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Higher levels of diet-derived antioxidants don’t protect against heart disease

Journal of the American College of Cardiology
Reuters Health - 04/01/2021 - Dietary antioxidants offer no protection against the development of coronary heart disease (CHD), suggesting supplements may not do so either, according to a new Mendelian-randomization study.

The findings do not support a beneficial role of high dietary-derived vitamins E or C, beta-carotene, lycopene or retinol on CHD risk in the general population, the researchers say in the Journal of the American College of Cardiology.

"Therefore, it is unlikely that taking antioxidants to increase blood antioxidants levels will have a clinical benefit for the prevention of primary CHD," they conclude.

There is conflicting evidence on the role of diet-derived antioxidants (vitamins E and C and carotenoids) in primary CHD prevention, Dr. Raymond Noordam and colleagues from Leiden University, in the Netherlands, note in their paper.

Observational studies have identified associations between higher levels of diet-derived antioxidants and lower risk of CHD, while randomized clinical trials showed no reduction in CHD risk following antioxidant supplementation, they point out.

Using Mendelian randomization, the study compared "individuals who had a genetically predicted higher antioxidant level in blood with individuals who had a genetically predicted lower antioxidant level in blood," Dr. Noordam explained in an email to Reuters Health.

From an analytic sample of more than 768,000 individuals from three large cohorts, including 93,230 CHD cases, "we found no protective effect and therefore conclusive evidence antioxidant levels are not causally related to the risk of coronary artery disease," he said.

For absolute antioxidants, the odds ratio for CHD ranged between 0.94 (95% confidence interval, 0.63 to 1.41) for retinol and 1.03 (95% CI, 0.97 to 1.10) for beta-carotene per unit increase in antioxidant values.

For metabolites, the odds ratio ranged between 0.93 (95% CI, 0.82 to 1.06) for gamma-tocopherol and 1.01 (95% CI: 0.95 to 1.08) for ascorbate per 10-fold increase in metabolite levels.

"The robust null results in our studies suggest that a lifelong exposure to somewhat higher antioxidant levels did not decrease the risk of CHD, in line with earlier findings from the trials and meta-analyses on trials," the authors write in their paper.

Dr. Gordon Huggins and Dr. Eli Simsolo of Tufts Medical Center, in Boston, offer their perspective on the study in a JACC editorial.

They note that Mendelian randomization provides "unique insights to environmentally modifiable causes of disease and has proven effective at identifying effective therapeutic targets. Using this approach, the genetic factors associated with vitamin E (alpha-tocopherol and gamma-tocopherol), beta-carotene, lycopene, vitamin C (L-ascorbic acid or ascorbate), and retinol were not found to be associated with major CHD defined as angina pectoris, myocardial infarction, ischemic heart diseases, cardiac death, or sudden death. The consistency of negative findings observed in three large cohorts further strengthens the conclusion that the antioxidants under study do not prevent CHD."

The editorial writers emphasize that the conclusions from this study and randomized clinical trials "do not negate the essential function oxidative stress plays in the development of atherosclerosis."

SOURCE: https://bit.ly/2XbicLe and https://bit.ly/3b62RDE Journal of the American College of Cardiology, online December 4, 2021.

By Megan Brooks

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