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Omega-3s’ Genetic Effects Bolster Health Benefits
10/5/2009
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Clinical trial results shed light on the ways in which omega-3s enhance cardiovascular health; findings show parallels to statin drugs’ anti-inflammatory effects
by Craig Weatherby


A great deal of evidence indicates that omega-3s can reduce the risk of stroke, sudden cardiac death, and second heart attacks.

Omega-3s are believed to reduce the risk of sudden cardiac death by modulating heart rhythms.

Key Points
  • Clinical trial finds omega-3s exert anti-inflammatory effects in artery and immune-system cells.
  • Findings confirm that omega-3s bring additional anti-inflammatory benefits via their influence on key genetic switches.
  • Omega-3s’ anti-inflammatory effects in artery and immune cells resemble the ways in which statin drugs reduce inflammation.
But omega-3s also reduce the risk of stroke and second heart attacks, and are associated with reduced risk or severity in various chronic conditions characterized by inflammation… such as auto-immune disorders, allergies, asthma, cardiovascular disease, osteoporosis, and Alzheimer’s disease.

We know that omega-3s serve as precursors to immune-system messenger chemicals called eicosanoids (ee-coh-sah-noids)… key compounds that will be familiar to anyone who’s read the bestselling Zone diet books by Barry Sears, Ph.D.

The eicosanoids made from omega-6 fats tend to be pro-inflammatory, whereas those the body makes from omega-3s are invariably anti-inflammatory.

In addition, omega-3s serve as precursors to recently discovered immune-system compounds called resolvins, which, as their name implies, resolve inflammation to keep it from causing harm when it is no longer needed.

Inflammation: Why America’s omega-3/omega-6 imbalance matters
When the body needs to make eicosanoids, it starts by grabbing polyunsaturated fats from cell membranes.

If your membranes are chronically lacking in omega-3 polyunsaturated fats, they body will tend to use omega-6 polyunsaturated fats to make eicosanoids… and the result will be a tendency toward chronic inflammation.

Eating too many omega-6s and not enough omega-3s
as in the average American dietpromotes the kind of silent, low-level inflammation associated with cardiovascular disease, osteoporosis, and Alzheimer’s disease.

This is one big reason why the ratio of omega-3 and omega-6 polyunsaturated fats in the diet matters.

Most Americans consume far too few omega-3s and far too many omega-6s. For a sobering look at the consequences of this “mega imbalance,” see “Report Finds Americans Need More Omega-3s and Less Omega-6s” and search our newsletter archive.

Now, new research is showing that omega-3s exert beneficial immune system effects beyond their roles as precursors to anti-inflammatory eicosanoids.

Inflammation, atherosclerosis, and cardiovascular disease
Cardiovascular disease is characterized by buildup of arterial plaque… a condition called atherosclerosis.

And atherosclerosis begins when oxidized cholesterol and fats invade artery walls… a process that causes the body to initiate an inflammatory immune-system response that actually promotes more plaque buildup.

This inflammatory immune system response is triggered when a key genetic switch or “nuclear transcription factor” called NF-kB activates genes associated with inflammation and cell defenses.

Normally, NF-kB is no villain. In fact, it guards our cells against radiation, free radicals, and infections by instigating production of a host of proteins that help protect against damage and alert the immune system (In cancer cells, NF-kB is always active, which effectively makes the cells immortal).

But continuous, unnecessary activation of the NF-kB switch is dangerous when it happens in the cells of tissues within and surrounding cardiovascular patients’ atherosclerotic plaques… or in key immune system agents called peripheral blood mononuclear cells or PBMCs.

NF-kB will be familiar to readers of the many anti-aging bestsellers by dermatologist Nicholas Perricone, M.D.

Dr. Perricone’s pioneering regimen rests on omega-3s from fish and polyphenol antioxidants from colorful produce… precisely because these food factors help keep NF-kB and other pro-inflammatory gene switches from getting stuck in the “on” position.

Today's pro-inflammatory diets tend to keep NF-kB turned on even when it is not needed... a situation that causes unneeded inflammation with dire long-term consequences.

Statins cut inflammation via genetic switches… and so do omega-3s

Statin drugs such as Lipitor and Zocor are proven to reduce inflammation within arterial plaques, thereby slowing further accumulation of plaque and helping to keep plaque from bursting and releasing clots that can block arteries.

And statin drugs do this in part by preventing the activation of pro-inflammatory genetic switches like NF-kB, both within arterial cells and within immune system cells such as PBMCs.

We’ve known for some time that omega-3s inhibit the expression of NF-kB, and that they do it very strongly (Mishra A et al. 2004).

Thanks to new clinical research from Holland, we can be sure that omega-3s exert beneficial influence on over NF-kB and other genes in the artery and immune system cells of living people.

For more on the overlapping effects of statins and omega-3s, see “Does Statins' SuperStar Status Make Sense?," “Omega-3s Seen Rivaling Statins at Reducing Risk of Death,” and “Heart Failure Findings Favor Omega-3s over Statin Drug."

We should stress that statin drugswhich are synthetic variations on natural statin compounds found in red yeast ricedo things that omega-3s don't, and vice versa.

If a nutrition-savvy physicianshould you find oneprescribes a statin drug after dietary and other measures have failed, we suggest that you consider that advice seriously.

Clinical trial details the anti-inflammatory effects of omega-3s
Dutch researchers from Wageningen University wanted to examine the effects of omega-3 fish oil supplements on the genetic switches within PBMC cells, so they recruited 111 healthy seniors for a double-blind clinical trial lasting 26 weeks (Bouwens M et al. 2009).

The subjects were randomly assigned to one of three groups:
  • High-Omega-3 Group – 36 participants took 1.8 grams of EPA+DHA daily.
  • Low-Omega-3 Group – 37 participants took 0.4 grams EPA+DHA daily
  • Control Group – 38 participants took 4 grams of high-oleic sunflower oil daily. (This kind of sunflower oil is very low in omega-6s and omega-3s, and has little effect on inflammation one way or the other.)
Blood samples were collected before and after the 26 week trial.

The researchers’ analysis of the blood samples showed beneficial effects only in the High-Omega-3 Group, whose blood cells showed decreased expression of pro-inflammatory genes, reduced production of pro-inflammatory eicosanoids, and other anti-inflammatory changes.

As the Dutch team wrote, “These results are the first to show that intake of EPA+DHA for [only] 26 weeks can alter the gene expression profiles of PBMCs to a more anti-inflammatory and anti-atherogenic status” (Bouwens M et al. 2009).

In other words, the immune-system cells of participants in the High-Omega-3 group underwent beneficial changes to genetic switches, including NF-kB… changes that made these cells less likely to promote plaque buildup or the inflammation that can cause arterial plaques to rupture with deadly consequences.

And because they help show why omega-3s would be beneficial, these findings lend further credence to the positive results of clinical trials showing that omega-3 fish oil supplements reduce the risk of cardiovascular disease and death.


Sources
  • Bouwens M, van de Rest O, Dellschaft N, Bromhaar MG, de Groot LC, Geleijnse JM, Müller M, Afman LA. Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr. 2009 Aug;90(2):415-24. Epub 2009 Jun 10.
  • Kew S, Mesa MD, Tricon S, Buckley R, Minihane AM, Yaqoob P. Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans. Am J Clin Nutr. 2004 Apr;79(4):674-81.
  • Mishra A, Chaudhary A, Sethi S. Oxidized omega-3 fatty acids inhibit NF-kappaB activation via a PPARalpha-dependent pathway. Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1621-7. Epub 2004 Jul 1.
  • Vedin I, Cederholm T, Freund Levi Y, Basun H, Garlind A, Faxén Irving G, Jönhagen ME, Vessby B, Wahlund LO, Palmblad J. Effects of docosahexaenoic acid-rich n-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: the OmegAD study. Am J Clin Nutr. 2008 Jun;87(6):1616-22.
  • Wallace FA, Miles EA, Calder PC. Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects. Br J Nutr. 2003 May;89(5):679-89.

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