The pillar of all knowledge (Wikipedia) describes the Hygiene Hypothesis as, "a lack of early childhood exposure to infectious agents, symbiotic microorganisms (such as the gut flora or probiotics), and parasites, increases susceptibility to allergic diseases by suppressing the natural development of the immune system. In particular, the lack of exposure is thought to lead to defects in the establishment of immune tolerance."  Great, but what does this really mean? 

Simple; if you are not being exposed to a wide array of germs and organisms (bacteria, viruses, molds, fungi, PARASITES, etc) from the time you are born, your chances of developing any number of diseases goes up significantly.  The kicker is that once you lose Immune Tolerance (OR FAIL TO ESTABLISH IT IN THE FIRST PLACE), your body begins seeing itself --- its various organs, glands, cells, tissues, enzymes, etc --- as foreign.  And once the body recognizes something as foreign, it begins attacking.  Can anyone say AUTOIMMUNITY?

Although people have been talking about this theory for centuries, the first person to actually coin the term 'Hygiene Hypothesis' was one David Strachan, a Professor of Epidemiology at London's St. George's University.  His discoveries were published in a 1989 issue of the British Medical Journal (Hay Fever, Hygiene, and Household Size).  Interestingly enough, he began that study by saying, "Hay fever has been described as a post-industrial revolution epidemic".  In other words, Hay Fever was not an issue as long as people largely lived agrarian lifestyles, with regular exposure to dirt, dust, manure, animals, etc, etc, and were not being exposed to the medications we'll discuss in a moment.  He went on to say that, "infection in early childhood, transmitted by unhygienic contact with older siblings," prevented said allergic diseases (Hay Fever) in the younger siblings.  Needless to say, in a society whose physicians basically promote cradle-to-grave germophobia, this idea went over like a proverbial lead balloon --- at least initially.  But by Y2K momentum was shifting.

Quick history fact; the Berlin Wall came down in 1989.  In the early 1990's, Dr Erika Von Mutius, a German pediatrician, ran a series of experiments comparing the rates of ASTHMA and ALLERGIES between East German children who typically grew up poor and dirty under the effects of COMMUNISM-INDUCED POVERTY, and West German children, who on average had about as high a standard of living as you'll find anywhere in Europe.  She expected to see that cleanliness really is next to Godliness; at least as far as allergies and asthma were concerned.  Instead she saw the exact opposite.  The dirtier the children, the less likely they were to have A&A.  Today there are literally thousands upon thousands of similar studies --- many having to do with autoimmune diseases (HERE'S ONE).  To see where Dr. Erika's work has taken her over the past two decades, HERE is a cool study from last March's issue of the Journal of Allergy and Clinical Immunology that sums up this topic.

Are there legitimate physicians and researchers who actually know their way around this subject, yet still deny the Hygiene Hypothesis exists?  Sure there are --- kind of.  After reading last July's Perspectives in Public Health (Time to Abandon the Hygiene Hypothesis: New Perspectives on Allergic Disease, the Human Microbiome, Infectious Disease Prevention and the Role of Targeted Hygiene), I began to see what the "deniers" looked like and were really after.  Despite having to admit that the premises of the Hygiene Hypothesis are real --- "Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease." --- the scientists went on to complain that what they hated most was that one of their medical words (hygiene) had been hijacked.  Thus, their demand that, "The term ‘hygiene hypothesis’ must be abandoned."  I saw this same theme repeated in numerous articles and studies --- never denying that the phenomenon is real, but detesting the language used to describe it.

Case in point; writing for PNAS back in February (News Feature: Cleaning up the Hygiene Hypothesis), Megan Scudellari made essentially the same appeal, which carried two distinct points.  The first is what I talked about in the last paragraph --- that the term "Hygiene Hypothesis" does not really explain what's going on because it's too broad, covers too much territory, and alters the common medical meaning of the word "hygiene".  The second had to do with the fact that even though the data does not lie (there is an inarguable relationship between hygiene --- or the lack thereof --- and a slew of health-related factors and diseases), the Hygiene Hypothesis cannot be true because there is no one-size-fits-all probiotic "cure".

"The second major concern among researchers is a lack of evidence demonstrating how to reduce rates of allergic and autoimmune diseases. Although there are hundreds of observational and epidemiological studies supporting a more nuanced theory that moves beyond the hygiene hypothesis, there are only a few randomized, controlled prospective studies testing interventions to reregulate the immune system. These include an experimental infection with helminths to treat IBD, which met with mixed results, and probiotics treatments for illnesses ranging from severe acute pancreatitis to eczema. In some cases, probiotics alleviated symptoms, but, in others, they had no effect."

Scudellari's mistake is that she is looking at this problem through the lens of other medical treatments. Your testosterone is low?  We'll just give you some testosterone (HERE).  Not enough insulin to lower your blood sugar?  We have drugs that do the same thing (HERE).  Feeling a bit down because presumably your body is not making enough neurotransmitters (serrotonin / dopamine)?  We'll start pumping the ANTIDEPRESSANTS. And of course all women need HRT. 

The problem is, not only does this short-sighted approach always fail over the long run, it suppresses your body's natural negative feedback loops, frequently leaving you worse than when you started (when's the last time insulin helped a TYPE II DIABETIC actually solve their problem?).  And here's the rub; there are only about a jillion studies showing that all of these problems are INFLAMMATORY IN NATURE and intimately linked to one's MICROBIOME (the numbers and ratios of the various strains of bacteria found in the Gut).   If that's really the case, why can't we just give everyone a probiotic?  It's really quite easy to understand.

Scudallari is certainly right about one thing --- studies on PROBIOTICS are all over the map (my friend Dr. Eric Serrano -- an OB/GYN, past head of a major ICU, expert in FUNCTIONAL MEDICINE, and nutritional specialist for elite strength athletes --- sometimes lectures on the potential side effects of probiotics).  For every study that "proves" a certain disease can be beneficially affected by taking a probiotic, another study seems to "prove" otherwise.  In other words, probiotics are the definition of a 'mixed bag'.  Frankly, I'm not surprised, and you shouldn't be either. 

Depending on whose research you look at, a normal human microbiome contains something like 300 to 600 strains of bacteria, give or take.  These bacteria must work in tandem with each other; like members of an orchestra.  All it takes is one member out of tune or rhythm for the music to start sounding "off".  Get a few more members off key or out of rhythm and the whole thing starts devolving into chaos.

It's why even though I do not do them in my clinic, I have a DOZEN OR SO ARTICLES on FMT (Fecal Microbiota Transplants); one of them explaining why taking generic probiotic formulas with 1, 2, 8, or even 15 strains of bacteria, is not going to be enough to reestablish and heal the microbiota of many people --- especially really sick people (HERE).  But when the alternate to probiotics is DANGEROUS DRUGS, what have you got to lose?  Worst case scenario, it doesn't work.  What are you out?  A couple bottles of probiotics?  Who cares!  And as for those weird studies showing amazing benefits for many people purposefully being infected with parasitic worms known as HELMINTHS, there isn't "a" study as in one, there are dozens of such studies; many of which show promising results for those with IBS or IBD that has not responded to anything else. 

Today, there are tens of thousands of studies concerning the HYGIENE HYPOTHESIS --- many, if not most, having to do with the MICROBIOME (on Pubmed, search for Gut Flora, Microbiome, Microbiota, Hygiene Hypothesis, Autoimmunity, etc, etc).  The thing that's so astounding is that you can name virtually any disease that's NOT 100% GENETIC (something like Down's or Cystic Fibrosis), head on over to PubMed, and find studies linking it to GUT HYGIENE.  In fact, I just showed you how all diseases are intimately related to each other and are only slightly different variations of the exact metabolic dysfunctions (HERE).  You can also find thousands of studies showing how severely antibiotics affect your natural "hygiene" as well --- causing almost every disease you can imagine, including cancer (HERE).

You've read this far, what's the point?  Why does any of this really matter --- especially when there is so much debate within the medical research community (sorry, but 99% of the practicing medical community is either purposefully clueless or not interested in rocking the boat they are currently sailing through their career on)?  The point is that you probably need to think about health a bit differently than you have in the past. 

We already know that antibiotics will destroy your health in more ways than you can shake a stick at (Hygiene Hypothesis in action --- HERE).  We also know that most drugs, to at least some degree, act like antibiotics (HERE).  The cherry on top is that the absurd number of CHEMICALS (vaccines included --- see some of the links in the next paragraph) that we are exposed to daily always have deleterious effects on gut flora and microbiome (HERE); never beneficial.

If you are interested in reading more on this topic, I put several posts together (HERE, HERE, HERE, HERE, and HERE).  If you are chronically ill or dealing with CHRONIC PAIN, you might want to take a look at THIS POST as well.  The super cool thing about my site is that I have nothing up my sleeve and am not trying to sell you anything.  I'm simply trying to help you find the most up-to-date information in the field of natural health --- information that will hopefully help you begin the process of transforming your health and your life.  Oh; and if you like what you are seeing, be sure to like, share, or follow us on FACEBOOK.

"Glyphosate has become the most commonly used herbicide worldwide, with a reputation of being environmentally benign, non-toxic and safe to wildlife and humans. However, studies have indicated its toxicity has been underestimated, and that its persistence in the environment is greater than once thought. Its actions as a neurotoxin and endocrine disruptor indicate its potential to act in similar ways to persistent organic pollutants. Exposure to glyphosate and glyphosate-based herbicides for both wildlife and people is likely to be chronic and at sub-lethal levels, with multiple and ongoing exposure events in both urban and agricultural landscapes."  From this month's issue of Conservation Biology (The Rise of Glyphosate and New Opportunities for Biosentinel Early-Warning Studies)

"Use of glyphosate-based herbicides (GBHs) increased over 100-fold from 1974 to 2014. Additional increases are expected due to widespread emergence of glyphosate-resistant weeds, increased application of GBHs, and preharvest uses of GBHs as desiccants. Current safety assessments rely heavily on studies conducted over 30 years ago.  Human exposures to glyphosate are rising, and a number of in vitro and in vivo studies challenge the basis for the current safety assessment of glyphosate and GBHs. We conclude that current safety standards for GBHs are outdated and may fail to protect public health or the environment."  From next month's issue of the Journal of Epidemiology and Community Health (Is it Time to Reassess Current Safety Standards for Glyphosate-Based Herbicides?)

"Glyphosate is now the world’s most heavily applied herbicide.  Evidence has accumulated over the past two decades, especially, that several vertebrate pathways are likely targets of action, including hepatorenal damage, effects on nutrient balance through glyphosate chelating action and endocrine disruption. Other early assumptions about glyphosate, for example that it is not persistent in the environment, have also been called into question. In addition, the prediction that glyphosate would never be present widely in surface water, rainfall, or groundwater has also been shown to be inaccurate."   From the February 2016 issue of Environmental Health (Concerns Over Use of Glyphosate-Based Herbicides and Risks Associated with Exposures: A Consensus Statement)

"Glyphosate, the active ingredient in Roundup®, is the most popular herbicide used worldwide. The industry asserts it is minimally toxic to humans, but here we argue otherwise. Residues are found in the main foods of the Western diet, comprised primarily of sugar, corn, soy and wheat.  Glyphosate's inhibition of cytochrome P450 (CYP) enzymes is an overlooked component of its toxicity to mammals. CYP enzymes play crucial roles in biology, one of which is to detoxify xenobiotics. Thus, glyphosate enhances the damaging effects of other food borne chemical residues and environmental toxins. Negative impact on the body is insidious and manifests slowly over time as inflammation damages cellular systems throughout the body.  The foodstuffs of the Western diet, primarily grown by industrial agriculture, are increasingly being produced using a two-part system of engineered plant seeds and toxic chemical application. Novel bacterial genes are incorporated through genetic engineering, and toxic chemical residues are readily taken up by the engineered plants.  Our systematic search of the literature has led us to the realization that many of the health problems that appear to be associated with a Western diet could be explained by biological disruptions that have already been attributed to glyphosate. These include digestive issues, obesity, autism, Alzheimer’s disease, depression, Parkinson’s disease, liver diseases, and cancer, among others."  From a 2013 issue of Entropy (Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases).  PART III of this paper can be found by clicking the link.

I've talked about DR. STEPHANIE SENEFF before in relationship to her work on STATIN DRUGS. While it's easy to discount people like myself (a small-town Missouri chiropractor with a special interest in FUNCTIONAL MEDICINE), it's not so easy to blow off someone with Seneff's credentials (she co-authored the study in the bullet above).  Her Massachusetts Institute of Technology bio states, "She received the B.S. degree in Biophysics in 1968, the M.S. and E.E. degrees in Electrical Engineering in 1980, and the Ph.D degree in Electrical Engineering and Computer Science in 1985, all from MIT."  Furthermore, her CV reads like an encyclopedia.  And to top it all off, she has been studying and warning people about Glyphosate for a very long time (HERE).  Hang with me because we will eventually make our way back to Dr. Seneff's work, which you can check out on video below.

When it comes to man-made toxins, few are better known and more widely used than BPA and glyphosate.  Glyphosate is a broad leaf herbicide, meaning it kills weeds with large leafs (as opposed to grasses), and was originally manufactured by Monsanto under the trade name Roundup.  The aspect that has brought it the most attention however (fame or infamy, depending on which side of the debate you are on) is the fact that numerous companies (Monsanto being the biggest by far), have produced genetically modified grains which, despite being broad leaf (corn and soy are great examples) can withstand being doused in the stuff.  Because of this, it is by far the most widely used herbicide on the planet for many years running.  Unfortunately, glyphosate also happens to be a potent ENDOCRINE DISRUPTOR which, as we saw in Dr. Seneff's earlier study, also fouls the P-450 Cytochrome System (the body's chief DETOX SYSTEM), making it that much tougher to clear from your system.

Before we delve specifically into the relationship between glyphosate and AUTISM, let's take just a moment to look at a smattering of the most recent studies showing the various ways this stuff affects fish, animals, and people.  Bear in mind that the number of studies on this compound is mind-boggling (nearly 2,500). Thus, when I tell you that I am barely scratching the surface of this topic, what that really means is that I am barely scratching the surface of the surface.  Also note that since I dealt with endocrine disruptors the other day (see earlier link), I am not going to do so today even though there are hundreds of such glyphosate studies out there.

• WHAT DOES LONG TERM EXPOSURE TO GLYPHOSATE GENERALLY DO TO THE BODY?  Although you should have noticed from the studies mentioned previously, here are a couple more to show you just how bad this stuff is for overall health.   Because so many of these studies have to do with animals and fish, I'll go ahead and include this one --- on goldfish. This month's issue of Aquatic Ecology (Metabolic Profiling of Goldfish after Long-term Glyphosate-Based Herbicide Exposure) determined that, "Long-term glyphosate exposure caused disorders of blood biochemical indexes and renal tissue injury. Metabolomics analysis combined with correlation network analysis uncovered significant perturbations in oxidative stress, energy metabolism, amino acids metabolism and nucleosides metabolism in glyphosate dosed fish, which provide new clues to the toxicity of glyphosate."  And if you are not sure what the field of METABOLOMICS is, just click the link.
  

 

• HOW VISIBLY SEVERE ARE THE AFFECTS OF GLYPHOSATE?  A group of ten researchers published a study in last month's copy of The Science of the Total Environment called Agricultural Expansion as Risk to Endangered Wildlife: Pesticide Exposure in Wild Chimpanzees and Baboons Displaying Facial Dysplasia.  The authors, scientists from both Africa and around the world, said that, "Prenatal exposure to environmental endocrine disruptors can affect development and induce irreversible abnormalities in both humans and wildlife."  Because the game refuge in this study (Kibale National Park) is surrounded by industrial tea plantations that use lots of chemicals, including glyphosate, the authors concluded that, "Sixteen young individuals of the 66 chimpanzees monitored (25%) exhibit abnormalities including reduced nostrils, cleft lip, limb deformities, reproductive problems and hypopigmentation.  Chemical analysis of samples collected from 2014 to 2016 showed that mean levels of pesticides in fresh maize stems and seeds, soils, and river sediments in the vicinity of the chimpanzee territory exceed recommended limits.  Since some of these pesticides are thyroid hormone disruptors, we postulate that excessive pesticide use in the Sebitoli area may contribute to facial dysplasia in chimpanzees and baboons through this endocrine pathway."  This, folks, is not slow and subtle toxicity, but overt and in your face --- literally.

 

• WHAT IS GLYPHOSATE RESISTANCE? A common theme with virtually every drug is that the more of it you take, the less effective it becomes.  A great example is Insulin Resistance. When there is a large amount of insulin in the bloodstream on a perpetual basis, it "clogs" the receptors leaving the body "resistant" to it's effects.  Last month's issue of Pest Management Science stated that, "The first case of glyphosate-resistant weeds in the United States was documented in 1998, two years after the commercialization of genetically-engineered herbicide-resistant (HR) corn and soybeans. Currently, over 15 glyphosate-resistant weed species affect U.S. crop production areas. These weeds have the potential to reduce yields, increase costs, and lower farm profitability."    How widespread is the problem?  It's everywhere, but particularly problematic in the deep South.  This month's copy of Nature Plants (Glyphosate Resistance: Of Superweeds and Survivors) concluded, "Glyphosate resistant weeds not only harm agriculture and human health, but divide the scientific community in regard to who is to blame for the weeds, and what they should even be called."  There are scores of studies on this topic.
  

 

• NON-GLYPHOSATE FARMERS WILL ALWAYS BE AFFECTED BY GLYPHOSATE USERS:  Last month's copy of Environmental Toxicology and Chemistry ran a study on "Herbicide Drift".  They determined that when just a little of your neighbor's Roundup or other glyphosate-containing spray drifts into your fields, it has significant effects on your crops. "Herbicide effects differed with species, year, and, to a lesser extent, farm. Generally, 10% to 20% of the herbicides were required to affect reproduction in Camassia leichtlinii, Elymus glaucus, Eriophyllum lanatum, Festuca idahoensis, Iris tenax, and Prunella vulgaris."  In other words, it did not take much glyphosate to adversely affect these six grasses.
  

 

• WHY ARE PEOPLE REACTING TO GMO GRAINS: Roundup ready seeds are genetically engineered to tolerate being doused with glyposate.  What do people "react" to immunologically if they are going to react?  Proteins --- either by themselves or attached to some sort of toxin, metal, chemical, etc.    Less than a year ago, the Colombian journal Revista Salud Publica showed that when flour being sold in Bogota was checked for "transgenic proteins," they found seven of them.  Transgenic proteins are proteins that are transferred via GMO techniques from plants or animals into completely unrelated plants or animals.  For instance, cold-resistant tomatoes have been created using genetic material from cold-water fish.  If the body's immune system recognizes these proteins as foreign invaders (which it does in GM products with increasing frequency), it will begin to mount immune system attacks of varying magnitudes.  It's one reason that today's GRAINS are so much more likely to be problematic to health than they used to be, and why a good ELIMINATION DIET can help sort this issue out for you.  It's another reason to grow your own food using heirloom seeds.
  

 

• GLYPHOSATE DAMAGES DNA AND CAUSES CANCER:  Despite a number of recent studies from industry saying that glyphosate does not cause CANCER, there is ample proof that it causes a number of DNA mutations. The March issue  of Food and Chemical Toxicology (DNA Damage and Methylation Induced by Glyphosate in Human Peripheral Blood Mononuclear Cells) revealed that,  "Human peripheral blood mononuclear cells were unable to repair completely DNA damage induced by glyphosate.  To sum up, we have shown for the first time that glyphosate may induce DNA damage in leucocytes such as peripheral blood mononuclear cells and cause DNA methylation in human cells."   Leukocytes --- white blood cells -- area critical part of the immune system.  Mutations there lead to "LEUKEMIA". Another study, this one from last month's issue of Regulatory Toxicology and Pharmacology (Evaluation of Various Glyphosate Concentrations on DNA Damage in Human Raji Cells and its Impact on Cytotoxicity), concluded that, "Glyphosate is a highly used active compound in agriculturally based pesticides. The literature regarding the toxicity of glyphosate to human cells has been highly inconsistent. We studied the resulting DNA damage and cytotoxicity of various glyphosate concentrations on human cells to evaluate DNA damaging potential.  We found that glyphosate treatment is lethal to Raji cells at concentrations above 10 mM. Treatment concentrations of 1 mM and 5 mM induce statistically significant DNA damage to Raji cells following 30-60 min of treatment, however, cells show a slow recovery from initial damage and cell viability is unaffected after 2hrs. At these same concentrations, cells treated with additional compound did not recover and maintained high levels of DNA damage." In other words, while most of us may be degrading toxic chemicals and fixing mutations, the damage is, as is the case with most chemicals, accumulative.  BTW, Raji Cells are "research" cells whose lineage is from an 11 year old Nigerian boy with Burkitt's Lymphoma (a cancer of the lymphatic system) ---- from back in 1963.
  

  
As a side note to this issue, last September, the journal Critical Reviews in Toxicology published a series of five studies about the cancer-causing potential of glyphosate.  These reviews essentially concluded that glyphosate is safe and that it's potential for being mutagenic has been overblown and not supported by EVIDENCE-BASED MEDICINE.  While that's all well and good, the paper also revealed that the journal's publisher --- one Roger O. McClellan --- "serves as an independent advisor to private... entities on environmental and occupational health issues.   From 1988 to 1999, he was the President and Chief Executive Officer of the Chemical Industry Institute of Toxicology (CIIT), a not-for-profit research institute whose extensive research program, focusing on mechanisms of action of chemicals, was supported by dues payments from member companies. The Monsanto Company was a founding member of the CIIT.  This article is part of a supplement, sponsored and supported by Intertek Scientific & Regulatory Consultancy. Funding for the sponsorship of this supplement was provided to Intertek by the Monsanto Company, which is a primary producer of glyphosate and products containing this active ingredient."  I can just visualize Dana Carvey's "church lady" character cocking her head just so and looking through her cat glasses while saying, 'isn't that special.'  This is why many experts (HERE for example) are saying that we cannot trust the biggest portion of the research coming from peer-review.  In other words, there is no mystery as to what the conclusions will be when Monsanto funds the studies. 

• EARLY LIFE EXPOSURE TO GLYPHOSATE LEADS TO METABOLIC SYNDROME AND OBESITY: Interestingly enough, most Endocrine Disruptors tend to be "Obesigens" as well (by mimicking hormones they make you fat).  Two months ago, the journal Diabetes, Metabolic Syndrome, and Obesity: Targets and Therapy published a study called Early-Life Chemical Exposures and Risk of Metabolic Syndrome.  The authors concluded that, "The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS) have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood) may have a more profound effect on life-long risk of obesity and MetS.  The number of new chemicals that are synthesized and marketed increases exponentially each year; from 2005 to 2015, the number of chemicals registered by the Chemical Abstract Service increased from 25 to 100 million substances.  There is now compelling evidence in mammals that exposure to environmental pollutants can alter endogenous hormonal axes. These chemicals have been termed endocrine disruptors. Historically, research attention has focused largely on the ability of these xenobiotic compounds to alter estrogenic and/or androgenic pathways by acting as agonists/antagonists at hormone receptors, altering the number of hormone receptors in a cell-specific manner or causing perturbations in circulating concentrations of the endogenous hormones. More recently, however, there has been an increased awareness that these same chemicals can also disrupt metabolic homeostasis."  You should read this free (and very scary) study in its entirety.  BTW, at least in America, their stats on the number of adults with metabolic syndrome have been underestimated by 100% (HERE) --- it is now estimated that 50% of adults have the Metabolic Syndrome.   I hate to break it to you, but if you have metabolic syndrome, you are at best a "functional" DIABETIC.  There were dozens of similar studies.
  

 

• GLYPHOSATE IS FOUND IN SOY-BASED BABY FORMULAS:  In January of this year, Frontiers in Nutrition published a study on the pros and cons of soy baby formula called Soy-Based Therapeutic Baby Formulas.  As far as the benefits of soy formula --- a known endocrine disruptor (PHYTOESTROGEN) --- the main selling points were economics (it's both cheap to produce and to deliver therapeutics with) and safety (minimal adverse health events over the past century --- it was even touted as a "health food" for part of that time).  On the other side of the coin, however, "The major argument opposing the use of SIF (soy infant formula) and therapeutic SIF is that safety has not been rigorously tested, particularly potential health effects associated with phytoestrogens, agrochemicals, and GM components."  And while the peer-review concerning these ADVERSE EVENTS is indeed lengthy, I will only deal with a small part of what they said about glyphosate.  "93% of soybean crops in the United States are GM. Glyphosate-tolerant soybeans were genetically engineered, which infers resistance to the Roundup® herbicide glyphosate. Since the mid-1990s, there has been a steady increase in the use of GM soybeans in agriculture along with the concomitant use of glyphosate. Glyphosate is sprayed on GM crops where is acts as both a pesticide and herbicide as well as on other crops (for example, wheat) where it serves as a drying agent. This chemical accumulates in the soil, is not easily degraded, and is a known antibiotic and endocrine disruptor. Moms Across America found high levels of glyphosate in breast milk samples from lactating mothers.  The increased use of glyphosate has been linked with numerous modern diseases.  Glyphosate is absorbed by soybean plants with higher concentrations...."  Look folks, I could have gone one and on, or I could have included many many similar studies.  Hopefully you get the point.
  

 

• GLYPHOSATE AND SOY MILK:  In a study from February's issue of Food and Chemical Toxicology (Prepubertal Subchronic Exposure to Soy Milk and Glyphosate Leads to Endocrine Disruption) we learn that, "Soy contains phytoestrogens, substances with known estrogenic activity, besides, glyphosate-based herbicides are extensively used in soy crops, being frequently a residue in soy beans, bringing to a concern regarding the consumption of soy-based products, especially for children in breastfeeding period.  Endocrine disruption was observed through decrease in testosterone levels, decrease in Sertoli cell number and increase in the percentage of degenerated Sertoli and Leydig cells [the cells that make both sex hormones and sperm / eggs] in animals receiving soy milk supplemented with glyphosate and in animals treated only with soy milk. Animals treated with soy milk with glyphosate showed decrease spermatids number and increase of epididymal tail mass compared to control, and decrease in the diameter of seminiferous tubules compared to soy milk control group. Animals receiving soy milk supplemented with glyphosate showed decrease in round spermatids and increase in abnormal sperm morphology, compared to control."  Bottom line, soy is bad enough, but add glyphosate to it and you have a hormonal nightmare on your hands.

 

• GLYPHOSATE ASSOCIATED WITH AUTOIMMUNITY:  Although there are a myriad of INFLAMMATORY DISEASES associated with glyphosate, it has been linked to AUTOIMMUNITY as well --- in this case RHEUMATOID ARTHRITIS. This fascinating study from November's issue of Environmental Health Perspectives starts out with the words, "Farming has been associated with rheumatoid arthritis (RA)..."  Having grown up on a Kansas farm, I am interested in knowing why.  Well, here it is.  "Overall, women with RA were somewhat more likely to have reported lifetime use of any specific pesticide versus no pesticides. Of the 15 pesticides examined, maneb/mancozeb and glyphosate were associated with incident RA compared with no pesticide use. Incident RA was also associated with the application of chemical fertilizers and cleaning with solvents, but inversely associated with lifetime livestock exposure as a child and adult compared with no livestock exposure."  Be aware that technically speaking, glyphosate is an herbicide and not a pesticide.  Also note that exposure to livestock (ANIMALS) is protective due to its effects on the MICROBIOME.  Speaking of microbiome......
  

There are so many studies linking various forms of DYSBIOSIS and fouled up GUT HEALTH to Autism, it would be simple to write a book (HERE is a post I did a few years ago, or you can cruise on over to PubMed to see any of the hundreds of studies).  The real question is whether or not glyphosate destroys bacteria and normal flora; whether in the soil, the water, or the body.  Although there are any number of studies saying this is not the case, most of these, not surprisingly, happen to be funded by (ahem) industry.

A few months ago, the journal Integrative Medicine discussed this link in a study that was essentially a CASE HISTORY of triplets, two of which had autism and one with seizure disorders.  Dr. William Shaw who not only happens to be the Director of Great Plains Labs in the KC area, but a board certified clinical chemist and toxicologist, had this to say on the topic of glyphosate and Autism as related to microbiome.  "The pattern of metabolites in the urine samples of the males with autism are consistent with a recent theory of autism that connects widespread glyphosate use with alteration of animal and human gastrointestinal flora. That theory is that the normally beneficial bacteria species that are sensitive to glyphosate are diminished and harmful bacteria species, such as Clostridia, that are insensitive to glyphosate, are increased following exposure to glyphosate. Excessive dopamine, caused by inhibition of dopamine-beta-hydroxylase by Clostridia metabolites, in turn, produces oxidative species [FREE RADICALS] that damage neuronal Krebs cycle enzymes, neuronal mitochondria, and neuronal structural elements such as the neurofibrils."

Every once and awhile you see courageous scientists going out on a limb.  What do I mean?  Only that when it comes to BIG PHARMA or corporate America, bucking the system is not going to get you promoted or given a raise.  In fact, odds are it will first earn you a pink slip and then get you blackballed to the point that you will be lucky to ever work again at a mainstream research institution or major university.  The best example I can think of off the top of my head is DR. HUGH FUDENBERG --- the renowned immunogeneticist who connected the dots between FLU SHOTS and ALZHEIMER'S back in the early 70's and was promptly excommunicated.  This despite his authoring well over 750 studies since the 1950's.  The Boulevard of Broken Dreams is lined with many others (HERE and HERE are a couple).  Still the message continues to get out.

In March of 2016, the journal Environmental International carried a study (Environmental Factors in the Development of Autism Spectrum Disorders) which concluded, "Autism spectrum disorders (ASD) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior and repetitive movements. Social interaction impairments are the most characteristic deficits in ASD. There is also evidence of impoverished language and empathy, a profound inability to use standard nonverbal behaviors (eye contact, affective expression) to regulate social interactions with others, difficulties in showing empathy, failure to share enjoyment, interests and achievements with others, and a lack of social and emotional reciprocity. Genetic research involving twins and family studies strongly supports a significant contribution of environmental factors in addition to genetic factors in ASD etiology. A comprehensive literature search has implicated several environmental factors associated with the development of ASD. These include pesticides, phthalates, polychlorinated biphenyls, solvents, air pollutants, fragrances, glyphosate and heavy metals, especially aluminum used in vaccines as adjuvant. Importantly, the majority of these toxicants are some of the most common ingredients in cosmetics and herbicides to which almost all of us are regularly exposed to in the form of fragrances, face makeup, cologne, air fresheners, food flavors, detergents, insecticides and herbicides."  If you are not sure what an "ADJUVANT" is, get up to speed if you value the health and mental acuity of your unborn children or grandchildren. 

Remember when I told you I would get back to Dr. S?  As crazy as it may have sounded before you read today's post, Dr. Seneff's STATEMENT FROM JUST TWO DAYS AGO --- that she believes that half of all children born after 2025 will develop Autism --- is scarier than it seems on the surface.  While I'm not convinced we will hit that mark (1 in 2) --- at least not by 2025 --- the current trends are shocking, with the most recent stats saying that just over 1 in 30 American children have Autism right now (HERE).  When I started practice the numbers were something like one in a thousand.  Just a few years before that they were 1 in 10,000 (HERE).  Whatever you believe to be true about Autism, make sure to READ THIS to see why a Paleo Diet (or similar) has the potential to be the cornerstone of your recovery.  And for those that might already have other types of neurological or inflammatory diseases, you might find THIS interesting.

Most of us think of our body's fat incorrectly.  While we hate the way it looks, we know next to nothing about what it really does or how it works.  Without going into detail concerning other physiological functions of the fatty tissue known in the scientific community as "adipose," I want to discuss in more detail a subject that I BRIEFLY TOUCHED ON the other day --- the fact that your body's fat deposits function as an endocrine organ.   For the record, your ENDOCRINE SYSTEM is the part of your body that makes hormones, including THYROID, ADRENAL GLANDS, THYMUS, Pancreas (both INSULIN & GLUCAGON), PITUITARY, and sex hormones (be aware that ovaries and testes make both TESTOSTERONE and ESTROGEN).

If you cruise on over to PubMed and type in the words, "Adipose Tissue as an Endocrine Organ," you'll find hundreds of studies bearing that exact name or similar.  For instance, you'll learn that when it comes to this topic.....

• THIS IS NOT NEW INFORMATION:  Fifteen years ago, a 2002 study from Clinical Endocrinology and Metabolism (Adipose Tissue as an Endocrine Organ) stated simply that, "Adipose tissue is a highly active endocrine organ secreting a range of soluble products with both local and distant actions. These hormones have important roles in metabolism, reproduction, cardiovascular function and immunity."  Please be aware that any time you see the word "immunity" or variations thereof associated with adipose tissue, it is likely talking about its relationship to the chemicals / compounds we refer to collectively as INFLAMMATION. 

 

• ADIPOSE TISSUE IS PART OF YOUR IMMUNE SYSTEM:  In March of 2015, the journal Obesity (Adipose Tissue as an Immunological Organ) dealt with this issue.  "This review will focus on the immunological aspects of adipose tissue and its potential role in development of chronic inflammation that instigates obesity-associated co-morbidities.  Adipose tissue is a large immunologically active organ during obesity that displays hallmarks of both and innate and adaptive immune response.  The adipose tissue of obese subjects becomes inflamed and contributes to the development of insulin resistance, type 2 diabetes and metabolic syndrome. Numerous immune cells including B cells, T cells, macrophages and neutrophils have been identified in adipose tissue, and obesity influences both the quantity and the nature of immune cell subtypes which emerges as an active immunological organ capable of modifying whole body metabolism through paracrine and endocrine mechanisms.  Overwhelming evidence suggests that prolonged adipose tissue remodeling in response to caloric excess leads to chronic inflammation at the expense of reduced insulin-sensitivity."  You get the point.  Adipose tissue is seriously inflammatory.  The biggest group of these inflammatory markers are collectively referred to as "adipokines".

 

• ADIPOKINES ARE CELLULAR CYTOKINES (MESSENGERS) THAT COME FROM FAT CELLS: In 2010, July's Molecular and Cellular Endocrinology (The Development and Endocrine Functions of Adipose Tissue) concluded, "Classically known for storing the body's fuel reserves, adipose tissue is now recognized as an endocrine organ. As such, the secretions from adipose tissue are known to affect several systems such as the vascular and immune systems and play major roles in metabolism. Numerous studies have shown nutrient or hormonal manipulations can greatly influence adipose tissue development. In addition, the associations between various disease states, such as insulin resistance and cardiovascular disease, and disregulation of adipose tissue seen in epidemiological and intervention studies are great. Evaluation of known adipokines suggests these factors secreted from adipose tissue play roles in several pathologies."  The previous link talks a bit about cytokines.   As you might suspect, adipokines are the cytokines that come from adipose tissue.

A brief note about cytokines.  Cytokines are small proteins secreted and released by cells or tissues to have specific effects on the interactions and communications with other cells or tissues --- sometimes quite distantly.  Ten years ago, an issue of International Anesthesiology Clinics (Cytokines, Inflammation and Pain) concluded that, "There is significant evidence showing that certain cytokines/chemokines are involved in not only the initiation but also the persistence of pathologic pain by directly activating nociceptive sensory neurons. Certain inflammatory cytokines are also involved in nerve-injury/inflammation-induced central sensitization, and are related to the development of contralateral hyperalgesia/allodynia."  The two cytokines most associated with ALLODYNIA / HYPERALGESIA (sometimes called hyperalgia) as well as CENTRAL SENSITIZATION are also two of the most common --- the two that will come up repeatedly today ---- Interleukin six (IL-6) and Tumor Necrosis Factor Alpha (TNF-α).  The study went on to talk about the way these particular cytokines trigger GLIAL CELLS and MICROGLIA. 

• ADIPOSE IS INFLAMMATORY:   Although you've been given a taste of this, I could literally have put dozens upon dozens of studies under this bullet point.  A Spanish study from a 2016 issue of Molecular and Cellular Endocrinology (Role of Bioactive Lipid Mediators in Obese Adipose Tissue Inflammation and Endocrine Dysfunction) said, "Special emphasis is given to polyunsaturated fatty acids of the omega-6 and omega-3 families and their conversion to bioactive lipid mediators through the cyclooxygenase and lipoxygenase pathways. The participation of omega-3-derived lipid autacoids in the resolution of adipose tissue inflammation... is also thoroughly discussed."  What this means is that the fats that you consume are creating mediators (adipokines) that are either driving your body toward inflammation and pathology or away from inflammation and pathology (HERE).  Speaking of pathology...

 

• ADIPOKINES ASSOCIATED WITH PATHOLOGY:  Although we see it in most of these bullets, the German journal Internist spelled it out in 2014 study called --- you guessed it ---- Adipose Tissue as an Endocrine Organ.  The authors stated, "With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines) changes towards a proinflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity and chronic inflammation......"  Remember this; LOCAL INFLAMMATION is a critical part of any healing process.  However, SYSTEMIC INFLAMMATION always creates pathological healing processes, namely because inflammation always leads to fibrosis (scar tissue) --- HERE.   This is a big deal because fibrosis is the leading cause of death here in America (HERE).

 

• ADIPOKINES ARE RELATED TO CANCER:  The journal Hormone Molecular Biology and Clinical Investigation devoted their July, 2015 issue to the subject of CANCER as it relates to adipose tissue, publishing some freaky studies on BREAST CANCER among others.  One of these studies ---- Adipose Tissue, Obesity and Adipokines: Role in Cancer Promotion ---- concluded that, "Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term "adiposopathy" is used to describe this promotion of pathogenic adipocytes and associated adipose-related disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipokines and cancer risk.  Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis."  I have talked about this via several posts in two different forms --- the first being the most obvious in relationship to this study (HERE), but the second (HERE) being the most important.

 

• ADIPOSE REGULATES GROWTH, PUBERTY, & METABOLISM:  A study from the 1999 issue of the Soviet journal Biochemistry (Adipose Tissue as an Endocrine Organ Regulating Growth, Puberty, and other Physiological Functions), published a study on adipokines, most of which pertained to the adipokine Leptin as related to the study's title.    Last December, the Journal of Endocrinology published a fantastic overview of today's topic called Adipose Tissue in Control of Metabolism.  In it they concluded, "Adipose tissue plays a central role in regulating whole-body energy and glucose homeostasis through its subtle functions at both organ and systemic levels. On one hand, adipose tissue stores energy in the form of lipid and controls the lipid mobilization and distribution in the body. On the other hand, adipose tissue acts as an endocrine organ and produces numerous bioactive factors such as adipokines that communicate with other organs and modulate a range of metabolic pathways. Therefore, adipose tissue dysfunction plays a prominent role in the development of obesity and its related disorders such as insulin resistance, cardiovascular disease, diabetes, depression and cancer. In this review, we will summarize the recent findings of adipose tissue in the control of metabolism, focusing on its endocrine and thermogenic function. An enormous amount of evidence has demonstrated that impaired biosynthesis, assembly, secretion and signalling transduction of adipokines are associated with the development of obesity and its related disorders." Think about it folks; this was a 20th century study.

 

• NOT ALL FAT IS THE SAME:  The June 2006 issue of Diabetes (Adipose Tissue: From Lipid Storage Compartment to Endocrine Organ) revealed that, "Our understanding of how cellular events in the adipocyte affect the local environment and how systemic effects are achieved through endocrine interactions is rudimentary. While storage and release of lipids are major functions of adipocytes, the adipocyte also uses specific lipid molecules for intracellular signaling and uses a host of protein factors to communicate with essentially every organ system in the body. The intensity and complexity of these signals are highly regulated, differ in each fat pad, and are dramatically affected by various disease states."  What I really want you to notice here is that different fat pads (the fat found in different parts of your body) are very different from each other.  For instance, BELLY FAT is going to be quite different metabolically than the fat on the bottoms of your feet.

 

• MALE ADIPOSE IS DIFFERENT THAN FEMALE ADIPOSE:  Last month's issue of Redox Biology published a study whose title tells the whole story --- Sex Matters: The Effects of Biological Sex on Adipose Tissue Biology  and Energy Metabolism --- in which the authors concluded, "Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions.  In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders." And on a similar note.....

 

• ADIPOSE AND REPRODUCTIVE FUNCTION, ESTROGEN, TESTOSTERONE:  A 2010 issue of Fertility and Sterility (Adipose Tissue and Reproduction in Women) showed us that it's not just the fat itself that affects reproduction (for instance, women won't get pregnant if they fall below a certain percentage of body fat) but it's distribution (where it's found). In other words, too much adipose in general can lead to problems, but Belly Fat can be a deal-breaker for any number of physiological processes and HOMEOSTASIS. "Adipose tissue is a key endocrine organ involved in multiple processes, including glucose homeostasis, steroid production, immunoregulation, hematopoesis, and reproduction. The distribution of adipose tissue may also have a significant impact on reproductive function."  Beyond this, I've shown you how Belly Fat affects both estrogen and testosterone and vice versa (HERE and HERE) in ways that can be worse than freaky.

 

• ADIPOSE TISSUE ALLOWS ORGANS TO COMMUNICATE WITH EACH OTHER: Oxford's journal Acta Physiologica (Adipose Tissue and its Role in Organ Crosstalk) gave us a basic yet informative abstract.  "Adipose tissue is a true endocrine organ that produces and secretes a wide range of mediators regulating adipose tissue function and important distant targets, such as the liver, skeletal muscle, the pancreas and the cardiovascular system. In metabolic disorders such as obesity, enlargement of adipocytes leads to adipose tissue dysfunction and a shift in the secretory profile with an increased release of pro-inflammatory adipokines."  BTW, there were tons of studies on this topic --- especially concerning the way that the heart and cardiovascular system are affected by adipokines (usually adversely).       

              

• ADIPOSE COMMUNICATES WITH YOUR CNS:  The March 2016 issue of the Journal of Neuroinflammation took this idea a bit further in a study called Secret Talk between Adipose Tissue and Central Nervous System via secreted factors—an emerging frontier in the neurodegenerative research.  "Adipokines are Not only Produced by the white adipose tissue but can also be expressed in the central nervous system [brain & cord] where receptors for these factors are present. When produced in periphery and to affect the CNS, these factors may either cross the blood brain barrier (BBB) or modify the BBB physiology by acting on cells forming the BBB. Adipokines could regulate neuroinflammation and oxidative stress which are two major physiological processes involved in neurodegeneration and are associated with many chronic neurodegenerative diseases."  The authors even went on to talk about LEAKY BRAIN SYNDROME --- a topic I have discussed at length that is on some level, related to LEAKY GUT SYNDROME.  "For instance, studies established positive correlations between mid-life adiposity in women with disruption of BBB integrity, showing that overweight/obesity could favor the onset of vascular disorders increasing BBB permeability later in life. In the same line of evidence, rats fed with Western diet, known for promoting diabetes and obesity, display a leakier BBB due to the decreased expression of tight junctions."  If you want to see some of the science behind today's subject, simply take a look at this free study.  Amazing proof that what you eat matters (even though your doctor is probably NOT WARNING YOU).

 

• ADIPOSE COMMUNICATES WITH YOUR HPA-AXIS:  This study is so important, I am going to leave you with just a single sentence of the abstract.  In similar fashion to the post I did last week where we learned that adipose tissue generates significant amounts of estrogen (a definite factor in ESTROGEN DOMINANCE and HORMONE DISRUPTION), we now see that adipose manufactures the stress hormone CORTISOL as well.  The February 2014 issue of Hormone Molecular Biology and Clinical Investigation (Cross-Talk Between Adipose Tissue and the HPA Axis in Obesity and Overt Hypercortisolemic) stated that, "adipose tissue is also able to generate cortisol from cortisone." In other words, not only can your hormones make you fat, but fat itself creates some of these very hormones.  Talk about a vicious cycle!

 

• ADIPOSE AND LACK OF TISSUE OXYGENATION:  Lack of OXYGEN ("hypoxia") is common in adipose tissue as confirmed up by dozens of studies.  Here are a couple.  A 2008 issue of the British Journal of Nutrition (Hypoxia in Adipose Tissue: A Basis for the Dysregulation of Tissue Function in Obesity?) stated, "Hypoxia has now been directly demonstrated in adipose tissue of several obese mouse models.  Cell-culture studies on murine and human adipocytes show that hypoxia (induced by low O2 or chemically) leads to stimulation of the expression and secretion of a number of inflammation-related adipokines, including angiopoietin-like protein 4, IL-6, leptin, macrophage migration inhibitory factor... It is suggested that hypoxia has a pervasive effect on adipocyte metabolism and on overall adipose tissue function, underpinning the inflammatory response in the tissue in obesity and the subsequent development of obesity-associated diseases."  Five years later, a 2013 copy of Physiological Reviews (Hypoxia and Adipose Tissue Function and Dysfunction in Obesity) concluded that, "There is substantial evidence that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in Po(2) is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of  over 1,000 genes [this is a prime example of EPIGENETICS]. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity."  How do you prevent hypoxia?  Don't SMOKE, maintain a normal weight, and exercise (breathe hard) regularly.
  

As you can see, carrying around too much fat --- especially in the midsection --- has the potential to open Pandora's Box, releasing the adipokines, inflammation, and subsequent fibrosis related to numerous disease processes --- but don't be afraid of eating fat (HERE).  If you follow some of the links on this page (especially hormonal and endocrine disruptor stuff), you can see why losing weight for some of you has been nigh impossible.  To be successful you'll have to address this problem from many angles. The super cool thing is that the underpinning of most of these angles is the same thing.  HERE is is, free of charge to you.  Oh, and if you appreciate the effort that goes into creating free information that has the power to be transformational, share it on FACEBOOK with those you love and care about most.

For more than three decades, the peer-reviewed scientific literature has said that most tendinopathies (TENDINOSIS included) are not inflammatory --- in other words, when the tendons were biopsied, there were no inflammatory cells present.   I reported this but always said that even though these tendinopathies might not contain inflammation, inflammation undoubtedly helps drive the process.  It seems the science is changing in this area and that tendinosis is inflammatory after all.   What's the evidence for this assertion and what difference does it make as far as your issues are concerned? Follow along.

• Last year's book, Metabolic Influences on Risks for Tendon Disorders, carried a chapter called Inflammation in Tendon Disorders which described the criteria for inflammation to be an issue in tendon disorders.  "The role of inflammation in tendon disorders has long been a subject of considerable debate. Developments in our understanding of the basic science of inflammation have provided further insight into its potential role in specific forms of tendon disease, and the circumstances that may potentiate this. Such circumstances include excessive mechanical stresses on tendon and the presence of systemic inflammation associated with chronic diseases."  The last half of the last sentence is paramount.  Not sure what SYSTEMIC INFLAMMATION is or what causes it?  Just click the link. Remember this concept because we will briefly revisit it at the end of the post.

 

• Remember the famous tendon researcher and orthopedic surgeon Dr. GA Murrell that I have quoted many times (see "tendinosis" link above)?  Here is one of his more recent studies.  This January's issue of the journal Nature Reviews: Rheumatology (Inflammatory Mechanisms in Tendinopathy – Towards Translation) concluded, "These disorders are common, account for a high proportion (30%) of referrals to musculoskeletal practitioners, and confer a large socioeconomic burden of disease.  The advent of modern molecular techniques has highlighted the presence of immune cells and inflammatory mechanisms throughout the spectrum of tendinopathy in both animal and human models of disease. Key inflammatory mediators — such as cytokines, nitric oxide, prostaglandins and lipoxins — play crucial parts in modulating changes in the extracellular matrix within tendinopathy."  In other words, the ECM is "scarred" and there are inflammatory markers in the tendons.   Thanks to METABOLOMICS we can now see this. 

 

• April's issue of the inflammation journal Cytokine (The Influence of Chronic IL-6 Exposure, in Vivo, on Rat Achilles Tendon Extracellular Matrix) simply stated in its abstract that, "Elevated levels of IL-6 are associated with tendinopathy."  IL-6 (interleukin six) is probably the most common and well known of the numerous biomarkers of inflammation.

 

• March's Frontier in Aging Neuroscience (Commentary: Role of VEGF, Nitric Oxide, and Sympathetic Neurotransmitters in the Pathogenesis of Tendinopathy: A Review of the Current Evidences) provided a comment by a researcher, arguing by listing numerous other studies, that yes, tendinosis is indeed inflammatory.

 

• March's issue of PLoS One (The Effects of Substance P and Acetylcholine on Human Tenocyte Proliferation Converge Mechanistically Via TGF-β1) showed how certain inflammatory mediators caused a thickening of the tendons via "proliferation" of the cells that make tendon material (tenocytes).  While a degree of this is needed, when the process gets out of kilter the tendons get too thick, which makes them less functional and weaker.

 

• Last July's issue of Scientific Reports (A Possible Link Between Loading, Inflammation and Healing: Immune Cell Populations During Tendon Healing....) revealed that the link discussed in the study's title is present. "Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected....  Mechanical loading has a profound influence on tendon healing. Reduced loading has been shown in numerous models to impair healing.  Recently, we have noticed that anti-inflammatory drugs impair tendon healing mainly by impairing the response to loading or microdamage, and also that the expression of inflammation-related genes was involved. This points to a possible connection between loading, inflammation and healing.  By analyzing the cell populations from healing tissue by flow cytometry with markers for several inflammatory and regulatory cell types, we can describe the composition of the population and use it as an “inflammatory signature”. Changes in the signature over time can then show how the inflammatory reaction is influenced under varying conditions."  BTW, the idea that anti-inflammation drugs impair healing is not new and will be discussed at the end of the post.
  

 

• The term "apoptosis" refers to a cell's propensity to die in a pre-programed fashion, and is controlled by a part of the immune system known as the TH-17 SYSTEM, which, by the way, is heavily associated with AUTOIMMUNE DISEASES.  In fact, the Polish journal Archivum Immunologiae et Therapiae Experimentalis (The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases) concluded that, "The identification of the new subpopulation of T helper cells producing IL-17 modified our model of the Th1–Th2 paradigm and it was named Th17. High abilities to stimulate acute and chronic inflammation made these cells an ideal candidate to be the crucial player in the development of autoimmune disorders."  Last June's issue of Scientific Reports (IL-17A Mediates Inflammatory and Tissue Remodeling Events in Early Human Tendinopathy) talked about the heavy-hitters of the inflammatory modulator community, saying that, "Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy.  Endogenous expression of TNFα, IL-1β, IL-6, IL-10, VEGF and TGFβ has been demonstrated in tenocytes.  Increased expression of IL-17A was detected in ‘early tendinopathy’ compared to both matched samples and non-matched control samples. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines, altered matrix regulation with increased Collagen type III, and increased expression of several apoptosis related factors."  I have said forever that Systemic Tendinosis, which we will discuss shortly, is almost always autoimmune ---even though it does not have an official name because the specific auto-antigen remains unknown.
  

 

• As I have shown you many times, inflammation always leads to fibrosis --- the medical word for Scar Tissue (HERE).  Thus, when last November's issue of Arthritis Research and Therapy (Profibrotic Mediators in Tendon Disease: A Systematic Review) started talking about fibrosis in tendinopathies, I was interested.  Their conclusions; "Tendon disease is characterized by the development of fibrosis," were not surprising as we were already aware of this.  The fact that the authors linked any number of inflammatory mediators to the process was, however, interesting.  Especially considering that for decades this was believed not to be the case.  Be aware that the progression of virtually all disease, tendinopathies included, is Inflammation, Fibrosis, Degeneration (REPEAT).
  

Again, the questions we'll answer at the end of the post; does it matter, and what can we do about this other than simply prescribe more drugs to MOP UP the inflammation rather than shutting off the Systemic Inflammation at its source?

Further evidence that inflammation is involved in tendinopathies comes in the form of just how many studies are talking not only about inflammatory markers, but about the numerous inflammatory comorbidites (concurrent diseases caused by inflammation --- HERE is a list of some of them) that are commonly found in folks struggling with tendinosis.  In other words, if you are fighting tendinosis, your chances of having some serious health issues, CANCER INCLUDED, go up dramatically.

• SHOULDER ARTHRITIS AND TENDINOSIS:  The suffix "itis" lets you know that something is inflammatory as it is the Latin term for inflammation.  A recent study from PLoS One (TREM-1, HMGB1 and RAGE in the Shoulder Tendon: Dual Mechanisms for Inflammation Based on the Coincidence of Glenohumeral Arthritis) revealed that, "Rotator cuff injury is a major disorder in the adult population where inflammation and pain are contributing factors. Coincidence of other clinical conditions like glenohumeral arthritis aggravates inflammation and delays the healing response.  The principal findings in this study reveal significant expression of TREM-1, RAGE and HMGB1 in the shoulder tendon tissue with respect to severity of glenohumeral arthritis."  As you might suspect, these substances are yet other inflammatory biomarkers / mediators that we have not discussed previously.

 

• DIABETES AND TENDINOSIS:  March's issue of Scientific Reports stated that, "People with diabetes are susceptible to tendinopathy and tendon rupture. Diabetic tendons are characterized by weaker mechanical properties than non-diabetic tendons, including lower stiffness, maximum load, Young’s modulus, and strain at break point. Tendons are mainly composed of highly organized collagen fibers as well as various minor structural molecules, such as proteoglycans and glycoproteins. In tendons, tenocyte is the fundamental cell population responsible for maintaining tissue homeostasis, and loss of its genetic traits can cause tendon dysfunction."  The same month the cancer journal Oncotarget concluded, "Patients with diabetes are at great risk to suffer many musculoskeletal disorders, such as tendinopathy, tendon rupture and impaired tendon healing.  In this study, we found that high glucose could inhibit cell proliferation and induce cell apoptosis of TDSCs (tendon-derived stem cells) in vitro. The tenogenic differentiation ability of TDSCs was decreased in the initial stage in vitro. All these findings proved our hypothesis and accounted for the potential pathogenesis of diabetic tendon disorders including diabetic tendinopathy, tendon rupture and impaired tendon healing." By the way, most of this is not really new information.

 

• NEUROPATHY AND TENDINOSIS:  While certainly not the only reason for neuropathic pain, DIABETES is by far the most common.  February's British Journal of Pain concluded that, "This study suggests that neuropathic pain as identified by the painDETECT questionnaire may be common in patients with chronic lower limb tendinopathy conditions.  28% of respondents scored 19 or higher with painDETECT (neuropathic component to pain likely), 29% scored 13-18 (equivocal result)." 

 

• HEART DISEASE AND TENDINOPATHY:   February's issue of the Journal of Occupational and Environmental Medicine (Association Between Cardiovascular Disease Risk Factors and Rotator Cuff Tendinopathy: A Cross-Sectional Study) revealed that, "Recent evidence has found potential associations between cardiovascular disease (CVD) risk factors and common musculoskeletal disorders.  A strong association was observed between CVD risk scores and both glenohumeral joint pain and rotator cuff tendinopathy. The results show a dose-response trend of increasing risk.  Individual risk factors were associated with both outcomes. Combined, CVD risk factors demonstrated a strong correlation with glenohumeral joint pain and an even stronger correlation with rotator cuff tendinopathy. Results suggest a potentially modifiable disease mechanism."  I've talked about this particular link before HERE).

 

• DYSBIOSIS AND/OR INFECTIONS CAUSE TENDON RUPTURE?  We know that virtually all forms of DYSBIOSIS and INFECTION are inflammatory.  March's copy of The American Journal of Sports Medicine (Presence of Bacteria in Spontaneous Achilles Tendon Ruptures) showed that, "The structural pathology of Achilles tendon (AT) ruptures resembles tendinopathy.  Recently, a number of diseases were found to be attributed to bacterial infections, resulting in low-grade inflammation and progressive matrix disturbance [fibrosis / scar tissue].  AT rupture samples exhibited histopathological features characteristic of tendinopathy, and most healthy hamstring tendon samples displayed normal tendon features.  The authors have demonstrated the presence of bacterial DNA in ruptured AT samples."  You need to be aware that not only is sugar one of the most inflammatory things you can consume (HERE), but that it actually feeds both dysbiosis and infection (HERE).
  

 

• OBESITY AND TENDINOSIS:  What do we know about OBESITY?  Only that it is one of the chief of the myriad of inflammatory conditions.  One of last year's copies of Advances in Experimental Medicine and Biology (How Obesity Affects Tendons?) had this to say on the subject.  "Several epidemiological and clinical observations have definitely demonstrated that obesity has harmful effects on tendons."  Notice, however, that this is not simply a "weight" issue. "In addition to overload, attributable to the increased body weight, which significantly affects load-bearing tendons, systemic factors play a relevant role. Several bioactive peptides (chemerin, leptin, adiponectin and others) are released by adipocytes, and influence tendon structure by means of negative activities on mesenchymal cells."  This is very similar to what we saw in THIS POST where I showed you how adipose tissue becomes it's own endocrine gland. "The ensuing systemic state of chronic, sub-clinicical, low-grade inflammation can damage tendon structure. Metabolic disorders (diabetes, impaired glucose tolerance, and dislipidemia), frequently associated with visceral adiposity [BELLY FAT], are concurrent pathogenetic factors. Indeed, high glucose levels increase the formation of Advanced Glycation End-products, which in turn form stable covalent cross-links within collagen fibers, modifying their structure and functionality."  We are warned all the time about AGES from grilled foods, when the biggest form of AGES comes from inflammatory sugar.
  

Here are a few of the tidbits gleaned from recent peer-review (mainstream journals, one and all), showing what's being studied and contemplated as far as solving tendon issues are concerned.

• PRP IS A MICROBIOME THING:  There are lots of studies on PRP INJECTIONS for tendinosis, some saying it works, just as many saying not so much.  Interestingly, a new study from March's issue of Acta Orthopedica (Effect of Platelet-Rich Plasma on Rat Achilles Tendon Healing is Related to Microbiota) concluded --- as might be imagined from the study's title --- that, "In 3 papers in Acta Orthopaedica 10 years ago, we described that platelet-rich plasma (PRP) improves tendon healing in a rat Achilles transection model. Later, we found that microtrauma has similar effects, probably acting via inflammation."  This is exactly why potentially "HARSH" methods such as TISSUE REMODELING have merit, and why GUT HEALTH is so blamed critical to truly solve your issue.  BTW, the authors concluded that rats with Staph (not an active infection but as part of their normal MICROBIOME) actually healed better than those without.

• LOW LEVEL LASER THERAPY IS HELPFUL FOR TENDINOSIS: This month's issue of the Dutch / German journal Zeitschrift für Rheumatologie (Low Level Laser Therapy : A Narrative Literature Review on the Efficacy in the Treatment of Rheumatic Orthopaedic Conditions) concluded that, "While earlier studies often failed to demonstrate the efficacy of LLLT, several recent studies of increasing quality proved the efficacy of LLLT in the treatment of multiple musculoskeletal pain syndromes like neck or lower back pain, tendinopathies (especially of the Achilles tendon) and epicondylolpathies, chronic inflammatory joint disorders like rheumatoid arthritis or chronic degenerative osteoarthritis of the large and small joints. In addition, there is recent evidence that LLLT can have a preventive capacity and can enhance muscle strength and accelerate muscle regeneration.  LLLT shows potential as an effective, noninvasive, safe and cost-efficient means to treat and prevent a variety of acute and chronic musculoskeletal conditions."  Interested in my LOW LEVEL LASER THERAPY posts?  Just click the link.

• TREATING TENDINOPATHIES WITH SUPPLEMENTS:  A group of six Italian orthopedists published a study in a 2016 copy of Muscles, Ligaments, and Tendons called Nutraceutical Supplement in the Management of Tendinopathies: A Systematic Review, in which they looked at 46 studies concerning the popular joint supplements glucosamine and chondroitin sulphate, vitamin C, hydrolazed type 1 collagen, arginine alpha-keto-glutarate, bromelain, curcumin, boswellic acid, and methil-sulfonil-methane.  The authors concluded that, "In the last years, the increase of sport activities, life expectancy, and other factors such as environment, diet, systemic diseases and some drug therapies have led to a rise in the incidence of tendinopathies.  Nutraceuticals are not only used in the general population, but also in athletes.  Preclinical results are very encouraging..."  As noted in this paper, certain drugs (THESE ANTIBIOTICS ARE THE MOST DANGEROUS AND BRUTAL) actually cause inflammation.  And once again we see that Systemic Inflammation / Systemic Disease is a big deal.

 

• INJECTING TENDONS WITH VARIOUS HORMONES CAUSES?  There are tons of studies on DRY NEEDLING techniques, with most of them showing promise for tendinopathies and similar musculoskeletal issues.  A study from the February issue of Muscles, Ligaments, and Tendons (Therapeutic Use of Hormones on Tendinopathies: A Narrative Review) looked at the efficacy of injecting various hormones (ESTROGEN, TESTOSTERONE, THYROID, etc, etc) directly into tendons.  Conclusions?  "At present, experimental studies and preliminary observations in humans suggest that parathyroid and growth hormones, locally administered, are promising therapeutic tools in specific tendon disorders. Local injections of glucocorticoids are useful in several tendinopathies, exploiting their anti-inflammatory and anti-proliferative properties, but carry the risk of further tendon degeneration and ruptures, due to the detrimental direct effect of glucocorticoids on the tendon structure."  Speaking of glucocorticoid (corticosteriods and cortisone) risks...........

We've repeatedly seen that tendinopathy accounts for about 1/3 of the visits to the doctor's office in people going in with musculoskeletal issues.  And while there are a few cutting-edge doctors and clinics out there that are using these and other not-quite-mainstream treatment methods, the standard medical fare for tendinosis is still anti-inflammation medication ---- CORTICOSTEROIDS and NSAIDS.  I have shown you study after study and textbook after MEDICAL TEXTBOOK that say in various ways just how bad these drugs are as far as fouling the healing process is concerned.  Here are a couple more (I could have given you dozens, if not hundreds).

• NSAIDS EFFECTS ON TENDON HEALING:  Two medical doctors (one a Ph.D as well) wrote a well-bibbed article (48 sources) for Rhematology Network called Do NSAIDs Impair Healing of Musculoskeletal Injuries? "NSAIDs are among the most frequently used and prescribed medications in the management of musculoskeletal pain and injury. Many physicians consider them to be the medication of choice.  However, a number of studies have questioned the value of NSAIDs in the healing process of bone, muscle, tendon, and ligament injuries. Studies have demonstrated that prostaglandins and leukotrienes are produced during the acute phase of a tendon injury... In the first few days after acute tendon injury, there is an initial inflammatory phase and entry of inflammatory cells into the injury site.  There appears to be little role for NSAIDs outside of the initial symptomatic pain relief during the first few days after injury."  This is an interesting paper because while actually acknowledging PGE2, LEKOTRIENES, and other inflammatory mediators, the authors are not high on the long-term effects of blocking these mediators we refer to as "inflammation".
  

 

• INJECTING TENDONS / JOINTS WITH STEROIDS: Listen folks; I've only shown you about a hundred times how bad this stuff is over the long haul.  Here's one more for those who may have missed the rest.  December's Expert Opinion on Drug Safety (Clinical Benefits and Drawbacks of Local Corticosteroid Injections in Tendinopathies) showed us yet again that the short-term relief sometimes provided by corticosteroids is not worth the long term grief.  "Local glucocorticoids injections are widely administered for the treatment of tendinopathies. positive results have been observed in some tendinopathies but not in others. moreover, worsening of symptoms, and even spontaneous tendon ruptures has been reported. Several experimental studies suggest that the direct action of glucocorticoids on tendons is detrimental. Loss of collagen organization, impaired viability of fibroblasts, depletion of stem cells pool, and reduced mechanical properties have been observed."   How about boosting COLLAGEN production and FIBROBLASTIC ACTIVITY instead of suppressing it!  This bullet helps explain why I've repeatedly argued that that IMMUNE SYSTEM SUPPRESSION is America's number one form of medical treatment.
  

Have you ever been so far behind you thought you were in the lead?  For decades, the research side of the medical community told us that TENDINOSIS is not an inflammatory condition --- it's purely mechanical (fibrosis).  Since most docs never got that memo --- continuing to treat with their usual array of drugs --- the fact that the science has changed yet again didn't affect them one iota.  But what does this information mean to you, the individual struggling with tendinosis, who does not want the drugs? 

It means that as I just showed you, the "alternatives" are every bit as effective as mainstream care (drugs, chiefly steroids and NSAIDS).  And while inflammation is certain a factor in tendinosis, addressing the inflammation (the "itis") without addressing the fibrotic changes (the "osis") is just as ineffective today as it was yesterday, last week, last year, or back in the 20th century.  Sure, I want you to deal with the inflammation.  What you have to remember, however, is that the local inflammation is a critical part of the healing process (HERE).  It's the SYSTEMIC INFLAMMATION that must be addressed, and unfortunately, you can't take care of this kind of inflammation with a pill, potion, or lotion.  Remember the last part of the last sentence of the very first bullet point of this post that I said I would come back to? Local inflammation is probably not your problem ---- it's the presence of systemic inflammation associated with chronic diseases that is making your tendon train go off the rails in so many different ways.

What you need to do is deal with underlying systemic inflammation like you would for any other inflammatory problem (HERE) --- after all, study after study (as I showed you again today) reveals just how inter-related these disease processes really are.  That's why they refer to these as "comorbidites" (Co = "along with or beside; concurrent" and Morbidity = "illness or sickness").  A failure to address the systemic inflammation means that you will probably be repeating the whole tendinopathy thing over and over again along with at least some of THESE DISEASES.  However, address the systemic inflammation successfully and you end up taking care of any number of "comorbidites".  HERE'S a really cool example of someone who addressed a handful at the same time.

As for treating tendinosis in my clinic, this information doesn't really change anything I'll be doing other than warning people about the relationship between diet / lifestyle and their chronic pain by handing out more copies of my CLINIC'S "ONLINE" WEB CHECKLIST.  In other words, it's not like this information completely snuck up on me --- I've been increasingly talking about the role of inflammation in tendinopathy for awhile now (HERE and HERE).  And for those of you struggling with SYSTEMIC TENDINOSIS (not the stuff caused by fluoroquinolone antibiotics such as Cipro), I have plenty of info for you as well.  Not surprisingly, I have always maintained that it's largely an autoimmune issue driven by --- you guessed it --- inflammation.  And truthfully, if you swapped out the word FASCIA for tendon in this post, it would probably all still be true.

I had an individual in the office on Friday who had experienced a phenomenon I've seen any number of times previously.  Her frustration was palpable because despite the fact she'd recently lost 60lbs through a combination of ending her HIGH CARB LIFESTYLE and taking up EXERCISE, she'd been repeatedly SKINNY SHAMED.  Today I want to show you why her recent weight loss is going to help her tremendously --- and could help you as well --- as far as long-term HORMONAL HEALTH is concerned.

Although I've become a huge advocate of the PALEO DIET or similar (there are lots of similar), the reasons are simple --- it totally controls blood sugar, while limiting the amount of chemicals and toxins in the body (HERE).  Why is controlling BLOOD SUGAR critically important if you want any hope of being truly healthy?  Because as I've shown you many times, virtually every disease that we could list that is not 100% genetic, has origins in blood sugar (HERE and HERE are great examples).  Allow me to show you, via peer-review, how our collective SUGAR / CARB ADDICTIONS are leading us down a path to destruction as far as our sexual / hormonal health is concerned.

Historically, women have always had the tendency to put weight on their hips and rear end.  On some level, this is exactly how things are supposed to be --- it's how they're made.  And while men put weight on around the midsection (the old "spare tire"), thanks to copious amounts of carbs and sugar, this is exactly what's now being seen in the female population.   BELLY FAT in both sexes has become the new norm.  What does this do?  It creates "Sugar Daddies" and "Sugar Mamas".

As is always the case, health problems tend to start with INFLAMMATION.  In case you were not aware, OBESITY falls into this category of diseases, same as CANCER, heart disease, diabetes, arthritis, and a slew of others.  Also remember that sugar and junk carbs are one of the single most inflammatory things you can consume (HERE).  What does this do to men?  According to any number of studies, Low T, belly fat, and the METABOLIC SYNDROME are so interlinked, they cannot really be separated from each other.

Have you ever heard of SKINNY FAT (sometimes referred to as MONW)?  In a study from a 2013 issue of PLoS One (Prediabetes Is Associated with an Increased Risk of Testosterone Deficiency, Independent of Obesity and Metabolic Syndrome), eight Taiwanese physicians and researchers concluded that, "current evidence suggests that the causative relationship between testosterone deficiency and diabetes might be bidirectional, or even multidirectional and interrelated with obesity, metabolic syndrome, sex hormone-binding globulins (SHBG), and other factors."  In other words, whichever comes first is not so important since either one can cause the other.

A 2009 issue of the Argentinian journal, Arquivos Brasileiros de Endocrinologia & Metabologia (The Role of Testosterone in Type 2 Diabetes and Metabolic Syndrome in Men), concluded that, "Over the last three decades, it has become apparent that testosterone plays a significant role in glucose homeostasis and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol), and a pro-inflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus."  This is saying that not only is the person described here a heart attack / stroke looking for a place to happen, it's only a matter of time before things stop working in the bedroom.

Another 2009 study, this one from the Journal of Andrology (The Dark Side of Testosterone Deficiency: Metabolic Syndrome and Erectile Dysfunction) stated, "The metabolic syndrome is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia. Reduced androgen levels [testosterone and precursors] increase cardiovascular risk factors and produce marked adverse effects on cardiovascular function. Metabolic syndrome has been associated with erectile dysfunction, and may be considered a risk factor for erectile dysfunction."  Like I said, ED is probably the least of your worries once this vicious cycle starts spinning.

One of the things that DIABETES and blood sugar dysregulation does is foul up the body's ability to circulate blood --- one of the chief reasons (along with NEUROPATHY) that virtually all diabetics struggle with foot ulcers.  Be aware, however, that this lack of blood flow is not confined to feet, but affects the genitals as well.  Not surprisingly, ED is the result.  But it's actually much worse than initially appears as far as sugar turning men into women is concerned, and as you might suspect, it has to do with THE ENDOCRINE SYSTEM.

Did you realize that body fat (adipose tissue) --- particularly the belly fat packed around your internal organs --- has the potential to act as it's own estrogen-producing gland (HERE, HERE, or HERE)?  If you cruise on over to PubMed and search the term "Adipose Tissue as an Endocrine Organ," you'll find page after page after page of studies --- hundreds of them --- that have either this exact name or a similar variation.  Here's one from a 2013 issue of the kidney journal, Seminars in Nephrology (The Adipose Tissue as an Endocrine Organ), where the authors concluded that, "Since 1994, white adipose tissue was recognized as an endocrine organ and an important source of biologically active substances with local and/or systemic action called adipokines. Inappropriate secretion of several adipokines by the excessive amount of white adipose tissue seems to participate in the pathogenesis of obesity-related pathologic processes including endothelial dysfunction, inflammation, atherosclerosis, diabetes mellitus, and chronic kidney disease."  Hold on to your seats because here is where the train start to go off the rails.

Although there were about 2,500 studies in this specific topic, I'm going to leave you with just one --- a piece of research from last September's issue of Biochemistry and Molecular Biology Reports (Extra-Gonadal Sites of Estrogen Biosynthesis and Function)........

"Recent evidence indicates that estrogens play important roles in the immune system, cancer development, and other critical biological processes related to human well-being. Obviously, the gonads (ovary and testis) are the primary sites of estrogen synthesis, but estrogens synthesized in extra- gonadal sites play an equally important role in controlling biological activities......    Adipose tissues are considered to be the major source of circulating estrogen after the gonads in both men and women, and the contribution made by the adipose tissues to the total circulating estrogens increases with advancing age."

If you did not grasp the importance of this paragraph, read it until you do.  As you get older --- or fatter --- your fatty tissues are going to make more estrogen.  If everything were in perfect HOMEOSTASIS, this would be wonderful as your body fat takes the place of your post-menopausal ovaries.  The problem is that with ESTROGEN DOMINANCE already being a huge issue in both females and males here in America, we can begin to see how BELLY FAT (visceral adiposity) is affecting our population, setting up a vicious cycle of obesity and hormonal disruption.

And in case you were not aware, estrogen is the hormone given to commercially-raised livestock (beef & pork) in order to make them fat (peer-review frequently refers to commercially-raised animals --- particularly beef --- as "obese").  Estrogen is why the average woman carries about 10% more body fat than the average man.  While men certainly need a bit of estrogen to function normally, anything more than that is a problem --- a big problem.  Enter the Endocrine Disruptors and Aromatases (yes, they are affected by sugar because NAFLD (Non-Alcoholic Fatty Liver Disease), caused mostly by being overweight, dramatically affects your ability for your liver to clear excess hormones (HERE). 

I recently showed you how we are all being exposed to a vast array of XENOHORMONES (most of which are estrogen-based 'obesigens') and ENDOCRINE DISRUPTORS.  In case you think that this is no big deal, let me hit you with a study from the 2007 of a Spanish journal Revista de Investigacion Clinica (Endocrine Disruptor Compounds and their Role in the Developmental Programming of the Reproductive Axis).  This study showed that, "Different perturbations during fetal and postnatal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming." Endocrine disruptor compounds are widely spread in the environment and display estrogenic, anti-estrogenic or anti-androgenic [anti-testosterone] activity; they are stored for long periods in the adipose tissue. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of endocrine disrupting compounds into the environment affects both human health and ecosystems in general."  In other words, many of us --- maybe most of us, whether male or female --- are being doused in estrogen from conception to death, and unfortunately, the problems it's causing are "permanent".  And we wonder why our hormones are screwed up.

The commonest medical solution for men with Low T is giving them testosterone in various forms. While this sometimes helps for awhile, the results are usually short-lived.  This is because your body's stunted / altered feedback loops are not only not addressed by this method of therapy, it actually makes the situation worse. Why? It's common knowledge that when men take Anabolic Steroids, their own testicles, sensing that there is plenty of testosterone in their system, shut down production.   And this doesn't even begin to address the issue of STRESS.

When we get stressed,  (the stress can come in numerous forms including emotional, physical, and / or dietary --- ie JUNK FOOD and JUNK CARBS) we release the ADRENAL HORMONE, cortisol. Among other things, cortisol makes us fat (see previous link).  Bear in mind that it is impossible to solve adrenal issues without first addressing blood sugar.  And unfortunately, the hits keep coming.

If you have not heard of aromatase, you need to become informed.  According to Wikipedia, "Aromatase, also called estrogen synthetase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into estrogens. The aromatase enzyme can be found in many tissues, as well as in tissue of endometriosis, uterine fibroids, breast cancer, and endometrial cancer."  Since we have a P-450 ENZYME that among other things, turns testosterone into estrogen, it's critical that we figure out what upregulates it.

As might make sense, aromatase inhibitors are used by the medical community to block estrogen in women dealing with BREAST CANCER.  Interestingly enough, I found a number of studies from mainstream medical journals touting various anti-inflammatory HERBS, vitamins (C and D) or other compounds that act as inhibitors of estrogen as well.  For instance, just two years ago, the Asian Pacific Journal of Cancer Prevention (Inhibitory Aromatase Effects of Flavonoids from Ginkgo Biloba Extracts on Estrogen Biosynthesis) concluded that, "Our results support the usefulness of flavonoids in adjuvant therapy for breast cancer by reducing estrogen levels with reduced adverse effects."

As far as upregulating the aromatase enzyme, I found almost 10,000 studies on the subject.  And although there are slews of studies about biochemical compounds that I've frankly never heard of before, the big picture is fairly clear.  What do I mean by "Big Picture"?  A few years ago, the journal Molecular and Cellular Endocrinology (Aromatase Up-Regulation, Insulin and Raised Intracellular Estrogens in Men, Induce Adiposity, Metabolic Syndrome and Prostate Disease) put it this way. 

"For some years now, reduced testosterone levels have been related to obesity, insulin resistance, type 2 diabetes, heart disease, benign prostatic hypertrophy and even prostate cancer, with little attention paid to the important role of increased estrogen, in the pathogenesis of these chronic diseases. Testosterone is metabolized to estradiol by P450 aromatase, to increase estradiol concentration at the expense of testosterone.  It follows therefore, that any compound that up-regulates aromatase, or any molecule that mimics oestrogen, will not only increase the activation of the mainly proliferative, classic ER-α, estrogen receptors to induce adipogenesis [obesity] and growth disorders [cancer / endometriosis] in oestrogen-sensitive tissues....  This paper simplifies how stress, xeno-oestrogens, poor dietary choices and reactive toxins up-regulate aromatase to increase intracellular oestradiol production." 

The authors went on to explain how the described situation is related to insulin resistance, fat deposition (especially around the midsection), metabolic syndrome, BPH, PROSTATE CANCER, obesity, gynecomastia [man boobs], Type II diabetes, low testosterone, and increased estrogen levels in men, among many others. 

Although I came across many similar, I also found a study in a 2010 issue of Toxicology Letters (Bisphenol A-induced Aromatase Activation is Mediated by Cyclooxygenase-2 Up-regulation in Rat Testicular Leydig Cells) showing that the combination of inflammation and BPA created, "increased aromatase gene expression and its enzyme and promoter activity, but reduced testosterone synthesis; increased COX-2 mRNA expression and promoter activity, the production of prostaglandin E(2) (PGE(2)), and the gene expression of PGE(2) (EP2 and EP4) receptors."   PGE2 and the COX-2 enzyme are both extremely inflammatory (COX-2 INHIBITORS are ultra common in Western Society). 

And finally, we get to the hormonal FUBAR that occurs thanks to brain dysfunction (HPA-AXIS).  When the body is low on either sperm or testosterone in males, the feedback loop kicks in and tells the HYPOTHALAMUS to send out a hormone called GRH (Gonaditrophin Releasing Hormone).  This acts on the PITUITARY GLAND, telling it to release FSH to make sperm and LH to make both testosterone and SHBG.  Any number of brain dysfunctions or certain kinds of drugs (particularly THIS MED taken by over 10% of the American population) can throw a monkey wrench into this pathway, leading to all sorts of dysfunction with the sex hormones.

What does sugar do to women?  Unfortunately, it does about everything we've shown it does to men, plus a bit more.  Unfortunately, it is intimately related to something called PCOS (PolyCystic Ovarian Syndrome).  Because so many women are not only having hormonal problems, but spending small fortunes on fertility treatments such as IVF, it would serve us well to understand a few basics about PCOS.  Although I have written a number of articles specifically about PCOS, suffice it to say that not only is it America's number one source of INFERTILITY, but it is a prime example of women being turned into men.  What do I mean by this?

PCOS is the number one female issue in America, affecting approximately 10% of the women of child-bearing age (some studies say the actual number is closer to 1 in 5) --- more than half of which are unaware or undiagnosed.  Intimately linked to INSULIN RESISTANCE, there are many who believe it is another manifestation of diabetes / pre-diabetes in similar fashion to the way that Alzheimer's is widely known in the scientific community as TYPE III DIABETES.  And while numerous stories and studies will tell you that PCOS is genetic, at best this is only partially true.  Like hundreds of other health issues with a genetic component, the problem is far more related to EPIGENETICS than genetics. 

Because there are no definitive blood or lab tests, the diagnosis is usually made clinically.  What does it look like?  The tell-tale cluster of symptoms includes....

• EXCESS TESTOSTERONE:   Along with IR, this is the symptom that drives the others.  Be aware that as I showed you earlier, testosterone overproduction is often the result of overproduction of LH (luteinizing hormone), which is a pituitary hormone.  Another theory gaining traction in the scientific community is that this excess testosterone is the result of Androgen Receptor Resistance (HERE) --- which, kind of like Insulin Resistance, simply means the body has become "resistant" to the effects of testosterone (often times because the receptor sites are saturated), telling the body to make even more.  While this is certainly true, It's hard to argue that it's not ultimately the result of IR.
• EXCESS HAIR GROWTH: Known as "hirsutism" medically, women with PCOS will grow hair in places they otherwise would not (particularly the face), as well as growing excess body hair in places they normally would.  Interestingly enough, it is not uncommon to see women with PCOS develop or begin to develop male pattern baldness --- sometimes confused with THYROID ISSUES --- which are also not uncommon with PCOS.
• ACNE:  ACNE (including "backne") is a common sequelae of PCOS.
• INFERTILITY: Already discussed and left a link.
• CHRONIC FATIGUE, ALTERED MOOD, AND LOW LIBIDO:  All of these are characteristic of excess testosterone in women.  Even though testosterone is the hormone that drives libido in both men and women, when women get too much of a good thing, it becomes a bad thing --- a very bad thing. For the record, realize that PCOS is one of the myriad of health issues considered to be "inflammatory".  DEPRESSION is on this list as well.
• WEIGHT ISSUES:  Women with PCOS have, or eventually will have if they are currently teenagers, difficulty losing weight.  And, as we have already discussed, a common scenario is to see women who have man-like bellies (Central Obesity).  As for those of you who say that this can't be your issue because you are normal weight, make sure to check out my earlier link on "Skinny Fat".
• DARKENING OF THE SKIN AROUND THE NECK:  Known as "acanthosis nigricansis," it also occurs beneath the breasts and in the groin areas.
• SKIN TAGS:  These are usually found in the armpit or the neck region.
• SLEEP APNEA:  SLEEP APNEA is extremely common in women with PCOS.

Although the most common medical treatments include androgen-blockers, DIABETES DRUGS, STATINS, and going on "The Pill," these aren't very effective over the long term, while creating an array of extremely nasty SIDE EFFECTS.  Be aware that plugging "PCOS" into PubMed brought up 12,500 studies to wade through. Although I only looked through a few dozen, not surprisingly I found plenty linking it to Endocrine Disruptors.  Some others included CHRONIC SYSTEMIC INFLAMMATION, reduced TREGS (making you susceptible to AUTOIMMUNITY), increased HOMOCYSTEINE and decreased GLUTATHIONE levels, not enough VITAMIN D, OSTEOPOROSIS, and NAFLD.  If I had more time, I could have found studies linking it to any number of others.

Is it any wonder that in our carb-driven society --- a culture so loaded with Endocrine Disruptors that they are simply thought of as a normal part of life --- we have an exploding national Gender Dysphoria (a conflict between a person's physical gender and the gender with which they think of themselves)? While there are certainly any number of reasons for this phenomenon, it has become impossible to discount the scientific literature as presented in today's post --- literature that only barely scratched the surface of this issue.

Although there might be any number of people dealing with the situations discussed in today's post who could use some help from a FUNCTIONAL MEDICINE SPECIALIST, the truth is, many of you --- probably the majority of you (possibly even the vast majority of you) --- can start addressing this crisis on your own.  And here's the doubly cool part of all this.  I've given you a generic protocol free of charge (HERE) for helping resolve the behind-the-scenes inflammation.  Getting started might be the hardest thing you've ever done, but after a week or two, it gets easier.  Stick with it and you may even end up with results like THIS.

The most conservative estimates reveal that 1 in 6 Americans are dealing with some sort of CHRONIC PAIN issue.  Many organizations suggest the actual number is closer to 1 in 3.  Regardless of the exact numbers, it's a serious problem --- particularly if you're the one in pain.  Dealing with people struggling with various PAIN SYNDROMES is a major thrust of my practice.  While our clinic's success rate is as good as it gets (HERE), there are two major roadblocks to people getting the results they want.

• THE AVERAGE AMERICAN IS SEDENTARY: Face it, the average American is not being regularly active in any meaningful sense of the word. Even if they are constantly "busy," they are frequently not active.  In light of the peer-reviewed scientific literature, the body needs movement to function on a high level.  Not necessarily a huge amount of movement, but movement nonetheless.  A sedentary lifestyle will seriously inhibit your ability to solve your problem, no matter what your problem may be (HERE & HERE are examples having to do with CHRONIC PAIN).
  

 

• THE AVERAGE AMERICAN IS INFLAMED:  Even in those who don't yet show the signs of overt disease or pain, INFLAMMATION is almost assured since it is virtually synonymous with being American.  We are literally an "INFLAMMATION NATION".  For the record, OVERWEIGHT / OBESITY is an inflammatory disease that affects almost 70% of our population.   Another 10% are METABOLICALLY OBESE even though they fit nicely onto a height / weight chart.  While a certain amount of ACUTE INFLAMMATION is needed for the body to heal properly, SYSTEMIC INFLAMMATION can be a deal-breaker for getting out of pain and solving your chronic problem(s).
  

Unfortunately, too many people are let off the hook by their doctors.  They're told that their HIGH CHOLESTEROL is genetic (when it's actually EPIGENETIC).  They're told that their problem is "ARTHRITIS" and that their joints are just worn away to nothing --- almost time for that REPLACEMENT.  They're told that no one has any idea why they have FIBROMYALGIA and that beyond covering symptoms, there's nothing they can do.  They're told that AUTOIMMUNE DISEASES are just an unfortunate luck of the draw for some people; no rhyme, reason, or solution.  They're even told that deadly inflammatory diseases such as CANCER are nothing more than blind, random chance (HERE).  Chalk it all up to bad luck and bad genes.

The result of all this?  That's easy --- drugs.  Even though the United States contains less than 5% of the world's population, our own government admits that we consume 75% of the world's medication (HERE).  I see so many people on "THE BIG FIVE" it makes my head spin.  Becoming a "DRUG CULTURE" has provided an easy way out for us.   We never really have to take responsability for our own health because we pay others to do that for us --- that's our doctor's job.  Unfortunately, the medications never really work over the long haul, and thanks to our "no fault" society, we can always find someone or something to blame for our collective plights.  I want to show you a better way --- a way that actually addresses underlying causes of pain and inflammation, shutting it down at the source.

It's why I suggest that if you are dealing with any sort of pain syndrome, it's helpful to treat it as though it were a systemic problem, probably because often times it is (HERE, HERE, or HERE).  Don't get me wrong; I'm happy to see you and help you find your way out of the ditch you are in --- usually with way less time and expense than anyone else suggests is possible (HERE).  What I want to see, however, is you (that would be "you" as in you) take some personal responsibility.  Frankly, I don't want to see you over and over again for the same old problem(s), simply because you won't take the initiative to start addressing them on your own.  What do I mean by 'addressing them on your own'?   Hang tight for ten more seconds.

If you are one of those people who has struggled with any sort of chronic health or pain issue, by all means, come and see me --- if I tell you I can help you I probably can (HERE).  However, if you want to break away from the endless stream of doctor visits, get off the MEDICAL MERRY-GO-ROUND, and start taking your life back, you'll have to take some action steps.  I promise I've helped people worse off than you are (HERE).  And here's the thing; I've even provided you a blueprint for getting started completely free of charge.  HERE is the brand new revamped version.  The truth is, if you don't treat your pain / problem systemically, it may be tough to really get better (HERE is a person who took this message to heart).

The liver is a truly amazing organ.  Acting as the body's chemical factory, the liver has enough functions to make your head swim.  Aside from storing fuel in the form of liver glycogen, it makes BILE (stored in the GALL BLADDER), is critical for protein synthesis, makes certain enzymes and hormones, and breaks down and recycles red blood cells --- and that's just for starters.  But as critical as these are, its penchant to perform a a function widely known in the scientific and medical communities as "Biotransformation" is quite possibly its most important.

Unfortunately, our collective livers are under assault, not only from the thousands of chemicals we expose it to regularly, but from our typically crappy diets.  For instance, a 2014 issue of the World Journal of Gastroenterology says this of Non-Alcholoic Fatty Liver Disease (NAFLD).  "Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic.  Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality and is strongly associated with insulin resistance / type 2 diabetes and the metabolic syndrome [PREDIABETES]."  Same journal, same month, different authors....  "In the United States, NAFLD is the most common cause of liver disease, representing over 75% of the chronic liver disease."  In other words, even though you probably learned growing up that alcoholism is what destroys livers, in the big picture it accounts for a relatively small percentage.  OBESITY is what destroys livers (even if you are "SKINNY").

The question arises, what can we do to keep our livers functioning optimally?  It should be obvious that maintaining a healthy weight is paramount.  Beyond that the research talks at length about many of the same things I talk about on my site ---- controlling BLOOD SUGAR and staying far away from the HIGH CARB LIFESTYLE, GUT HEALTH, INFLAMMATION (this covers huge amounts of ground), EXERCISE, and any number of others (SLEEP APNEA has also been associated with NAFALD, possibly because it's so intimately linked to obesity).  Today I want to talk about some of the detoxificiation / biotransformation pathways and show you, using the scientific literature, what you can do to support them.  

I'll start with a brief overview taken from THIS POST written about what it takes to clear out excess female hormones and artificial female hormones.  The same principles are at play for virtually every toxin and chemical in your body, whether made from within or there from the outside exposure.

• PHASE I describes the first step of your body's ability to turn various toxins to forms that can be excreted from the body.  It is the body's first metabolic defense against foreign chemicals.   Phase I reactions are primarily performed by via oxidation (oxygen) and the P450 Cytochrome Enzymes. This involves either adding or "uncovering" an active site so that the various components of Phase II can do their job.
  

 

• PHASE II reactions attach or "conjugate" the toxins to various compounds in order to increase their ability to be voided.  This part of the equation is where the oxidized chemicals are combined with sulfur, specific amino acids, or organic acids, so that they can be excreted in the bile and eventually the feces, or in the urine.  There are several different enzymes and different metabolic pathways for accomplishing this that can and will become depleted without replenishing them via a nutritious diet.  Phase II can be inhibited by alcohol, drugs (prescription, OTC, or recreational), and nutritional deficiencies (including  too little dietary protein).  
  
  

• PHASE III is simply the process of your system actually removing / excreting the conjugated toxic chemicals from your body ---- without reabsorbing them.  Be aware that this is virtually impossible without ample amounts of dietary fiber (something you must be careful of with SIBO / IBS).
  

As a side note, the field of Toxicokinetics or Pharmacokinetics studies how rapidly and effectively certain substances can be cleared from the body, or whether they or their metabolites accumulate in fatty tissue.  I also want to take just a moment to discuss the term xenobiotics, since they will come up over and over again.

Xenobiotics are defined in many ways and can be chemicals (toxins) that should never be found in the human body, chemicals that should be there but are present in amounts that are far too high to be considered normal (ESTROGEN DOMINANCE), or chemicals that are put into your body on purpose but are not found there naturally (MEDICINES / ANTIBIOTICS).  You will frequently hear the term xenobiotic and ENDOCRINE DISRUPTOR used synonymously. 

Other xenobiotics include things like known carcinogens, cigarette smoke, pollutants, food additives, hydrocarbons (byproducts from oil and gas / gasoline), as well as pesticides and herbicides.  Current research says that there are between eighty and ninety thousand chemicals that did not exist prior to WWII with an additional two thousand or so created annually.  Thus, the question we need to be constantly asking ourselves is two-fold; what can we do to diminish our exposure, and what do we need to do to insure our Biotransfer / Detox pathways are working optimally in order to clear toxicity from our systems?

The goal of Phase I Biotransformation / Detoxification is to take fat-soluble toxins that do not dissolve in water (they have no polarity {+ or -} and are thus non-charged) and make them more water soluble so that they can either be excreted by the body (urine, feces, sweat, breath, etc) or used as attachment sites (conjugation sites) in Phase II detox.  Phase I is characterized by three different reactions that add or expose a functional group to said toxin...

• OXIDATIVE REACTIONS (OXIDATION or OXIDIZING):  Increasing the oxidation state of the toxin being worked on involves a net loss of electrons.  The enzymes involved in this are Aldehyde Oxidase (AO), Flavin-containing Monooxygenases (FMOs), Monoamine Oxidases (MAOs), Xantine Oxidase (XO), and the most important and well known of the lot, the P-450 Cytochrome System (CYP450). These reactions tend to happen a bit slower, and are by far the most common and well known of the Phase I reactions.  Oxidation is the most common of the Phase I pathways and happens to be the route whereby most xenobiotics are dealt with.  Also realize that while oxidation is vital and necessary, it can present problems as well.  Examples of oxidation reactions include rust on metal and the brown color of the part of the apple you took a bite of and then set down for a few minutes.

 

• REDUCTION REACTIONS (REDUCING):  An increase in the reduction state of the toxin being worked on involves a net gain of electrons.   These reactions involve enzymes such as Carboxylesterase, Peptidase, Epoxide Hydrolase, Choiniesterease, Paraoxonase, Alcohol Dehydrogenase, and Carbonyl Reductase.

 

• HYDROLYTIC REACTIONS (HYDROLYSIS):  This simply means that chemical bonds of toxins are being broken down by the addition of water --- hydro (water), lysis (to unbind).

 

• OTHERS:  Although there are others, we are not too concerned with them right now.

Of all these reactions, the one that you will hear about most often (by far) is the P-450 Cytochrome System, which also happens to be used for things like the production of CHOLESTEROL, steroid hormones (sex hormones and adrenal hormones), vitamin D, and fatty acid production (Cholesterol is the precursor of everything on this list).  Like Hemoglobin, the molecule that carries oxygen throughout the body, the CYP450 molecule has a iron / heme center --- one more reason why ANEMIA is a deal-breaker as far as solving chronic health issues is concerned.

CYP-450 enzymes are found mostly in the small intestine and the liver, with as great as 5% of the total number of liver proteins said to be of the CYP450 family.  As strange as it might seem, one of the tests used to see how well a person's Phase I CYP450 Cytochrome System is working is with coffee / caffeine as indicated by any number of studies (for instance Caffeine as a Marker Substrate for Testing Cytochrome P450 Activity in Human and Rat in a 2008 issue of Pharmacological Reports).  You can test yourself to some degree.  People who are really affected by coffee tend to have less ability to clear toxins via their CYP450 system.  Likewise, those who are unaffected tend to clear Phase I faster.

If the intermediate metabolites created by Phase I outstrip the ability of Phase II to conjugate, the body will be exposed to increasingly higher levels of said metabolites as they back up and accumulate.  One of the more common intermediates of Phase I is Free Radicals.  Free Radicals are relatively simple to understand.  Electrons never like to be alone, always wanting a partner to cozy up to.  So when an electron is "free" or unpartnered, rest assured that it will be on the prowl for any available electron to pair up with.  Unfortunately, these "Free Radicals" will attach themselves to an almost unlimited number of electrons, often times making compounds that can be very toxic.  Free Radicals are always looking for stability (pairing up), even at the expense of other compounds.  When the body's natural chemistry is robbed of it's electrons, these chemicals --- needed for normal metabolism --- no longer work.  While the production of Free Radicals is a normal part of Phase I, anything that inhibits the conversion of the Free Radical to safer compounds is a problem.

When too many Free Radicals build up (CRUDDY DIETS, EXPOSURE TO RADIATION, STRESS, DRUGS (yes, prescription drugs), ANTIBIOTICS, overtraining (too much exercise), coffee, alcohol, and even CHRONIC PAIN), metabolic deficiencies, it creates something called "Oxidative Stress".  In other words, the body can't get rid of these toxins by pushing them over to Phase II.  Not only is Oxidative Stress associated with inflammation, it is associated with almost every chronic illness we can think of today --- the biggest being cancer.  This is why we need the power of antioxidants in our diets --- things like YELLOW SPICES, FRUITS AND VEGGIES with plenty of color, certain berries, along with other foods that have a high ORAC value (Oxygen Radical Absorbance Capacity). There are lots of them. While cocoa can be a fantastic antioxidant, it needs to be at least 85% dark to be beneficial.  And while there are any number of chemicals shown to be good antioxidants, the scientific literature has shown that these frequently do not work well in isolation (HERE).

Although there are many toxins / chemicals that are ready to be removed from the body after Phase I, many others (intermediate metabolites) will move on to Phase II, which consists of things like thiol conjugation, methylation, glucuronidation, glutathione conjugation (the heavy-hitter of the bunch), amino acid conjugation, sulfation, or acetylation.  Today we are going to spend most of our time in the mythylation and Glutathione pathways.

It is important to be aware that the 'intermediate metabolites' created by Phase I can actually be more toxic to your system than when they were previously.  This is why it is absolutely vital to have Phase II working properly.   When Phase I is not working properly (or is working in overdrive while Phase II is suppressed), your chances of developing any number of serious diseases, including AUTOIMMUNITY, CANCER, PARKINSON'S, and many others, increases dramatically.  Not surprisingly, there is even evidence showing that AUTISM is related to a diminished ability to undergo proper Biotransformation.

When we talk about Phase II of Biotransformation / Detoxification, we are talking about the body's ability to actually attach a molecule to the active areas created or uncovered in Phase I so the toxic compound or chemical can be removed from the body in Phase III. Please be aware that a significant portion of Phase II occurs in the small intestine.  An unhealthy small intestine (SIBO/IBS) means that the Biotranformation that should be occurring in the small intestine gets shifted over to the liver, working it double overtime.  Interestingly enough, an important component of this process is bile, which is made by the liver (stored in the gallbladder), and used, among other things, to help get waste products out of the body.  Let's take a look at the biggest factors in Phase II

GLUTATHIONE CONJUGATION
This is the big boy; the heavy-hitter of phase II that is said to account for over 60% of the toxins in the bile as well as MERCURY, ALUMINUM, ARSENIC, industrial wastes, and the xenobiotics we spoke of earlier.  An amazing thing about the GLUTATHIONE PATHWAY is that it takes an extremely toxic byproduct of aminio acid metabolism --- homocysteine --- and if it has the proper nutrients and enzymes, converts it to Glutatione and SAMe (S-adenosyl methionine), which has several health benefits of its own as far as Phase II is concerned.  However, when this conversion is blocked or hindered to varying degrees, homocysteine levels will rise, causing all sorts of health problems (homocysteine is easy to test via blood work).

For instance, when people have a high toxic burden, Glutathione is depleted faster than it can be consumed dietarily (or recycled from homocysteine / cysteine as I just showed you above).  If you want to see just how big a deal Glutathione depletion is, cruise on over to PubMed and search "Glutathione (disease of choice)".  For instance, a search for "Glutathione Alzheimer's" pulled up over 1,200 studies. I'll show you just one.  Last month's issue of Neuroscience and Biobehavioral Reviews (The Effect of N-Acetylcysteine (NAC) On Human Cognition - A Systematic Review) concluded that 12 studies of Alzheimer's patients treated with NAC --- a metabolic precursor to Glutathione --- showed, "statistically significant cognitive improvements following treatment."   Not to freak you out, but when I plugged in "Glutathione Cancer," it resulted in nearly 21,000 studies.

WHAT THE HECK IS METHYLATION?
Let me first say that if you really want to understand methylation (I do not consider myself an expert in the least), you need to follow Dr. Suzy Cohen (pharmacist and specialist in FUNCTIONAL MEDICINE), Dr. Ben Lynch (a naturopath with a degree in cellular and molecular biology), Dr. Datis Kharazzian (FUNCTIONAL NEUROLOGIST, Functional Endocrinologist, Chiropractor, Harvard researcher, and author of THYROID BOOK and Why Isn't My Brain Working?), or Dr. Amy Yasko (a Ph.D in Microbiology / Immunology / Infectious Disease as well as a Naturopathic degree, her curriculum vitae reads like a veritable Who's Who. Among others, she worked on the autism front with DR. HUGH FUDENBERG at South Carolina University as well as being a researcher at Yale).  Since I have the brain power of a peanut compared to people like this, I am going to give you the Methylation For Dummies condensed version (those in the know might say it's closer to the Mad Magazine version). 

With a lot of talk about methylation and MTHFR (methylenetetrahydrofolate reductase) these days, it would behoove us to know a bit about this as it relates to Biotransformation and Detoxification.  I've seen experts say that nearly half of the population contains mutations in the MTHFR family of genes. While this sounds scary on the surface, the most important thing to remember is that EPIGENETICS TRUMPS GENETICS, meaning that in many important ways, you are not nearly as defined by your DNA as you have been led to believe, and that "bad genes" are usually switched on via bad lifestyle choices.  But why do problems with MTHFR or methylation matter in the first place?

Not that the average Joe cares, but a methyl group consists of a carbon atom surrounded by three hydrogen atoms (CH3), which is structurally related to methane gas.  Methyl groups are important in almost every physiological function that occurs in the body, and a failure to methylate properly is indicative of such a wide array of illnesses that it almost not worth listing them.  These include neurological, endocrinological, malfunctioning thought processes, inflammatory, and mood disorders.  Oh; and for the record, methylation dysfunction is not always genetic, but can be due to deficiencies in methylfolate (a vitamin catalyst) and subsequently Glutathione as well as others.  Also realize that the most commonly methylated compound in the body is one we talked about earlier, SAMe.

A common method of treatment for methylation disorders is to essentially bypass both the MFTHR issue and your body's natural feedback loop by giving megadoses of folic acid (you always hear about folic acid --- VITAMIN B-9 --- being a critical part of fortified foods, including ORANGE JUICE, to prevent neural tube defects).  This is why you need to use natural or food sources of folate (methylfolate aka 5-MTHF).  A deficiency of folate is related to a specific kind of anemia, which is also related to STOMACH ACID PROBLEMS.

Some of the best foods for pumping up your methylation and Glutathione pathways include.... REAL FOOD.  The internet abounds with lists of foods, herbs, and supplements that boost the methylation and Glutathione pathways.  I discussed this earlier and showed you that while supplements can get you through a pinch, they are not typically the best long-term solution.  Now allow me to share with you a quick note about liver as related to liver nutrition. 

German Physician, Dr. Max Gerson, wrote his famous book (I own it --- preface by his amazing daughter CHARLOTTE) about sixty years ago; A Cancer Therapy: Results of Fifty Cases and the Cure of Advanced Cancer by Diet Therapy.  The basis of his "cure" was organic WHOLE FOODS as opposed to SYNTHETIC NUTRITIONAL SUPPLEMENTS.  The thing, however, that sticks out in my mind was the way he used liver.  Liver was the foundation of his remedy --- raw and blended into a drink.  I am certainly not suggesting anyone do that, but what I am suggesting is that if you can get your hands on completely organic beef liver (no hormones / meds) and eat it regularly, there are some amazing health benefits.  Same with some of the other organ meats as well.

An article written by Kevin Cann for Paleo expert, ROBB WOLF (Understanding and Combating Oxidative Stress in Huntington’s Disease) echoed some of these sentiments in a quote from a conversation with medical doctor and MS expert (she essentially cured herself), TERRY WAHLS.  Dr. Wahls said to Cann, "When I used supplements – I slowed my decline, when I designed my food supply to get those same nutrients – my strength began to return. Print that and put up where you work – stare it every day. The supplement studies are best used to guide how we create the food plans."  An amazing truth from an amazing woman!

OTHER BIOTRANSFORMATION /DETOXIFICATION PATHWAYS
Truth is, there are several different pathways for Biotransformation and Detox. 

• The Amino Acid Conjugation Pathway requires ample protein to get the five aminos involved --- the most important being glycine. 
  
• The Sulfation Pathway (similar to the Thiol Conjugation Pathway) uses sulfur-containing foods (many of the cruciferous veggies, for instance, or eggs) and helps conjugate all the nasties we've already discussed, as well as dealing with your body's natural hormones and neurotransmitters. It happens to be a critical part of your body's ability to manufacture proteins and protein / carbohydrate complexes as well.
  
• The Acetylation Pathway uses acetyl-CoA instead of a methyl group to do its work.  People with problems in this pathway tend to not conjugate antibiotics very well, as well as affecting the conversion of SEROTONIN to melatonin --- critical for the sleep / wake cycles known as Circadian Rhythms.
  
• The Glucuronidation Pathway uses glucuronic acid to attach itself to toxic substances, particularly PAH's (Polycyclic Aromatic Hydrocarbons such as creosote, exhaust fumes, petroleum byproducts) and nitrosamines (found in cosmetics, pesticides, rubber products and tobacco products --- both smokes and chew).
  

It wasn't that long ago, there were only two phases of Biotransformation / Detox; Phase I and Phase II to discuss.  When Phase III was added, many assumed it was quite simple --- get the conjugated junk out that was created in the first two phases.  Like most biological systems, it's more complex than meets the eye.

The first references I saw to this system in peer-review were in the late 1980's (they were talking about how this system could adversely affect the potency of chemotherapy drugs).  Just after I started practice in the early 1990's, there were a pair of studies in Trends in Biochemical Science (The ATP-Dependent Glutathione S-Conjugate Export Pump and The Phase III Detoxification System) that stated, "The glutathione S-conjugate export pump (GS-X pump) plays a physiologically important role as a member of the 'phase III' system in xenobiotic metabolism as well as in the release of biologically active endogenous substances from cells. In addition, this export pump is potentially involved in the modulation of the antiproliferative action of certain antitumor agents."  In other words, both exogenous chemicals (coming from outside your body) and endogenous chemicals (made by your body) are removed via Phase III.

Sometimes Phase III is referred to as the Antiporter System, and contains something like 350 different proteins, the most common being P-glycoprotein.  These proteins typically hang out in the intestinal wall (epithelial lining) and grab hold of the conjugated chemicals so they can be kept in the digestive tract and eventually out in the feces instead of being reabsorbed by the body, back into the blood stream, where the process can start all over again.  This is also another of the reasons, as mentioned earlier, that good bile production is needed by the liver (bile is important for good bowel function as well --- HERE).  In Dr. Danny Urbinder's article for FX Medicine (What is Phase III Detoxification?), he states.....

"According to Dr Chris Shade, an environmental and analytical chemist who specializes in the human detoxification system, the most significant cause of Phase III dysfunction is inflammation, especially in the gut. When Phase III is blocked a negative feedback loop results in the down-regulation of Phase II enzymes. Intermediate metabolites produced in Phase I are then at risk of building up resulting in increased oxidative damage, which further impairs detoxification capacity."

Your intestines are constantly using energy to keep minerals, water, nutrition, and other "good" substances in your body, while getting rid of waste products, including the toxic byproducts of Biotransformation and Detoxification.  Furthermore, if you are familiar with my site, you already realize that I tend to talk a lot about inflammation --- particularly as it relates to GUT HEALTH.  If you can keep your Gut and liver clean and healthy, and your body free of inflammation, you are far more likely to be able to clear the junk that we citizens of 21st century earth are exposed to virtually every minute of every day (think about how much more toxic our lives are than they were throughout most of human history).

If you feel you've done due diligence as far as taking charge of your health (HERE), but cannot seem to get over the hump, it's not rare to have issues with these various pathways.  Fortunately, there are some very cool oral swab, blood and saliva genetic tests available that can reveal whether or not an inability to detox might be at the root of your problem (currently 23 and me seems to be the best and least expensive option on the market).  There are also some very cool tests by Cyrex Labs that reveal if you are making antibodies against some of the more common toxic chemicals such as BPA.  Also, the OAT test for organic acids as well as a COMPREHENSIVE GI / STOOL TEST can be beneficial as well.

Finally, remember that this article was not in any way, shape, or form, meant to be definitive, but only to give you an idea of where to start researching.  Hope it was helpful.

Dealing with endocrine issues (THYROID, DIABETES, FEMALE HORMONES, MALE HORMONES, DIGESTIVE ISSUES, ADRENAL FATIGUE, etc, etc, etc) can be extremely complex.  Just remember that the first thing that must be taken care of with any chronic health issue is ANEMIA.  When dealing with a chronically ill female patient, the questions are always, "are you anemic, how anemic are you, what kind of anemia is it, let me see your blood work, how long have you been bleeding every month, and what sort of AUTOIMMUNE DISEASE(S) do you have?"  Fail to address underlying anemia and the rest of this post is essentially worthless.

Once any anemia has been addressed, there are four distinct metabolic areas that need to be discussed and addressed, blood sugar regulation, fatty acid metabolism, the liver's detox pathways (Endocrine Disruptors live here as well), and of course, gut health.  Today we are going to talk about the PALEO DIET for endocrine problems and why it is the cat's meow for dealing with each and every one of these points.

When it comes to problems of the endocrine system, they are not only ultra-common, they almost always get worse grow over time.  This is because changing one hormone's ability to work properly can have adverse effects on all hormone's ability to work properly.  This is because hormones are almost all on negative feedback loops.  What is a negative feedback loop?  A thermostat keeps your house at 72 degrees because when the temp drops below 72 or climbs above 72, the furnace or air-conditioner kicks, whichever is needed, kicks on and regulates the temperature.  When your thermostat goes out, it becomes difficult to regulate the temperature of your home. 

Successfully addressing endocrine system dysfunction is all about correcting aberrant or dysfunctional feedback loops so that the body starts to regulate itself.  Sure, your doctor can look at a blood test and prescribe the hormones that might be low.  But what if the problem is not that there is not enough of said hormone, but that the receptors for said hormone are either saturated or have lost their sensitivity. This is exactly what occurs in TYPE II DIABETES, including the earliest stages (Prediabetes aka CARDIOMETABOLIC SYNDROME).  It's also the reason that while giving these people DIABETES DRUGS or even insulin might normalize their blood sugar for the short term, without diet and lifestyle changes, it will never do what it claims over the long haul.  Let's take a brief moment to look at the Paleo Diet as related to these various aspects of endocrine support.

• BLOOD SUGAR REGULATION:  We start here simply because a failure to control BLOOD SUGAR makes everything else impossible.  Why?  Show me a health-related issue that is not 100% GENETIC (Downs Syndrome, Cystic Fibrosis, etc), and I will show you studies --- in many cases, hundreds of studies --- linking it back to blood sugar dysregulation (HERE'S A KILLER EXAMPLE).  Bear in mind that just because you are "NORMAL WEIGHT" or your blood sugar numbers fall within "normal" range, does not mean you aren't losing glycemic control.  To better understand what I mean, take a gander and the numerous posts filed under the first link in this bullet.
  

 

• FATTY ACID METABOLISM:  As I showed you just the other day (HERE), the fats you consume are either driving inflammation or controlling inflammation.  Also, it is critical to understand that CHOLESTEROL (a fat of sorts) is the precursor for many, if not most of, your hormones. STATIN DRUGS and TRANS FATS, along our national fear of fat (HERE), have at best, contributed to, and at worst, caused, untold amounts of hormonal dysregulation.  The Paleo Diet helps regulate fatty acid metabolism in a number of ways, not the least of which is the fact that it skews metabolism away from inflammatory PGE2 and toward anti-inflammatory PGE1 & PGE3, particularly pushing the body toward Omega-3's (see the first link in this bullet).

 

• LIVER DETOXIFICATION PATHWAYS:  Although most of us (self included) refer to the body's ability to clear junk (CHEMICALS, MEDICATIONS, METALS, etc, EXCESS HORMONES, XENOHORMONES, etc, etc, etc --- most of which loosely fall into a category known as "ENDOCRINE DISRUPTORS") as detoxification, the scientific literature has a different name for the process --- "Biotransformation".  Biotransformation includes the many various processes that "transform" these toxins into the biological forms that the body can excrete and get rid of in one way or another, most of which occur largely in the liver.  While mopping up and getting rid of toxic chemicals is great, what's even better is not having to deal with them in the first place.  Once you understand this simple concept, it's not hard to understand why avoiding said substances is a big deal.  When you eat animals and animal products that were never given hormones or antibiotics to begin with, the end result is an endocrine system that is more capable of functioning as it was created and designed to from the beginning. Never forget that commercially-raised livestock are given estrogen-based hormones for the express purpose of making them fat (females carry far more body fat than males thanks to estrogen). 

 

• GUT HEALTH:  Understanding the two facets of GUT HEALTH (MICROBIOME and BARRIER INTEGRITY) is absolutely critical if you want to get your hormonal system under control.  And no, I haven't forgotten the whole FODMAPS / IBS / SIBO THING either.  Because 4/5 of your immune system (HERE) and 90% OF YOUR SEROTONIN come from the Gut, you'll have to get serious about Gut Health in order to solve problems in your hormonal system (BTW, serotonin is intimately related to melatonin --- the sleep hormone).   Commercially-raised animals or the animal-based foods that come from them, have the ability to foul Gut Health.  For starters, these animals are regularly fed low-dose antibiotics with their GRAIN for the express purpose of making them gain weight (HERE).  ANTIBIOTICS cause DYSBIOSIS, while sugar along with highly processed carbohydrates feeds it (HERE). Furthermore, you can effectively use an ELIMINATION DIET to figure out what foods might be creating INFLAMMATORY RESPONSES in your body. 

Bottom line, Paleo or something similar, is critical for you to get your life back --- so much so that I created a mega post on the Gut / Endocrine relationship called ENDOGUT.  If you are struggling with hormonal issues and still eating a SAD (Standard American Diet), you've got to change that immediately.  Use an ANTI-INFLAMMATORY, PROTEIN-RICH, VEGETATION-BASED, I'M-NOT-SCARED-OF-HEALTHY-FATS, diet to curb SYSTEMIC INFLAMMATION, allowing your body --- endocrine system included --- to start healing itself and regaining it's normal feedback mechanisms.  

Trying to solve your endocrine problems without restoring the integrity of these feedback loops (ie, simply and only taking supplemental hormones --- see the list at the top of the page), while sometimes necessary short term, can be short-sighted, making you feel better and improving your blood work numbers for awhile, but never really restoring the body and hormonal systems to their natural state of balance and HOMEOSTASIS.   While you certainly might require a FUNCTIONAL MEDICINE specialist to dig deeper, the Paleo Diet should help you get started on your journey (HERE).

"In patients with SIBO, bacteria ferment ingested carbohydrates in the small intestine causing increased gas production. Accumulation of this gas in the intestine results in bloating and flatulence. Excessive luminal [intestinal] distension may even cause abdominal pain or discomfort. Bacteria in the intestine may produce toxic by-products after fermentation, which may damage the inner lining of the small intestine and colon."  From the March 2014 issue of the World Journal of Gastroenterology (Irritable Bowel Syndrome and Small Intestinal Bacterial Overgrowth: Meaningful Association or Unnecessary Hype?)

I've shown you in the past what SIBO is.  I've also shown you what IBS is (for those that were not aware, it's an AUTOIMMUNE DISEASE that many researchers believe to be a precursor to IBD).  What if I showed you that these two health issues are essentially the same --- or if not completely identical, so intimately related that untangling them from each other is all but impossible.  Follow along as we explore the numerous links between these two common problems.  How common?

The September issue of Therapeutic Advances in Chronic Diseases (Gastrointestinal Bacterial Overgrowth: Pathogenesis and Clinical Significance) said that, "Small intestinal bacterial overgrowth (SIBO) is defined as the presence of an abnormally high number of coliform bacteria [bacteria present in the large intestine and feces] in the small bowel. The most common symptoms associated with SIBO include diarrhea, flatulence, abdominal pain and bloating.  The prevalence of SIBO in IBS varies from 30 to 85% depending on the source used. The prevalence of SIBO in liver cirrhosis is 50% and in celiac disease, the prevalence of SIBO in some studies is also estimated to be 50%. Interestingly, in asymptomatic morbidly obese patients the prevalence of SIBO was noted to be 17%."  In other words, SIBO is far from uncommon.

As far as IBS is concerned, About IBS dot com says that, "Irritable bowel syndrome is the most common functional gastrointestinal disorder with worldwide prevalence rates in the area of 10–15%.  IBS is the most common disorder diagnosed by gastroenterologists and accounts for up to 12% of total visits to primary care providers.  There are between 2.4 and 3.5 million annual physician visits for IBS in the United States alone."  MedScape parrots these statistics, adding to it that "only 3.3% are medically diagnosed."  In essence, this means that these doctor visits are being driven by the very worst of the worst.  The others --- like many of you --- are just sucking it up and living with it.  BTW, I saw a major study from the past few months saying the international prevalence of IBS could be be over 20%.  That would be 1 in 5 or about 65,000,000 Americans and about 1,500,000,000 worldwide.

As for the gas --- one of the single most distinguishing characteristics of both SIBO and IBS --- it is both foul-smelling and toxic.  That's right; toxic.  Several studies actually discuss IBS/SIBO-associated health issues in relation to CDT's (Cytolethal Distending Toxins), about which Wikipedia says, "toxins produced by certain gram-negative bacteria that trigger cell cycle arrest, leading to the enlarged or distended cells for which these toxins are named.  Affected cell lines (including human fibroblasts, epithelial cells, endothelial cells, and keratinocytes) die by apoptosis [programmed cellular destruction].  CDT's are classified as AB toxins, with an active ("A") subunit that directly damages DNA.  Many of these bacteria infect humans. Bacteria that produce CDTs often persistently colonize their host."  In other words, not only are these creatures vile, they can be tough to get rid of as well.  We'll talk more about how that's done later in the post.  Oh, and don't ever underestimate the importance of the epithelial cells they mention (THE LEAKIES) or FIBROBLASTS.

Because the stomach is (OR AT LEAST SHOULD BE) extremely acidic, it acts as one of the defense mechanisms preventing bacteria from getting into the small intestine from the top of the GI tract (for an overview of digestion, ENDOGUT is the place to go).   At the beginning of the small intestine the relatively few bacteria found there will be gram positive and at the end of the GI tract, they'll be gram negative.  Due to the gas producing features of these bacteria, the bowel (large intestine) distends, compromising the doorway between small and large intestine (the illeocecal valve), thus allowing large amounts of gas to enter the small intestine.  Interestingly enough, these gasses can be easily tested for using various breath tests.  Hydrogen-based gases tend to cause diarrhea, while methane-based gases tend to cause constipation.  One of the hallmarks of IBS for many individuals is that they make both gasses, depending on what they eat --- one reason they have alternating diarrhea and constipation

Although there are some physicians and researchers who say that the relationship between IBS and SIBO is controversial (for instance, this month's issue of Current Opinion in Gastroenterology published a study called Small Intestinal Bacterial Overgrowth as A Cause for Irritable Bowel Syndrome: Guilty or Not Guilty?), my humble opinion is that peer-review is clear on the subject. Not only is there a relationship, the scientific literature shows it to be both robust and underestimated --- a thought echoed by the title of a study in the August 2015 issue of Neurogastroenterology and Motility (Possible Underestimation of SIBO in IBS Patients). 

Before we get into the nuts and bolts of the SIBO / IBS relationship, I want to show you a few things you need to at least thinking about.  Because IBS is autoimmune, and because autoimmune diseases tend to travel in packs, there are very specific health issues that have been associated with this problem.  Not surprisingly, it's been linked to INCREASED INTESTINAL PERMEABILITY in the large intestine (do not confuse this with diarrhea) as well as autoimmunity itself (HERE).  Other studies have linked things as seemingly unrelated as rosacea (facial redness) and RESTLESS LEG SYNDROME (both are autoimmune diseases) to both SIBO and IBS.  We'll get to the Depression / IBS / SIBO link shortly.

There are so many studies on this topic it can make your head spin.  Just realize that the link between IBS and SIBO, although not completely understood, is undeniable.  I could have used dozens upon dozens of studies to prove this point.  To keep things rolling along I only used a few that I thought had good overviews, one of them having to do with children.

• The March 2017 issue of Gut and Liver (Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy) revealed who is most susceptible to the IBS / SIBO combo.  "Female gender, older age, diarrhea-predominant IBS, bloating and flatulence, proton pump inhibitor and narcotic intake, and low hemoglobin are associated with SIBO among IBS patients."  What should we take away from this?  Remember that ANEMIA is a deal-breaker as far as fixing any chronic issue is concerned.  Also, women are far more likely to develop autoimmunity than men.  I'll deal with PPI's later.  Furthermore, we see why the breath tests work so well.  "Eighty percent of the gases like hydrogen and methane are eliminated with the flatus and the remaining 20% are absorbed and exhaled by lung, which can be measured in breath."  Lastly we learn about the, "paradigm shift in understanding this disorder, hitherto thought to be predominantly psychogenic in nature."  In other words, even though the problem is FUNCTIONAL AND NOT PATHOLOGICAL, it's not simply in the patient's head as was believed for decades.

• Last June's issue of Gastroenterology Research and Practice (Small Intestinal Bacterial Overgrowth in Patients with Irritable Bowel Syndrome: Clinical Characteristics, Psychological Factors, and Peripheral Cytokines) dealt with the INFLAMMATION both created and caused by this issue, saying "Bacterial products, such as endotoxins, can affect gut motility.  Gut bacteria are also important for activating an immune response. Immune-mediated cytokines have multiple actions.  there is a large body of work demonstrating that patients with IBS have low-grade immune activation, and associations between psychological state and stress and immune activation have been detected in mucosa. Results from animal experiments suggest that low-grade gut inflammation can alter gastrointestinal tract motor function and that gut motility abnormalities can further predispose to bacterial overgrowth....  Previous studies have confirmed that anxiety and depression are more common in patients with functional gut and intestinal disorders than in the healthy population, particularly in patients with IBS, as confirmed here. Anxiety, depression, and life event stress were more prevalent in patients with IBS than in healthy controls." Inflammatory ENDOTOXINS (lipopolysaccharides) are commonly seen in the IBS / SIBO combo, while ANXIETY / DEPRESSION are both considered to be inflammatory disorders.

• Just so you are aware, this is not just an adult problem --- not by a long shot.  Back in 2009, the journal Pediatrics published a study called Prevalence of Small Intestinal Bacterial Overgrowth in Children with Irritable Bowel Syndrome.  The authors, seven gastroenterologists from Rome's University of Sacred Heart Gemelli Hospital, concluded that, "The prevalence of abnormal [breath test] results were significantly higher in patients with IBS (65%) with respect to control subjects (7%).  Results from this study suggest a significant epidemiologic association between SIBO and IBS in childhood."  What does this ultimately mean for your children?  Stick around to find out.

All of this is great information and important to know if you struggle with this problem.  But so far, I haven't covered much having to do with addressing / solving / fixing the problem.  This section is short folks, and is where the rubber meets the road as far as dealing with IBS and SIBO are concerned!  Oh; as far as diagnosis is concerned, you can do the breath tests, but honestly, if you have problems with gas coming from either end of your digestive tract after a meal, you have some degree of SIBO.

As you saw earlier, the IBS / SIBO combo is not only common, it is the number one reason people visit gastroenterologists (digestive specialists).  What's the average GI specialist doing for these patients?  You see it over and over again in the studies; they are prescribing antibiotics --- chiefly an antibiotic by the name of rifaximin; the same most commonly used to treat C. DIFF INFECTIONS.  The thing about C. Diff is that, like other GI infections / DYSBIOTIC CONDITIONS, the treatment (antibiotics) is at least a substantial part of the very thing that's likely causing the problem in the first place.  And even though study after study recommends rifaximin, saying it is about 75% or so effective for ten weeks, it creates dysbiosis. So regardless of how much antibiotic you take or how effective it is over the short haul, unless you radically change your diet (more on this momentarily), the problem will continue to come back over and over again.

A year ago in January, the World Journal of Gastroenterology asked a question via the title of a study --- Is Irritable Bowel Syndrome an Infectious Disease?  Listen to their own conclusions.  "Irritable bowel syndrome (IBS) is the most common of all gastroenterological diseases, with a worldwide prevalence of 7%-21%. The presence of small intestinal bowel overgrowth (SIBO) has been documented in patients with IBS and reductions in SIBO as determined by breath testing correlate with IBS symptom improvement in clinical trials. The incidence of new onset IBS symptoms following acute infectious gastroenteritis also suggests an infectious cause. Alterations in microbiota-host interactions may compromise epithelial barrier integrity, immune function, and the development and function of both central and enteric nervous systems explaining alterations in the brain-gut axis."  Not surprisingly the authors concluded that IBS is an infectious disease.

Don't, however, confuse infectious with communicable (at least in most cases).  Due to the pressure of the excess gas, the bacteria is being forced up the small intestine from the bottom via post-meal distension and bloating --- the most defining characteristic of IBS / SIBO.  This pressure opens the illeocecal valve, allowing both gas and bacteria into the small intestine.   But besides ANTIBIOTICS, which we know will automatically create more dysbiosis, what can be done?  For starters, let's look at a study done by nine gastroenterologists from the University of Pittsburgh's Department of Internal Medicine (Herbal Therapy Is Equivalent to Rifaximin for the Treatment of Small Intestinal Bacterial Overgrowth) and published in the May 2014 issue of Global Advances in Health and Medicine.

"SIBO is widely prevalent in a tertiary referral gastroenterology practice.  Patients with SIBO have chronic intestinal and extraintestinal symptomatology which adversely affects their quality of life. Present treatment of SIBO is limited to oral antibiotics with variable success. One hundred and four patients who tested positive for newly diagnosed SIBO by lactulose breath testing were offered either rifaximin 1200 mg daily vs herbal therapy for 4 weeks.  Of the 37 patients who received herbal therapy, 46% had a negative follow-up LBT compared to 34% of rifaximin users.  Adverse effects were reported among the rifaximin treated arm including 1 case of anaphylaxis, 2 cases of hives, 2 cases of diarrhea and 1 case of Clostridium difficile. Only one case of diarrhea was reported in the herbal therapy arm, which did not reach statistical significance.   Herbal therapies are at least as effective as rifaximin for resolution of SIBO. Herbals also appear to be as effective as triple antibiotic therapy for SIBO rescue therapy for rifaximin non-responders."

Did you catch that folks?  Nine GI specialists from a major medical institution said that HERBAL TREATMENT is not just as good as, but better than, the medical standard of care --- rifaximin. Furthermore, said herbal remedies are at least as effective as the triple antibiotic therapy given to those who don't respond to rifaximin.  Let the magnitude of these conclusions sink in for a moment.  Not surprisingly there are some very good herbal formulas out there.  There is also some total junk.  The bottom line, however, whether we are talking about antibiotics or herbs, there are other steps that must be taken if you hope to solve the SIBO / IBS combination over the long haul.

• CHANGE YOUR DIET:  Foods that produce gas (sugar -- especially fructose in the form of something called FODMAPS) must be eliminated.  I've dealt with FODMAPS extensively in the past.  FODMAPS also happen to mimic the GI portion of Gluten Sensitivity (HERE).  Also be aware that FIBER and many common PROBIOTICS have the potential to cause bloating and distension as well. For those of you with hardcore sugar / carb addictions, THESE POSTS might be right up your alley.  Bottom line is that you will need to be on a FODMAP-free, GLUTEN FREE, PALEO DIET that cuts all GRAINS and BEANS as well as DAIRY and many FRUITS.   You'll also want to focus on consuming GOOD FATS.  I always recommend an ELIMINATION DIET to figure out exactly what you are sensitive to.
  

 

• GET OFF THE ANTIBIOTICS:  I've shown you in the past why antibiotics are arguably the single most dangerous drugs that people are regularly prescribed from cradle to grave (HERE). Worse yet is that the more of them you take, the more you'll need because they hammer the bacteria that make up 80% OF YOUR IMMUNE SYSTEM. Antibiotics create all sorts of physiological vicious cycles that will sooner or later destroy your health (see first link in bullet).

 

• GET OFF THE PROTON PUMP INHIBITORS:  Without going into great deal here, suffice it to say that the acid-blocking drugs known as PPI'S are both extremely common and heavily associated with the double-headed monster known as IBS / SIBO.  BTW, the warning labels on these drugs say that you cannot be on them more than three times a year for more than two weeks at a time.

 

• ADDRESS MOTILITY ISSUES:  Based on the work of FUNCTIONAL NEUROLOGIST Dr Ted Carrick, there are exercises to address the motility issues by stimulating certain parts of your brain, your cranial nerves, or your enteric nervous system.  Some of these include gargling, gagging, and ENEMAS / COLONICS.  As your healthcare provider because all of them might not be right for your particular situation.

 

• ADDRESS GUT HEALTH:  Because many of those dealing with these sorts of issues can't do fermented foods or probiotics, it makes it tough to not only address their intestinal permeability issues, but their MICROBIOME as well.  Depending on what's feeding the problem or how severe it is, FMT might prove beneficial in some situations.

Every day there are people getting off the MEDICAL MERRY-GO-ROUND by creating their own EXIT STRATEGIES.  And while there are no one-size-fits-all "cures," there are steps to take that will help most of you not only understand what's wrong with you, but start successfully addressing it as well.

You've only heard me say it about a million times --- when it comes to your health, inflammation is everything.  The problem is that it's rare to find people who truly understand what inflammation is, let alone the fact that it's a necessary component of your immune system (HERE) that can be driven to excess by any number of things, including diet.  Although there are a myriad of things that can cause inflammation, I've shown you how certain foods such as GRAINS, DAIRY, FODMAPS, GLUTEN, NIGHTSHADES, etc, etc, etc, have the potential to be inflammatory --- for some people, extremely inflammatory.  Conversely, there are foods that are anti-inflammatory (ANTI-INFLAMMATORY DIET). Today we are going to talk about how the fats that you consume are either driving or squelching inflammation in your body.  

The first thing you have to be aware of when it comes to fatty acid metabolism is that it's not only possible, it's rather common to see people who have trouble digesting fats.  This is frequently due to a lack of DIGESTIVE ENZYMES and diminished function of the liver / gallbladder, although it can certainly come from the pancreas as well (for the digestion of fats, STOMACH ACID is not the critical factor it is for protein).  Let's take a brief look at how the metabolism of fats relates to the amount of inflammation you will deal with on a day to day basis.

Although it's probably an unrealistic goal for most of us, the ideal ratio of dietary Omega-6's to Omega-3's would be 1:1 (experts say it should not exceed 3:1).  The problem is that when you start looking at studies on fish oil, you quickly see how bad things are in this department.  Thanks to the SAD (Standard American Diet), the ratio is between 25:1 and 40:1. Although Omega-6 fatty acids get a bad rap for being "inflammatory," this is not automatically so since there are two separate metabolic pathways on this side of the equation; only one of them being inflammatory, the other being anti-inflammatory.

The first fatty acid in this pathway is Linoleic Acid --- an essential fatty acid, meaning your body does not make it; it must be consumed dietarily.  Unfortunately, most people get way to much LA in their diet in the form of various cheap cooking oils such as SOYBEAN, corn, safflower, and cottonseed oil --- oils that are almost universal to heavily processed foods. There is, however, a better form of LA --- CLA or Conjugated Linoleic Acid.  Where does CLA come from?  It comes from consuming the sorts of fats that were considered deadly while I was growing up --- RED MEAT, EGGS, BUTTER, and full-fat dairy (whole milk).  It's important to realize that CLA has numerous health benefits as seen in peer-review, some of which include weight loss (in particular, it helps mobilize and burn fat), hunger control, blood sugar regulation, and down-regulating the part of the immune system responsible for inflammation.  

A dysfunction or deficiency of the enzyme that converts LA to GLA (Gamma Linolenic Acid) is yet another way that people skew their Omega-6 metabolism toward the pro-inflammatory AA (Arachidonic Acid) pathway.  What are the most common causes of this sort of metabolic dysfunction?  Honestly, it's the usual suspects --- the same actors we see with any number of other health issues --- OBESITY, BLOOD SUGAR DYSREGULATION, hormonal issues (including THYROID), ADRENAL FATIGUE (stress as measured by HRV), alcohol and drugs (this includes PRESCRIPTION DRUGS), TRANS FATS, along with any number of others.  The result is a myriad of inflammatory diseases that I have linked to throughout this post.  As far as supplementing, the two best sources of GLA are Black Currant and Borage Oils.  And while many people use it, the problem you get into with Evening Primrose Oil is that like soy, it tends to be a xenohormone (estrogenic).

DGLA is where we see the Omega-6 pathway split.  Depending on any number of factors, most having to do with diet and lifestyle (EPIGENETIC FACTORS), this pathway will either be driven to the left --- the anti-inflammatory PGE1 pathway, or the right --- the pro-inflammatory pathway that leads to AA (Arachidonic Acid).  While AA is certainly not a bad thing (it is a chief component of CELL MEMBRANES, THE BRAIN, MUSCLES, and liver), too much of a good thing is often a bad thing --- exactly what we see with virtually all INFLAMMATORY MEDIATORS. Too many highly processed, frequently rancid, grain, vegetable, and peanut oils, and you are going to make lots of leukotrienes and PGE2 --- both of which are highly inflammatory.  Not only that, but LIVING THE HIGH CARB LIFESTYLE is one of the biggest blockers of the PGE1 pathway.  As some of you might know, the AA pathway is blocked by NSAIDS and CORTICOSTEROIDS, but the side effects are numerous, accumulative, and potentially brutal.

Despite all the information on this topic, Americans continue to drive the inflammatory side of Omega-6 fatty acid metabolism to excess.  Since the early 1980's, hundreds upon hundreds of studies have shown how inflammatory leukotrienes and PGE2 are (they are two of the many cellular messengers we refer to collectively as "inflammation").  What does peer-review have to say about these two mediators?  As much as I would love to take the time to give you a long list of the problems associated with, you can freak yourself out by doing your own research (PubMed).  Within five minutes you will realize that both of them (particularly PGE2) are associated with a slew of INFLAMMATORY DISEASES, including nasty creatures like CANCER, ARTHRITIS, DIABETES, and HEART DISEASE.

The anti-inflammatory PGE1 pathway is mostly about promoting circulation and blood flow as seen by numerous studies on PubMed.

"α-Linolenic acid is relatively more susceptible to oxidation and will become rancid more quickly than many other oils. Oxidative instability of α-linolenic acid is one reason why producers choose to partially hydrogenate oils containing α-linolenic acid, such as soybean oil.  Soybeans are the largest source of edible oils in the U.S., and 40% of soy oil production is partially hydrogenated."  From Wikipedia's entry on ALA

As I stated earlier, Americans over-consume Omega-6's, while under-consuming Omega-3's by a factor of 25 to 40, depending on whose research you believe to be most accurate.  Furthermore, not all Omega-3's are created equally.  Linolenic Acid (in the form of Alpha Linolenic Acid or ALA) comes from seeds of Chia, Hemp, Flaxseed, Rapeseed (Canola), Soy, and a number of others.  Unfortunately, many ALA supplements use soy because it is cheap and abundant (it also happens to be a PHYTOESTROGEN / XENOHORMONE).  I also saw where Perilla (a form of mint that I've called "Strawberry Mint" for years --- around here it's considered a weed --- is considered a good source, although I've heard it's mildly toxic to cattle).   Here's the rub.

I've run into lots of people over the years, who for various reasons, don't want to take fish oil (even the PHARMACEUTICAL GRADE FISH OIL that has had all the protein removed making it non-burpy). Instead, they think they can get their Omega-3's by taking flax seed oil.  While I am personally a big fan of cold-pressed flax oil, it is critical to understand why it's not a substitute for animal-based sources of Omega-3's.  It all has to do with the crappy conversion of LN to EPA / DHA.  Again, according to numerous studies, and depending whose research you believe is most viable....

• To convert flax seed oil to equivalent amounts of EPA, you would have to consume approximately 15 times the amount of flax oil as fish oil since the conversion is only about 5 to 10%.
  
• To convert flax seed oil to equivalent amounts of DHA, you would have to consume between twenty to fifty times the amount of flax oil as fish oil since the conversion is even worse --- only about 2 to 5%.
  

The end-product of consuming EPA (it's better for inflammation) and DHA (it's better for brain function) is that you produce lots of Prostaglandin E3 (PGE3), which is extremely anti-inflammatory.  I could easily sit here and give you study after study on the benefits of PGE3 for a wide array of inflammatory problems.  Today I'm only giving you one. 

Three years ago next month, the journal Cancer Letters published a study called Prostaglandin E3 Metabolism and Cancer.  The authors, three oncologists from the University of Texas and MD Anderson Cancer Treatment Center in Houston, had this to say about EPA and DHA.  "The anticancer activity of Omega-3 fatty acids, especially those derived from fish, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid) (DHA), has been studied for centuries. A number of studies have suggested that the anticancer activities of EPA and DHA are associated with their effects on eicosanoid metabolism by which they inhibit prostaglandin E2 (PGE2) production."  Here's what's amazing about this study.  Not only do EPA and DHA promote anti-inflammatory PGE3, they inhibit pro-inflammatory PGE2.  This is true whether you are fighting cancer or arthritis, ASTHMA or ADHD, IBS or IBD. 

The first thing you need to understand is that where you get your fats from matters.  Dr David Seamans, a FUNCTIONAL NEUROLOGIST and nutritional expert, has a simple rule of thumb when it comes to diet --- eat vegetation (not GRAINS) and animals that ate vegetation (HERE).  In other words, the diet of the animal whose meat or by-products (eggs, milk, etc) you are consuming matters because it changes the fatty acid profile.  In the scientific literature, feedlot-raised beef is referred to as "obese" (which is exactly the goal of commercial feeding).  Naturally, grain changes the fatty acid profile, skewing it toward Omega-6 and Arachidonic Acid, increasing both inflammation and the likelihood of major weight gain (yes, obesity is considered a disease of inflammation). 

The second part of this equation is that there are any number of things that can adversely affect fatty acid metabolism, many of which have been mentioned today in passing.  Furthermore, if you take a look at the Fatty Acid Metabolism Chart above, it's critical to realize that even though I have not included them, there are enzymes driving each and every conversion step.  As I stated earlier, poor lifestyle choices are going to foul these conversions --- especially the conversions to PGE1 and PGE3 --- the anti-inflammatory part of this equation, while making the conversion to inflammatory AA the default pathway.

As per the title of today's post, this means that while LOW CARB DIETS (KETOGENIC included) can knock it out of the park as far as controlling the single most important factor as far as your health is concerned (blood sugar), it doesn't necessarily help you solve your SYSTEMIC INFLAMMATION as greatly as you were hoping it would.  The beauty of the PALEO DIET is that you are eating meats and fats that have been raised in a "SUSTAINABLE" fashion, not only getting the blood sugar benefits of Low Carb, but the fatty acid / inflammation benefits as well as the benefits of cutting the endocrine disruptors / xenohormones / artificial estrogens (see earlier link).  It's largely why I suggest that if you are doing low carb, it's just a hop, skip, and a jump over to paleo (HERE).

If you are struggling with chronic health issues and are not sure where to turn, realize that your case might require the intervention of a specialist in FUNCTIONAL MEDICINE.  Also realize that before going the FM route, there are any number of things you can do to take matters into your own hands and start taking your life back.  A basic outline of those steps can be found HERE.  No, it's not a solution for everyone.  But following steps that have been proven over and over again in the peer-reviewed scientific literature only makes sense.