Omega fatty acid balance can alter immunity and gene expression

Appearing in the June 5 issue of JBC

30 may 2009--For the past century, changes in the Western diet have altered the consumption of omega-6 fatty acids (w6, found in meat and vegetable oils) compared with omega-3 fatty acids (w3, found in flax and fish oil). Many studies seem to indicate this shift has brought about an increased risk of inflammation (associated with autoimmunity and allergy), and now using a controlled diet study with human volunteers, researchers may have teased out a biological basis for these reported changes.

Anthropological evidence suggests that human ancestors maintained a 2:1 w6/w3 ratio for much of history, but in Western countries today the ratio has spiked to as high as 10:1. Since these omega fatty acids can be converted into inflammatory molecules, this dietary change is believed to also disrupt the proper balance of pro- and anti- inflammatory agents, resulting in increased systemic inflammation and a higher incidence of problems including asthma, allergies, diabetes, and arthritis.

Floyd Chilton and colleagues wanted to examine whether theses fatty acids might have other effects, and developed a dietary intervention strategy in which 27 healthy humans were fed a controlled diet mimicking the w6/w3 ratios of early humans over 5 weeks. They then looked at the gene levels of immune signals and cytokines (protein immune messengers), that impact autoimmunity and allergy in blood cells and found that many key signaling genes that promote inflammation were markedly reduced compared to a normal diet, including a signaling gene for a protein called PI3K, a critical early step in autoimmune and allergic inflammation responses.

This study demonstrates, for the first time in humans, that large changes in gene expression are likely an important mechanism by which these omega fatty acids exert their potent clinical effects.

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From the article: Effect of dietary fatty acids on inflammatory gene expression in healthy humans, by Kelly L. Weaver, Priscilla Ivester, MIchael C. Seeds, L. Douglas Case, Jonathan Arm and Floyd H. Chilton
Article Link: http://www.jbc.org/cgi/content/abstract/M109.004861

Omega-6 PUFAs and risk of cardiovascular disease

AHA stands by advice to include omega-6 PUFAs in heart-healthy diet

31 jan 2009--A new Science Advisory report from the American Heart Association recommends that omega-6 polyunsaturated fatty acids (PUFAs), as found in vegetable oils, nuts and seeds, are beneficial when part of a heart-healthy eating plan. Consumers should aim for at least 5-10% of energy (calories) from omega-6 PUFAs, and will derive most benefit when omega-6 PUFAs replace saturated or trans fats in the diet. Precise recommended daily servings will depend on physical activity level, age and gender, but range between 12 and 22 grams per day.

The AHA report also addresses the recent controversy that omega-6 fatty acids, via linoleic acid, which accounts for 85-90% of dietary omega-6, may actually increase inflammation and thereby increase rather than reduce cardiovascular risk. Any link between omega-6 and inflammation, says the AHA, comes from the fact that arachidonic acid, which can be formed from linoleic acid, is involved in the early stages of inflammation, but anti-inflammatory molecules are also formed; these suppress the production of adhesion molecules, chemokines and interleukins, all of which are key mediators of the atherosclerotic process. Thus, concludes the report, it is incorrect to view the omega-6 fatty acids as pro-inflammatory.

The report also reviewed epidemiological data and found that, in randomised controlled trials, those assigned to the higher omega-6 diets had less heart disease. 
A meta-analysis of several trials indicated that replacing saturated fats with PUFA lowered risk for heart disease events by 24%. Reducing omega-6 intakes, said the report, would be more likely to increase than to decrease the risk of CHD.

Professor Heinz Drexel from the VIVIT Research Institute at Feldkirch, Austria, speaking on behalf of the European Society of Cardiology, adds that the report not only recommends the consumption of at least 5-10% of energy from omega-6 PUFAs but indicates that intakes higher than 10% of energy appear safe and may even be even beneficial. This latter statement, says Professor Drexel, "is somewhat discordant with earlier recommendations made by other authorities".

Commenting on the report, Professor Drexel adds: "This advisory is a resurrection of older recommendations on omega-6 PUFAs, in particular on linoleic acid. It is based on new ecological, case-control, prospective cohort and randomised controlled studies. Concerns raised in the past decade that omega-6 PUFAs may be pro-inflammatory are dispelled with evidence that omega-6 PUFAs have anti-inflammatory properties at the level of vascular endothelial cells. On balance, the advantages outweigh the disadvantages.

"However, the effects of Omega-6 PUFAs appear weak and require long-term interventions. Many studies in the past were not long enough for a nutritional intervention. Moreover, in the intervention studies other nutrients were changed along with the enrichment of omega-6 PUFAs."

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REFERENCES:

1. Harris WS, Mozaffarian D, Rimm E, et al. Omega-6 fatty acids and risk for cardiovascular disease. Circulation 2009; DOI: 10.1161/CIRCULATIONAHA.108.191627.

Omega-6 fatty acids: Make them a part of heart-healthy eating

American Heart Association science advisory

28 jan 2009-- Omega-6 fatty acids found in vegetable oils, nuts and seeds – are a beneficial part of a heart-healthy eating plan, according to a science advisory published in Circulation: Journal of the American Heart Association.

The association recommends that people aim for at least 5 percent to 10 percent of calories from omega-6 fatty acids. Most Americans actually get enough of these oils in the foods they are currently eating, such as nuts, cooking oils and salad dressings, the advisory reports. Recommended daily servings of omega-6 depend on physical activity level, age and gender, but range from 12 to 22 grams per day.

Omega-6, and the similarly-named omega-3 fatty acids (found in fattier fish such as tuna, mackerel and salmon), are called polyunsaturated fatty acids (PUFA), and can have health benefits when consumed in the recommended amounts, especially when used to replace saturated fats or trans fats in the diet. Omega-6 and omega-3 PUFA play a crucial role in heart and brain function and in normal growth and development. PUFA are "essential" fats that your body needs but can't produce, so you must get them from food.

"Of course, as with any news about a single nutrient, it's important to remember to focus on an overall healthy dietary pattern – one nutrient or one type of food isn't a cure-all," said William Harris, Ph.D., lead author of the advisory. "Our goal was simply to let Americans know that foods containing omega-6 fatty acids can be part of a healthy diet, and can even help improve your cardiovascular risk profile."

The American Heart Association's dietary recommendations suggest a broadly defined healthy eating pattern over time – with an emphasis on fruits, vegetables, high-fiber whole grains, lean meat, poultry, and fish twice a week. Diets rich in fruits, vegetables and whole grains have been associated in a large number of studies with reduced cardiovascular risk.

Linoleic acid (LA) is the main omega-6 fatty acid in foods, accounting for 85 percent to 90 percent of the dietary omega-6 PUFA.

There has been some debate within the nutrition community regarding the benefits of omega-6 based on the belief that they may promote inflammation, thus increasing cardiovascular risk. "That idea is based more on assumptions and extrapolations than on hard data," said Harris, a research professor for the Sanford School of Medicine at the University of South Dakota and director of the Metabolism and Nutrition Research Center at Sanford Research/USD

The linking of omega-6 intake to inflammation stems from the fact that arachidonic acid (AA), which can be formed from LA, is involved in the early stages of inflammation. However, the advisory explains that AA and LA also give rise to anti-inflammatory molecules.

For example, in the cells that form the lining of blood vessels, omega-6 PUFA have anti-inflammatory properties, suppressing the production of adhesion molecules, chemokines and interleukins — all of which are key mediators of the atherosclerotic process. "Thus, it is incorrect to view the omega-6 fatty acids as 'pro-inflammatory,'" Harris explained. "Eating less LA will not lower tissue levels of AA (the usual rationale for reducing LA intakes) because the body tightly regulates the synthesis of AA from LA."

The advisory reviewed a meta-analysis of randomized, controlled trials, and more than two dozen observational, cohort, case/control and ecological reports.

Observational studies showed that people who ate the most omega-6 fatty acids usually had the least heart disease. Other studies examined blood levels of omega-6 in heart patients compared with healthy people and found that patients with heart disease had lower levels of omega-6 in their blood.

In controlled trials in which researchers randomly assigned people to consume diets containing high versus low levels of omega-6 and then recorded the number of heart attacks over several years, those assigned to the higher omega-6 diets had less heart disease.

A meta-analysis of several trials indicated that replacing saturated fats with PUFA lowered risk for heart disease events by 24 percent. "When saturated fat in the diet is replaced by omega-6 PUFA, the blood cholesterol levels go down," Harris said. "This may be part of the reason why higher omega-6 diets are heart-healthy."

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Co-authors are: Dariush Mozaffarian, M.D.; Eric Rimm, D.Sc.; Penny Kris-Etherton, Ph.D.; Lawrence Rudel, Ph.D.; Lawrence Appel, M.D.; Marguerite Engler, Ph.D.; Mary Engler, Ph.D.; and Frank Sacks, M.D. Author disclosures are on the manuscript.