Plasma Alpha-tocopherol Concentrations Research Articles

Multivitamin and mineral supplementation modulates oxidative stress and antioxidant vitamin levels in serum and follicular fluid of women undergoing in vitro fertilization

We investigated effects of multivitamin and mineral supplementation on lipid peroxidation, reduced glutathione, glutathione peroxidase, vitamin A, vitamin C and vitamin E values in serum and follicular fluid of 56 women undergoing IVF and 13 age matched control. We concluded that multivitamin and mineral supplementation in serum and follicular fluid of women undergoing IVF may strengthen the antioxidant defense system by decreasing oxidative stress.

Modulation of ozone-sensitive genes in alpha-tocopherol transfer protein null mice

Alpha-tocopherol transfer protein (ATTP) null mice (ATTP−/−) have a systemic alpha-tocopherol (AT) deficiency, with their lung AT levels being < 10% of those in AT-replete ATTP+/+ mice when fed a standard rodent chow diet. ATTP+/+ and ATTP−/− mice (4 wk old male mice, n = 16 per group) were fed a standard diet (35 IU AT/kg diet) for 8–12 wk, exposed 6 h/day for 3 days to either to O3 (0.5 ppm) or filtered air, then sacrificed. No significant differences in plasma or lung AT concentrations were observed in response to this level of O3 exposure. Lung genomic responses of the lungs to O3 were determined using Affymetrix 430A 2.0 arrays containing over 22,600 probe sets representing 14,000 well-characterized mouse genes. As compared with filtered air exposure, O3 exposure resulted in 99 genes being differentially expressed in ATTP−/− mice, as compared to 52 differentially expressed genes in ATTP+/+ mice. The data revealed an O3-induced upregulation of genes related to cell proliferation/DNA repair and inflammatory-immune responses in both ATTP+/+ and ATTP−/− mice, with the expression of 22 genes being common to both, whereas 30 and 77 genes were unique to ATTP+/+ and ATTP−/− mice, respectively. The expressions of O3 sensitive genes—Timp1, Areg, Birc5 and Tnc—were seen to be further modulated by AT status. The present study reveals AT modulation of adaptive response of lung genome to O3 exposure.

Evaluation of Factors Contributing to Daily Within-Horse Variation of Plasma Alpha-Tocopherol Concentration

The current study was conducted to evaluate daily within-horse variation of plasma alpha-tocopherol concentration (TOC) (Experiment 1 [EXPT1]) and to determine the effect of a single meal on plasma TOC (Experiment 2 [EXPT2]). In EXPT1, venous jugular blood samples were collected from four pregnant (6–7 months of gestation), light horse mares (8.8 ± 2.9 years of age, mean ± SD; range, 5–11 years of age) between 7:30 AM and 8:30 AM, followed by eight hourly samples, and analyzed for plasma TOC. All horses were fed 5 kg dry matter (DM) grass hay 18 hours before sample collection and received no additional feed during the sampling period. Mean within-horse coefficient of variation for TOC was 3.5% ± 0.01%. In EXPT2, seven mature light horses, four mares and three geldings (4.9 ± 4.4 years of age, mean ± SD; range, 2–14 years of age), were randomly assigned to one of two treatments (fasted [FST; n = 7] or fed [FD; n = 7]), followed by reversal of treatments 24 hours later. At 7:30 AM, FD horses were fed 2.1 kg DM grain-mix concentrate (187 IU vitamin E/kg DM) plus 3.3 kg DM mixed-grass hay, whereas FST horses received no feed. Neither group received any feed for 18 hours before 7:30 AM. Venous jugular blood samples were collected at 10:30 AM from all horses and analyzed for plasma TOC. The mean (±SD) within-horse paired-treatment difference was not significant (0.05 ± 0.12 μg/mL). The results suggest that variation in within-horse plasma TOC is relatively small over an 8-hour period in fasting horses and is unaffected 3 hours after a hay grain meal.

Plasma .ALPHA.-Tocopherol is Negatively Correlated with Hepatocyte Apoptosis in Chronic Hepatitis B Patients

Hepatocyte apoptosis is involved in the pathogenesis of liver diseases, while at the same time oxidative stress plays an important role in liver cell damage. This prompted us to evaluate the possible relationship between hepatocyte apoptosis and oxidative stress in patients with chronic hepatitis B. CHB patients were placed in groups A (ALT >40 IU/L) and B (ALT <or=40 IU/L). Healthy controls were considered as group C (all ALT <or=40 IU/L). Serum concentrations of alpha-tocopherol, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were determined and liver cell apoptosis was evaluated by using terminal deoxynucleotydil transferase-mediated d-UTP biotin nick-end labeling (TUNEL). SOD, GSH-Px, and MDA did not differ between groups. alpha-Tocopherol was significantly decreased in groups A (p<0.01) and B (p<0.05) when compared with group C and it was negatively correlated with the apoptosis index (r=-0.575, p<0.01). Only the plasma concentration of alpha-tocopherol rather than the other oxidative stress markers changed significantly in patients with normal alanine aminotransferase levels (ALT <40 IU/L) when compared with healthy controls and correlated significantly with the apoptosis index, suggesting that alpha-tocopherol may be a possible marker to reflect liver cell damage, especially in the absence of serum aminotransferase elevation.

Alpha-Tocopherol in Captive Falcons: Reference Values and Dietary Impact

To determine reference values for plasma alpha-tocopherol concentrations in falcons and to investigate a possible dietary impact, 29 falcons were randomly selected from a collection of 500 captive breeding falcons fed with 4-week-old chicks. Blood samples collected from each falcon were analyzed for plasma alpha-tocopherol concentrations. Reference values were 16.7-46.1 mg/L with a mean plasma alpha-tocopherol concentration of 27.5 +/- 8.7 mg/L. A group of 5 gyr-saker falcon hybrids (Falco rusticolus x Falco cherrug) were fed 1-day-old chicks for 4 weeks; the resultant mean plasma alpha-tocopherol concentration was 34.9 +/- 5.6 mg/L. When the diet was changed to turkey breast meat for 4 weeks, the mean plasma alpha-tocopherol concentration decreased significantly to 13.1 +/- 2.6 mg/L. Results appeared to support the influence of diet on plasma alpha-tocopherol concentrations in falcons.

Plasma vitamins E and A and risk of bladder cancer: a case–control analysis

Current results on the association between serum micronutrients and bladder cancer risk have been inconsistent. We assessed plasma vitamin E (alpha-tocopherol, and gamma-tocopherol), vitamin A (retinol), and bladder cancer risk using data collected from a case-control study. Epidemiologic data were collected via in-person interview. Plasma concentrations of alpha-tocopherol, gamma-tocopherol, and retinol were determined by a high-performance liquid chromatography assay. Multivariate logistic regression analyses were used to estimate bladder cancer risk in association with plasma vitamins E and A. 386 bladder cancer patients and 389 age-, gender-, and ethnicity-matched controls were included in the study. The mean plasma alpha-tocopherol and retinol were significantly lower in cases than in controls (alpha-tocopherol: 23.93 microg/ml vs. 27.48 microg/ml, P < 0.001; retinol: 1.41 microg/ml vs. 1.53 microg/ml, P < 0.001). There was a significant reduction in bladder cancer risk associated with increasing plasma alpha-tocopherol level (Adjusted OR: 0.91; 95% CI: 0.85-0.97). In quartile analysis, using subjects with the lowest alpha-tocopherol level as the reference group, the adjusted ORs and 95% CIs for the second, third, and fourth quartiles were 0.75 (0.50-1.14), 0.69 (0.46-1.05), and 0.50 (0.32-0.78), respectively (P for trend = 0.003). Increased retinol level was also associated with reduced risk with OR of 0.57 (95% CI: 0.40-0.81). The ORs and 95% CIs for the second, third, and fourth quartiles were 0.92 (0.61-1.39), 0.66 (0.43-1.01), and 0.62 (0.40-0.95), respectively, with significant dose-response trend (P for trend = 0.01). Finally, there were significant correlations between plasma levels and dietary intakes for the three micronutrients. Our results suggest potential protective effect of alpha-tocopherol and retinol on bladder cancer risk. Future large prospective studies are needed to confirm the findings.

An evaluation of natural (RRR-α-tocopheryl acetate) and synthetic (all-rac-α-tocopheryl acetate) vitamin E fortification in the diet or drinking water of weanling pigs1,2,3

Three experiments conducted with weanling pigs evaluated the effects of vitamin E added to the drinking water or diet on plasma and tissue alpha-tocopherol concentrations. When natural or synthetic vitamin E was used, it was added at an IU-equivalent basis, but natural vitamin E was 73.5% (mg basis) of the synthetic vitamin E. Experiment 1 used 18-d-old weanling pigs (n = 120) in a 3 x 2 factorial arrangement of treatments in a randomized complete block design with 4 replicates. The first factor evaluated the dietary levels of natural vitamin E (RRR-alpha-tocopheryl acetate) added at 0, 50, or 300 IU/kg, whereas the second factor was the natural vitamin E added to the drinking water at 0 or 100 IU/L. Pigs were bled at periodic intervals, and 1 pig per pen was killed at the end of the 21-d trial and tissues (liver, heart, lung, and loin) were collected for alpha-tocopherol analysis. When vitamin E was not added to the diet or water, plasma alpha-tocopherol declined over the 21-d period. Although there were some interactions (P < 0.01), tissue and plasma alpha-tocopherol concentrations increased linearly when vitamin E was added to the diet or water. Experiment 2 was a 3 x 2 factorial in a randomized complete block design with 4 replicates. A total of 96 pigs weaned at 18 d of age, with an initial BW of 6.2 kg, were fed a nonvitamin E fortified diet, but natural or synthetic (all-rac-alpha-tocopheryl acetate) vitamin E was added to their drinking water at 50, 100, or 150 IU/L. Pigs were bled at 0, 3, 7, 10, 14, and 21 d postweaning, with tissues (liver, lung, heart, and loin) collected for alpha-tocopherol analysis at d 21. The results indicated that plasma alpha-tocopherol concentrations increased (P < 0.01) as vitamin E increased, with greater tissue alpha-tocopherol concentrations (P < 0.01) when natural vitamin E was provided. Experiment 3 was conducted in 2 replicates, but pigs (n = 60) were not provided vitamin E in the diet or water for 7 d postweaning, and then natural or synthetic vitamin E was added to the drinking water as in Exp. 2 (50, 100, or 150 IU/L). Pigs were bled at 0, 2, 4, 6, 8, 10, and 24 h after being provided vitamin E to evaluate the absorption from each vitamin E source and level. Plasma alpha-tocopherol increased quadratically (P < 0.01) and plateaued at 8 to 10 h for each treatment group. These results indicate that adding vitamin E to the pig's water supply at weaning was more effective in increasing plasma alpha-tocopherol than when it was added to the diet during the initial 14 d postweaning, and that natural vitamin E was a superior source compared with synthetic vitamin E.

Effects of vitamin E on cholesterol levels of hypercholesterolemic patients receiving statins

The effects of vitamin E supplementation on the cholesterol levels of hypercholesterolemic patients receiving statin therapy were studied. In this prospective, single-blind, placebo-controlled, randomized trial, patients who were currently taking either lovastatin or simvastatin for a primary diagnosis of hypercholesterolemia were given placebo for two weeks and then randomized to receive a supplement of either 400 IU of vitamin E or matching placebo after dinner for eight weeks, followed by a two-week washout period. Vitamin E supplementation increased plasma alpha-tocopherol concentrations approximately 1.6-fold and increased excretion of its urinary metabolite 4-fold significantly from week 2 to week 6 (p < 0.001 for both comparisons). During the eight-week supplementation period, no statistically significant differences in any lipoprotein cholesterol fraction were detected between groups; however, a 6% decrease in high-density-lipoprotein (HDL) cholesterol was detected within the vitamin E group from week 2 to week 6 (p < 0.05), but the decrease was not sufficient to change the cardiac risk ratio. Neither cytochrome P-450 isoenzyme (CYP) 3A (as measured by hydroxylation of urinary cortisol) nor cholesteryl ester transfer protein (CETP) activity was significantly altered during the study. Vitamin E supplementation did not affect total or low-density-lipoprotein cholesterol levels in hypercholesterolemic patients receiving lovastatin or simvastatin. A small but significant decrease in HDL cholesterol levels was observed in the group that received vitamin E supplementation during the supplementation period, but this decrease was no longer significantly different from the placebo group's levels two weeks postsupplementation. The decrease in HDL cholesterol levels did not appear to be related to either CYP3A or CETP.

Dietary intakes and plasma concentrations of tocopherols of 2‐6 y old children in Republic of Korea

To determine dietary intakes and plasma concentrations of tocopherols and to evaluate vitamin E status of Korean children, three consecutive 24-h food recalls and fasting blood samples were obtained from healthy children (n=131, 66 girls and 65 boys), aged 2–6 y, living in Kwangju, Republic of Korea. Twenty-one subjects were aged 2 y; 25, 3 y; 31, 4 y; 32, 5 y; and 22, 6 y. Dietary kcal, total fat, monounsaturated and polyunsaturated fat, but not saturated fat, were significantly different (P<0.05) among the age groups, but not by gender. Alpha-tocopherol intakes, but not gamma- and delta-tocopherol, for the 3 y age group were significantly different (P<0.05) from those of other groups. Sixty-seven percent consumed less than the Adequate Intakes for vitamin E of the Republic of Korea. Seventy-six percent of the subjects had alpha-tocopherol intakes less than the US/Canadian Estimated Average Requirements for vitamin E. Plasma alpha-tocopherol concentrations, but not gamma- or delta- tocopherol, were significantly higher (P<0.05) for the 2 y group as compared to other age groups; plasma tocopherol concentrations were similar by gender. Two-thirds of the subjects had plasma alpha-tocopherol concentrations less than 12 μmol/L, which is indicative of vitamin E inadequacy. Many of these Korean children had inadequate vitamin E status. Supported by the University of Nebraska Agricultural Research Division.

Plasma and dietary vitamin E in relation to insulin secretion and sensitivity

In the Insulin Resistance and Atherosclerosis Study (IRAS), we have previously shown a protective effect of plasma alpha-tocopherol concentration against diabetes incidence among persons not taking vitamin E supplements. The biologic mechanism for such a protective effect could involve improvement in either insulin sensitivity (S(I)), insulin secretion or both. Thus, we examined vitamin E in relation to insulin secretion and S(I) among persons not taking vitamin E supplements. This analysis included 457 adults aged 40-69 years without a previous diabetes diagnosis or vitamin E supplement use at baseline and seen at the 5-year follow-up examination. Baseline nutrient intake was estimated from a validated 1-year food frequency questionnaire; plasma levels of alpha-tocopherol were also assessed. At follow up, a frequently sampled intravenous glucose tolerance test determined S(I), acute insulin response to glucose (AIR), and the disposition index (DI) was calculated as the sum of the log-transformed AIR and S(I) to reflect pancreatic compensation for insulin resistance. In multivariable regression analyses, no relationship was observed for vitamin E intake and either S(I), AIR or DI. However, plasma alpha-tocopherol concentration was positively associated with log-transformed S(I) (beta= 0.27 +/- 0.09, p < 0.01) and DI (beta= 0.41 +/- 0.14, p < 0.01), but not with log-transformed AIR. Plasma concentration of alpha-tocopherol may improve S(I) and pancreatic compensation for insulin resistance, although it does not seem to be related to acute insulin response.

Vitamin E: maternal concentrations are associated with fetal growth

Few data exist on the effects of the 2 most abundant isomers of vitamin E (alpha- and gamma-tocopherols) on fetal growth. We measured maternal plasma concentrations of alpha- and gamma-tocopherols and examined their relation with measures of fetal growth. We also examined the relation, controlled for associated maternal factors, of diet and supplement use to tocopherol concentrations at week 28 of gestation. A cohort of 1231 gravid women from Camden, NJ, was studied from entry to care (16.0 +/- 0.15 wk gestation); plasma tocopherol concentrations were measured at entry and at week 28. Plasma concentrations of alpha-tocopherol at entry and at week 28 were positively related to increased fetal growth (birth weight for gestation), a decreased risk of small-for-gestational-age births, and an increased risk of large-for-gestational-age births. Concentration of alpha-tocopherol at week 28 was positively related to use of prenatal multivitamins and dietary intake of vitamin E; concentration of gamma-tocopherol was related positively to dietary fat intake and negatively to multivitamin use. Early and late circulating concentrations of alpha-tocopherol are positively associated with fetal growth.

High dietary alpha tocopherol improves attention deficit/hyperactivity (ADHD)‐like behavior in juvenile spontaneously hypertensive rats (SHR)

The juvenile SHR, a widely used animal model for ADHD, was previously shown to have low levels of alpha tocopherol (AT) in plasma and brain compared to Sprague-Dawley (SD) rats on the same diet. In this study we asked if AT levels are related to the behavior abnormalities associated with ADHD (inattention, hyperactivity, and impulsivity), using measures previously shown to distinguish these behaviors. Because AT might affect behavior by protection of important brain PUFAs such as arachidonic and docosahexaenoic acids (AA and DHA), fatty acid analysis was also done. Three groups of SHR (n=8 each) were fed synthetic AIN93 diets containing, respectively, 0, 50 and 250 U/kg AT acetate, and 8 SD rats were given the 50 U/kg AT diet. The diets were fed ad libitum from the age of 4 weeks. Behavior testing was done from 8 weeks to 12 weeks in conditioning cages equipped with infrared monitors. The animals were killed at 12 weeks. AT concentrations in plasma of SHRs increased with increasing dietary AT (1.47 ± 0.64, 56.3 ± 6.39, 69.4 ± 12.8 μM), approaching that of SDs (71.0 ± 12.1 μM). AT concentrations in brain followed a similar pattern (5.49 ± 0.54, 14.5 ± 0.69, 17.2 ± 1.06 μg/g compared to 18.6 ± 2.00 μg/g). Total n-3 PUFA in SHR plasma and the AA + DHA sum in SHR brain also increased in response to dietary AT. SHR behavior showed significant effects of dietary treatment. Measures of learning (attention), inhibition, and impulsivity improved with increasing AT. Total activity was not reduced by AT. Replenishment of AT in the SHR can improve behavior. Supported by the Purdue Research Foundation.

Estimate of antioxidant capacity and lipid peroxidation in plasma of healthy subjects

Abstract Serum contains various antioxidant molecules that may provide important protection against free radical attack. The aim of this work was to assess the total antioxidant capacity of plasma and a marker of lipid per oxidation [(thiobarbituric acid-reactive substances (TBARS)] in plasma of healthy smoking and non-smoking young and elderly subjects. In addition, we investigated plasma concentrations of α-tocopherol, β-carotene, and ascorbic acid. In in vitro experiments, the effects of exogenous compounds (ascorbic acid, uric acid, Trolox) on total ferric-reducing activity of plasma (FRAP) were also tested. We demonstrated that total antioxidant capacity of plasma obtained from healthy non-smoking young subjects was significantly higher than plasma antioxidant capacity of smoking elderly subjects. The concentration of TBARS in young non-smoking volunteers was lower than that in young smokers. The concentration of TBARS in elderly non-smoking volunteers was lower than in elderly smokers. Plasma concentrations of alpha-tocopherol, beta-carotene and ascorbic acid were significantly lower in elderly smoker than in elderly non-smokers of the same age. No difference in the plasma levels of alpha-tocopherol, beta-carotene and ascorbic acid were found in 22-year-old smoking and non-smoking subjects. In vitro addition of ascorbic acid, uric acid, or Trolox to plasma samples significantly increased their total antioxidant capacity. Decrease of FRAP values and increase of TBARS concentrations is a significant physiologic condition of the aging process. Supplementation of antioxidants could be useful for the enhancement of antioxidant screen in plasma.

Recent advances in vitamin E metabolism and deficiency

Alpha-, beta-, gamma- and delta-tocopherol are present in many foods and are, in the absence of fat malabsorption, well absorbed from the gut. Their anti-oxidant property is well known and protects arteries and capillaries as well as blood lipids and nervous tissue against oxidative stress. In contrast to beta-, gamma- and delta-tocopherol, alpha-tocopherol is preferentially conserved by the discriminating action of the liver alpha-tocopherol transfer protein, which also maintains plasma alpha-tocopherol concentration within a range of 20 to 40 microM. In the circulation, alpha-tocopherol, in association with the transfer-protein, is assembled into the very low-density lipoprotein and low-density lipoprotein particles and released for use by the peripheral tissues. Recent data suggest that alpha-tocopherol is not only an anti-oxidant but also a regulator of gene expression through its binding to nuclear receptors. The precise mechanism of regulating gene expression, however, is still unknown. The four tocopherols are ultimately degraded by omega-oxidation and subsequent beta-oxidations followed by the elimination of the metabolites in the bile and in the urine. Patients with a defect of the alpha-tocopherol transfer protein are unable to maintain their alpha-tocopherol reserves and progressively lose tendon reflexes and have signs and symptoms of spinocerebellar ataxia while plasma vitamin E level drops below 2 microg/ml.

Positive association between plasma antioxidant capacity and n−3 PUFA in red blood cells from women

PUFA are susceptible to oxidation. However, the chain-reaction of lipid peroxidation can be interrupted by antioxidants. Whether an increased concentration of PUFA in the body leads to decreased antioxidant capacity and/or increased consumption of antioxidants is not known. To elucidate the relationship between plasma total antioxidant capacity (TAC), the concentration of antioxidant vitamins, and the proportion of PUFA in red blood cells (RBC), plasma TAC was measured by a Trolox equivalent antioxidant capacity assay in blood samples from 99 Icelandic women. Concentrations of tocopherols and carotenoids in the plasma were determined by HPLC, and the FA composition of RBC total lipids was analyzed by GC. Plasma TAC and the plasma concentration of alpha-tocopherol correlated positively with the proportion of total n-3 PUFA, 20:5n-3, and 22:6n-3 in RBC, whereas the plasma lycopene concentration correlated negatively with the proportion of total n-3 PUFA and 20:5n-3. On the other hand, plasma TAC correlated negatively with the proportion of n-6 PUFA in RBC. Plasma TAC also correlated positively with the plasma concentration of alpha-tocopherol, alcohol consumption, and age. Both the plasma concentration of alpha-tocopherol and age correlated positively with the proportion of n-3 PUFA in RBC; however, n-3 PUFA contributed independently to the correlation with plasma TAC. Because the proportion of n-3 PUFA in RBC reflects the consumption of n-3 PUFA, these results suggest that dietary n-3 PUFA do not have adverse effects on plasma TAC or the plasma concentration of most antioxidant vitamins.

Regulation of the α‐tocopherol transfer protein in mice: Lack of response to dietary vitamin E or oxidative stress

The alpha-tocopherol transfer protein (TTP) plays an important role in the regulation of plasma alpha-tocopherol concentrations. We hypothesized that hepatic TTP levels would be modulated by dietary vitamin E supplementation and/or by oxidative stress. Mice were fed either a High E (1150 mg RRR-alpha-tocopheryl acetate/kg diet) or a Low E (11.5 mg/kg diet) diet for 2 wk. High E increased plasma and liver alpha-tocopherol concentrations approximately 8- and 40-fold, respectively, compared with Low E-fed mice, whereas hepatic TTP increased approximately 20%. Hepatic TTP concentrations were unaffected by fasting (24 h) in mice fed either diet. To induce oxidative stress, chow-fed mice were exposed for 3 d to environmental tobacco smoke (ETS) for 6 h/d (total suspended particulate, 57.4 +/- 1.8 mg/m3). ETS exposure, while resulting in pulmonary and systemic oxidative stress, had no effect on hepatic alpha-tocopherol concentrations or hepatic TTP. Overall, changes in hepatic TTP concentrations were minimal in response to dietary vitamin E levels or ETS-related oxidative stress. Thus, hepatic TTP concentrations may be at sufficient levels such that they are unaffected by either modulations of dietary vitamin E or by the conditions of environmentally related oxidative stress used in the present studies.

Human vitamin E requirements assessed with the use of apples fortified with deuterium-labeled α-tocopheryl acetate

Little is known about factors that modulate dietary alpha-tocopherol bioavailability. The study aimed to assess the efficacy of vitamin E-fortified apples as a low-fat vitamin E delivery system, the influence of fat on vitamin E absorption, and human vitamin E requirements by using plasma alpha-tocopherol kinetics at a dosage of alpha-tocopherol found in food. Apples fortified with deuterium-labeled alpha-tocopheryl acetate were consumed by 5 participants at a breakfast containing 0%, 6%, or 21% kcal from fat in 3 sequential trials. The trials were separated by a 2-wk washout period. Blood samples were obtained up to 72 h, and plasma was analyzed for labeled and unlabeled alpha-tocopherol. Compared with observations in the 0% fat trial, the maximum observed plasma d6-alpha-tocopherol concentrations (Cmax) and the areas under the curve increased 2- and 3-fold during the 6% and 21% fat trials, respectively. The mean (+/-SD) estimated percentage d6-alpha-tocopherol absorbed increased from 10 +/- 4% during the 0% fat trial to 20 +/- 3% and 33 +/- 5% during the 6% and 21% fat trials, respectively. The mean time to Cmax (9 +/- 2 h), fractional disappearance rates (0.022 +/- 0.003 pools/d), and half-lives (32 +/- 4 h) did not differ significantly between the trials. With the use of fractional disappearance rates and baseline plasma alpha-tocopherol concentrations, the estimated daily plasma alpha-tocopherol efflux was 13-14 mg. The estimated rate of alpha-tocopherol delivery to tissues was 5 mg/d. Given an estimated 33% absorption, the amount of dietary vitamin E needed daily to replace irreversible losses is </=15 mg. These estimates support the current human vitamin E requirements despite the claims that the median amount of vitamin E that Americans consume is 7 mg/d.

Status of carotenoids, vitamin A, and vitamin E in the mother-infant dyad and anthropometric status of infants in Malawi.

This prospective study was carried out during February 2000-April 2003 to characterize the relationship between the status of carotenoids, vitamin E, and retinol and anthropometric status in apparently healthy infants and their mothers in Blantyre, Malawi. Anthropometric status of infants and concentrations of carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene), retinol, and alpha-tocopherol in plasma were measured in 173 infants at 12 months of age, and concentrations of carotenoids, retinol, and a-tocopherol in plasma were measured in their mothers two weeks postpartum. In multivariate analyses, concentrations of retinol, total carotenoids, non-provitamin A carotenoids, and alpha-tocopherol in infants were associated with under-weight (p = 0.05). Concentrations of a-tocopherol were associated with wasting (p = 0.04). Concentrations in mothers and infants were all correlated (correlation coefficients from 0.230 to 0.502, p < 0.003). The findings suggest that poor status of carotenoids, retinol, and alpha-tocopherol in infants is associated with their poor anthropometric status, and status of carotenoids, retinol, and alpha-tocopherol in mothers and infants has a low-to-moderate association in the mother-infant dyad.

Plasma carotene and α-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: the Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA)

Only a few observational studies have related plasma carotene and alpha-tocopherol to mortality in elderly subjects. The objective was to study the association of plasma carotene (alpha-and beta-carotene) and alpha-tocopherol with all-cause and cause-specific mortality in elderly subjects who participated in a European prospective study. Plasma concentrations of carotene and alpha-tocopherol were measured in 1168 elderly men and women. After a follow-up period of 10 y, 388 persons had died. The association between plasma antioxidants and mortality was analyzed by using Cox proportional hazard models. To put our results in context, we performed a meta-analysis of 5 studies on plasma antioxidants and all-cause mortality in elderly populations. Plasma carotene concentrations were associated with a lower mortality risk [adjusted rate ratio (RR) for an increment of 0.39 micromol/L: 0.79; 95% CI: 0.70, 0.89]. This lower mortality risk was observed for both cancer (RR: 0.59; 95% CI: 0.44, 0.79) and cardiovascular disease (RR: 0.83; 95% CI: 0.70, 1.00). The lower risk of cardiovascular death was confined to those with a body mass index (in kg/m2) <25 (RR: 0.67; 95% CI: 0.49, 0.94). Plasma concentrations of alpha-tocopherol were not associated with all-cause or cause-specific mortality. The results for both plasma antioxidants and all-cause mortality were confirmed by the meta-analysis. This prospective study suggests that high plasma concentrations of carotene are associated both with lower mortality from all causes and with cancer in the elderly. For cardiovascular mortality, the inverse association was confined to elderly with body mass indexes <25.

Increase in liver antioxidant enzyme activities in non‐alcoholic fatty liver disease

Steatosis may increase oxidative stress, which is counteracted by cellular enzymatic (cytosolic and mitochondrial superoxide dismutases (Cu/Zn-SOD and Mn-SOD), glutathione peroxidase (GPx), catalase) and non-enzymatic antioxidant systems. We aimed to determine, in patients with non-alcoholic fatty liver disease (NAFLD), the level of antioxidant defenses (1) in liver biopsies, to demonstrate the existence of oxidative stress; (2) in erythrocytes and plasma, to determine whether their antioxidant defenses reflect liver oxidative stress. Erythrocyte and plasma antioxidant defenses were prospectively studied in two groups of 16 patients: patients with NAFLD and controls. Liver biopsies were performed in eight NAFLD patients; liver antioxidant enzyme activities were measured and compared with those in 12 control livers used for transplantation. Cu/Zn-SOD, GPx and catalase activities were significantly higher in NAFLD livers than in controls whereas no significant differences were observed in Mn-SOD activity, and thiobarbituric acid-reactive substance (TBARS) concentration. No differences were observed in erythrocyte antioxidant enzyme activities (GPx, catalase, Cu/Zn-SOD), erythrocyte TBARS concentration, and plasma alpha-tocopherol concentration. Liver antioxidant enzyme activities were high in patients with NAFLD, reflecting an oxidative stress possibly involved in inflammation and fibrogenesis. However, erythrocyte and plasma antioxidant defenses did not reflect intrahepatic peroxidation.