Almost 6,000 volunteers took part in the study, with 4052 receiving beta-carotene supplements for 18 years. The long-term beta-carotene supplementation was associated with a significantly higher mean global score, compared to placebo. This group also performed significantly better than placebo for verbal memory. On the other hand, men taking part in the study for less than ten years displayed no differences in cognition regardless of whether they took beta-carotene or placebo. The study, published in the Archives of Internal Medicine, is the first to look at long-term antioxidant supplementation in relation to a decline in cognitive function that occurs with naturally with age, and that precedes diseases such as Alzheimer's. Participants in the Physicians' Health Study (PHS) trial (started in 1982) and newer recruits from the Physicians' Health Study II (PHSII) (started in 1998) received 50 mg beta-carotene supplements or placebo on alternate days.
"In this generally healthy population, the extent of protection conferred by long-term treatment appeared modest," wrote Francine Grodstein and co-workers from Brigham and Women's Hospital and Harvard Medical School, Boston. "Nonetheless, studies have established that very modest differences in cognition, especially verbal memory, predict substantial differences in eventual risk of dementia; thus, the public health impact of long-term beta carotene use could be large." Mechanism of protection Beta-carotene is converted to vitamin A in the body, and it is the vitamin's effect on beta-amyloid protein production that is thought to be behind the protective effects.
The build-up of plaque from beta-amyloid deposits is associated with an increase in brain cell damage and death from oxidative stress. This is related to a loss of cognitive function and an increased risk of Alzheimer's. In an accompanying editorial in the same journal, Kristine Yaffe from the University of California, San Francisco stated: "The authors suggest that long-term exposure to antioxidants may be needed to have an effect on the underlying pathologic processes linked to changes in cognition. "This is certainly plausible, given that the neuropathologic changes underlying clinically significant cognitive impairment appear to take years, if not decades. Thus, neuroprotection may have the greatest benefit early on in the process. " Furthermore, Yaffe noted that five other randomized trials of antioxidants and cognitive function have been published, but only one suggested a protective effect. None of these lasted for more than 10 years.
Note of caution In her independent comment, Yaffe stated that some issues were to be found in interpretation of the data since the study "had a complex design". Indeed, both Harvard researchers and Yaffe describe several limitations, including only one measure of cognitive function was performed, and this was towards the end of the supplementation period. Therefore, no comparison with baseline values was obtainable. Both Grodstein and co-workers, and Yaffe also note that no evaluation of cognitive function in all subjects who had participated in the original PHS was performed.
The authors also note that beta carotene supplementation is not without its risks, with studies reporting an increase in lung cancer risk among smokers. Despite these limitations and questions, the benefits of long-term supplementation in a healthy population are encouraging, said Grodstein and co-workers. "As these data support the possibility of successful interventions at early stages of brain aging in well-functioning subjects, investigations of additional agents that might also provide such neuroprotection should be initiated." Again, Yaffe poured water on the flames of excitement, noting: "While strategies aimed at midlife (or possibly even earlier) may make sense, they will prove to be difficult to study, since they would involve conducting trials that last for 25 to 30 years." Currently, about 12 million people in the US plus the EU suffer from Alzheimer's, with some estimates predicting this figure will have tripled by 2050. The direct and indirect cost of Alzheimer care is over $100 bn (€ 81 bn) in the US alone. The direct cost of Alzheimer care in the UK was estimated at £15 bn (€ 22 bn).
Source: Archives of Internal Medicine Volume 167, Number 20, Pages 2184-2190 "A Randomized Trial of Beta Carotene Supplementation and Cognitive Function in Men: The Physicians' Health Study II" Authors: F. Grodstein, J.H. Kang, R.J. Glynn, N.R. Cook, J.M. Gaziano Editorial: Archives of Internal Medicine Volume 167, Number 20, Pages 2167-2168 "Antioxidants and Prevention of Cognitive Decline: Does Duration of Use Matter?"
Author: K. Yaffe