To the Editor: The meta-analysis on omega-3 PUFAs and major cardiovascular disease end points concluded that supplementation was not associated with lower risk of cardiovascular disease events.1 Such a conclusion, based on a summary statistical analysis of highly variable treatments, conflates specific drug therapies with the nutrients that supplements are intended to deliver.
Meta-analysis is best applied to treatment with manufactured drugs of well-defined composition indicated for particular pathological effects. In contrast to drugs, omega-3 PUFAs are obligatory nutrients, being constituents of normally functioning, highly specialized cells (myocardium, neurons, red blood cells) in which they play key structural and signaling roles. Their intake throughout life, mainly through diet, is required in amounts influenced by individual factors such as genotype and physiological conditions. Unlike drugs, long-chain PUFA supplements are variable in their content of active ingredients (eg, EPA and DHA) and excipients, which can lead to heterogeneous effects. Therefore, studies should not ignore initial omega-3 status.