Research drives new medical paradigm and prioritizes omega-3 for prevention

by Randy Hartnell and Craig Weatherby

Despite decades of research on cardiovascular disease, adult diabetes, and Alzheimer's disease, our understanding of their causes and contributory factors remains incomplete. Research into these “degenerative” conditions has produced some successes: especially the use of statins to reduce the risk of heart attacks. Otherwise, scientists have encountered multiple dead ends.

Now, the results of new research suggest that inflammation may be the common thread uniting these seemingly diverse diseases. In fact, while cancer was once seen as distinct from cardiovascular disease, adult diabetes, Alzheimer's, and other degenerative diseases, the results of recent research indicate that in many cases, it too may share an underlying link to chronic inflammation.

Last month, we attended the second annual Nutrition & Health Conference organized by Andrew Weil, M.D., founder/director of the Program in Integrative Medicine at the University of Arizona. Many of the presentations—including Dr. Weil's own talk, titled “Anti-inflammatory Diet”—focused on this topic.

Dr. Weil kindly allowed us to share some of his observations, which are based on a flood of exciting new research and his own clinical experiences.

Dr. Weil on inflammation and disease

“One of the interesting medical hypotheses that I see forming is the idea that chronic, inappropriate inflammation is the root cause of the diseases that appear with greater frequency as people age: cardiovascular disease, cancer, and neurodegenerative disease.

“For example, for years it has been thought that the atherosclerotic plaques resulted from abnormal lipid metabolism and deposition of cholesterol in artery walls.

There is a new consensus in cardiology that inflammation in the lining of arteries is a more basic disease process, and the damage to arterial walls that occurs as a result of that inflammation may create defects that the body is trying to plug by depositing cholesterol there. So in some sense, the cholesterol deposits may be a flawed healing attempt of the body that is trying to repair the damage cause by inappropriate inflammation.

“Alzheimer's disease clearly starts as an inflammatory process in the brain, and the creation of its characteristic amyloid plaques and neurofibrillary tangles may be the result of chronic inflammation. That may be one reason ibuprofen and other anti-inflammatory drugs have a preventive effect in Alzheimer's disease.

“Classically, cancer has been considered as a neoplastic disease, separate from the degenerative conditions, but the same hormones that up-regulate inflammation also up-regulate cell division, and any time cell division increases, risk of malignancy is increased.

“One cause for optimism from this hypothesis is that the same prevention strategies apply across these broad categories of degenerative diseases.  When you begin to analyze the nutrition aspect of this—how diet affects this process—it turns out the decisions you make about foods to reduce this chronic inflammation are the same decisions you would make on other grounds to optimize health. What I would call an anti-inflammatory diet is also the diet you would recommend for optimal health across the board.

“If these diseases are increasing in our society, what are the pro-inflammatory pressures that are causing the body to react this way? A lot of the pro-inflammatory pressures stem from the uninformed food choices people are making.

“Many of you have heard about the influence of fats on the inflammatory process. The omega-6 fats are substrates of hormones that up-regulate inflammation, and the omega-3 fats are substrates of hormones that down-regulate inflammation. Clearly, we need both of them, but in this culture, people are getting way too many omega-6 fats and way too few omega-3 fats.”

Dr. Perricone on inflammation

Bestselling author Nicholas Perricone. M.D. is another well-informed physician who is convinced that inflammation is at the root of degenerative disease, and that the unmatched value of omega-3s in reducing inflammation.  Our readers may recall that we reported on a recent New York Times magazine article titled “Perriconology.”  The article made prominent mention of his advocacy of eating wild Alaskan salmon, and the photo accompanying it showed Dr. Perricone seated behind a plate with a large salmon head on it.

In addition to an excess of omega-6 fats from vegetable oils, Dr. Perricone notes that refined starches are a key dietary factor driving inflammation. Much attention has focused on increasing antioxidant intake to slow aging—which is wise. But it is easy to overlook the other side of the equation. Every bagel, slice of white bread, doughnut, candy bar, and sugary drink (juice or soda) adds to a toxic excess of dietary glucose.

Dietary starches drive a process called protein glycation—an internal generator of inflammation-promoting free radicals.  Dr. Perricone says that protein glycation is one of the greatest forces underlying silent, “sub-clinical” inflammation and premature aging, and he notes that diets high in sugars and refined starches are a major contributor to protein glycation.

The dramatic acceleration of signs of aging seen in diabetes demonstrates the insidiously pro-inflammatory nature of sugars and refined starches. It's also known that chronic elevated levels of insulin in the blood—which results from chronic hyperglycemia (high blood sugar levels)—is pro-inflammatory.

Glycation is harmful because glycation bonds are virtual free radical factories.  In addition to promoting healthful omega-3 sources—primarily wild salmon—Dr. Perricone urges his readers to cut back on intake of carbohydrates—especially sugars and white flour products.

Omega-3s and inflammation

The anti-inflammatory effects of long-chain omega-3 polyunsaturated fatty acids—the kind found only in fish—were amongst their earliest identified properties.

But in recent years, research has shown that omega-3s exert anti-inflammatory effects through a wider variety of metabolic pathways than thought previously, and affect some of the key pro-inflammatory factors linked to cardiovascular disease.

Readers of Barry Sears' Zone diet books are familiar with the term ecosanoid, which refers to ephemeral, hormone-like molecules in the body. For decades, it was thought that omega-3s exerted all their antiinflammatory effects by reducing production of pro-inflammatory ecosanoids, largely by displacing a pro-inflammatory fatty acid—arachidonic acid—in cell membranes.

As reported here, recent studies have identified a novel group of anti-inflammatory mediators called E-series resolvins, which are formed from EPA in the presence of aspirin. In addition, DHA-derived anti-inflammatory mediators termed D-series resolvins, docosatrienes and neuroprotectins have been identified and appear to be antiinflammatory. This is an exciting new area of research in omega-3s, with implications for a variety of conditions.

As readers of Dr. Perricone's books may recall, a nuclear transcription factor called NF?B is involved in regulating expression of a large number of genes that promote pro-inflammatory enzymes and cytokines, including COX-2 (the enzyme that Celebrex and Vioxx block), TNF, IL-1, and adhesion molecules. And, cell culture studies show that EPA prevents activation of NF?B, which suggests that omega-3s reduce expression of inflammatory genes.

In summary, the original view that omega-3s exert anti-inflammatory effects only by blocking arachidonic acid metabolism was too simplistic. It appears that they also alter expression of inflammatory genes, and generate a broad variety of anti-inflammatory mediators.

This broad spectrum of anti-inflammatory effects explains why omega-3s help so much in the prevention—and possibly the amelioration—of diseases with an inflammatory component,  including diabetes, Alzheimer's, cancer, and cardiovascular disease.

Stay tuned for an exploration of the role of inflammation and heart disease in our next issue, including a follow-up on our prior article on statins.


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