Tag Archives: autoimmune disease

The Broken Brain on-line “docuseries” is running now.

I would encourage everyone to watch this series of daily interviews and discussions on lifestyle and brain health. This was organized and produced by Mark Hyman MD, director of the Functional Medicine Clinic at Cleveland Clinic, well known author, speaker and physician, Discussions cover many topics including environmental toxins (such as heavy metals and Roundup), nutrition, exercise, sleep, stress reduction, gut bacteria, and more with specific reference to the effects on your brain and risk for dreaded conditions such as Alzheimer’s and other forms of dementia, Parkinson’s disease, multiple sclerosis, etc. These conditions can be prevented and when present, they can be treated with interventions not usually employed by modern medicine, unless you are fortunate enough to be working with a Functional Medicine practitioner.

You can sign up to receive a daily email with a link to the on-line video. Each video in the series is available for 24 hours starting at 3 PM PST, 6 PM EST.

Here is the link to get started with the third episode in this series.

Episode 3: Dementia and Alzheimer’s [LIVE] | Broken Brain

To Your Health,

Bob Hansen MD

Great lecture videos available on line

In January I attended the annual meeting of Physicians for Ancestral Health. There were great presentations on many topics related to lifestyle and health. Take a look at the website linked below to learn about many topics relating nutrition, exercise, and lifestyle to health.

Open Video Archives | Physicians for Ancestral Health

I presented a lecture titled “The Lipoprotein Retention Model, What’s Missing?” This discusses many factors (root causes) that contribute to the formation of plaque in arteries and what can be done to prevent this insidious process by adopting a “Paleo Lifestyle“.

Other videos include:

Paleopathology and the Origins of the Paleo Diet. Keynote speaker Michael Eades MD, author of several books and a well known website.

Medicine Without Evolution is like Engineering Without Physics– Randolph M Neese, MD Director of the Arizona State University Center for Evolution.

The Roles of Intermittent Fasting and Carbohydrates in Cancer Therapy– Dawn Lemanne, MD, MPH, integrative oncologist.

 23 and Me: Practical First Steps-Deborah Gordon MD, discusses a practical approach to utilizing information from this genetic test.

Histamine Intolerance-Why (food) Freshness Matters– Georgia Ede MD.

 

Mood and Memory: How Sugar Affects Brain Chemistry-Georgia Ede, MD.

Systems Analysis and Multiple Sclerosis– Tommy Wood MD, author, blogger and lecturer, frequently interviewed on topics related to exercise and nutrition.

Cholesterol OMG– Jeffry Gerber, MD “The Diet Doctor” in Denver Colorado

Bob Hansen MD

 

 

 

Endocrine Disrupting chemicals in food, containers and environment results “in a range of human diseases and abnormalities.”

The findings of four articles recently published in the Journal of Clinical Endocrinology and Metabolism were presented on March 5 at a press briefing held at the Endocrine Society’s annual meeting, ENDO 2015, Despite the incredible public health implications of these four studies little has been reported in the popular press.

I have previously discussed the Environmental Working Group’s list of the Clean Fifteen and the Dirty Dozen toxic chemicals | Practical Evolutionary Health as well as the impact of environmental toxins on our epidemic of auto-immune disease Babies born with more than 200 toxic chemicals in their blood | Practical Evolutionary Health .

The press briefing and the findings of these four studies were reported on-line Endocrine Disruptors Cause Range of Diseases; Cost 157 Billion Euros

The estimated health effects of pesticides, chemicals used in personal care products, aluminum can liners, flame retardants in clothing, mattresses, furniture,  etc., included the following

From pesticides:

  • 59,300 infants born with intellectual disability
  • 28,200 people aged 50-64 years with type 2 diabetes
  • 13 million lost IQ points in each EU country

From Phtalates used in food wraps, cosmetics, shampoos, vinyl flooring

  • 24,800 deaths among 55-64 year old men
  • 618,000 additional assisted-reproductive technology procedures to treat infertility
  • excess of obesity and diabetes among women aged 50 to 64

Flame retardants in electronics, furniture, mattresses:

  • 3290 intellectually disabled children
  • 873,000 lost IQ points
  • 6830 cases of testicular cancer
  • 4615 children born with undescended testes

Other estimates from endocrine disruptors included:

  • 316 autistic 8 year olds EACH YEAR
  • 31,200 ten year olds with ADHD

Here are some snippets from the on-line Medscape report.The economic costs are reported in Euros since this was a study of European data. Bear in mind that the European Union has more stringent environmental protection than the United States. As a result, a study using US data would likely show even greater damage.

The papers cover overall costs of selected disorders attributed to specific endocrine-disrupting chemicals, as well as more detailed analyses of costs related to endocrine-disrupter–linked obesity and diabetes, neurobehavioral deficits/disease, and male reproductive disorders/diseases.

“Limiting our exposure to the most widely used and potentially hazardous endocrine-disrupting chemicals is likely to produce substantial economic benefit,” lead author of the overview study, Leonardo Trasande, MD, from New York University, said at the briefing.

The European Union defines an endocrine-disrupting chemical as an “exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function.”

With exposures occurring via pharmaceuticals, industrial solvents, personal-care products, aluminum-can linings, plasticizers, pesticides, and environmental pollutants, chemicals known to be endocrine disrupting include diethylstilbestrol, polychlorinated biphenyls (PCBs) , dioxins, perfluoroalkyl compounds, solvents, phthalates, bisphenol A (BPA), dichlorodiphenyldichloroethylene organophosphate/organochlorine pesticides, and polybrominated diphenyl.

Affected hormones include estrogen, androgen, thyroid, retinol, aryl hydrocarbon, and the peroxisome proliferator-activated receptor (PPAR) pathway. In all, 13 chronic conditions have strong scientific evidence for causation by endocrine-disrupting chemicals, Dr Trasande said.

“There are safe and simple steps that families can take to limit their exposure to endocrine-disruptive chemicals. They can avoid microwaving plastic. They can avoid eating from aluminum cans or drinking fluids from aluminum cans. They can eat organic. Or even simply air out their homes every couple of days to remove some of the chemical dust…that can disrupt hormones in their bodies.”

Using estimates based on the literature and established statistical methods adapted from those used by the Intergovernmental Panel on Climate Change, Dr Trasande led a 12-member scientific steering committee, which determined that there was probable causation of endocrine-disrupting chemicals for IQ loss and associated intellectual disability, autism, attention-deficit/hyperactivity disorder (ADHD), childhood obesity, adult obesity, adult diabetes, cryptorchidism, male infertility, and mortality associated with reduced testosterone.

Using mid-point estimates for probability of causation, the panel calculated a median cost of €157 billion, or 1.23% of the EU gross domestic product, with a lower median range of €119 billion and a high end estimate of €270 billion.

Dr Trasande summarized results from the four papers at the briefing, including these data points:

  • By health effect, the greatest cost was for neurological problems, including ADHD, at €132 billion. By endocrine-disrupting chemical type, pesticides were the most costly, accounting for €120 billion.
  • Pesticides accounted for 13 million lost IQ points in each EU country, costing €124 billion in earning potential. They were also responsible for 59,300 infants born with intellectual disability (€24.6 million), and 28,200 people aged 50-64 years with type 2 diabetes, at a cost of €835 million.
  • Phthalates, used in food wraps, cosmetics, shampoos, and vinyl flooring, resulted in 24,800 additional deaths among 55- to 64-year-old men, costing €7.96 billion in lost economic productivity; and 618,000 additional assisted-reproductive-technology procedures, costing €4.71 billion, Dr Trasande reported. Phthalates also accounted for an excess of obesity and diabetes among women aged 50 to 64, totaling more than €15.6 billion.
  • Flame retardants used in electronics, furniture, and mattresses resulted in 873,000 lost IQ points, leading to €8.4 billion in lost earning potential; 3290 intellectually disabled children, costing an additional €1.9 billion; 6,830 new cases of testicular cancer, at €850 million; and 4615 children born with undescended testes, at €130 million.
  • Other estimates of burden and disease and costs include 316 autistic 8-year-olds each year from multiple endocrine disrupting chemicals, costing €199 million; 31,200 10-year-olds with ADHD (also from multiple endocrine-disrupting chemicals), at €1.7 billion; and BPA used in aluminum-can linings and thermal-paper receipts, being associated with 42,400 obese 4-year-olds at an annual cost of €1.54 billion.

Dr Trasande said that a similar analysis for the United States would be “the logical next step” and that he would anticipate analogous findings, although there are some differences. Brominated flame retardants are more stringently limited in Europe, for example, but levels of phthalates have decreased 17% to 37% in the United States between 2001 and 2010.

Keep in mind that these studies were published in the peer-reviewed Journal of Clinical Endocrinology and Metabolism. They do not represent a governmental agency report, which is frequently tainted by the influence of lobbyists and scientists with conflicts of interest. Whether the European governments respond to this data in a meaningful way remains to be seen. Given the Republican majority in both the US Congress and US Senate as well as the sad state of journalism in the US it is likely that this scientific data will fall on deaf ears.

Nevertheless, we all have the opportunity to educate ourselves about these dangers to the health of our families and make changes in our daily lives that might limit the damage to our personal health and the health of those we love.

Do not drink water from plastic bottles. Do not drink soda or fruit juices from plastic or aluminum containers. Do not microwave food in plastic containers or store warm food in plastic containers. Eat organic vegetables and fruits whenever possible and avoid especially non-organic produce from the Dirty Dozen

Despite the manufacturers claims to the contrary, BPA used to line aluminum cans is not safe, same for BPA used in thermal paper receipts. “BPA free” hard plastic containers and metal containers lined with BPA replacements will likely prove to be unsafe in the future.

That “new-car” smell and “new-furniture” smell may contain endocrine disrupting flame retardants off-gassing. So open your windows and get rid of those odors, use HEPA air-filters at home. Consider having your old furniture reupholstered instead of buying new furniture. Apply only safe personal care products to your body (visit the EWG website for more information)Consumer Products | Environmental Working Group

Live clean, eat clean.

BOB

Babies born with more than 200 toxic chemicals in their blood

The  Environmental Working Group (EWG) is a non profit organization devoted to protecting the public from one of our greatest health threats, pollution in all of it’s forms. The EWG supported a study in which newborn infants were tested for known industrial and agricultural toxic chemicals. All of the infants had > 200 and some up to 300 toxic chemicals found circulating in their blood at birth. These babies were not born to parents living in or near toxic waste dumps, or working in dangerous industrial environments. They were born to parents living like you and me. You can read about this and many other issues here.

The 1976 Toxic Substances Control Act grandfathered >70,000 industrial and agricultural chemicals already in use as “safe” and provided for no effective standardized testing requirements for the introduction of new chemicals. Heather White, Executive Director of the EWG was recently interviewed for an  Autoimmune Summit. I have attended this health related summit on-line while recovering from my surgery and was shocked to hear and then read about out environmental exposure and lack of protection.

We often think about pollution and environmental toxins as contributing to cancer, birth defects, asthma and similar problems but auto-immunity is another problem with links to our toxic exposure.

During the Auto-Immune Summit Aristo Vojdani, Ph.D., M.Sc., M.T. scientist and editor of a peer-reviewed journal on auto-immunity, estimated that 60% of auto-immune diseases are “triggered” by environmental toxins, 30% triggered by dietary components, and 10% triggered by infectious disease. He distinguished triggers from predisposing factors which represent the physiologic milieu that leads to auto-immunity. This terminology of triggers vs. predisposing factors may seem confusing and arbitrary. In a nutshell, underlying the molecular mimicry theory of auto-immunity is “leaky gut”.  The “gateway to autoimmunity” is “leaky gut” (increased intestinal permeability) which allows foreign substances to cross the intestinal barrier, enter the circulation and challenge our immune system. Leaky gut  has many contributing factors including but not limited to diet, stress, gut dysbiosis and infections.  Although the % of auto-immune disease that is “triggered by” environmental toxins (versus diet and infections) remains speculative, there is mounting evidence that all of these factors contribute to greater or lesser degrees in various patients.

The paleo community has often stressed the importance of eliminating specific foods and replacing sugar laden flour foods with nutrient dense foods. But emphasis has also been placed on eating organic foods to avoid pesticides, herbicides and hormones.

Dr Vojdani has suggested that in addition to the gut-immune related mechanisms of molecular mimicry, environmental toxins, especially heavy metals, BPA and organic solvents,  act not only has foreign invaders stimulating the immune system but also stimulate the immune system by causing tissue damage directly and thereby presenting damaged or transformed tissue to the immune system as foreign. Environmental toxins do not require a leaky gut to enter our bodies. Many are absorbed through our lungs and skin, and many are directly absorbed through our guts even in the absence of a “Leaky gut”. Heavy metals including mercury, lead and cadmium do not require a leaky gut for intestinal absorption, nor do pesticides, herbicides or hormones administered to the animal we consume. They wreak havoc not only by directly damaging our organs but also by altering our immune system.

Dr Noel Rose, Director of Center for Autoimmune Research (John’s Hopkin’s University) and Dr. Ahmet Hoke, Director, Division of Neuomuscular Disease (John’s Hopkins NIMH Center) opine that our rising rates of auto-immune disease are the result of our “unsuccessful adaptation to new environmental agents”. (See Forward written in Last Best Cure | Donna Jackson Nakazawa.)

The  Government Accountability Office (GAO) is the Federal Government’s internal watchdog agency. A GAO report ( U.S. GAO – Environmental Justice: EPA Needs to Take Additional Actions to Help Ensure Effective Implementation) revealed that 85% of the new chemicals introduced into our environment are not accessed for safety. The  Environmental Protection Agency receives 90 days notice prior to the introduction of new chemicals (industrial, agricultural, etc). Industry does not have the burden of proof relative to safety. Instead, the EPA must determine, within 90 days, if a new chemical is “safe”. Shouldn’t it be the other way around?

Beyond that issue we have the problem of multiple  low grade simultaneous exposures. If a given level of toxin is “safe” based on short term studies of animals or humans, how do we know that a combination of hundreds or thousands of toxins over many years are “safe”. Likewise, if  air concentrations or water concentrations of a single toxin are deemed “safe” how can we possible test the combined effects of hundreds and thousands of environmental toxins in our air, water, soil and food?

The EPA, created under the Nixon administration, was decimated during the Bush administration when budget cuts resulted in the loss of > 50% of it’s senior scientists. With that executive action most of the EPA’s institutional memory was lost and along with it many of the already limited safeguards we had in place.

The concept of “eating clean” minimizes exposure to the potentially harmful effects of anti-nutrients  and immune stimulants (harmful plant lectins and saponins, excess phytic acid, excess omega 6 fatty acids) and more importantly encourages the consumption of nutrient dense foods (lots of colorful vegetables, grass fed meats, wild seafood). But “eating clean” also requires avoiding environmental toxins, including pesticides and herbicides.

To achieve that goal within a budget you can consult the EWG’s lists of foods that have the most and the least amount/variety of pesticides/herbicides. These lists are called the “dirty dozen” and the “clean fifteen”.

To avoid heavy metal exposure (especially mercury) eat seafood that is low on the food chain (less opportunity to accumulate mercury in their tissue). Many people do not realize that most of the mercury in our seafood comes from burning coal. Multiple heavy metals are present in coal. When coal is burned to generate electricity the heavy metals are released into the air and are then washed into our rivers, streams, lakes and oceans where they can accumulate in fish. As the heavy metals work up the food chain they accumulate in tissues. The best/safeest sources of healthy omega three fats are in smaller cold water fish (sardines, anchovies, small mackeral, salmon, trout). And do not forget oysters, scallops,  mussels,  and clams which may have less amounts of omega 3 fats but are safe with respect to heavy metals being low down on the food chain.

The concept of “living clean” involves more than being selective about food and cooking techniques. It involves avoiding exposure to toxic chemicals which can be found in our water (drinking and bathing), air, soil, clothing, furniture, make-up, deodorant, toothpaste and household cleaners. You can learn about these exposures at the EWG’s website. Consumer Guides | Environmental Working Group

Here is a fact that might get your attention, 90% of red lipstick has mercury in it. That’s right, 90%. Every day women around the world are painting their lips with lipstick that has mercury. The average American uses 10-12 personal care products per day which exposes us to 120 or more toxic ingredients. The law that regulates personal care products was written in 1938 (after a woman became blind from using mascara). It needs to be updated and there is much lobbying against better regulation (lots of money in personal care products an make-up). In the meantime we need to be more aware about what we put on and in our bodies.

Our environment is filled with “endocrine disruptors” which mimic and interfere with our hormones. The most common one is BPA (plastic) which has estrogen like effects.

What are our greatest exposures to BPA? Answer: plastic lids on coffee/tea to-go cups, plastic bottles of soda and plastic bottles containing citrus juices. Heat and acid both leech BPA (and probably other toxins) out of plastic into the liquids we drink. The most acidic beverage by far is SODA (as low as pH 2.2). So toxic chemical exposure is yet another reason to avoid soda. Do not serve your guests soda or water in plastic containers at parties. Set an example. Store your foods in glass containers and especially do not put warm or hot food into plastic containers. Get a water filter for your drinking water. Some even go so far as to get a water filter for their showers and baths.

Finally, flame retardants (furniture and clothing) required by law represent major health hazards by filling the air of our homes and exposing our skin to toxic substances. Mothers and toddlers have an estimated 3 times greater risk for this exposure which has been linked to neuro-development disorders, ADHD and endocrine disruption. Firefighters have very elevated levels of toxic chemicals derived from flame retardants. Some patients with a variety of illnesses have seen improvement in symptoms by having their furniture re-upholstered with coverings that do not contain flame retardants (anecdotal reports). Consider getting a HEPA air filter for your home and office. Remember hurricane Katrina? Remember the great number of illnesses reported by families made homeless by Katrina who were relocated to live in temporary portable housing. Those buildings were releasing formaldehyde and other toxic chemicals and produced illness within just a few days.

In my next post I will provide the “dirty dozen” and “clean fifteen” lists to help you make decisions about organic food purchases if you cannot afford to purchase 100% organic. In the meantime check out the EWG website. Also coming soon is a recipe for tumeric-ginger tea/marinade as an anti-inflammatory alternative to NSAIDs.

Live Clean and Prosper

Bob Hansen MD.

The Bacteria in your Gut are essential to your health Part I

Our human body consists of about 100 trillion cells but we carry about 1000 trillion bacteria in our intestines, that represents 10 times the amount of our own cells. (1) These bacteria are variously called our micro-flora, microbiome, gut flora, etc, along with viruses and other organisms that co-exist and co-evolved with us. Advances in rapid gene identification have enabled an explosion of knowledge related to our micro-flora, health and disease. We each carry an estimated 500 to 1000 different species of bacteria in our intestines and the balance/mix of these bacterial species can have profoundly positive or negative affects on our health. Patterns of micro-flora have been identified for a variety of human disorders including obesity, diabetes type I, several kinds of cancer and  inflammatory bowel disease to name a few. The issue of association vs. causation remains to be resolved but the beneficial and therapeutic effects of pro-biotics and fecal transplant (in rodent and human studies) in a variety of situations along with the observed deleterious effects of interrupting our micro-flora speak in favor of a causative or contributory role. (2) (3)

Accumulating evidences indicate that some diseases are triggered by abnormalities of the gut microbiota. Among these, immune-related diseases can be the promising targets for probiotcs. Several studies have proved the efficacy of probiotics for preventing such diseases including cancers, infections, allergies, inflammatory bowel diseases and autoimmune diseases. Lactobacillus casei strain Shirota (LcS) is one of the most popular probiotics, benefits of which in health maintenance and disease control have been supported by several science-based evidences.(2)

Early microbial colonization of the gut reduces the incidence of infectious, inflammatory and autoimmune diseases. Recent population studies reveal that childhood hygiene is a significant risk factor for development of inflammatory bowel disease, thereby reinforcing the hygiene hypothesis and the potential importance of microbial colonization during early life. (3)

Early-life environment significantly affects both microbial composition of the adult gut and mucosal innate immune function. We observed that a microbiota dominated by lactobacilli may function to maintain mucosal immune homeostasis and limit pathogen colonization. (3)

The human GI tract starts with the mouth and ends with the rectum. In between lay the esophagus, stomach, and intestines which consist of the duodenum, jejunum, ileum, and colon.

The surface area of the intestines equals that of a tennis court providing a huge area for absorption, digestion and interaction between our immune system and the micro-flora. This large surface area is the result of the intestinal micro-villi which produce an undulating surface resembling a series of peaks and valleys. The constant interplay between our immune system (4) and our micro-flora from birth to death along with the signaling and communication that occurs between our micro-flora and our nervous system (5,6,7) present two physiologic mechanisms for potential symbiosis (mutually beneficial interaction) vs dysbiosis (disease causing relationship).

Before birth the mouth, skin and intestine of the fetus is sterile. The first major introduction of bacteria to the infant occurs with birth  when the infant swallows bacteria in the mother’s birth canal and the infant’s skin becomes colonized by the mother’s bacteria. Infants born by cesarean section lack this initial exposure and they suffer increased risk of allergic and auto-immune disease (8). The rate of cesarean section in the US is now about 30 % and along with that increase there has been an observed increase in allergy, auto-immune and other diseases.

The second major addition to human gut and skin flora occurs with breast feeding and again breast-fed infants show decreased rates of allergy and auto-immune disease as well as decreased infections compared to bottle fed infants.

The interaction between the micro-flora and the immune system presents many complex relationships and interactions. Immune tolerance allows the immune system to recognize “self” and “friendly bacteria”  limiting the development of auto-immune disease and enhancing anti-inflammatory processes. At the other extreme recognition of “non-self”  allows for the recognition and disposal of “foreign” invaders such as infections or mutated cancer cells.

“The Old Friends Hypothesis”
Common organisms interact with dendritic cells in the GI tract, leading to increased maturation of dendritic cells. When there is interaction with these organisms again, the dendritic cells increase Treg maturation; not Th1 or Th2. This increases the baseline amount of anti-inflammatory cytokines, producing a Bystander Suppression. Another consequence of the increased number of mature dendritic cells is as they interact with self antigens, they increase the number Treg specific to these antigens. This is referred to as Specific Suppression. Together these two arms lead to tolerance of both self antigens as well as those of helpful gut organisms. (8)

Translation:  Treg or Regulatory T cells regulate the immune system and help prevent auto-immune disease and allergic reactions. Th1 and Th2,  T helper cells , on the other hand, increase inflammation and help our bodies defend against infection. The balance between Tregs and Th1, Th2 cells governs inflammatory responses.

Premature infants have an increased risk of a developing a very severe illness called necrotizing enterocolitis. Human studies have demonstrated significant risk reduction for this problem with the administration of pro-biotics to infants in neonatal intensive care units. (9)

Similarly, administration of pro-biotics during the first few years of life (to mother and child)  have been associated with decreased risk of eczema in children. While some studies suggest reduction of allergies and asthma in children, the regular use of probiotics remains undecided relative to preventing food allergies or asthma (10, 11).

Due to the recent exponential increase in food allergies and atopic disorders, effective allergy prevention has become a public health priority in many developed regions. Important preventive strategies include the promotion of breastfeeding and vaginal deliveries, judicious use of perinatal antibiotics, as well as the avoidance of maternal tobacco smoking. Breastfeeding for at least 6 months and introduction of complementary solids from 4-6 months are generally recommended. Complex oligosaccharides in breast milk support the establishment of bifidobacteria in the neonatal gut which stimulate regulatory T lymphocyte responses and enhance tolerance development…Perinatal supplementation with probiotics and/or prebiotics may reduce the risk of atopic dermatitis, but no reliable effect on the prevention of food allergy or respiratory allergies has so far been found. A randomized trial on maternal fish oil supplementation during pregnancy found that atopic dermatitis and egg sensitization in the first year of life were significantly reduced, but no preventive effect for food allergies was demonstrated. (10)

Thus birth by cesarean section increases risk and  breast feeding decreases risk of immune related problems (allergies, auto-immune disease and infection ). Use of probiotics for mother and child decrease the risk of eczema but the use of probiotics in preventing asthma or food allergy remains unsettled. There are a host of possible probiotics available that include various combinations of “healthy bacteria”. Future posts will discuss some of these.

Our micro-flora are constantly exposed to potential changing agents. Known influences include antibiotics (as medications or in the foods that we eat), stress, sleep, and diet. Because of the ubiquitous use of antibiotics in agriculture and animal husbandry, and the sometimes excessive use of antibiotics in medicine our microbiome is frequently changed by external factors. Many experts on the microbiome  consider these influences harmful and attribute the rising rates of several diseases as consequences of disruption in our gut flora.

Clostridium Difficile Colitis , a serious infection or overgrowth of the bacterium Clostridium difficile in the intestine occurs most commonly as a result of antibiotic administration to treat infections. This serious problem responds to anti-biotic treatment (ironically both the cause and cure) 90% of the time with the first round of treatment but there is a high incidence of recurrence due to the fact that C-difficile spores are resistant to antibiotics and can cause recurrent infection. In refractory or recurrent C-difficile cases a fecal transplant (FMT or fecal microbiota transplant) from a healthy human results in a 90 to 95% cure rate with the first treatment.

Antibiotic usage disrupts the normal gut flora and leads to an increased predisposition to CDI. The risk of recurrent CDI after initial treatment of the first infection is approximately 20–25% [Kelly and Lamont, 2008; Khanna et al. 2012g] and is further increased up to 60% with the use of additional systemic antibiotics and subsequent CDI recurrences [Hu et al. 2009]. The pathophysiology of recurrent CDI involves ongoing disruption of the normal fecal flora and an inadequate host immune response. Standard CDI treatment with antibiotics such as metronidazole and vancomycin further disrupts colonic microbial communities that normally keep expansion of C. difficile populations in check. Since C. difficile spores are resistant to antibiotic therapy for CDI, they can germinate to vegetative forms after treatment has been discontinued and lead to recurrent CDI. (12)

The authors of this study review the data for fecal microbiota transplant and summarize by stating:

Therefore, existing literature suggests that fecal transplant is safe and effective with over 500 cases of recurrent CDI with no serious adverse events reported to date. FMT appears to be an appropriate treatment option for multiple CDI recurrences and may be considered for refractory moderate to severe C. difficile diarrhea, failing standard therapy. The FDA had recently announced that an Investigational New Drug Application would be required for use of FMT for CDI, but this was later changed to the use of an informed consent process to ensure communication of potential risks.

In the area of obesity rodent studies have demonstrated that fecal transplants from thin to obese subjects results in significant weight loss. Measurable differences in the microbiome of obese vs thin humans have been identified.

The prevalence of obesity and related disorders such as metabolic syndrome has vastly increased throughout the world. Recent insights have generated an entirely new perspective suggesting that our microbiota might be involved in the development of these disorders. Studies have demonstrated that obesity and metabolic syndrome may be associated with profound microbiotal changes, and the induction of a metabolic syndrome phenotype through fecal transplants corroborates the important role of the microbiota in this disease. (13)

The issue of gut flora and obesity deserves a dedicated post. Multiple research articles and review articles have been published on the topic of fecal transplantation in relation to obesity, diabetes, metabolic syndrome, autoimmune disease and cancer. (14,15,16)

Diabetes, obesity, allergy, auto-immune disease, infections, psychiatric disorders and cancer represent examples of the potential interplay between the human microbiome, human health and disease. Multiple sources of information suggest a cause and effect relationship. The results of fecal transplantation in human and rodent studies, manipulation of the gut flora with pro-biotics and pre-biotics, data on the effects of vaginal vs cesarean delivery, and the benefits of breast feeding all proclaim the importance of our micro-flora.

Most traditional cultures have one or more forms of fermented foods. Examples include yogurt, kefir, sauerkraut, kim chee, beet kvass, kombucha. Almost any food can be fermented to produce health promoting probiotics and there is a growing movement for home-fermentation and/or consumption of purchased fermented foods. In addition to the pro-biotic nature of fermented foods and beverages, fermentation offers other potential health benefits. These include reduction of the anti-nutrients found  in various neolithic  foods (such as mineral binding phytic acid found in grains and legumes, digestive enzyme inhibitors found in soy and other legumes). Other potential health benefits include the production of Vitamin K2 found in many fermented foods.

This discussion barely scratches the surface of gut flora, health and disease. Future posts will address how our gut bacteria produce essential nutrients and affect mental health as well as physical health. Other important topics include how our activity, food, sleep and stress affect the our gut ecology. The system is dynamic with effects going in both directions.

Following the references below you will find links to NPR discussions of related topics. You can choose to read the articles and/or listen to the NPR interviews and reports.

Peace, happiness and longevity.

BOB

(1) Microbes in Gastrointestinal Health and Disease

(2) Probiotics as efficient immunopotentiators: Translational role in cancer prevention

(3) Environmentally-acquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces.

(4) Has the microbiota played a critical role in the evolution of the adaptive immune system?

(5) It’s a Gut Feeling – how the gut microbiota affect… [J Physiol. 2014] – PubMed – NCBI

(6) Metabolic tinkering by the gut microbiome: Impl… [Gut Microbes. 2014] – PubMed – NCBI

(7) The gut-brain axis rewired: adding a functional vaga… [FASEB J. 2014] – PubMed – NCBI

(8) Cesarean versus vaginal delivery: long-term infant outcomes and the hygiene hypothesis.

(9) Probiotics for prevention of necrotizing enterocolitis in preterm infants.

(10) Preventing atopy and allergic disease.

(11) Gut microbiota and allergic disease: new findings.

(12) Clostridium Difficile Colitis ,

(13) Gut microbiome, obesity, and metabolic dysfunc… [J Clin Invest. 2011] – PubMed – NCBI

(14) Fecal microbiota transplantation: indications, methods, evidence, and future directions.

(15) Fecal microbiota transplantation: past, present and future.

(16) Therapeutic potential of fecal microbiota transplantation.

Here are the NPR and other links.

Interview: Martin Blaser, Author Of ‘Missing Microbes’ : NPR

FDA Backs Off On Regulation Of Fecal Transplants : Shots – Health News : NPR

Human Microbiome Project – Home | NIH Common Fund

Staying Healthy May Mean Learning To Love Our Microbiomes : Shots – Health News : NPR

Gut Bacteria Might Guide The Workings Of Our Minds : Shots – Health News : NPR

Worried That Your Baby’s Sick? There May Be An Upside : Shots – Health News : NPR

Stomach bacteria can cause and worsen heart disease

A recent study from Italy (1) has identified a relationship between the bacteria that causes stomach ulcers and heart disease. H Pylori is a bacteria that can colonize the lining of the stomach and remain there for a lifetime unless diagnosed and eliminated with antibiotics. This bacteria was demonstrated to be a major cause of stomach ulcers by two physicians ( Dr. Barry Marshall and Dr. Robin Warren) who won the Nobel Prize for their finding.

Atherosclerosis the formation of plaque in the walls of arteries, is in large part an inflammatory process (2,3). The coronary arteries supply oxygenated blood to heart muscle and heart valves. A heart attack (myocardial infarction) occurs when a plaque  ruptures or tears, sending debris downstream in a coronary artery. That debris and/or the exposed ruptured plaque causes  a blood clot that obstructs blood flow to a portion of the heart and if the clot remains untreated a heart attack (muscle damage) occurs within minutes to hours. This process can also result in a fatal abnormal heart rhythm (ventricular fibrillation).

A major source of inflammation that is known to contribute to atherosclerosis and heart attacks is infection (2). Many patients suffer heart attacks following an acute infection or severe emotional stress.  Inflammation is involved in forming plaques, creating unstable plaques, causing plaque to tear or rupture and inflammation is involved in the dynamic process that leads to a heart attack (3). To quote the authors of this study:

Ischaemic heart disorders are the consequence of an atherosclerotic process. A concomitant cause of atherosclerosis is inflammation. Infections represent the single most frequent determinant of inflammation. In case of H pylori infection, the organism colonises the human stomach for life (if infection is not properly treated); therefore, the trigger is continuous and inflammation lasts for a lifetime.

The authors of this study found that a certain subset of H Pylori bacteria carry a protein that is similar to two or more very important and essential proteins in heart muscle. Those proteins are called human tropomyosin and cardiac ATPases. Both types of proteins are essential to the ability of the heart muscle to pump blood through the heart.

The authors postulate a mechanism called molecular mimicry. Because H Pylori proteins are very similar to certain proteins in the heart, colonization or infection in the GI tract by H Pylori results in an immune response directed against these foreign proteins which are very similar to proteins in heart muscle. The immune system”mistakes” these heart muscle proteins for the foreign proteins in H Pylori and mounts an immune response against the heart muscle. The study found that patients infected with certain H Pylori strains had higher circulating levels of inflammatory markers and BNP . BNP is associated with heart failure, (loss of heart muscle contracting ability) and loss of heart muscle function results in a poorer prognosis in patients with coronary artery disease.

Thus this study supports a direct link between bacterial infection in the GI tract and heart disease, mediated through the immune system.

This sort of molecular mimicry has been recognized in medicine as it relates to two very well known diseases caused by infections with a species of streptococcus (as in strep throat). Those diseases are rheumatic heart disease (also called rheumatic fever)  and glomerulonephritis, Either of these can occur as a complication of strep infections, ergo the importance of diagnosing and treating strep throat.

H Pylori represents one of many examples of the interplay between bacteria in our GI tract, the immune system and disease causation. Intestinal dysbiosis (imbalance between healthy and disease causing bacteria that reside in our gut) has been associated with a  multitude of disease processes including obesity, diabetes, psychiatric disorders and cancer (5,6,7,8,9,10).

An essential component of this process is the entry of foreign proteins or other antigens (immune stimulants) across the gut wall into the body where the immune system gets activated. Intestinal Permeability is a term that describes the ability of substances to cross the GI barrier (intestinal wall) and enter the circulation (blood or lymph glands). I have discussed this before. There are many potential causes of increased intestinal permeability (leaky gut) including small intestinal bacterial overgrowth (a specific kind of dysbiosis) dietary sources such plant lectins and saponins found in grains and legumes, stress, sleep deprivation and medications such as NSAIDS. When an individual suffers from leaky gut (increased intestinal permeability) the probability that toxic substances can enter the blood stream increases. Endotoxin (produced by pathogenic bacteria in the gut) has been related to many inflammatory disease processes wreaking havoc when it penetrates the intestinal barrier.

Intestinal permeability, auto-immune disease, molecular mimicry, and gut dysbiosis are topics often discussed in the Paleo community. These topics represent physiologic processes that relate to humans deviating from our evolutionary habits, diets and lifestyles.

References are below.

Peace.

BOB

(1)  Cross-sectional Study: CagA–positive Helicobacter pylori Infection, Acute Coronary Artery Disease and Systemic Levels of B-type Natriuretic Peptide Journal of Clinincal Pathology. 2014;67(3):251-257.

(2) 11. Epstein SE, Zhou YF, Zhu J. Infection and atherosclerosis: emerging mechanistic paradigms. Circulation 1999;100:e20–8.

(3)  Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999;340:115–26

(4)  Mayr M, Kiechl S, Mendall MA, et al. Increased risk of atherosclerosis is confined to CagA-positive Helicobacter pylori strains: prospective results from the Bruneck study. Stroke 2003;34:610–5.

(5) Diabetes, obesity and gut … [Best Pract Res Clin Gastroenterol. 2013] – PubMed – NCBI

(6) Involvement of gut microbiota in the de… [Gut Microbes. 2012 Jul-Aug] – PubMed – NCBI

(7) Crosstalk between the gut microbiota a… [Clin Microbiol Infect. 2012] – PubMed – NCBI

(8) [The role of gut microbiota in… [Postepy Hig Med Dosw (Online). 2013] – PubMed – NCBI

(9) [Research advances in th… [Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2013] – PubMed – NCBI

(10) The gut microbiota, obesity and insulin resi… [Mol Aspects Med. 2013] – PubMed – NCBI

Intestinal Permeability, Food and Disease

In medical school I learned some fundamental concepts about nutrition and digestion that turn out to be wrong. For example, we were taught that proteins in our diet are completely broken down into single amino acids in the gut, then absorbed through the wall of the intestine as individual amino acids. Turns out that not all proteins are completely digested in this manner and that fragments of proteins that are several amino acids long can be absorbed through the gut and enter our blood. Examples of such proteins include wheat gluten and bovine serum albumin (found in cows milk and whey protein) to name a few. The problem with absorbing such nutrients into our bloodstream is that these protein fragments are “foreign” and can be recognized by our immune systems as foreign, triggering an immune (inflammatory) response.

Some peptides (short chains of amino acids) in bovine serum albumin have structural similarity to peptides in human tissues. This foreign protein has been implicated in autoimmune diseases such as Multiple Sclerosis, Rheumatoid Arthritis and Type 1 Diabetes.

Other substances such as bacterial endotoxin similarly can be absorbed into the blood and cause trouble. Endotoxin, also called LPS or  Lipopolysaccharide, is a major component of the outer membranes of certain kinds of bacteria (gram negative bacteria such as E-coli) that live in the  Lumen of our gut. High levels of endotoxin circulating in the blood occur during septicemia and can result in death from septic shock. Lower levels of circulating endotoxin have been demonstrated to contribute to alcoholic and non-alcoholic liver disease, both of which can cause liver failure and death.

Intestinal wall permeability is governed by many factors. There are regulatory proteins that open and close the gaps (tight junctions) between the cells that line the walls of our intestines, thereby allowing more and larger foreign substances to enter our blood. This mode of entry is referred to as “paracellular” since it does not involve the usual absorption mechanism through the walls of the cells that line the intestines.

Substances regularly consumed by Americans known to increase intestinal permeability include gluten (the sticky protein found in wheat, barely, rye, oats), alcohol, non-steroidal anti-inflammatory drugs  like ibuprofen (Motrin, Advil), naprosyn (Alleve), and aspirin.  Refined “vegetable oils” that are high in a specific Polyunsaturated fatty acid called linoleic acid (examples of these vegetable oils include corn oil, soy oil, cottonseed oil) have also been demonstrated to increase intestinal permeability.

Vegetable oils have also been found to enhance the liver inflammation and destruction caused by  alcohol which is at least in part mediated by absorption of endotoxin and ultimately also caused by oxidative stress.

The same applies to non-alcoholic liver fatty liver disease. (Progression of alcoholic and non-al… [Drug Metab Pharmacokinet. 2011] – PubMed – NCBI)

Interestingly, consumption of saturated fat (as found in beef tallow, coconut oil, butter and cocoa butter-the oil of dark chocolate) protects the liver from inflammation and destruction caused by alcohol, while polyunsaturated fat consumption (vegetable oils)  do the opposite. (References above and below)

There is growing evidence for a link between auto-immune disease and Alterations in intestinal permeability. Increased intestinal permeability (IP) has been observed in a substantial percentage of individuals with Type I diabetes. It is commonly observed in populations at high risk of developing Crohn’s disease and has been observed in patients who subsequently develop Crohn’s disease. Patients with ankylosing spondylitis have increased IP and although these patients are typically treated with NSAIDs which increase IP, the effects of NSAIDS have been isolated from a primary defect in IP which is shared by relatives without the disease.

“increased intestinal permeability is observed in association with several autoimmune diseases. It is observed prior to disease and appears to be involved in disease pathogenesis.”

A paleolithic diet avoids all sources of gluten (paleo is grain-free) and it also avoids refined “vegetable oils”. These food items present a double hit relative to inflammation. First, they increase IP which increases circulating levels of various “foreign” proteins and other foreign macromolecules which can stimulate the immune system. The second hit from these food items represents their direct inflammatory effects once absorbed into the body. I have previously discussed the  inflammatory response to excess omega six fats here.

An excellent review of the importance of the ratio of omega six fats found in “vegetable oil”  to omega three fats found in fish oil can also be found here ,  here   and  here.

The potential inflammatory response and anti-nutrient effects of cereal grains and in particular the gliadin portion of wheat gluten has been discussed and reviewed in multiple papers including:

Do dietary lectins cause disease?

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

BMC Medicine | Full text | Spectrum of gluten-related disorders: consensus on new nomenclature and classification

BMC Medicine | Abstract | Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

Bioactive antinutritional peptides derived from cere… [Nahrung. 1999] – PubMed – NCBI

Antinutritive effects of wheat-germ agglutinin and… [Br J Nutr. 1993] – PubMed – NCBI

This discussion just scratches the surface of the effects of intestinal permeability and health. Future discussion will address how the micro-flora (bacteria and viruses that live in our GI system) affect intestinal permeability, our brains, our immune system and our health.

Avoiding foods that we have not evolved to eat will result in decreased inflammation and will often reduce the symptoms of auto-immune and other inflammatory diseases. Many present day diseases are considered by evolutionary biologists to represent a mismatch between our culture, food, and our evolutionary biochemistry. These diseases were likely rare or non-existent  before the advent of agriculture and the subsequent industrialization of society with highly processed foods.

Eat only pastured meat, free range poultry and eggs, wild seafood, fresh vegetables, fruit and nuts and you will avoid the problems discussed above as well as a host of other problems to be discussed in future posts.

Peace,

Bob Hansen MD