Fish Oil - Negative Press

Response to 2012 JAMA Article on Fish Oil and Cardiovascular Health

On September 12th 2012, the Journal of the American Medical Association published a meta-analysis of 20 human trials on fish oil and cardiovascular health. Their finding: fish oil supplements do not appear have any effect on heart attack, stroke or cardiac-related mortality. This analysischallenges numerous other findings on omega 3 fatty acids and human health, so before we lose faith in fish oil, let’s look at why the authors’ conclusion might not be as credible as it seems.

First, let’s look at the methods and results of the analysis. For this study, data was combined from 20 randomized controlled trials (RCTs) that includednearly 70,000 individuals. All trials evaluated the effect of various forms of omega-3 fatty acids, including food sources, dietary supplements, and prescription omega-3 products on cardiovascular outcomes. The study found no significant association between fish oil interventions and all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke. The authors conclude that their findings do not justify the routine use of omega-3 supplements to improve cardiovascular health.

Before discussing the pitfalls of this study, let’s recall one important fact: omega 3s are essential nutrients that we must take in through our diets. Our bodies require omega 3s to function optimally, and most Americans are not getting enough of them. Two particularly important omega 3s, EPA and DHA, are found exclusively in fish and have been shown to support health in a multitude of ways. EPA and DHA are necessary for the function of the brain,and support positive moods,1 joint health, breast health, prostate health, and immune system function.2,3Theyhave also been shown to support healthy triglyceride levels4,5anda healthy inflammatory response,2,3both of which support cardiovascular health.On account of the evidence in favor of EPA and DHA, the World Health Organization and the American Heart Association have developed recommended daily intakes ranging from .25 grams (2,500 mg) to 4grams (4,000 mg) combined EPA and DHA per day.6,7By contrast, the average American consumes about .1 – .2 grams combined EPA and DHA per day.8The2010Dietary Guidelines for Americans recommends consuming 8 oz. of seafood per week in order to get enough EPA and DHA,9yet Americans are consuming less than half of that.10These dietary insufficiencies may be easily and safely corrected with supplemental EPA and DHA.

Now back to the JAMA study: it is important to note that this study was a meta-analysis of previous trials, meaning that previous findings were pooled and analyzed according to some criteria, but no new evidence was gathered.  Meta-analyses are controversial in the scientific community because several conditions are critical to a sound meta-analysis, and small violations of those conditions can lead to misleading results. This particular meta-analysis combines twenty studies that have different interventions, doses, and patient populations to reach a general conclusion on the effectiveness of omega-3 fatty acids in improving cardiovascular outcomes. Due to significant dissimilarities between studies, it is hard to justify a unified conclusion. Some of the dissimilarities between the studies used are:

  • Different concentrations and ratios of EPA to DHA, or in other words, entirely different products.
  • Some studies did not assess baseline omega 3 status or omega 3 biomarkers throughout the study.
  • Some studies did not take into account dietary intake of omega 3s. Dietary intake of fish, flax, and other sources of omega-3 fatty acids at baseline and throughout a study will impact both treatment and placebo groups and study conclusions.
  • Populations in the studies ranged from healthy (primary prevention) to patients with cardiovascular disease of varying severity.
  • Many of the studies relied on large RCTs of patients already receiving drugs (e.g., a statin) to combat CVD.  This variable can mask or confound the results of supplementing with fish oil.

Another significant shortcoming of this analysis was its failure to address the importance of balancing the omega-6 to omega-3 fatty acid ratio. Emerging science indicates that the benefit of omega-3 fatty acids is in part a result of its influence on inflammation in the body.3,11 Therefore results are not only dependent on absolute intake of omega-3 fatty acids, but are dramatically influenced by dietary intake of omega-6 fatty acid and the subsequent ratio of these two fatty acids in vivo.11 The authors make no mention of this important factor.

Despite the authors’ bold statement that fish oils do not appear to positively impact cardiovascular health, the actual outcomes of this analysis didshow a reduction in cardiovascular events associated with fish oil supplementation. When viewed together, the 20 studies showed that all-cause mortality was reduced by 4%, cardiac death was reduced by 8%, sudden death was reduced by 13%, and MI was reduced by 11% in association with omega-3 supplementation. This was an overall trend that was disregarded by the authors because it was seen as insignificant.

Overall, the findings of the recent JAMA study are not solid enough to refute previous findings that fish oil supports cardiovascular health. Like all meta-analyses, this one is subject to its own bias based on study inclusion and exclusion criteria and methods of statistical analysis. It is for these reasons that other meta-analyses investigating the efficacy of fish oil on cardiovascular outcomes reach different conclusions.12,13


References

  1. Challem, Jack. The Food-Mood Solution. Hoboken, NJ: John Wiley & Sons, 2007. 73-74, 179, 210, 231, 235.
  2. Calder, Philip C., and ParveenYaqoob. “Omega-3 Polyunsaturated Fatty Acids and Human Health Outcomes.” BioFactors3 (2009): 266-72
  3. Challem, Jack. The Inflammation Syndrome. Hoboken, NJ: John Wiley & Sons, 2010. Chapter 8.
  4. Harris WS. “n-3 Fatty acids and serum lipoproteins: human studies.” Am J ClinNutr65 (1997):1645–1654.
  5. Kris-Etherton, PM, William Harris, et al. “Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease.” Circulation 106 (2002): 2747-757
  6. Interim Summary of Conclusions and Dietary Recommendations on Total Fat and Fatty Acids. Rep. Geneva: FAO/WHO, 2008. Print
  7. http://www.heart.org/HEARTORG/GettingHealthy/NutritionCenter/Fish-101_UCM_305986_Article.jsp. Accessed 9/13/12.
  8. Kris-Etherton, PM, and Denise Taylor, et al. “Polyunsaturated Fatty Acids in the Food Chain in the United States.” The American Journal of Clinical Nutrition1 (2000): 179-88.
  9. http://seafoodhealthfacts.org/compare_benefits/patients.php. Accessed 9/13/12.
  10. http://www.nmfs.noaa.gov/aquaculture/faqs/faq_seafood_health.html. Accessed 9/13/12.
  11. Simopoulos, A.p. “Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases.” Biomedicine & Pharmacotherapy9 (2006): 502-07.
  12. Delgado-Lista Javier, Perez-Martinez Pablo, et al. “Long-chain omega-3 fatty acids and cardiovascular disease: a systematic review.” Br J Nutr107 (2012):S201-13.
  13. Marik, Paul E, Varon, Joseph. “Omega-3 Dietary Supplements and the Risk of Cardiovascular Events: A Systematic Review.” ClinCardiol7 (2009):365-372.