Total Alpha-tocopherol Research Articles

Nutrients from Fruit and Vegetable Consumption Reduce the Risk of Pancreatic Cancer

Pancreatic cancer is a devastating disease for which the role of dietary factors remains inconclusive. Our objective was to evaluate the risk of pancreatic cancer associated with nutrients found in fruits and vegetables and nutrient supplementation using a clinic-based case-control design. Our study included 384 rapidly ascertained cases and 983 controls frequency-matched on age at time of recruitment (in 5-year increments), race, sex, and region of residence. All subjects provided demographic information and completed a 144-item food frequency questionnaire in which they reported no change to their diet within 5 years prior to entering the study. Logistic regression was used to calculate odds ratios and 95 % confidence intervals, adjusted for age, sex, smoking, body mass index, energy intake, and alcohol consumption. Results show a significant (trend p value < 0.05) inverse association between pancreatic cancer and nutrient/supplement groupings in a dose-dependent manner including magnesium, potassium, selenium, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, niacin, total alpha-tocopherol, total vitamin A activity, vitamin B6, and vitamin C. Adjusting for diabetes or total sugar intake did not result in significant changes. We conclude that most nutrients obtained through consumption of fruits and vegetables may reduce the risk of developing pancreatic cancer.

Effects of vitamin E on bone turnover markers among US postmenopausal women

Increased oxidative stress and inflammation resulting from aging and declining estrogen levels can lead to increased bone loss in postmenopausal women. Alpha-tocopherol and gamma-tocopherol, the two predominant isomers of vitamin E, have antioxidant and anti-inflammatory properties, but their effects on bone metabolism have not been well studied in humans. We examined the associations between dietary and total (diet and supplements) alpha-tocopherol intake, serum alpha-tocopherol and gamma-tocopherol levels and their ratio, and bone turnover markers (BTMs) among postmenopausal women aged ≥45 years. We used cross-sectional data from the National Health and Nutrition Examination Survey 1999–2002. Multiple regression models with adjustments for relevant confounders were used to examine the associations between intake and serum levels of tocopherols, and serum bone-specific alkaline phosphatase (BAP), a biomarker of bone formation, and urinary N-telopeptides/creatinine (uNTx/Cr), a biomarker of bone resorption. The study sample included 497 postmenopausal women who were not taking estrogen, steroids, or osteoporosis medications, were free from kidney and liver disease, cancer, and rheumatoid arthritis, and were fasting >9 hours prior to examination. Participants had a mean age of 65.5 ± 0.6 years and over 45% used vitamin E (alpha-tocopherol) supplements in the past month. Vitamin E supplement users had significantly lower serum gamma-tocopherol, higher serum alpha-tocopherol levels, and higher ratio of serum alpha-tocopherol to gamma-tocopherol than nonusers. High serum gamma-tocopherol levels and low ratio of serum alpha-tocopherol to gamma-tocopherol were associated with increased BAP levels (p < 0.01 for both). There were no associations between any of the vitamin E variables and uNTx/Cr. In conclusion, we hypothesize that gamma-tocopherol may uncouple bone turnover, resulting in more bone formation than resorption. Vitamin E supplements in the form of alpha-tocopherol suppress serum gamma-tocopherol levels and may have negative effects on bone formation. Further research is needed to investigate the potential anabolic effect of gamma-tocopherol from food sources on bone.

Oxidative Stress in Patients with Acute Heart Failure

Oxidative stress (OS) is a keystone in the pathology of the ischemia reperfusion sequence (acute coronary syndromes, cardiac surgery, transplantation). In heart failure, the implication of OS is less understood. This study was intended to evaluate OS in acute heart failure. Criteria for inclusion were consecutive patients hospitalized in our cardiology department for a first pulmonary edema that revealed a dilated cardiomyopathy (DCM). Exclusion criteria included known cardiomyopathy, smoker, acute coronary syndrome, and treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARAII). OS was evaluated in blood samples: thiobarbituric acid-reactive substances (TBARS), total antioxidant status (TAS), plasma alpha-tocopherol, vitamin A, and beta-carotene. Standard biochemical parameters including CRP, fibrinogen, lipid, and creatinine were assayed. Ten patients (80% men, mean age 55.3 +/- 7.9 years) were included and followed during a 6 month period. The etiologies of DCM were alcohol (n = 3), anti-cancer drugs (n = 2), valvulopathies (n = 2), or idiopathic (n = 3). In acute heart failure, TBARS were elevated (1.69 micromol/L; normal value 0.6-4.2 micromol/L) and TAS status was decreased (0.96 mmol/L; normal value 1.3-1.9 pmol/L). OS was more important when patients had atrial or ventricular arrhythmia. Nevertheless, liposoluble antioxidant parameters (beta-carotene, vitamin A, alpha-tocopherol) had a usual value. At the term of the follow-up, patients returned to a stable condition, OS markers revealed normal values, and every Holter ECG showed no supraventricular or ventricular arrhythmias. In acute heart failure, oxygen-free radicals are increased. We thus hypothetized that a modification in OS could be responsible for arrhythmias and complications of acute heart failure.

Changes in Contents of Carotenoids and Vitamin E during Tomato Processing

The aim of this study was to investigate the effect of different types of tomato processing on contents of lycopene, beta-carotene, and alpha-tocopherol. Samples of tomato sauce, tomato soup, baked tomato slices, and tomato juice were taken at different times of heating, respectively, after each step of production. HPLC was used to analyze contents of carotenoids and vitamin E. Due to the loss of water during thermal processing, contents of lycopene, beta-carotene, and alpha-tocopherol on a wet weight basis increased. On a dry weight basis, contents of lycopene increased or decreased depending on the origin of the tomatoes used, whereas the beta-carotene contents decreased or were quite stable. In contrast to lycopene, beta-carotene isomerized due to thermal processing. The alpha-tocopherol contents significantly rose during short-term heating. The increase was not caused by release of alpha-tocopherol from the seeds containing predominantly gamma-tocopherol and accounting for 2% of total alpha-tocopherol content only.

Reasonable Estimates of Serum Vitamin E, Vitamin C, and β-Cryptoxanthin Are Obtained with a Food Frequency Questionnaire in Older Black and White Adults

Few studies provide correlations between different indicators of the dietary intakes of older (>or= 65 y) black and white adults. This study compared the usual intakes of vitamin E, vitamin C, and selected carotenoids estimated by a modified Harvard food frequency questionnaire (FFQ) to those estimated by multiple 24-h recalls, and to blood concentrations of components in a randomly selected sample of participants in the Chicago Health and Aging Project (CHAP). Subjects (n = 59) were interviewed to complete multiple 24-h recalls over a year's time, then completed an FFQ and subsequently provided a fasting blood specimen within 2 mo. Dietary estimates were energy-adjusted separately for men and women. Significant (P < 0.05) correlations between total (diet and supplement) FFQ estimates and serum measures of vitamin E and vitamin C were as follows: 0.49 and 0.39 for blacks, and 0.42 and 0.29 for whites, respectively. The highest correlations between serum and FFQ indicators were for dietary beta-cryptoxanthin (0.46), total alpha-tocopherol (0.46) and total beta-carotene (0.44) among whites; among blacks, the highest correlations were for dietary alpha-carotene (0.81), total alpha-tocopherol (0.53) and total beta-cryptoxanthin (0.50); all were significant (P < 0.05). Further adjustment for age, gender, BMI, and educational level minimally altered these coefficients. These findings indicate that the modified Harvard FFQ provides reasonable estimates of serum levels of vitamin E, vitamin C and beta-cryptoxanthin among CHAP participants.

Lactating Sows and Suckling Piglets Preferentially Incorporate RRR- over All-rac-α-Tocopherol into Milk, Plasma and Tissues

Synthetic vitamin E, all-rac-alpha-tocopherol, contains eight different stereoisomers, only one of which, RRR-alpha-tocopherol, occurs naturally. The objective of this investigation was to evaluate the relative abilities of these two vitamin E forms to enrich piglet tissues when fed as alpha-tocopheryl acetates to sows during pregnancy and lactation. alpha-Tocopherol delivery to fetuses and to suckling piglets was monitored by feeding 150 mg each of d(3)-RRR-alpha- and d(6)-all-rac-alpha-tocopheryl acetate to three pregnant sows daily from 7 d before to 7 d after giving birth. Labeled and unlabeled vitamin E concentration ratios were measured in sow plasma and milk, and in piglet (n = 9) plasma and tissues at birth, 7 and 21 d. At birth, despite elevated sow plasma deuterated alpha-tocopherol concentrations, no labeled alpha-tocopherol was detected in piglet plasma or tissues. Sow plasma and milk d(3)-alpha- to d(6)-alpha-tocopherol concentrations were 2:1, leading to a 2:1 ratio in suckling piglet plasma and tissues. In piglets at d 7 compared with birth, most tissues contained a 10-fold increase in total alpha-tocopherol; the highest deuterated vitamin E concentrations were in the liver, followed by the lung, heart, kidney, muscle, intestine and brain. In conclusion, pigs discriminate between RRR- and all-rac-alpha-tocopherol with a preference for RRR-alpha-tocopherol; thus, the official bioequivalence ratio of 1.36:1 RRR- to all-rac-alpha-tocopherol is underestimated. After initiation of suckling, piglet plasma and tissues demonstrated a dramatic increase in vitamin E concentrations, emphasizing the limited placental vitamin E transfer and the importance of milk for enhancing the vitamin E status of the newborn.

Incorporation of deuterated RRR- or all-rac-α-tocopherol in plasma and tissues of α-tocopherol transfer protein–null mice

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. 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. Adult alpha-TTP null (Ttpa(-/-); n = 5), heterozygous (Ttpa(+/-); n = 7), and wild-type (Ttpa(+/+); n = 3) mice consumed equimolar RRR-alpha-[5,7-(C(2)H(3))(2)]-(d(6))- and all-rac-alpha-[5-(C(2)H(3))]-(d(3))-tocopheryl acetates (30 mg/kg diet each) for 3 mo. Subsequently, we measured labeled and unlabeled alpha-tocopherols in plasma and 17 tissues. In all mice, plasma and tissue d(6)- + d(3)-alpha-tocopherols represented approximate 80-90% of total alpha-tocopherol. In the Ttpa(-/-) 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(+/+) mice. Peripheral tissue ratios of d(6)- to d(3)-alpha-tocopherol were 1.1 plus minus 0.1 and 1.8 plus minus 0.2 in Ttpa(-/-) and Ttpa(+/+) 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-tocopherol. 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.

The effect of added dietary soybean oil on vitamin E status of the horse

Fourteen 2-yr-old Quarter Horses and Quarter Horse x Thoroughbreds were randomly assigned to either a control (CTRL) diet or a diet supplemented with 6.4% soybean oil (SBO). The amounts of both diets that were fed met current NRC nutrient requirements and were isoenergetic with similar nutrient:energy ratios. Venous blood samples (20 mL) were taken at d 0, 30, 60, and 90 of the experiment and analyzed for serum alpha-tocopherol, serum cholesterol, and serum triglyceride. The sum of serum cholesterol and serum triglyceride values was used as an estimate of serum total lipid. The ratio of serum alpha-tocopherol:serum total lipid was used as a measure of vitamin E status of horses. The SBO group had higher serum cholesterol concentrations (P < .001) at 30, 60, and 90 d. Serum triglyceride was not affected by diet. Serum total lipids tended to be greater (P < .06) for the SBO group. Serum alpha-tocopherol was greater (P < .001) at 90 d in the SBO group. There was a significant correlation (P < .001, r = .62) between serum total lipids and serum alpha-tocopherol concentrations in the SBO group. This correlation was not significant (P < .07, r = .35) in the CTRL group. The ratio of serum alpha-tocopherol:serum total lipid was not affected by diet. The results of this experiment suggest that vitamin E status in non-exercising, 2-yr-old horses fed currently recommended levels of vitamin E was not affected by the addition of 6.4% SBO to the diet.

Interrelationships of alpha-tocopherol with plasma lipoproteins in African green monkeys: effects of dietary fats.

The distributions of plasma lipoprotein alpha-tocopherol and lipids were studied in African green monkeys consuming diets enriched in saturated, monounsaturated, or polyunsaturated fatty acids. Plasma total alpha-tocopherol concentrations were not different among the animals fed the three diets, whereas plasma total cholesterol concentrations were significantly different among the diet groups. The alpha-tocopherol: total lipid molar ratio in plasma high density lipoproteins (HDL) was significantly higher compared to low density lipoproteins (LDL) and very low plus intermediate-sized low density lipoprotein (VLDL + ILDL) of each diet group, suggesting that HDL may exhibit a greater affinity for alpha-tocopherol. The presence of a positive correlation between HDL alpha-tocopherol and plasma apoA-I concentration and the absence of a correlation between HDL alpha-tocopherol and total lipid in HDL suggested that alpha-tocopherol associates with the protein moiety of HDL on the surface of the particle. A direct relationship between the plasma apoA-I: apoB molar ratio and the percentage of alpha-tocopherol found in the HDL fraction indicated that a greater proportion of alpha-tocopherol associates with HDL as the number of HDL particles in plasma increases relative to LDL particles. LDL from monkeys fed diets high in saturated fat contained 40% and 33% fewer alpha-tocopherol molecules per particle than LDL from monkeys fed polyunsaturated and monounsaturated fats, respectively. The phase transition temperature of LDL cholesteryl esters, indicative of the physical state of the lipids in the particle core, was well above body temperature in LDL from saturated fat-fed monkeys and was significantly higher compared to the other diet groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary habits and mammographic patterns in patients with breast cancer.

Between 1983 and 1986, dietary history interviews were conducted with 238 women aged 50-65 years who had surgery for stage I-II breast cancer. Diagnostic mammograms were coded in line with Wolfe's criteria in N1, P1, P2, and Dy patterns. Women with Dy pattern reported significantly higher intake of total fat, monounsaturated fatty acids (FA), polyunsaturated FA, n-3 FA, n-6 FA in per cent of energy (E%), and alpha-tocopherol in mg/10 MJ. Fat intake was lowest in women with N1 pattern and highest in those having Dy pattern. Patients having ER-rich cancers and Dy pattern reported significantly higher intake of total fat, monounsaturated FA, polyunsaturated FA, n-6 FA (E%), and alpha-tocopherol (mg/10 MJ), as well as significantly lower intake of carbohydrate (E%) and calcium (g/10 MJ). In the stepwise multivariate analysis, the multivariate-odds ratio (OR) for having P2 + Dy patterns was 1.06 (95% confidence interval (CI), 1.02-1.12) for each increment in E% of total fat. In women with ER-rich tumors this OR was 1.09 (95% CI, 1.02-1.16). The highest self-reported body mass index (BMI) was observed in women with N1 + P1 patterns. OR for having P2 + Dy patterns was 0.91 (95% CI, 0.83-0.98) for each increment in 1 kg/m2 of BMI. The results suggest that dietary habits affect the mammographic parenchymal pattern in women with breast cancer and that a high fat intake is associated with a higher proportion of mammograms with Dy pattern in such patients.

Inverse modifications of heart and liver alpha-tocopherol status by various dietary n-6/n-3 polyunsaturated fatty acid ratios.

The effect of dietary n-6/n-3 fatty acid ratio on alpha-tocopherol homeostasis was investigated in rats. Animals were fed diets containing fat (17% w/w) in which the n-6/n-3 ratio varied from 50 to 0.8. This was achieved by combining corn oil, fish oil, and lard. The polyunsaturated to saturated ratio and total alpha-tocopherol remained constant in all diets. Results showed that enrichment of n-3 polyunsaturated fatty acids in the diet, even at a low amount (3.9% w/w), resulted in a dramatic reduction of blood alpha-tocopherol concentration, which, in fact, is the result of a decrease in plasma lipids, since the alpha-tocopherol to total lipids ratio was not significantly altered. The most striking effect observed was a considerable alpha-tocopherol enrichment (x 4) of the heart as its membranes became enriched with n-3 polyunsaturated fatty acids. This process appeared even with a low amount of fish oil (3.9% w/w) added to the diet. Accordingly, a strong positive correlation was found between heart alpha-tocopherol and docosahexaenoic acid (r = 0.86) or docosahexaenoic acid plus eicosapentaenoic acid levels (r = 0.84). Conversely, the liver alpha-tocopherol level dropped dramatically when n-3 polyunsaturated fatty acids were gradually added to the diet. It is concluded that fish oil intake dramatically alters the alpha-tocopherol homeostasis in rats.

Plasma vitamins A and E and hydrogen peroxide-induced in vitro erythrocyte haemolysis in common marmosets (Callithrix jacchus).

Plasma total lipid, cholesterol, all-trans retinol (vitamin A) and alpha-tocopherol (vitamin E) concentrations, and the susceptibility of erythrocytes to hydrogen peroxide-induced haemolysis in vitro were investigated in healthy laboratory-bred common marmosets (Callithrix jacchus). The concentrations of alpha-tocopherol and total cholesterol were similar to those of control human subjects. The mean lipid concentration was higher (P less than 0.025) and the retinol concentration lower (P less than 0.001) in the marmosets. The susceptibility of the erythrocytes of the marmosets to hydrogen peroxide-induced haemolysis was high, both in absolute value and relative to the controls. Changes in phospholipid and fatty acid composition might have rendered the red cells susceptible to oxidative stress.

Tocopheroxyl Radical Persistence and Tocopherol Consumption in Liposomes and in Vitamin E-enriched Rat Liver Mitochondria and Microsomes

Substantial loading of rat liver mitochondrial and microsomal membranes with D-alpha-tocopherol was achieved by dietary supplementation with no adverse effects of this loading being apparent, e.g. on treadmill exercise endurance. The tocopheroxyl radical was readily detected by ESR in the enriched microsomes and mitochondria. Continuous enzymatic oxidation with horseradish peroxidase and a hydrophilic phenol, to favor selective oxidation of tocopherol without the involvement of lipid peroxidation, allowed the tocopheroxyl radical to be observed for up to 1 h in liposomes of dioleoylphosphatidylcholine and for about 15 min in the subcellular membranes. Total alpha-tocopherol decreased throughout this period, but a significant residual fraction remained after all the ESR signal of tocopheroxyl had disappeared. Decay kinetics of the tocopheroxyl radical ESR signal produced by a burst of intense UV irradiation consisted of a rapid initial phase and a slower exponential decay. A more narrow and more persistent ESR signal, not yet chemically identified, was observed after the tocopheroxyl radical had disappeared under prolonged oxidation. Ascorbic acid prevented formation of the tocopheroxyl radical until the ascorbyl radical ESR signal had decayed, whereas uric acid, up to saturating concentration in phosphate buffer, had no effect.

Plasma alpha-tocopherol, total lipids and total cholesterol in wild rockhopper, magellanic and gentoo penguins before and after moulting.

Post moult rockhopper penguins (Eudyptes crestatus) had significantly higher plasma alpha-tocopherol (vitamin E), total lipid and total cholesterol concentrations than their pre-moult counterparts. In the magellanic penguins (Spheniscus magellanicus) there were post moult increases in total lipid, cholesterol and alpha-tocopherol concentrations, but only the increase in alpha-tocopherol was significant. Plasma alpha-tocopherol, total lipid and total cholesterol concentrations in post moult gentoo (Pygoscelis papua) chicks were similar to those in non-moulting adult gentoos. Species differences in the levels of these nutrients in plasma may be due to differences in their dietary habits.

Levels of alpha- and gamma-tocopherol in human eyes: evaluation of the possible role of IRBP in intraocular alpha-tocopherol transport

Alpha-tocopherol was distributed almost equally between the retina and its underlying pigmented layers (pigment epithelium and choroid). Only 8.4% of the total alpha-tocopherol occurred in the iris and ciliary body. Alpha-tocopherol content was expressed as amount per eye, per cm2, and per 100 g wet weight. The combined retina and pigment epithelium-choroid contained 2.9 +/- 1.0 mg/100 g wet weight (means +/- SD, n = 30 donors). Gamma-tocopherol represented 20.9 +/- 12.2 mol % of the alpha-tocopherol. The anterior tissues contained 0.4 +/- 0.2 mg/100 g (n = 19 donors). No significant correlation with age was found. Purified bovine interstitial retinol-binding protein (IRBP) bound exogenous 3H-alpha-tocopherol, which could be displaced by unlabeled all-trans retinol (KD = 10(-6) M). Much higher concentrations of unlabeled alpha-tocopherol were required to achieve a partial displacement of bound 3H-all-trans retinol. No endogenous alpha-tocopherol could be detected in bovine interphotoreceptor matrix.

Inhibitory effect of alpha-tocopherol on the formation of nitrosomorpholine in mice treated with morpholine and exposed to nitrogen dioxide.

The possibility that alpha-tocopherol (vitamin E) inhibits the formation of nitrosomorpholine (NMOR) in vivo was investigated in mice orally pretreated with alpha-tocopherol (2.5-100 mg/kg body wt) once daily for 6 days. Twenty-four hours later, the animals were injected i.p. with 2 mg of morpholine (MOR) per animal followed by exposure to 47 p.p.m. of NO2 for 2 h. Under these conditions, low oral doses of alpha-tocopherol (2.5-5 mg/kg body wt) significantly decreased NMOR formation in vivo. As total body alpha-tocopherol levels increased, in vivo NMOR formation decreased, and a maximal 50-70% inhibition of NMOR formation occurred at alpha-tocopherol levels of 5 micrograms/g body wt. Additional results showed that NMOR was rapidly eliminated in mice, so that studies which measure the levels of NMOR found in animals treated with MOR and then exposed to NO2 may underestimate the amount of NMOR that is actually formed. Finally, oral pretreatment of up to 100 mg of alpha-tocopherol/kg body wt had no effect on NMOR elimination.

The effect of fluoride intake on the total lipid, cholesterol and vitamin E levels in a sera and liver of guinea pigs on high fat diet

Guinea pigs were raised on a diet containing 18 percent fat and were provided 25 or 0 ppm fluoride in the drinking water. Animals were sacrificed at the end of 0, 3, 6, 9 and 13 weeks on the dietary regimen and blood serum was analyzed for fluoride, total lipid, cholesterol and alpha tocopherol. The serum total lipid levels, cholesterol and alpha tocopherol levels were increased in the high fluoride group between 9 and 13 weeks. An increase in total lipid and alpha tocopherol levels was also observed in the livers of these animals. The increase in liver content of alpha tocopherol was proportional to the increase in total lipid content whereas the corresponding increase in serum alpha tocopherol content was significant even when the increase in total lipid was taken into account. The data suggest a specific effect of fluoride on the serum alpha tocopherol levels of the high fluoride animals.

Effect of High Levels of Dietary Vitamin E on Liver and Plasma Lipids and Fat Soluble Vitamins in Rats

The effect of low, moderate and high dietary vitamin E (ranging from 0 to 25,000 IU/kg diet) on the levels of alpha-tocopherol, total lipids, cholesterol and vitamin A in liver and plasma of rats fed for 8 and 16 months was studied. A logarithmic relationship was observed between dietary levels of vitamin E and the concentrations of this vitamin in liver and plasma. The total alpha-tocopherol in whole liver of rats fed different levels of dietary vitamin E for 16 months was approximately double in comparison to rats fed for 8 months. Totoal lipids in liver were significantly increased by excess vitamin E supplementation in rats fed for 8 months, but not in rats fed for 16 months. There was no significant change observed in liver cholesterol level at 16 months. Plasma total lipids and cholesterol were lowered by vitamin E deficiency and also by dietary levels higher than 2,500 IU vitamin E/kg diet in rats fed for 16 months. Liver vitamin A storage was 4.5 times higher in rats supplemented with vitamin E than in rats without any supplement, but the effect of excess dietary vitamin E was no different from that of normal level (25 IU/kg diet). The findings of our long-term study are compared with the results of other short-term studies and the implications are discussed.