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The New England Journal of Medicine Apr 1994Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables, as well as high serum levels of vitamin E (alpha-tocopherol) and beta... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables, as well as high serum levels of vitamin E (alpha-tocopherol) and beta carotene, are associated with a reduced risk of lung cancer.
METHODS
We performed a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta carotene, or both would reduce the incidence of lung cancer and other cancers. A total of 29,133 male smokers 50 to 69 years of age from southwestern Finland were randomly assigned to one of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo. Follow-up continued for five to eight years.
RESULTS
Among the 876 new cases of lung cancer diagnosed during the trial, no reduction in incidence was observed among the men who received alpha-tocopherol (change in incidence as compared with those who did not, -2 percent; 95 percent confidence interval, -14 to 12 percent). Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not (change in incidence, 18 percent; 95 percent confidence interval, 3 to 36 percent). We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not. Beta carotene had little or no effect on the incidence of cancer other than lung cancer. Alpha-tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not. Total mortality was 8 percent higher (95 percent confidence interval, 1 to 16 percent) among the participants who received beta carotene than among those who did not, primarily because there were more deaths from lung cancer and ischemic heart disease.
CONCLUSIONS
We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene. In fact, this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects.
Topics: Aged; Carotenoids; Cause of Death; Double-Blind Method; Finland; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Smoking; Vitamin E; beta Carotene
PubMed: 8127329
DOI: 10.1056/NEJM199404143301501 -
Molecular Nutrition & Food Research Jun 2016Tocopherols exist in four forms designated as α, β, δ, and γ. Due to their strong antioxidant properties, tocopherols have been suggested to reduce the risk of... (Review)
Review
Tocopherols exist in four forms designated as α, β, δ, and γ. Due to their strong antioxidant properties, tocopherols have been suggested to reduce the risk of cancer. Cancer prevention studies with tocopherols have mostly utilized α-tocopherol. Large-scale clinical trials with α-tocopherol provided inconsistent results regarding the cancer-preventive activities of tocopherols. This review summarizes our current understanding of the anticancer activities of different forms of tocopherols based on follow-up of the clinical trials, recent epidemiological evidences, and experimental studies using in vitro and in vivo models. The experimental data provide strong evidence in support of the anticancer activities of δ-tocopherol, γ-tocopherol, and the natural tocopherol mixture rich in γ-tocopherol, γ-TmT, over α-tocopherol. Such outcomes emphasize the need for detailed investigation into the cancer-preventive activities of different forms of tocopherols to provide a strong rationale for intervention studies in the future.
Topics: Animals; Anticarcinogenic Agents; Antioxidants; Cell Line, Tumor; Disease Models, Animal; Humans; Meta-Analysis as Topic; Neoplasms; Randomized Controlled Trials as Topic; Tocopherols
PubMed: 26751721
DOI: 10.1002/mnfr.201500847 -
Journal of Immunology (Baltimore, Md. :... Nov 2022In humans and mice, offspring of allergic mothers are predisposed to development of allergy. In mice, allergic mothers have elevated β-glucosylceramides (βGlcCers)...
In humans and mice, offspring of allergic mothers are predisposed to development of allergy. In mice, allergic mothers have elevated β-glucosylceramides (βGlcCers) that are transported to the fetus via the placenta and to offspring via milk. The elevated βGlcCers increase the number of fetal liver CD11c+CD11b+ dendritic cells (DCs) and offspring allergen-induced lung eosinophilia. These effects are modifiable by maternal dietary supplementation with the plant-derived lipids α-tocopherol and γ-tocopherol. It is not known whether βGlcCers and tocopherols directly regulate development of DCs. In this study, we demonstrated that βGlcCers increased development of GM-CSF-stimulated mouse bone marrow-derived DCs (BMDCs) in vitro without altering expression of costimulatory molecules. This increase in BMDC numbers was blocked by α-tocopherol and potentiated by γ-tocopherol. Furthermore, βGlcCers increased protein kinase Cα (PKCα) and PKCδ activation in BMDCs that was blocked by α-tocopherol. In contrast, γ-tocopherol increased BMDC PKCα and PKCδ activation and enhanced the βGlcCer-induced increase in PKCδ activation in a DC subset. Ag processing per DC was minimally enhanced in βGlcCer-treated BMDCs and not altered ex vivo in lung DCs from pups of allergic mothers. Pups of allergic mothers had an increased proportion of CD11b+CD11c+ subsets of DCs, contributing to enhanced stimulation of T cell proliferation ex vivo. Thus, βGlcCer, which is both necessary and sufficient for development of allergic predisposition in offspring of allergic mothers, directly increased development and PKC activation in BMDCs. Furthermore, this was modifiable by dietary tocopherols. This may inform design of future studies for the prevention or intervention in asthma and allergic disease.
Topics: Humans; Female; Pregnancy; Animals; Mice; Tocopherols; gamma-Tocopherol; Glucosylceramides; alpha-Tocopherol; Protein Kinase C-alpha; Hypersensitivity; Asthma; CD11c Antigen; Dendritic Cells
PubMed: 36426950
DOI: 10.4049/jimmunol.2101188 -
Journal of Oleo Science 2023Using sunflower oil as the oil matrix, the antioxidant effects and types of interactions of three natural components, α-tocopherol, β-carotene and epigallocatechin...
Using sunflower oil as the oil matrix, the antioxidant effects and types of interactions of three natural components, α-tocopherol, β-carotene and epigallocatechin gallate (EGCG), were investigated and the kinetic model of oxidation reaction was established. The results showed that the ability of the three antioxidants to scavenge DPPH radicals was ranked as EGCG > β-carotene > α-tocopherol in the concentration range of 0~100 mg/kg. 15 samples were obtained by combining two of three natural components. When the concentration ratios of β-carotene and EGCG were 1:20 and 1:7.5, α-tocopherol and EGCG were 1:13.3, 1:6, and 1:2, and α-tocopherol and β-carotene were 1:0.2 and 1:0.05, the type of interaction was synergistic, while the rest of the samples showed antagonistic effects. The sample with a 1:13.3 concentration of α-tocopherol and EGCG showed the longest induction period, the lowest oxidation rate constant, the highest activation energy, the best oxidative stability, and the longest shelf life at different temperatures. This compounded natural antioxidant was the most favorable for the stability of sunflower oil. This provides some theoretical basis for the development and application of compounded natural antioxidants in vegetable oils.
Topics: Antioxidants; alpha-Tocopherol; beta Carotene; Sunflower Oil; Oxidation-Reduction; Oxidative Stress
PubMed: 37121677
DOI: 10.5650/jos.ess22348 -
Molecular Vision 2009Vitamin E is an important natural antioxidant, and its most common and biologically active form is alpha-tocopherol. In addition to this, specific regulatory effects of... (Review)
Review
Vitamin E is an important natural antioxidant, and its most common and biologically active form is alpha-tocopherol. In addition to this, specific regulatory effects of vitamin E have been revealing. The body exerts a certain effort to regulate its tissue levels with specific tocopherol transport proteins and membrane receptors. Antiproliferative and protein kinase C-suppressing effects of alpha-tocopherol have been previously demonstrated, which have not been mimicked by beta-tocopherol or probucol. Protein kinase C promises to be an important area of interest in the means of glaucoma and cataractogenesis. It has been shown in different models that retinal vascular dysfunction due to hyperglycemia could be prevented by alpha-tocopherol via the diachylglycerol-protein kinase C pathway. Glutamate transporter activity has been shown to be modulated by protein kinase C. This pathway is also important in intraocular pressure-lowering effects of prostaglandin and its analogs in glaucoma therapy. Filtran surgery became another possible area of usage of alpha-tocopherol since its antiproliferative effect has been demonstrated in human Tenon's capsule fibroblasts. Prevention of posterior capsule opacification is another area for future studies. It is evident that when correct and safe modulation is the objective, alpha-tocopherol merits a concern beyond its mere antioxidant properties.
Topics: Animals; Antioxidants; Humans; Protein Kinase C; Signal Transduction; alpha-Tocopherol
PubMed: 19390643
DOI: No ID Found -
Journal of Dairy Science Jan 2021The effectiveness of using serum vitamin concentrations as biomarkers to predict diseases in dairy cows during the periparturient period is not well known. The objective...
The effectiveness of using serum vitamin concentrations as biomarkers to predict diseases in dairy cows during the periparturient period is not well known. The objective of this study was to evaluate the association between serum β-carotene, retinol, and α-tocopherol concentrations and periparturient cow diseases in commercial dairies. We measured serum concentrations of these vitamin-active compounds at dry-off and during close-up (approximately 3 wk before calving) and early lactation (approximately 7 d post-calving), and we examined their association with clinical diseases in the first 30 d in milk. Diseases were diagnosed by trained personnel and recorded using database software. Blood samples were taken from 353 cows from 5 different farms over a 3-yr period. Blood samples were analyzed for β-carotene, retinol, α-tocopherol, and cholesterol. We built separate mixed logistic regression models for each disease outcome: hyperketonuria, lameness, mastitis, uterine diseases (retained placenta or metritis), and an aggregate outcome. For the aggregate outcome, a cow was considered positive if she had one or more of the following: hyperketonuria, lameness, mastitis, uterine disease, pneumonia, milk fever, or displaced abomasum. Concentrations of all 3 fat-soluble vitamins decreased significantly in early lactation relative to the 2 prepartum sampling times. Serum retinol concentrations at close-up and early lactation were negatively associated with odds of developing postpartum hyperketonuria. At early lactation, cows with uterine disease had lower serum retinol concentrations than cows without uterine disease. Similarly, lower serum retinol concentrations were associated with greater odds of having any one disease in the aggregate outcome. First-test 305-d mature-equivalent milk yield was positively correlated with increased serum α-tocopherol and negatively correlated with β-carotene concentrations. This study demonstrates the potential for serum β-carotene, retinol, and α-tocopherol to serve as biomarkers for disease risk.
Topics: Animals; Biomarkers; Cattle; Cattle Diseases; Cholesterol; Female; Lactation; Milk; Postpartum Period; Pregnancy; Risk Assessment; Vitamin A; Vitamins; alpha-Tocopherol; beta Carotene
PubMed: 33162081
DOI: 10.3168/jds.2020-18693 -
Zeitschrift Fur Naturforschung. C,... 2003New and known structural and functional insights in the role of beta-carotene and of alpha-tocopherol in photosytem II are reviewed. A concept is presented connecting... (Review)
Review
New and known structural and functional insights in the role of beta-carotene and of alpha-tocopherol in photosytem II are reviewed. A concept is presented connecting the failure of P680 triplet quenching by beta-carotene with the formation of singlet oxygen and its scavenging in the turnover of the D1 protein and by tocopherol in the maintenance of PS II structure and function.
Topics: Photosynthesis; Photosystem II Protein Complex; Tocopherols; beta Carotene
PubMed: 14577617
DOI: 10.1515/znc-2003-9-1001 -
Antioxidants (Basel, Switzerland) Nov 2017Vitamin E is a generic term frequently used to group together eight different molecules, namely: α-, β-, γ- and δ-tocopherol and the corresponding tocotrienols. The... (Review)
Review
Vitamin E is a generic term frequently used to group together eight different molecules, namely: α-, β-, γ- and δ-tocopherol and the corresponding tocotrienols. The term tocopherol and eventually Vitamin E and its related activity was originally based on the capacity of countering foetal re-absorption in deficient rodents or the development of encephalomalacia in chickens. In humans, Vitamin E activity is generally considered to be solely related to the antioxidant properties of the tocolic chemical structure. In recent years, several reports have shown that specific activities exist for each different tocotrienol form. In this short review, tocotrienol ability to inhibit cancer cell growth and induce apoptosis thanks to specific mechanisms, not shared by tocopherols, such as the binding to Estrogen Receptor-β (ERβ) and the triggering of endoplasmic reticulum (EndoR) stress will be described. The neuroprotective activity will also be presented and discussed. We propose that available studies strongly indicate that specific forms of tocotrienols have a distinct mechanism and biological activity, significantly different from tocopherol and more specifically from α-tocopherol. We therefore suggest not pooling them together within the broad term "Vitamin E" on solely the basis of their putative antioxidant properties. This option implies obvious consequences in the assessment of dietary Vitamin E adequacy and, probably more importantly, on the possibility of evaluating a separate biological variable, determinant in the relationship between diet and health.
PubMed: 29156559
DOI: 10.3390/antiox6040093 -
Circulation Research Jun 2019Although there has been a long-standing interest in the human health effects of vitamin E, a comprehensive analysis of the association between circulating vitamin E and...
RATIONALE
Although there has been a long-standing interest in the human health effects of vitamin E, a comprehensive analysis of the association between circulating vitamin E and long-term mortality has not been conducted.
OBJECTIVE
Determine whether serum α-tocopherol (the predominant form of vitamin E) is related to long-term overall and cause-specific mortality and elucidate the dose-response relationships with better quantification of the associations.
METHODS AND RESULTS
We conducted a biochemical analysis of 29 092 participants in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention) that originally tested vitamin E and β-carotene supplementation. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and during a 30-year follow-up we identified 23 787 deaths, including deaths from cardiovascular disease (9867), cancer (7687), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2698). After adjusting for major risk factors, we found that men with higher serum α-tocopherol had significantly lower all-cause mortality (hazard ratios=0.83, 0.79, 0.75, and 0.78 for quintile 2 (Q2)-Q5 versus Q1, respectively; P<0.0001), and significantly decreased mortality from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, and other causes, with risk reductions from 17% to 47% for the highest versus lowest quintile. The α-tocopherol association with overall mortality was similar across subgroups of smoking intensity, years of smoking, alcohol consumption, trial supplementation, and duration of follow-up. The association was, however, significantly modified by baseline age and body mass index, with stronger inverse associations for younger men and men with a lower body mass index ( P≤0.006).
CONCLUSIONS
In this long-term prospective cohort study, higher baseline serum α-tocopherol biochemical status was associated with lower risk of overall mortality and mortality from all major causes. Our data support the long-term health benefits of higher serum α-tocopherol for overall and chronic disease mortality and should be replicated in other more diverse populations.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Cause of Death; Cohort Studies; Dietary Supplements; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; alpha-Tocopherol
PubMed: 31219752
DOI: 10.1161/CIRCRESAHA.119.314944