Second, systemic oxidant stress due to tobacco use decreases blood polyunsaturated fatty acids, especially omega-3 long-chain polyunsaturated fatty acids, and increases lipoperoxidation products (6). Supplemental vitamin E can partly counteract these effects (6). Thus, the effects of omega-3 polyunsaturated fatty acids in smokers possibly depend on their antioxidant status and antioxidant intake. Because the subjects in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study were given supplements of either vitamin E, beta-carotene, both, or a placebo during the follow-up, the presence and direction of an association between omega-3 long-chain polyunsaturated fatty acid intake and depression can depend on the intervention group. Therefore, it would perhaps be worth looking at the possible interaction of omega-3 fatty acid intake with vitamin E and/or beta-carotene intervention before concluding an absence of association with depression. The size of the sample (8,612 subjects with depressed mood) allows this more detailed analysis.