Observational data have identified associations between carotenoids, folic acid, and vitamin E, or metabolites altered by these nutrients, and cardiovascular disease (CVD) risk. Despite biological plausibility, for the most part, data derived from nutrient supplement trials using moderate to high doses of single nutrients or nutrient combinations (exceeding amounts to avoid nutrient deficiency) have been disappointing. The data for vitamin D is not yet adequate to evaluate; observational data suggest were a relationship to exist it would be related to nutrient insufficiency. There is some evidence that use of nutrient supplements intended to decrease CVD risk has resulted in unanticipated adverse consequences. Potential discrepancies between observational and interventional data include concerns of residual confounding by diet and lifestyle patterns, publication bias against studies with null or negative outcomes, reliance on secondary rather than primary prevention trials, and unaccounted for contribution of genotypic variations. At this time there are insufficient data to recommend the routine use of nutrient supplements to prevent or treat CVD. In the recent past we have learned a great deal about anticipated and unanticipated consequences of nutrient supplementation and cardiovascular outcomes. As a result, we are in a better position to adjudicate new potential relationships as data emerge
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