While both alpha- and gamma-tocopherols exhibit anti-inflammatory effects in vitro and in vivo, gamma-enriched mixed tocopherols may be more potent compared to alpha tocopherols. This may help explain the negative outcomes of recent large-scale intervention studies that used only the alpha homologue (34).
Sesso, HD, Buring JE, Christen WG, et al. Vitamins E and C in the prevention of cardiovascular disease in men. The Physicians' health study II Randomized Controlled Trial. JAMA. 2008;300(18):2123-2133.
This long-term study sought to evaluate the role of vitamin C or E supplementation in reducing the risk of cardiovascular disease, and involved over 14,000 men aged 50 or older. The participants were randomized to 400 IU of vitamin E every other day or its placebo and 500 mg of vitamin C daily or its placebo. The primary outcome of the study was onset of major cardiovascular events including, nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular disease.
At the 8-year follow-up, researchers observed the same number of cases in both vitamin and the placebo groups, with increased risk of hemorrhagic stroke in the vitamin E group. These findings suggest no significant effects of vitamins in lowering the risk of cardiovascular disease as widely believed.
It should be noted that both the vitamins used in the study were synthetic and at much higher levels than those achieved via dietary intake, which may have led to the effects observed. More studies at different doses and involving other populations are warranted to fully assess the role of vitamin supplementation for cardiovascular health.
Slatore CG, Littman AJ, Au DH, et al. Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer. Am J Respir Crit Care Med. 2008;177(5):524-30.
The VITAL (Vitamins and Lifestyle) cohort of 77,221 men was used to determine association between vitamin supplementation (multivitamins, vitamin C, vitamin E, and folate) and occurrence of lung cancer. Researchers identified 521 cases of lung cancer and observed that vitamin supplementation did not decrease the risk of lung cancer. They also report that supplemental vitamin E was associated with a small increase in risk of lung cancer.
Peters U, Littman AJ, Kristal AJ, et al. Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort. Cancer Causes Control. 2008;19(1):75-87.
In this prospective study of 35,242 men recruited between 2000 and 2002, researchers documented 830 new cases of prostate cancer from baseline through December 2004. They also report that a 10-year average intake of supplemental vitamin E and selenium did not reduce the risk of prostate cancer. However, the risk of advanced prostate cancer was reduced with long-term vitamin E supplementation.
Taylor HR, et al. Vitamin E supplementation and macular degeneration: randomised controlled trial. BMJ 2002;325:11-16.
A RCT of vitamin E 500 IU versus placebo for 4 years in 1193 healthy volunteers aged 55-80. Patient characteristics were similar between groups, but the vitamin E arm had a slight excess in the number of patients with cortical lens opacities. Power to detect a 50% reduction in the incidence of early age related macular degeneration (AMD) was 82%. Primary outcome was development of early AMD in annual retinal photographs, which was 8.6% in the treatment arm versus 8.1% in the placebo group. For late disease, incidence rates were also similar. These results indicate that daily supplementation with vitamin E does not prevent the development or progression of AMD. However, the relatively short follow-up and low proportion of cigarette smokers are weaknesses of this study.
Engelhart MJ, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002;287:3223-9.
A population-based, prospective cohort study evaluating antioxidant intake and risk of developing Alzheimer disease. Subjects (n=5393) were at least 55 years old, free of dementia, noninstitutionalized, and had reliable dietary assessment at baseline. Dietary intake was assessed by self-reported checklist and interview with dietitian using the semiquantitative food-frequency questionnaire (SFFQ). After mean follow-up of 6 years, 146 patients developed Alzheimer disease. After adjustments for age, sex, baseline Mini-Mental State Examination score, alcohol intake, education, smoking habits, pack-years of smoking, body mass index, total energy intake, presence of carotid plaques, and use of supplements, high intake of vitamin C and vitamin E were correlated with lower risk of Alzheimer disease. However, as has been pointed out, the apparent association may be caused by the influence of a preclinical illness on diet or diet recall/reporting, since the SFFQ itself may indirectly assess cognitive functioning. Furthermore, the multiple comparisons suggest that some associations may be due to chance and that the critical P value should be set lower than .05.