Vitamins and Stroke Prevention: Is a Healthy Diet Good Enough?
Vitamins and Stroke Prevention: Is a Healthy Diet Good Enough?
abstracts & commentary
Sources: Yokoyama T, et al. Serum vitamin C concentration was inversely associated with subsequent 20-year incidence of stroke in a japanese rural community: The shibata study. Stroke 2000;31:2287-2294; Hirvonen T, et al. Intake of flavonoids, carotenoids, vitamins C and E, and risk of stroke in male smokers. Stroke 2000;31:2301-2306; Cherubini A, et al. Antioxidant profile and early outcome in stroke patients. Stroke 2000;31:2295-2300.
In this series of investigations, data suggest that vitamin intake may reduce the risk of ischemic or hemorrhagic stroke. Such benefits might be achieved from the dietary consumption of fruits and vegetables or they may be derived from the intake of exogenous vitamins. Furthermore, the particular relative effects of different vitamins are not well understood. Because LDL oxidation is an important and, possibly, a necessary step in the development of atherosclerosis, compounds with antioxidant properties, such as vitamin C or beta-carotene, may attenuate or arrest this process. Compounds such as vitamin E and flavinoids have been shown to reduce platelet aggregation. In addition, a moderate but significant drop in blood pressure, a major stroke risk factor, has been associated with vitamin C. Finally, the benefits of vitamin intake may depend on stroke pathophysiology. Subytpes of ischemic stroke, such as embolic or lacunar types, as compared to intracerebral hemorrhage, may show variable effects.
In a Japanese rural community, Yokoyama and associates report on a cohort of 880 men and 1241 women. Over a 20-year observation period, 196 strokes occurred (109 cerebral infarctions, 54 hemorrhages). Vitamin C intake was derived solely from dietary sources with no one in the cohort taking vitamin supplements. Higher serum vitamin C levels measured at baseline were associated with a decrease in stroke rates (odds ratios of 0.89, 0.72 and 0.59, for the second, third and fourth quartiles compared with the first; P = 0.002). This relationship applied separately to both ischemic stroke and ICH and was not reduced after corrections for stroke risk factors such as hypercholesterolemia. Although a weak inverse association between vitamin C levels and blood pressure was detected, this did not explain its benefit. Vitamin C remained protective for stroke even after correction for blood pressure.
Hirvonen and associates report results from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, a primary prevention, interventional trial among male smokers in Finland. Primarily designed to examine cancer rates, this cohort unexpectedly showed increased lung cancer rates among men taking beta-carotene supplementation. By contrast, in the present study, a follow-up report on the same population, intake of beta-carotene was favorable, associated with a decreased risk of ischemic stroke (relative risk [RR] 0.74). This remained significant in multivariate analysis. Other nutrients were also shown to have benefits. These were not supplemented, as beta-carotene, but rather intake was quantitated based on dietary questionnaires. Vitamin C was associated with a decreased risk of intracerebral hemorrhage (ICH; RR = 0.39), lutein plus zeaxanthin with fewer occurrences of subarachnoid hemorrhage (RR = 0.47), and lycopene with decreased incidence of both ischemic stroke and ICH (RR = 0.74 and 0.45, respectively). None of these remained significant in multivariate analyses. An increased intake of fruits and vegetables showed a protective effect against stroke, but this effect was attenuated when corrected for beta-carotene intake. Prior studies of flavonols, flavones, or vitamin E intake have shown variable results. None of these agents showed benefit in the ATBC study, either in isolation or in grouped analysis. In contrast to the Japanese cohort, intake of vitamin C had no effect on blood pressure.
In a related report, Cherubini and associates studied levels of antioxidant compounds (vitamin C, A, and E) and antioxidant enzymes (superoxide dismutase [SOD] and glutathione peroxidase) in the aftermath of stroke. Cherubini et al hypothesized that levels of these agents would drop on the basis of oxidative stress. Indeed, patients showed lower vitamin C and A levels as well as plasma SOD activity when compared with controls. Also, decreased plasma levels of vitamin C were directly correlated with poorer functional outcome and neurological status. Vitamin levels returned to control levels at one week post-stroke. As Cherubini et al indicate, the maintenance of higher antioxidant activity post-stroke may lessen the effects of free radical mediated excitotoxic damage or prevent the potentially injurious effects of reperfusion.
Commentary
These studies add to a growing body of evidence that antioxidant vitamins may prevent or reduce the adverse effects of stroke. A variety of putative mechanisms have been proposed. Despite these findings, however, a mandate for widespread supplementation as primary prevention is far from clear. Prior investigations of beta-carotene supplementation, such as the Physicians Health Study (Hennekens CH, et al. N Engl J Med 1996;334:1145-1149), showed a lack of benefit not only for prevention of neoplasms or cardiovascular disease but also for the specific endpoint of stroke. Both the ATBC and CARET study (Omenn GS, et al. N Engl J Med 1996;334:1150-1155) showed increased cancer rates in the setting of beta-carotene supplementation. Furthermore, as suggested by the Japanese study, natural dietary intake (in this case, of vitamin C) rather than supplementation may produce a reduction in stroke incidence. In the ATBC study, although dietary effects were perhaps clouded by supplementation, the suggestion remained that unknown dietary factors might affect outcomes, despite added vitamins. Until futher data comes forth, we should continue to heed the advice of our mothers, "Eat your vegetables, they’re good for you." —Alan Z. Segal
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