Milk Casein, Amyloid, Pasteurization, Homogenization

Milk is a very special food for mammalian babies. It provides essential nutrients; stimulates development of the gut; promotes the growth of the unique neonate gut flora; and kills everything else. Milk is anti-bacterial, anti-fungal and anti-viral. It is used in fruit orchards as a pruning tool dip to prevent the spread of disease between trees, and it is used as a foot dip after ceremonial walking on hot coals. But is cow's milk healthy for adult humans and is milk compromised by pasteurization and homogenization?

Mother's Milk is Fierce
Milk as it is transferred from breast to baby is loaded with molecular weapons for the protection of the baby's respiratory and digestive systems. Cells from the mother are transferred along with the milk and quickly spread out on the surface of the mouth and digestive system to patrol for pathogens. The mother's immune system detects potential risks as the baby's mouth contacts the mother's lymphatic system at the breast, and the antibodies that are subsequently produced are transferred into the milk. Enzymes in the milk digest bacterial cell walls and other milk proteins are converted into anti-bacterial peptides in the baby's stomach before ultimately being digested into amino acid nutrients. Many of the fat/lipid nutrients in milk are also anti-bacterial or anti-viral. Most of the carbohydrate in milk is the simple disaccharide lactose that most bacteria can't use for food. The remaining 10% of the carbohydrates are extensions of the lactose to make galacto-oligosaccharides (GOS, a.k.a. bifidus factor) that are toxic to all but the few bacterial species that make up the highly specialized microbial community of the human baby gut flora. (Cow's milk has an entirely different composition, e.g. lacks bifidus factor, and supports a different gut flora.)

Milk is Liquid Fat
It is hard to transport fat in water, because it isn't soluble. That is true for blood or milk. We have all heard about good and bad cholesterol, LDL and HDL, and the problems of transporting blood lipids from gut to liver to tissues. Specialized carrier proteins are needed for lipid transport in blood and the same is true for milk. Caseins are the milk proteins that coat droplets of fats that make milk white and then form digestible curds in response to the baby's stomach acid and digestive enzymes. We exploit the natural curd forming response of milk proteins and lipid droplets to form yogurts and cheeses.

Pasteurization and Homogenization Put Milk in the Dairy Case
Milk behaves optimally when immediately transferred from the mother's mammary tissue to the baby's digestive tract. Bacteria that contaminate breast milk are quickly killed by cellular and molecular defenses of the milk itself. Thus, breast milk has a long storage life at room temperature, chilled or frozen. The natural defenses of milk also permit regional milk banks, where donated milk is minimally processed and screened, for subsequent use by hospitals to avoid problems, such as necrotizing colitis, associated with the use of artificial feeding substitutes. Commercial preservation of cow's milk in stores has resulted in attempts to extend the shelf-life by heat treatment (pasteurization) to provide additional protection from microbial contamination and homogenization to prevent curd formation.

Milk is for Babies
So why isn't milk the perfect food? Part of the reason may come from the highly specialized and essential role of milk for mammals like people. Millions of years of extreme selection pressure have made sure that every woman produces ample milk for all of her babies. Until very recently, if the baby could not successfully nurse, it would die. That made breast milk the perfect food for babies and milk was integral to the development of the baby gut, baby gut flora and baby immune system. But that didn't mean that cow's milk would be a healthy commercial food for human adults.

Milk Processing May Accentuate Casein Amyloid Fiber Formation
Proteins are made of a long sequence of a thousand amino acids. At each of those thousand positions there is one of twenty different amino acids. Some of the amino acids are hydrophilic and bind to water, whereas other amino acids are hydrophobic and bind only to lipids. Proteins in water fold and unfold in thousands of alternative configurations until the final shape is reached in which there is not enough energy in the molecular vibrations and movements of the water molecules to knock the protein into an alternative shape.

Heating/pasteurization and torturous mixing/homogenization can force milk casein and fats into new configurations that make the proteins stackable into fibers/amyloids. These milk protein fibers may be of interest, because protein fibers are important in many diseases, e.g. type I diabetes, Alzheimer's disease. The problem with amyloids, is that these fibers form a natural repetition of the same amino acid on each of the stacked proteins. This repetitive amino acid, e.g. positively charged lysine or arginine, can provide a binding site for a similarly spaced, oppositely charged molecule, such as heparin, which is involved in dragging molecules from the surface into cells. Beta amyloid fibers with positively charged amino acids in a band along their edges are what kills nerve cells in Alzheimer's disease.

Research has recently demonstrated that milk casein forms amyloid fibers in response to pasteurization and homogenization. It would be interesting to know if these fibers bind to heparin and if these fibers are toxic to intestinal cells.

I have raw cream from grass fed cows in my morning coffee and my three daughters never tasted formula.

Dr. Oz, Pain, Hot/Cold Receptors

The production of endorphins in tissues in response to nerve stimulation relieves inflammation and pain. Dr. Oz and the medical community seem to forget that hot and cold receptors in the skin can be readily triggered by natural products in foods, to stimulate the release of endorphins and treat inflammation in nearby tissues.

Hot and Cold Don't Easily Penetrate the Skin
Athletic trainers commonly apply hot and cold packs to avoid swelling and inflammation from injuries, and they are always discussing the virtues of various hot/cold regimens. They ignore the extraordinary efficiency of the circulatory system in regulating tissue temperatures and avoiding temperature changes. They also ignore the fact that chemical "hot and cold" salves and ointments are effective without actually changing the temperature of the skin. The essential observation is that triggering hot and cold sensing nerves is more important than changing the temperature of the damaged tissues.

Common Food Molecules Activate Hot/Cold Nerve Receptors
Peppers are hot, because they contain capsaicin that binds to protein receptors on nerves in the skin, which results in the brain sensation of heat. Camphor and castor oil bind to the same receptors. Menthol binds to corresponding cold receptors. Vicks Vaporub has both menthol and camphor, and therefore stimulates both hot and cold sensors. Vicks is also an effective treatment for tissue inflammation.

Vicks and Castor Oil are Effective Treatments for Pain and Inflammation
A bee sting or a burn on a finger will produce reddening, swelling and pain, that can be quickly alleviated by applying Vicks to the wrist. The hot and cold sensors of the wrist would be stimulated and the returning nerve signals would be generally detected in the whole hand and produce endorphins that would calm the inflammation and sooth the injured finger. In a similar way, an inflamed joint can be treated by topical menthol and castor oil, and lower abdominal discomfort can be alleviated by castor oil applied to the belly.

Tendonitis can be Treated with Peppermint Soap
I have treated a persistent tendonitis in my shoulder by applying Dr. Bronner's Peppermint Soap liberally to my shoulder and waiting a few minutes before continuing my shower. This gentle, persistent treatment produced relief within a week. This was a cure for this persistent inflammation and pain. It also works on joints.

What Dr. Oz needs to communicate is that there are simple ways to stimulate hot/cold receptors that have nothing to do with changing the temperature of deeper tissues, but these treatments are very effective in stimulating general endorphin production that reduces troublesome inflammation and pain. As an addendum, vagal stimulation, i.e. through yoga postures such as shavasana or the Valsalva maneuver, can produce a reduction in general inflammation.

New Antibiotics, Biofilm Inhibitors, Vitamin Deficiency

I was not expecting my recent reading of an article on femtosecond reaction kinetics to produce another discussion of quorum sensing, biofilms and vitamins. The idea behind the article was to identify new targets for drug design based on the ephemeral transition states that occur as enzymes bind substrates, stabilize transition states and yield product molecules. Drugs that mimic the transition states make good enzyme inhibitors. One of the target enzymes for the control of disease is an enzyme, MTAN, involved in the synthesis of quorum sensing molecules that orchestrate the construction of common biofilms. The idea is to inhibit MTAN and also avoid selection for antibiotic resistance. Unfortunately, targeting quorum sensing molecules also may produce vitamin deficiencies, since many of these molecules, in this case vitamin K, are also quorum sensing molecules.

Drugs have too many Side Effects
Specificity in the binding of molecules to the thousands of proteins that are coded by the ca. 20,000 human genes depends on a very tight fit between the molecular "key" and the binding site "lock" of the protein. Just as in physical world, a small key/drug molecule with limited surface detail is not as safe/specific as a larger key with many surface features, and a larger lock/enzyme active site that is harder to pick/has fewer interactions with random enzymes. Unfortunately, most drugs are small molecules with limited surface features that make them like molecular skeleton keys that produce many side effects by interacting with unintended proteins/enzymes.

Transition States are more Specific
A recent focus on drug research is to exploit molecular computation and modeling to design molecules that will bind to the part of an enzyme that actually participates in binding substrates and catalyzing chemical reactions. These designed molecules can interact with an expanded region of the enzyme and bind more strongly than the normal substrate. The designed molecules can be very effective inhibitors that will not react as nonspecifically as inhibitors identified by trial an error, e.g. statins.

Biofilm Inhibitors are Targets for Antibiotic Development
The enzymes involved in the synthetic pathways of biofilm quorum sensing signals have been identified and powerful inhibitors of some of these enzymes have now been designed and synthesized. These inhibitors are very effective in inhibiting biofilm formation by some common bacterial pathogens (and essential gut flora.)

Biofilm Inhibitors will also Block Vitamin Production in Gut Biofilms
The new biofilm inhibitor antibiotics may have enhanced specificity, but they target enzymes that also provide essential functions in biofilms that are needed for healthy gut and immune system function. Many of the vitamins that are produced by gut flora are also quorum sensing signal molecules in healthy gut biofilms. Thus, blocking MTAN to block biofilm formation of a pathogen, will also block gut synthesis of vitamin K, which is made in gut bacteria using the MTAN pathway. These inhibitors would be expected to be particularly damaging to the specialized gut flora of breastfed babies, since these gut bacteria are known producers of vitamin K.

Genetics of Food Intolerance

Food intolerance is based on missing bacteria in the the gut rather than inadequacy of human enzymes, e.g. lactase, or altered immune system.

I make the extreme statement that food intolerance is not genetic, to emphasize that the vast majority of intolerance can be cured by changing the bacterial composition of the gut's microbiological community, the gut flora, rather than attempting to accommodate a permanent deficiency. The two common "intolerances" that are offered by my readers to invalidate my sweeping statement are lactose and gluten (celiac) intolerance.

Lactose Intolerance is Not Due to Inadequate Lactase
Everybody has the same gene for lactase, but some people have altered upstream control elements and continue to express lactase in their intestinal cells after infancy, whereas others don't. The racial pattern of adult lactase expression is an interesting note on human evolution, but is irrelevant with respect to an individual's ability to tolerate the lactose sugar in dairy products.

Lactose is the major sugar present in milk and the ability of the intestines to utilize lactose directly like glucose is a selective advantage for human evolution. Absent that ability, lactose would just pass through the gut without impact. However, bacteria in the colon also have lactose digesting enzymes. These bacteria produce hydrogen and methane gases, and these products in turn can feed other bacteria. If all of the products are consumed, then the lactose has been treated as a soluble fiber and the result is more gut bacteria and a happy gut. If some of the bacteria are missing, then the lactose acts as a laxative, e.g. lactulose, and the bowels are not so happy.

All that is needed to cure lactose intolerance, as in all food intolerances, is to provide the gut bacteria that are missing to fully metabolize the offending sugars or polysaccharides. Just continuing to eat dairy without also eating or introducing new species of bacteria into your gut, will just provide more symptoms, but eating yogurt still containing live probiotic bacteria (Read the label. Any live bacteria listed will work.) that have the enzymes to ferment lactose, will lead to a rapid cure. (See reference below.) As the fermenting bacteria grow in the gut, they transfer their genes to gut bacteria in the biofilms lining the gut and these new species of bacteria keep the lactose out of trouble.

The point is that having a food intolerance means that the aggregate of all of the genes in all of your gut microorganisms is lacking the genes/enzymes needed to completely digest a food component. In the case of lactose intolerance, the missing genes are present in typical probiotics, bacteria that grow on milk/lactose.

Celiac is not a Typical Food Intolerance
Celiac is a complex interaction between major toxic proteins in wheat (gliadin), detox gut enzyme (tissue transglutaminase, tTg) and antibodies. Gliadin is a wheat protein adapted to attack the intestines of herbivores. Herbivores, such as insects and humans, can in turn protect themselves from gliadin and other polyglutamine proteins with the enzyme transglutaminase. tTg binds to glutamines in gliadin and converts them to glutamic acids. Unfortunately, while the gliadin is bound to the tTg, inflammation can predispose the gut to present these proteins to the immune system for processing to trigger antibody production. This is the start of the autoimmune disease.

The major histocompatibility antigens (MHAs) code for the proteins that display fragments of proteins on cell surfaces for antigen presentation and immune response. There is a lot of MHA variation and evolutionary adaptation. Some MHAs favor antibody production to gliadin and tTg. This just shows that celiac and grain/gluten intolerance is not a typical food intolerance, which will be remedied by simply altering gut bacteria, even though establishing gut bacteria that metabolize gliadin or that reduce autoimmunity, may be part of the cure.


Enhancing Gut Flora is Part of the Cure for all Autoimmune Diseases
There are rare food allergies, even though the majority are misdiagnosed intolerances. The production of antibodies to food antigens is a symptom of the breakdown in communication between the gut immune system and gut flora. Particular species of bacteria are responsible for the development of both the aggressive and suppressive components of the immune system, which occurs in the lining of the gut. Loss of the suppressive cells, Tregs, can result from unhealthy diets and exposure to antibiotics, and results in autoimmune disease, in which the aggressive immune system is out of control and attacks self antigens.

Symptoms of all autoimmune diseases can be improved by reestablishing normal control of the aggressive part of the immune system via healthy gut flora. Clostridium species of bacteria normally induce healthy development of the suppressive immune system and these types of bacteria are common in soil clinging to fresh vegetables prior to extensive washing. Which of the bacteria that are eaten become established in the gut flora is unpredictable, because the bacteria interact with each other, food and cells lining the gut. The only safe and simple procedure currently available is the fecal transplant. Some experimental fecal transplants are facilitated by the use of encapsulated freeze-dried gut flora. There is great resistance to this simple, safe, cheap approach from the medical industry.

Reference:
Almeida CC, Lorena SL, Pavan CR, Akasaka HM, Mesquita MA. 2012. Beneficial Effects of Long-Term Consumption of a Probiotic Combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult May Persist After Suspension of Therapy in Lactose-Intolerant Patients. Nutr Clin Pract., 27(2):247-51.

Dr. Oz, Vitamins, Biofilms

Vitamins supplement enzyme action, but they are produced by gut flora for biofilm communication.

Dr. Oz and the general biomedical community promote the idea that vitamin supplements or in foods are needed or improve health. Of course, several research studies show that typical multivitamin supplements or the levels of vitamins in "enriched" foods do not provide improvements in health. Since gut flora produce all of the needed vitamins, this should be no surprise. But why do gut bacteria release vitamins needed for the normal functions of the human body?

Vitamins are Enzyme Cofactors

Vitamins are small molecules that bind to particular cellular enzymes and provide functions that can't be provided by proteins. Enzymes are linear strings, polymers, of about a thousand amino acids. The 23,000 human genes code for the sequence of amino acids in as many enzymes. The amino acid strings fold up systematically into three dimensional balls that bring together chemical groups of the amino acids that can catalyze biochemical reactions. The twenty different amino acids in proteins are limited in the scope of their reactions. Binding of some metabolic products, such as vitamins, expands the types of reactions possible. Vitamins are enzyme cofactors. Bacteria can synthesize all of the vitamins needed for metabolism, but humans can't.

Vitamin D is a Hormone

Vitamin D is not a typical vitamin.  It is not an enzyme cofactor, but rather it is a steroid hormone that is produced in the skin from cholesterol through the action of ultraviolet light. The production of antibacterial peptides in the small intestines, for example, is a response of intestinal cells to vitamin D. Exposing arms and legs to sunlight produces about 10,000 IU of vitamin D per minute. (Typical supplements contain only 1,000 IU.) Production of vitamin D is reduced by skin pigmentation, sunscreen and inflammation. People exposed to daily sunlight for hours in San Diego, for example, may still be deficient in vitamin D, if their production of vitamin D has been shut down by chronic inflammation, as indicated by typical inflammatory conditions, such as arthritis, allergies, inflammatory bowel diseases, obesity, dental/oral infections, prostatitis, thyroiditis and other autoimmune diseases.

Vitamins are Produced by Gut Biofilms

People with healthy, diet-adapted gut flora, can subsist on very limited diets without vitamin deficiency diseases, because all of the vitamins can be obtained from bacteria growing in films coating the lining of the gut. These biofilms are complex communities of dozens of different bacteria and fungi. The bacteria synthesize polysaccharides in which these and other bacteria and fungi become embedded. The biofilms release vitamins that are taken up by intestinal cells to provide the needs of the body.

Vitamins are Chemical Signals for Biofilm Assembly

Bacteria, such as E. coli, do not form biofilms, if they are just grown at low concentrations on laboratory nutrients. If the concentrations of bacteria become very high, however, the bacteria respond by activating genes that coordinate biofilm formation. Bacteria detect the presence of other bacteria by releasing and detecting chemical signals in a process called quorum sensing. The chemical signals used in quorum sensing and biofilm maintenance are vitamins. Thus, human intestines are adapted to exploit the presence of biofilms and vitamin secretion. Humans need not synthesize vitamins, because they are always produced by gut biofilms as an essential biofilm function.

Antibiotics and Multivitamin Supplements

Antibiotic use is known to disrupt gut flora and produce vitamin deficiencies. Killing off healthy gut biofilms with casual use of antibiotics should be anticipated. The medical industry is remiss, however, in not repairing gut flora after medically mandated antibiotic use. Probiotics can temporarily supply some of the functions of the hundreds of bacterial species in each healthy individual, but they do not replace complex biofilms.

 The vitamin production of some of the bacterial species eliminated from the gut by antibiotics can be replaced by vitamin supplements, but supplements may disrupt the normal vitamin/quorum sensing communication and further disrupt biofilms. Thus, vitamin supplements may be unhealthy, if they disrupt biofilms that are necessary for healthy function of the gut-based immune system, which is needed to avoid, for example, allergies and autoimmune diseases.

Major Points about Vitamins, Biofilms and Health

• Health requires gut biofilms to supply vitamins and control the immune system.
• Biofilms produce and use vitamins for maintenance of biofilms.
• Eating vitamins may disrupt normal biofilm formation.
• Antibiotics disrupt gut biofilms and cause vitamin deficiencies and immune system disfunction.
• Biofilm repair requires ingestion of missing bacterial species (150 total) and may be inhibited by excessive hygiene.

Dr. Oz, Constipation, Soluble Fiber, Food Intolerance

--- all 200 posts here ---
The medical industry doesn't seem to understand the basics about the interaction of gut flora with food and the immune system.

I respect Dr. Mehmet Oz for creating a media personality to communicate medical information for public consumption and I know that there are many constraints placed on his freedom to discuss his personal and professional insights on health. That said, it seems to me that the public Dr. Oz, the voice of mainstream medicine and to some extent the food industry, fails to understand some essential features of the transformation of food to poop.

Dr. Oz has described on his television series, the impact of major disease on diagnostic changes in the color and appearance of poop, but he doesn't seem to understand that poop is mostly bacteria that have grown in the gut. The major implication of the predominance of gut bacteria in poop is seen in constipation. The pounds of bacteria in the colon provide the bulk and hydration of the poop, and when the bacteria are not abundant, the result is compacted, undigestible dietary fiber, which is the hard poop of constipation. That is why antibiotics, which have the major effect of killing gut bacteria, result in constipation. Chronic use of antibiotics, or frequently even a single use, can produce prolonged constipation.

The impression that I get from listening to Dr. Oz discuss soluble fiber, is that these food polysaccharides pass through the small intestines and then contribute to the texture/hydration of poop. This would be the case, if there were not bacteria in the gut, because the only polysaccharides/carbohydrates digested by human enzymes in the gut are starch and sucrose. Plants (and animals) produce hundreds of other types of polysaccharides that can only be digested by bacterial (and fungal) enzymes. All of the types of polysaccharides, abundantly present in fruits and vegetables, that can be digested by gut bacteria are called soluble fiber. (Undigestible fiber, such as grain fiber, is of no benefit.) Soluble fiber is the main source of food for gut bacteria and is also converted into the short chain fatty acids, e.g. acetic acid, that are the major nutrients for the human cells that line the colon. Thus, soluble fiber, such as the inulin in leeks or the pectin in apples, is essential for healthy poop and intestines.

Dr. Oz advises eating dairy and fermented foods with their live bacteria to supplement gut flora and to compensate for antibiotic treatments. This suggests that providing just a few different species of fermenting bacteria, probiotics, can produce a healthy community of gut bacteria. Unfortunately, each human gut requires hundreds of different species of bacteria that are not present in common dairy products, such as yogurt. The hundreds of different types of bacteria needed for a healthy gut are normally acquired from other people and animals, and from uncooked, raw vegetables. Cooking and excessive sanitation eliminates the exchange and acquisition of healthy bacteria. Exposure to antibiotics can lead to a lasting deficiency of gut bacteria that is unrecognized by modern medicine.

Dr. Oz recommends that people who have trouble eating certain foods or have good intolerances, should avoid the problem foods. This suggests that the problem is somehow in the intolerant person, even though there are no genes for food intolerance and very few cases of food intolerance result from an immune reaction. Food intolerance is actually the inability of an individual's incomplete gut flora to digest certain types of food. Antibiotics, for example, can kill off species of bacteria that are needed to completely digest certain types of soluble fiber or other plant products, phytochemicals, so instead of producing the needed short chain fatty acids, other irritating molecules are produced and the digestive system is upset. Simple intolerances, such as lactose intolerance, can be remedied by just eating small amounts of yogurt containing fermenting bacteria, probiotics, that have the genes for enzymes that can digest lactose. In a couple of weeks, most people are permanently able to tolerate lactose. More complex intolerances may require more persistent pursuit of the missing bacterial species by eating many different types of raw vegetables with clinging soil bacteria. The medical community has failed to acknowledge the need to repair gut flora compromised by antibiotics and to provide simple guidelines for reacquiring missing gut bacteria.

Dr. Oz provides a great service by promoting some healthy ideas, but it would be even better if he helped the public to understand how the gut and gut flora produce healthy poop.

Baldness Cure: Low Dose Naltrexone?

Naltrexone can be used to block opioids and provide the basis for treatment for drug abuse, but in low doses (LDN) it provides a paradoxical increase in natural endorphins that reverses inflammation and provides an effective treatment for autoimmune diseases, e.g. MS.

Receptors
A recent anonymous post brought the role of cannabinoid and opioid receptors in baldness to my attention. The relationship between these receptors, inflammation and autoimmunity is very complex. The heat and cold sensors, which also bind capsaicin and menthol, appear to be mediated by endorphins. Acupuncture also seems to function by similar mechanisms and is inhibited by high dose Naltrexone.

Low Dose Naltrexone
A side effect of high dose Naltrexone (e.g. 50 mg/d) is hair loss. Low dose Naltrexone (e.g. 1 mg/day, taken at night) appears to stimulate hair production and it may reverse the effects of Finasteride, since LDN improves libido.

Endorphin-Suppressed Inflammation
I would expect hair loss to be prevented/reversed by topical treatments that block inflammation and autoimmune attack on hair follicles. Curcumin, from turmeric, blocks NFkB and appears to help hair loss. Capsaicin can block inflammation via endorphin production and also helps hair loss. I would also expect that topical menthol and castor oil would reduce hair loss.

Anti-Inflammatory Diet
The anti-inflammatory diet that I recommend, may not be sufficient to block hair loss, but it may provide a good foundation for other anti-inflammatory treatments. In fact, other topical treatments may not be effective unless chronic, diet-based inflammation is eliminated. It may also be important to reduce oxidative stress by optimizing glutathione and vitamin C.

I would appreciate comments by others who may have experience with LDN and balding.

Baldness/Prostatitis Treatment, Impotence, Inflammation

Male pattern baldness appears to result from the interaction between enzyme-modified male sex hormones (DHT) and receptors in some hair follicles of the scalp.  Inhibition of the enzyme by topical (Rogaine) or oral administration (Propecia) of an inhibitor, e.g Finasteride, can stop hair loss.  One of the significant side effects of oral use of Finasteride is loss of all sexual functions, which can be temporary and reversible after the drug is stopped, or permanent.  I think that inflammation may play a critical role in both hair loss (and prostatitis) and loss of sexual functions in response to Finasteride and an anti-inflammatory approach my be helpful.

Testosterone is Converted to  Dihydrotestosterone (DHT) by 5-Alpha Reductase

The male hormone, testosterone, is produced in the testes and travels to hair follicle or to other parts of the body via the blood in either a free state, or bound to a carrier protein.  Only the free form interacts with the 5-alpha reductase enzyme in the scalp to produce the DHT that diminishes hair follicles.  Application of the Reductase inhibitor, Finasteride, directly to the scalp stops the production of DHT in the scalp.  Taking oral Finasteride blocks DHT production throughout the body, and unlike topical application, can also result in apparent changes in the brain, which can explain loss of sexual behavior.

DHT Role in Hair Loss and Brain-Based Sexual Behavior is Poorly Understood

Surprisingly, the molecular biology of male pattern baldness (MPB) is not known, even though this is one of the classic examples of a dominant, sex-associated phenotype, i.e. a single copy of the baldness allele in males produces baldness.  Of course, this is not a sex linked gene, since baldness is not inherited from mothers with their X chromosome, and in some cases as many as 80% of the males in a single family exhibit male pattern baldness.  It appears to me that baldness is also likely to have an environmental, e.g. gut flora, heritability similar to obesity.  In fact, metabolic syndrome and type 2 diabetes are substantial risk factors for male pattern baldness.

There is also an association between MPB and polycystic ovary syndrome (PCOS) in females of the same family.  I would also expect that MPB is related to prostatitis, since the prostate is a major processor of testosterone to DHT via 5-alpha reductase and prostatitis can be treated with Finasteride.  PCOS is also treated with Finasteride.  PCOS is also associated with obesity and metabolic syndrome.  Prostatitis, PCOS, obesity and metabolic syndrome can all be treated as inflammatory diseases with significant contribution of dysfunction of gut flora.

  

PMB, Testosterone, 5-Alpha Reductase and Aromatase

In PMB, testosterone levels are lower and 5-alpha reductase is higher.  This suggests that testosterone has been converted into DHT in scalp hair follicles.  In order for DHT levels to make a difference, the hair follicles have to have specific receptors for DHT.  Testosterone/DHT receptors, like all steroid hormone receptors, are proteins in the cytoplasm of cells, which bind the hormone and become activated as transcription factors that migrate to the nucleus and control the expression of particular genes.

Testosterone can also be converted by another enzyme, aromatase, into estrogen.  DHT cannot be converted enzymatically into estrogen.  Estrogen has a separate receptor and controls a different set of genes.  Thus, enhanced conversion of testosterone into DHT in MPB follicles, may shift the balance away from estrogenic in favor of androgenic effects.  Women exposed to aromatase inhibitors, stop converting their limited testosterone into estrogen and more is converted into DHT, resulting in rapid signs of baldness.   All brain estrogen is produced from testosterone via aromatase in the brain and aromatase inhibitors can reduce libido in women.

DHT Activates Inflammatory NFkB (and Block Nerve Apoptosis?)

Prolonged exposure of cerebral blood vessels to DHT has been shown to activate the inflammatory transcription factor NFkB.  Conversion of testosterone to DHT by 5-alpha reductase may amplify the inflammatory impact of testosterone by virtue of the stronger activation of the androgen receptor by DHT.  Activation of NFkB also suppresses apoptosis and may be necessary to maintain some neural cells.  Reducing DHT production by 5-alpha reductase inhibitors, may reduce NFkB activation in the brain and expose androgen-sensitive parts of the brain to apoptosis.  This loss of brain cells may result in loss of sexual behavior.

Vitamin D is also Steroid Hormone/Co-Transcription Factor

It should be remembered that vitamin D also has a cytoplasmic receptor that acts as a transcription factor and that vitamin D deficiency can result in hair loss.  If fact, vitamin D is required for the normal hair growth cycle, as well as intestinal villi development (defensin production).   The vitamin D receptor can also inhibit the inflammatory transcription factor NFkB.

Thus, multiple steroid hormone receptors are involved in hair development, prostate function and brain sexual behavior.  Modification of the conversion of testosterone into DHT or estrogen can have diverse consequences directly or indirectly by modification of inflammation/development signaling.  This is also true of fertility/menstrual cycles, mammary tissue and perhaps intestinal epithelial villi or skin/follicle development in the case of rosacea.  All of these processes are affected by enzymatic interconversion of steroid hormones and interaction of hormone/receptor and NFkB transcription factors.

Questions

The questions that I have about hair loss (or prostatitis), treatment with 5-alpha reductase inhibitors, and subsequent loss of sexual function are:

1. Why are the genetics of MPB so unusual/non-Mendelian?  There are too many males with MPB in the same family.  This points to some hereditary predisposition, but with a major environmental component, e.g. “inherited gut flora.”
2. Why are only a few of the people treated with 5-alpha reductase inhibitors rendered permanently impotent?
3. There is anecdotal evidence that dexamethasone (or prostate message and antibiotics) can reverse some impotence.  Does this indicate that inflammation is involved in hair loss and/or impotence?  Where do the antibiotics act and is their action to kill bacteria?

Treatment for Finasteride-Induced Impotence

Impotence is a severe side effect of a few men using Finasteride to treat baldness or prostatitis.  I doubt that those with induced impotence are genetically predisposed, but rather these individuals probably had an altered immune system.  I suspect two types of alterations:  a compromised blood/brain barrier and a compromised suppressive immune system.  Diet-based chronic inflammation is a typical path to a leaky blood/brain barrier that facilitates the penetration of Finasteride into the brain to alter 5-alpha reductase in the DHT-responsive regions responsible for sexual function.  I presume that the subsequent reduction of DHT also results in inflammation that contributes to loss of function.  Dexamethasone and some antibiotics could attenuate the inflammation and return normal function.

Suppression of attack of normal tissues by the immune system is mediated by development of the suppressive immune system in the gut in response to specific bacteria of the gut flora.  A history of antibiotic treatment can yield a dysfunctional gut flora and a compromised immune system that results in allergies and autoimmunity.  Prostatitis may have an autoimmune component and may result from compromised gut flora.

All of the symptoms discussed from hair loss to prostatitis to impotence should be improved by normal function of the gut and immune system by my anti-inflammatory diet and normal gut flora.  Use of antibiotics will always lead to further side effects by perturbing and limiting the function of gut flora and the immune system that is dependent on the gut flora.

I particularly suspect that vitamin D deficiency is a significant contributor.  Most “anti-inflammatory diets” will lead to chronic inflammation, because they are just high carb diets with a few vegetables.  All of the complex phytochemicals produced by plants will be “antioxidants”.  Adding these antioxidants to an inflammatory diet has no impact.  Look at my anti-inflammatory diet and note that it requires attention to serum vitamin D levels, gets most calories from saturated fat and not carbs (low carb/high saturated fat), no vegetable oils and high omega-3 (EPA, DHA) to 6 ratio.  That means meat/fish/eggs/dairy and lots of fresh vegetables for new gut bacteria.

Podcast on Jimmy Moore's Low Carb Show

Jimmy Moore

Jimmy Moore invited me to speak on his Livin' La Vida Low Carb show.  So I recorded a conversation with him about low carb diets, inflammation and disease.  It was great fun to talk about fixing gut flora and the benefits of an anti-inflammatory diet that is based on low carbs and high saturated fats.

Here is the link for show # 476, June 12, 2011.

Soluble Fiber: Food for Gut Flora

The human body only produces enzymes to digest proteins, fats, starch and a few simple sugars. The remaining components of food either pass through the intestines undigested (insoluble fiber) or are digested by bacteria and fungi in the colon (soluble fiber.) Soluble fiber feeds gut flora. Insoluble fiber is usually minimized by traditional food preparation, for example grains, because it contains unhealthy materials, such as phytic acid. Soluble fiber is healthy and required for normal development of the gut/immune system, whereas insoluble fiber should be avoided.

Soluble Fibers in Vegetables are Carbohydrates/Polysaccharides

Plant cells are surrounded by cell walls composed of long chains of sugars, polysaccharides. These wall polysaccharides, e.g. pectin, arabinogalactans, xyloglucans, and storage glucans and fructans, are highly complex in structure and can only be digested down to simple sugars by the action of dozens of different enzymes produced by dozens of different bacterial species in the colon. Many plants (as well as fungi and bacteria) also produce unique polysaccharides that are only susceptible to additional unique bacteria enzymes. Thus, digestion of diverse vegetables requires hundreds of different species of bacteria in the gut. Healthy gut flora consists of more than 150 different species of bacteria, which were eaten with food and adapt to the gut environment.

Food Intolerances/Most Food "Allergies"/Constipation Reveal Missing Enzymes

Enzymatic treatment of complex polysaccharides in the gut is a complex process that also yields many intermediate products that can influence both gut flora and the gut itself. A well adapted gut flora can systematically digest most of the food molecules that pass into the colon and produce only short chain fatty acids (CFAs) that feed the colon and pass through the liver to the rest of the body.

Antibiotics or a history of limited food choices and excessive hygiene can result in a simplified gut flora that only partially digests soluble fiber and results in accumulation of unusual byproducts that irritate the gut, and cause bloating and gas. Adverse reactions are called food intolerances or food allergies. Since bowel stools are composed predominantly of loosely packed gut flora, inability to fully digest and convert soluble fiber into more gut flora, also results in constipation.

Soluble Fiber in Meat is also Polysaccharide

Meat is made of fibers of protein connected to bone by polysaccharides. The tendons, gristle and other chewy parts of meat are made of chondroitin sulfate and other glycosaminoglycans (GAGs). Heparin is another GAG, which is released onto the surface of the intestines to block the adhesion of viruses and pathogens to the gut, and is subsequently digested by colon bacteria. Other components of meat (and vegetables), such as nucleic acids and some fats are also digested by enzymes of the gut flora. The versatility of gut flora to adapt to a huge variety of foods permits people to live on very diverse diets, ranging from vegan to paleo.

Modern Diets Starve and Simplify Gut Flora

Modern diets consist of processed foods that are made of fat, protein and starch, all of which are digested and absorbed before reaching the colon. These simplified foods produce a simplified gut flora that may also produce more CFAs rather than stool forming gut bacteria. In other words, eating larger amounts of simpler foods can result in more of the nutrients being absorbed and making it easier to gain weight on less food with a tendency toward constipation. These diets may also select for bacteria that maintain the simplified, "efficient" gut flora community and provide the potential for the spread of obesity through a population. Having friends and relatives who are obese and presumably have gut bacteria that favor obesity, increases the risk of obesity. It seems likely that obesity is contagious.

Simplified Gut Flora also Means a Compromised Immune System

Complexity in the gut flora is also needed to produce a healthy immune system, because different species of bacteria in the gut stimulate the development of different parts of the immune system, which develop in the lining of the gut. Soluble fiber is the normal food for the colon bacteria that control the part of the immune system that regulates autoimmunity and allergy, for example. Obesity is also associated with increased risk of degenerative and autoimmune diseases, which is consistent with defects in the gut flora that reside in the colon. Thus, the modern high carb diet contributes to the symptoms of obesity by elevating blood sugar, blood CFAs, as well as compromising the gut flora needed for normal functioning of the immune system.

Healthy Gut Flora = Anti-Inflammatory Diet + Eating New Bacteria

A damaged or simplified gut flora can be fixed by eating foods that supply nutrients for the body as well as feeding the gut flora, e.g. plenty of different types of soluble fiber. It is also necessary to eat the missing bacteria. Just adding a few probiotics with yogurt will not fix the problem and cooking kills all of the good bacteria. Fermented foods, especially those based on bacteria from your own home and garden, are good sources of health-providing bacteria. Raw vegetables will also provide bacteria that may be useful in your gut flora, as long as the vegetables are not too thoroughly washed. Sterilizing and cooking vegetables may avoid rare pathogens, but will certainly prevent contributions to a healthy gut flora.

Food Poisoning and Manmade E. coli

Bacteria on food is a problem for diet-compromised people.   

Gut Flora are Required for a Healthy Immune System

Healthy people don't get sick from food poisoning, because their gut flora provide protection.  Gut bacteria control the development of the human immune system by producing interesting compounds, including short chain fatty acids and vitamins.  In response to the gut bacteria, the healthy immune system produces white blood cells that can effectively attack bacteria, and also control this aggressive behavior to spare human cells and avoid unnecessary attacks on beneficial bacteria.

Disrupted Gut Flora Lead to Susceptibility to Disease/Infection

Gut flora can be compromised by what we eat and antibiotics.  Those normally affected by food poisoning are the very young (on formula), the old (constipated) and those treated with antibiotics.  Each of these groups have abnormal gut flora.  Food poisoning is rarely observed in exclusively breastfed babies being introduced to foods, because human milk contains potent antimicrobial polysaccharides (human milk oligosaccharides) that only permit the growth of a few species of Bifidobacteria.  Formula (in any amount) disrupts the normal development of the gut and immune system by stimulating an inflammatory growth of adult gut bacteria, making these babies more susceptible to intestinal and respiratory diseases, including food poisoning.

Constipation, which is more common in older people, reflects a disruption of the gut flora and decreases the effectiveness of the immune system in these individuals.  In most cases the compromised gut flora results from a long history of a restricted diet and  reduced access to environmental sources of bacteria.

Antibiotics are usually ignored as major corruptors of the immune system, even though they are known to produce diarrhea and constipation.  Doctors reluctantly suggest that people taking antibiotics should just eat some yogurt.  This is a silly oversight that severely compromises future health, because probiotics supply only a tiny fraction of the 150 different species of bacteria needed for a healthy body and immune system.

Pathogenic E. coli is Made by Antibiotic Use in Cattle

E. coli is a common and essential resident of the human gut and the best studied bacterium.  This bacterium is not normally resistant to antibiotics nor does it produce deadly toxins.  Antibiotic resistance and toxin production results from treating cattle with antibiotics to increase fat production prior to butchering.

Antibiotics Select for E. coli that Stick to Rectal Surface of Cattle

Pathogenic E. coli are not found throughout cattle fecal material, but rather they are only in the outermost surface layer.  This outer layer of material contains bacteria from the surface of the rectum just as the cow pies are deposited.  E. coli does not normally stick to this surface, because it lacks a protein, such as a hemagglutinin capable of binding to the surface polysaccharides, heparan sulfate.  Antibiotics kill off the bacteria normally residing on the surface.  As a member of the intestinal biofilm community, E. coli continually exchanges DNA/genes with other bacteria in the gut and picks up three useful genes, to become a pathogen:

1. Antibiotic resistance
2. Hemagglutinin for sticking to surfaces
3. Toxin to release nutrients from the intestinal walls.

E. coli with these three genes can colonize the rectal tissue of cattle in feed lots.

Pathogenic E. coli Can be Easily Avoided

We have to work hard as a society to have problems with E. coli.  Pathogenic E. coli results from absurd use of huge quantities of antibiotics just to disrupt the normal gut flora of cattle so that they become unhealthy and store fat in their tissues, i.e. prime beef.  The same effect can also be achieved just by feeding the cattle some short chain fatty acids, or better still avoiding this step by feeding exclusively on grass.  It would also be easy to treat the few cattle that have pathogenic E. coli, so that it doesn't become a problem.  Proper treatment of manure and meat processing would also block transmission of pathogenic E. coli to agricultural crops or meat.  Finally, an Anti-inflammatory Diet and Lifestyle would provide a healthy gut flora and immune system that would make people less susceptible to the pathogen.

Udder Nonsense

Recent articles in the popular press have heralded the genetic engineering of cows with some human milk proteins.  Milk produced by these transgenic cows is advertised as being similar or the same as human  breast milk.

This is like claiming that the udder in the picture is an all natural, low BPA container for fortified water.  

The breakthrough in humanized cow's milk, announced by Chinese researchers in PLoS One, actually documents replacement of cow lysozyme with the corresponding human enzyme.  That does not make the milk human anymore than adding egg white lysozyme would turn the cows into chickens. If it moos like a cow...

Cow's milk-based formula harms infants, because the carbohydrates it contains do not support the normal development of infant gut flora.  The result is gut inflammation, and not normal gut and immune system development.  Even human proteins produced in cows will have characteristic cow sugars attached.  It is these cow sugars on milk proteins that are associated with colic. The chains of sugars (milk oligosaccharides) free and/or associated with milk proteins are different in cows and humans, and cow carbs are a problem in formula.

I think that it is silly to support humanizing cow's milk formula, when the sensible solution is to support breast feeding and licensed human milk banks.  The natural approach is much cheaper and far healthier.  Only human milk and human milk-derived fortifiers should be used for infants (especially preterm) in hospitals.  It is time for the healthcare industry to realize that disruption of gut flora by antibiotics or artificial formula is a health risk.  The data are clear -- cow's milk (including transgenic cow’s milk) in the hospital may be profitable, but it is unhealthy, e. g. contributes to Clostridium difficile and necrotizing enterocolitis infections, and contributes to long term health problems, such as inflammatory and autoimmune diseases.

References:

China Genetically Modifying Cows To Produce Human Breast Milk

Characterization of Bioactive Recombinant Human Lysozyme Expressed in Milk of Cloned Transgenic Cattle

Contagious Health

Healthy gut flora: bacteria from family, friends, Fido and food provide the foundation for the complex microbial community of the intestines, which controls the immune system.  Antibiotics and hygiene are detrimental to gut flora and health.

Gut Flora Are Complex

Recent studies of the gut flora, e.g. the human gut biome, show that each individual maintains more than 150 different species of bacteria.  Worldwide, that means that about a thousand different bacterial species are common residents of the human gut and together those gut bacteria use more than 1 million different genes.  Many of those genes code for the enzymes used by gut bacteria to digest plant polysaccharides, i.e. soluble fiber.

Hygiene Isolates People from Healthy Sources of Gut Flora

Every time we speak, we release a mist of bacteria from our lungs, mouth and GI tract.  These bacteria are on our skin, clothes and personal items, and provide a source of the bacteria that make us healthy.  Parents and older siblings pass these bacteria on to younger children.  These donated bacteria are essential for the development of a healthy immune system and children growing up with healthy relatives and exposed to soil bacteria via pets, farm animals, etc. are healthier than children who are more isolated.  

In this sense, hygiene is unhealthy, because an individual is isolated from new sources of bacteria that could replace those lost by limited diets, antibiotics, etc.  Otherwise, health is contagious, since gut bacteria from healthy individuals can spread among the population.  Washing hands and food is unnatural and unhealthy.

Few Bacteria Make You Sick, but Many Are Essential for Good Health

Food intolerance can result from “good” family hygiene, limited diets and exposure to antibiotics.  A common intolerance results from the absence of bacteria that produce an enzyme to digest dairy lactose, i.e. lactose intolerance.  Lactose intolerance can be readily cured by eating a dairy product, such as yogurt, that contains both lactose and live bacteria (probiotics) that can digest the lactose.  Simply eating moderate amounts of live yogurt daily for a couple of weeks resupplies the gut flora with bacteria that can digest lactose, and the intolerance is gone.

Soluble Fibers Are Plant Polysaccharides that Are Digestible by Bacterial Enzymes

Humans only produce enzymes to digest one polysaccharide, starch.  All of the other hundreds of polysaccharides present in plants are only digestible by bacterial (and fungal) enzymes of the gut flora.  If the bacteria and enzymes needed to fully digest a particular food polysaccharide are absent, then digestive problems ensue and the polysaccharide can act as a laxative.  Continual eating of the problem food with a new source of diverse bacteria, e.g. lightly rinsed vegetables right from the garden, then the gut flora will incorporate new bacteria that can digest the problem polysaccharide and the gut is happy.  

Soluble fiber feeds the gut bacteria that convert it into short chain fatty acids that nourish the colon. Constipation results from the absence of the bacteria needed to digest dietary fiber and to produce the large volume of bacteria that make up well hydrated stools. 

Gut Bacteria Are Needed for Healthy Immunity

Cells of the human immune system are stored predominantly in the lining of the intestines.  Intensive study of the interaction of the gut bacteria with the gut has revealed that both the aggressive half of the immune system that attacks pathogens and the suppressive half that protects the body itself from attack, develop in the gut in response to particular types of bacteria.  Thus, the absence of one type of bacteria can cripple responses to infection, while other bacteria are needed to block autoimmune diseases and allergies.  Most diseases are caused by disruption of the normal interactions between gut bacteria and the immune cells developing in the gut.

Antibiotics Lead to Autoimmunity

Antibiotics have dramatic and lasting impact on gut flora.  Cattle treated with antibiotics and a high carbohydrate diet have an altered metabolism (obesity) that leads to rapid fat accumulation in their tissues.  This is good for making tasty beef, but the same approach in people produces the suite of diseases in affluent societies.  

Children treated with an antibiotic for a simple ear infection, are much more likely to return to pediatricians for treatments of subsequent obesity, infections and diseases.  Compromised gut flora can take years to return to normal function after antibiotic treatment.  Loss of the appendix, which is the normal source of bacteria to replenish gut flora after diarrhea, results in an increased risk of abnormal gut flora and numerous autoimmune diseases.  It is likely that most autoimmune diseases are preceded by prior treatment with antibiotics that disrupted normal gut flora and permanently altered the immune system.

Interventions to Treat Disease:  the Anti-Inflammatory Diet and Fecal Transplants

It should be obvious that a disrupted or unhealthy gut flora will compromise the immune system and contribute to disease.  Treatment of diseases is complicated by the use of drugs that also impact the gut flora and produce additional side effects.  An alternative approach would be to support the healthy gut flora and normal development of the gut immune system.  As always, the answer is a supportive diet and a source of gut bacteria.  The diet is obviously the Anti-Inflammatory Diet that provides support for almost anything that ails you.  Probiotics are not retained in the gut, but they can contribute a few of the genes needed for a healthy gut flora. The source of bacteria for a  healthy gut flora may range from minimally washed garden vegetables, to the more aggressive total replacement of gut flora with a fecal transplant from a healthy donor.  

Honey, Hydrophobicity and Biofilms

A reader (Jay Bryant) recently pointed out a PNAS article on the structure of a bacterial enzyme that uses sucrose to make the glucan matrix of dental biofilms.  This article released a cascade of associations in my mind and illustrated why honey does not contribute to dental plaques, but is antimicrobial and aids wound healing.  People forget that sugars combine both hydrophilic and hydrophobic properties, and thereby act as soaps.

The starting point of the chemical versatility of carbohydrates is the inability of the central portion of a sugar ring structure to form hydrogen bonds.  Each sugar is made of  a linear chain of carbon atoms with each carbon linked also to a hydrogen and a hydroxyl.  Only the hydroxyl can participate in hydrogen bonds, so each carbon has a hydrophilic side (bonds with water to make hydrogen bonds) and a hydrophobic side (that makes van der Waals bonds with other hydrophobic molecules.)  The sugars circularize and the rings have faces that are predominantly hydrophobic and perimeters with hydroxyls that are hydrophilic.  Polysaccharides (long chains of sugars), such as cellulose, can sometimes form long fibers that form a hydrophobic context for hydrogen bonds between the hydroxyls of adjacent polymers.  These cellulose fibers are very resistant to chemical or biological attack and accumulate as the most abundant biological molecules on Earth.

The PNAS article provides another example of how protein enzymes interact with carbohydrates, in this case sucrose and a polymer of glucose.  Typical weak bonds between the amino acid residues of proteins and other molecules are hydrogen, ionic or van der Waals bonds with energies of a couple of kcals/mol.  In contrast, the bonding of the hydrophobic face of a sugar to the hydrophobic face of an hydrophobic amino acid, e.g. tryptophan, phenylalanine, histidine, lysine or arginine, releases more than ten kcals/mol of energy.  Thus, the structure of the bacterial enzyme that makes biofilm glucan chains from dietary sucrose, the sucrose is bound to the enzyme on the face of a prominent tryptophan.  Examination of enzymes that bind to polysaccharides will show a series of tryptophans arrayed across the surface of the enzymes with spacing appropriate to bind to the individual sugars of the polysaccharide.

Biofilms are communities of multiple species of bacteria held together by a polysaccharide matrix.  In the case of dental plaque, the polysaccharide is made of glucose links, whereas many other matrix polysaccharides are negatively charged and held together by positively charged metal ions.  The bacteria bind to the polysaccharides using protein receptors that exploit the display of hydrophobic binding sites of the polysaccharides.  It takes energy to make polysaccharides and the dental plaque bacteria use the energy already expended in the formation of sucrose to produce a polymer of glucose, an alpha-glucan, and free fructose.  Thus, sucrose is essential in forming this type of biofilm and without this sugar, the dental plaque cannot form.  Milk lactose, or glucose would be a more appropriate sweetener.  Unfortunately, high fructose corn syrup would be a poor substitute, because of the high liver toxicity of the fructose (it causes fatty liver, just like alcohol) and very high activity in forming advanced glycation end products (AGEs), which contribute to the symptoms of  diabetics.

Honey seems to be magical, because at low concentrations the sugars present in honey  (mostly glucose and fructose, and not sucrose) are nutrients for bacteria, but at high concentrations honey is anti-bacterial and useful as a wound treatment.  I think that the explanation for its antimicrobial activity is that sugars are amphipathic, that is they have both hydrophilic and hydrophobic properties, just like soap, and at high concentrations they kill bacteria, just as soaps at high concentrations kill bacteria.  In fact, the gentle soaplike properties of sugars are exploited experimentally to dissolve proteins that are normally embedded in cellular membranes.  This explanation predicts that corn syrup, which can also be used to form very stable soap bubbles, should also be useful in wound healing.

Why Discuss Mother’s Milk on an Inflammation Blog?

Milk Is Perfectly Adapted for Infant Nutrition/Development

I think that I should explain, if it is not obvious, why I keep bringing up breastfeeding/infant nutrition on this blog about diet, inflammation and disease.  The starting point is that infants need nutrition, protection from disease and continued normal development or they won’t be able to reproduce.  That means that milk is the focal point of a lot of natural selection and absence of the natural functions of milk, e.g. use of formula, would be expected to lead to inflammation and disease, which it does.  Analysis of milk and how formula makes infants susceptible to disease and alters normal development, provides an extreme example of the interactions of diet, gut flora and the immune system.

Since this is World Breastfeeding Week and my wife is an Internationally Board Certified Lactation Consultant, I think that writing a few articles on milk is good for my health.

Milk Provides Complete Nutrition, Controls Gut Flora, Promotes Gut Development -- Formula Doesn’t

I find it amazing that supplements are encouraged for exclusively breastfeeding infants.  It doesn’t make sense to suspect that breast milk is inadequate and why is formula fortified with ingredients at ten to a hundred times the levels in breast milk?  The answer is in the infant gut flora and perhaps in poor maternal nutrition/gut flora.

Mother’s Milk Promotes Normal Infant Gut Flora -- Bifidobacteria

The normal infant gut flora is very simple, Bifidobacteria.  Adults have gut flora composed of hundreds of different species of bacteria and infants have just Bifidobacteria.  The name of the infant bacterium should be familiar if you read labels on yogurt.  Bifidobacteria are common probiotics.  That also explains why the diapers of exclusively breast fed babies smell like yogurt.  

Formula Promotes Adult Gut Flora

One bottle of formula kills the Bifidobacteria and replaces it with adult gut bacteria.  The diapers are forever changed, because the adult gut flora is very persistent.  The presence of the adult gut flora also explains why formula has the high levels of supplements.  The adult gut flora consumes the supplements and leaves only tiny amounts for the infant.  All of the breast milk nutrients go to the baby if only Bifidobacteria is present, but after the adult gut flora are established much higher levels are needed and the infant may still be deficient.  Adult, formula-supported gut flora also digest antibodies and other protective factors in mother’s milk.

Supplement Mothers to Improve Infant Nutrition

Modern mothers are also eating modern diets that produce deficiencies.  Chronic diet-based inflammation leads to a compromised ability to produce vitamin D in sunlight.  Nursing mothers with poor diets may not be transferring enough vitamin D to their nursing babies.  Since formula and the adult gut flora that it stimulates, causes gut inflammation, I suspect that formula fed infants are also compromised in their ability to produce their own vitamin D in sunlight.  It makes more sense to supplement mothers than babies.

Formula Is not Breast Milk, It’s Not Even Close

Formula is cheap to produce, but expensive to buy.  Formula is promoted as the next best substitute for milk from a baby’s own mother, but that isn’t true either.  The next best alternative is mother’s milk from a certified human milk bank.  It is available at a reasonable cost.  Hospitals should know better and provide the only appropriate alternative.  Early formula use dramatically increases healthcare costs.

Formula Lacks the Oligosaccharides Needed to Support only Bifidobacter

Fructose oligosaccharides (FOS) and other short chains of sugars are being promoted to support the growth of beneficial gut flora.  These oligosaccharides do promote the growth of adult gut flora, but not just infant Bifidobacteria.  Formula plus FOS and/or other prebiotic oligosaccharides other than those present in human milk support the growth of bacteria that rob nutrients from and degrade the protective components of breast milk.  If the diaper smells like adult gut flora, then the baby was not fed mother’s milk.

Development of Gut and Brain

The newborn gut and brain are only partially developed.  Mother’s milk is needed to supply growth factors to close and differentiate the gut epithelium, and long chain omega-3 fatty acids for brain growth.  Formula may eventually be supplemented with the needed fatty acids, but the growth factors/hormones present in mother’s milk will not be provided in formula.  Recent studies have shown that hundreds of different genes are activated in gut cells from infants fed either breast milk or formula.  Formula leaves the gut leaky and fails to stimulate the development of the immune system that is dependent on interaction with normal infant gut flora.  These dysfunctions partially explain the increased (10X to 100X) gut and respiratory infections resulting from formula use.  The reduced brain development with formula explains the five point reduction in IQ of formula fed infants.

It’s worldwide breastfeeding week.  Support healthy, non-inflammatory gut flora (infant Bifidobacteria) around the globe!

Autoimmune Diseases, Bacteria and GALT (Gut Associated Immune System)

Celiac, Oxidative Stress, Peroxiredoxin, Alopecia

Grain/gluten intolerance, celiac is an immunological attack on the small intestines with increased risk for numerous autoimmune diseases.  Hashimoto’s thyroiditis is a common sequela of celiac and the two diseases share the same autoantigen, tissue transglutaminase (tTG).  Thus, the development of celiac and the production of antibodies to the tTG produced in the intestines, results in a subsequent immunological attack on other tissues that produce lots of tTG, e.g. the thyroid.  Gluten intolerance, because of its attack on the intestines and the proximity of a major part of the immune system (GALT), may play a major role as the foundation for autoimmune diseases.

Gluten Intolerance First Step in Autoimmune Diseases

Celiac may also lead to herpatic lesions of the skin, dermatitis herpetiformis and loss of hair, alopecia.  In these cases, the autoantigen is peroxiredoxin, an enzyme that eliminates hydrogen peroxide produced as a result of accumulation of reactive oxygen species, e.g. superoxide, associated with inflammation.  Peroxiredoxin is also implicated as an autoantigen in periodontal disease, suggesting that celiac may also contribute to dental gum inflammation.

Peroxiredoxin 5 Gene Associated with Alopecia Risk

A recent study (see ref. below) of genes associated with alopecia identified genes involved in Treg and Th-17 development, as well as peroxiredoxin 5 as contributors.  As expected, several genes involved in antigen presentation (HLA-DRA, HLA-DQA)  were also identified.  Th-17 lymphocytes are involved in immune attacks on self tissue, i.e. autoimmune diseases, such as alopecia, in which hair follicles are attacked by the immune system.  Tregs control immune attacks on self tissues.  Peroxiredoxin is an autoantigen and is produced in elevated amounts around hair follicles attacked in alopecia.

Basic Amino Acids of Peroxiredoxin as Expected for Autoantigen

I checked the amino acid sequence of human peroxiredoxin 5 and found an alternative (-nrrlkrfsmv-) to the triplet of basic amino acids that I expect for an autoantigen.  In this case there are two adjacent pairs of basic amino acids (blue rr and kr) that I think precipitate immunological presentation of peroxiredoxin.  Peroxiredoxins are produced in response to oxidative stress at sites of  inflammation and the presence of celiac compromises the gut associated immune system (GALT) that provides Tregs to restrict autoimmunity, so celiac sets the stage for peroxiredoxin presentation to the immune system and for subsequent production of anti-peroxiredoxin antibodies, autoimmunity and destruction of hair follicles, alopecia.

Anti-Inflammatory Diet Should Avoid and Treat Autoimmunity

Control of autoimmune diseases mediated by peroxiredoxin should benefit from a reduction in the conditions that spawned the diseases:

• Th-17 elevation -- celiac inflammation stimulated by grain/gluten
• Treg loss -- GALT inactivation due to inflammatory diet and inappropriate gut flora
• Autoantigen (basic amino acid concentration) presentation -- oxidative stress stimulation of peroxiredoxin

Treatment would be supported by dietary changes:

• anti-inflammatory diet to control gut inflammation and minimize celiac symptoms (vitamin D, low carb/high saturated fat, high omega-3 to -6 fatty acid ratio, no grains)
• probiotics and soluble fiber (e.g. pectin, inulin) to re-establish gut flora (cure dysbiotic constipation) and GALT function, and development of Tregs
• supplements to compensate for depletion of vitamin C and glutathione by oxidative stress, e.g. vitamin C and acetylcysteine (NAC)

Th-17 and Tregs in HIV Infections

Th-17 cells are also reduced by HIV infection, producing susceptibility to infection, but this infection should also reduce autoimmune disease.  The reduction in Th-17 also may be a consequence of problems in the GALT.  Therapy for HIV infection should also include diet considerations to increase Th-17 and also Tregs to reduce autoimmune diseases due to unbalanced Th-17.

ref.

Petukhova L, Duvic M, Hordinsky M, Norris D, Price V, Shimomura Y, Kim H, Singh P, Lee A, Chen WV, Meyer KC, Paus R, Jahoda CA, Amos CI, Gregersen PK, Christiano AM.  2010. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity.  Nature. 466(7302):113-7.