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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 -
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 -
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 -
European Journal of Clinical Nutrition Sep 2022The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological...
BACKGROUND/OBJECTIVES
The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolites through agnostic metabolomics analyses can contribute to elucidating the specific associations and disease etiology. This study aims to investigate the association between circulating metabolites and serum α-tocopherol concentration in an un-supplemented state.
SUBJECTS/METHODS
Metabolomic analysis of 4,294 male participants was conducted based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The associations between 1,791 known metabolites measured by ultra-high-performance LC-MS/GC-MS and HPLC-determined α-tocopherol concentration were estimated using multivariable linear regression. Differences in metabolite levels per unit difference in α-tocopherol concentration were calculated as standardized β-coefficients and standard errors.
RESULTS
A total of 252 metabolites were associated with serum α-tocopherol at the Bonferroni-corrected p value (p < 2.79 × 10). Most of these metabolites were of lipid and amino acid origin, with the respective subclasses of dicarboxylic fatty acids, and valine, leucine, and isoleucine metabolism, being highly represented. Among lipids, the strongest signals were observed for linoleoyl-arachidonoyl-glycerol (18:2/20:4)[2](β = 0.149; p = 8.65 × 10) and sphingomyelin (D18:2/18:1) (β = 0.035; p = 1.36 × 10). For amino acids, the strongest signals were aminoadipic acid (β = 0.021; p = 5.01 × 10) and l-leucine (β = 0.007; p = 1.05 × 10).
CONCLUSIONS
The large number of metabolites, particularly lipid and amino acid compounds associated with serum α-tocopherol provide leads regarding potential mechanisms through which vitamin E influences human health, including its role in cardiovascular disease and cancer.
Topics: Amino Acids; Humans; Lipids; Male; Neoplasms; Vitamin E; alpha-Tocopherol; beta Carotene
PubMed: 35322169
DOI: 10.1038/s41430-022-01112-7 -
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 -
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 Agricultural and Food... Jan 2015Four vitamins were analyzed in several fruit and vegetable commodities to evaluate the differences between fresh and frozen produce. Ascorbic acid, riboflavin,... (Comparative Study)
Comparative Study
Four vitamins were analyzed in several fruit and vegetable commodities to evaluate the differences between fresh and frozen produce. Ascorbic acid, riboflavin, α-tocopherol, and β-carotene were evaluated in corn, carrots, broccoli, spinach, peas, green beans, strawberries, and blueberries. Samples of each commodity were harvested, processed, and analyzed for nutrient content at three storage times per treatment. Ascorbic acid showed no significant difference for five of the eight commodities and was higher in frozen samples than fresh for the remaining three commodities. Apart from broccoli and peas, which were higher and lower in frozen vs fresh samples, respectively, none of the commodities showed significant differences with respect to riboflavin content. Three commodities had higher levels of α-tocopherol in the frozen samples, while the remaining commodities showed no significant difference between fresh and frozen. β-Carotene was not found in significant amounts in blueberries, strawberries, and corn. Peas, carrots, and spinach were lower in β-carotene in the frozen samples, while green beans and spinach showed no significant difference between the two storage methods. Overall, the vitamin content of the frozen commodities was comparable to and occasionally higher than that of their fresh counterparts. β-Carotene, however, was found to decrease drastically in some commodities.
Topics: Ascorbic Acid; Cold Temperature; Food Preservation; Freezing; Fruit; Riboflavin; Vegetables; Vitamins; alpha-Tocopherol; beta Carotene
PubMed: 25526594
DOI: 10.1021/jf5058793 -
Annals of Nutrition & Metabolism 2004The main research activities of the last decades on tocopherols were mainly focused on alpha-tocopherol, in particular when considering the biological activities.... (Review)
Review
The main research activities of the last decades on tocopherols were mainly focused on alpha-tocopherol, in particular when considering the biological activities. However, recent studies have increased the knowledge on gamma-tocopherol, which is the major form of vitamin E in the diet in the USA, but not in Europe. gamma-Tocopherol provides different antioxidant activities in food and in-vitro studies and showed higher activity in trapping lipophilic electrophiles and reactive nitrogen and oxygen species. The lower plasma levels of gamma- compared to alpha-tocopherol might be discussed in the light of different bioavailability, but also in a potential transformation from gamma- into alpha-tocopherol. From the metabolism end product, only that of gamma-tocopherol (2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman), but not that of alpha-tocopherol, was identified to provide natriuretic activity. Studies also indicate that only the gamma-tocopherol plasma level served as biomarker for cancer and cardiovascular risk. Therefore, this paper provides a comprehensive review on gamma-tocopherol with emphasis on its chemistry, biosynthesis, occurrence in food, different intake linking to different plasma levels in USA and Europe, absorption and metabolism, biological activities, and possible role in human health.
Topics: Antioxidants; Biological Availability; Chromans; Humans; Intestinal Absorption; Neoplasms; Nutritive Value; Propionates; alpha-Tocopherol; gamma-Tocopherol
PubMed: 15256801
DOI: 10.1159/000079555 -
Diabetologia Jan 2008Type 2 diabetes is associated with reduced antioxidant defence. Only a few human studies have investigated the role of antioxidants in the pathogenesis of diabetes. This... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS/HYPOTHESIS
Type 2 diabetes is associated with reduced antioxidant defence. Only a few human studies have investigated the role of antioxidants in the pathogenesis of diabetes. This study aimed to examine whether alpha-tocopherol or beta-carotene affected the occurrence of type 2 diabetes.
METHODS
In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, controlled trial, 29,133 male smokers aged 50-69 years were randomised to receive either alpha-tocopherol (50 mg/day) or beta-carotene (20 mg/day) or both agents or placebo daily for 5-8 years (median 6.1 years). Baseline serum samples were analysed for alpha-tocopherol and beta-carotene using HPLC. Cases of diabetes were identified from a nationwide Finnish registry of patients receiving drug reimbursement for diabetes. Of 27,379 men without diabetes at baseline, 705 men were diagnosed with diabetes during the follow-up of up to 12.5 years.
RESULTS
Baseline serum levels of alpha-tocopherol and beta-carotene were not associated with the risk of diabetes in the placebo group: the relative risk (RR) between the highest and lowest quintiles of alpha-tocopherol was 1.59 (95% CI 0.89-2.84) and that for beta-carotene was 0.66 (95% CI 0.40-1.10). Neither supplementation significantly affected the incidence of diabetes: the RR was 0.92 (95% CI 0.79-1.07) for participants receiving alpha-tocopherol compared with non-recipients and 0.99 (95% CI 0.85-1.15) for participants receiving beta-carotene compared with non-recipients.
CONCLUSIONS/INTERPRETATION
Neither alpha-tocopherol nor beta-carotene supplementation prevented type 2 diabetes in male smokers. Serum levels of alpha-tocopherol and beta-carotene were not associated with the risk of type 2 diabetes.
Topics: Aged; Antioxidants; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Humans; Incidence; Male; Middle Aged; Placebos; Risk; Smoking; Time Factors; alpha-Tocopherol; beta Carotene
PubMed: 17994292
DOI: 10.1007/s00125-007-0864-0 -
Journal of Dairy Science Nov 2022Little is known about transfer of dietary β-carotene into colostrum, its absorption by the calf, and its effects on retinol and α-tocopherol in the calf when the dam's...
Little is known about transfer of dietary β-carotene into colostrum, its absorption by the calf, and its effects on retinol and α-tocopherol in the calf when the dam's dietary vitamin A is adequate. Our objective was to assess the effect of β-carotene supplementation during the close-up dry period on the colostrum and calf. The study was conducted on a large commercial dairy farm in Indiana during early summer of 2015. Ninety-four multiparous Holstein cows were blocked by calving data, parity, and previous production, and then randomly assigned to either control or β-carotene (BC) treatments. While locked in headgates each morning, each cow received a topdress of β-carotene (Rovimix, DSM Nutritional Products, 8 g/d; provided 800 mg β-carotene) or carrier from 21 d before expected calving until calving. Colostrum was collected within 2 h of parturition. Calf blood samples were obtained within 2 h of birth before receiving the dam's colostrum, at 24 h after birth, and at 7 d and 60 d of age. Blood serum was analyzed for β-carotene, retinol, α-tocopherol, and other metabolites and enzymes. Colostrum was analyzed for β-carotene, retinol, α-tocopherol, colorimetry profile, and milk components. Data were analyzed using mixed-effects models in SAS (SAS Institute Inc.). Calf serum β-carotene data were analyzed using the FREQ procedure. Colostrum β-carotene was higher for BC cows. Colostrum from BC cows had increased a* [measures red (positive) to green (negative)] and b* [measures yellow (positive) to blue (negative)] colorimeter values, indicating that β-carotene altered colostrum color toward red and yellow. Supplementation did not affect colostral or calf IgG concentrations. Colostrum color indices were correlated with IgG concentrations as well as concentrations of β-carotene, retinol, and α-tocopherol. Before receiving colostrum, the concentration of β-carotene in calf serum was below the detectable threshold of 0.05 μg/mL. At 24 h of age, the number of calves with detectable β-carotene concentrations increased, with more calves from BC cows (52.1%) having detectable concentrations than calves from cows in the control group (6.1%). No differences in concentrations of retinol or α-tocopherol were observed in calf serum. Supplementation of β-carotene to cows decreased activities of gamma-glutamyl transpeptidase and glutamate dehydrogenase in calf serum. In pregnant cows already receiving adequate vitamin A, supplementation of β-carotene increased concentration of β-carotene in colostrum, altered colostrum color, and increased serum β-carotene in calves at birth.
Topics: Pregnancy; Female; Cattle; Animals; Colostrum; beta Carotene; Vitamin A; alpha-Tocopherol; gamma-Glutamyltransferase; Glutamate Dehydrogenase; Dietary Supplements; Immunoglobulin G
PubMed: 36175221
DOI: 10.3168/jds.2022-22210