French adults’ cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) trial

Journal Title (Medline/Pubmed accepted abbreviation): J Am J Clin Nutr
Year: 2011
Volume: 94
Page number: 892-899
doi : 10.3945/ajcn.110.007815

Summary of background and research design:

Background: Oxidative stress and a proinflammatory state may have key roles in cognitive decline. In general, observational studies have reported a positive correlation between cognitive function and antioxidant intake. However, results may be confounded by covariates such as a healthy diet or other healthy behaviors, and clinical evidence from randomized studies is scarce.

Hypothesis:Healthy behaviors before antioxidant supplementation may lead to differential effects on cognitive function during antioxidant supplementation.

Subjects: French participants of the SU.VI.MAX trial who had completed all neuropsychologic testing and were 45 to 60 years old at baseline were included in this analysis (N = 4,447).

Experimental design: Randomized, double-blind, placebo-controlled

Treatments Protocol: Participants received either a daily placebo or antioxidant supplementation (120 mg ascorbic acid, 30 mg vitamin E, 6 mg β-carotene, 100 μg selenium, and 20 mg zinc) for 8 years. A cognitive assessment was performed 6 years after supplementation ended and tested episodic memory (RI-48 delayed cued-recall test), lexical-semantic memory (verbal-fluency tasks), short-term and working memory (forward and backward digit span), and mental flexibility (Delis-Kaplan TMT).

Summary of research findings:
  • Episodic memory was better in the supplementation group compared with the placebo group (P = .04).
    • No differences between the groups were observed in the other memory tests.
  • Subgroup analyses showed that supplementation was associated with better verbal memory among nonsmokers (P interaction = .06) and in participants who had low baseline vitamin C levels (interaction = .05).
    • Supplementation was also associated with better executive function among men (interaction = .03) and in participants who had low baseline vitamin E levels (interaction = .02).
  • Results did not substantially change when participants who had depressive symptoms or who were less compliant were excluded.
    • Backward digit span achieved a significant difference in compliant vs noncompliant participants (P = .01).

Interpretation of findings/Key practice applications:

These results suggest that the beneficial effects of antioxidants on certain cognitive functions may persist for a long time, especially in subgroups with low antioxidant status. In this study, the levels of supplementation were low and are achievable through diet. High doses of antioxidants may have negative effects on health and mortality, and supplementation in well-nourished populations may increase risk of adverse health effects and not result in cognitive benefits. Limitations in this study include no baseline cognitive testing, antioxidants were administered in combination (no individual antioxidant effect could be evaluated), supplementation was allowed in the placebo group following the initial study, and the participants were health conscious and compliant (leading to homogeneity in cognitive profiles between the groups).
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