Common Medicines Make Superbugs, Not Prescription Antibiotics

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Careless prescriptions and cattle fattening antibiotics are blamed for the rise of superbugs resistant to everything in the hospital arsenal, but that’s all wrong.  Antibiotics fail, because we are all abusing common medicines that also have powerful antibiotic activity.  All painkillers, anti-inflammatories, statins, antidepressants, and the whole list of common pharmaceuticals are the problem.  We simply use too many drugs.

Common drugs should also be labeled as antibiotics, because they kill the sensitive bacteria in your gut and leave behind just the resistant bacteria.  Unfortunately, the genetic mutations that make your gut bacteria resistant to drugs, also provide resistance to antibiotics needed to stop infections and that broad resistance to antibiotics can spread to pathogens that then become the dreaded superbugs.

Here are the simple facts that I have discussed at length in another post:

• Statins were antibiotics that were repurposed to lower LDL, “bad cholesterol.”

• Aspirin was an antibiotic that was shown to relieve pain and inflammation.

• Metformin was an antibiotic that later proved useful for treatment of diabetes.

• Many chemotherapy drugs are antibiotics developed for cancer treatment.

• Diuretics were antibiotics that indirectly reduce blood pressure.

• Antidepressants, such as Prozac, Zoloft, etc. are antibiotics.

Common Drugs Are Actually Antibiotics

Most pharmaceuticals are derived from phytochemicals, a.k.a antioxidants, adapted in plants to kill microorganisms, i.e. as natural antibiotics.  It is not surprising that drugs = antibiotics.  What is surprising is that people assume that if antibiotics are labeled with some other activity, that they cease to be antibiotics.  All drugs are also antibiotics and that is why a major side effect of most medicines is upset gut bacteria.

Overuse of Common Drugs Produces Superbugs

Simply put, common medicines you swallow, kill bacteria in your bowels.  Some bacteria survive and are called “drug resistant.”  Bacteria accumulate resistances to several different kinds of drugs and are called “multidrug resistant.”  As might be expected, hospitals are the breeding grounds for multidrug resistant, mutant bacteria of all different types.  Unfortunately, anyone who takes several types of medications is also a source for multidrug resistant bacteria, so nursing homes are the most frequent sources of superbugs that cause outbreaks of hospital infections.

The Only Way to Stop Superbugs is to Use Less Drugs

The bottom line is that even if doctors start to use antibiotics more rationally and antibiotic use in agriculture is eliminated, superbugs will still be a big problem, because they will be produced by excessive use of common drugs, i.e. those found on the shelves of drug stores and supermarkets, as well as prescribed by doctors.  

The only solution to the superbug problem is to reduce pharmaceutical use by 99%.

HELLP, Preeclampsia, Antiphospholipid Antibodies and Basic Triplets

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Clotted RBCs in Capillary

Some of my research involves the unique properties of milk and the development of the immune system, so I talk to medical people, lactation researchers and occasionally discuss the control of inflammation involved in ovulation, fertilization, implantation, gestation, labor and lactation.  It is clear to me that there are a few trends in disruption of these pregnancy processes resulting from the modern increase in inflammation and gut-related problems linked with immune tolerance.  Infertility is increasing, because women are becoming more chronically inflamed.  Miscarriages and premature births/low birth weight are increasing, because chronic inflammation enhances labor.  Pre-eclampsia (high blood pressure and protein leaking into the urine) results from chronic inflammation and omega-3 fatty acid depletion.  Now an even scarier form of pre-eclampsia, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) is on the rise.  I want to discuss HELLP to put all of these pregnancy-related problems into perspective.

HELLP, Cause and Cure Unknown?

HELLP is an autoimmune disease and I have repeatedly discussed the cause of autoimmune diseases:  1) inflammation, 2) deficiency of Tregs (immune tolerance) and 3) antigen basic triplets (antigen presentation).  When HELLP was recently brought to my attention with a sudden rise in local hospitals, I decided to see if it could be easily explained and cured, just by examining the available medical literature.  Wikipedia indicated that the cause and cure was not known and that was confirmed by local doctors, who just treat the symptoms by early deliveries and long stays for the babies in neonatal intensive care units.  My work was cut out for me.

Autoimmune Disease with Unknown Autoantigen 

An examination of the symptoms, rupture of blood cells (fibrin production), liver damage, clotting (low serum heparin), high blood pressure (capillary apoptosis), proteinuria (low heparan sulfate (HS) to prevent protein loss), pointed to some obvious treatments and the causes.  Infertility is often treated by in vitro fertilization/insemination, supported with aspirin and heparin injections to maintain gestation.  These treatments are consistent with high levels of chronic inflammation that block implantation and stimulate labor.  Infertility is also associated with antiphospholipid antibodies.  A closer look at the antiphospholipid antibodies showed that they were directed against β₂-glycoprotein-I.  So, I expected the β₂-glycoprotein-I protein to be the original target for the antibodies, the initiating antigen, but when I looked up the sequence of that protein, it lacked the expected basic triplet I have found in all  other autoantigens and allergens.  This meant to me that there was a different protein with a related sequence that started the HELLP autoimmune disease.

Attack on P-Selectin Starts Immune Autoimmunity

I checked for other proteins with related sequences and basic triplets (RKR in the carboxy terminal sequence below), and found P-selectin that is produced most abundantly in liver and on the surface of blood cells.  A quick search of the literature showed that P-selectin reacts with anti-phospholipid antibodies and has a pair of basic triplets that enhance immune presentation and make this protein a strong candidate for becoming an autoantigen.  Antibodies against P-selectin will cause clotting as seen in HELLP.

ref|NP_002996.2| P-selectin precursor [Homo sapiens]:

......carboxy terminalGTLLALLRKRFRQKDDGKCPLNPHSHLGTYGVFTNAAFDPSP

Antibiotics and Liver Damage

I suspect that HELLP is caused by a combination of liver damage and prior exposure to antibiotics (or common drugs that have antibiotic activity) that cause gut dysbiosis, i.e. loss of gut bacteria that stimulate development of the suppressive part of the immune system, e.g. deficiency in regulatory T cells, Tregs.  Examples of the type of liver damage that may lead to HELLP are excessive consumption of alcohol (alcoholic fatty liver) or high fructose corn syrup (non-alcoholic fatty liver).

HELLP from Cause to Cure

• Diet and/or infection causes liver inflammation.
• Antibiotics/drugs and/or processed foods lacking prebiotic fiber produce gut dysbiosis.
• Lack of gut bacteria needed for development of the immune system in the gut produces a deficiency of Tregs and dysfunction of immune tolerance.
• Liver inflammation, deficiency of Tregs and availability of antigens with basic triplets leads to antibodies against liver proteins.
• Chronic inflammation leads to decrease in HS production and leaky kidneys/proteinuria.
• Chronic inflammation/liver damage produces fibrin production.
• Fibrin production and low HS enhances clotting and leads to apoptosis/cell death in capillaries.
• Loss of capillaries leads to high blood pressure.
• Cure of HELLP, anti-phospholipid antibodies and pre-ecampsia, involves lowering chronic inflammation (aspirin and heparin treatment) with an Anti-Inflammatory Diet, fixing vitamin D deficiency, increasing omega 3/6 ratio,  and repairing gut dysbiosis to fix immune tolerance.
• Without these interventions, HELLP symptoms will become more severe, especially in subsequent pregnancies and additional autoimmune diseases will develop.

Making Monsters, Renegade C. butyricum and E. coli

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Clostridium

It is common knowledge that our gut is teeming with good bacteria that we feed with prebiotic fiber to keep us healthy.  But a sick gut, caused by antibiotics or fiber deficient processed food, can make us susceptible to infection with pathogens, such as the notorious, toxin-producing strains of E. coli that cause food poisoning or Clostridium difficile, a.k.a. C. diff. of hospital infections.  What prompted me to write this post, was reading that premature babies in neonatal intensive care units are dying from gut infections caused by a pathogenic strain of C. butyricum, known as a probiotic that provides protection from C. diff.

Healthy Gut Microbiota

New Toxin-Producing, Antibiotic Superbugs are Manmade

Closer examination of the report revealed that the new strain of C. butyricum is a toxin producer.  This made a lot of sense to me.  When I started working with E. coli in the early 70’s, it was known as the safe ubiquitous lab bacterium that everyone cultivated in their colons.  Similarly, C. butyricum is present in commercial probiotics and is a hero for producing butyric acid from resistant starch, promoting immune system development and reducing inflammation.  How did these beneficial gut bacteria become converted into pathogens?

Source of Antibiotic Resistant Superbugs

Antibiotic and Drug Use in Hospitals and Farms Select for Antibiotic Resistance

C. butyricum and E. coli have been converted into toxin-producing, antibiotic resistant pathogens by common procedures of meat production and hospital treatments.  These bacteria do not normally produce toxins nor are they resistant to antibiotics.  They have been systematically selected for those pathogenic properties.

Formula Contributes to NEC

Common Practices in Neonatal Intensive Care Units Lead to NEC

Chronic inflammation is one of the common contributing factors to premature births, because labor is stimulated by a spike of inflammation, normally occurring at 40 weeks of gestation.  Chronic inflammation from autoimmune disease, infection, or obesity, can cause labor to be early and a newborn to be unprepared for life without some special care.  Unfortunately, there is not uniform enlightenment about the development of newborn gut flora, and immature newborns are exposed to antibiotics and formula, which prevent normal gut flora development.  C. butyricum is not present in low birth weight babies exclusively fed breast milk, but the combination of antibiotics and formula select for colonization by antibiotic resistant hospital strains of C. butyricum.  This sets the stage for necrotizing enterocolitis, NEC, which is as nasty and lethal as the name suggests.

Toxin Producing E. Coli are Manmade

Antibiotics Used to Make Fat Cattle Select for Toxin Production

The development of toxin producing E. coli in cattle suggests how pathogenic C. butyricum was produced in the hospital environment.  E. coli was a healthy component of the digestive system of cattle, until the gut flora community was reengineered by antibiotics, so that short chain fatty acids that were normally converted into more gut bacteria and more steer manure, were instead absorbed by the gut to produce a fatter steak.  Unfortunately, this newly designed gut flora community left no place for E. coli.  Some of the E. coli spontaneously mutated to antibiotic resistance and/or picked up multi-drug resistant plasmids from other bacteria, but that still didn’t provide a niche in the new community.  Picking up a toxin-producing gene solved that problem, because the toxin releases needed nutrients from host cells.  Thus, antibiotic use in cattle directly selected for the evolution of toxin-producing, antibiotic resistant E. coli.

Antibiotics and Formula Use Lead to NEC Bacteria

Toxin-producing C. butyricum would be expected to develop in the hospital environment, because high antibiotic use will select for multiple drug resistant C. butyricum, and the disrupted gut flora produced in the presence of antibiotics will also favor toxin producing strains.  Thus, the hospital environment selects for toxin-producing, multiple drug resistant C. butyricum.  The gut flora of newborns in a neonatal intensive care unit are acquired from the staff and relatives that handle the babies.  Since the babies are routinely treated with antibiotics and drugs, multiple drug resistant bacteria, including C. butyricum, are common in fecal samples of neonates and persist for at least two years. 

Breastmilk Prevents NEC in Newborns

Breastfeeding or Donor Bank Milk Avoids NEC Caused by Formula

Exclusive use of breastmilk from mothers, donor banks or breastmilk products, eliminates NEC.   Some hospitals respond to the scientific evidence and use only breastmilk for newborns.  Other hospitals simply stick to old practices until law suits force them to change.  They continue to use formula and cow’s milk products,  even though breastmilk is available, and as a consequence NEC is still a problem. Prejudice against breastmilk persists and there is intense promotion of commercial alternatives that contribute to NEC.  None of the alternatives containing probiotics and prebiotics have been found to be adequate.   Hospitals are slow to change, because patients are uninformed and low birthweight babies continue to die.

Healthy Gut Microbiota Means: No Supplements, No Cleanses, No Drugs, No Processed Foods

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A healthy, functional gut microbiota (bacteria and fungi) supplies all of the vitamins needed, stimulates the development of a balanced immune system and promotes vitality.  If you feed and maintain the diversity of the pounds of bacteria in your gut, you will be healthy.  If you listen to the medical and food industries, you will be sick, i.e. a good patient/consumer.

Supplements Compensate for Deficiencies/Sickness

The key to this discussion is the functions of the healthy communities of bacteria and fungi called the gut microbiota.  These pounds of bacteria produce all of the vitamins that your body needs, and spiking your diet with multivitamins may disrupt your microbiota, because vitamins are actually the chemical signals used for communications between bacteria in biofilms.  Numerous studies have shown that daily multivitamins are not beneficial, so if you see extra vitamins on the ingredients label, try some whole foods instead.  If, however, you have been exposed to antibiotics or other medications, since most have potent antibiotic activities, then your gut bacteria may not be producing vitamins normally, and you may need to supplement.  Vitamin deficiencies are a symptom of gut dysbiosis, damaged gut microbiota.

Vitamin D is a Steroid Hormone Produced from Cholesterol in Skin by Sunlight

Most people know that sunlight striking skin produces vitamin D, but they still think that they can get a significant amount of vitamin D from their diet.  The confusion comes from the fact that vitamin D is a major hormone that influences many body systems including bone production and immunity.  So in the absence of skin production of vitamin D, the low amounts added to milk are sufficient to prevent deficiency/rickets.  However, chronic inflammation can block solar production of vitamin D, so that even individuals near the equator and basking daily still remain deficient.  Vitamin D deficiency may also, insidiously, be a major source of chronic inflammation.  Thus, most individuals treated for deficiency with supplemental vitamin D3, do not reach high enough levels to suppress chronic inflammation and restart solar production, so they remain deficient.  Chronic inflammation is a symptom of vitamin D deficiency.

Bowel Cleanses Damage Gut Microbiota

The bowels are a long tubelike conveyance and it takes food about a day to travel from table to toilet.  In the colon, all of the plant polysaccharide fibers remaining after removal of sugar, starch, fat and protein, are digested by enzymes of the microbiota and converted into more bacteria and short chain fatty acids that feed the colon tissue. There is nothing toxic left behind in the colon. Protein from meat is readily digested in the stomach and the first part of the small intestines.  Plant materials cannot be digested without the help of a complex array of hundreds of enzymes produced by gut bacteria.  Food intolerances are caused by the loss of particular bacterial species needed for complete digestion of one type of plant fiber.  The bacteria form the stools, and insufficient healthy bowel bacteria, normally fed by the fiber, is the cause of constipation.  Clearly, flushing out bacteria with a "cleanse" is unhealthy and counterproductive.  There is nothing in the colon but gut bacteria and fiber to feed the bacteria. Those bacteria are needed for vitamin production, normal development of the immune system and normal stools.  A cleanse merely removes healthy gut bacteria and leads to constipation or replacement by pathogens. 

Processing Removes Prebiotic Fiber from Food and Starves Gut Microbiota

Diverse and complex plant polysaccharides, e.g. pectin, arabinogalactan, various glucans and fructans, are systematically digested by hundreds of different bacterial enzymes of the healthy gut microbiota.  The sugars that result are eventually converted into short chain fatty acids, such as butyrate, that feed the cells lining the colon.  The plant polysaccharides that feed gut bacteria are called prebiotics.  Unfortunately, prebiotics are removed during food processing to enhance ease of preparation and palatability.  The result of decreased dietary prebiotics is selective starvation and removal of bacterial species needed for the development of the immune system, and autoimmune diseases.

Most Medicines Have Substantial Antibiotic Activity and Damage Gut Microbiota

It is not surprising that antibiotics damage the bacteria in the gut.  What most people don’t realize is that most pharmaceuticals/medicines are developed from the natural antibiotics of plants, phytoalexins.  Numerous recent studies have demonstrated most common medicines, e.g. statins, NSAID, antidepressants, etc. have substantial antibiotic activity and damage gut bacteria.  Surgeons commonly suggest that patients eat yogurt to help repair their gut micro biomes after operations and antibiotics, but they don’t tell them how to fix their gut and immune system as they take medications for the rest of their lives.  The permanently damaged gut just causes further deterioration of the immune system and health.

Damaged Gut Microbiotas/Immune Systems Can Be Fixed

I have several other posts on repair of gut microbiota.

Examination of antimicrobial activity of selected non-antibiotic medicinal preparations.

Kruszewska H1, Zareba T, Tyski S.   Acta Pol Pharm. 2012.  69(6):1368-71.

Essential Oils, Phytoalexins, Drugs Are All Antibiotics

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Superbug multidrug resistant plasmid

A recent, informative article by Tori Rodriguez for The Atlantic suggests that,

Essential Oils Might Be the New Antibiotics.

I want to discuss other ramifications of using essential oils as antibiotics to avoid multiple antibiotic resistant superbugs.

The logic for using essential oils in place of medical antibiotics is compelling: 

• Essential oils are extracts of plants, which have myriad traditional uses, including food.
• Most antibiotic use is to increase livestock production. 
• Antibiotics selectively kill gut bacteria in livestock and make them obese.
• Antibiotic resistance occurs within a week of use in livestock (or people.)
• Medical antibiotics are quickly losing efficacy.
• Antibiotic resistance genes quickly move from agriculture to superbugs to people.
• Plants/essential oils contain natural antibiotics that kill gut flora and increase livestock productivity.
• Resistance to essential oil antibiotic activity is slower, because of simultaneous use of multiple antibiotics.

Obesity is a Symptom of Antibiotic Damage to Gut Microbiome

Antibiotics make meat fatter

We may enjoy a fat marbled steak, but the corn and antibiotics used to produce that mouth-watering plate of satiety, is not so healthy.  Corn and antibiotics make that meat on the hoof fit for human consumption, but the cattle are quickly dying and the fat marbling is a symptom of cattle metabolic syndrome.  The corn and antibiotics disrupt the bovine gut microbiota and alter energy flow.  The result is prime beef. 

As It Is with Cattle, so It Is with Middle Americans

General descriptions of Americans with metabolic syndrome and steers ready for the abattoir are similar.  That should not be surprising, because both are caused by damaged gut microbiota and consequences of metabolic syndrome.  Americans routinely damage their gut microbiota with antibiotics (processed food, etc.) and the major symptoms of the resulting gut dysbiosis are chronic inflammation, depression, autoimmune diseases, obesity and metabolic syndrome.  Repairing gut microbiota reverses all of these symptoms. 

But Essential Oils Are Just Natural Antibiotics

Essential oils are natural antibiotics

Is it better to use essential oils than medical antibiotics to fatten cattle or treat Lyme disease or hospital infections such as C. diff.?  Most pharmaceuticals were derived from plants or fungi and were originally used to kill microorganisms, i.e. they were natural antibiotics.  We call these phytochemicals by a variety of names, e.g. antioxidants or essential oils, but they are more appropriately called phytoalexins, all natural, all plant, all toxic antibiotics.  It is entertaining that essential oils have had so many different traditional and pharmaceutical uses, and yet they have always been experienced by microorganisms (and our livers) as simply toxic.  Essential oils do have the significant advantage of being a mixture of antibiotics and might be very useful where pharmaceutical antibiotics have problems.  The toxicity of essential oils, especially toward gut bacteria, should not be ignored.

Resistance to Essential Oils as Antibiotics

Antibiotic resistance develops in sewage

I previously kept track of laboratory strains of bacteria by simply exposing large numbers of the bacteria to an antibiotic and selecting for the rare individual that had already spontaneous mutated (DNA replication error of one in a million).  We could then use the new drug resistant strain in experiments and identify it by its resistance.  The same thing happens to your gut bacteria with an overnight exposure to an antibiotic.  And of course it also occurs immediately in livestock exposed to antibiotics or in sewage plants where tons of antibiotics and gut bacteria are mixed.  Resistance to each of the chemicals in an essential oil also would rapidly occur, if bacteria were exposed to each alone and in a  toxic concentration.  This is repeatedly observed, since commonly used drugs are just individual components of essential oils that have been produced in large amounts in pills and marketed based on their predominant physiological activity, rather than just another antibiotic.  Thus, resistance to a statin or Metformin, as antibiotics, could be easily observed (even on multiple drug resistance plasmids), but is just ignored.

Essential Oils Are just Mixtures of Natural Antibiotics

Statins from fungal antibiotics

The impact of essential oils on gut microbiota is unpredictable, because the composition of essential oils is highly dynamic and so are gut microbiota.  Each component of an essential oil has a different spectrum of toxicities to hundreds of different target proteins to each of the hundreds of different species of bacteria in the human gut.  Ingested essential oils are modified by the detox enzymes of the intestine and liver.  The modified phytochemicals have different toxicities and act as additional antibiotics.  Mixtures of antibiotics, as in essential oils, less likely to select for resistance than individual antibiotics, but an antibiotic is still just an antibiotic, regardless of whether it is straight from the plant or via a pharmaceutical salesman. 

Common Medicines Are the Source of Superbugs

Common meds are antibiotics

Doctors with prescription pads and steers eating antibiotics are blamed, I think unjustly, for the crisis of antibiotic resistance.  The real culprit is you taking NSAIDs, statins, proton pump inhibitors, antidepressants and other common medicines.  Since they are all developed from plant antibiotics, they are still antibiotics, and they still select for antibiotic resistance.  It is important to remember that pharmaceuticals are repurposed natural antibiotics from plants.  The answer to the superbugs that are resistant to all of the common antibiotics is to dramatically reduce the use of all pharmaceuticals.  The initial goal should be a 90% reduction.  Costly pharmaceutical chemicals could be replaced with preventive diets and less disruptive manipulations of gut microbiota, e.g. ingestion of capsules containing freeze-dried gut flora.  This more gentle approach to health care would also provide huge cost savings, as well as vastly improving health.

Frankincense and Myrrh, Terpenoids

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Frankencense Resin

 'Tis the season to discuss phytochemicals.  Plants produce a vast array of organic chemicals starting from molecules produced by all organisms, including humans.  Essentially all of these phytochemicals are potent adaptations to kill.  Phytochemicals kill plant pathogens, bacteria and fungi, as well as insects.  Thus, the natural, plant extracts that humans use for flavor enhancers (herbs, spices, and teas), fragrances, recreational/medicinal mind and attitude modifiers (alkaloids, psychopharmaceuticals, etc.), herbal medicines, etc. are present in plants, first and foremost, as antibiotics and insecticides.  Humans have evolved to taste (bitter) and smell phytochemicals to avoid their toxicity, and have adapted culturally to exploit the impact of phytochemicals on body and mind.  In this seasonal post, I focus on the terpenoids in Frankincense and Myrrh, to explore how plant biochemistry contributed to the gifts of the Magi.

It All Starts with Central Metabolism

Phytochemicals are complicated plant chemicals that are produced by a series of enzyme-controlled reactions (Central Metabolism) from the array of chemicals used by plants to convert photosynthetic carbohydrates (fructose and glucose) into the molecules (sugars, amino acids, fatty acids, nucleic acids) used to make the macromolecules of cells (polysaccharides, proteins, fats, DNA/RNA).  Alkaloids and phenolics, e.g. phytoalexins, are made from amino acids (phenylalanine) and terpenoids are made from fatty acids (acetyl CoA/Mevalonate) or other intermediates in glycolysis.  Thus, central metabolism that converts glucose/fructose into pyruvate and the acetyl CoA (see mevalonate pathway left) of mitochondrial fatty acid metabolism, is further converted into amino acids and plant secondary compounds, phytochemicals.  I am going to talk mainly about terpenoids in Frankincense (triterpenoid Boswellic acids) and Myrrh, and many related molecules (steroids) also produced by humans.  

The major thesis here is that carbon dioxide is converted by photosynthesis into either sugars used to build the cell wall polysaccharides (soluble fiber) or larger toxic defensive chemicals, e.g. phytoalexins, resins, essential oils or lignin.  Phytoalexins, e.g. the natural antibiotic resveratrol in wine, are made from phenylalanine along the same biochemical pathway used to produce lignin.  Glyphosate, the herbicide, kills by blocking this unique plant pathway.  Essential oils and resins are another group of natural antibiotics produced by converting acetyl CoA into a five carbon unit, IPP, which is then linked into larger and larger (10, 15, 20 carbons) molecules, terpenoids, that can rearrange into multiple ring structures.  Only the smallest chemicals in the series evaporate to provide identifiable smells, e.g. Frankincense and Myrrh, while larger forms, e.g. cholesterol or testosterone in animals, are odorless solids.

Acetyl CoA to IPP

IPP

For those who enjoy the beauty of biochemistry:  The most abundant enzyme on earth is RibisCo (ribulose bisphosphate carboxylase), the plant enzyme that combines carbon dioxide from air with a five-carbon phosphorylated sugar, ribulose bisphosphate, to produce two, three-carbon intermediates of glycolysis that can be converted into glucose or into acetyl CoA, the starting chemical for fatty acids, the mitochondrial TCA cycle, or via mevalonic acid to isopentanyl pyrophosphate (IPP), the building block for terpenoid synthesis.

In brief:  Photosynthesis uses the energy from sunlight to convert carbon dioxide into sugars (glucose and fructose).  Those sugars can be converted into a five-carbon, molecular building block for terpenoids, IPP.  IPP molecules can then be linked together to make increasingly longer chains and those chains can be ultimately twisted into rings to make resins in plants and steroids in humans.

Five, Ten, Fifteen, Thirty; IPP (5), GPP (10), Sesquiterpenoids (15), Triterpenoids (30)

Terpenoid Polymerization

Terpenoid synthesis begins with IPP, which has five carbons in a branched chain and has a pair of phosphates, pyrophosphate that provide the energy to form chains of 5, 10, 15, etc.  In plants, molecules of each of the incremental lengths are produced together and additional enzymes in different species of plants result in mixtures of molecules with different rings and functional groups.  The smaller molecules evaporate more readily, so that mixtures are extruded from damaged trees as oils and gradually form resins as the remaining larger molecules predominate and solidify.

Shark Livers and the Horn of Africa

IPP with five carbons, an isoprene, is used to make GPP with ten, a monoterpene.  Common monoterpenes are geranol and limonene that make the characteristic odors of geraniums and lemons. Sesquiterpenoids (15 carbons made from three IPPs) include the fragrance of patchouli. Diterpenes, such as sweet steviol, have twenty carbons, which can be chemically twisted into the chemicals that predominate in Myrrh resin, the Balm of Gileade.  The triterpenes with 30 carbons can be rearranged with five rings to form steroids, such as cholesterol in animals or Frankincense.  Linear squalene, is the major component in shark liver oil and provides the same function as a swim bladder in a boney fish.

Essential Oils Are Mixtures of Distilled Terpenoid and Phenylpropanoid Phytoalexins

Boswellic Acid

Phytoalexins and terpenoids have evolved as plant defenses against bacteria, fungi and insects, and they are toxic, because they interact aggressively with proteins through their chemical ring structures that are hydrophobic.  These ring structures make the smaller versions volatile and soluble in organic solvents.  Many of these chemicals have properties similar to petroleum products and may be used as solvents themselves, e.g. paint strippers or thinner.  Steam distillation of plants produces mixtures of phytoalexins and terpenoids commonly called essential oils, which contain the volatile components “essential” for the odor identity of a plant.

Statins Block Cholesterol Synthesis

Statins were identified among a group of fungal antibiotics for their ability to block an early enzyme (marked in the mevalonate pathway above) in the production of cholesterol.  The toxic side effects of statins derive from wholesale disruption of all of the essential pathways (everything below the inhibited enzyme) that are related to cholesterol, such as blood heme A found in hemoglobin, and ubiquinone (CoQ) found in mitochondrial electron transport and needed to reduce oxidative stress and glucose intolerance.  Thus, for these examples, statins would contribute to anemia and type II diabetes/metabolic syndrome.  The side effects are not surprising, since statins are fungal antibiotics that target pathways common to bacteria and human mitochondria.  It is also not surprising that statins have unpredictable impacts on gut flora and the immune system.

Peanut Allergy Cause and Cure

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Summary:  The cure for peanut allergy should follow naturally from knowledge of the cause.  Since most allergies and autoimmune diseases result from the combination of 1) inflammation, 2) breakdown of immunological tolerance and 3) presentation of a primary immunogen, it follows that some types of peanut allergy are based on a continued problem with immune tolerance and fixing that defect should eliminate an allergic response to peanuts.  The current cure to resurrect immune tolerance is by enhancing regulatory T cells (Tregs) in the gut using resistant starch to improve the growth of Clostridia in the gut.

Peanut allergies are dangerous and this post does not advocate any medical treatments, but rather attempts to explain the cause and cures of allergies.

Just Treat the Immunological Tolerance Problem Instead of Mast Cells

Most people in fear of anaphylaxis from peanut dust, just try desperately to avoid peanuts in any guise.  That avoids the problem, but why not cure the allergy?  Recent research shows that peanut allergens can be prevented from establishing an allergic response in mice by addition of Clostridium species of bacteria in the gut flora.  It was shown that the Clostridia increased Tregs (regulatory T cells responsible for immune tolerance) in the lining of the intestines via interleukin 22 production.  So the cure to some peanut allergies may be increasing Tregs and fixing tolerance.

I Said It All Before

It is not a large step to combine my previous posts covering potato resistant starch for treatment of deficiencies of immunological tolerance with my explanation of the cause of allergies and autoimmunity to provide a simple explanation of the cause and cure for some peanut allergies.

Peanut Allergen is a Typical Bean Storage Protein Except for the Basic Triplet

It is not difficult to find out why peanuts are allergenic.  I just went to the National Center for Biotechnology Information (NCBI) web site and queried the protein sequence databases for “peanut allergen.”  Here is the complete amino acid sequence (each of the 20 amino acids of the protein is assigned a letter) of the major peanut [Arachis hypogaea] allergen:

MMVKLSILVALLGALLVVASATRWDPDRGSRGSRWDAPSRGDDQCQRQLQRANLRPCEEHMRRRVEQEQEQEQDEYPYSRRGSRGRQPGESDENQEQRCCNELNRFQNNQRCMCQALQQILQNQSFWVPAGQEPVASDGEGAQELAPELRVQVTKPLRPL

The triplet of basic amino acids (R=arginine, K=lysine), RRR in this case, which is found in all allergens and autoantigens, is highlighted in red.  If you eat peanuts with an inflamed gut and you have wiped out your Clostridia and associated Tegs with antibiotics, you have a good chance of developing autoimmunity, as well as a peanut allergy.  The cause of allergies is that simple and the cure is equally simple.

Shellfish Allergy Shows the Relationship between Allergy and Autoimmunity

I ran across a list of other food allergens when I was checking up on peanuts.  Shellfish was listed as another of the big allergies.  I looked up “shellfish allergen” and ran into thousands of entries.  The first couple of dozen proteins lacked the characteristic basic triplet, so I had to step back and try to guess the most typical shellfish for first exposure, i.e. the primary immunogen.  All of the other shellfish allergens were various versions of the muscle protein, tropomyosin, so I looked up “shrimp allergen.”

MDAIKKKMQAMKLEKDNAMDRADTLEQQNKEANNRAEKSEEEVHNLQKRMQQLENDLDQVQESLLKANIQLVEKDKALSNAEGEVAALNRRIQLLEEDLERSEERLNTATTKLAEASQAADESERMRKVLENRSLSDEERMDALENQLKEARFLAEEADRKYDEVARKLAMVEADLERAEERAETGESKIVELEEELRVVGNNLKSLEVSEEKANQREEAYKEQIKTLTNKLKAAEARAEFAERSVQKLQKEVDRLEDELVNEKEKYKSITDELDQTFSELSGY

Note the predicted basic triplet in red.  Since I was on a roll, I also checked out related tropomyosin sequences in humans:

MDAIKKKMQMLKLDKENALDRAEQAEADKKAAEDRSKQLEDELVSLQKKLKGTEDELDKYSEALKDAQEKLELAEKKATDAEADVASLNRRIQLVEEELDRAQERLATALQKLEEAEKAADESERGMKVIESRAQKDEEKMEIQEIQLKEAKHIAEDADRKYEEVARKLVIIESDLERAEERAELSEGKCAELEEELKTVTNNLKSLEAQAEKYSQKEDRYEEEIKVLSDKLKEAETRAEFAERSVTKLEKSIDDLEDELYAQKLKYKAISEELDHALNDMTSM

Once again the basic triplet indicated that there was a related human tropomyosin that could interact with antibodies to the shellfish allergen or could be an autoantigen participating in autoimmune diseases.  So I checked PubMed for “tropomyosin autoantigen” and quickly found that antibodies to tropomyosin are important in ulcerative colitis (UC).  Thus, shellfish allergy may be an indication of an underlying predisposition to UC.  And, the traditional cure for allergy by injection with small amounts of the allergen to convert from IgE to IgG, would convert a shellfish allergy into UC.

Avoiding Allergens Makes No More Sense Than Trying to Avoid Autoantigens

To fix allergies, it is necessary to eliminate the cause and block perpetuation of the condition.  The cause is based on 1)inflammation, 2) broken immune tolerance and 3) primary immunogen.  Peanuts are the primary immunogen, but that is unimportant if the causing conditions are eliminated and tolerance is reestablished.  Clearly, if immunological tolerance is reestablished, then it's just a matter of time before peanuts are no longer a problem, because increasing Tregs will silence the dramatic immunological response to peanuts.  Tolerance is based on Tregs and Tregs develop in the intestines in response to Clostridia feeding on soluble fiber/resistant starch.

Curing Peanut Allergies is Based on Repairing Gut Flora

There are a couple of hundred different species in the pounds of bacteria in the healthy human gut.  Most of those bacteria require soluble fiber that is systematically removed during food processing.  For most people, the cure for peanut allergies will be resistant starch/Clostridium therapy, followed by further repair with fermented foods that provide the typical lactic acid bacteria and soluble fiber along with companion bacteria that can recolonize the gut.  The cure for many allergies and autoimmune diseases is just to eat a couple of tablespoons of resistant starch each day and if needed, supplement with probiotics containing Clostridium butyricum.  If there is severe dysbiosis, as indicated by constipation, then fixing the gut flora is a little more difficult, but for most people cures are much cheaper and effective than just treating symptoms.

A guide for the use of resistant starch is provided by Richard Nikoley, et al. at Free the Animal.

Metformin, Antibiotic with Autoimmune Side Effects

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Metformin

Major points linked in this article:

• Metformin is commonly used in the treatment of diabetes.
• Metformin is structurally and chemically related to arginine, guanine and Canavanine.
• Side effects of Metformin include GI upset and autoimmune lupus (same with Canavanine.)
• Metformin also kills bacteria, i.e. it is an antibiotic.
• Many pharmaceuticals, e.g. statins, were first identified as antibiotics produced by fungi.
• Antibiotics select for antibiotic resistance genes, i.e. essential bacterial genes that have mutated to no longer be inactivated by antibiotics.
• New antibiotic resistance genes are combined with other resistance genes on multiple resistance plasmids that are transferred as a group.
• Because of its wide use, resistance to Metformin (and statins) as an antibiotic probably already exists and has been incorporated into multiple drug resistance plasmids.
• Many common pharmaceuticals are also antibiotics and probably select for multiple drug resistance.
• A major contributor to multiple drug resistance, “super bugs”, and the rapid loss of efficacy of antibiotics is the over use of pharmaceuticals in general, in addition to the specific abuse of antibiotics designed to kill pathogens.

Metformin is a Good Anti-Diabetic, but...

Arginine

Metformin is the treatment of choice for type 2 diabetes and yet, like many other common drugs, the full extent of its impact on the body (and the body’s essential microbiome of bacteria and fungi) has not been studied.  This article should not be seen as a criticism of the pharmacological efficacy of Metformin in lowering blood sugar.  The point here is that Metformin alters gut flora and its major pharmacological impact may result from alteration of the gut flora and not direct action on cells of body organs.  Metformin, because of its structure and size would be expected to act relatively indiscriminately in numerous cell functions, but I don't think that these interactions are as important as the impact on gut flora.  Metformin has all of the properties of an antibiotic selected to lower blood sugar and have limited side effects.  It would not be expected to cause a dramatic increase in autoimmunity, because diabetics already have elevated autoimmunity and associated deficiencies in gut flora.

Metformin is a Diguanide
 I previously explored the interesting properties of Metformin in my laboratory and through computer modeling experiments, and found it would react with many cellular enzymes and receptors similarly to the amino acid arginine.  This was no surprise, since the working end of arginine is a guanide and Metformin is a Siamese twin of guanides, i.e. a biguanide.  I might as well also say that another guanide, Canavanine, a toxic, antimicrobial phytoalexin in bean sprouts, has similar properties.

Canavanine

Phytochemicals as Antibiotics

  

I have studied (and written about) the natural plant antibiotics, phytoalexins, in legumes, and particularly in soy beans, so I would expect all of the chemicals, (a.k.a. phytochemicals or “antioxidants”) extracted from plants, e.g. alkaloids, polyphenols and essential oils, to kill bacteria and be toxic to human cells.  The selective advantage to plants in producing phytochemicals is the antibiotic activity of those chemicals.  Pathogens that have adapted for growth on one species of plant have resistance genes to that plant’s phytoalexins.  Thus, bacterial genes for resistance to the antibiotic activity of drugs derived from phytochemicals are common in nature and broad use of these drugs merely selects for the transfer of these genes to gut flora.

Canavanine and Lupus
What put together more pieces of the gut flora/antibiotic/autoimmune disease puzzle for me, was coming across Dr. Loren Cordain's recent reiteration of the toxicity of legumes and his singular example of Canavanine from alfalfa sprouts as a contributor to the autoimmune disease, lupus.  When I looked up the structure of Canavanine and found it to be a guanide, I immediately started making comparisons to Metformin and was amazed to see that these chemicals share the same list of side effects focused on the gut.  Moreover, lupus is also a side effect of both Metformin and Canavanine.  It was initially surprising, that a recent study suggests that the anti-diabetic action of Metformin may result indirectly from its antibiotic effects on gut flora.  I now expect that Canavanine causes lupus by killing or altering the metabolism of particular species of bacterial gut flora involved in the normal functions of the immune system, e.g. Tregs required for immune tolerance.  It is now a common observation that many pharmaceuticals act indirectly via their impact on gut flora, i.e. many pharmaceuticals are fundamentally antibiotics, and particular antibiotics can duplicate the activity of pharmaceuticals.

Pharmaceuticals Select for Multiple Antibiotic Resistance
I have one other concern about the wide use of drugs derived from phytoalexins.  Metformin can be considered one of those drugs, and just like phytoalexins, it is a potent antibiotic.  There is no difference between purified natural plant antibiotics/ phytoalexins/ polyphenols/ antioxidants and commercially synthesized antibiotics with respect to selecting for resistance.  I would expect that resistance to Metformin, as an antibiotic, has already developed in common gut flora and consequently, that multiple drug resistance plasmids from hospital pathogens now contain Metformin resistance.  Thus, I would also expect Metformin and many other pharmaceuticals to select for multiple antibiotic resistance. [An additional example is the antibiotic activity of NSAIDs on Helicobacter pylori.  I think that prevalent use of NSAIDs in many countries is responsible for the decline in H. pylori.]

SweetMyx Taste Enhancers, Alapyridains?

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I was just reading announcements of new synthetic chemicals (SweetMyx) to enhance the taste and help reduce sugar and salt in "health foods".  The new taste enhancers have already been approved by industry organizations that designate the chemicals as GRAS, generally recognized as safe.  I, of course, was curious about how the SweetMyx chemicals made food taste sweeter with less added sugar.  Notice how convenient it is that the food industry has found a way to charge more for less sugar, just as labels have been changed to specifically designate "sugar added:".

Alapyridains are Taste Enhancers

I searched the chemical literature for new taste enhancers, since the chemical ingredients in SweetMyx are trade secrets and will not be disclosed on food labels.  It didn't take long to find that the likely suspects are called alapyridains.  This group of related chemicals are synthesized with a central pyridine ring familiar from the related cytosine and thymidine of nucleic acids, the plant alkaloid nicotine and the vitamin niacin.  A guanide group (half of the diabetes drug metformin, which is a biguanide) is added to make a salt enhancer, and a benzene ring is added to make a sugar enhancer.  Without these additions, the central structure inhibits the ability to taste the bitterness associated with "healthy plant antioxidants," phytochemicals and essential oils.

Will SweetMyx Just Tickle your Taste Buds?

The alapyridains that I expect to be in SweetMyx seem to be similar to common plant alkaloids, which are natural pesticides and antibiotics, i.e. phytoalexins.  So I would expect these compounds to also be antibiotics with unknown impact on our gut flora, nervous and immune systems, just like all of the medical antibiotics.  Based on the general putative structure of the taste enhancers and similarity to other molecules with known reactivities I would also expect these molecules to react with enzymes that bind sugars, e.g. glycosidases, or with hundreds of other proteins that bind to heparin, e.g. embryological growth factors, clotting factors, cytokines, amyloids, etc., etc., etc.  It would also be expected that these enhancers will encourage consumption without satiety and therefore, just as artificial sweeteners, contribute to further obesity.  In other words, these taste enhancers can be expected to have numerous, unpredictable medical and ecological side effects that will not be understood for decades.