Controversies about the cardiovascular effects of OM3FA. Did inappropriate placebos skew clinical trial results?

Several observational studies suggest that greasy fish may reduce cardiovascular risk, whose benefits have been attributed to the presence Omega-3 polyunsaturated fatty acids (OM3FA). However, there are some randomized controlled trials (RCTs) that have shown contradictory results concerning the cardiovascular benefits of OM3FA. Analyzing these RCTs we found that the use of olive oil in some RCTs could be responsible for contradictory results, since both. since both olive oil and OM3FA, in addition to reduce triglycerides, have anti-platelet and anti-inflammatory activities, considered important for the stabilization of atherosclerotic plaques. This pharmacodynamic profile may have a cardio protective effect that was confirmed by several RCTs. Therefore, olive oil seems an active substance, and its use might have reduced the differences between groups masking the efficacy of OM3FA. This inferred lack of OM3FA cardiovascular benefits due to bias induced by a "false placebo" control, raises epistemological considerations on the choice of placebos that always should be pharmacologically inert substances. More studies are necessary to clarify the real efficacy of OM3FA that is more innocuous than many medicines, but it seems useful in future RCTs the use of a truly inert substance as a placebo, as well as the outline of a semi quantitative dose-response curve suggestive of a causal nexus between active substances and their outcomes.