The observation that excess oxidative stress is associated with diverse pathologic consequence has been consistently coupled with the obvious next intellectual step: antioxidants should be beneficial to prevent these consequences. Unfortunately, no Goldilocks has stepped forward to inform us which antioxidant is too much, which is too little, and which is just right. Or maybe the antioxidant hypothesis is just a fairy tale, after all?
This is not the first time that observational hypotheses have disappointed. In two clinical trials of antioxidant supplementation in persons at risk for lung cancer (combined n > 45,000), the first trial found an increase in lung cancer and mortality, and the follow-up trial was discontinued almost 2 years early because of similar outcomes.
This most recent Cochrane systematic review included 78 trials (n = 296,707) performed in both primary and secondary prevention modes. The “bottom line” is worth quoting: “Antioxidant supplements are not associated with lower all-cause mortality. Beta carotene, vitamin E, and higher doses of vitamin A may be associated with higher all-cause mortality.” Some naysayers would suggest that we have not yet fulfilled the Goldilocks systematic approach: Maybe we used too little, maybe we used too much, or maybe we used the wrong formulation, and have not yet found the approach that’s “just right.” For now, the science does not support a role for antioxidants in primary or secondary prevention.
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