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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 -
PloS One 2023Antioxidants can prevent osteoporosis, but the association between serum antioxidants and the cause of osteoporosis remains unknown. We aimed to utilize Mendelian...
BACKGROUND
Antioxidants can prevent osteoporosis, but the association between serum antioxidants and the cause of osteoporosis remains unknown. We aimed to utilize Mendelian randomization (MR) to determine whether genetically predicted serum levels of diet-derived antioxidants can affect the risk of osteoporosis, to determine the effect of dietary supplementation of antioxidants.
METHODS
Genetic variants associated with diet-derived antioxidants were selected from the genome-wide association studies. A total of 12,946 osteoporosis cases and 506,624 healthy controls were obtained from UK Biobank (UKB) and Genetic Factors of Osteoporosis (GEFOS) consortia. We implemented a two-sample MR design and performed several sensitivity analyses to evaluate the causal relationship.
RESULTS
In UKB, the genetically predicted higher β-carotene (OR = 0.863, p = 7.37 × 10-6, power = 100%) and γ-tocopherol (OR = 0.701, p = 0.021, power = 5%) had an inverse relationship with osteoporosis. However, only the association of serum β-carotene passed FDR correction. In GEFOS, there were no significant diet-derived antioxidants. The direction of the association of β-carotene with osteoporosis (OR = 0.844, p = 0.106, power = 87%) was consistent with that in the UKB dataset. A fixed-effects meta-analysis confirmed that β-carotene (OR = 0.862, p = 2.21 × 10-6) and γ-tocopherol (OR = 0.701, p = 2.31 × 10-2) could decrease the risk of osteoporosis. To reduce exclusion limit bias, we used total body bone mineral density, lumbar spine bone mineral density and femoral neck bone mineral density as surrogates and found that the genetically elevated circulating β-carotene level could increase total body BMD (beta = 0.043, p-value = 8.26 x 10-5, power = 100%), lumbar spine BMD (beta = 0.226, p-value = 0.001, power = 100%) and femoral neck BMD(beta = 0.118, p-value = 0.016, power = 100%).
CONCLUSIONS
We observed that genetically predicted serum β-carotene could elevate BMD and prevent osteoporosis.
Topics: Humans; Antioxidants; beta Carotene; Bone Density; Diet; gamma-Tocopherol; Genome-Wide Association Study; Lumbar Vertebrae; Mendelian Randomization Analysis; Osteoporosis; Polymorphism, Single Nucleotide
PubMed: 38019728
DOI: 10.1371/journal.pone.0293145 -
Biochemistry and Biophysics Reports Dec 2021One of the neuropathological hallmarks of Alzheimer's disease (AD)-causing neurodegeneration and consequent memory deterioration, and eventually, cognitive decline-is...
One of the neuropathological hallmarks of Alzheimer's disease (AD)-causing neurodegeneration and consequent memory deterioration, and eventually, cognitive decline-is amyloid-β (Aβ) aggregation forming amyloid plaques. Our previous study showed the potential of a tocotrienol-rich fraction-a mixture of naturally occurring of vitamin E analogs-to inhibit Aβ aggregation and restore cognitive function in an AD mouse model. The current study examined the effect of three vitamin E analogs-α-tocopherol (α-TOC), α-tocotrienol (α-T3), and γ-tocotrienol (γ-T3)-on Aβ aggregation, disaggregation, and oligomerization in vitro. Thioflavin T (ThT) assay showed α-T3 reduced Aβ aggregation at 10 μM concentration. Furthermore, both α-T3 and γ-T3 demonstrated Aβ disaggregation, as shown by the reduction of ThT fluorescence. However, α-TOC showed no significant effect. We confirmed the results for ThT assays with scanning electron microscopy imaging. Further investigation in photo-induced cross-linking of unmodified protein assay indicated a reduction in Aβ oligomerization by γ-T3. The present study thus revealed the individual effect of each tocotrienol analog in reducing Aβ aggregation and oligomerization as well as disaggregating preformed fibrils.
PubMed: 34541343
DOI: 10.1016/j.bbrep.2021.101131 -
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 -
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 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 -
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 -
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 -
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