In my last post I reviewed an article about health risk factors and premature deaths (1). One of the authors′ more surprising findings was that, in the U.S. alone, an estimated 84,000 lives could be saved annually if everyone′s omega-3 fatty acid intakes were optimized, either through diet or supplementation. By comparison, cholesterol-lowering strategies were estimated to save about 113,000 lives annually. I was of course aware of the importance of n-3 (omega-3) fatty acids, but I was surprised by the numbers. Maybe I shouldn′t have been.

In 2003 the Nutrition Committee of the American Heart Association (AHA) had this to say about omega-3 fatty acids and cardiovascular disease (2):

"Omega-3 fatty acids have been shown in epidemiological and clinical trials to reduce the incidence of cardiovascular disease. Large-scale epidemiological studies suggest that individuals at risk for coronary heart disease benefit from the consumption of plant- and marine-derived omega-3 fatty acids, although the ideal intakes presently are unclear. Evidence from prospective secondary prevention studies suggests that EPA + DHA supplementation ranging from 0.5 to 1.8 g/day (either as fatty fish or supplements) significantly reduces subsequent cardiac and all-cause mortality. For α-linolenic acid, total intakes of ∼ 1.5 to 3 g/day seem to be beneficial."

The authors go on to say that even patients with existing heart disease can benefit from omega-3 supplementation (2):

"A dietary (i.e. food-based) approach to increasing omega-3 fatty acid intake is preferable. Still, for patients with coronary artery disease, the dose of omega-3 (∼1 g/day) may be greater than what can readily be achieved through diet alone. These individuals, in consultation with their physician, could consider supplements for CHD risk reduction. Supplements could also be a component of the medical management of hypertriglyceridemia, a setting in which even larger doses (2 to 4 g/day) are required."

In 2005 a meta-analysis of randomized controlled trials of the effects of various lipid-lowering interventions on all-cause and cardiovascular deaths appeared (3). In all, 97 trials involving nearly 140,000 patients and a roughly equal number of controls were included in that analysis. The lipid-lowering interventions consisted of statins, fibrates, resin, niacin, n-3 fatty acids or dietary intervention. This is how the authors summarized their findings (3):

"Statins and n-3 fatty acids are the most favorable lipid-lowering interventions with reduced risks of overall and cardiac mortality."

The actual risk ratios for all-cause mortality were 0.87 for statins and 0.77 for n-3 fatty acids. For death from cardiovascular disease the corresponding values were 0.78 for statins and 0.68 for n-3 fatty acids. The authors point out, though, that in the n-3 fatty acid intervention group the risk reduction was significant only in secondary prevention, i.e. for patients who already had cardiovascular disease.

They might have added that the reduction in the risk of death was even greater in the n-3 fatty acid than in the statin group, that n-3 fatty acids don′t come with the side effects of statins, and that they are a good deal cheaper as well.

The authors do suggest though that "future trials should explore whether n-3 fatty acids in combination with statins lead to additional reductions in coronary heart disease mortality, especially in patients with metabolic syndrome". It′s possible that combination therapy might confer additional benefits, since statins and n-3 fatty acids act differently. Statins reduce cholesterol synthesis, whereas n-3 fatty acids tame inflammation.

n-3 and n-6 polyunsaturated fatty acids are precursors for a group of hormone-like substances — summarily referred to as eicosanoids — which control, among other things, the body′s inflammatory response. Eicosanoids derived from n-6 fatty acids up-regulate inflammation, whereas n-3 eicosanoids keep it in check.

We cannot interconvert n-3 and n-6 fatty acids, which means that the dietary mix of n-3 and n-6 fatty acids determines our ability to initiate and control inflammation. Unfortunately, we get far too much dietary n-6 fatty acids from seed oils (sunflower, safflower, peanut, canola), which leaves us at risk for chronic inflammation, atherosclerosis and cardiovascular disease.

By increasing our intake of n-3 polyunsaturated fatty acids, either through diet or supplementation, and/or by decreasing n-6 fatty acid consumption, we can rebalance the inflammatory response and reduce our risk of cardiovascular and other inflammatory diseases.

Sources:

1. Danaei G, Ding EL, Mozaffarian D et al. The preventable causes of death in the United States: Comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Medicine April 2009;6(4)
   http://dx.doi.org/10.1371/journal.pmed.1000058
2. Kris-Etherton PPM, Harris WS, Appel LJ. Fish consumption, fils oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 2003;23:e20-e30.
   http://dx.doi.org/10.1161/01.ATV.0000038493.65177.94
3. Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC. Effect of different antilipidemic agents and diets on mortality. A systematic review. Arch Intern Med 2005;165:725-730.
   http://archinte.ama-assn.org/cgi/reprint/165/7/725