Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats.

Berberine chloride (BBR) is a natural isoquinoline alkaloid extracted from medicinal herbs. It has been reported that the intestinal absorption of BBR is very low. In this study, the absolute bioavailability of BBR was studied, and the enhancing effects of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on intestinal absorption were investigated in rats. BBR injection was administrated via the femoral vein at a dose of 1.0 mg kg(-1) in intravenous group, and BBR oral formulations were administrated by oral gavage at a dose of 100 mg kg(-1) in BBR control (control) group and BBR-TPGS (test) group, respectively. The result showed that BBR had a very low absolute bioavailability of 0.68%, and TPGS could enhance intestinal absorption of BBR significantly. TPGS at a concentration of 2.5% could improve peak concentration (C(max)) and area under the curve (AUC(0-36)) of BBR by 2.9 and 1.9 times, respectively. The absorption enhancing ability of TPGS may be due to its ability to affect the biological activity of P-glycoprotein and thereby reduce the excretion of absorbed BBR into the intestinal lumen. This study indicated that absolute bioavailability of BBR was 0.68% in rats, and TPGS was a good absorption enhancer capable of enhancing intestinal absorption of BBR significantly.

Antioxidants: what role do they play in physical activity and health?

Exercise appears to increase reactive oxygen species, which can result in damage to cells. Exercise results in increased amounts of malondialdehyde in blood and pentane in breath; both serve as indirect indicators of lipid peroxidation. However, not all studies report increases; these equivocal results may be due to the large intersubject variability in response or the nonspecificity of the assays. Some studies have reported that supplementation with vitamins C and E, other antioxidants, or antioxidant mixtures can reduce symptoms or indicators of oxidative stress as a result of exercise. However, these supplements appear to have no beneficial effect on performance. Exercise training seems to reduce the oxidative stress of exercise, such that trained athletes show less evidence of lipid peroxidation for a given bout of exercise and an enhanced defense system in relation to untrained subjects. Whether the body's natural antioxidant defense system is sufficient to counteract the increase in reactive oxygen species with exercise or whether additional exogenous supplements are needed is not known, although trained athletes who received antioxidant supplements show evidence of reduced oxidative stress. Until research fully substantiates that the long-term use of antioxidants is safe and effective, the prudent recommendation for physically active individuals is to ingest a diet rich in antioxidants.

Vitamin E, vitamin C, and exercise.

Exercise increases the generation of oxygen free radicals and lipid peroxidation. Strenuous exercise in a person who is unconditioned or unaccustomed to exercise will induce oxidative damage and result in muscle injury. However, aerobic exercise training strengthens the antioxidant defense system by increasing superoxide dismutase. Vitamin C and, especially, vitamin E are shown to decrease the exercise-induced increase in the rate of lipid peroxidation. No ergogenic effects of either vitamin C or E have been shown. Vitamin E was shown to significantly increase circulating neutrophils in older, but not younger, subjects performing eccentric exercise that causes an increase in skeletal muscle damage. In addition to its effect in augmenting the neutrophil response to eccentric exercise, vitamin E causes a greater increase in circulating creatine kinase activity, perhaps indicating increased skeletal muscle repair. Increased vitamin E intake has been associated with enhanced glucose tolerance and insulin action as well as improved lipoprotein status. Future research should examine the combined effects of exercise training and vitamins E and C on these health-related outcomes.

Evaluation of multiple micronutrient supplementation in the management of oral submucous fibrosis in Karachi, Pakistan.

Oral submucous fibrosis (OSF) is an oral precancerous condition characterized by symptoms such as intolerance to spicy food, altered salivation, progressive difficulty in opening the mouth, and signs like vesiculation, ulceration, blanching, rigidity, and stiffening of the oral mucosa and depapillation and altered mobility of the tongue. It is seen mostly among people of Indian subcontinent origin. The major structural change is extensive fibroelastic scarring of the lamina propria and deeper connective tissues. A combination of micronutrients (vitamins A, B complex, C, D, and E) and minerals (iron, calcium, copper, zinc, magnesium, and others) was evaluated for its efficacy in controlling the symptoms and signs of OSF in 117 compliant subjects in Karachi, Pakistan, in a single-arm preliminary study. The subjects received supplementation for one to three years. Significant improvement in symptoms, notably intolerance to spicy food, burning sensation, and mouth opening, was observed at exit. The interincisor distance deteriorated in 11 subjects (10%) at exit; it was stable in 56 subjects (49%) and improved in 48 (41%). The mean interincisor distance was 19.1 +/- 10.8 (SD) mm at exit compared with 16.2 +/- 7.5 mm at baseline. A significant proportion of concomitant lesions like leukoplakia also regressed at exit. The major outcome from this study was a beneficial clinical response in subjects with OSF to multiple micronutrient intervention, which justifies its further evaluation in well-designed randomized controlled trials in other settings in South Asia.

Assessment of vitamin E nutritional status in yearling beef heifers.

Effects of four dietary levels of DL-alpha-tocopheryl acetate (0, 500, 1,500, and 3,000 IU.animal-1.d-1) on serum, red blood cell (RBC), and tissue alpha-tocopherol concentrations were investigated in 32 yearling cattle during an 84-d trial. Supplemental vitamin E was fed for 28 d, withdrawn for 28 d, and then resumed for another 28 d. Blood was collected on d 1 before treatment administration, d 3, and biweekly thereafter. Serum alpha-tocopherol increased rapidly from pretreatment values (1.8 micrograms/mL) with linear (P < .05) treatment effects on d 3 and 14 and cubic treatment effects on d 28. Upon withdrawal of vitamin E supplementation, serum tocopherol concentrations declined and again increased rapidly and linearly by d 84 after supplementation was resumed. Concentration of alpha-tocopherol in RBC did not respond appreciably to supplemental vitamin E. There were no vitamin E treatment effects on blood lipid fractions (cholesterol and triglycerides). When serum tocopherol was expressed relative to the sum of cholesterol and triglycerides, response to vitamin E intake followed similar trends as serum alpha-tocopherol. The relationship between serum alpha-tocopherol concentrations or serum tocopherol:cholesterol plus triglycerides ratio and vitamin E intake was linear (P < .05) for d 14, 28, and 84 and linear with liver for d 84. Serum and liver tocopherol reflected vitamin E intake and can be used reliably to estimate vitamin E status in young cattle.

Assessment of vitamin E nutritional status in sheep.

The effects of supplemental dietary vitamin E (as DL-alpha-tocopheryl acetate; 0, 15, 30, and 60 IU/d) on serum, platelet, and muscle tocopherol and lipid (cholesterol and triglycerides) concentrations in 32 sheep were investigated in a 60-d trial. Serum, platelet, and muscle alpha-tocopherol concentrations increased linearly (P < .05) with treatment. Platelet tocopherol concentrations were more sensitive to vitamin E intake than either serum or muscle tocopherol. There were no effects on serum lipid concentrations. There were low correlations (P > .05) between serum or platelet tocopherol and either cholesterol or triglycerides or the sum of the two lipid fractions. Correlations between serum or platelet tocopherol and muscle tocopherol were also low (P > .05). Although platelet tocopherol was more sensitive to vitamin E intake than serum tocopherol, serum tocopherol concentrations can be reliably used to estimate vitamin E status. Expressing serum tocopherol relative to blood lipids did not improve the relationship between serum tocopherol and vitamin E intake.

Biopotency of vitamin E in lucerne meal for chickens.

In order to estimate the biopotency of vitamin E in lucerne/alfalfa meal in comparison to that of dl-alpha-tocopheryl acetate (dl-alpha-Ta; all-rac-alpha-Ta) a study was conducted with newly hatched White Leghorn male chicks. An increase in the vitamin E level in the liver and plasma, and the prevention of nutritional encephalomalacia (NE) were used as criteria for biopotency. After a vitamin E depletion period of one week posthatching, the chicks continued on a semipurified, vitamin E free basal diet without vitamin E supplementation, or were repleted with graded levels of that vitamin for six weeks, provided as extracted lucerne oil or as dl-alpha-Ta. High performance liquid chromatography (HPLC) with fluorescence detection was used for the analysis of the vitamin E homologues. The diagnosis of NE was based on clinical and histopathological observations. A significant increase (P < 0.05) in vitamin E content in the liver and plasma was observed in response to dietary supplementation with both vitamin E sources. The linear increase both in the liver and plasma storage assays was associated with a reduced incidence of NE. The disease was totally prevented by a dietary supplement of 7.50 and 5.40 mg vitamin E/Kg feed provided as dl-alpha-Ta or lucerne oil, respectively. The natural biopotency of the vitamin E in lucerne meal compared with that of dl-alpha-Ta in the liver and plasma storage assays and in the prevention of NE was 123, 105 and 99%, respectively, as calculated by the slope ratio technique.

Upper limit of vitamin E in infant formulas.

Reports of toxicity to enterally administered vitamin E are rare in infants. However, increased risks of sepsis and necrotizing enterocolitis have been reported after both enteral and parenteral vitamin E, primarily when plasma (or serum) vitamin E levels exceed 3.5 mg/dl. Levels this high are seldom seen with enteral vitamin E when intake is 25 mg d-alpha-tocopherol equivalent/(kg.d) or less. Intakes below this threshold will be provided by infant formulas with vitamin E to energy ratios of up to 20 mg/100 kcal (30 IU/100 kcal) so long as energy intake does not exceed 125 kcal/(kg.d). To allow a margin of safety, it would be reasonable to limit the amount of vitamin E added to the formula during its manufacture to half this amount, or 10 mg/100 kcal (15 IU/100 kcal). This level coincides with the highest levels of vitamin E found in human colostrum and is 20 times the recommended lower limit for vitamin E in infant formula of 0.5 mg/100 kcal.

Identification of d- or dl-alpha-tocopherol in pharmaceuticals, food supplements, or feed supplements: a collaborative study.

A collaborative study was conducted to evaluate a method for identifying d- or dl-alpha-tocopherol in pharmaceuticals, food supplements, or feed supplements. The sample is extracted and saponified, the extraneous color is removed by chromatography, and the sample is assayed for vitamin E. Optical rotations are determined before and after formation of the ferricyanide oxidation product. The specific optical rotation of the oxidation product is negligible for the dl-form and +25.5 degrees for the d-form. Statistical analysis of the data reported by 8 collaborators for the standard d-alpha-tocopheryl acetate and for 6 unknown samples indicates a significant interaction between laboratories and samples. The mean coefficients of variation among laboratories for the determinations of the corrected specific optical rotation of the standard and the rotation ratio for the unknown samples containing d-alpha-tocopherol were 11.7 and 21.6%, respectively, for all laboratories and 5.8 and 11.8%, respectively, for experienced laboratories. This identification test for vitamin E is acceptable for determining the form of vitamin E as either d or dl, but is not acceptable for accurately determining mixtures of the 2 forms. The method has been adopted as official first action for the identification of d- or dl-alpha-tocopherol.