Whitehead et al. Respond.

We agree that fruit and vegetable consumption is likely to confer health benefits by substituting refined carbohydrates, saturated fats, and other foodstuffs that are unambiguously deleterious to health. We argue, though, that fruit and vegetables convey additional active benefits to human health. While it is true that trials have consistently indicated that the impact of antioxidant supplement intake is null or negative, these studies highlight an overly reductionist approach. There exist important synergistic relationships between antioxidants(1); therefore, high-dose supplementation of a circumscribed subset of phytochemicals is unlikely to be beneficial. Breakdown products of some antioxidants are themselves toxic,(2) and because these antioxidants are readily expended by oxidizing agents when reserves of alternate endogenous antioxidants are low, administering high doses of single antioxidants could inadvertently precipitate oxidative tissue damage. As an example of the synergic relationships that exist, α-tocopherol oxidation toxicity is mitigated by carotenoids.(3)