A Randomized Trial of Beta Carotene Supplementation and Cognitive Function in Men<subtitle>The Physicians' Health Study II</subtitle>

Abstract

Background: Oxidative stress contributes to brain aging. Antioxidant treatment, especially over the long term, might confer cognitive benefits. Methods: We added cognitive testing to the Physicians' Health Study II (PHSII), a randomized trial of beta carotene and other vitamin supplements for chronic disease prevention. The PHSII is a continuation of the Physicians' Health Study (PHS), which had randomized male participants to low-dose aspirin and beta carotene. Participants include those continuing their original beta carotene assignment from the PHS, begun in 1982, and newer recruits randomized as of 1998. The beta carotene arm (50 mg, alternate days) was terminated; follow-up is ongoing for the remaining arms. Near the close of the beta carotene arm, we interviewed 5956 participants older than 65 years to assess general cognition, verbal memory, and category fluency. The primary end point was a global score averaging all tests (using z scores); the secondary end point was a verbal memory score combining results of 4 tests. We compared mean cognition among those assigned to beta carotene vs placebo. We separately examined new recruits and continuing participants. Results: Among 1904 newly recruited subjects (mean treatment duration, 1 year), cognition was similar across treatment assignments. Among 4052 continuing participants from the PHS (mean treatment duration, 18 years), the mean global score was significantly higher in the beta carotene group than in the placebo group (mean difference in z scores, 0.047 standard units; P=.03). On verbal memory, men receiving long-term beta carotene supplementation also performed significantly better than the placebo group (mean difference in z scores, 0.063; P=.007). Conclusion: We did not find an impact of short-term beta carotenesupplementationoncognitiveperformance,butlongterm supplementation may provide cognitive benefits.

Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models

“…The results of the two largest ongoing trials cited above are eagerly awaited. As suggested by the PHS-II [157], treatment with antioxidants may require long-term studies, a consideration for planning future trials. Meanwhile, major efforts should be undertaken to define more effective and safe antioxidant agents for clinical trials.…”

“…Grodstein et al [157] reported on the effect of β-carotene on cognition in the Physician's Health Study II (PHS-II), a long-term randomized trial with the primary outcomes of cardiovascular disease and cancer prevention. Subjects received 50 mg β-carotene on alternate days or placebo.…”

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

“…These results are supported by studies showing that vitamin E and vitamin C supplementation, and=or a multivitamin regimen results in an improvement in aging-related cognitive decline and vascular cognitive impairment (278). Clinical trials in elderly men receiving b-carotene supplementation suggest that short-term antioxidant supplementation had no effect on cognitive dysfunction, whereas long-term supplementation positively impacted it (156). In a randomized, controlled trial of multivitamin supplementation to an aging population, it was reported that there was no significant effect on age-related cognitive dysfunction.…”

Plants antioxidants: From laboratory to clinic

“…It should be noted that some substances that act as antioxidants in one situation may act as prooxidants in other situations (2). Antioxidants are different substances such as vitamin C, vitamin E, carotenoids, minerals such as selenium and manganese, as well as glutathione, coenzyme Q10, lipoic acid, phytoestrogens, flavonoids, phenols, polyphenols, and so on (3)(4)(5). Antioxidants have come to attention since 1990s, when scientists found that free radicals were involved in atherosclerosis, vision loss, cancer and some of other chronic diseases.…”