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salicylatesIn my last post—Part 2 of this diet and inflammation series—I discussed the cells—called macrophages—which actually affect the inflammatory response, and how the amino acid glycine is crucial in regulating the activation of the macrophages at the level of the cell surface membrane. In the present installment, I’ll be discussing the propagation and amplification of the inflammatory response, and the key roles played by two other nutrients: salicylic acid and omega-3 (v. omega-6) fatty acids.

The cell membrane itself is made up mainly of molecules called phospholipids; natural soap-like molecules which each contain two fatty acids. Upon cellular activation, some of these phospholipid molecules are broken down such that one of the fatty acids is enzymatically converted to a messenger molecule—a prostaglandin—which diffuses away to activate—or inhibit the activation of—other cells it reaches (Such local messenger molecules are known as paracrine factors.) The enzyme that catalyzes the key step in the process is called a cyclooxygenase 2 (COX2). Salicylic acid inhibits the activity of COX2. (The synthetic drug aspirin, or acetylsalicylic acid, is a much more potent COX2 inhibitor; more on this later.)

The type of prostaglandin molecule released reflects the composition of the type of fatty acids that make up the membrane, which in turn reflects the fatty acid composition of the diet. The prostaglandins that amplify the inflammatory activation are made from the omega-6 fatty acid, arachidonic acid (AA); whereas prostaglandins that inhibit this activation are made from the omega-3 fatty acid, eicosapentaenoic acid (EPA).

Hence, the greater the preponderance of omega-6 fatty acids in the diet (largely from seed oils, e.g., corn, soybean, sunflower, peanut) as opposed to omega-3 (fish or krill oil, flaxseed oil), the greater the amplification of the pro-inflammatory prostaglandin signal. (The optimal dietary ratio of omega-6 to omega-3 is about 3 or 4 to one; although whether either type of these polyunsaturated fatty acid types—”PUFAs”—are even essential to the human diet is still debated. Oils that seem to have a perfect balance of fatty acid types include walnut and olive oils.) Since the mass campaign to replace saturated fats with PUFAs over the latter half of the 20th century was largely successful in saturating the Western diet (and that of its livestock) with omega-6 PUFAs, it has clearly contributed to the high prevalence of chronic inflammation.

Meanwhile, the extent of COX2 activity is largely controlled by the concentration of salicylic acid. For some reason, salicylic acid is often viewed as a “nutraceutical”, rather than an everyday nutrient. In fact, it is often not viewed as a nutrient at all, although aspirin is viewed as something middle-aged and older individual are encouraged to take daily to prevent thrombotic events such as heart attacks and strokes. Aspirin, however, is a potent synthetic drug. Although it acts like salicylic acid (as well as increasing the actual salicylic acid content of the blood), it has potentially dangerous side-effects, like excess bleeding. Meanwhile, salicylic acid itself is a widespread botanical compound, particularly high in berry fruits, grapes and kiwis, and also present in significant amounts in nuts like almonds and walnuts. (It is also a key component of EVOO that is removed when olive oil is refined.)

It is my belief that it is salicylic acid, rather than the much touted polyphenols in fruits and nuts which are key to “anti-inflammatory diets”, and which lower risk of cardiovascular disease, for example. These polyphenols (e.g., resveratrol, quercetin) are great anti-oxidants, but the value of anti-oxidants is largely to mitigate the effects of inflammation. I think it’s better to stop inappropriate inflammation from getting started. I also believe, for example, that the “French paradox”—why French people eat such a high-fat diet but suffer a low rate of heart disease—is not due to the polyphenols in the wine they drink daily, but from the high salicylic acid content of grapes, and therefore, wine.

So it’s pretty clear how the typical Western diet that is low in fruits and vegetables, and low in omega-3—but high in omega-6 fats—contributes to excess inflammation, by helping to amplify—and therefore exaggerate—the inflammatory response. But getting back to the initiation of inflammation in the first place, why should glycine levels be low in the first place, and allow inflammation to develop inappropriately? After all, glycine is a non-essential amino acid, so you really should not have to eat any of it, right? And if the diet is rich in high-protein foods (meat, fish, poultry, eggs, dairy), we are also eating plenty of it.

The answer turns out to be quite simple: Although we discovered a century ago that we need to eat whole grains to avoid devastating deficiency diseases like pellagra, we never thought that we also need to eat whole cows, pigs, chickens and fish! But it turns out that the key to a healthy omnivorous diet is to balance the content of essential amino acid methionine that predominates in muscle with the glycine that predominates in the bones and connective tissues, the parts we usually throw away.

The specifics of the biochemistry—the metabolic interactions of glycine and methionine and key intermediate metabolites and cofactors—are now understood, and present a fascinating picture of how our bodies’ metabolic machinery works as best it can with what we feed it to keep us alive and healthy. That will be the focus of my next post.

About the Author

Joel BrindJoel Brind, Ph.D. has been a Professor of Biology and Endocrinology at Baruch College of the City University of New York for 28 years and a medical research biochemist since 1981. Long specializing in steroid biosynthesis and metabolism and endocrine-related cancers, he has specialized in amino acid metabolism in recent years, particularly in relation to glycine and one-carbon metabolism. In 2010 he founded Natural Food Science, LLC to make and market glycine supplement products via http://sweetamine.com , which includes his own blog HERE.