Antibiotic Resistance, Superbugs and Drugs

--- All 200 posts here ---

Antibiotic resistance results, because spontaneous mutations occur so frequently that all bacteria are different.  It is just a matter of exposing enough bacteria to an antibiotic to find one that is insensitive to a particular antibiotic.  More bacteria mean a greater chance of mutations to antibiotic resistance.  The gut contains a lot of bacteria and sewage treatment plants are loaded with gut flora.

Health in Diagrams

Antibiotics are Ubiquitous

All organisms, plants, fungi and animals/humans produce chemicals that kill bacteria, i.e. antibiotics.  I have written many articles about the natural antibiotics of plants, a.k.a. phytoalexins or “antioxidant” polyphenolics, and the human defensins that are peptides with heparin binding domains.  Bacteria also produce viruses, called bacteriophages, that kill other bacteria.  All of these natural antibiotics are small molecules that interact with many different human proteins, and it is these side effects that permit their exploitation as pharmaceuticals.  Thus, statins were selected from fungal antibiotics that inhibited an enzyme needed for human synthesis of cholesterol, metformin was a phytoalexin found to reduce blood sugar and resveratrol is a grape phytoalexin.

Plant Antibiotics are Natural

The flavoring chemicals in herbs and spices have a far more important use in food preparation than titillation of taste buds, since those chemicals kill common food pathogens.  More profoundly, it is important to realize that the selective advantage of phytochemicals/polyphenols/alkaloids/essential oils to the plants that make them, is as natural antibiotics.  Plants kill bacteria, as well as fungi and insects, for a living.

Plant Chemicals Attack all Aspects of Bacteria

Most of the thousand genes that are present in a bacterium code for proteins/enzymes and most antibiotics target those enzymes.  Penicillin binds to an enzyme needed to make bacterial cell walls, streptomycin target protein synthesis, rifampicin blocks RNA synthesis, actinomycin D inhibits DNA synthesis, etc.

Mutation to Antibiotic Resistance is Automatic in Bacteria

Each time a cell replicates, mistakes are made and the new DNA molecule of each chromosome is slightly different than the original.  There are about a thousand genes on the single chromosome of a bacterium and about the same number on each of the 23 human chromosomes.  About a dozen mistakes, mutations, are made each time bacteria replicate.  The mutations that alter the gene target of an antibiotic and produce a bacterial enzyme that is unaffected by the antibiotic, yield an antibiotic resistant bacterium.  The mutant gene now codes for antibiotic resistance and the presence of several resistance genes in the same bacterium produces multiple antibiotic resistant "superbugs."

Mutations are Random, but Antibiotics Select for Resistance

Each cellular replication produces random mutations throughout the bacterial DNA, but of the billion sites along the DNA that can mutate, only a few will produce a modified enzyme that will no longer interact with a particular antibiotic and thus be resistant.  Antibiotic resistance mutants are rare, less than one in a million, but a million bacteria can grow from a single cell in a day and occupy a volume less than a crystal of salt.  Ten hours later, after ten more doublings of the million bacteria, there will be a billion, and there will be a good chance that among those will be a mutant that is resistant to a particular antibiotic.  In the pound of bacteria in the human gut, there are mutants that are resistant to most antibiotics, including the antibiotics that have not yet been developed.  Of course, most of those antibiotic resistant bacteria are just flushed down the toilet.  Treatment with antibiotics kills all of the sensitive bacteria and leaves only the resistant.  Thus, antibiotic treatments select for antibiotic resistant bacteria.

Common Use of Antibiotics Selects for Resistance on Plasmids

Genes are transferred between bacteria by bacteriophages, conjugation (a kind of bacterial sex) and transformation, which is the release of DNA from one bacterium with subsequent uptake by another.  Biofilms, which are communities of many different species of bacteria, stimulate transformation and exploit bacterial DNA as a matrix material to hold the communities together.  The human gut is lined with biofilms and the biofilm bacteria secrete vitamins as the quorum sensing signals that coordinate community activity.  Thus, some vitamins must stimulate transformation, the exchange of DNA among members of the different species of bacteria in the biofilms with evolution of new and novel species.  Rapid change in the gut environment selects for a shift in genes that provide for adaptation to the new environment to small DNA fragments, plasmids, that move most readily between bacteria.  Antibiotic treatment results in antibiotic resistance genes on plasmids.

Use of Multiple Antibiotics Selects for Multiple Antibiotic Resistance Plasmids

Persistent use of an antibiotic will spread resistance to a particular antibiotic through the gut flora, facilitated by antibiotic resistant plasmids.  Replacement of a second antibiotic will result in a new plasmid with both antibiotic resistance genes.  Hospitalization and exposure to a plethora of bacteria with multiple antibiotic resistance plasmids will result in rapid conversion of gut flora to multiple antibiotic resistance upon exposure to any antibiotics.  Hospital staff would be expected to be natural repositories for multiple resistance genes, especially if they are exposed to any antibiotic (or pharmaceutical.)

Most Pharmaceuticals Select for Multiple Antibiotic Resistance Plasmids and Superbugs

The frightening rise of superbugs resistant to all known antibiotics has been attributed to the accelerated use of antibiotics in medicine and agriculture.  Mixing megatons of bacteria in the guts of billions of people with tons of antibiotics, and still more in sewage treatment plants and agriculture, is bound to produce bacteria with every type of multiple antibiotic resistance plasmid imaginable.  But that is not the biggest problem, since fingering the commercial use and misuse of antibiotics ignores biggest exposure of bacteria to antibiotics.  It ignores the fact that most popular pharmaceuticals, NSAIDs, statins, anti-depressants, anti-diabetics, etc., also have substantial antibiotic activity.  Most of these pharmaceuticals started out as phytoalexins and then were found to also have pharmaceutical activity.  Pharmaceuticals are just repurposed natural antibiotics.  When you take an aspirin or Metformin or a statin, you are taking an antibiotic.  When you take a pharmaceutical, you are selecting for multiple antibiotic resistance plasmids in your gut flora and you may be making the next superbug.

SweetMyx Taste Enhancers, Alapyridains?

---  Here are the other 200 blog posts ---
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.

Phytochemicals, Natural Antibiotics and Antioxidants

Plants are mean and sneaky.  They are natural organic chemists and make the nastiest toxins on earth.  Never trust a plant.  Eat them at your peril… or because they taste good.

Phytoalexins

Plants are Fast and Lethal

I was shocked when people started to laud the virtues of phytochemicals.  I thought that they must have alkaloid poisoning.  My PhD training involved separating and measuring the antifungal chemicals produced by soybean cotyledons exposed to the wall polysaccharides of a pathogenic fungus.  The plants would go crazy and produce a witch’s brew of toxins to provide protection from the fungus.  I eventually wrote a chapter on these toxic natural antibiotics, phytoalexins, for the Encyclopedia of Science and Engineering.  All plants produce these chemicals and as one might expect, seeds/nuts are provided with special protection to avoid being digested.

Lignin

Plants are Natural Chemical Killers

I developed a profound respect for the ability of plants to protect themselves.  Fungal spores germinate on the surface of leaves and their slender, threadlike hyphae attach and glue themselves to the waxy outer surface and then forcefully and enzymatically penetrate to the spongy cells below.  When the tip of the hypha touches the wall of the underlying cell, the plant nucleus lurches as its cytoskeleton reorients.  The surrounding plant cells respond in sympathy and all of these neighbors mobilize their biochemical processes to kill everything in their vicinity.  In a few hours, the plant chemicals kill the cells producing them along with the pathogen, and would continue to kill more and more of the leaf, but plant cell walls also contain enzymes that convert the phytoalexins to more wall material, lignin, and protect cells outside of the influence of the fungus.  As lignin in wood and plant litter is slowly degraded by microorganisms, it forms humus, the natural organic material in compost and soil, and also releases a potpourri of potent plant phenolics like BPA.  Compost is also a rich source of cell wall polysaccharides, a.k.a. soluble fiber, that feeds soil bacteria.

Phytochemicals are Natural Antibiotics

Most phytochemicals have evolved in plants as pathogen or herbivore defenses.  Since the nervous system is adapted to detect other organisms, it is not surprising that plants target the sensory system, brain and nerves of herbivores, and we detect the flavor and smell of plants/herbs/spices by their defensive molecules.  All of the flavor and taste components of herbs and spices are phytochemicals that kill bacteria, fungi and other pathogens.  Nicotine and caffeine are insecticides.  A detailed, worldwide study showed that spices are used in specific global areas, because of the local availability of the spices and their effectiveness against local food storage pathogens.  People develop a taste for the plant defensive chemicals that they must be exposed to for sustenance.  Cuisine represents a knife edge that separates attractive stimulation from death.  Natural or organic does not mean safe or healthy.  Plants are as dangerous to eat as pufferfish.

Phytoalexins are Useful, but Be Very Careful

Perfume Ingredients

If a grape notices a nearby fungal pathogen, it produces its phytoalexins, including resveritrol, which is a notable “antioxidant” that has been recognized as contributing to longevity.  People are encouraged to drink red wine for the health benefits of its phytoalexins.  Most of the pharmaceuticals derived from plants are phytoalexins in disguise.  Of course, the evolutionary origins of phytoalexins as natural broad spectrum antibiotics, makes it no surprise that phytoalexins are commonly toxic, carcinogenic and very dangerous to fetuses.  Morning sickness has been explained as nature’s way of telling a mother carrying a vulnerable fetus to not eat plants and potentially phytoalexins.  It is wise for women to avoid plants, perfumes and essential oils during their first trimester.  Essential oils are phytoalexin extracts from plants and many of these components are the essence of perfumes.  These same chemicals, e.g. limonene, serve dual purposes as fragrances and paint strippers, recreational drugs and insecticides.  We can smell these natural plant chemicals, because they are attacking our nervous system.  Multipurpose mixtures of essential oils, such as Vick’s Vaporub, contain menthol, camphor, eucalyptus oil and terpentine that kill bacteria and fungi (toe nail fungus) and also stimulate cold/hot sensing nerves in the skin, which triggers endorphin production and reduces underlying joint inflammation.

Fruits are Fake Seduction

Fructose is fruit sugar.  That is very appropriate.  Fructose derivatives are the most central intermediates of central metabolism, glycolysis; glucose is immediately converted to fructose after it enters a cell as the fundamental source of energy and carbon building blocks.  Fructose is not normally transported in plants or animals, because it is too chemically reactive and toxic.  It rapidly bonds and crosslinks proteins and is ten times worse than glucose in forming AGE (advanced glycation end products) such as hemoglobin A1C.  If you feed fructose to cattle, it makes their meat tough by cross linking protein fibers and it does the same thing to human skin.  Fructose in fruit is a fake, because it is cheap and sweet.  Animals eat fruit hoping to find starch, which is the only polysaccharide that animals can convert to glucose with their own (not bacterial gut flora) enzymes.  Starch quickly becomes sweet, because amylase in saliva digests the long chains of glucose molecules of starch into shorter dextrins that trigger sweet sensors in the tongue.  Fructose masquerades as starch by binding to sweet sensors a hundred times more strongly than dextrins.  The evolutionary advantage to using fructose to make plants sweet is that it takes much less energy and carbon, and it also poisons insects and microorganisms.  That is why honey is made of equal amounts of fructose and glucose, rather than sucrose, for example.  Fructose in high concentrations is toxic to microorganisms and honey can be used to dress wounds.  I can’t understand why fruits, especially juices, are recommended as part of a nutritional diet.  At best, fruit should be converted into juice.  The juice should be discarded and the pulp eaten as a source of soluble fiber, pectin, to feed gut flora. 

Phytochemicals Must be Detoxified to be Edible

Bacterial and fungal pathogens must avoid detection by plants to avoid death by phytoalexins.  Insects, similarly must avoid preformed phytochemicals that would kill or poison them with their first bite.  Pathogens and pests that are effective on one species of plant cannot eat others with different chemical defenses; plants and their pests/pathogens are mutually adapted.  Primates browse on new shoots of many different types of plants, to avoid building up lethal doses of particular phytochemicals.  The same is true of humans, who also have intestines and livers that chemically treat and neutralize plant toxins.  These same human defenses determine the rate at which other related chemicals, i.e. pharmaceuticals, most of which are derived from phytoalexins, are transformed and excreted.  Turmeric contains curcumin, which is the most potent inhibitor of inflammation yet identified.  Unfortunately, curcumin is “detoxified” in the intestine and large amounts must be eaten to suppress inflammation.  Fortunately, pepper contains another phytoalexin, piperine, which inhibits the detox system, so that most cuisines that use turmeric combine it with black pepper.

Trade Your Liver for Vegetables

The liver is the only organ that can be continually regenerated and that is because humans have evolved to eat plants, and phytoalexins take their toll on the liver.  As plants are digested and absorbed in the small intestines and transported to the liver, phytoalexins accompany the nutrients.  Most of the phytochemicals are chemically detoxified by liver enzymes, but the phytoalexins kill some liver cells with each meal and some of the phytoalexins circulate in the blood and reach other tissues.  The phytoalexins are evolutionarily adapted to bind to proteins to disrupt essential enzymes of microorganisms and herbivores, and like pharmaceuticals to which they are chemically and functionally related, they have numerous side effects.  The chemical reactivity is what is detected as the “antioxidant” property of phytoalexins.  Antioxidant is nutritionally meaningless and basically reflects the chemical toxicity of phytochemicals.  After all, you can’t easily sell chemicals that are inherently toxic.  Meat and humans are made of the same easily digestible stuff, i.e. protein, fat, plus indigestible polysaccharides in connective tissue, i.e. chondroitin sulfate and heparan sulfate.  Plants are essentially anti-human and are made of protein, vegetable oils (omega-6), digestible starch, undigestible cell wall polysaccharides, undigestible lignin and toxic phytoalexins.  Humans have adapted to eating plants with liver enzymes, liver regeneration, gut flora (to eat otherwise indigestible polysaccharides, soluble fiber to produce short chain fatty acids) and elaborate cultural habits.  We avoid most plants as too toxic and have domesticated some to produce reduced and tolerable levels of phytochemicals.  Of course this also means that the domesticated, defanged crop plants have a hard time defending themselves and we have to continually worry about blights and pestilences, and end up applying our own witch’s brew of fungicides, pesticides, and herbicides.

Polyphenols and Hormesis
I am going to add a few comments on the benefits of phytochemical "antioxidants", a.k.a. polyphenols, to clarify what I think is a misuse of the term "hormesis", which I thought meant the dilution of a toxin until it reached a magic lower concentration which was beneficial.  The trade offs of phytochemicals are nicely discussed by the Whole Health Source blogger, Dr. Stephan Guyenet.  I just don't think that the benefit of toxic chemicals stimulating the body's own antioxidant arsenal is an example of hormesis.  The point is that phytochemicals always act as toxins and stimulate toxin defenses.  Phytochemicals don't act as anti-oxidants in the body, even though they stimulate antioxidant defenses at all concentrations.  They provide a dubious benefit of unnecessarily heightening defenses with concomitant energy expenditure at low amounts and net damage at higher amounts.

Hakuna Matata and Sip the Tea

Tea Fanatic

I seem to have painted a compromising picture of plants as less than the perfect food.  They are tough and potentially toxic.  Plants clearly don’t like to be eaten and the best that can come of eaten plants is a full belly and a damaged liver.  But if you cook or ferment the plants first and bacteria start to digest and dull the chemical arsenal, plants can be safely and perhaps even enjoyably eaten.  We need not eat just safe meat.  We can also kick back and sip the tea.

Dr. Oz Diet and Gut Flora Myths

….All 190 posts here….

I just watched a Dr. Oz program on health myths, including corrections, such as recognition of the high fructose content of agave syrup (especially bad for diabetics.)  So I thought I would go ahead and correct some of the perspectives on his show that I don't think are supported by biomedical research.

The Big Truth about Diet and Gut Flora

Health results primarily from a matched Diet AND Gut Flora, with minor contributions by exercise, personal genetics, environmental toxins, etc.  You can eat the extremes of just meat or only vegetables or any mixture and be healthy, as long as your gut flora is made up of about two hundred different species of bacteria that can fully digest the soluble fiber in your diet.  Health requires a gut flora adapted to your diet.  Those bacteria, the gut flora, produce all of your needed vitamins, eliminate constipation, block inflammation and control the development of your immune system, which takes place in the lining of your intestines in response to gut bacteria.

Assorted Health Truths

Truth:  Saturated fats are healthy, but polyunsaturated omega-6 vegetable oils are inflammatory.  Oz can't bring himself to read the literature and acknowledge the heart benefits of saturated fats and meat.

Truth:  Soluble fiber, e.g. pectin in fruit or inulin in leeks or chondroitin in meat, is healthy food for gut flora, but insoluble fiber, such as in whole grains is a scam and just sucks out micronutrients.  Oz could really help the public by explaining that the hundreds of different polysaccharides produced by plants, i.e. soluble fiber, are digested by hundreds of different enzymes in gut flora.  Gut flora digest soluble fiber into sugars that are converted into short chain fatty acids that feed intestinal cells.

Truth:  GMOs have been studied intensively, are relatively boring and healthy, but organically grown veggies have not been shown to provide any additional health benefits over conventional.  Oz adheres to a very political line and attacks GMOs without any reasoned arguments and touts organic veggies without reference to supporting research.

Truth:  Grass grown beef has healthier fats with more omega-3 oils, but omega-3 plant oils, such as ALA in flax, provide only minor benefits and can't substitute for the long chain DHA and EPA in fish/algae oil.  Oz keeps pushing flax seed even though the benefits are minimal and the problems of high insoluble fiber have not been tested.

Truth:  Constipation is a sign of unhealthy gut flora and can lead to autoimmune disease, allergy or food intolerance, but laxatives such as magnesium only fix the symptoms and not the missing essential gut bacteria.  Oz is really confused about constipation and focuses on dehydration rather than the bacterial content of stools.

Truth:  Antibiotics may be essential for surgery or life threatening bacterial diseases, but antibiotic-damaged gut flora must be repaired (not just probiotics) or the immune system will be compromised.  Antibiotics are major contributors to autoimmune disease and I don't think that Oz realizes the damage that he starts or continues by not repairing gut flora after he repairs hearts.

Truth:  Dairy probiotics, e.g. Lactobacillus or Acidophilus, can provide a quick fix for some functions of gut flora, but these limited probiotic bacteria do not survive in the gut and do not substitute for normal gut bacteria.  I think that Oz still sends his patients home with yogurt after heavy antibiotic treatment and leaves his patients with damaged gut flora and long term disease risk.

Truth:  An Anti-Inflammatory Diet can reduce sources of inflammation that is the foundation for cancer, autoimmunity, allergy and most diseases, but adding new bacteria (not dairy probiotics) through social contacts and live fermented foods is essential for a healthy gut and immune system.

Truth:  All needed vitamins are supplied by healthy gut flora (as biofilm chemical signals) and healthy people do not benefit from multivitamin supplements, but people with damaged gut flora, e.g. because of antibiotic use or autoimmune disease, may require specific vitamins.

Truth:  Antioxidants are just plant defense chemicals, i.e. plant antibiotics, that are unimportant in general health, but they may alter gut flora in unpredictable ways.  Oz likes all antioxidants, but can't explain why these generally toxic chemicals are not used by plants as antioxidants.

Truth:  All of the vitamin D that we need is supplied by minimal skin exposure to sunlight, but most Americans are vitamin D deficient, because chronic inflammation blocks solar production of vitamin D in the skin.  Oz doesn't seem to understand the role of inflammation in vitamin D deficiency.

Truth:  We don't need Grains and other sources of starch, but grains also typically cause health problems, e.g. sensitivity, intolerance or celiac, for most people and can cause inflammation of the gut and disruption of the gut flora that can lead to autoimmune diseases.  Most thyroid disease and back problems are autoimmune diseases that start with celiac.  Oz still promotes whole grains even though added bran lowers nutritional quality and many people are healthier without grains.  He also seems to ignore the relationship between grain, antibiotics and autoimmune disease.

Truth:  Breakfast is not a necessary meal and there are health benefits to lengthening the time between the last and first meal of the day, but if breakfast is eaten, it should be low in sugar and starch, i.e. avoid cereal, since cereal causes a severe spike in insulin when eaten after a fast.  Breakfast makes you hungry, because even protein in the morning will raise insulin and cause an eventual abrupt drop in blood sugar that is experienced as hunger.  Why does Oz believe in breakfast?

Truth:  Food intolerances and allergies (rare) are due to missing species of gut bacteria, but these eating problems cannot be fixed by diet alone, since new bacteria (other than dairy probiotics) must be eaten.  Dairy probiotics are only useful to cure lactose intolerance.

Truth:  Hygiene should be minimal, because most people repair damaged gut flora due to antibiotics, for example, by intimate contact with friends and pets.  Antimicrobial soaps and sterile home surfaces prevent gut flora repair, because the vast majority of bacteria killed by hygiene are beneficial.  Appropriate hygiene is a real problem for Oz and he is obsessed with closing toilet covers.

Truth:  Cardiovascular disease starts with inflammation and is aggravated by fat deposits, but statins and lowered serum cholesterol only reduce heart attack risk, because statins have a weak side effect of lowering inflammation.  Diet changes and repair of gut flora, e.g. my Anti-Inflammatory Diet, fish oil supplements and wild fermented foods, are much more effective at reducing inflammation and curing cardiovascular disease without the severe risks of statins.  Oz is slowly becoming skeptical of statins, but still hasn't read the research literature critically.

Truth:  Poor health and most diseases have only minor genetic risk factors, but diet and gut flora are "inherited" directly and shared by the whole family.  When your doctor asks what diseases run in your family, she is asking about your shared gut flora.  Oz still gives the impression that genes are significant in disease and for example asks audience members if relatives have had heart disease.  He should tell them to repair their gut flora!

Summary Diet Truths

Truth:  There is nothing magic about healthy foods.  All that is needed are protein (meat, fish, eggs, dairy, beans, etc.; plant and animal proteins are equivalent), fats (from leaf and meat, not omega-6-rich seeds) and soluble fiber (to feed gut flora) from their original sources to retain naturally abundant micronutrients (vitamins, except C, are usually unimportant.)  That is my Anti-Inflammatory Diet and supplements should not be needed.  Natural, local foods are healthy, but there are no super foods and exotic does not mean better.  Variety does not compensate for low quality.  Your gut flora needs time to adjust, especially to new soluble fiber, so just change foods with the seasons, not daily, and make sure that you are sampling new bacteria in live fermented foods to make your gut community adaptable.

Omega-3 Fatty Acids, Antioxidants and Cancer

It is hard to sort out the inflammatory effects of short/long-chain omega-6 and omega-3 fatty acids. Vegetable antioxidants make the picture even worse. The absolute, as well as relative amounts, of the various types of fatty acids make a difference. It also now appears that oxidation prior and during digestion may be important to the impact of polyunsaturated fatty acids (PUFAs). The source (perhaps even the meal composition) of the PUFAs was as important as omega-3 versus omega-6, for common, short chain PUFAs.

In some studies, omega-3 PUFAs, such as the short-chain alpha linolenic acid (ALA) common in flax seed or the long-chain fish oil FUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduced cancer in human and mice. Earlier work in cell cultures showed that all of PUFAs suppressed the growth of cancer cells.

A large French study (reference below) began in 1993. Approximately 100,000 women between the ages of 40 and 65 volunteered to provide dietary and breast malignancy information and ca. 75,000 qualified for the study (the French component of EPIC, European Investigation of Cancer and Nutrition) . The dietary data provided information on the fatty acid composition of meals and revealed who was eating vegetable antioxidants and vitamins.

Major findings:

• Neither omega-6 nor omega-3 fatty acids were related directly to breast cancer risk.
• Long chain omega-3 fatty acids (EPA and DHA) reduced breast cancer in the group of women with the highest consumption of omega-6 PUFAs.
• High LA or ALA consumption in the form of vegetable oils or vegetables reduced cancer incidence.
• High LA or ALA consumption in the form of processed foods or nuts was associated with a higher incidence of breast cancer.
• Longer chain PUFAs were not associated with increased risk, regardless of source.

What does this mean?

• The source of the PUFA is of paramount importance. This study may apply more specifically to cancers and less to other inflammation-based degenerative diseases. The general anti-inflammatory diet may need refinement. I would suggest the following additions:
• Retain the preference for the more omega-3 friendly olive oil or perhaps flax oil versus the omega-6 rich vegetable oils (corn, soy, safflower), but focus on freshness and do not heat these oils.
• The data seem to be in favor of saturated fats for cooking. That means a shift to coconut oil.
• Vegetable antioxidants may be most important in the gut during digestion. Do these antioxidants even enter the blood stream? Certainly some alkaloids get to the brain, but much of the impact of the less mobile, large molecules may be restricted to the gut.
• An extension of this discussion may be to encourage eating more leafy vegetables with meat. That may be the paleo-diet connection.

reference:
Thiébaut AC, Chajès V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, Riboli E, Bénichou J, Clavel-Chapelon F. 2009. Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer. Feb 15;124(4):924-31.

Antioxidants or Fermenting Gut Flora?

Long life is the result of a good diet and exercise. Plant antioxidants are eaten to sop up the reactive oxygen species (ROS) and omega-3 fatty acid-rich fish oils are consumed to reduce the production of inflammatory prostaglandins. Avoiding inflammation that has been linked to essentially all degenerative and autoimmune diseases should make us live better and longer. Unfortunately it is more complex than that, and studies in the simple nematode, Caenorhabditis elegans, show that your gut flora may have something to say about your longevity.

C. elegans nematodes live in the laboratory fed on Escherichia coli, the common colon bacterium. Since the bacteria are the sole diet of the worms, to change the worm’s diet, mutant bacteria must be used. To study the impact of various vitamins on longevity, mutant bacteria unable to synthesize particular vitamins were fed to worms and their average length of life was measured.

Deleting coenzyme Q (10) resulted in a surprising increase in longevity. It was assumed that since coQ10 was needed for effective bacterial electron transport, the disruption would result in an increase in inflammatory ROS. What actually happened was that the bacteria shut down their use of aerobic metabolism and turned on fermentation.

Fermenting bacteria are probiotic in human guts and it appears that the same is true of worms. These results suggest that probiotic, fermenting gut flora may be profoundly important in determining longevity. What we eat may determine how long we keep eating.

reference:
Saiki R, Lunceford AL, Bixler T, Dang P, Lee W, Furukawa S, Larsen PL, Clarke CF. 2008. Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q. Aging Cell. 7(3):291-304.

Inflammation Score

Most people need some feedback to monitor the impact of their diet and exercise on their health. I tried to point out some of the major contributors to chronic inflammation with a little check list. See how you score (choose one of the list for each category) and give me your feedback on the how you think each part contributes to inflammatory diseases.

Fat Content ____
lean 0
extra abdominal fat 4
obese 8

Carbs ____
small meals, no cereal for breakfast 0
fistful of starch with each meal 2
pasta/rice/potato as a meal 4

HFCS ____
high fructose corn syrup banned from your diet 0
don’t avoid HFCS, but avoid soft drinks 2
have replaced sucrose with HFCS, enjoy soft drinks 4

Unsaturated Fats ____
have removed vegetable oils (except olive oil) from your kitchen 0
use canola oil 2
have replaced saturated fats with corn oil 4

Trans fats ____
eat no trans fats 0
avoid trans fats on your chips 2
don’t know what trans fats are 4

Fish oil ____
supplement with two or more fish oil (DHA/EPA) capsules per day 0
eat at least two helpings of oily fish per week 2
avoid all fish products 4

Antioxidants ____
know that coffee, tea and chocolate are good sources of vegetable antioxidants 0
eat five servings of fruits and veggies 0
take vitamin C supplement, because you avoid veggies 2
avoid veggies; meat and potatoes type 4

Exercise ____
take a stroll after meals and maintain your muscle mass 0
run when you feel guilty 2
couch potato 4

If you smoke, add an extra 15 points

Add ‘em up. How much are you stoking the inflammation furnace?
0-5 Cool! You will never look your age.
6-10 You are getting warm. Hope that you don't have any genetic predispositions to disease.
11-15 You may postpone inflammatory illness until middle age. The flame is lit. Pick your disease.
16-25 If you aren’t showing a chronic disease, you will soon.
26+ You can reverse your disease symptoms with the inflammatory diet and exercise.

Palm Oil

One of my favorite chocolates is Truffettes de France. I tell myself that just one serving (1.5 oz) or five pieces will provide an excellent supplement to may daily plant anti-oxidants. I am almost tempted to consider it one of the five recommended servings of fruits and vegetables. Alas, examination of the ingredients lists palm oil first, sugar second and low fat cocoa third.

Palm oil is a story in itself. This oil is about half palmitic acid (C16), one third oleic (C18) and one tenth linoleic (C18). The soap made from palm oil was developed in the US by the Palmolive company. Notice the name, palm-olive, from the two prominent fatty acids, which are also named after their original sources, palm and olives.

Another rather shocking use of palm oil is with naphthalene to produce a sticky flammable mixture called napalm.

Oil palms were brought to Malaysia from West Africa in the beginning of the 20th century. When I stayed in Singapore in 1997 for a research sabbatical, the monsoon season was delayed so that the rainforests of Malaysia and Indonesia were drier than usual. Entrepreneurial plantation owners took advantage of the opportunity to send out thousands of workers to start fires. Fire is the tool used to clear forests and subsistence farmers from lands that cannot be used for profit, and to turn those cleared lands into plantations that use the landless as employees. The smoke was so thick throughout the whole region that street traffic in some areas of Malaysia and Indonesia had to be restricted for safety. I could see smoke even in the lecture halls at the National University of Singapore and my daughters had to check the smoke level outdoors before traveling to the university swimming pool. There were reports that birds fleeing the burning forests were lost at sea and took refuge on ships. Orangutans in Borneo Sumatran Tigers and the Asian rhinoceros are endangered by encroaching plantations.

My big worry about eating the delicious truffles is the linoleic acid. This shouldn’t be too much of a worry, even though it is an omega-6 fatty acid, because it is too short. Most vegetable fatty acids are shorter than the C20 needed to make inflammatory prostaglandins. The trouble is that short fatty acids can be elongated from 18 to 20 to 22 by cellular enzymes and omega-6 fatty acids block the elongation of omega-3 fatty acids. Omega-6 fatty acids that are heavily marketed by the US agribusiness industry, are essential in small amounts and a health risk when present in the diet in a higher ratio to omega-3 oils of greater than approximately three or four to one. The US diet is typically more than 10:1, highly inflammatory.

The single serving of five truffles contains about a gram, 1000 milligrams, of linoleic acid, so it will take about a single fish oil supplement capsule to balance that much omega-6 fatty acid. Maybe I will try to cut back to just a couple of truffles and eat more kale.