Association of prenatal vitamin E levels with child asthma and wheeze.

BACKGROUND: We investigated the individual and interaction effects of maternal plasma 𝛂- and ϒ-tocopherol levels (vitamin E isomers) on child asthma and wheeze at age 8-9. METHODS: Mother-child dyads were enrolled between 2006 and 2011 into the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) prenatal cohort. Maternal second-trimester samples were analyzed for tocopherol and lipid concentrations. We assessed child asthma/wheeze using the International Study of Asthma and Allergies in Childhood (ISAAC) and other self-reported Ent wheeze. In multivariable logistic regression analyses, we assessed associations between vitamin E isomers and child asthma/wheeze outcomes (n = 847 mother-child dyads) and tested for prespecified interaction terms. RESULTS: Median cholesterol-corrected tocopherol levels (interquartile range (IQR)) were 5.0 (4.3-5.7) and 0.8 (0.7-0.9) (umol/mmol) for 𝛂- and ϒ-tocopherol, respectively. Associations between 𝛂-tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for ϒ-tocopherol, associations were in the positive direction, but also nonsignificant. Interactions analysis between tocopherols did not reach statistical significance for any outcome. Among children of women with a history of asthma, the likelihood of ever asthma in the child appears to be decreasing with increasing maternal 𝛂-tocopherol levels, whereas this trend was not observed among those without a history of asthma (p-interaction = .05). CONCLUSION: We observed no associations for prenatal 𝛂- or ϒ-tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between 𝛂-tocopherol and child asthma.

Associations of α- and γ-tocopherol during early life with lung function in childhood.

BACKGROUND: Tocopherol isoforms may regulate child lung growth and spirometric measures. OBJECTIVE: Our aim was to determine the extent to which plasma α-tocopherol (α-T) or γ-tocopherol (γ-T) isoform levels in early childhood or in utero are associated with childhood lung function. METHODS: We included 622 participants in the Project Viva cohort who had lung function at a mid-childhood visit (age 6-10 years). Maternal and child tocopherol isoform levels were measured by HPLC at the second trimester and 3 years of age, respectively. Multivariable linear regression models (adjusted for mid-childhood body mass index z scores, maternal education, smoking in pregnancy, and prenatal particulate matter with diameter of <2.5 micrometers (PM2.5) particulate exposure) stratified by tertiles of child γ-T level were used to assess the association of α-T levels with FEV1 and forced vital capacity (FVC) percent predicted. Similarly, models stratified by child α-T tertile evaluated associations of γ-T levels with lung function. We performed similar analyses with maternal second trimester tocopherol isoform levels. RESULTS: The median maternal second trimester α-T level was 63 µM (interquartile range = 47-82). The median early-childhood level was 25 µM (interquartile range = 20-33 µM). In the lowest tertile of early-childhood γ-T, children with a higher α-T level (per 10 µM) had a higher mid-childhood FEV1 percent predicted (ß = 3.09; 95% CI = 0.58-5.59 and a higher FVC percent predicted (ß = 2.77; 95% CI = 0.47-5.06). This protective association of α-T was lost at higher γ-T levels. We did not see any consistent associations of second trimester levels of either α-T or γ-T with mid-childhood FEV1 or FVC. CONCLUSION: When γ-T levels were in the lowest tertile, a higher early-childhood α-T level was associated with better lung function at mid-childhood. Second trimester maternal plasma α-T concentration was 3-fold higher than in the adult nonpregnant female population.

Alpha- and gamma-tocopherol levels in human semen and their potential functional implications.

Vitamin E is a potent antioxidant that has been considered involved in fertility, but studies have mostly focused on α-tocopherol. Our study aimed at measuring, by an isotope dilution gas chromatography-mass spectrometry method, α- and γ-tocopherol concentration in human semen in a large and well-characterised population (134 men with different semen parameters and in varicocele patients), as well as their potential role in male fertility. We carried out freeze/thaw experiments in 15 samples with the two isomers in the cryoprotective medium. Moreover, our study included 10 subjects supplemented in vivo with α-tocopherol for 90 days. In seminal plasma, γ-tocopherol concentration was significantly lower in the varicocele group than in the normozoospermic group. We observed that γ-tocopherol, supplemented to cryopreservation medium, induced a higher post-thaw human sperm viability and motility than α-tocopherol. The results of in vivo α-tocopherol supplementation showed a decrease in γ-tocopherol concentration with increasing α-tocopherol level in blood. This is the first report related to γ-tocopherol distribution in human semen analysed by gas chromatography-mass spectrometry. γ-tocopherol would not seem to be related to semen parameters but to cellular oxidative condition. This tocopherol may contribute to human health in a yet unexplored way.

Delineation of the Individual Effects of Vitamin E Isoforms on Early Life Incident Wheezing.

OBJECTIVES: To test the hypothesis that maternal plasma alpha-tocopherol levels are associated with protection from childhood wheeze and that this protection is modified by gamma-tocopherol. STUDY DESIGN: We conducted a prospective nested study in the Infant Susceptibility to Pulmonary Infections and Asthma Following Respiratory Syncytial Virus Exposure birth cohort of 652 children with postpartum maternal plasma vitamin E isoforms used as a surrogate for pregnancy concentrations. Our outcomes were wheezing and recurrent wheezing over a 2-year period, ascertained using validated questionnaires. We assessed the association of alpha- and gamma-tocopherol with wheezing outcomes using multivariable adjusted logistic regression, and tested for interaction between the isoforms with respect to the risk for wheezing outcomes. RESULTS: Children with wheezing (n = 547, n = 167; 31%) and recurrent wheezing (n = 545, n = 55; 10.1%) over a 2-year period were born to mothers with significantly lower postpartum maternal plasma concentrations of alpha-tocopherol, P = .016 and P = .007, respectively. In analyses of IQR increases, alpha-tocopherol was associated with decreased risk of wheezing (aOR 0.70 [95% CI 0.53,0.92]) and recurrent wheezing (aOR 0.63 [95% CI 0.42,0.95]). For gamma-tocopherol, the aOR for wheezing was 0.79 (95% CI 0.56-1.10) and the aOR for recurrent wheezing was 0.56 (95% CI 0.33-0.94, with nonmonotonic association). The association of alpha-tocopherol with wheezing was modified by gamma-tocopherol (P interaction = .05). CONCLUSIONS: Increases in postpartum maternal plasma alpha-tocopherol isoform concentrations were associated with decreased likelihood of wheezing over a 2-year period. Gamma-tocopherol modified this association.

Patterns of circulating fat-soluble vitamins and carotenoids and risk of frailty in four European cohorts of older adults.

PURPOSE: To investigate the cross-sectional and prospective associations between patterns of serum fat-soluble micronutrients and frailty in four European cohorts of older adults 65 years of age and older. METHODS: Participants from the Three-City (Bordeaux, France), AMI (Gironde, France), TSHA (Toledo, Spain) and InCHIANTI (Tuscany, Italy) cohorts with available data on serum α-carotene, ß-carotene, lycopene, cryptoxanthin, lutein + zeaxanthin, retinol, α-tocopherol, γ-tocopherol and 25-hydroxyvitamin D3 (25(OH)D) were included. A principal component (PC) analysis was used to derive micronutrient patterns. Frailty was defined using Fried's criteria. Multivariate logistic regression models adjusted for socio-demographic and health-related covariates were performed to assess the association between micronutrient patterns and prevalent frailty in 1324 participants, and the risk of frailty in 915 initially non-frail participants. RESULTS: Three different patterns were identified: the first pattern was characterized by higher serum carotenoids and α-tocopherol levels; the second was characterized by high loadings for serum vitamins A and E levels and low loadings for carotenes level; the third one had the highest loading for serum 25(OH)D and cryptoxanthin level and the lowest loading for vitamin A and E. A significant cross-sectional association was only observed between the seconnd PC and prevalent frailty (p = 0.02). Compared to the highest quartile, participants in the lowest quartile-i.e., high carotenes and low vitamins E and A levels-had higher odds of frailty (Odds ratio = 2.2; 95% confidence interval 1.3-3.8). No association with the risk of frailty was observed. CONCLUSIONS: These findings suggest that some specific micronutrient patterns are markers but not predictors of frailty in these European cohorts of older adults.

Association of physical activity, vitamin E levels, and total antioxidant capacity with academic performance and executive functions of adolescents.

BACKGROUND: Although various studies have shown the effect of vigorous physical activity on academic achievements, no studies have investigated the effect of vitamin E levels on academic performance. The present study aimed to assess the association between physical activity, vitamin E levels and total antioxidant capacity on the academic performance and executive functions of adolescents aged 15-18 years. METHODS: The physical activity of participants was assessed according to the time spent engaging in moderate and intense exercise programs. Participants were classified into three groups representing mild, moderate, and high activity. Serum total antioxidant capacity was measured using a colorimetric assay kit. Vitamin E was estimated by the α- and γ-tocopherol levels in fasting serum samples using high-performance liquid chromatography paired with a diode array detector. School grades (ranging from 1.0, very poor; to 10.0, outstanding) were obtained at the end of the academic year to evaluate academic performance and executive functions. RESULTS: A total of 120 school students (mean age 16.36 ± 0.77 years; 70 boys, 50 girls) participated in the study. Academic performance was higher for students classified as moderately or highly active compared with those in the mild activity group. Serum levels of vitamin E, total antioxidant capacity, and leisure-time physical activity were also higher in the moderate and high activity groups. There was a significant correlation between age, gender, body mind index, α- and γ-tocopherol, total antioxidant capacity, leisure-time physical activity and academic performance. CONCLUSIONS: The academic performance and executive function scores were found to be positively correlated with age, gender, α- and γ-tocopherol, total antioxidant capacity, and physical activity; and were negatively correlated with body mind index. Our findings indicate that physical activity should be promoted during and after school hours, along with a healthy balanced diet including vitamin E.

Shorter Time to Pregnancy With Increasing Preconception Carotene Concentrations Among Women With 1-2 Previous Pregnancy Losses.

Although maternal nutrition may affect fecundity, associations between preconception micronutrient levels and time to pregnancy (TTP) have not been examined. We assessed the relationship between preconception fat-soluble micronutrient concentrations and TTP among women with 1-2 prior pregnancy losses. This was a prospective cohort study of 1,228 women set within the Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial (United States, 2007-2011), which assessed the association of preconception-initiated daily low-dose aspirin with reproductive outcomes. We measured preconception levels of zeaxanthin, cryptoxanthin, lycopene, α- and ß-carotene, and α- and γ-tocopherol in serum. We used discrete Cox regression models, accounting for left-truncation and right-censoring, to calculate fecundability odds ratios and 95% confidence intervals. The models adjusted for age, body mass index, race, smoking, alcohol, physical activity, income, vitamin use, cholesterol, treatment arm, and study site. Serum α-carotene levels (per log unit (µg/dL) increase, fecundability odds ratio (FOR) = 1.17, 95% confidence interval (CI): 1.00, 1.36) and serum α-carotene concentrations at or above the US average (2.92 µg/dL) versus below the average (FOR = 1.21, 95% CI: 1.02, 1.44) were associated with shorter TTP. Compared with levels below the US average (187 µg/dL), γ-tocopherol concentrations at or above the average were associated with longer TTP (FOR = 0.83, 95% CI: 0.69, 1.00). The potential for these nutrients to influence fecundability deserves further exploration.

Circulating γ-Tocopherol Concentrations Are Inversely Associated with Antioxidant Exposures and Directly Associated with Systemic Oxidative Stress and Inflammation in Adults.

Background: Although α- and γ-tocopherol are co-consumed antioxidants, circulating γ-tocopherol concentrations were paradoxically found to be inversely associated with total vitamin E intake and circulating α-tocopherol concentrations. There are limited data on this apparent paradox or on determinants of circulating γ-tocopherol concentrations. Objective: To help clarify possible determinants of circulating γ-tocopherol concentrations, we investigated associations of circulating γ-tocopherol concentrations with various dietary and lifestyle factors and biomarkers of oxidative stress and inflammation. Methods: We pooled cross-sectional data from 2 outpatient, adult, elective colonoscopy populations (pooled n = 419) on whom extensive dietary, lifestyle, and medical information was collected, and the following plasma concentrations were measured: α- and γ-tocopherol (via HPLC), F2-isoprostanes (FiPs; via gas chromatography-mass spectrometry), and high-sensitivity C-reactive protein (hsCRP; via latex-enhanced immunonephelometry). Multivariable general linear models were used to assess mean γ-tocopherol differences across quantiles of plasma antioxidant micronutrients, FiPs, and hsCRP; an oxidative balance score [OBS; a composite of anti- and pro-oxidant dietary and lifestyle exposures (a higher score indicates higher antioxidant relative to pro-oxidant exposures)]; and multiple dietary and lifestyle factors. Results: Adjusted for serum total cholesterol, mean γ-tocopherol concentrations among those in the highest relative to the lowest tertiles of circulating α-tocopherol and ß-carotene, the OBS, and total calcium and dietary fiber intakes were 31.0% (P < 0.0001), 29.0% (P < 0.0001), 27.6% (P = 0.0001), 29.7% (P < 0.0001), and 18.6% (P = 0.008) lower, respectively. For those in the highest relative to the lowest tertiles of circulating FiPs and hsCRP, mean γ-tocopherol concentrations were 50% (P < 0.0001) and 39.0% (P < 0.0001) higher, respectively. Conclusions: These findings support the conclusion that circulating γ-tocopherol concentrations are inversely associated with antioxidant exposures and directly associated with systemic oxidative stress and inflammation in adults. Additional research on possible mechanisms underlying these findings and on whether circulating γ-tocopherol may serve as a biomarker of oxidative stress, inflammation, or both is needed.

Serum lipophilic antioxidants levels are associated with leucocyte telomere length among US adults.

BACKGROUND: To examine the association between serum concentrations of antioxidant and telomere length (TL) in U.S adults. METHODS: Participants of the National Health and Nutrition Examination Survey (NHANES) with data available on TL measures from 2001 to 2002 were included. Serum lipophilic antioxidants level was measured using high performance liquid chromatography with photodiode array detection. We used analysis of co-variance and multivariable-adjusted linear regression models, accounting for the survey design and sample weights. RESULTS: Of the 5992 eligible participants, 47.5% (n = 2844) were men. The mean age was 46.9 years overall, 47.2 years in men and 46.6 in women (p = 0.071). In age, sex, race, education, marital status, adiposity, smoking, C-reactive protein adjusted linear regressions, antioxidant, serum α-carotene, trans-ß-carotene, cis- ß-carotene, ß-cryptoxanthin and combined Lutein/zeaxanthin were positively and significantly associated with TL (all p < 0.001). CONCLUSIONS: Our findings support a possible positive association between serum concentrations of lipophylic antioxidant and TL. The implications of this association deserve further investigation.

Associations between serum vitamin E concentration and bone mineral density in the US elderly population.

Mixed findings regarding effects of vitamin E on bone metabolism existed. We were the first to find a negative association between serum α-tocopherol concentration and bone mineral density in the US elderly population. Using vitamin E supplement as α-tocopherol to promote bone health was not warranted at this time. INTRODUCTION: The aim of the study is to examine the associations between serum vitamin E (α-tocopherol and γ-tocopherol) status and bone mineral density (BMD) among the US elderly population. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. This cross-sectional study finally included 989 subjects who were not having liver diseases, kidney diseases, rheumatoid arthritis, or cancers; were not treated for osteoporosis; and were not taking steroids or female hormones. Multivariable linear regression models were employed to examine the associations between serum vitamin E (α-tocopherol and γ-tocopherol) concentration and BMDs of total spine and femoral neck after adjusting for covariates and potential confounders. RESULTS: Significant differences in serum α-tocopherol and γ-tocopherol levels, dietary intake of vitamin E as α-tocopherol, and BMDs of total spine and femoral neck were presented between male and female participants. Serum α-tocopherol and γ-tocopherol concentrations were found to be inversely correlated (r = -0.169, P < 0.001). In univariable linear models, significant negative associations between serum α-tocopherol and both total spine BMD (ß = -0.0014, P = 0.002) and femoral neck BMD (ß = -0.0017, P < 0.001) were found. Accounting for covariates, serum α-tocopherol level was negatively associated with femoral neck BMD (ß = -0.0007, P = 0.028). CONCLUSIONS: This study found a negative association between serum α-tocopherol concentration and femoral neck BMD in the US elderly population, suggesting a harmful effect of α-tocopherol on bone health. Future studies are warranted to further examine the dose-response relationships between individual vitamin E isomers and bone metabolism.

Serum Folate, Vitamin B-12, Vitamin A, γ-Tocopherol, α-Tocopherol, and Carotenoids Do Not Modify Associations between Cadmium Exposure and Leukocyte Telomere Length in the General US Adult Population.

Background: Leukocyte telomere length (LTL) is a biomarker of the aging process and is associated with the risk of chronic disease. Higher exposure to cadmium may be associated with shorter LTL, and adequate nutrient concentrations may be associated with longer LTL; however, the potential interaction between metals and nutrients on LTL has yet to be examined.Objectives: The objective of this study was to evaluate whether serum concentrations of vitamins and carotenoids were associated with LTL, and whether they modified the association between blood cadmium and LTL in the US NHANES (1999-2002).Methods: We evaluated cross-sectional associations between LTL and serum concentrations of vitamin A, γ-tocopherol, α-tocopherol, folate, and vitamin B-12 (1999-2002; n = 7458) and α-carotene, ß-carotene, ß-cryptoxanthin, lutein + zeaxanthin, and lycopene (2001-2002; n = 4018) in a nationally representative sample of US adults (≥20 y of age) with the use of multivariable linear regression. We further investigated whether vitamin and carotenoid concentrations modified associations between blood cadmium and LTL with models stratified by serum nutrient concentrations and the inclusion of an interaction term.Results: Blood cadmium was inversely associated with LTL (percentage of LTL difference per 1 µg/L = -3.74; 95% CI: -5.35, -2.10). Serum vitamin A was positively associated (percentage of LTL difference per 1 µg/L = 4.01; 95% CI: 0.26, 7.90) and γ-tocopherol was inversely associated (percentage of LTL difference per 1 µg/dL = -2.49; 95% CI: -4.21, -0.73) with LTL. Serum folate (P-trend = 0.06) and α-tocopherol (P-trend = 0.10) were marginally positively associated with LTL, whereas vitamin B-12 (P-trend = 0.78) was not associated with LTL. Serum carotenoids were generally positively associated with LTL. Serum vitamin and carotenoid concentrations did not modify blood cadmium and LTL associations (P-interaction > 0.10).Conclusions: Results from this cross-sectional study suggest that exposure to cadmium and certain nutrients may be associated with LTL in US adults, but the serum concentrations of the vitamins and carotenoids evaluated did not modify cross-sectional associations between cadmium exposure and LTL.

Interaction of vitamin E isoforms on asthma and allergic airway disease.

Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population-based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms α-tocopherol and γ-tocopherol on asthma risk. Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of α-tocopherol and γ-tocopherol isoforms in mice on the outcome of allergic airway inflammation. We found that in the highest γ-tocopherol tertile, low levels of α-tocopherol were associated with increased asthma risk, while highest tertile α-tocopherol levels trended to be protective. Similarly, in a mouse model of asthma, diet supplementation with α-tocopherol decreased lung inflammation in response to house dust mite (HDM) challenge. In contrast, diet supplementation with γ-tocopherol increased lung inflammation in response to HDM. These human and animal studies provide evidence for the competing effects of the vitamin E isoforms, in physiological concentrations, on asthma and allergic airway disease.

Circulating interleukin-6 is not altered while γ-tocopherol is increased in subjects scheduled for knee surgery with low vitamin D.

The purpose of this study was to identify if circulating interleukin (IL)-6 and γ-tocopherol (γT) fluctuate with vitamin D status in subjects with an underlying knee joint injury or disease. We hypothesized that low vitamin D associates with an increase in plasma γT while serum IL-6 remains unchanged in subjects with an underlying knee joint trauma or disease. Fifty-four subjects scheduled to undergo primary, unilateral anterior cruciate ligament reconstructive surgery (ACL; n=27) or total knee arthroplasty (TKA; n=27) were studied. Circulating γT, α-tocopherol (αT), lipids (cholesterol and triglycerides), IL-6, and 25-hydroxyvitamin D (25(OH)D) were measured in fasting blood samples obtained prior to surgery. Subjects were classified as vitamin D deficient, insufficient, or sufficient if they had a serum 25(OH)D concentration <50, 50-75, or >75nM, respectively. The majority (57%) of the subjects possessed a serum 25(OH)D less than 50nM. Circulating cholesterol, triglycerides, and IL-6 were not significantly (all p>0.05) different between vitamin D status groups. However, lipid corrected αT was significantly (p<0.05) decreased and both lipid- and non-lipid-corrected plasma γT concentrations were significantly (both p<0.05) increased with low serum 25(OH)D (i.e., <50nM). A significant (p<0.05) multi-variate analysis revealed that an increase in plasma γT per lipids was significantly (p<0.05) predicted by a decrease in serum 25(OH)D but not by a decrease in plasma αT per lipids. We conclude that low vitamin D associates with an increase in plasma γT but not IL-6 in subjects with an underlying joint injury or disease.

Vitamin E homologues α- and γ-tocopherol are not associated with bone turnover markers or bone mineral density in peri-menopausal and post-menopausal women.

UNLABELLED: In a large cohort of older women, we investigated the relationships that different forms of vitamin E may have with bone turnover markers and bone mineral density (BMD). We found a suggestive positive association between serum alpha-tocopherol and BMD at the femoral neck, but no other clinically relevant observations. INTRODUCTION: Vitamin E has anti-oxidant and anti-inflammatory properties hypothesized to benefit bone, but limited studies exist regarding its homologues. We examined circulating and dietary α- and γ-tocopherols with bone turnover markers (BTMs) and bone mineral density (BMD), and the role of inflammation in this relationship. METHODS: We performed two cross-sectional analyses from two visits (V2, 1997-1999, n = 3883; V3, 2007-2011, n = 2130) of the Aberdeen Prospective Osteoporosis Screening Study. Dietary and supplement intakes by food frequency questionnaire were assessed at both visits. V2 BTMs (urinary free pyridinoline and deoxypyridinoline, serum N-terminal propeptide of type 1 collagen) and V3 serum α- and γ-tocopherols, inflammatory markers (interleukin-6 [IL-6], serum amyloid A [SAA], high-sensitivity C-reactive protein [hs-CRP], E-selectin) and dual X-ray absorptiometry BMD at the femoral neck and lumbar spine were collected. Food sources of tocopherol homologues and diet-serum correlations were determined. The relationships between dietary tocopherols and BTMs (V2), and dietary and serum tocopherols with BMD (V3) were examined by multivariable regression (adjusting for age, cholesterol, inflammatory markers, carotenoids, body mass index, physical activity level, alcohol intake, smoking status and national deprivation category). RESULTS: Serum γ-tocopherol was associated with increasing concentrations of hs-CRP, SAA and E-selectin (P-trend all <0.0001), while α-tocopherol was associated with decreasing concentrations of IL-6 and hs-CRP (P-trend all <0.001). Controlling for covariates, serum α-tocopherol was positively associated with BMD at the femoral neck (ß = 0.002, P = 0.04) among those not reporting vitamin E supplementation. CONCLUSION: We did not find biologically meaningful results between dietary and tocopherol homologues with BTMs or BMD.

Serum Antioxidants Are Associated with Serum Reproductive Hormones and Ovulation among Healthy Women.

BACKGROUND: Evidence is growing that the equilibrium between reactive oxygen species and antioxidants plays a vital role in women's reproductive health. OBJECTIVE: The objective of this study was to evaluate variations in serum antioxidant concentrations across the menstrual cycle and associations between antioxidants and reproductive hormones and anovulation among healthy women. METHODS: The BioCycle Study, a prospective cohort, followed 259 women aged 18-44 y for up to 2 menstrual cycles. Serum fat-soluble vitamin and micronutrient (α-tocopherol, γ-tocopherol, retinol, lutein, lycopene, and ß-carotene), ascorbic acid, and reproductive hormone concentrations were measured 5-8 times/cycle. We used weighted linear mixed models to assess associations between antioxidants and hormone concentrations, after adjustment for age, race, body mass index, parity, sleep, pain medication use, total energy intake, concurrent hormones, serum cholesterol, F2-isoprostanes, and other antioxidants. Generalized linear models were used to identify associations with anovulation. RESULTS: Serum antioxidant concentrations varied across the menstrual cycle. Retinol and α-tocopherol were associated with higher estradiol [RR: 1.00 pg/mL (95% CI: 0.67, 1.34 pg/mL); RR: 0.02 pg/mL (95% CI: 0.003, 0.03 pg/mL), respectively] and testosterone [RR: 0.61 ng/dL (95% CI: 0.44, 0.78 ng/dL); RR: 0.01 ng/dL (95% CI: 0.001, 0.01 ng/dL), respectively]. Ascorbic acid was associated with higher progesterone (RR: 0.15 ng/mL; 95% CI: 0.05, 0.25 ng/mL) and with lower follicle-stimulating hormone (RR: -0.06 mIU/mL; 95% CI: -0.09, -0.03 mIU/mL). The ratio of α- to γ-tocopherol was associated with an increased risk of anovulation (RR: 1.03; 95% CI: 1.01, 1.06). CONCLUSIONS: These findings shed new light on the intricate associations between serum antioxidants and endogenous hormones in healthy premenopausal women and support the hypothesis that concentrations of serum vitamins affect steroidogenesis even after adjustment for oxidative stress.

A Plasma α-Tocopherome Can Be Identified from Proteins Associated with Vitamin E Status in School-Aged Children of Nepal.

BACKGROUND: The term vitamin E describes a family of 8 vitamers, 1 of which is α-tocopherol, that is essential for human health. Vitamin E status remains largely unknown in low-income countries because of the complexity and cost of measurement. Quantitative proteomics may offer an approach for identifying plasma proteins for assessing vitamin E status in these populations. OBJECTIVE: To improve options for vitamin E status assessment, we sought to detect and quantify a set of plasma proteins associated with α- and γ-tocopherol concentrations in a cohort of 500 rural Nepalese children aged 6-8 y and, based on nutrient-protein associations, to predict the prevalence of vitamin E deficiency (α-tocopherol <12 µmol/L). METHODS: Study children were born to mothers enrolled in an earlier antenatal micronutrient trial in Sarlahi District, Nepal. Plasma α- and γ-tocopherol concentrations were measured by high-performance liquid chromatography. Plasma aliquots were depleted of 6 high-abundance proteins, digested with trypsin, labeled with isobaric mass tags, and assessed for relative protein abundance by tandem mass spectrometry. Linear mixed-effects models were used to evaluate the association between α-tocopherol status and relative protein abundance and to predict deficiency. RESULTS: We quantified 982 plasma proteins in >10% of all child samples, of which 119 correlated with α-tocopherol (false discovery rate, q < 0.10). Proteins were primarily involved in lipid transport, coagulation, repair, innate host defenses, neural function, and homeostasis. Six proteins [apolipoprotein (apo)C-III; apoB; pyruvate kinase, muscle; forkhead box 04; unc5 homolog C; and regulator of G-protein signaling 8] explained 71% of the variability in plasma α-tocopherol, predicting an in-sample population prevalence of vitamin E deficiency of 51.4% (95% CI: 46.4%, 56.3%) compared with a measured prevalence of 54.8%. Plasma γ-tocopherol was associated with 12 proteins (q < 0.10), 2 of which (apoC-III and Misato 1) explained 20% of its variability. CONCLUSIONS: In this undernourished population of children in South Asia, quantitative proteomics identified a large plasma α-tocopherome from which 6 proteins predicted the prevalence of vitamin E deficiency. The findings illustrate that protein biomarkers, once absolutely quantified, can potentially predict micronutrient deficiencies in populations. The maternal micronutrient supplementation trial from which data were derived as a follow-up activity was registered with clinicaltrials.gov as NCT00115271.

Serum α-Tocopherol Has a Nonlinear Inverse Association with Periodontitis among US Adults.

BACKGROUND: Previous experimental models suggest that vitamin E may ameliorate periodontitis. However, epidemiologic studies show inconsistent evidence in supporting this plausible association. OBJECTIVE: We investigated the association between serum α-tocopherol (αT) and γ-tocopherol (γT) and periodontitis in a large cross-sectional US population. METHODS: This study included 4708 participants in the 1999-2001 NHANES. Serum tocopherols were measured by HPLC and values were adjusted by total cholesterol (TC). Periodontal status was assessed by mean clinical attachment loss (CAL) and probing pocket depth (PPD). Total periodontitis (TPD) was defined as the sum of mild, moderate, and severe periodontitis. All measurements were performed by NHANES. RESULTS: Means ± SDs of serum αT:TC ratio from low to high quartiles were 4.0 ± 0.4, 4.8 ± 0.2, 5.7 ± 0.4, and 9.1 ± 2.7 µmol/mmol. In multivariate regression models, αT:TC quartiles were inversely associated with mean CAL (P-trend = 0.06), mean PPD (P-trend < 0.001), and TPD (P-trend < 0.001) overall. Adjusted mean differences (95% CIs) between the first and fourth quartile of αT:TC were 0.12 mm (0.03, 0.20; P-difference = 0.005) for mean CAL and 0.12 mm (0.06, 0.17; P-difference < 0.001) for mean PPD, whereas the corresponding OR for TPD was 1.65 (95% CI: 1.26, 2.16; P-difference = 0.001). In a dose-response analysis, a clear inverse association between αT:TC and mean CAL, mean PPD, and TPD was observed among participants with relatively low αT:TC. No differences were seen in participants with higher αT:TC ratios. Participants with γT:TC ratio in the interquartile range showed a significantly lower mean PPD than those in the highest quartile. CONCLUSIONS: A nonlinear inverse association was observed between serum αT and severity of periodontitis, which was restricted to adults with normal but relatively low αT status. These findings warrant further confirmation in longitudinal or intervention studies.

α-Tocopherol Stereoisomers in Human Plasma Are Affected by the Level and Form of the Vitamin E Supplement Used.

BACKGROUND: Studies examining vitamin E intake and the percentage of the population meeting dietary guidelines do not distinguish between natural (RRR-α-tocopherol) and synthetic (all-rac-α-tocopherol) intake, even though these different isomeric forms differ in bioactivity. OBJECTIVE: This study aimed to determine the effect of RRR-α-tocopherol vs. all-rac-α-tocopherol intake on the percentage of the population meeting the vitamin E recommendation and on plasma α-tocopherol stereoisomer distribution. METHODS: With the use of data from the Irish National Adult Nutrition Survey (NANS), this study examined the percentage of the Irish population meeting the European Union (EU) RDA for vitamin E of 12 mg/d, correcting for a bioactivity difference in all-rac- vs. RRR-α-tocopherol, where 1 mg of all-rac-α-tocopherol is considered to be equivalent to 1:1.36 (0.74) mg in the EU RDA. In a subcohort of supplement users and nonusers, plasma α- and γ-tocopherol concentrations and α-tocopherol stereoisomer distribution were measured. Receiver operating characteristic (ROC) curve analysis was conducted to determine ability to discriminate supplement user types. RESULTS: Analysis of the NANS showed that 100% of participants still met the recommended intake of 12 mg/d, after all-rac-α-tocopherol intake was corrected for α-tocopherol equivalent bioactivity. In the subcohort analysis, the percentage of plasma RRR-α-tocopherol was significantly lower in high all-rac-α-tocopherol supplement (>11 mg/d) users (82%) compared with nonusers and with high RRR-α-tocopherol supplement (>35 mg/d) users (91% and 93% respectively, P < 0.01). High RRR-α-tocopherol supplement users had a significantly higher plasma α-tocopherol than low all-rac-α-tocopherol supplement (<2.5 mg/d) users (34 vs. 25 µmol/L, P = 0.01). ROC analysis demonstrated an ability to distinguish between RRR- and all-rac-α-tocopherol consumers, which may be useful in investigating the potential effect of RRR- and all-rac-α-tocopherol intake on health. CONCLUSIONS: This study demonstrated that the percentage of the population meeting the vitamin E recommendation was unaffected when all-rac-α-tocopherol intake was corrected for α-tocopherol equivalent bioactivity. all-rac-α-Tocopherol intake led to a decrease in the percentage of plasma RRR-α-tocopherol relative to RRR-α-tocopherol intake.

Effects of vitamin E from supplements and diet on colonic α- and γ-tocopherol concentrations in persons at increased colon cancer risk.

The available evidence indicates that γ-tocopherol has more potential for colon cancer prevention than α-tocopherol, but little is known about the effects of foods and supplements on tocopherol levels in human colon. This study randomized 120 subjects at increased colon cancer risk to either a Mediterranean or a Healthy Eating diet for 6 mo. Supplement use was reported by 39% of the subjects, and vitamin E intake from supplements was twofold higher than that from foods. Serum α-tocopherol at baseline was positively predicted by dietary intakes of synthetic vitamin E in foods and supplements but not by natural α-tocopherol from foods. For serum γ-tocopherol, dietary γ-tocopherol was not a predictor, but dietary α-tocopherol was a negative predictor. Unlike with serum, the data supported a role for metabolic factors, and not a direct effect of diet, in governing concentrations of both α- and γ-tocopherol in colon. The Mediterranean intervention increased intakes of natural α-tocopherol, which is high in nuts, and decreased intakes of γ-tocopherol, which is low in olive oil. These dietary changes had no significant effects on colon tocopherols. The impact of diet on colon tocopherols therefore appears to be limited.

Adherence to cancer prevention recommendations and antioxidant and inflammatory status in premenopausal women.

For cancer prevention, the World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) emphasise recommendations to improve individual behaviour, including avoidance of tobacco products, maintaining a lean body mass, participating in physical activity, consuming a plant-based diet, and minimising the consumption of energy-dense foods, such as sodas, red and processed meats and alcohol. In the present study of 275 healthy premenopausal women, we explored the association of adherence scores with levels of three biomarkers of antioxidant and inflammation status: serum C-reactive protein (CRP), serum γ-tocopherol and urinary F2-isoprostane. The statistical analysis applied linear regression across categories of adherence to WCRF/AICR recommendations. Overall, seventy-two women were classified as low ( ≤ 4), 150 as moderate (5-6), and fifty-three as high adherers ( ≥ 7). The unadjusted means for CRP were 2.7, 2.0 and 1.7 mg/l for low, moderate and high adherers (P trend= 0.03); this association was strengthened after adjustment for confounders (P trend= 0.006). The respective values for serum γ-tocopherol were 1.97, 1.63 and 1.45 µg/ml (P trend= 0.02 before and P trend= 0.03 after adjustment). Only for urinary F2-isoprostane, the lower values in high adherers (16.0, 14.5, and 13.3 ng/ml) did not reach statistical significance (P trend= 0.18). In an analysis by BMI, overweight and obese women had higher biomarker levels than normal weight women; the trend was significant for CRP (P trend< 0.001) and γ-tocopherol (P trend= 0.003) but not for F2-isoprostane (P trend= 0.14). These findings suggest that both adherence to the WCRF/AICR guidelines and normal BMI status are associated with lower levels of biomarkers that indicate oxidative stress and inflammation.