Is all-rac-alpha-tocopherol different from RRR-alpha-tocopherol regarding cardiovascular efficacy? A meta-analysis of clinical trials.

A meta-analysis of 14 clinical studies with RRR- or all-rac-alpha-tocopherol (83,800 subjects) was performed to evaluate whether RRR and all-rac differ in cardiovascular efficacy based on those clinical endpoints that are most consistently documented in the publications of the studies. Odds ratios of treatment versus control for individual studies and for studies pooled by form were centered around unity, with no significant differences between vitamin E forms. The results corroborate the present opinion that vitamin E supplements up to 800 mg/d for up to 6.5 years are safe.

Serum beta-carotene and alpha-tocopherol in horses fed beta-carotene via grass-meal or a synthetic beadlet preparation with and without added dietary fat.

The serum response of beta-carotene as an indicator of bioavailability was compared after feeding beta-carotene (0.8 mg/kg body weight) either from grass meal or a synthetic beadlet preparation (Lucarotin). Both were each given without or with added dietary vegetable fat (2-2.5% vs. 6.6% fat in dry matter) in a Latin square design with four horses. The nutritionally complete diet was supplemented with alpha-tocopherol (4 mg/kg body weight). Each treatment period (4 weeks, two serum samples) was followed by a washout period of 4 weeks with low intakes of beta-carotene (traces) and alpha-tocopherol (0.5 mg/kg body weight). Within 4 weeks of supplementation, serum beta-carotene increased about 10-fold, from a mean initial concentration of 0.05-0.53 micromol/l. There was no effect of beta-carotene source and of fat addition, respectively. Faecal excretion of beta-carotene ranged from 55 to 81% of intake. No beta-carotene was detected in any urine sample. Serum alpha-tocopherol (across all time points and animals, n=64) was 14.5 micromol/l. During supplementation, the values were significantly higher than during washout-periods. Additional dietary fat did not affect the serum response. Faecal excretion of alpha-tocopherol ranged from 69 to 121% of intake. Fat addition resulted in a significant decrease of serum cholesterol. In conclusion, the natural and the synthetic source of beta-carotene showed significant and identical bioavailability independent of additional fat.

Enrichment of eggs with n-3 polyunsaturated fatty acids: effects of vitamin E supplementation.

Eggs enriched with n-3 polyunsaturated fatty acids (PUFA) could contribute to dietary intake of these healthful fatty acids (FA). Because n-3 PUFA are highly susceptible to peroxidation, a first part of the study with Leghorn laying hens was carried out to investigate the influence of different levels of fish oil (0, 0.7, 1.4, 2.8, or 5.6%, respectively) in the diet on n-3 PUFA, cholesterol, vitamin E, and lipid peroxidation product contents in eggs. Addition of fish oil to a complete diet based on wheat, rye, tapioca, and soybean constituents containing 11 IU vitamin E/kg resulted in increased n-3 PUFA content in egg yolk, mainly due to accumulation of docosahexaenoic acid. Cholesterol was not altered up to 2.8% fish oil in the diet. The vitamin E content of the yolk was insufficient for the protection of PUFA from peroxidation. Addition of up to 2.8% fish oil to laying hen diets increased the n-3 PUFA content of yolks with a concomitant imbalance between vitamin E and PUFA, leading to increased levels of cytotoxic aldehydic lipid peroxidation products such as malondialdehyde (MDA). In a second part of the studies, the balance between vitamin E, PUFA, and lipid peroxidation was analyzed during the period of storage of n-3 PUFA-enriched eggs produced after feeding the laying hens with 1.5% fish oil diets with different concentrations of vitamin E (0, 5, 10, 20, 40, 80, 160 IU/kg). Storage of eggs resulted in a marked loss of vitamin E in yolk. In stored eggs, the cytotoxic lipid peroxidation products MDA, 4-hydroxynonenal, and 4-hydroxyhexenal were reduced in response to vitamin E supplementation. To prevent the increase of cytotoxic aldehydic lipid peroxidation during production and storage of n-3 PUFA-enriched eggs, a high vitamin E supplementation with at least 80 IU vitamin E/kg is needed.

Bioavailability and potency of natural-source and all-racemic alpha-tocopherol in the human: a dispute.

Alpha-tocopherol occurs in nature as a single stereoisomer (RRR) while synthetic vitamin E is a mixture of eight stereoisomers (all-racemic, all-rac). The presently accepted ratio of biopotency (RRR: all-rac) is 1.36, based on the fetal resorption test in rats. This ratio has been disputed for humans. Clinical endpoint studies in humans are lacking, but plasma responses to RRR- and all-rac were measured in bioavailability studies. In nine studies comparing unlabeled forms, the ratio of plasma parameters (AUC, Cmax or steady-state concentration) concurred with the accepted ratio of biopotency within accepted bounds of equivalence. Four recent studies with simultaneous application of trideutero-RRR and hexadeutero-all-rac resulted in ratios of up to 2 for plasma, and of approximately 2.7 and approximately 3.4 for alpha-CEHC (a urinary metabolite) and umbilical cord plasma, respectively. Because these results have been widely assumed to reflect the difference in biopotency, this has prompted a proposal to the Food and Nutrition Board, National Academy of Sciences, USA to change the biopotency factor to 2 : 1. We challenge the validity of bioavailability data in lieu of clinical endpoints. Because RRR and all-rac are not chemically identical and differ in plasma and tissue kinetics and metabolism, the ratio of bioavailability parameters does not reflect the ratio of biopotency. This needs to be determined in adequately designed studies using clinical and biochemical endpoints. Until such studies have been performed it does not appear prudent to exchange the presently accepted ratio based on valid bioassays, albeit in a model animal, for another that is based on erroneous conclusions from human studies.

Studies of LDL oxidation following alpha-, gamma-, or delta-tocotrienyl acetate supplementation of hypercholesterolemic humans.

In vitro tocotrienols (T3s) have potent vitamin E antioxidant activity, but unlike tocopherols can inhibit cholesterol synthesis by suppressing 3-hydroxy-3-methyl-glutarylCoA (HMG-CoA) reductase. Because hypercholesterolemia is a major risk factor for coronary artery disease and oxidative modification of low-density lipoprotein (LDL) may be involved in atherogenesis, we investigated whether daily supplements of placebo, or alpha-, gamma-, or delta- (alpha-, gamma-, or delta-) tocotrienyl acetates would alter serum cholesterol or LDL oxidative resistance in hypercholesterolemics in a double-blind placebo controlled study. Subjects were randomly assigned to receive placebo (n = 13), alpha- (n = 13), gamma- (n = 12), or delta- (n = 13) tocotrienyl acetate supplements (250 mg/d). All subjects followed a low-fat diet for 4 weeks, then took supplements with dinner for the following 8 weeks while still continuing diet restrictions. Plasma alpha- and gamma-tocopherols were unchanged by supplementation. Plasma T3s were undetectable initially and always in the placebo group. Following supplementation in the respective groups plasma concentrations were: alpha-T3 0.98 +/- 0.80 micromol/l, gamma-T3 0.54 +/- 0.45 micromol/l, and delta-T3 0.09 +/- 0.07 micromol/l. Alpha-T3 increased in vitro LDL oxidative resistance (+22%, p <.001) and decreased its rate of oxidation (p <. 01). Neither serum or LDL cholesterol nor apolipoprotein B were significantly decreased by tocotrienyl acetate supplements. This study demonstrates that: (i) tocotrienyl acetate supplements are hydrolyzed, absorbed, and detectable in human plasma; (ii) tocotrienyl acetate supplements do not lower cholesterol in hypercholesterolemic subjects on low-fat diets; and (iii) alpha-T3 may be potent in decreasing LDL oxidizability.

Bioavailability of water- and lipid-soluble thiamin compounds in broiler chickens.

The bioavailability of thiamin mononitrate, thiamin chloride-hydrochloride and benfotiamin was compared in broiler chickens. A thiamin-deficient diet was supplemented with either 1.8 and 1.5 mg/kg thiamin equivalent as water-soluble salts, or with 1.5 and 1.2 mg/kg thiamin equivalent as benfotiamin, respectively, and fed to 3 replicate groups/treatment for 21 days. Weight gain, feed consumption and feed conversion rate were not significantly affected by solubility or dietary level of thiamin. Likewise, using biochemical indices of thiamin status (erythrocyte transketolase activation coefficient, and thiamin concentrations in blood and liver), no differences were found between the water-soluble thiamin salts, indicating that they have identical potency. In contrast, biochemical indices of thiamin status showed a significantly higher bioavailability for benfotiamin than for the water-soluble sources.

Plasma alpha-tocopherol, beta-carotene, and lipid levels in semi-free-ranging Przewalski horses (Equus przewalskii).

Circulating concentrations of alpha-tocopherol, beta-carotene, and lipids were quantified in 19 Przewalski horses (Equus przewalskii) inhabiting the steppes of Ukraine during June 1991. Foals (n = 3) had lower mean plasma alpha-tocopherol (4.7 micrograms/ml) and beta-carotene (0.3 microgram/ml) levels than did adults (n = 16; 6.6 and 0.7 micrograms/ml, respectively) and higher mean cholesterol concentrations (1.42 vs. 0.98 mg/ml). Mean triglyceride levels did not differ between foals and adults (0.46 mg/ml). Alpha tocopherol concentrations were substantially higher than those considered normal for domestic and zoo equids, but beta-carotene, cholesterol, and triglyceride levels were within expected ranges. These limited data suggest excellent circulating vitamin E concentrations in these horses and may provide useful comparative guidelines for assessment of fat-soluble nutrient concentrations and establishment of optimal dietary management of Przewalski horses.

Dietary beta-carotene elevates plasma steady-state and tissue concentrations of beta-carotene and enhances vitamin A balance in preruminant calves.

Preruminant calves are regarded as a model for studying beta-carotene bioavailability in humans. The objectives of this trial were to determine the relationship between multiple beta-carotene doses and plasma steady-state concentration, accumulation in selected tissues, and vitamin A balance in liver. Seventy newborn Holstein calves in six treatments (n = 10/treatment) were fed a complete milk replacer diet low in vitamin A and supplemented with beta-carotene doses of 0, 0.23, 0.46, 0.92, 1.84 or 3.68 mumol/(kg body wt.d) for 28 d. Ten calves were killed on d 1. Plasma beta-carotene increased in relation to log transformations of dose and time (P < 0.05) in all supplemented calves and steady state was attained after 4 wk. For doses up to 0.92 mumol/(kg body wt.d), the dose-response relationship was linear. A dose-dependent accumulation of beta-carotene was found for liver, heart, lungs, adrenals and adipose tissue. All-trans-beta-carotene was the only isomer in plasma and adrenals and the predominant isomer in the remaining tissues. In liver, vitamin A increased with beta-carotene uptake. Hepatic balance between vitamin A accumulation and loss was achieved at beta-carotene intake of 0.36 mumol/(kg body wt.d) for a calf of 45 kg. It is concluded that preruminant calves within 1 mo of age utilize beta-carotene as a source of vitamin A, and that for testing bioavailability of beta-carotene sources, doses up to 0.92 mumol beta-carotene/(kg body wt.d) are most appropriate.

[Reducing lipid peroxidation of stored frozen trout fillet by supplementing feed with vitamin E]. / Reduzierung der Lipidperoxidation in gefroren gelagertem Forellenfilet durch Supplementierung des Futters mit Vitamin E.

Rainbow trouts were fed a complete diet with 12 mg vitamin K3 and supplemented with 20, 200 or 2,000 mg all-rac-alpha-tocopheryl-acetate/kg for 18 weeks. The ratio of the vitamin E-supplementation was 1:10:100. Fillets were minced and stored at -18 degrees C. Concentrations of alpha-tocopherol and phylloquinone and parameters of lipid peroxidation were measured after 4, 6, and 8 months of storage. The effects of alpha-tocopherol incorporated into fillets on storage stability were assessed by measuring free fatty acids, peroxides, malondialdehyde and lipofuscin. Mean alpha-tocopherol-concentrations in fillets were 1.4, 2.7 and 16.3 mg/100 g, respectively representing ratios of 1:2:12. The increase in alpha-tocopherol concentration resulted in a significant improvement of storage stability. The phylloquinone concentration in fillet was reduced in treatments with > or = 200 mg vitamin E/kg; however, this did not affect the prothrombin time. No peroxides were detectable at any time. The concentrations of malondialdehyde significantly decreased with increasing supplementation of vitamin E. Lipofuscin concentrations were higher with low than with high vitamin E supplementation. The dose-related inhibition of lipid peroxidation became apparent in decreased concentrations of free fatty acids in the crude fat. These results confirm the effectiveness of alpha-tocopherol as antioxidant in fish flesh. In this study the incorporation of alpha-tocopherol from dietary supplementation improved the long-term storage quality of trout fillets due to the effective inhibition of the lipid peroxidation. A measurable improvement of the storage stability was achieved with a supplementation of 200 mg vitamin E/kg feed.

Effect of graded dietary alpha-tocopherol supplementation on concentrations in plasma and selected tissues of pigs from weaning to slaughter.

Five groups of six purebred German Landrace barrows were fed from 7 to 100 kg live weight restricted amounts of a complete basal feed containing 5 IU vitamin E/kg and supplemented with 0, 20, 40, 80 or 160 IU all-rac-alpha-tocopheryl acetate/kg. The concentrations of alpha-tocopherol were analysed by HPLC in plasma collected throughout the experiment and in cardiac muscle, M. longissimus, liver and adipose tissue at slaughter after 24 h fasting. Body mass gain, feed intake and feed conversion rate were not affected by vitamin E. Plasma alpha-tocopherol was related to the logarithm of supplemental dietary vitamin E (r2 = 0.61). A spell of diarrhea was associated with a significant decrease of plasma levels. In tissues, a clear rank-order of vitamin E storage was found with adipose tissue containing the highest concentrations followed by, in order of decreasing concentrations, liver, cardiac muscle and M. longissimus. Tissue alpha-tocopherol concentrations were related to the logarithm of supplemental dietary vitamin E. Linear correlations were found between alpha-tocopherol concentrations in plasma and tissues allowing an assessment of tissue vitamin E status from plasma alpha-tocopherol analysis.

Effects of dietary retinol on hepatic retinol storage and on plasma and tissue alpha-tocopherol in pigs.

A feeding experiment was carried out with pigs to investigate the effects of graded dietary retinol supplements on hepatic and plasma retinol and on alpha-tocopherol in plasma and selected tissues. Four groups of twelve weanling pigs each with a mean body weight of 7 kg were fed a complete ration containing 54 IU vitamin E/kg and supplemented with 5, 10, 20 or 40 x 10(3) IU retinol/kg for Treatments 1 to 4, respectively. The feed was fed in restricted amounts for 150 days when the pigs were slaughtered at 105 kg body weight. Overall daily body weight gain and feed conversion ratio were 660 g and 2.49, respectively, without treatment differences (p less than 0.01). Hepatic retinol concentration (y, IU/g fresh weight) was linearly related to dietary retinol concentration (x, IU/kg feed) as expressed by y = -88.9 + 0.077 x [r2 = 0.94]. Total hepatic retinol (y, IU) and total retinol intake (x, IU) were linearly related as expressed by y = -194.9 x 10(3) + 0.4585 x [r2 = 0.98]. Hepatic retinol retention relative to intake ranged from 30.0% to 44.9%. Plasma retinol concentration was not affected by dietary retinol (p less than 0.01). Plasma alpha-tocopherol levels remained on a plateau for 42 days in all treatments. After 150 days plasma levels exceeded those at 42 days in Treatments 1 to 3, but not in Treatment 4. The effect of retinol on tissue alpha-tocopherol varied with tissues. While there was no effect on M. Longissimus and backfat, alpha-tocopherol levels in heart and liver showed an inverse relationship with dietary retinol.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of plasma alpha- and gamma-tocopherols after oral and intramuscular administration of RRR-alpha-tocopherol or RRR-gamma-tocopherol to weanling pigs.

Equimolar amounts of either RRR-alpha-tocopherol (alpha-TOH) or RRR-gamma-tocopherol (gamma-TOH) were given as single doses orally and, as water-based emulsions, by intramuscular (i.m.) injection to weanling pigs. Venous blood was sampled at regular intervals and plasma was analyzed for comparison of alpha-TOH and gamma-TOH kinetics. Irrespective of the method of application no significant differences were found between alpha-TOH and gamma-TOH in (a) the maximum increase above initial concentration (delta C), (b) the time of peak concentration (tmax), and (c) the time from half-maximum concentrations on the ascending and the descending parts of the plasma curve. However, alpha-TOH was retained longer in plasma than gamma-TOH, and the areas-under-curve from Oh to 24 h and from Oh to 48 h (AUC0-24 and AUC0-48) were significantly greater for alpha-TOH. In diarrheic pigs given oral gamma-TOH, tmax was prolonged, delta C was lower and AUC0-24 and AUC0-48 were reduced compared with healthy pigs (p less than 0.05). The results indicate that pigs absorb both vitamers to a similar extent but that gamma-TOH is eliminated from plasma more rapidly.

Blood gas changes during panting in a small East African antelope, the dik-dik.

Five adult male dik-dik (Madoqua kirkii) were exposed in a climatic chamber to an air temperature of 45 degrees C. Measurements were made of rectal temperature (Tre) and respiratory frequency (f) and arterial blood samples taken before and during heat exposure were analyzed for pH, PCO2 and PO2. During exposure, Tre and f increased in all animals. In the first 80 min dik-dik displayed thermal tachypnea and minor changes in blood gases. Continued exposure lead to hyperpnea accompanied by a fall in PaCO2 and a rise in pH. PaCO2 at first fell and then increased toward or above control levels. The dik-dik did not display second phase breathing. This observation confirms that second phase breathing is not essential to the development of respiratory alkalosis. The main conclusion of the study is that the dik-dik, unlike another heat-adapted antelope, the wildebeest (Taylor, Robertshaw, and Hoffmann. Am. J. Physiol. 217:907-910, 1969), is unable to resist alkalosis during heat stress.