The response of γ vitamin E to varying dosages of α vitamin E plus vitamin C

Abstract

Background Vitamin E has been studied extensively in the prevention of atherosclerosis. Cross-sectional population studies as well as randomized controlled intervention trials have demonstrated conflicting results. A recent meta-analysis of these trials has emphasized the ineffectiveness of vitamin E in atherosclerosis prevention with a possibility of harm at higher dosages. However, vitamin E has several isomers, with the alpha form being available via dietary supplements and the gamma form being available via dietary foodstuffs. The gamma form of vitamin E demonstrates several superior properties (such as trapping reactive nitrogen species and detoxifying nitrogen dioxide) compared with alpha vitamin E. All clinical trials have utilized the alpha isomer with little concern that this isomer of vitamin E may actually suppress the gamma isomer of vitamin E. Objective We undertook a dose response study in type 2 diabetic volunteers to include all the dosages of alpha vitamin E that have been utilized in cardiovascular prevention trials to determine the effect of alpha vitamin E on gamma vitamin E. We also assessed the effect of alpha vitamin E on several traditional markers of atherosclerotic risk. We added vitamin C to the vitamin E because several clinical trials included this vitamin to enhance the antioxidant effects of alpha vitamin E. Design Volunteers received, in randomized order for a two week period, one of the following vitamin dosage arms: 1) no vitamins, 2) low dose supplemental vitamins E plus C, 3) medium dose supplemental vitamins E plus C, and 4) high dose supplemental vitamins E plus C. Blood levels of both alpha and gamma vitamin E were measured as well as surrogate markers of oxidative stress, hypercoagulation, and inflammation during a high fat atherogenic meal (to increase the ambient oxidative stress level during the study). Results The results demonstrate that alpha vitamin E levels increased in proportion to the dose administered. However, at every dose of alpha vitamin E, gamma vitamin E concentration was significantly suppressed. No beneficial changes in surrogate markers of atherosclerosis were observed, consistent with the negative results of prospective clinical trials utilizing alpha vitamin E. Conclusions Our results suggest that all prospective cardiovascular clinical trials that utilized vitamin E supplementation actually suppressed the beneficial antioxidant gamma isomer of vitamin E. No beneficial effects on several potential cardiovascular risk factors were observed, even when the vitamin E was supplemented with vitamin C. If a standardized preparation of gamma vitamin E (without the alpha isomer) becomes available, the effects of gamma vitamin E on atherosclerotic risk will warrant additional studies.

Effect of vitamins C and E on insulin resistance in diabetes: a meta‐analysis study

“…Chen et al [43] found nonsignificant changes in FBS or insulin concentration after the intake of VC in diabetic patients with inadequate levels of vitamin. In contrast, coadministration of vitamins C and E in T2DM for 14 days did not show any improvement in BG, insulin, c-peptide and surrogate markers of atherosclerosis or inflammation [60]. In addition, the protective effect of VC against NO was not observed in subjects with diabetes [43], which may indicate that VC produces beneficial effects when administered during the early onset of CVD [61].…”

Relation of Serum ^|^alpha;- and ^|^gamma;-Tocopherol Levels to Cardiovascular Disease-Related Mortality Among Japanese Men and Women

“…Platelet aggregation was 16% lower in rats fed α-tocopherol and 43% lower in rats fed γ-tocopherol as compared with controls. 40 In humans, α-tocopherol supplementation alone reduced serum γ-tocopherol levels, 41 while a supplement with equal amounts of α- and γ-tocopherols raised plasma α- and γ-tocopherol levels. 42 A supplement with mixed tocopherols (100 mg γ-, 40 mg δ-, and 20 mg α-tocopherol; corresponding to a 20 mg α-tocopherol equivalent) reduced platelet aggregation by 14% as compared with pre-supplementation platelet aggregation values.…”

Vitamin E in aging, dementia, and Alzheimer's disease

“…Indeed, epidemiological evidence suggests that the protective effect of vitamin E against AD can be due to the contribution of its different forms, while intake of high doses of a-tocopherol can decrease the bioavailability of the other congeners potentially increasing mortality risk [77][78][79]. Indeed, epidemiological evidence suggests that the protective effect of vitamin E against AD can be due to the contribution of its different forms, while intake of high doses of a-tocopherol can decrease the bioavailability of the other congeners potentially increasing mortality risk [77][78][79].…”