On 'Is vitamin E the only lipid-soluble, chain-breaking antioxidant in human blood plasma and erythrocyte membranes?' by Graham W. Burton, Anne Joyce, Keith U. Ingold.

Application of a time-tested quantitative method of measuring peroxyl radical production in conjunction with the determination of the stoichiometry of the reaction of peroxyl radicals with α-tocopherol has permitted the conclusion that α-tocopherol is the major lipid-soluble chain-breaking antioxidant in human plasma and red cell membranes.

Effect of oxidized ß-carotene on the growth and feed efficiency of broilers.

Fully oxidized ß-carotene (OxBC) containing ß-carotene-oxygen copolymers is proposed as an alternative to antimicrobial growth promoters. Two trials were conducted to determine the efficacy of OxBC in enhancing growth and feed intake (FI) in male and female Ross × Ross 308 broilers in Ontario, Canada, and in Ross 308 male broilers in the United Kingdom. In the first trial, 0, 1, 2, or 5 ppm OxBC were added to diets in a 20% cornstarch premix, whereas in the second trial, 0, 2, or 5 ppm OxBC were added in a 1% cornstarch or 1% corncob grits premix. In trial 1, 2, and 5 ppm OxBC improved bird final body weights (BW) compared with the unsupplemented, nonmedicated (no bacitracin methylene disalicylate included), negative control birds after 39 d of feeding under commercial conditions (P < 0.05). All levels of OxBC improved feed conversion (FCR) during the finisher period (P < 0.05), whereas 2 and 5 ppm OxBC enhanced FCR relative to the negative control group during the full production cycle (P < 0.05). Average daily FI was not affected by OxBC, whereas 2 and 5 ppm OxBC increased broiler average daily gain (ADG) (P < 0.05). Oxidized ß-carotene did not affect bird mortality. The optimal OxBC dose was 2 ppm under the conditions used. In trial 2, 2 or 5 ppm OxBC on cornstarch and 5 ppm OxBC on corncob grits improved ADG, BW, and FI when fed for 35 d, as compared with the negative, nonmedicated control (P < 0.05). Feed conversion was not improved in the OxBC groups compared with the control group (P > 0.05). There were no differences among the 3 OxBC groups (P > 0.05). When birds were fed 2 ppm OxBC on corncob grits, the overall ADG, BW, and FI were lower than the respective control values (P < 0.001). Overall bird mortality was higher than expected for all groups, including the control group, but no dose effect was evident. Cornstarch was the preferred carrier for OxBC, and 2 ppm OxBC was the optimal dose under the conditions used.

Influence of Cropping Systems on Stem Rot (Sclerotium rolfsii), Meloidogyne arenaria, and the Nematode Antagonist Pasteuria penetrans in Peanut.

The effect of crop rotation (main plots) and pesticide treatment (subplots) on stem rot (Sclerotium rolfsii), Meloidogyne arenaria, and the nematode antagonist Pasteuria penetrans was determined in a field experiment. The field site was naturally infested with all three organisms. Peanut (P) was rotated with 2 years of either cotton (Ct), corn (C), or bahiagrass (B). The pesticide treatments for the peanut crop were aldicarb (31 g a.i. per 100-m row), flutolanil (1.7 kg a.i./ha), aldicarb + flutolanil, and a control without either pesticide. Populations of M. arenaria were lower in peanut in the Ct-Ct-P than in P-P-P, C-C-P, or B-B-P plots and tended to be lower in plots treated with aldicarb. Abundance of P. penetrans endospores was highest in the P-P-P plots, intermediate in the B-B-P rotations, lowest in all other rotations, and was unaffected by aldicarb. The high endospore densities in the P-P-P plots may have contributed to the uncharacteristically low nematode populations in the monoculture. Incidence of stem rot in peanut was lowest in treatments with flutolanil, intermediate in the control, and highest in treatments with aldicarb alone. The greater canopy cover in aldicarb-treated plots may have created a conducive environment for S. rolfsii infection.

Inter- and intra-individual variation in plasma and red blood cell vitamin E after supplementation.

To establish the range of individual blood responses to supplemental vitamin E, 30 healthy subjects ingested 75 mg of deuterium-labelled alpha-tocopherol with a standard breakfast. Blood was collected at 6, 9, 12, 27 and 51 h post ingestion and deuterated (d6) and non-deuterated (do) alpha-tocopherol concentrations were determined in plasma and red blood cells (RBC) by GC-MS. To examine intra-individual responses, 6 of these subjects were re-examined at 6-month intervals over a 30-month period. Post ingestion, the amount of d6-alpha-tocopherol in blood increased rapidly with time with maximal concentrations seen at 12 h (plasma) and 27 h (RBC) in most subjects. At these times, d6-alpha-tocopherol concentration ranged from 0.3-12.4 micromol/l in plasma and 0.6-4.09 micromol/l packed cell in RBC. Area under the curve calculations indicated inter-individual differences of alpha-tocopherol uptake to be 40-fold for plasma (12.9-493.3 micromol h/l) and 6-fold for RBC (24.4-146.1 micromol h/l packed RBC). Intra-individual variation in alpha-tocopherol uptake was small in comparison and remained relatively constant over the 30-month period. We conclude that vitamin E uptake varies widely in the normal population, although it is comparatively stable for an individual over time. These differences likely arise from variations in the regulation of vitamin E uptake and metabolism between subjects. Factors regulating this process must be better understood before the optimal intake of vitamin E can be ascertained.

Urinary excretion of 2,7, 8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman is a major route of elimination of gamma-tocopherol in humans.

Little is known of the post-absorptive, metabolic fate of gamma-tocopherol, the major form of vitamin E in North American diets. The objective of this study was to determine the extent of urinary excretion of 2,7, 8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a recently identified metabolite of gamma-tocopherol. A method for measurement of urinary gamma-CEHC was developed, using gas chromatography-mass spectrometry (GC-MS) with a deuterated internal standard, 2,7,8-trimethyl-2-(beta-carboxyethyl)-(3, 4-2H2)-6-hydroxychroman (d2-gamma-CEHC). This standard was synthesized by dehydrogenation of 6-acetyl-gamma-CEHC followed by deuteration of the resulting 3,4-double bond. The use of d2-gamma-CEHC resulted in accurate determinations of the concentration of d0-gamma-CEHC in human urine. Urine samples containing added d2-gamma-CEHC were treated with beta-glucuronidase, extracted with an organic solvent, and analyzed by GC-MS. Analysis of 24-h urine pools from healthy subjects revealed gamma-CEHC concentrations, normalized against creatinine, ranging from 2.5 to 31.5 micromol/g creatinine, or a total of 4.6 to 29.8 micromol per day. These results correspond to 2-12 mg gamma-tocopherol excreted daily as gamma-CEHC in the urine. Given an estimated mean intake of gamma-tocopherol of 20 mg/day, catabolism of gamma-tocopherol to gamma-CEHC, followed by glucuronide conjugation and urinary excretion, is a major pathway for elimination of gamma-tocopherol in humans.

Bahiagrass, corn, cotton rotations, and pesticides for managing nematodes, diseases, and insects on peanut.

Florunner peanut was grown after 1 and 2 years of Tifton 9 bahiagrass, corn, cotton, and continuous peanut as whole-plots. Pesticide treatments aldicarb (3.4 kg a.i./ha), flutolanil (1.7 kg a.i./ha), aldicarb + flutolanil, and untreated (control) were sub-plots. Numbers of Meloidogyne arenaria second-stage juveniles in the soil and root-gall indices of peanut at harvest were consistently lower in plots treated with aldicarb and aldicarb + flutolanil than in flutolanil-treated and untreated plots. Percentages of peanut leaflets damaged by thrips and leafhoppers were consistently greater in flutolaniltreated and untreated plots than in plots treated with aldicarb or aldicarb + flutolanil but not affected by cropping sequences. Incidence of southern stem rot was moderate to high for all chemical treatments except those that included flutolanil. Stem rot loci were low in peanut following 2 years of bahiagrass, intermediate following 2 years of corn or cotton, and highest in continuous peanut. Rhizoctonia limb rot was more severe in the peanut monoculture than in peanut following 2 years of bahiagrass, corn, or cotton. Flutolanil alone or combined with aldicarb suppressed limb rot compared with aldicarb-treated and untreated plots. Peanut pod yields were 4,186 kg/ha from aldicarb + flutolanil-treated plots, 3,627 kg/ha from aldicarb-treated plots, 3,426 kg/ha from flutolanil-treated plots, and 3,056 kg/ha from untreated plots. Yields of peanut following 2 years of bahiagrass, corn, and cotton were 29% to 33% higher than yield of monocultured peanut.

Root Diseases and Nematodes in Bahiagrass-Vegetable Rotations.

A double-crop of cucumber-snap bean was grown continuously for 4 years and compared with rotations of 1, 2, or 3 years of bahiagrass followed by vegetables. No nematicides or soil fungicides were applied. Root and hypocotyl disease severity in snap bean from Rhizoctonia solani AG-4 and Pythium spp. was decreased after 2 years of bahiagrass compared with 1 year of bahiagrass and 1 year of vegetables or continuous vegetables. Root galling caused by Meloidogyne incognita was less following 2 or 3 years, but not 1 year, of bahiagrass than following continuous vegetables. The beneficial effect of the rotation with bahiagrass lasted only 1 year. Then root injury from soilborne pathogenic fungi and root-knot nematodes was similar to that in continuous vegetables. Plant populations and yield of vegetables were greater following 3 years of bahiagrass than following 1 year of bahiagrass and 3 years of vegetables or continuous vegetables. Two years of bahiagrass followed by 1 or 2 years of vegetables did not increase yield of vegetables consistently.

Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E.

We report a comparison of natural and synthetic vitamin E in humans using deuterium labeling to permit the two forms of vitamin E to be measured independently in plasma and tissues of each subject. Differences in natural and synthetic vitamin E concentrations were measured directly under equal dosage conditions using an equimolar mixture of deuterated RRR-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate. Two groups of five adults took 30 mg of the mixture as a single dose and as eight consecutive daily doses, respectively. After a 1-mo interval the schedule was repeated but with a 10-fold higher dose (ie, 300 mg). In each case, the ratio of plasma d3-RRR-alpha-tocopherol to d6-all-rac-alpha-tocopherol (RRR:rac) increased from approximately 1.5-1.8 to approximately 2 after dosing ended. In an elective surgery study in which 22 patients were given 150 mg/d for up to 41 d before surgery, the RRR:rac in tissues was lower than in plasma and the percentage of deuterated alpha-tocopherol was lower in all tissues except gallbladder and liver. In a terminally ill patient given 30 mg/d for 361 d, plasma and tissue (x+/-SD) RRR-rac ratios (and % deuterated alpha-tocopherol) at autopsy were 2.06 (6.3%) and 1.71+/-0.24 (5.9+/-2.2%), respectively. In a second terminally ill patient given 300 mg/d for 615 d, the corresponding values were 2.11 (68%) and 2.01+/-0.17 (65+/-10%), respectively. The results indicated that natural vitamin E has roughly twice the availability of synthetic vitamin E. This 2:1 ratio is significantly higher than the currently accepted RRR:rac of 1.36:1.00. Gamma-Tocopherol, expressed as a fraction of total unlabeled tocopherols in 15 elective surgery patients, was 1.4-4.6 (mean: 2.6) times greater in adipose tissue, muscle, skin, and vein than in plasma, which is a substantially larger fraction than had been recognized previously.

Design and synthesis of analogs of vitamin E: antiproliferative activity against human breast adenocarcinoma cells.

Analogs of alpha-tocopherol (vitamin E; compounds 3-9) have been synthesized and tested for their antiproliferative activity using the human breast cancer cell line, MCF7. Compounds 6-9 were synthesized from a common symthom, rac-Trolox (14) and are soluble/miscible at physiological pH. Compounds 4, 8, and 9 were found to have antiproliferative activity at micromolar concentrations.

Taurocholate-induced dimerization of bovine cholesterol esterase in sodium dodecylsulfate.

Purified bovine cholesterol esterase (CE) showed one major band with an apparent molecular mass of 58 kDa on sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In the presence of taurocholate another major band with an apparent molecular mass of 116 kDa, corresponding to the dimer, appeared. Longer heating times and higher concentrations of CE in SDS-sample buffer increased the relative amount of the dimer. Higher SDS concentration in the sample buffer reduced the amount of dimer. Mercaptoethanol concentration had no effect. The dimer did not contain taurocholate and readily reverted to the monomer. It is concluded that taurocholate mediates the dimerization of CE in SDS by facilitating the formation of hydrophobic interactions between monomeric subunits.

Coastal bermudagrass rotation and fallow for management of nematodes and soilborne fungi on vegetable crops.

The efficacy of clean fallow, bermudagrass (Cynodon dactylon) as a rotational crop, and fenamiphos for control of root-knot nematode (Meloidogyne incognita race 1) and soilborne fungi in okra (Hibiscus esculentus), snapbean (Phaseolus vulgaris), and pepper (Capsicum annuum) production was evaluated in field tests from 1993 to 1995. Numbers of M. incognita in the soil and root-gall indices were greater on okra than on snapbean or pepper. Application of fenamiphos at 6.7 kg a.i./ha did not suppress numbers of nematodes on any sampling date when compared with untreated plots. The lack of efficacy could be the result of microbial degradation of the nematicide. Application of fenamiphos suppressed root-gall development on okra following fallow and 1-year sod in 1993, but not thereafter. A few galls were observed on roots of snapbean following 2- and 3-year fallow but none following 1-, 2-, and 3-year bermudagrass sod. Population densities of Pythium aphanidermatum, P. myriotylum, and Rhizoctonia solani in soil after planting vegetables were suppressed by 2- or 3-year sod compared with fallow but were not affected by fenamiphos. Yields of snapbean, pepper, and okra did not differ between fallow and 1-year sod. In the final year of the study, yields of all crops were greater following 3-year sod than following fallow. Application of fenamiphos prior to planting each crop following fallow or sod did not affect yields.

Vitamin C nutriture has little short-term effect on vitamin E concentrations in healthy women.

To determine whether the postulated sparing effect of vitamin E by ascorbic acid (AA) is important for human nutrition, we studied vitamin E status in 20 healthy pre-menopausal women (age 20-43 y) with high or low vitamin C intakes for 6 wk in a live-in metabolic unit. The experimental diet contained no fruits and vegetables and provided 5 mg/d of AA (Recommended Dietary Allowance = 60 mg/d), 3 mg/d of alpha-tocopherol (RDA = 10 mg/d) and 42 g/d of tocopherol-stripped safflower oil to increase the vitamin E requirement. Half of the subjects revived a daily AA supplement of 495 mg (high AA group). A biochemical ascorbate deficiency was attained in the low AA group as indicated by plasma AA concentrations that reached the lower limit of normal by study d 15. Oral doses (20 mg) of hexadeuterated RRR-alpha-tocopherol acetate (d6-alphaT) were given daily to all subjects on d 15-21. Measures of vitamin E status included d6-alphaT and unlabeled alpha-tocopherol concentrations in plasma, platelets, buccal cells and adipose. The levels of unlabeled alpha-tocopherol decreased over time in plasma and platelets and were unchanged for buccal cells and adipose, but were not significantly affected by AA intake. Likewise, the rise and fall of plasma and platelet d6-alpha T, and measures of lipid peroxidation, were not affected by AA intake. Although vitamin C nutriture did not significantly affect vitamin E status within the 6-wk time period of this experiment, further study of this question is warranted, because some of the present results indicate a trend toward sparing of tissue tocopherol by high AA intake.

Effect of vitamin E on human glutathione peroxidase (GSH-PX1) expression in cardiomyocytes.

To determine the effect of vitamin E on cellular antioxidant enzymes, human ventricular cardiomyocytes were incubated with 200 microM all-racemic-alpha-tocopheryl acetate for 14 d at pO2s of 150 and 40 mm Hg. Cellular Cu, Zn superoxide dismutase, catalase, and GSH-Px1 activities were measured. Although SOD and catalase activities were unaffected by alpha-tocopherol, GSH-Px1 activities increased (p < .0001) as much as twofold. This increase was independent of oxygen tension and selenium. The increase in GSH-Px1 activity became significant (p < .01) by day 4. A nonantioxidant analog of alpha-tocopherol, 200 microM RRR-alpha-tocopherol methyl ether, did not affect GSH-Px1 activities. Although GSH-Px1 mRNA levels mirrored the changes in enzyme activities, the de novo nuclear GSH-Px1 transcript synthesis was unaffected by alpha-tocopherol. Because the increase in GSH-Px1 activities also occurred after cellular alpha-tocopherol levels had plateaued, the above results were most consistent with posttranscriptional stabilization of GSH-Px1 mRNA by alpha-tocopherol or an alpha-tocopherol-related metabolic product.

Rotations with Coastal Bermudagrass and Fallow for Management of Meloidogyne incognita and Soilborne Fungi on Vegetable Crops.

The efficacy of fallow and coastal bermudagrass (Cynodon dactylon) as a rotation crop for control of root-knot nematode (Meloidogyne incognita race 1) and soilborne fungi in okra (Hibiscus esculentus cv. Emerald), squash (Cucurbita pepo cv. Dixie Hybrid), and sweet corn (Zea mays cv. Merit) was evaluated in a 3-year field trial. Numbers of M. incognita in the soil and root-gall indices were greater on okra and squash than sweet corn and declined over the years on vegetable crops following fallow and coastal bermudagrass sod. Fusarium oxysporum and Pythium spp. were isolated most frequently from soil and dying okra plants. Numbers of colony-forming units of soilborne fungi generally declined as the number of years in sod increased, but were not affected by coastal bermudagrass sod. Yields of okra following 2-year and 3-year sod and squash following 2-year sod were greater than those following fallow. Yield of sweet corn was not different following fallow and coastal bermudagrass sod.

Vitamin E for coronary bypass operations. A prospective, double-blind, randomized trial.

BACKGROUND: Free radical lipid peroxidation contributes to the abnormal metabolism and ventricular function frequently seen after cardiac operations. Antioxidants may improve metabolic and functional recovery. METHODS: A prospective, randomized, double-blind clinical trial was conducted to determine the effects of vitamin E (alpha-tocopherol) (n = 14) or a corn oil placebo (n = 14) in patients undergoing elective coronary bypass operations. The RRR-alpha-tocopheryl acetate doubled the alpha-tocopherol levels in the heart. Myocardial metabolism and ventricular function were assessed after the operation. RESULTS: Atrial pacing induced myocardial lactate production in the control patients but lactate consumption in the alpha-tocopherol-treated patients on bypass 25 minutes after crossclamp release. Left ventricular stroke work indices were higher, at similar ventricular volumes, in the alpha-tocopherol-treated group, which indicates improved preload recruitable stroke work, and diastolic compliance was greater 4 hours after the operation. The postoperative creatine kinase cardiac isoenzyme levels were lower in the patients who received alpha-tocopherol. CONCLUSIONS: Pretreatment with alpha-tocopherol sufficient to double the myocardial concentrations had a small but significant metabolic and functional effect after elective coronary bypass operations when compared with placebo. These results do not justify pretreatment of low-risk patients, but they do justify an evaluation in high-risk patients.

Vitamin E: molecular and biological function.

There is a growing body of evidence implicating free radicals in a wide variety of medical diseases and conditions, especially the diseases of ageing, such as cancer and cardiovascular disease, which appear to be ultimate expressions of long-term, cumulative and sustained cellular damage. Vitamin E is an excellent lipid-soluble, chain-breaking antioxidant in the presence of other co-operative antioxidants such as vitamin C or ubiquinol, but it can act as a pro-oxidant in their absence. Epidemiological findings and animal studies support the belief that vitamin E is protective against cardiovascular disease and possibly cancer. The wide range of symptoms associated with vitamin E deficiency is consistent with a loss of antioxidant protection in those long-lived cells in which there is sufficient opportunity for accumulation of free radical damage. The cellular damage is proposed to arise from the generation of free radicals during normal aerobic metabolism. Some susceptible tissues may have enhanced levels of radicals that are produced, for example, by the action of cytochrome P-450 enzymes in steroidogenic tissues, or by the generation of NO in neural tissues.

Forage quality and grazing steer performance from Tifton 85 and Tifton 78 bermudagrass pastures.

A new high-yielding bermudagrass hybrid, Tifton 85, produced 26% higher DM yield (P = .05) with 11% higher IVDMD (P = .05) than Coastal in two 3-yr yield trials. Tifton 78 and Tifton 85 were established in duplicate .81-ha pastures in 1988 and were grazed during 1989, 1990, and 1991 using a variable stocking rate method. Four tester steers per pasture with 269 kg initial BW grazed continuously for 169 d/yr beginning in April. Forage mass, targeted at 2,800 kg of DM/ha, was maintained by adjusting stocking rates at 14-d intervals to correspond with ground-level forage samples taken at 14-d intervals. Pastures received 84 kg of N/ha in March, June, and August of each year. Nutritive value was assessed using whole masticate samples from two esophageal cannulated steers grazing each pasture in late May, mid-July, or early September. The 3-yr mean masticate analyses revealed similar CP for Tifton 78 and Tifton 85 in May and July, but higher (P < .05) CP for Tifton 85 than for Tifton 78 in September. The IVDMD was higher (P < .05) in May and September for Tifton 85 than for Tifton 78; and, mean and medium particle sizes were greater (P < .05) for Tifton 85 than for Tifton 78 in May, July, and September samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Infusion nomograms.

Seven infusion nomograms are presented for the rapid and accurate composition of continuous infusions. The construction of these nomograms is described.

Discrimination between forms of vitamin E by humans with and without genetic abnormalities of lipoprotein metabolism.

To study the mechanisms of discrimination between various forms of vitamin E, four normal subjects, one patient with lipoprotein lipase deficiency, and three patients with abnormal apolipoprotein B-100 production were given an oral dose containing three tocopherols labeled with differing amounts of deuterium (2R,4'R,8'R-alpha-(5,7-(C2H3)2)tocopheryl acetate (d6-RRR-alpha-tocopheryl acetate), 2S,4'R,8'R-alpha-5-(C2H3)tocopheryl acetate (d3-SRR-alpha-tocopheryl acetate), and 2R,4'R,8'R-gamma-(3,4-2H)tocopherol (d2-RRR-gamma-tocopherol). The tocopherol contents of plasma, red cells, and lipoproteins were measured up to 76 h after the dose. In normal subjects all three tocopherols were absorbed and secreted in chylomicrons with equal efficiencies. Both d2-gamma- and d3-SRR-alpha-tocopherols peaked at similar concentrations in the other lipoprotein fractions, then decreased similarly, but 2-4 times more rapidly than did d6-RRR-alpha-tocopherol. A lipoprotein lipase-deficient patient and a patient with prolonged production of chylomicrons with absent apolipoprotein B-100 also demonstrated the lack of discrimination between tocopherols during absorption. Despite abnormal apolipoprotein B-100 production in two patients, the "VLDL" was preferentially enriched in d6-RRR-alpha-tocopherol. Our results show that there is no discrimination between the three tocopherols during absorption and secretion in chylomicrons, but subsequently there is a preferential enrichment of very low density lipoprotein (VLDL) with RRR-alpha-tocopherol. Catabolism of this VLDL results in the maintenance of plasma RRR-alpha-tocopherol concentrations.

Effect of orally administered alpha-tocopheryl acetate on human myocardial alpha-tocopherol levels.

Free radical injury may contribute to the delayed postoperative recovery of myocardial metabolism and ventricular function after elective coronary artery revascularization. This clinical study was designed to evaluate, in stable angina patients having aortocoronary bypass surgery, whether orally administered alpha-tocopheryl acetate was effective in increasing myocardial alpha-tocopherol levels and the effect of cardioplegic arrest followed by reperfusion on the myocardial alpha-tocopherol levels. Twenty-four patients with stable angina pectoris for elective revascularization received preoperatively the natural stereoisomer of alpha-tocopheryl acetate labelled with deuterium (D3) and six patients were used as controls. Since four patients who received 300 mg of D3-alpha-tocopheryl acetate preoperatively for 1 and 2 days did not have significant increases in their myocardial total or D3-tocopherol levels, the remaining 20 patients received 100 mg (n = 6), 300 mg (n = 8), or 900 mg (n = 6) of D3-alpha-tocopheryl acetate for 14 consecutive preoperative days. The left ventricular deuterated and nondeuterated alpha-tocopherol levels were measured by gas chromatography/mass spectrometry. Although there was a decrease (p less than 0.05) in myocardial alpha-tocopherol levels with the onset of reperfusion (cross-clamp removal), the myocardial tocopherol levels were not statistically different from preoperative levels by 20 minutes of reperfusion. At least 300 mg of alpha-tocopherol must be taken orally for 14 consecutive days to double the myocardial alpha-tocopherol levels.