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Background: We previously showed that thermal injury depletes plasma vitamin E in pediatric burn patients; however, plasma changes may reflect immediate alterations in vitamin E nutriture. Adipose tissue [alpha]-tocopherol concentrations are generally accepted to reflect long-term vitamin E status. Objective: To test the hypothesis that thermal injury depletes body stores of vitamin E, [alpha]-tocopherol concentrations were measured in adipose tissue samples. Design: Pediatric patients (n = 8) were followed up to 1 y after burn injury. Surgically obtained samples were collected at various intervals and stored at -80[degrees]C in a biorepository. [alpha]- and [gamma]-Tocopherols, cholesterol, and triglycerides were measured in the same tissue aliquot. Results: During the first week after injury, adipose tissue [alpha]-tocopherol concentrations were within the expected normal range of 199 [+ or -] 40 nmol/g adipose tissue but were substantially lower at weeks 2 and 3 (133 [+ or -] 13 and 109 [+ or -] 8 nmol/g adipose tissue, respectively). Individual rates of decrease, estimated by linear regression, showed that adipose tissue [alpha]-tocopherol decreased by an average of 6.1 [+ or -] 0.6 nmol/g daily. During the first month after injury, adipose tissue triglyceride concentrations also decreased, whereas no changes in cholesterol concentrations occurred. Conclusions: These data emphasize that the burn injury experienced by these pediatric patients altered their metabolism such that vitamin E status diminished during the month after injury. Further studies are needed to evaluate the mechanism and consequences of the observed vitamin E depletion. This trial was registered at clinicaltrials.gov as NCT00675714. Am J Clin Nutr 2010;92:137884. doi: 10.3945/ajcn.2010.30017.

Background: [gamma]-Tocopherol has unique properties that may be beneficial in sustaining optimal human health, but hepatic vitamin E metabolism enhances [gamma]-tocopherol turnover. Objective: Our aim was to determine the extent to which dietary sesame lignans alter human [alpha]- and [gamma]-tocopherol metabolism and elimination as carboxyethyl hydroxychromanols (CEHCs). Design: Healthy participants (n = 5 women and 5 men) in a randomized, crossover study (with 4-wk washout) consumed muffins prepared with either corn oil or unrefined sesame oil (sesamin, 94 mg; sesamolin, 42 mg), along with a capsule containing a 1:1 molar ratio of deuterium-labeled [d.sub.6]-[alpha]- and [d.sub.2]-[gamma]-tocopherol acetates ([approximately equal to] 50 mg each). Plasma and urine were collected up to 72 h; unlabeled and labeled tocopherol and CEHC concentrations were determined by liquid chromatography-mass spectrometry. Results: Sesame oil muffin consumption in men, but not in women, decreased (P < 0.05) areas under plasma [d.sub.2]-[gamma]-CEHC concentration-time curves (area under the curve) and maximum concentrations. However, in both sexes urinary [d.sub.2]-[gamma]-CEHCs were decreased for 24 h following sesame oil muffin consumption. Conclusions: In humans, [gamma]-tocopherol metabolism can be inhibited by the simultaneous consumption of [gamma]-tocopherol and sesame lignans. The observed differences between men and women with respect to vitamin E metabolism warrant further investigation.

Background: Little is known about factors that modulate dietary [alpha]-tocopherol bioavailability. Objectives: 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. Design: 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. Results: Compared with observations in the 0% fat trial, the maximum observed plasma [d.sub.6]-[alpha]-tocopherol concentrations ([C.sub.max]) and the areas under the curve increased 2- and 3-fold during the 6% and 21% fat trials, respectively. The mean ([+ or -] SD) estimated percentage [d.sub.6]-a-tocopherol absorbed increased from 10 [+ or -] 4% during the 0% fat trial to 20 [+ or -] 3% and 33 [+ or -] 5% during the 6% and 21% fat trials, respectively. The mean time to [C.sub.max] (9 [+ or -] 2 h), fractional disappearance rates (0.022 [+ or -] 0.003 pools/d), and half-lives (32 [+ or -] 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. Conclusions: Given an estimated 33% absorption, the amount of dietary vitamin E needed daily to replace irreversible losses is [less than or equal to] 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. Am J Clin Nutr 2006;83: 299-304. KEY WORDS [alpha]-Tocopherol, vitamin E requirements, bioavailability, deuterium, biokinetics, dietary fat

Background: Cigarette smoking increases the fractional disappearance rates of [alpha]-tocopherol and is associated with increased oxidative stress, but its effects on [alpha]-tocopherol metabolism are unknown. Objective: We hypothesized that smokers would have less [alpha]-tocopherol available and consequently lower plasma [alpha]-carboxyethyl-hydroxychroman ([alpha]-CEHC), the [alpha]-tocopherol metabolite produced by a cytochrome P450--mediated process. Design: Smokers and nonsmokers (n = 10 per group) were supplemented with deuterium-labeled [alpha]-tocopheryl acetates (75 mg each [d.sub.3]-RRR-[alpha]-tocopheryl and [d.sub.6]-all-rac-[alpha]-tocopheryl acetate) from day -6 to day -1, and plasma tocopherols and CEHCs were measured (day -6 through day 17). Results: After 6 d of supplementation, plasma [d.sub.3]- and [d.sub.6]-[alpha]-tocopherol concentrations did not differ significantly between groups. Plasma [d.sub.3]- and [d.sub.6]-[alpha]-CEHCs were detectable only from day -5 to day 5. Before supplementation, unlabeled [alpha]- and [gamma]-CEHCs were [approximately equal to]60% and 40% lower, respectively, in smokers than in nonsmokers (P [greater than or equal to] 0.05). In addition, do-, [d.sub.3]-, and [d.sub.6]-[alpha]-CEHC areas under the curves were [approximately equal to] 50% lower in smokers (P < 0.05), and smokers had lower maximal [d.sub.3]-[alpha]-CEHC (P = 0.004) and [d.sub.6],-[alpha]-CEHC (P = 0.0006) concentrations. Notably, 2.9-4.7 times as much [alpha]-CEHC was produced from all-rac-[alpha]-tocopherol than from RRR-[alpha]-tocopherol. During supplementation, smokers had about one-half (P < 0.05) the plasma total, [d.sub.6]-, or [d.sub.3]-[alpha]-CEHC concentrations that nonsmokers did given similar [alpha]-tocopherol concentrations. Conclusions: Smoking did not increase [alpha]-tocopherol disappearance through P450-mediated tocopherol metabolism. Therefore, the mechanism of increased [alpha]-tocopherol disappearance in smokers likely operates through oxidation pathways, which is consistent with [alpha]-tocopherol's antioxidant function. Consequently, evaluating the molecular mechanism or mechanisms responsible for tocopherol metabolism under conditions of oxidative stress and the mechanisms that regulate [alpha]-tocopherol status is warranted. KEY WORDS Oxidative stress, carboxyethyl-hydroxychroman, CEHC, smokers, tocopherols, metabolism, cytochrome P450

Background: Most vitamin E supplements contain synthetic all-rac-[alpha]-tocopherol [2,5,7,8-tetramethyl-2RS-(4'RS, 8'RS, 12-trimethyltridecyl)-6-chromanol] with 8 stereoisomers; only 1 is identical to the natural stereoisomer, RRR-[alpha]-tocopherol [2,5,7,8-tetramethyl-2R-(4'R,8'R, 12-trimethyltridecyl)-6-chromanol]. In humans, 2R-[alpha]-tocopherol stereoisomers are preferentially maintained in the plasma, a function that has been attributed to hepatic [alpha]-tocopherol transfer protein ([alpha]-TTP), but this hypothesis has not been tested. Objective: We sought to determine the functions of [alpha]-TTP by comparing mice that express [alpha]-TTP with mice that are genetically unable to express [alpha]-TTP. Design: Adult [alpha]-TTP null ([Ttpa.sup.-/-]; n = 5), heterozygous ([Ttpa.sup.+/-]; n = 7), and wild-type ([Ttpa.sup.+/+]; n = 3) mice consumed equimolar RRR-[alpha]-[5,7-[([C.sup.2][H.sub.3])].sub.2]-([d.sub.6)- and all-rac-[alpha]-[5-([C.sup.2][H.sub.3])]-([d.sub.3])-tocopheryl acetates (30 mg/kg diet each) for 3 mo. Subsequently, we measured labeled and unlabeled [alpha]-tocopherols in plasma and 17 tissues. Results: In all mice, plasma and tissue [d.sub.6]- + [d.sub.3]-[alpha]-tocopherols represented [approximately equal to] 80-90% of total [alpha]-tocopherol. In the [Ttpa.sup.-/-] mice, low total [alpha]-tocopherol concentrations were found in plasma (5.4%) and most other tissues (2-20%), but liver concentrations were 39% of those of [Ttpa.sup.+/+] mice. Peripheral tissue ratios of [d.sub.6]- to [d.sub.3]-[alpha]-tocopherol were 1.1 [+ or -] 0.1 and 1.8 [+ or -] 0.2 in [Ttpa.sup.-/-] and [Ttpa.sup.+/+] mice, respectively (P < 0.0001), showing that [alpha]-TTP preferentially selects 2R-[alpha]-tocopherols for secretion into plasma. This 2:1 ratio does not support the currently defined international unit of 1.36:1 RRR-[alpha]-tocopherol to all-rac-[alpha]-toeopherol. Conclusion: Deletion of the [alpha]-TTP gene in mice results in an accumulation of dietary [alpha]-tocopherol in the liver and depletion of peripheral tissue [alpha]-tocopherol. Am J Clin Nutr 2002;75: 555-60. KEY WORDS Vitamin E, deuterium-labeled [alpha]-tocopherol, [alpha]-TTP knockout mice, mass spectrometry, vitamin E requirement, liver, brain

Retention of bile acids within the liver is a primary factor in the pathogenesis of cholestatic liver disorders, which are more common in human infants. The objective of this study was to evaluate developmental changes in mitochondrial factors involved in bile acid-induced hepatocyte injury. Hepatic mitochondria from adult rats (aged 9 wk) underwent a mitochondrial permeability transition (MPT) and release of cytochrome c upon exposure to glycochenodeoxycholic acid. In contrast, mitochondria from young rats (age 6–36 d) were resistant to MPT induction and cytochrome c release. Neither mitochondrial levels of MPT-associated proteins (voltage-dependent anion channel, cyclophilin D, or adenine nucleotide translocase), Bcl-2 family proteins, nor antioxidant enzymes explained this resistance. Mitochondria from young rats contained 2- to 3-fold higher a-tocopherol (a-TH). In vivo a-TH enrichment of adult hepatic mitochondria increased their MPT resistance. Tetra-linoleoyl cardiolipin (TL-CL), the primary molecular species of CL, was reduced in mitochondria of the young rat; however, enrichment with CL and TL-CL only modestly increased their MPT susceptibility. In conclusion, we observed an unexpected resistance in young rats to bile acid induction of mitochondrial cell death pathways, which may be related to developmental differences in membrane composition.

Retention of bile acids within the liver is a primary factor in the pathogenesis of cholestatic liver disorders, which are more common in human infants. The objective of this study was to evaluate developmental changes in mitochondrial factors involved in bile acid-induced hepatocyte injury. Hepatic mitochondria from adult rats (aged 9 wk) underwent a mitochondrial permeability transition (MPT) and release of cytochrome cupon exposure to glycochenodeoxycholic acid. In contrast, mitochondria from young rats (age 6–36 d) were resistant to MPT induction and cytochrome crelease. Neither mitochondrial levels of MPT-associated proteins (voltage-dependent anion channel, cyclophilin D, or adenine nucleotide translocase), Bcl-2 family proteins, nor antioxidant enzymes explained this resistance. Mitochondria from young rats contained 2- to 3-fold higher -tocopherol (-TH). In vivo-TH enrichment of adult hepatic mitochondria increased their MPT resistance. Tetra-linoleoyl cardiolipin (TL-CL), the primary molecular species of CL, was reduced in mitochondria of the young rat; however, enrichment with CL and TL-CL only modestly increased their MPT susceptibility. In conclusion, we observed an unexpected resistance in young rats to bile acid induction of mitochondrial cell death pathways, which may be related to developmental differences in membrane composition.