will very often be negative. And you’ve also got to stop some of the inhibitors of histamine for five days prior to the test. Otherwise, you will get suppression of the histamine response. If people are on, you know, H1 or H2 blockers, you won’t get a positive test. And many people do take them intermittently you know.

Then we look for N-methylhistamine, which is a 24-hour urine also needs to be chilled. And then probably the one test that I get the most positives out of is the prostaglandin D2 plasma test, also must be chilled. And for that test, patients need to be off of all nonsteroidal anti-inflammatories, Motrin, Advil, or aspirin, or salicylate-containing foods. They can’t have a high salicylate diet. Anything containing aspirin for up to five days.

And then the one that is also done is the prostaglandin D2, 24-hour urine, also must be chilled with the same criteria of having to be off of all these medications. And then the last one is chromogranin A, and for that test you have to be off proton pump inhibitors and H2 blockers like famotidine. So, if you do go on proton pump inhibitors and so forth, they can falsely elevate chromogranin A.

And then after that, we’ve got prostaglandins 11 beta F2 alpha, a 24-hour urine, also must be chilled. And then the one that most MDs know about, which is serum tryptase. But this is rarely elevated in mast cell activation syndrome. It’s very important that every doctor who wishes to sort of work with mast cell patients knows this to be true. Because if the tryptase comes back normal, very often, the entire sort of clinical diagnostic differential gets thrown out, “Oh, they don’t have mast cell activation syndrome.” Big mistake, big, big, big mistake.

One of the criteria, one of the two different schools of the consensus criteria, they say that you have to have the serum tryptase elevated over 20% of baseline, or have a baseline greater than 15 nanograms per mil. But Dr. Afrin, who’s somewhat opposed to the consensus statement put out by Aiken and others, he highly disputes this finding and he doesn’t agree entirely that this is one of the main criteria to make the diagnosis. And I tend to agree with him.

Leukotriene E4, a 24-hour urine. Plasma heparin because heparin gets secreted by mast cells. And then a blood clotting profile, thrombin, PTT and INR is often done. And those are the top 10 and then after that, there’s many others; anti-IgE receptor antibodies, pheochromocytoma workup. We often do factor VIII deficiency workup, we do urinary metanephrines often. We almost always get an immunoglobulin profile IgG, IgA, IgE, and IgM. You might see IgE elevated or not. Often you won’t have an elevated IgE. So many people think “Oh, if a high IgE, then it can’t be this.” But that’s not true you can get a non-IgE-mediated mast cell activation. People then do bone marrow biopsies. People can do gastrin, serum gastrin levels. And then as you mentioned, the CBC with eosinophils and basophils can sometimes are elevated. Antiphospholipid antibodies are also often done.

And one test I like to do in the functional world is the Dunwoody Lab test for zonulin, histamine, and the DAO enzyme activity because that’s the diamine oxidase enzyme that sits on the villi that can be genetically compromised. Or because the villi are compromised, you cannot produce enough diamine oxidase. And that’s when you start to put people on low histamine diets and use the HistDAO enzyme to help break down any remaining histamine in food.

But I can tell you the one test that I tend to rely on more than any other right now, apart from the serum and urine test, is to get restaining of any gastric biopsies people have done. This has been overwhelmingly sort of helpful to some of my chronic GI tract patients in particular. So they would have gone, you know, to a GI specialist, they would have had the normal Giemsa tissue stain, and they comment on lymphocytosis. But they don’t actually comment on mast cell activation. And unless they get what’s called the CD117 stain, you won’t isolate the mast cells.

And almost 90% of people that I’ve clinically suspected of having mast cell activation syndrome turn up once they have their biopsies restained of having over 20 cells per high-power field being positive for mast cells. Which is the cut-off criteria that’s been agreed upon by numerous researchers, highly contested, by the way, by some pathologists and gastroenterologists. But we use a cut-off point of greater than 20 mast cells per high-power field to make a diagnosis of mast cell activation syndrome, particularly in the GI tract. The mast cells are very rich in the GI tract, particularly in the duodenum, not so much in the gastric tissue, but particularly in the duodenum.

So, if they ever had a biopsy in the duodenum, phone up the pathologist or write a letter and say, “Please will you restain for the CD117 stain.” And as I said, probably 9 out of 10 come back positive, very helpful. And then the patient sees that and the penny drops then they start reading up all the literature. And then they get on board for the treatment protocols which are, you know, quite…it can be onerous, and they can be extensive. But they’re very clearly delineated with multiple challenges along the way. Because people react to the medications and/or the supplements that you give them because that’s the nature of the condition.

EXCIPIENTS

pills

So, they’ll come back and say, “I can’t take the H1 blocker because I got worse.” Well, most of the time, it’s because it’s the excipient, the additive, the filler, or dye inside the medication that triggered the mast cell syndrome and it’s not the actual problem. You know, they’re not reactive to the supplement, they’re reactive to the excipient within the supplement or the drug. So those are some thoughts.

TREATMENTS

Doctors in meeting

Dr. Hedberg: Right. So once you’ve identified that someone has this syndrome, let’s talk about some of the natural treatments. You just mentioned that some of them are very difficult to follow. And some of these patients are…there’s probably a fair amount of trial and error with some of these patients figuring out what works for them. So, can you just talk a little bit about some of the treatments you’re using?

Dr. Hoffman: Sure. One of the hallmarks of this condition and one of the setups in my interaction with patients is a description of the complexity of the diagnosis and the challenges. And if you don’t have that conversation, you’ll often get a frustrated patient because they’ll come back with flare-ups and they understand it. So, I encourage that all your practitioners who wish to dive into this field really wont understand how patients can flare and how they

may have multiple triggers at any given time. And that the treatment may need to change, and that they mustn’t become frustrated, they must just stay for the long course. And they are sort of part of the team of trying to work out these multiple moving targets.

So the education is number one. I have two handouts, where I’ve described mast cell activation syndrome and mast cell activation syndrome treatment. I make sure they’ve read that. If they’re more interested, I give them Dr. Afrin’s book, “Never Bet Against Occam.” There are many patients who love to read because it’s filled with case histories. So once they get sort of an insight into other cases of complex presentation, they get encouraged to push on. So, education is first.

Second is to try and identify the triggers that trigger their mast cell activation. And this is one of the greatest challenges because there are many triggers from, you know, hot, too much heat, too much cold, stress, poor sleep, as mentioned. And then we get into the more obvious triggers, chemicals, heavy metals, dietary antigens, and then infections or inflammatory triggers like mold.

So, part of the process of working up mast cell patient is not just diagnosing the syndrome, but also trying to work up the triggers. So, in most patients, I do multiple food sensitivity profiles. I don’t just do IgG. I do IgG, IgG4, I do the so-called LEAP test. I do…am I allowed to mentioned lab names on your podcast?

Dr. Hedberg: Yes, definitely.

Dr. Hoffman: Okay. I do the lymphocyte sensitivity tests, the LEAP test. I do, as I said, IgE testing, IgG, IgG4. And I do Cyrex Lab food, I do the 10x, I think it is, with all three panels looking for dietary antigens. So, the Cyrex panel is different from the Meridian Valley food panel. Meridian Valley says it’s an IgG, IgE panel, but I disputed that once, and I’m not too sure there’s much IgE in the Meridian Valley panel. I think it’s more IgG. Whereas the Cyrex panel is more IgG and IgA. And you’ll often get contradictory findings. They’re very frustrating. That’s part of why allergists like to just throw them out, they say, “Don’t bring me this nonsense.”

But once you’ve been doing functional medicine for a long time and you have an understanding of the different complexities of dietary triggers, you can look at these profiles and you can sort of pull out the relevant data. And I encourage those of you who may be new practitioners is not to take each test literally. So, if they have a high say a banana on the one test and it’s not on the other, you want to look at the general profile of the dietary antigen testing. You don’t want to be too specific because if you get too specific, most people will have nothing left to eat. So, I’d look at the dietary antigens and most of the time, but not all the time, controversially or not, I tend to put people on the Paleo, autoimmune, low histamine diet for the first month or two. And I can’t tell you how many people immediately settle down just on that one intervention.

And I take out the high histaminic foods, and that is a very important part of it. And one of the great crazes right now is to use all these fermented foods to heal gut permeability, but it’s a disaster for the mast cell person. So, I’m always pulling people off sauerkraut, and kombuchas, and bone broth, it’s a huge trigger. So, all the fermented foods, and then all the leftover foods. As foods break down, then the proteins, the histamine gets broken down by bacteria that releases histamine. So, leftovers are no, no. We also ask people to, once they’ve cooked a meal, to put in the freezer and then to take it out and unfreeze it, but not to leave it sitting in the fridge for days.

And then things like tuna fish, huge triggers, the nightshades (tomato, potato, eggplant, peppers), huge triggers in many people. And even amongst, you know, some of the vegetable kingdom, you know, peas and beans can be triggers of mast cell activation. And so, you have to be careful when you look at the testing, you’re going to sort of see… when I look at particularly the Meridian Valley test, you can often see a mast cell patient, they’ll show up, all the legumes will be positive, all the histaminic fruits will be positive. Candida will often be positive.

And there’s like a trend you can see it and then immediately, you know this is a mast cell activation profile for food antigens. So, we remove the foods, we always treat gut dysbiosis as you know. I use two different labs for gut analysis. I use the Genova GI Effects, and I use the Diagnostic Laboratory Solution’s GI-MAPs. They contradict each other all the time, you know, one will have a zonulin of 700, the other one has zonulin as normal.

But then you just got to use your clinical acumen and your experience and correlate the labs against the symptom profile of the patient and do the best thing. I do tend to use Dunwoody Labs for the zonulin, the DAO, and histamine, as I mentioned. And then the second page of that test is all the LPS, the lipopolysaccharides, to see if there’s been any endotoxemia. And if there’s been any bacterial endotoxemia, you start entering into a whole new world of immune upregulation, which, you know, you have to down regulate in your treatment protocols and heal the leaky gut, etc. which I’m sure your listeners are very well aware of.

PHARMACEUTICALS

Stethescope sitting on open book

So A. is education, B. is testing, C. is removing the histaminic foods and downregulating inflammation in general. And then we get to specific treatments. And I differentiate between pharmaceuticals and botanicals. I tend to preferentially go to the pharmaceuticals to start with because they work quickly, if they’re going to work. And I tend to secondly, add botanicals. But I tend to be an MD, you know, it’s just my preference. I’m sure many naturopaths would go the other way. And many patients refuse to do pharmaceuticals and then I just have to use botanicals.

Pharmaceutical perspective, they must be compounded, you can’t get over-the-counter. Although paradoxically, some people do better on the over-the-counter than they do on the compounded. This is one of the challenges is what you think is going to work doesn’t work. This is why try, try, and try again, you know.

So, first thing, H1 blockers. Histamine 1 blockers, and I tend to use levocetirizine in a dose of 5 milligrams going up to 7.5, even 10 milligrams. And I think the trick to using H1 blockers is you have to dose it round the clock. You know on the box it will say “24-hour relief” that’s not true. You need to dose it at least 12 hourly and sometimes 8 hourly to create full round the clock mast cell blockade. And you’ve got your H1 blockers, you’ve got your first-generation and your second-generation. The first-generation H1 blockers like Benadryl, or ketotifen, cross the blood-brain barrier and have a sedating effect so those are often given at night.

I love to use ketotifen, I use lots of it on a dose ranging from 0.25mg, which is a homeopathic dose almost, right up 2 to 3 milligrams at night. And if there’s any issues with insomnia, it works like a dream. It’s absolutely spectacular for sedation. The problem is sometimes they over sedate when you have to lower the dose. But it also downregulates mast cell activity at night. So first-generation H1 blockers, I prefer ketotifen over Benadryl. Second-generation H1 blockers, I use levocetirizine as my preferred go-to H1 blocker.

And then I use H2 blockers, and I use famotidine in a dose of 20 milligrams twice a day, sometimes going up to three times a day. And this tends to downregulate all the mast cell activation activity in the GI tract.

One of the little tricks of the trade I’ve picked up over time is if you do the Genova GI Effects, you’ll often see that eosinophil protein X marker a little high, that’s almost a slam dunk for mast cell activation…not always because there’s other things that trigger that. But if you see that with a constellation of other positives, you follow that marker closely because when that starts to downregulate, you know, you’ve got your mast cell activity under control. So those are my first two go-to medications H1 and H2 blockers.

Probably my next is cromolyn. Cromolyn is a mast cell stabilizer particularly for people who are very food sensitive. You take it before meals. I give it along with the HistDAO enzyme. And that dose you can take it from 100 to 300 milligrams, and that can also be a major game-changer in many people’s lives. You have to play with the dose, you have to play with the different companies that make it. It’s a bit of a tricky thing, but it can really have a huge effect on downregulation of mast cell activation.

And then the fourth drug that I use, and many patients have come back to me with this fourth drug, Singulair, montelukast. This downregulates leukotrienes, which are one of the thousand mediators of inflammation. One of the things that we’ve noticed in mast cell syndrome is that when you think a patient has an upregulated leukotriene pathway, which is typical for asthma, you give the montelukast or the Singulair and the asthma is managed.

Well, it so happens that one can’t predict which class of drugs is going to work on which mediator. So, if you give a mast cell stabilizer for food sensitivities, guess what? The asthma may go away. Or if you give Singulair for asthma symptoms, the hives go away. So, thereis crosstalk amongst many of the mediators. And it’s a great mystery as to why that occurs, nobody’s worked it out yet. Dr. Afrin said he doesn’t know. He doesn’t know why this happens and he’s going to keep researching till he works it out. So those are the four drugs I use, probably the top four drugs I use over and over again.

SUPPLEMENTS

supplements

Nutraceuticals, of course, Quercetin, tops the list, no question about it. There’s a product called Natural D-Hist made by Ortho Molecular, that’s my go-to supplement over and over again. Two, three times a day seems to be the magic dose. And then using HistDAO one to two before each meal that seems to be the number one nutraceutical.

Number two would be vitamin C, either orally or intravenously, sometimes can have a huge benefit as well. Green tea has an effect. Turmeric or curcumin can have an effect but some people react to it. If you see on the food sensitivity profile, if you see that it’s positive in at least one or two tests, you can use it, but you want to be cautious because it can sometimes activate mast cell activation. You got to be careful with turmeric. Resveratrol is another one. And chamomile tea has some calming effects. So those are my sort of…they’re called the A team of my nutraceutical approach.

And the B team is sort of…there are many others like luteolin, Ginkgo biloba, Pycnogenol. Pycnogenol is a great one too I use quite a lot of Pycnogenol. Feverfew works. There are many things that can work. So, I pick and choose and go through them and change them. I ask everybody to first identify the triggers, if they can, and then to start rotating the pharmaceuticals and/or nutraceuticals and see which has the biggest blockade effect. And people soon work it out, you know. You’ve got to get a good compounding pharmacist on your side. And you got to make sure that they don’t fill the compounded pharmaceuticals with lots of fillers and dyes because some people react to that.

And then one of the other challenges…I just had a very seriously ill patient present to a hospital with anaphylaxis and she was on polypharmacy. She was on 10 different drugs. And many of the drugs she was on were triggers for her mast cell activation. And those were never identified as triggers by her medical team. And so, we asked the pharmacist to go through each drug and look for the additives. Many of them had iodine in them, many of them, there was soy extract base, and those had to be changed accordingly. And she settled down. So those are some of the challenges I have.

Dr. Hedberg: And one of the drugs that wasn’t mentioned was LDN, low-dose naltrexone, I know some practitioners are using that for this. Have you tried that or used it?

Dr. Hoffman: I do use low-dose naltrexone. It’s part of the many other…there’s many other alpha-lipoic, and so forth. And LDN is definitely part of it. And LDN has an effect particularly on autoimmune responses and downregulation of an inflammatory response. It’s not my first drug though, I don’t go to LDN as my first line. I use it if there’s autoimmunity and lots of gut permeability then I bring in LDN. And LDN is challenging because people give it at night but it can be very activating. Just yesterday, I saw a patient who since she started LDN hasn’t slept a wink. We changed it to morning.

Dr. Hedberg: Right. So how do you deal with the psychoneuroimmunology aspects of this condition? You know, some people, they develop a deep identification with their illness, and then they develop a lot of beliefs about things that they’re sensitive to. And we’re not saying that it’s all in their head, but we do know from the PNI research that what we believe, and what we emphasize, and think about, and focus on can affect the immune system and our biochemistry. So, are you using any kind of cognitive behavioral therapy or things like that, that could help some of these patients who are so focused on their condition and their hypersensitivities?

Dr. Hoffman: Yeah, because this opens up a huge area of the work that I’ve been forced to look at over time and for which I use quite a complex algorithm to sort of diagnose and treat. I’ve studied Ayurveda for years and I use the Ayurvedic model of layers and levels of healing. And when a person presents with specific belief systems around their condition, I have to sort of look through the layers and levels of what may be playing a role in that belief system.

Just very briefly, I tend to look at these diagnostic criteria. I look at the family system to see what family system they were born into and what beliefs the family system carried. Because I can’t tell you how many cases get resolved when we do what’s called family constellation therapy and look at the entanglements of the forefathers and ancestors, and how those epigenetically got transferred down to the offspring. Very profound piece of work, I cannot emphasize it enough. And I encourage all functional medicine practitioners to get a very sound footing on the epigenetic transfer of family system trauma and the entanglements that can be inherited, completely silently, unknown consciously to the patient, only uncovered through work in family constellation therapy whereby certain methodology is employed to determine what these factors may be. So that’s number one.

Number two, I look at early developmental trauma patterns, and ego strength, and defense systems of a patient. And I employ a number of ways to identify that. The number one system that I look at is looking at defense structures of the patient and the ego strength. And you can tell after, you know, half an hour, is this person…do they have good ego strength? Are they resilient or they do have a fragile ego structure? And I send people for quite a lot of psychometric testing to establish some of these criteria.

I have a psychologist I work with who is able to help me with some of the psychometrics. And we even do, you know, some of the simple psychometrics testing, and even the Burns Inventory, the ACE Questionnaire. When we do qEEGs, we do the in-depth psychological assessment that’s provided by the CNS Vital Signs software to look at which of their psychological profiles are most dominant. Is it anxiety, OCD, is it depression, etc.?

So we look at that level of their development, the ego strength and their defenses. And then we look at early developmental trauma. And as you know from literature, people who have early developmental trauma have very different brain structures. They have, you know, very often this hugely enlarged anterior cingulate gyrus. They have in their beta, their fast brainwaves, there’s two to three standard deviations above normal. Their capacity to inhibit the sort of reptilian, limbic brain is diminished. And those are challenging patients, very challenging, and you have to address that level of healing.

This is not a biological intervention. There’s not much you can do biologically unless you identify what the core ego strength resilience of the patient is. How much projection of will the patient has? Many patients will sit in front of you, project the will to heal on you. And that’s a slippery slope. If they are not invested in sort of figuring it out on their own with you, you have a problem on your hands, you know. And patients will often project their early developmental trauma of parents on to you, whether it’s positive or negative. Best to have a positive projection in the beginning. But if you are the evil father that you get projected onto you, you’re in trouble.

So it behooves all of us as functional medicine practitioners to kind of try and identify, who is this person sitting in front of me, what did they inherit, how was the early developmental life? And then what defenses are they employing to keep away feelings they don’t want to feel? And I use a psychological technique called ISTDP. And I refer that out to somebody who’s specialized in it. That person I use is also very well versed in CBT. But CBT, without the underpinnings of the complexity of the presentation, can sometimes not stick. It can be very helpful to some, but for those who are fragile with projection of will, CBT will not hold. You can’t use CBT, it washes off them, you know, they won’t be able to hold that.

The next thing I do, I do NeuroQuant MRIs on everybody as well as a qEEG. And I look at the brain patterns and I can’t tell you how helpful that is. If you’ve got this high beta brainwave, and you’ve got maybe high theta brainwaves with not enough alpha, you’ve got work to do. And then you correlate that with the NeuroQuant MRI, and we look particularly for the amygdala upregulation. Many of these people with anxiety, OCD, and belief systems around the illness, who are multiple chemically sensitive and environmentally sensitive and are triggered by everything, will have a very…..the amygdala will be 2 standard deviations above normal, being like in the 97th percentile. The thalamus will be in the 97th percentile.

Hand holding image of brain

And the thalamus is rich in mast cells. So, when the thalamus is high, the amygdala is high, you want to ask about mast cell activation, and you want to ask about early developmental trauma. Because the amygdala gets increased in size when there’s repeated stresses on the fear-based part of the limbic brain. And if I see that, I often start inquiring about other techniques to downregulate the amygdala. And that we use DNRS, as you’re probably aware of the Dynamic Neural Retraining System.

We do refer people to that, we do neurofeedback, we do biofeedback, we do vagal tone stimulation. And we start to bring in the Porges polyvagal theory of, you know, sympathetic, parasympathetic dorsal vagal shutdown. And we try to work out where in this constellation of symptoms is this patient presenting? Are they in dorsal vagal shutdown with a rigid defense and sort of no will to get better? Are they getting secondary gain? That’s a very different patient from the one who’s, you know, loved by the parents, no developmental trauma, is loved and seen by a mother, develop appropriate right prefrontal cortex to self-regulate, has financial resources, is loved by the husband, the kids are doing well, they have a home to go to. This is how it works.

And we have to work out who are we sitting in front of when it comes to addressing some of these complex beliefs about, you know, is this a biological overreactive reactive mast cell syndrome, or is this a psychologically overreactive amygdala? Or is this person highly defended? Do they have the ego structure to take on what I’m about to tell them? It’s complex, as you know. I think that…

Dr. Hedberg: Right. And it’s a difficult situation for everyone because, you know, we don’t really get a lot of training, if at all, in all these things you just mentioned. So, we have to learn these things on our own, learn how to incorporate them. And then at the same time, present these to the patient in a way that isn’t telling them that you know, “This is just all in your head” or helping them understand that some of this could be due to your childhood and the way that your parents treated you, and all these kinds of things that happen. And I have done a few podcasts with some experts on adverse childhood experiences and things like that.

So, it’s refreshing to hear you talk about all these things, and it just creates a very complex picture on how to put it all together. And you know, like you said, they come to see you and they put all the burden on you for the healing. And then, you know, you come back with recommendations that, “Well, we need to work on your childhood trauma or your relationships,” and things like that. So, this is a very difficult, you know, condition to take on as a practitioner. I mean its massive amount of mental and emotional output that you have to take on.

Dr. Hoffman: Yes, one of the commonest words I see in the referrals back from specialists is this so-called, awful term, somatization disorder. And it’s just not true 90% of one of the most stressful diagnoses for one of these patients to get is the so-called somatization disorder but it’s often handed out. You know, and, “Yeah, it’s all in your head,” this is so awful. There may be a component that is filtered through the neurological pathways and then synapses. And they may tend to have an upregulated sensory system that processes things somatically. But it doesn’t mean to say that we have to discard this as all psychological, which is very often the insurance companies like to do things like that and some of the specialties too.

I recently referred a patient to a psychiatrist for insurance purposes and I sent five articles plus a written response. “Please do not diagnose this patient as being psychiatric, he has the following conditions.” And then we listed the mast cell activation, the mold sensitivities, electromagnetic sensitivities, etc. And I sent him five papers in support of the validity of this diagnosis. I haven’t heard back yet; I’m waiting to see what the response is. We often have to advocate for our patients in this way because they do present with neuropsychiatric manifestations, but it’s as a consequence, it’s not the cause. Although there may be some issues which provoked, you know, an expression of a mast cell disorder, but you can’t separate you know, mind-body, you’ve got to work with the whole continuum.

Dr. Hedberg: Exactly. Well, this has been really excellent. How would you like people to find you online, what’s your website and contact information?

Dr. Hoffman: The website is hoffmancentre.com. And the phone number here is 403-206-2333. That’s the phone number for my clinic. I do have a number of blogs on my website, and I post to Facebook and Instagram. But my website has a lot of the histaminic articles as blogs, so they can access them on there.

Dr. Hedberg: Excellent. So, to all the listeners, I have created a transcript of this conversation, which will be on drhedberg.com. So just search for Dr. Hoffman and you’ll be able to get the entire transcript there in case you missed anything. Well, thanks for tuning in, everyone. Talk to you next time. This is Dr. Hedberg, and take care.

Functional Medicine Podcast: Healing Wisdom With Dr Bruce Hoffman

Dr. Bruce Hoffman joins Pandora Peoples on WOMR and WFMR radio to discuss the origins of The Hoffman Centre and the benefits of the integrative approach to functional medicine. Dr. Bruce Hoffman utilizes the ayurvedic model through a program he developed called, The Seven Stages of Health & Transformation™ that brings to light the hidden causes of what may be making you sick, and what you can do to heal yourself.

Full Transcript

00:12

You’re tuned in to 92.1 WOMAR, FM Provincetown and 91.3 WOMAR, FM Orleans, the voice and spirit of Cape Cod. I bid you welcome to another episode of Healing Wisdom. I’m your host Pandora people’s chartered herbalist and psychic medium healing wisdom explores Mind Body soul connections as we discussed the healing effects of the arts, metaphysical concepts, intuition and the spiritual aspects of everyday living. Healing wisdom begins in the heart. Our theme music is provided by mystic Pete

01:00

Hello, hello, hello, hello, Cape Cod and beyond. My guest today is functional medicine Dr. Bruce Hoffman, founder of the Hoffman Center for Integrative and Functional Medicine. His center encourages people to become involved with the process of health, restoration, self-master their health issues and make health a primary value. Dr. Hoffman has dedicated himself to research and education in cutting edge health care wellbeing and living a meaningful life. Welcome, Bruce, thank you so much for being with us.

01:28

Excellent. Thanks Pandora

01:29

So first off, what inspired you to go from an allopathic practice or a traditional practice to an integrative approach to functional medicine,

01:39

Curiosity more than anything and frustration at the drug-based model, you know, when you go to med school, you learn this is called n squared d squared, medicine = name of symptom name of drug. Although it’s interesting, it really limits your diagnostic and therapeutic options. So, when a patient presents say with complex illness, where there’s a mind -associated issue, and or environmental issue, nothing you can do with a drug based model, you know, you just diagnose a disease find a drug or refer to a specialist. And that’s it. It’s over. Whereas in an integrative model, you look far and wide for what they call in functional medicine, antecedents, mediators and triggers. So, you look upstream, you know, and in a functional model that I use functional medicine workup that I use, I’ve expanded beyond pure functional medicine into what I call the seven stages to health transformation. And I use an Ayurvedic model to explain the different layers and levels that come to the table when you’re trying to diagnose and treat somebody. Anywhere from the family systems into which they originated into the early emotional experiences and ego development and defenses, through to unresolved emotional traumas through the brain states and brain functions and then into biochemistry and toxicology. So, it’s a much broader diagnostic roadmap that we use ana a therapeutic roadmap, and I just found the drug-based model limiting. I enjoyed being a traditional MD. But now that I practice a much more expanded paradigm, it’s much more exciting and your results are tremendous when you apply this sort of wider model, you know.

03:17

Yes, indeed. So, after studying traditional Ayurvedic medicine, traditional Chinese medicine, homeopathy and looking at health care, from a mind, body, spirit perspective, I’m wondering what fundamental conclusions you’ve drawn about wellness that led you to your inspiration and the creation of the Hoffman Centre.

03:37

Wellness is a strange term because it denotes what I really try and help people with, which is to try and live in a state of maximum wellness, maximum potential. And that moves everybody from a disease-based paradigm into what we you know, what is called a wellness paradigm, but is somebody living at their maximum potential, are they fulfilling the desires of their most innate, instinctual talents and abilities, and illnesses and symptoms often sort of create a, what would the word be, they create a block in that person’s trajectory towards optimal performance of their destiny? And so, we use symptoms and diagnosis to, to sort of ask a lot more deeper questions and dive right into the potential reasons why a person may not be fulfilling their ordained destiny. And that’s what I love to do. And so that’s why I created the center to try and explore those possibilities with people and it’s very rewarding, and not everybody, somebody may just have something that’s physically based but many people with chronic illness have led many layers and levels of stressors on their systems, and the detective game of trying to diagnose and treat is what inspires me to keep doing what I love to do. 10 Center.

05:00

Very cool. I’m wondering what some of your fundamental theories that you’ve developed are as a result of your work that you could share with us or what some of your underlying ideas are, that are part of your mission.

05:18

Certain things that stand out, when I have somebody sitting in front of me with a complex illness, a) you’ve got to take into account all the basic lifestyle factors, diet, sleep, exercise, stress, if you don’t look at those in great detail and sort of dissect them into the multiple subsets, you know, like a diet, for example, there’s many different diets that you can therapeutically apply and what may fit one person may not work for the other. You have to really know your nutrition and dietary issues in great, great detail. A high histamine diet versus a ketogenic diet versus a paleo autoimmune diet versus the Ayurvedic Vata pacifying, that there’s many, many permutations, you got to know those things thoroughly. So that’s huge. And as you know, diet affects the gut microbiome. And the gut microbiome affects the vagus nerve and the vagus nerve runs into the brain. So, your brain-gut microbiome is huge. If you’re not looking at the gut-brain microbiome you can’t really work out what’s going on. So, diet is big. The gut microbiome is big.

Dentistry, I use a lot of dental insights in order to try and ascertain what may be going on particularly with people’s brains, because the inferior alveolar nerve in the lower part of the jaw runs back into the brainstem as well. So, you get a lot of toxic buildup in root canals, cavitation sites, etc, etc. So, dentistry, a lot of respect for dentistry. Everybody to get a panorex X ray and a 3D Cone Beam CT scan of the jaw, and then I send them to a biological dentist to do a complex workup and treat accordingly. So, dentistry is big. Diet is big.

Sleep, sleep, almost everybody I see has a sleep study, not one of those sleep apnea tests they take home. Do a full in-house sleep study. And I rely on that tremendous extensive can’t tell you how many people suffer ill health from sleep issues, sleep is huge. Which brings me to the whole thing of emf, electromagnetic field exposures, radio frequencies and electrical fields, magnetic fields. That has become a very dominant part of my intake history taking to see what people are doing, how much screen time, are they using blue light blocking glasses, are they turning off their routers at night? So, I take that all of that into account? Huge, huge, huge.

And then another piece that is huge in my work is I really don’t start to work with somebody unless I understand the family system into which they originated. The ancestral lineage not from a genetic but from an epigenetic perspective, what are the experiences of their mothers and fathers and grandparents? I find that is where I really begin my curiosity through taking a history. Are you in relationship with your mother or in your relationship with your father, if people say I can’t stand my mother, I can’t stand my father, I don’t want anything to do with them’ I know right then my task of healing is being brought to a halt. You can’t heal somebody who isn’t aligned with their family system in a flow of love, can’t do it. It doesn’t work. You can treat a symptom but you’re not going to help that person reach their maximum potential if they’ve shut down the influences of their parents or their ancestors, because people are half their mother, half their father, if you say no to your mother or say no to your father you are saying no to half of your life force. And that needs to be worked through. And I use family constellation therapy for that. And things like that, you know?

08:45

Yes, I was going to ask what you do for that for that situation? Because that, you know, there are a number of folks who are.  Is it family therapy?

08:57

No, it’s not family therapy, its family constellation therapy. Its different form family therapy

09:01

Can you explain that?

09:02

Well, you take a history or you ask people certain questions about their family of origin. What do you blame your mother for? What do you blame your father for? Those are the first question. And if they have a whole string of complaints that begins the diagnostic and therapeutic process. It was developed by Bert Hellinger, called family constellation therapy. He just died a few weeks ago, actually. And it’s a method of working people up through understanding the entanglement of the family system. We try to understand the laws that operate in family systems and those things that lead to good outcomes and those things that blocked the flow of energy in a family. You have to sort of study it and learn it.

09:46

Yes, it’s very, very intriguing. I’m wondering if you could just mention briefly, you described turning off your routers at night. So, these electromagnetic fields that we’re constantly in relation to in this digital age. They are really, truly bad for us.

10:03

Depends, yeah, there’s certain subtypes of people are more susceptible than others. And some work is  being done on basic detox for liver cytochrome p 450 enzymes. Liver enzyme pathways, detox pathways, people with certain liver detox enzyme susceptibilities do much worse, in terms of the electromagnetic hypersensitivities. So, when you sleep at night, you should be in a very deep parasympathetic healing state. Most people you see, particularly say in inner cities, have about two volts running through their body from the electrical fields around them. And then they have these electromagnetic radio frequency fields. This is from the cell phone towers and routers, like if you live in a condo, you’ve got everybody’s router beaming into your bed at night. And when you’re sleeping at night, you are meant to be in this very deep, relaxed state. But if you are surrounded by radio frequencies and electric fields and magnetic fields, you’re in a stress state. And that opens up the blood brain barrier, opens up the gut barrier, leads to suppression of melatonin, the whole glymphatic system or brain detox system doesn’t work, you’re in big trouble. And it’s not being emphasized enough, you know. And then with dentistry, if bite problems and grinding, you don’t detoxify through the glymphatic system and down through the, you know, through the lymphatics that go down through your internal jugular vein and other parts of your neck and thoracic region. So, you want to know these things. I send in Baubiologists or building biologists into homes to measure all of these things before I start treating people with cognitive difficulties or sleep difficulties. They go turn off routers, they help people with sleep, you know, screen time, they use blue light blocking glasses, they do all of these things. So, it’s an integral part of the work I do?

11:41

Well, that’s very exciting. I’m just wondering, I used to erase floppy disks by just touching them. So, I obviously have some sort of electromagnetic thing going on. would that mean that I would be more susceptible to energy from digital influences or to electromagnetic? Well,

12:01

I don’t know. I used to feel tingly and confused when you arrived cell phone towers. They go crazy. They can’t handle it.

12:10

Well, I used to be affected by Bluetooth. So yeah, perhaps perhaps. So environmental and lifestyle factors are considered by functional medicine doctors to be as you’ve been speaking about it very important, especially in complex situations with patients with chronic illness. So have certain input environments or lifestyle factors been linked to chronic Lyme disease.

12:31

Well, lyme disease is an immune disease, right? So, the bug gets entry if your immune system is compromised. So, you need to have reduced natural killer cells for Lyme disease to take hold. And so, to treat Lyme disease, you know, there is a whole emphasis on using whole rotating antibiotics and, and using herbs and/or pharmaceuticals to treat it. But really, it’s an immune incompetency disease. So often when you have a compromised immune system, you’ve got to look at factors that may have led to that and one of them, apart from the genetic imbalances in immune competency is stress. Stress is the greatest suppressor of the immune system. We know, people with stress they get viruses, they get colds and things; that’s the same principle, your surveillance system of our immune system gets compromised under chronic stress. And what causes chronic stress. Well take your pick, hundreds of factors cause chronic stress, it doesn’t just have to be a boss that gives you a hard time, it can be poor sleep, it can be poor diet, there’s many things that cause chronic stress. That dental infection that hasn’t been treated; they all can cause chronic stress in the body. So, for Lyme disease, the thing you got to look for is immune competency and that’s why one of the tests we do is called natural killer cell function, or CD 57. And we look at that to see if that’s suppressed. If that’s suppressed, your ability to fight Lyme disease is compromised and Lyme disease and co infections can run rampant. So, it’s just one of the things we look. There are genetic components to this as well. One researcher has done work on the genetics of people with Lyme disease, and specific markers that are upregulated. And then anything that compromises your overall resilience and homeostasis and mitochondrial resilience, anything, diet, any other factors, lack of exercise, obesity, any of them.

14:23

And if you’re tuning in just now, you’re listening to healing wisdom on WOMR 92.1 FM in Provincetown and WFM are 91.3 FM in New Orleans and streaming at Womar.org. We are speaking with Dr. Bruce Hoffman, functional medicine doctor, founder of the Hoffman Center for Integrative and Functional Medicine.

What are risk factors in Alzheimer’s? Have you seen significant improvements in patients with Alzheimer’s using integrative approaches?

14:53

Yeah, Alzheimer’s is very fascinating. I don’t know if you’re aware of the recent work that’s put out by Dale Bredesen and his group. He wrote a book called The End of Alzheimer’s. And I wrote a summary of that book on my website, there is a blog on it. Alzheimer’s is fascinating. He’s worked out that there’s six subtypes of Alzheimer’s disease and 36 biochemical pathways that need to be addressed. And he basically says that Alzheimer’s has six subtypes. The first can be anything that’s inflammatory, then anything that’s deficient is number two, anything that’s blood sugar, glucose, insulin related is number three, anything that’s toxic, like mold and heavy metals is number four, anything that’s cardiovascular related is number five, and anything that is head injury related is number six.  Those are the six subtypes of Alzheimer’s disease. And there’s many biochemical pathways that you look at when treating Alzheimer’s. So, for instance, all the deficiency issues, one of the main deficiencies in Alzheimer’s is all the hormones: growth hormone, testosterone, estrogen, progesterone, DHEA. So, we look at all of those pathways and try and repeat them, when we are treating Alzheimer’s:  inflammatory, all inflammatory chronic conditions, you know, eating an inflammatory diet, mold, illness, heavy metals, look and treat all of those issues. People with high blood sugar, high insulin, insulin resistance, treat that, that has a huge effect on people’s brains. And then a key underlying factor that seems to be very problematic if anybody has what’s called the Apoe 4/3 or 4/4 gene, that predisposes to a much higher risk later on in life of Alzheimer’s disease. We test for that gene, hopefully, you know, if you have a 3/4 or 4/4 gene, you should really increase everything you can in terms of lifestyle factors to make sure that gene doesn’t get expressed later on in life. There’s a whole website devoted to people with the Apoe4 gene, what they need to do in order to down regulate the risk? Well,

17:08

Yes, it’s interesting, because I know with my own grandmother who suffers from Alzheimer’s and my mother-in-law, and also one of my clients, it’s amazing how quickly an anti-inflammatory diet can help heal the brain. I mean, it seems like overnight, a person can have access to memories that they didn’t have before.

17:31

The other thing we do is, down regulating the gut microbiome and neuroinflammation through the vagus nerve. But we also assess all the fats. I test with the Kennedy Krieger fatty acid analysis and we look at all the Omega 3/6/9 and saturated fats and we treat very aggressively with the ketogenic diet and high fat intake, particularly something called phosphatidyl choline. Choline is one of our key nutrients to help restore brain function back to normal. In fact, the patient I saw just now had a huge deficiency in phosphatidyl choline with cognitive deficits.

18:11

Wow, can you dispel the mold myth mold illness is not an allergy, correct?

18:21

You do get IgE mold allergies, but we do not worry about that. That’s the least of one’s worries. Mold is a huge trigger of the innate immune system causing a condition called CIRS; chronic inflammatory response syndrome. And that plays havoc with your inflammatory cytokines, which then down-regulate areas in the brain, particularly the melanocyte stimulating hormone, MSH. And MSH controls many things; sleep, pain, gut function, and all the sex hormones and the diuretic hormones. So, when you get exposed to mold and you get inflamed from mold, and it appears that only 25 to 35% of people have a susceptibility to mold illness. They don’t downregulate the mycotoxins that are expressed. And they get very inflamed with consequences to their brain, consequences to their hormone’s, consequences to  mitochondrial and to oxygen delivery, sleep, gut function. Amazing. So moldy allergies is the least of our worries.  I don’t see people with mold allrgies, I see people for mold toxicity, mold inflammation. It’s a whole different subset, not taught, not understood. Respirology don’t know about it. The insurance companies certainly don’t want to know about it. It’s a huge problem. And I treat mold illness all day. Huge. Most homes are moldy.

19:46

Yes, many, many homes on Cape Cod, for example, are moldy. There’s just a ton of dampness and can you talk a little bit about mold illness?

19:55

Yeah, well, I work like as much as I work with a dentist and I work with building biologists for EMF’s, I work with mold, remediating indoor air specialists, we send people into homes to do a visual inspection. Anybody that I suspect, with mold illness, we have a questionnaire. And if people score very high on the questionnaire, we immediately suspect mold. And then we ask questions. Do you have any water damage? Do you have any damp areas? Do you have any condensation on your windows? Do you have any visible mold downstairs, or air conditioning? Have your ducts been cleaned lately, a whole bunch of questions. Then we send in the mold inspectors to go and do a good visual inspection, which takes hours. If somebody walks in with an air sample and waves it around and says you don’t have any mold in the air, run for the hills, because that’s was not a proper mold assessment. We also send people home with ERMI kits where they actually take swabs for DNA particles of mold, they take a swiffer cloth, mold samples from dust collected, or they vacuum the carpets and they collect the DNA spores and send it off to a lab to measure it. And then if they’ve got mold in their home, we assess the degree of the mold. And then we send in a remediation crew, and then we start to treat the mold illness. And there’s about 12 steps in how to treat mold illness. First step is to get out of the moldy home. Second step, bind the mold with binders like cholestyramine or charcoal or whatever. And then there’s a whole series of other steps that you do.

21:29

What are your thoughts on ozone for killing, mildew and mold?

21:33

Doesn’t work?

21:35

Oh, no.

21:38

It affects our immune system. Yes.

21:42

Mold exposure causes inflammation upregulation of the innate immune system which causes inflammation.

21:51

Yes. So I’m wondering about andropause. And why is it worth talking about? It’s not something that you know, people talk a lot about menopause, but not so much about andropause.  And I noticed that was on your website. I’d love to hear

22:06

Andropause. Yeah, it’s grumpy old men. Yeah. Men age slower than woman so they’re not as you know, andropause, it takes a year or two.   Women and perimenopause take about a year, but they notice when they start getting hot flashes and night sweats, it’s pretty quick. Men, their testosterone levels fall slower. And they don’t go into like an acute sort of jump off a cliff so to speak, it’s a slow, gradual decline, they put on weight, they get grumpy, they get depressed and they ache.  Their libido goes down, erections go down. And when you start measuring all the sex hormones, you find that they are deficient or you know, low normal. And that you know, usually in the age 50 onwards, and we measure all those hormones and treat accordingly and it can have tremendous effect when you start treating, particularly testosterone, dhea, sometimes growth hormone very seldom, melatonin, and then using thyroid hormone and adrenal support, some can make a tremendous difference to people’s wellbeing. So andropause is a real and undiagnosed, under treated condition. It is very rewarding once diagnosed and treated appropriately, you know.

23:28

Yes. Now this might seem like a strange thought. But I’m wondering if there is an evolutionary reason that people as you know, over a certain age tend to get up earlier. And earlier. And you know, if the oldest troubled sleep, maybe has, you know, if that’s really how people were living, organically naturally. I mean, I know, overall, people are dying, at much older ages, and so on and so forth. But I always wonder about this early rising business that seems to happen and be so much a part of our hormonal evolution over our lives.

24:06

You mean why older people sleep less.

24:08

Yes.

24:11

So succinctly said,

24:15

Multiple factors for that, you know, I mean, it’s definitely based on diminishing hormones, particularly, melatonin, melatonin levels go down as we age, too.  Melatonin is a major brain antioxidant. It’s also what turns on the suprachiasmic nucleus, which tells you that it’s nighttime. So, melatonin deficiency, as we age, affects the suprachiasmic nucleus and affects the ability of somebody to stay asleep for longer periods of time. There are many, many factors, but that’s just one of them.

24:53

As we go into colder months, it’s very important that we use preventative measures and make sure that we’re as healthy as we can in the fall so that going into winter, our immune systems are as strong as possible. I’m just wondering what your thoughts are on just simple things, people can start doing better to take care of themselves in the colder months?

25:14

Well, the thing that I always worried about the colder months is when people go indoors, and they shut themselves in. And so I always want you to worry about the indoor air quality, and these tightly sealed homes. So, when we not exposed to the outside sunlight, when we get sealed into our homes for six months of the year, the question is, what is the quality of your home? What is the quality of the indoor air? Are you being exposed to mold spores and mold toxins, volatile organic compounds, off gassing? That’s the thing I’m most concerned about in winter months, and many, many patients will tell you “ in October when winter comes, I get sick, I get worse, I get depressed”, or I get this or that”  a lot of it’s to do with the fact that they get sealed into their homes, and they don’t spend any time outside, you know. So that’s what I started to think about – quality of indoor and environmental indoor homes.

26:16

Okay, so we have one more minute left. So, my final, final question is just, if you could, if you could tell everyone, one or two things that would help improve most people’s lives, you know, mind body spirit, what would that thing be?

26:34

If you’re not connected with your mother and your father, if they are alive or dead, go do some work and try and reconnect yourself to their life spirit and to their love. If you’ve got a complaint about your parents,  go do your work. I really mean that.

26:57

If you cannot say yes to your mother and father for giving you life, your work is incomplete. If you are in complaint about your mother and father, you have got work to do. They gave you life, be grateful. All the rest was just an excess. It’s just the fact they gave you life that was enough. That if you’re not aligned with them, and the flow of love isn’t from you, to them to your children, you need to do your internal work to try and correct that. That’s what I say is the principle, the cardinal aspect of healing.

27:29

Thank you so much, Dr. Bruce Hoffman for joining us today on healing wisdom.

27:34

Okay, thank you very much. Thank you so much. Bye.

You’ve been listening to healing wisdom. I’m your host Pandora people’s certified chartered herbalist and psychic medium. You can find healing wisdom podcasts at Womar.org. Contact me with any feedback questions or show ideas at peachy pandora@yahoo.com. A big thanks to the Wizard of operations Matthew Dunn. Join me again next week.