Longitudinal vitamin D status in pregnancy and the risk of pre-eclampsia.

OBJECTIVE: Whether vitamin D deficiency in pregnancy is a cause of pre-eclampsia remains controversial. Most previous studies to date have assessed exposure at only one time-point in pregnancy. We assessed longitudinal vitamin D status during pregnancy and the risk of pre-eclampsia. DESIGN: Prospective cohort study. SETTING: Seventeen urban obstetric hospitals, Canada. POPULATION: Pregnant women who were participants in a trial of vitamin C and E supplementation for the prevention of pre-eclampsia. Canadian participants who consented to participate in a biobank with plasma specimens available at the baseline visit were included (n = 697). METHODS: Maternal plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured at 12-18 and 24-26 weeks of gestation using chemiluminescence immunoassay. MAIN OUTCOME MEASURES: Pre-eclampsia. RESULTS: Of the women, 39% were vitamin D deficient (25(OH)D <50 nmol/l). A strong positive correlation was observed in maternal 25(OH)D concentrations between the two gestational age windows (r = 0.69, P < 0.0001). Mean maternal 25(OH)D concentrations at 24-26 weeks of gestation were significantly lower in women who subsequently developed pre-eclampsia compared with those who did not (mean ± SD: 48.9 ± 16.8 versus 57.0 ± 19.1 nmol/l, P = 0.03). Women with 25(OH)D < 50 nmol/l at 24-26 weeks gestation experienced an increased risk of pre-eclampsia (adjusted odds ratio 3.24, 95% confidence interval 1.37-7.69), whereas the association was not statistically significant for maternal 25(OH)D level at 12-18 weeks of gestation. CONCLUSIONS: Lower maternal 25(OH)D levels at late mid-trimester were associated with an increased risk of pre-eclampsia.

25-Hydroxyvitamin D in Canadian adults: biological, environmental, and behavioral correlates.

SUMMARY: We assessed vitamin D status and its correlates in the population-based Canadian Multicentre Osteoporosis Study (CaMos). Results showed that serum 25-hydroxyvitamin D levels <75 nmol/L were common. Given Canada's high latitude, attention should be given to strategies for enhancing vitamin D status in the population. INTRODUCTION: Inadequate vitamin D has been implicated as a risk factor for several clinical disorders. We assessed, in a Canadian cohort, vitamin D status and its correlates, based on serum 25-hydroxyvitamin D [25(OH)D], the best functional indicator of vitamin D status. METHODS: We studied 577 men and 1,335 women 35+ years from seven cities across Canada in the randomly selected, population-based Canadian Multicentre Osteoporosis Study (CaMos). Participants completed a comprehensive questionnaire. Serum 25(OH)D was measured by immunoassay. Multivariate linear regression modeling assessed the association between 25(OH)D and determinants of vitamin D status. RESULTS: Participants (2.3%) were deficient in 25(OH)D (<27.5 nmol/L); a further 18.1% exhibited 25(OH)D insufficiency (27.5-50 nmol/L). Levels <75 nmol/L were evident in 57.5% of men and 60.7% of women and rose to 73.5% in spring (men) and 77.5% in winter (women); 25(OH)D <50 nmol/L was ≤10% year round for those supplementing with ≥400 IU vitamin D/day but was 43.9% among those not supplementing in winter and spring. The strongest predictors of reduced 25(OH)D for both men and women were winter and spring season, BMI ≥30, non-white ethnicity, and lower vitamin D supplementation and its modification by fall and winter. CONCLUSIONS: In this national Canadian cohort, vitamin D levels <75 nmol/L were common, particularly among non-white and obese individuals, and in winter and spring. Vitamin D intake through diet and supplementation and maintenance of normal weight are key modifiable factors for enhancing vitamin D status and thus potentially influencing susceptibility to common chronic diseases.

Influence of sources of dietary vitamin E on the maternal transfer of alpha-tocopherol to fetal and neonatal guinea pigs as determined by a stable isotopic technique.

The accepted biological potencies of vitamin E (United States Phamacopeia, 1985) for 1 mg all-rac-alpha-tocopheryl acetate (synthetic form) is 1.00 IU and that of 1 mg (RRR)-alpha-tocopheryl acetate (natural form) is 1.36 IU. In the present study, a stable isotopic (2H) technique was employed to evaluate the bioavailability of natural v. synthetic forms of vitamin E and to determine whether the potency of the forms is the stated relationship of 1.36:1.00 (RRR)-alpha-tocopheryl acetate:all-rac-alpha-tocopheryl acetate. Sixty female in-bred guinea pigs received either 40 or 80 mg vitamin E/kg diet with equal levels of (RRR)-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate throughout gestation and lactation. At late-term pregnancy (day 50 or 60) and during early lactation, dams and their corresponding fetuses or neonates were killed and various tissues collected for subsequent alpha-tocopherol analysis. Vitamin E analysis of fetal and neonatal tissues indicated a substantial transfer of 2H-labelled alpha-tocopherol across the placenta and through the mammary gland. Total alpha-tocopherol concentrations were significantly influenced by tissue type and dose level, but not by stage of gestation or lactation. The relative bioavailability (d3:d6) across fetal and neonatal tissues was on average 1.81:1.00, with a range from 1.62:1.00 to 2.01:1.00. Maternal tissues had a mean ratio of 1.77:1.00. A higher relative bioavailability (P

Effects of vitamin E on urokinase-plasminogen activator receptor expression by bovine neutrophils.

OBJECTIVE: To determine the effect of vitamin E supplementation on urokinase-plasminogen activator (u-PA) receptor (u-PAR) expression by neutrophils of dairy cows. ANIMALS: 16 healthy Holstein dairy cows. PROCEDURE: 16 cows were assigned to 1 of 2 experimental groups: control (no vitamin E supplementation) and vitamin E supplementation. Supplementation of vitamin E started 4 weeks prior to and continued up to 4 weeks after parturition and included oral administration of vitamin E at 3,000 U/cow per day; these cows also received 1 injection of vitamin E (5,000 units), 1 week prior to the expected date of parturition. Blood samples were collected, and neutrophils were isolated weekly throughout the experimental period. The following variables were measured: u-PA (mRNA), total cell-associated u-PA activity, membrane-bound u-PA activity, and free unoccupied u-PA binding sites on the cell membrane of neutrophils. RESULTS: Stimulated neutrophils isolated from cows that received vitamin E supplementation had significantly higher u-PA mRNA and total cell-associated and membrane-bound u-PA activity at postpartum week 1, compared with those of stimulated neutrophils isolated from control cows. There were no differences between groups throughout the whole experimental period in u-PA binding sites of neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: The increased total cell-associated and membrane-bound u-PA activity in neutrophils isolated from cows that received vitamin E may facilitate the ability of neutrophils to extravasate and reach the mammary gland at postpartum week 1. Rapid recruitment of neutrophils is critical for proper defense of the gland.

Influence of sources of dietary oils on the life span of stroke-prone spontaneously hypertensive rats.

In recent studies, the life span of stroke-prone spontaneously hypertensive (SHRSP) rats was altered by a variety of dietary fats. It was relatively shorter in rats fed canola oil as the sole source of fat. The present study was performed to find out whether the fatty acid profile and the high content of sulfur compounds in canola oil could modulate the life span of SHRSP rats. SHRSP rats (47 d old, n = 23/group) were matched by body weight and systolic blood pressure and fed semipurified diets containing 10% canola oil, high-palmitic canola oil, low-sulfur canola oil, soybean oil, high-oleic safflower oil, a fat blend that mimicked the fatty acid composition of canola oil, or a fat blend high in saturated fatty acids. A 1% sodium chloride solution was used as drinking water to induce hypertension. After consuming the diets for 37 d, five rats from each dietary group were killed for collection of blood and tissue samples for biochemical analysis. The 18 remaining animals from each group were used for determining their life span. The mean survival time of SHRSP rats fed canola oil (87.4+/-4.0 d) was not significantly different (P > 0.05) from those fed low-sulfur canola oil (89.7+/-8.5 d), suggesting that content of sulfur in canola oil has no effect on the life span of SHRSP rats. The SHRSP rats fed the noncanola oil-based diets lived longer (mean survival time difference was 6-13 d, P < 0.05) than those fed canola and low-sulfur canola oils. No marked differences in the survival times were observed among the noncanola oil-based groups. The fatty acid composition of the dietary oils and of red blood cells and liver of SHRSP rats killed after 37 d of treatment showed no relationship with the survival times. These results suggest that the fatty acid profile of vegetable oils plays no important role on the life span of SHRSP rat. However, phytosterols in the dietary oils and in liver and brain were inversely correlated with the mean survival times,indicating that the differential effects of vegetable oils might be ascribed, at least partly, to their different phytosterol contents.

Effect of chronic ethanol dosing on hepatic triglyceride and phospholipid profile and fatty acids in the guinea pig.

An alcohol feeding study was conducted with guinea pigs to evaluate the influence of alcohol upon hepatic triglyceride and total phospholipid profile as well as phospholipid fatty acids. Twenty-seven guinea pigs were randomly assigned into four groups consisting of a control and alcohol-treated group and each group carried over a 105- or 135-day period . Alcohol was administered via the drinking water starting with a 2.5% solution (v/v) and gradually increased to 12.5% (v/v) over a 30-day period and thereafter maintained continuously for either 75 or 105 days, respectively. Control guinea pigs received glucose via the drinking water to match isocalorically the alcohol given to the test animals. At the end of the 105- and 135-day periods, animals were sacrificed and livers collected. Hepatic triglycerides were significantly elevated by alcohol dosing, whereas total phospholipid fraction remained essentially unaltered. No significant time effect was observed on hepatic triglyceride and phospholipid profiles. In ethanol-fed guinea pigs, significant increases in percentages of 18:1 n-9 and 18:2 n-6 and decreases in 16:0, 20:3 n-6 and 20:4 n-6 were observed in hepatic total phospholipid fatty acid profile compared to controls. In addition, other polyenoic acids including 22:4 n-6, 22:5 n-6, 22:5 n-3, and 22:6 n-3 were found to be highly significantly depressed in alcohol-treated animals in comparison to the controls. This study provides important baseline lipid data on guinea pig responses to ethanol and provides a starting point for the use of the guinea pig as an experimental model.

Gender and exercise influence on tissue antioxidant vitamin status in rats.

Although gender differences in antioxidant status based largely on differing estrogen levels have been postulated, it is not known if other gender based differences in tissue antioxidants exist. This experiment examined whether gender based differences in tissue vitamin C and vitamin E concentration exist, and investigated the possibility of gender based differences in indices of tissue oxidative stress following an acute exercise bout. It was determined that female rats had significantly higher levels of vitamin E in liver and heart tissues than males and that males had significantly more vitamin C in the plantaris muscle than females. However, female rats also had less liver glutathione than males. Acute exercise resulted in significant and equal tissue oxidative stress in both genders as indicated by tissue glutathione status. With some exceptions, tissue vitamin C and vitamin E concentrations were generally unaffected by acute exercise in either gender. Hence, while some gender differences in tissue antioxidant status in rats are evident, these differences do not affect tissue indices of oxidative stress following acute exercise.

Estrogen administration, postexercise tissue oxidative stress and vitamin C status in male rats.

Estrogen can putatively act as an antioxidant and protect tissues from exercise-induced oxidative stress. To test the in vivo efficacy of estrogen, the effects of 2 weeks of daily estrogen (40 microg x kg(-1) body weight beta-estradiol 3-benzoate) injection on indices of immediate postexercise oxidative stress and antioxidant status were determined in adult male rats, with and without 8 weeks of prior dietary vitamin E deprivation. The treadmill running protocol (60 min at 21 m x min(-1), 12% grade) induced significant oxidative stress as indicated by muscle glutathione status. Estrogen administration had little effect on postexercise tissue glutathione status, superoxide dismutase and glutathione peroxidase activity, and vitamin E levels. Estrogen administration induced significant reductions in muscle, liver, and heart vitamin C concentrations following exercise, as well as in unexercised male rats. Tissue vitamin C loss was not directly mediated through liver glycogen or glutathione status. Thus, estrogen administration generally did not appear to influence postexercise tissue indices of oxidative stress or antioxidant status and may have contributed to a decline in overall antioxidant protection by inducing losses in tissue vitamin C content.

Effects of vitamin E on mammary and blood leukocyte function, with emphasis on chemotaxis, in periparturient dairy cows.

OBJECTIVE: To determine the effect of vitamin E supplementation on the immune system of dairy cows. DESIGN: The following immune parameters were followed: production of chemotactic factors and superoxide by mammary macrophages and chemotactic responsiveness of blood neutrophils. ANIMALS: 16 healthy Holstein dairy cows. PROCEDURE: Dairy cows were assigned to 1 of 2 experimental groups: control (no vitamin E supplementation) and vitamin E supplemented. Supplementation of vitamin E started 4 weeks before and continued up to 8 weeks after parturition, and included oral supplementation of vitamin E at the rate of 3,000 IU/cow/d. In addition, the same group of cows received 1 injection of vitamin E (5,000 IU) 1 week prior to the expected date of parturition. Blood samples were collected weekly throughout the experimental period. RESULTS: Vitamin E supplementation enhanced by 30 to 83% (P < 0.05) chemotactic responsiveness of blood neutrophils beginning 2 weeks before to 4 weeks after parturition, compared with controls. There were no differences in production of superoxide or chemotactic factors by mammary macrophages between control and vitamin E-supplemented cows. CONCLUSIONS: Vitamin E supplementation prevents the periparturient inhibition of neutrophil chemotaxis. It is unlikely that vitamin E affects directly the function of mammary macrophages.

Relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate in humans: studies using deuterated compounds.

Vitamin E in nutritional supplements in its most common form is alpha-tocopheryl acetate. Available stereoisomeric forms are RRR- (1 stereoisomer) and all-rac- (8 stereoisomers). We evaluated the relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate using the deuterium-labeled isotopes [5-CD3] 2R, 4'R and 8'R-alpha-tocopheryl acetate (d3), and [5,7-(CD3)2]-all-rac-alpha-tocopheryl acetate (d6). Six adults (three males, three females), aged 25-59 y, received 150 mg each of d3 and d6 for 11 consecutive days. Blood samples were collected on days -1, 0, 1-11, 13, 14, 20, 25, 30, 60, 74, 88, 102, 122, and 137. Plasma and red blood cell tocopherol were evaluated by using HPLC and gas chromatography/mass spectrometry to distinguish between d3 and d6 tocopherols. Cholesterol, triglycerides, and LDL and HDL cholesterol were measured. Relative bioavailability of d3 when compared with d6 was 2.0 +/- 0.06 when area under the plasma time concentration curve (AUC d3/d6) by trapezoidal rule (P < 0.05) was used. Correcting for lipid yielded the same finding. Unlabeled tocopherol (d0) decreased (P < 0.05) with vitamin E administration. It was concluded that the ratio of bioavailability of RRR-/all-rac-alpha-tocopheryl acetate is significantly greater than the currently accepted ratio of 1.36.

Effect of chronic alcohol ingestion on hepatic folate distribution in the rat.

The mechanism by which ethanol impairs folate metabolism remains uncertain. In the present study, we used our new technique (affinity/HPLC) for folate analysis to study the effect of chronic alcohol ingestion on the content and distribution of folates in livers. Twelve male Sprague-Dawley rats (180 g) were divided into two groups, and fed for 4 weeks with Lieber-DeCarli semi-liquid isocaloric diets, with and without 5% ethanol. Livers were extracted in boiling, pH 9.3 borate buffers containing ascorbate/dithioerythritol. Folates in the supernatant fractions were purified by affinity chromatography and analyzed using ion pair high performance liquid chromatography. The data obtained showed that hepatic folate distribution in alcohol-treated rats differed from that of control animals in two ways. Livers from the ethanol-fed rats, when compared with those from control rats, exhibited increases in the percent concentrations of methylated tetrahydrofolates (21.46 +/- 2.21 vs 14.8 +/- 1.23), decreases in the percent concentrations of formylated tetrahydrofolates (25.62 +/- 4.02 vs 46.18 +/- 2.65) and higher concentrations of unsubstituted tetrahydrofolates (52.91 +/- 3.84 vs 38.88 +/- 2.50). In addition, alcohol ingestion was associated with longer glutamate chains of the folate molecules, characterized by lower relative concentrations of pentaglutamyl folates (29 vs 48%), and higher relative concentrations of hexa- and heptaglutamyl folates (55 vs 46% and 15 vs 6%) when compared with controls. The data are discussed in relation to the possibility that alcohol exerts its effect through: (1) inhibition of B12-dependent methyl transfer from methyltetrahydrofolate to homocysteine; (2) diversion of formylated tetrahydrofolates toward serine synthesis; and (3) interaction of acetaldehyde with tetrahydrofolates, thereby interfering with folate coenzyme metabolism.

Tissue alpha-tocopherol concentrations following supplementation with various forms of vitamin E in sheep.

Tissue alpha-tocopherol concentrations were determined in 40 lambs following oral supplementation of various forms of vitamin E. Lambs were allocated to 8 dietary groups of 5 animals each and supplemented with or without equimolar amounts (300 mg equivalence) of different vitamin E compounds daily for 60 d as follows: 1) control, no supplemental vitamin E; 2) D-alpha-tocopheryl acetate; 3) DL-alpha-tocopheryl acetate; 4) DL-alpha-tocopheryl nicotinate; 5) D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS); 6) DL-alpha-tocopheryl nicotinate+TPGS; 7) D-alpha-tocopheryl acetate+TPGS; and 8) D-alpha-tocopheryl succinate. At the end of the 60 d the lambs were killed and portions of adrenal, fat, heart, kidney, liver, lung, skeletal (brachiocephalicus and gluteus) muscles, pancreas and spleen were removed. Daily supplementation with various vitamin E compounds (equivalence) in lambs resulted in significant differences in tissue alpha-tocopherol concentration in heart, liver, gluteus medius muscle, and spleen. Correlations between the plasma and tissue alpha-tocopherol levels were highly significant for all tissues except adrenal, fat, and pancreas.

The relationship of ethanol feeding to the methyl folate trap.

Feeding rats a semiliquid ethanol diet for a period of four weeks produced a hepatic accumulation of the methylating agent N5-methyltetrahydrofolate (N5CH3THF). When the ethanol-containing diet was supplemented with 0.5% betaine, an agent known to promote the generation of methionine and S-adenosylmethionine (SAM) in ethanol-fed animals, the accumulation of N5CH3THF was prevented. One index that the methyl folate trap exists is the hepatic accumulation of N5CH3THF, and a second index is that the N5CH3THF accumulation can be relieved by methionine administration. Since ethanol is shown to produce N5CH3THF accumulation in this study, and since betaine (a generator of methionine and SAM) acts to eliminate this accumulation, it is suggestive that ethanol can contribute to the impairing hepatic condition referred to as the "methyl folate trap."

A dynamic evaluation of the bioavailability of the free and ester forms of vitamin E administered intramuscularly to beef cattle.

Two trials were carried out to evaluate the bioavailability of 2 vitamin E components, D-alpha-tocopherol and DL-alpha-tocopherol acetate administered to 6 cattle intramuscularly (IM). In the first trial, 6 heifers received 3 doses at 28-d intervals of 13,500 IU, 4,500 IU, and 4,500 lu respectively of D-alpha-tocopherol. The blood plasma alpha-tocopherol curve area (AUC) and maximum increase (Cmax) were higher following administration of the 13,500 IU than of the 4,500 IU doses. The lowest AUC and Cmax were observed after the third injection of D-alpha-tocopherol. However, no difference was found for the adjusted values of AUC between the second and third dose. Time to maximum increase was shorter following the 13,500 IU dose than the 4,500 IU. The data following administration of 13,500 IU vitamin E fitted to a 2-compartment open model. In a second trial, 6 heifers received 2 doses IM of 4,500 IU DL-alpha-tocopherol acetate at 28-d intervals. Differences were not observed for AUC, Cmax and the time required for maximum plasma concentration between the 2 phases of 28 d in the acetyl forms-dosed cattle.

Serum total cholesterol, high-density lipoprotein-cholesterol and triglyceride concentrations in lambs following supplementation with various forms of tocopherol.

A 61-d study involving 40 crossbred lambs evaluated the effect of various forms of tocopherol provided daily in equimolar amounts on total cholesterol, high-density lipoprotein-cholesterol and triglyceride concentrations in the serum of lambs. Thirty-five lambs were allotted to 7 treatment groups of 5 animals each, supplemented with 300 mg tocopherol either as: 1) DL-alpha-tocopheryl acetate; 2) D-alpha-tocopheryl acetate; 3) D-alpha-tocopheryl succinate; 4) D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS); 5) DL-alpha-tocopheryl nicotinate; 6) DL-alpha-tocopheryl nicotinate (150 mg) + 150 mg TPGS; and 7-D-alpha-tocopheryl acetate (150 mg) + 150 mg TPGS mixed with the commercial flock diet. In addition, another group of 5 lambs were used as control (no vitamin E supplementation). Dietary supplementation of various vitamin E sources resulted in no overall treatment effects for total cholesterol, triglycerides or high density lipoprotein-cholesterol. A significant variation was noticed among animals. The levels of all measured serum components varied throughout the experimental period (P < 0.0001). The day x treatment interaction was not significant (P > 0.05) for any serum measured component. The present data strongly suggest that short-term treatment (< 2 mo) with pharmacological oral doses of various forms of vitamin E did not influence serum lipid metabolism of lambs. The data also showed that the bioavailability of alpha-tocopherol is dependent on the form administered. D-alpha-tocopherol acetate is a highly available form, the bioavailability of which is further increased when combined with D-alpha-tocopheryl polyethylene glycol succinate.

Bioavailability of vitamin E compounds in lambs.

A study was carried out to assess the bioavailabilities of several forms of vitamin E in lambs. A total of 40 lambs was allotted to eight dietary groups of five each and supplemented or not daily for 60 d with equimolar amounts of different vitamin E compounds as follows: 1) control, no supplemental vitamin E, 2) DL-alpha-tocopheryl acetate, 3) D-alpha-tocopheryl acetate, 4), D-alpha-tocopheryl succinate, 5) D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS), 6) DL-alpha-tocopheryl nicotinate, 7) DL-alpha-tocopheryl nicotinate+ TPGS, or 8) D-alpha-tocopheryl acetate + TPGS. During these 60 d, serum alpha-tocopherol concentrations in the control lambs remained constant and lower (P less than .05) than in lambs that received all treatments. Various indices of bioavailability, including Cmax-C(i) (concentration maximum-concentration initial), Ct-C(i) (concentration terminal-concentration initial), areas under the serum concentrations profiles, and pooled increment were higher (P less than .05) with D-alpha-tocopheryl acetate+ TPGS than in the other groups, suggesting a synergism between these forms. No such effect was observed between nicotinate and TPGS. For the TPGS, a water-soluble form of vitamin E, the indices of bioavailability were lower (P less than .05) than for the other groups. D-alpha-tocopheryl acetate resulted in a bioavailability that outranked all the other forms of vitamin E, except those of D-alpha-tocopheryl acetate + TPGS. A slightly higher bioavailability index was observed for D-alpha-tocopheryl succinate than for DL-alpha-tocopheryl nicotinate.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma and hepatic alpha-tocopherol in cattle following oral or intramuscular supplementation.

Blood and hepatic tocopherol concentration following i.m. injection or oral supplementation was studied in nonlactating dairy cows and pregnant beef heifers, respectively. In Experiment 1, cows received a single i.m. injection of either 4500 IU of d-alpha-tocopherol or 4500 or 7500 IU of dl-alpha-tocopheryl acetate. Plasma and liver tocopherol concentrations were recorded before and up to 4 wk postinjection. In Experiment 2, heifers received either 0, 1000, 2000, or 4000 IU of dl-alpha-tocopheryl acetate daily in the ration for 3 wk. Serum and hepatic tocopherol concentrations were measured before, during, and 3 wk following supplementation. In Experiment 1, level of tocopheryl acetate given influenced plasma and hepatic tocopherol concentrations. Plasma alpha-tocopherol concentration was greater in cows given unesterified tocopherol than an equivalent amount of tocopherol acetate. There was a quadratic relationship between plasma and hepatic tocopherol concentration. In Experiment 2, increasing dietary intake of dl-alpha-tocopheryl acetate failed to increase markedly tocopherol levels in serum or liver. There was no relationship between serum and hepatic tocopherol concentrations. Prior to the trials, serum levels in Experiment 2 were less than plasma levels in Experiment 1, but hepatic levels were greater. Physiological state can influence the relation between circulating and stored reserves of tocopherol, and circulating tocopherol concentration may not be a good indicator of its reserves.

Comparative vitamin E requirements and metabolism in livestock.

It has been over 50 years since vitamin E was originally described as a lipid-soluble dietary constituent required for normal reproduction in rats. Vitamin E is recognized as an essential vitamin required for all classes of animals functioning predominantly as an intracellular antioxidant in maintaining the integrity of biological cell membranes. Although a wealth of information has been gathered on clinical signs of vitamin E deficiency, establishing its requirements for animals has been exceedingly difficult because of interrelationships with other dietary constituents. Vitamin E requirements for animals cannot be defined in isolation. Requirements are influenced by the amount and type of fat (particularly with monogastrics) and degree of fat oxidation in the diet; the presence of antioxidants; dietary selenium (closely interrelated with vitamin E), iron, copper, and sulphur amino acids, as well as the physiological status of the animal. Other factors to be considered in assessing vitamin E needs of animals under commercial production conditions include: a) variability of vitamin E content in feedstuffs; b) poor stability of vitamin E during processing and storage of feeds; and c) management practices resulting in overstressed animals. Information on the function of or requirements for vitamin E in animals is very incomplete. Estimated dietary vitamin E requirements for most animal species are in the range of 10-40 IU/kg of diet. Of particular concern is the lack of vitamin E requirement information regarding young dairy and beef calves. Although good experimental evidence indicates a beneficial role of supplemental vitamin E above physiological levels on overall performance, enhanced immunocompetence and preservation of meat and milk products, levels of vitamin E required to produce these desired effects needs to be firmly established. Present estimated dietary requirements for vitamin E across species may need to be redefined as new information becomes available about the role this nutrient plays in growth, health and overall metabolism.

Vitamin E kinetics after intraperitoneal administration of DL-alpha-tocopherol and DL-alpha-tocopherol acetate in sheep.

The disposition of radiotocopherol after intraperitoneal administration of 14C-labelled-DL-alpha-tocopherol (1 microCi/kg bw, dose 1) and 3H-labelled-DL-alpha-tocopherol (4 microCi/kg bw dose 4) and of D-alpha-tocopherol, after intraperitoneal administration of DL-alpha-tocopherol acetate (100 mg/kg bw) was investigated in sheep. Plasma samples were taken at regular intervals after dosing and assayed for radioactivity and D-alpha-tocopherol. Plasma profiles were modelized using a compartmental approach and the input entry rate (for radioactivity) was identified using a numerical deconvolution method. Based on plasma specific activity (dose 1 and dose 4) and D-alpha-tocopherol plasma concentration (unlabelled alpha-tocopherol acetate), half-lives were not significantly different (99.6 +/- 28.3 h, 121.3 +/- 38.5 h and 75.0 +/- 49.75 h after dose 1, dose 4 and unlabelled alpha-tocopherol respectively). The times to reach maximal plasma concentrations were similar for the 3 test articles (mean values ranging from 21.5 to 26.7 h). The only significant difference was observed for the apparent volume of distribution (with respect to bioavailability) which was much larger for the unlabelled test article. Deconvolution study of plasma specific activity showed: i), that the maximal input rate was reached only after a short delay (3 to 12 h); ii), that half of the activity was absorbed after a delay of 38.13 +/- 16.76 h (dose 1) and 44.3 +/- 6.50 h (dose 4); and iii), that 90% of the activity was absorbed after 151.2 +/- 27.3 h (dose 1) and 162.3 +/- 11.2 (dose 4). It is concluded that the intraperitoneal route is of interest for alpha-tocopherol administration, but that more information is required to determine the exact process of absorption.

Plasma and tissue vitamin E concentrations in sheep after administration of a single intraperitoneal dose of dl-alpha-tocopherol.

Blood plasma and tissue Vitamin E concentrations were determined in 20 sheep following a single i.p. dose of 5 g of dl-alpha-tocopherol. In addition, five sheep were used as controls (no treatment and killed at d 0). From the 20 vitamin E-dosed sheep, 4 were slaughtered on d 3, 6, 10, 15 and 28 after dosing. There was a significant time effect in alpha-tocopherol concentrations in all tissues. In most tissues, the peak alpha-tocopherol concentration was at 3 d postdosing. Uptake varied among the different tissues examined. Three days postdosing, a large uptake of vitamin E by the liver was observed; this supports the concept that hepatic tissues are a target organ for vitamin E action. Also at 3 d uptake was pronounced in spleen and lung. Vitamin E concentrations in the other body tissues at d 3 postdosing increased considerably, but to a lesser degree than those in liver, spleen and lung. Vitamin E concentration in all tissues declined 3 d after i.p. dosing.