Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
(find topics using search [upper left] or index [lower right]), and
more articles by Prof. Ayers on Suite101 .

Saturday, August 30, 2008

Preventing Allergies

The cause of allergies and autoimmune degenerative diseases is inflammation.

As a scientist, I am concerned with how the body works at the molecular level. I try to understand how molecules of cells interact to cause disease. So if you tell me that you have an allergy, I want to understand how you became allergic and I am much less interested in how you avoid triggering your allergy. If you say that your allergy is triggered by ragweed pollen, I want to know the shape and structure of the proteins or carbohydrates of the pollen that actually come in contact with receptors on the surface of your cells and trigger the allergic response, but I also want to trace those interactions back to the original events that started the allergy.

Allergies are mistakes of your immune system. Your body should learn to ignore common food and environmental molecules as it ignores itself. There is an elaborate system used by cells of your body to disassemble and display fragments of dangerous pathogens on the surface of cells for evaluation by the immune system. Inappropriate display of innocuous or self molecules is part of the problem in allergies and autoimmunity.

Ragweed pollen, for example, will cause no reaction unless pollen proteins bind to antibodies (IgE) held in receptors on the surface of mast cells. We know that ragweed pollen binds to anti-ragweed antibodies on the surface of mast cells of allergic individuals and triggers the release of histamine and other molecules that give the symptoms of allergy. That’s why you take antihistamines to remediate the allergic symptoms. The first questions are what are the ragweed molecules to which the antibodies bind, i.e. the ragweed allergens and why is this allergic person producing anti-ragweed antibodies?

We know that the ragweed allergens are common pollen proteins, but why are they particularly prone to producing allergies? I tried to figure out this riddle by asking if there is something about these proteins that make their transport into cells more likely. I had just discovered that a particular amino acid sequence, a triplet of basic amino acids, lysine or arginine, resulted in transport of proteins into cells. This triplet that provides binding to heparin is found, for example in the nasty HIV protein, called TAT that moves on heparan sulfate proteoglycans (HSPGs) from infected to uninfected human cells and paves the way for the spread of infection. This triplet is also found in heparanase, that is first secreted by cells in an inactive form, is brought back into cells by binding to HSPGs, is activated by partial digestion and resecreted for action in the extracellular environment. This heparin-binding triplet can also be added to other proteins, e.g. the fluorescent jellyfish protein, to transport those proteins into cells.

Examination of ragweed pollen and subsequently dozens of other common allergens revealed that each one (or a close relative) possessed the unusual heparin-binding triplet of basic amino acids. The basic charged character of these sequences also determined that these parts of proteins would be present as accessible coils on the surface of the proteins. It is interesting that people suffering from the autoimmune disease of lupus produce antibodies to most of the proteins found in the nucleus of their cells. These nuclear proteins bind to nucleic acids, that mimic the structure of heparin and in many cases have triplets of heparin-binding basic amino acids. Thus, it appears that allergenic proteins enhance the chance of uptake by cells that can display them to the immune system, because of their triplet heparin-binding domains and the immune system subsequently produces antibodies that bind to other regions of the protein allergens. This explains how the antibodies are produced to these allergens, but it does not explain why some people produce antibodies to environmental antigens and healthy people do not.

Allergic people readily expand their allergies to include new allergens. What is it about these susceptible people that makes them allergic? I think that the answer is inflammation. Inflammation leads to a disruption of normal production of heparan sulfate proteoglycans and as a consequence to a change in how external proteins interact with cells involved in processing antigens for presentation to the immune system. This means that people with chronic inflammation, also called the metabolic syndrome, are not only increasingly susceptible to diabetes, arthritis, heart disease, etc. but they are also at risk for picking up new allergies. This also suggests that an anti-inflammatory diet and lifestyle changes would be of great benefit to those with allergies. Unfortunately, because of immunological memory, it will take years to deplete the population of antibody secreting cells that provide the basis for a specific allergy and during this depletion time, the allergen would have to be scrupulously avoided. It might also mean that autoimmune diseases such as type I diabetes might be treated by depletion of anti-beta cell antibodies and their secreting B cells along with a shift to an aggressively anti-inflammatory diet.

It is my belief that many of the genetic components of allergies and autoimmune diseases would not be experienced in the absence of chronic inflammation as a precipitating condition.

Friday, August 29, 2008

Heparin and Inflammation

Heparin dominates the extracellular world and controls inflammation

Why is heparin such a big deal in inflammation? Heparin controls the communication between cells and to a great extent it also controls what goes in and out of cells. At the same time there appears to be a feedback system, so that cells that have their inflammation program triggered also change their production of heparin.

I am using the term “heparin” very loosely here to include all of the different forms of the highly sulfated polysaccharide. All of these different forms start as polysaccharides (long sugar chains) extending from proteins, i.e. proteo (protein) glycans (polysaccharides). The sugar chains are made by enzymes that alternately add a negatively charged sugar (glucuronic acid) and then a positively charged sugar (N-acetylglucosamine) in long chains to a four sugar linker attached to a protein. The “heparan” polysaccharide is then altered chemically and highly negatively charged sulfate groups are added. The alterations are not uniform along the length of the heparan, but rather form islands along the chains with special structures. In some cells, the long heparan sulfate chains are attacked by enzymes, so that the heavily sulfated islands are released as short chains, oligosaccharides, called heparin. Heparin is commonly secreted by mast cells as these cells secrete their companion molecule histamine during responses to allergens. Thus, one function of heparin, which is negatively charged, is to neutralize the positive charge on histamine as they are stored in vesicles prior to release.

Heparan sulfate proteoglycans (HSPGs) are continually secreted and then brought back into cells. This turnover is fairly rapid, so the HSPGs that dominate the surface of cells is renewed every six hours. This is true for most cells, including your cartilage cells, chondrocytes, that live in small HSPG-lined capsules within the cartilage (collagen fibers in another sulfated polysaccharide, chondroitin sulfate) as they mine the cartilage as their source of protein and carbohydrates at one end of the cell and synthesize new cartilage from the other end. Damaged cartilage must be pressed very firmly together, so that these chondrocytes can knit the damaged regions back together with their burrowing/synthesis action. At the same time that cartilage protein fibers and polysaccharides are being recycled on a tissue-wide scale (collagens have a lifetime of at least decades), the cells rapidly treadmill their HSPGs.

Some proteins travel on the HSPGs from one cell, to adjacent cells. The HIV protein called TAT is secreted from HIV-infected cells bound to HSPG. As the bound TAT is swept from one end of the cell to another, it encounters the HSPGs sweeping over the surface of neighboring cells and jumps ship, so to speak. The TAT is then swept into the unsuspecting neighbor that has not previously experienced HIV. The particular heparin-binding regions of the TAT protein are similar to the nucleic acid-binding regions of cellular proteins, so the TAT is transported to and into the nucleus, where the TAT acts as a transcription factor and prepares the cell for HIV infection.

Heparan sulfates dominate the extracellular region surrounding a cell and the heparan sulfate chains attach to both hormones and hormone receptors and mediate signaling. For example, the inflammatory and anti-inflammatory cytokines and their receptor proteins embedded in the cell surface all have heparin-binding domains. Heparin-binding domains are also present in proteins of the clotting system, most of the complement components and in many of the proteins that regulate development. Most defensive peptides with antimicrobial properties have heparin-binding domains and if heparin binding domains are removed from proteins, they are antimicrobial peptides.

Heparan sulfate proteoglycans dominate the extracellular interactions the way nucleic acids dominate the nucleus. Phospholipids and inositol phosphates may be similarly dominant in the cytoplasm. It is interesting that the active component in digestive fiber is inositol hexaphosphate, phytic acid. Also note that amyloid diseases, such as Alzheimer’s and type I diabetes are characterized by extracellular fiberous aggregates of proteins, e.g. beta-amyloid, on a scaffold of heparin. Some of the amyloid proteins don’t have heparin-binding domains, until they stack into fibers. The cellular scaffold for tau fibers has not yet been identified, but perhaps it is a form of polymerized inositol phosphate.

Many drugs act on heparin-binding or interacting domains and that is another reason why heparin and heparin-binding are critical elements of inflammation.

Thursday, August 28, 2008

Cowpies and Heparin

Heparin blocks E. coli O157:H7 binding in cattle

Bacteria bind to human cells via the sugars (oligosaccharides,e.g. heparin) and proteins on their surfaces. It is advantageous to keep bacteria that are potential pathogens moving through our gut. Thus tears containing bacteria swept from our eyes and mucous with bacteria swept from our lungs end up being swallowed and passed through our digestive system. Pathogens are adapted for their ability to stick to and penetrate the layer of cells on the surfaces of our body.

We need E. coli bacteria in our bowels to digest molecules in our diet and produce vitamins. Beneficial bacteria are called probiotics. But some strains of the E. coli have been produced in cattle under conditions that favor the production of nasty toxins. This is what I think happens. Cattle secrete heparin along the full length of their gut (pig or cattle intestines are the primary source of commercial heparin) and this blocks binding of pathogens that require binding to the heparin on the surface cells. The bacteria that are normally present in the complex digestive system of cattle are disrupted by routine use of antibiotics and altered feedstock. The net result is that the bacteria that normally coat the rectal area of the cattle, which lacks heparin production, are eliminated by antibiotics and are replaced by E. coli that has picked up a gene for secretion of a toxin normally produced by a bacterial pathogen. The toxin is required to induce the release of nutrients required by the new strain of E. coli. This new strain also produces a protein, hemagglutinin, that binds to the heparin immobilized on the surface of the rectal cells. Thus, cattle raising approaches have created a new pathogen, E. coli O157:H7.

When cattle produce cowpies, the rectal bacteria coat the cowpies. As a result, the screening of the surface of cowpies can identify the presence of cattle contaminated with the toxin-producing E. coli strains. During the processing of these cattle or others splashed with the toxin bacteria, the bacteria can be spread to meat, enter our food and be spread to people. I think that the increase of chronic inflammation in the U.S. population makes us particularly susceptible to this type of pathogen. Improved hygiene will help, but changes in animal husbandry may be the ultimate solution.


You don’t wear out, you flame out.

I don’t think that aging happens -- aging is just medically mismanaged chronic inflammation. The major observations are that older people have more degenerative/autoimmune diseases and they suffer from fewer infectious diseases. It would appear that the bodies of older people have figured out infections with an experienced immune system and that mechanical damage takes its toll over time -- joints wear out. I think that there may be a minor amount of truth in this cultural perspective, but there is something more profound at work, sarcopenia.

Sarcopenia (muscle loss) is the gradual loss of muscle and replacement by fat. Thus, by age fifty most people are physically less active and even if they appear to have the same weight and shape as in their active youth, the muscle of their abdomens and limbs has been partially replaced with fat surrounding their organs. This fat, as in those who are obese, releases inflammatory cytokines into the circulation and the body reacts as if it had a low grade infection.

Senior citizens are constantly expending energy and taxing their immune system by chronic inflammation. As a result they get fewer infections, but the chronic inflammation provides the foundation for cancer and autoimmune diseases. Their bodies aren’t mechanically wearing out, but they are wearing out by over use of the immune system.

Those seniors who are physically active and eat an anti-inflammatory diet, do not appear to age as fast as those who are sedentary, obese and display the typical symptoms of chronic inflammation, the metabolic syndrome. Most of the characteristics associated with advancing years are merely symptoms of poorly managed chronic inflammation that can be reversed by an anti-inflammatory diet and exercise.

Monday, August 25, 2008

Omega-3 fish oils

Omega-3 oils can only lower inflammation if you remove omega-6 vegetable oils from your diet

Wikipedia has a good explanation of fats and fatty acids. What is important here is what fatty acids are (long chains of carbon atoms with a carboxyl group on the end; the shortest is acetic acid [vinegar] that has one carbon on the chain attached to the acid group), how they are present in your diet, how they get to your cells and how your cells convert the fatty acids into inflammatory or anti-inflammatory short-range hormones, prostaglandins.

Fatty acids differ by the length of their carbon chains (always even numbers, since they are synthesized by the addition of pairs of carbons), and the number and positions of unsaturations (two bonds between the same carbon). Chemists would normally number the carbon atoms from the starting acid, but in this case the distance from the other end is what is important, so a fatty acid with a double bond between the last 3rd and 4th carbons would be call an “omega-3” fatty acid. The two most important omega-3 fatty acids are EPA (20 carbons) and DHA (22 carbons). They are both present in fish oil.


Most plant sources of omega-3 fatty acids, e.g. flax (ALA, 18), are much less effective in anti-inflammation, because they are too short.

Leafy plant materials have some useful omega-3 fatty acids, but seeds tend to have omega-6 fatty acids. Most vegetable oils, with the very important exception of olive oil, promote inflammation. In this context, I think that saturated fats, e.g. eggs and butter, are safer for your health than common vegetable oils, such as corn oil. The increase in degenerative and autoimmune diseases in the last fifty years can be attributed to the shift from dietary saturated fats to unsaturated vegetable oils (and trans fats). In the absence of chronic inflammation, I don’t think that saturated fats will contribute to heart disease -- deposition of fats and cholesterol at sites of inflammation is the problem.

Fatty acids are present in your diet attached to a short three carbon compound, glycerol. The glycerol with three attached fatty acids is called a triglyceride or fat. The fatty acids (also called soap) can be removed from the fats by boiling in lye = saponification. That’s the source of high glycerine soap.

You can’t digest fats without the soapy contents of bile from your pancreas. So if you swallow a couple of fish oil capsules on an empty stomach, the oil will just keep moving through your intestines. You need to take fish oil with other fat-rich foods to get the maximum benefit.

Fatty acids are removed from fats in the intestines and after transport to the liver. They are then transported out to the cells of your body and converted into phospholipids, glycerol with two fatty acids and a phosphate instead of a third fatty acid. Cell membranes are made of phospholipids and cholesterol. The phospholipids with longer fatty acid chains, e.g. DHA, EPA, form into thicker islands in the membrane. The fatty acids from these islands are removed and converted by an enzyme, COX, into the prostaglandins. Omega-3 fatty acids are converted into anti-inflammatory prostaglandins by COX and they also block the production of inflammatory prostaglandins from omega-6 fatty acids. Omega-3 oils are only effective in lowering inflammation if omega-6 vegetable oils are eliminated, if enough is present continuously to block conversion of omega-6 fatty acids already present, and the fish oil is consumed with other fats that trigger bile production.

Aspirin binds to COX and inactivates it so that fewer prostaglandins of either type are made. Since inflammatory prostaglandins are needed to produce healthy gut tissue, aspirin can be hard on your stomach and intestines.

Prostaglandins are very important in many natural processes. Birth for example, results from an increase in inflammatory prostaglandins and labor can be stopped with aspirin.

Stored fat is a constant source of prostaglandins. Unfortunately, the omega-6 fatty acids already present in your stored fat will be competing with the omega-3 fish oils that you consume. If you already have lots of stored fat, i.e. obesity, then you cannot afford to have vegetable oil in your diet and 6-12 fish oil capsules eaten with meals will be required to see a reduction in inflammation. Exercise will be even more important.

The simple dietary requirements for the anti-inflammatory impact of fish oil are the reason why many omega-3 trials have been inconclusive. When properly administered, omega-3 oils have been effective in the treatment of allergies, Alzheimer’s, asthma, arthritis, atherosclerosis, ADHD (just to start with the “As”). Omega-3 oils can also reduce many problems of pregnancy, such as some forms of infertility (male and female), pre-eclampsia, autism and low birth weight (short gestation).

Saturday, August 23, 2008


Your Diet is Depressing

It is no wonder that Americans are depressed. Workers are depressed. College students are depressed. Kids are depressed. New mothers are depressed. And they are all medicated with ineffective anti-depressants. It is an increasing epidemic of poor mental health care.

What is not uniformly recognized is that depression is a symptom of chronic inflammation. Moreover, the same diet changes that help with other degenerative and autoimmune diseases, also help with depression. There was a recent research article that found that postpartum depression in new mothers responded to anti-inflammatory drugs.

I am, of course, dealing in sweeping generalizations here and I explicitly am not attempting to replace medical evaluation in particular cases. There are many different kinds of depression. I just think that the impact of diet on mental health is depressingly ignored.

An evaluation of more than 250 studies on the usefulness of omega-3 oils in the treatment of many different mental health problems, including depression, observed conflicting results. One of the major problems with the studies, was that the researchers did not control the amount of omega-6 oils in the diets of the participants. Since it is the ratio of omega-3 to omega-6 oils in the diet that is important in controlling inflammation, this is a shocking mistake. The researchers seem to have been assuming that the omega-3 oils were treating a deficiency, instead of inhibiting the production of inflammatory prostaglandins from the omega-6 oils.
I think that most of the public dietary guidelines get it wrong, because they focus on reducing saturated fats. Replacing saturated fats with omega-6 unsaturated fats, e.g. corn oil, will lead to chronic inflammation. I don’t think that there is any good research that shows that there are health risks for saturated fats in your diet, unless you are in a chronic inflammatory state -- if you already exhibit the metabolic syndrome, then saturated fats are a double whammy.

It would seem obvious that anyone seeing a physician for depression, should be advised to shift to an anti-inflammatory diet. I think that the shift in diet will have greater impact than antidepressants. The first step is to ban trans-fats, high fructose corn syrup and omega-6 rich vegetable oils from the kitchen. Try to only use olive oil. The second step is to increase omega-3 oils by eating fatty fish and supplementing with fish oil capsules. I recommend an experiment to gradually increase omega-3 oils in your diet until you see relief from your depression. Each week keep track of how you feel each day. Starting with four fish oil capsules per day, increase each week by two more capsules per day, e.g. week 1 - 4 caps, week 2 - 6 caps, week 3 - 8 caps. The upper limit is probably about 12 caps/day. It will be harder if you are obese, because fat cells are inflammatory. Digestion of the oil is improved when eaten with other fat-rich foods. The capsules can be spread over several meals.

The bottom line: depression can result from chronic inflammation that has spilled over to become inflammation of the brain. Treating the chronic inflammation by correcting diet should reduce the symptoms of depression. It has been my observation that depressed people seem to benefit from gaining control of some part of their lives, so changing diet may be a good place to start.

Thursday, August 21, 2008

How Your Diet makes You Sick or Healthy

The Simple Equation of Life

We have all heard that health, for good or ill, is a result of genetics and lifestyle. This is the old nature and nurture discussion played out on our bodies. We also know that diet and exercise are major determinants of disease susceptibility and aging.

• My first point is that diet can trump the other factors, so that a healthy diet avoids genetic predispositions to disease or a bad diet displays those genetic defects.

• My second point is that diet can lead to chronic inflammation, a body condition also associated with the metabolic syndrome, which is a prelude to the degenerative and autoimmune diseases that plague the population of The United States. It should not be surprising that a change of diet is the answer to this suite of diseases.

The simple relationship between diet, inflammation and disease, explains many of the problems and solutions of U.S. healthcare. As Michael Pollan described with great clarity in The Omnivores Dilemma, our corn-based agricultural economy has led to huge incentives for domination of U.S. diet by corn products: corn oil, corn starch, corn syrup and fructose. Excessive use of each of these corn products individually can lead to inflammation and their combined use synergistically undermines our health.
This website is devoted to showing the intimate relationship between diet and disease, or more hopefully, between diet and health. The most hopeful aspect of current research is the view that aging is in large part a symptom of poorly managed chronic inflammation -- the typical symptoms normally associated with aging are actually symptoms of increasing inflammation.
An inflammatory diet is the foundation for diabetes, arthritis, allergies, intestinal inflammatory diseases, cancer, infertility, heart disease, Alzheimer’s disease, etc. All of these diseases are initiated and exacerbated by diet-based inflammation and all of these diseases can be ameliorated by appropriate diet.
Most of the dietary suggestions that you will find here will appear to be common sense. The problem of the U.S. diet is that we have strayed from common sense and have systematically compromised our health. The vast majority of disease is preventable by relatively simple changes in or national diet. The Zone diet developed by Barry Sears is basically an anti-inflammatory diet, and it works. The No Flour, No Sugar diet of Peter Gott also works, for similar reasons. Diets rich in starch and vegetable oils (with the exception of olive oil) are inflammatory and not healthy. On the other hand, complex carbohydrates (most polysaccharides other than starch), protein, low omega-6/high omega-3 oils, modest amounts of saturated fats, low fructose, and no trans-fats leads to low insulin, moderate blood glucose, happy gut flora, lean body, avoidance of chronic inflammation and health.
This website will focus on recent research published in the biomedical literature and I will attempt to place this research into perspective on how diet, inflammation and disease are related. In the process, I will also discuss:
• Why women become infertile on an inflammatory diet,
• How your stomach digests proteins into antibiotic peptides,
• How castor oil can relieve pains and inflammation,
• How inflammation is connected to allergies and autoimmune diseases,
• How your metabolism is controlled by the bacteria in your gut,
• How spices control inflammation,
• How fructose contributes to aging of your skin,
and much, much more.