Background: High intake of vitamin E from food (tocopherol), but not from supplements (which usually contain alpha-tocopherol), is inversely associated with Alzheimer disease. Objective: We examined ...whether food intakes of vitamin E, alpha-tocopherol equivalents (a measure of the relative biologic activity of tocopherols and tocotrienols), or individual tocopherols would protect against incident Alzheimer disease and cognitive decline over 6 y in participants of the Chicago Health and Aging Project. Design: The 1993-2002 study of community residents aged greater than or equal to 65 y included the administration of 4 cognitive tests and clinical evaluations for Alzheimer disease. Dietary assessment was by food-frequency questionnaire. Results: Tocopherol intake from food was related to the 4-y incidence of Alzheimer disease determined by logistic regression in 1041 participants who were clinically evaluated (n = 162 incident cases) and to change in a global cognitive score determined by mixed models in 3718 participants. Higher intakes of vitamin E (relative risk: 0.74 per 5 mg/d increase; 95% CI: 0.62, 0.88) and alpha-tocopherol equivalents (relative risk: 0.56 per 5 mg/d increase; 95% CI: 0.32, 0.98) were associated with a reduced incidence of Alzheimer disease in separate multiple-adjusted models that included intakes of saturated and trans fats and docosahexaenoic acid. alpha- and gamma-Tocopherol had independent associations. In separate mixed models, a slower rate of cognitive decline was associated with intakes of vitamin E, alpha-tocopherol equivalents, and alpha- and gamma-tocopherols. Conclusion: The results suggest that various tocopherol forms rather than alpha- tocopherol alone may be important in the vitamin E protective association with Alzheimer disease.
Scope
Tocomonoenols (T1) are little‐known vitamin E derivatives naturally occurring in foods. Limited knowledge exists regarding the cellular uptake and metabolism of α‐tocomonoenol (αT1) and none ...about that of γ‐tocomonoenol (γT1).
Methods and results
The study investigates the cytotoxicity, uptake, and metabolism of αT1 and γT1 in HepG2 cells compared to the α‐ and γ‐tocopherols (T) and ‐tocotrienols (T3). None of the studied tocochromanols are cytotoxic up to 100 µmol L−1. The uptake of the γ‐congeners is significantly higher than that of the corresponding α‐forms, whereas no significant differences are observed based on the degree of saturation of the sidechain. Carboxymethylbutyl‐hydroxychromans (CMBHC) are the predominant short‐chain metabolites of all tocochromanols and conversion is higher for γT1 than αT1 as well as for the γ‐congeners of T and T3. The rate of metabolism increases with the number of double bonds in the sidechain. The rate of metabolic conversion of the T1 is more similar to tocopherols than to that of the tocotrienols.
Conclusion
This is the first evidence that both αT1 and γT1 follow the same sidechain degradation pathway and exert similar rates of metabolism than tocopherols. Therefore, investigation into the biological activities of tocomonoenols is warranted.
Metabolism of α‐ and γ‐tocomonoenols (T1), tocopherols (T) and tocotrienols (T3) in liver cells shows that their metabolism increases with increasing number of double bonds in sidechain (T < T1 ≪ T3) and with the methylation of the chromanol ring (α ≪ γ). The main product of T1 metabolism is carboxymethylbutyl‐hydroxychroman (CMBHC) and αT1 metabolism closely resembles that of α‐tocopherol.
•Sacha inchi oil (SI) stability during deep-frying at 170 °C or 180 °C was tested.•SI had high linolenic acid (53.8% oil) and tocopherols (2540.1 mg/kg) contents.•Tocopherol, oil stability and ...antioxidant capacity decreased in zero-order kinetics.•During deep-frying SI withstood degradation better than soybean oil.•The tocopherols preserved the stability of SI polyunsaturated fatty acids.
Sacha inchi (Plukenetia volubilis) oil (SI) is appreciated for its nutritional and sensorial characteristics. The aim of this study was to evaluate SI changes during French fries deep-frying at 170 °C or 180 °C up to 119 and 50 min, respectively; commercial soybean oil (SO) was tested as control. SI had high α-linolenic acid (53.8%), linoleic acid (33.4%) and total tocopherols (2540.1 mg/kg). During frying tocopherol content, oil stability and antioxidant capacity (ABTS, DPPH) decreased following zero-order kinetics; γ-tocopherol showed the strongest decrease. Notwithstanding the high SI unsaturation and the commercial antioxidant (TBHQ) in SO, SI showed slightly higher or similar hydrolysis (free fatty acids and diacylglycerols), similar primary (K232, oxidized-triacylglycerols) and lower secondary (K268, triacylglycerol oligopolymers) oxidation. Because of the high tocopherol content, SI showed lower degradation than SO. Thus, SI is suitable for short-term deep-frying; additionally, it may enhance the nutritional value and the flavour of fried foods.
SCOPE: A single nucleotide polymorphism in the cluster determinant 36 (CD36) gene has recently been associated with plasma α‐tocopherol concentration, suggesting a possible role of this protein in ...vitamin E intestinal absorption or tissue uptake. METHODS AND RESULTS: To investigate the involvement of CD36 in vitamin E transport, we first evaluated the effect of CD36 on α‐ and γ‐tocopherol transmembrane uptake and efflux using transfected HEK cells. γ‐Tocopherol postprandial response was then assessed in CD36‐deficient mice compared with wild‐type mice, after the mice had been fully characterized for their α‐tocopherol, vitamin A and lipid plasma, and tissue contents. Both α‐ and γ‐tocopherol uptake was significantly increased in cells overexpressing CD36 compared with control cells. Compared with wild‐type mice, CD36‐deficient mice displayed a significantly decreased cholesterol hepatic concentration, and males exhibited significantly higher triacylglycerol contents in liver, brain, heart, and muscle. Although tissue α‐tocopherol concentration after adjustment for lipid content was not modified, γ‐tocopherol postprandial response was significantly increased in CD36‐deficient mice compared with controls, likely reflecting the postprandial hypertriglyceridemia observed in these mice. CONCLUSION: Our findings show for the first time that CD36 participates—directly or indirectly—in vitamin E uptake, and that CD36 effect on postprandial lipid metabolism in turn modifies vitamin E postprandial response.
Asthma and allergic disease result from interactions of environmental exposures and genetics. Vitamin E is one environmental factor that can modify development of allergy early in life and modify ...responses to allergen after allergen sensitization. Seemingly varied outcomes from vitamin E are consistent with the differential functions of the isoforms of vitamin E. Mechanistic studies demonstrate that the vitamin E isoforms α-tocopherol and γ-tocopherol have opposite functions in regulation of allergic inflammation and development of allergic disease, with α-tocopherol having anti-inflammatory functions and γ-tocopherol having pro-inflammatory functions in allergy and asthma. Moreover, global differences in prevalence of asthma by country may be a result, at least in part, of differences in consumption of these two isoforms of tocopherols. It is critical in clinical and animal studies that measurements of the isoforms of tocopherols be determined in vehicles for the treatments, and in the plasma and/or tissues before and after intervention. As allergic inflammation is modifiable by tocopherol isoforms, differential regulation by tocopherol isoforms provide a foundation for development of interventions to improve lung function in disease and raise the possibility of early life dietary interventions to limit the development of lung disease.
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•Increased prevalence of asthma/allergy and altered consumption of tocopherol isoforms.•α-tocopherol associates with better lung function but this is reduced by γ-tocopherol.•In mice, tocopherol isoforms regulate allergy in adults and their offspring.•α- and γ-tocopherol inhibit and enhance, respectively, protein kinase C activation.•Needed are studies for a basis to recommend daily tocopherol isoform doses in disease.
α-tocopherol (αT) in its natural form 2´ R, 4´R, 8´ RαT (RRR-αT) is more bioactive than synthetic α-tocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in ...formula-fed infant brain is unknown.
We sought to compare αT and stereoisomer status in infant rhesus macaques (Macaca mulatta) fed infant formula (RRR-αT or all rac-αT) with a reference group fed a mixed diet of breast milk and maternal diet.
From 1 d after birth until 6 mo of age, infants (n = 23) were either nursery reared and exclusively fed 1 of 2 formulas by staff personnel or were community housed with their mothers and consumed a mixed reference diet of breast milk (69 mL/d at 6 mo) transitioning to monkey diet at ~2 mo (MF;n = 8). Formulas contained either 21 μmol RRR-αT/L (NAT-F; n = 8) or 30 μmol all rac-αT/L (SYN-F; n = 7). Total αT and αT stereoisomers were analyzed in breast milk at 2, 4, and 6 mo and in monkey plasma and liver and 6 brain regions at 6 mo of age. α-tocopherol transfer protein (α-TTP), lipoprotein αT, and urinary α-carboxyethyl-hydroxychroman (α-CEHC) were measured. One-way ANOVA with Tukey's post-hoc test was used for analysis.
At study termination, plasma, liver, lipoprotein, and brain total αT did not differ between groups. However, the NAT-F–fed group had higher RRR-αT than the SYN-F–fed group (P < 0.01) and the MF group (P < 0.0001) in plasma (1.7- and 2.7-fold) and brain (1.5- and 2.5-fold). Synthetic αT 2 R stereoisomers (SYNTH-2 R) were generally 3- and 7-fold lower in brain regions of the NAT-F group compared with those of the SYN-F and MF groups (P < 0.05). SYNTH-2 R stereoisomers were 2-fold higher in MF than SYN-F (P < 0.0001). The plasma percentage of SYNTH-2R was negatively correlated with the brain percentage ofRRR-αT (r = -0.99,P < 0.0001). Brain αT profiles were not explained by α-TTP mRNA or protein expression. Urine α-CEHC was 3 times higher in the NAT-F than in the MF group (P < 0.01).
Consumption of infant formulas with natural (NAT-F) compared with synthetic (SYN-F) αT differentially impacted brain αT stereoisomer profiles in infant rhesus macaques. Future studies should assess the functional implications of αT stereoisomer profiles on brain health.
Background: Tocopherols were discovered for their role in animal reproduction, but little is known about the contribution of deficiencies of vitamin E to human pregnancy loss. Objective: We sought to ...determine whether higher first-trimester concentrations of α-tocopherol and γ-tocopherol were associated with reduced odds of miscarriage (pregnancy losses <24 wk of gestation) in women in rural Bangladesh. Design: A case-cohort study in 1605 pregnant Bangladeshi women median (IQR) gestational age: 10 wk (8–13 wk) who participated in a placebo-controlled vitamin A– or β-carotene–supplementation trial was done to assess ORs of miscarriage in women with low α-tocopherol (<12.0 μmol/L) and γ-tocopherol (<0.81 μmol/L; upper tertile cutoff of the γ-tocopherol distribution in women who did not miscarry). Results: In all women, plasma α- and γ-tocopherol concentrations were low median (IQR): 10.04 μmol/L (8.07–12.35 μmol/L) and 0.66 μmol/L (0.50–0.95 μmol/L), respectively. In a logistic regression analysis that was adjusted for cholesterol and the other tocopherol, low α-tocopherol was associated with an OR of 1.83 (95% CI: 1.04, 3.20), whereas a low γ-tocopherol concentration was associated with an OR of 0.62 (95% CI: 0.41, 0.93) for miscarriage. Subgroup analyses revealed that opposing ORs were evident only in women with BMI (in kg/m ²) ≥18.5 and serum ferritin concentration ≤150 μg/L, although low BMI and elevated ferritin conferred stronger risk of miscarriage. Conclusions: In pregnant women in rural Bangladesh, low plasma α-tocopherol was associated with increased risk of miscarriage, and low γ-tocopherol was associated with decreased risk of miscarriage. Maternal vitamin E status in the first trimester may influence risk of early pregnancy loss. The JiVitA-1 study, from which data for this report were derived, was registered at clinicaltrials.gov as NCT00198822.
SCOPE: The mechanisms underlying the preferential retention of a single compound (α‐tocopherol (αT)) of the eight vitamin E compounds in the body are incompletely understood. We hypothesized that ...vitamin E metabolism and not the hepatic α‐tocopherol transfer protein (TTP) is responsible for the discrimination against non‐αT congeners. METHODS AND RESULTS: TTP knockout and wild‐type mice (n = 12/group) were fed equimolar concentrations of αT and γ‐tocopherol (γT; 50 mg/kg diet each) alone or together with sesamin (2 g/kg diet) for 6 wk. Inhibition of vitamin E metabolism with sesamin, but not TTP knockout, increased γT tissue concentrations. TTP‐expressing and TTP‐free cells were incubated with equimolar concentrations of αT and γT (25 μmol/L each) with or without sesamin (2 μmol/L). The preferential degradation of γT independently of TTP expression was confirmed and a decrease in the production of the metabolite γ‐carboxyethyl hydroxychromanol (CEHC) with increasing TTP expression revealed. Displacing γT from TTP in these cells by incubation with increasing αT concentrations enhanced the secretion of γ‐CEHC in TTP‐transfected cells, suggesting that TTP might protect γT from β‐oxidation. CONCLUSIONS: We conclude that vitamin E metabolism and not TTP controls γT concentrations in vivo and observed an interaction of TTP with vitamin E metabolism that results in reduced production of the metabolite γ‐CEHC.
gamma-tocopherol is the major form of vitamin E in many plant seeds and in the US diet, but has drawn little attention compared with alpha-tocopherol, the predominant form of vitamin E in tissues and ...the primary form in supplements. However, recent studies indicate that gamma-tocopherol may be important to human health and that it possesses unique features that distinguish it from alpha-tocopherol. gamma-Tocopherol appears to be a more effective trap for lipophilic electrophiles than is alpha-tocopherol. gamma-Tocopherol is well absorbed and accumulates to a significant degree in some human tissues; it is metabolized, however, largely to 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), which is mainly excreted in the urine. gamma-CEHC, but not the corresponding metabolite derived from alpha-tocopherol, has natriuretic activity that may be of physiologic importance. Both gamma-tocopherol and gamma-CEHC, but not alpha-tocopherol, inhibit cyclooxygenase activity and, thus, possess antiinflammatory properties. Some human and animal studies indicate that plasma concentrations of gamma-tocopherol are inversely associated with the incidence of cardiovascular disease and prostate cancer. These distinguishing features of gamma-tocopherol and its metabolite suggest that gamma-tocopherol may contribute significantly to human health in ways not recognized previously. This possibility should be further evaluated, especially considering that high doses of alpha-tocopherol deplete plasma and tissue gamma-tocopherol, in contrast with supplementation with gamma-tocopherol, which increases both. We review current information on the bioavailability, metabolism, chemistry, and nonantioxidant activities of gamma-tocopherol and epidemiologic data concerning the relation between gamma-tocopherol and cardiovascular disease and cancer.
Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for vitamin E. In this Opinion, the Panel ...considers vitamin E as α‐tocopherol only. The Panel considers that Average Requirements (ARs) and Population Reference Intakes (PRIs) for vitamin E (as α‐tocopherol) cannot be derived for adults, infants and children, and therefore defines Adequate Intakes (AIs), based on observed intakes in healthy populations with no apparent α ‐ tocopherol deficiency in the EU. This approach considers the range of average intakes of α‐tocopherol and of α‐tocopherol equivalents estimated by EFSA from dietary surveys in children and adults in nine countries. The Panel notes the uncertainties in the available food composition and consumption data, the fact that most EU food composition databases contain values for vitamin E as α‐tocopherol equivalents, as well as the contribution of average α‐tocopherol intakes to average α‐tocopherol equivalent intakes in these countries. For adults, an AI for α‐tocopherol is set at 13 mg/day for men and 11 mg/day for women. For children aged 1 to < 3 years, an AI for α‐tocopherol is set at 6 mg/day for both sexes. For children aged 3 to < 10 years, an AI for α‐tocopherol is set at 9 mg/day for both sexes. For children aged 10 to < 18 years, an AI for α‐tocopherol is set at 13 mg/day for boys and 11 mg/day for girls. For infants aged 7–11 months, an AI for α‐tocopherol of 5 mg/day is derived by extrapolating upwards from the estimated α‐tocopherol intake in exclusively breast‐fed infants aged 0–6 months and rounding. For pregnant or lactating women, the Panel considers that there is no evidence for an increased dietary α‐tocopherol requirement, and the same AI is set as for non‐pregnant non‐lactating women.
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