Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

Abstract

α‐Tocopherol (α‐T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α‐T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α‐T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α‐T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ‐ and δ‐forms of tocopherols and tocotrienols (T3). In comparison with α‐T, these forms have much lower systemic bioavailability but have shown stronger cancer‐preventive activities in many studies in animal models and cell lines. γ‐T3 and δ‐T3 generally have even higher activities than γ‐T and δ‐T. In this article, we review recent results from human and laboratory studies on the cancer‐preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.

Integration of molecular profiles in a longitudinal wellness profiling cohort

“…Some notable examples of variable proteins include the growth hormone 2 (GH2) 29 which shows a large range of expression values and the alpha subunit of the glycoprotein hormones (CGA) which shows the expected higher expression in women than men. In addition, we see that among the most stable metabolites we find gamma (γ)-tocopherol 30 , a form of vitamin E. Evidence of γ-tocopherol effect in preventing endothelial injury, lipid peroxidation, and oxidative stress have been reported 30,31 . Indeed, γ-tocopherol is important in preserving endothelial function by protecting the degradation of tetrahydrobiopterin (BH4), a key cofactor in the synthesis of nitric oxide 32 .…”

Plasma, Prostate and Urine Levels of Tocopherols and Metabolites in Men after Supplementation with a γ-Tocopherol-Rich Vitamin E Mixture

“…Many studies showed a negative association between dietary VE intake or blood levels of VE (mostly a-tocopherol (T)) and cancer risk, suggesting a cancer preventive effect. However, other studies, including some recent largescale intervention studies, did not support the hypothesis that VE is cancer preventive (1,2,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In a large chemoprevention trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, supplementation with VE (given as all rac-a-tocopheryl acetate 50 IU daily) was associated with a 32% decrease in prostate cancer incidence and a 41% decrease in mortality of prostate cancer, when prostate cancer analyzed as a secondary endpoint (11).…”

“…Numerous epidemiological studies have investigated the relationship between vitamin E (VE) nutrition and cancer (reviewed in (1)(2)(3)(4)). Many studies showed a negative association between dietary VE intake or blood levels of VE (mostly a-tocopherol (T)) and cancer risk, suggesting a cancer preventive effect.…”

“…For example, c-T has been shown to inhibit prostate carcinogenesis dose-dependently in the transgenic rat for adenocarcinoma of prostate (TRAP) model (28). Dietary administration of a c-T-rich mixture of tocopherols (c-TmT) or purified c-T (or d-T) inhibited the prostate carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model as well as models for colon, lung, and mammary carcinogenesis, while a-T was not effective (1,2,(29)(30)(31)(32)(33)(34)(35)(36). Our recent study also demonstrated that dietary c-TmT prevented a dietary carcinogen, 2-amino-1-methyl-6-phenylmidazo[4,5b]pyridine (PhIP)-induced prostate carcinogenesis in CYP1A-humanized mice, and purified d-T had higher inhibitory activities than c-T and a-T (33).…”

Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals

“…These lipophilic compounds are abundant in vegetable oils and nuts and are widely studied as agents with an impact on human health and disease pathogenesis [143][144][145][146][147]. Numerous reviews have covered the topic of vitamin E and cancer [148][149][150][151]. Recently, γ-TmT, a commercially available by-product of vegetable oil refinery containing 57% γ-tocopherol, was linked to induction of the Nrf2 pathway via hypomethylation of the Nfe2l2 promoter in the TRAMP mouse and in TRAMP-C1 cells in vitro.…”