November 1, 2012 — Four decades ago, Danish medical students Jørn Dyerberg and Hans Olaf Bang traveled west across the Greenland ice sheet on dogsleds to test a theory. For many years prior to their journey, there had been anecdotal reports that Greenland Eskimos had an extremely low incidence of heart disease, and Dyerberg and Bang speculated that this was linked to the high levels of polyunsaturated fatty acids (PUFAs) in the fish the native people consumed on a daily basis. After collecting and analyzing scores of blood samples, their hypothesis was borne out, and ever since, the medical and scientific community has been on a quest to determine exactly how PUFAs impart protective effects, and what amount must be ingested in order to achieve such benefits. Nearly 40 years and thousands of published studies later, however, these questions remain largely unanswered.
Cardiovascular disease continues to have an enormous impact on the world’s health and economy, making it all the more urgent that health-care practitioners find and implement low-cost prevention strategies. Dietary intake of PUFAs, specifically the n-3 PUFAs found in fish (commonly known as omega-3s), could serve as a perfect solution, but the lack of understanding of how PUFAs work—and continuing controversy over whether they really do work—has made it nearly impossible to properly implement their use in the clinic. Thus, a coordinated effort is needed to establish a mechanism for how n-3 PUFAs function in normal metabolism in order to develop proper therapeutic paradigms and to clarify their effectiveness in the prevention and treatment of cardiovascular disease.
The results of large-scale meta-analyses and clinical trials involving PUFAs and heart-disease risk have been mixed, raising concerns that initial evidence regarding their effectiveness was misleading. A review published in September in The Journal of the American Medical Association, for example, found that increased PUFA intake failed to reduce the risk of stroke, heart attack, or death.4 Reasons for this disparity can be attributed to a variety of factors, including studies that lack sufficient statistical power and the use of differing methodologies to determine serum and tissue levels of PUFAs. Probably the greatest limitation to properly evaluating the results of many clinical trials is that they varied so widely in the type of n-3 PUFA given, dose, formulation (e.g. capsules or oil), and duration of intake. This widespread variation reflects the paucity of understanding regarding mechanism. If we better understood exactly how these compounds act in the body, then clinical trials regarding their use could be vastly improved and designed to be more reproducible. What researchers have learned about mechanisms of n-3 PUFA therapy has led us to propose a novel hypothesis that may help reconcile the controversy, uniting well-characterized n-3 PUFA effects with as-yet unresolved questions.
Read the full story at The Scientist