Primary Care Corner with Geoffrey Modest MD: W-3 Fatty Acids Decrease Heart Disease

By Dr. Geoffrey Modest

A meta-analysis including 19 studies and >45K individuals from 16 countries supported a small but significant cardiovascular benefit for both seafood and plant-derived w-3 fatty acids (see doi:10.1001/jamainternmed.2016.2925).

Details:

• 19 studies from 16 countries (US, Australia, Costa Rica, UK, Italy, Finland, Sweden, Singapore, France, Ireland, Germany…) with  45,637 individuals and 7973 total CHD (coronary heart disease), 2781 fatal CHD and 7157 nonfatal MI events (the studies did not all break down the CHD events the same way, so these numbers do not add up)
• Median baseline age 59, 63% male, BMI 26, up to 30% current smokers. Most were white, though some studies had racial/ethnic diversity. Overall alcohol consumption, mostly up to 1 drink/d. Fish oil supplements used infrequently. Median 10 year of follow-up
• Assessed biomarkers for w3 polyunsaturated fatty acids (measured in whole plasma or tissue, which turned out to be better predictors than adipose tissue and cholesterol ester estimates):
  • Seafood-derived: eicosapentaenoic acid (EPA; 20:5w-3), docosapentaenoic acid (DPA; 22:5w-3), and docosahexaenoic acid (DHA; 22:6w-3)
  • Plant-derived: a-linolenic acid (ALA; 18:3w-3)
• Results: significant associations were as follows, with multivariate-adjusted analyses, per 1-SD increase in the biomarkers:
  • ALA:
    • Fatal CHD: 9% decrease, RR 91 (95%CI, 0.84-0.98)
  • DPA:
    • Fatal CHD: 10% decrease, RR 90 (95%CI, 0.85-0.96)
    • Total CHD: 6% decrease, RR 0.94; 95%CI, 0.90-0.99),
  • DHA:
    • Fatal CHD: 10% decrease, RR 90 (95%CI, 0.84-0.96)
  • EPA:
    • Only reached borderline significant benefit

Commentary:

• The prior studies on w-3 polyunsaturated fatty acids and CHD events are a bit mixed, with many methodologic problems (including relying on dietary recall), and few have looked at plant-derived w-3’s
• Though there was no comment on what “fully-adjusted multivariate analysis” meant, likely because the studies varied, there was a comment that “No significant differences in associations of ω-3 PUFA biomarkers with incident CHD events were observed by age, sex, ω-6 PUFA (linoleic acid or arachidonic acid) concentrations, type 2 diabetes status, statin use, regular aspirin use, year of biomarker sampling, or (for ALA) EPA, DPA, and DHA concentrations”
• In terms of biological plausibility, there are randomized controlled trials showing these w-3 fatty acids lower triglyceride levels, blood pressure, heart rate, and improve endothelial function, membrane stabilization through changes in lipid composition (which could decrease ischemia-mediated ventricular fibrillation, and possibly explain why the clinical improvement was more evident for fatal events) and myocardial oxygen demand, all of which could translate into improved clinical cardiac outcomes.
• One highlight in the above study is the equal association of the plant-derived ALA to the seafood-derived rest of them: there are also data showing ALA decreases thrombosis, arrhythmias and inflammation, and improves endothelial function. And for much of the world, plant-derived w-3 is more affordable and accessible. By my review, the best single source of ALA is flaxseed, then also canola oil, and walnuts (esp. English). Other pretty high sources (actually, better than fish on a weight basis when comparing to the fish w -3’s) include soybeans, oats (germ), dried beechnuts and butternuts).
• There were some interesting subgroup analyses, showing that Chinese and African-American individuals may benefit more from w-3. ?why ?genetic component. ?how the food was prepared (minimally cooked vs deep-fried, etc.). It was also interesting that taking statins or aspirin did not affect the overall outcomes much, since they accomplish at least some of the positive biological effects as the w-3’s.
• I am always concerned about looking at single foods or food additives. In part because we eat a variety of foods, vitamins, etc., and there are likely interactions between the food components as well as optimal balances of different ones. And, even though this study was perhaps the best of the w-3 ones I’ve seen (in the sense that it combined lots of different studies from different areas, looked at hard-evidence both of actual w-3 levels in the body (vs dietary recall) as well as hard clinical endpoints, and seemed methodologically rigorous), there is always concern about the causal relationships in observational studies (i.e., did those who ate more w-3’s also do more other healthful behaviors (eat less red meat, eat more natural foods, do  more exercise, etc.)?
• So, I do think this study adds to and deepens the literature that w -3’s are good for you (and, contrary to some prior articles/concerns, it seems that w -6’s did not counteract the benefits of the w-3’s).