Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status.

BACKGROUND: Cases of enhanced anticoagulant effect in response to high-dose vitamin E supplementation have been reported among patients taking oral anticoagulants. Although a vitamin E-vitamin K interaction was proposed to underlie this effect, it has not been systematically investigated in adults with normal baseline coagulation status. OBJECTIVE: The objective was to study the effect of 12 wk of supplementation with 1000 IU RRR-alpha-tocopherol/d on biochemical measures of vitamin K status in men and women not taking oral anticoagulants. DESIGN: Vitamin K status, which was assessed with the use of plasma phylloquinone concentrations, the degree of under-gamma-carboxylation of prothrombin (proteins induced by vitamin K absence-factor II, PIVKA-II), and the percentage of undercarboxylated osteocalcin (ucOC), was determined in 38 men and women with rheumatoid arthritis (study A) and in 32 healthy men (study B) participating in 2 independent, 12-wk randomized clinical trials of vitamin E supplementation (1000 IU/d). RESULTS: Mean (+/- SD) PIVKA-II increased from 1.7 +/- 1.7 to 11.9 +/- 16.1 ng/mL (P < 0.001) in study A and from 1.8 +/- 0.6 to 5.3 +/- 3.9 ng/mL (P < 0.001) in study B in response to 12 wk of vitamin E supplementation. An increase in PIVKA-II is indicative of poor vitamin K status. In contrast, the other measures of vitamin K status (ie, plasma phylloquinone concentration and percentage of ucOC) did not change significantly in response to the supplementation. CONCLUSIONS: High-dose vitamin E supplementation increased PIVKA-II in adults not receiving oral anticoagulant therapy. The clinical significance of these changes warrants further investigation, but high doses of vitamin E may antagonize vitamin K. Whether such an interaction is potentially beneficial or harmful remains to be determined.

Vitamin E supplementation does not increase the vitamin C radical concentration at rest and after exhaustive exercise in healthy male subjects.

BACKGROUND: Extensive exercise may promote the formation of reactive oxygen species and subsequently contribute to tissue damage. A compound which can protect cells and tissues is vitamin E. The vitamin E radical, formed during the radical scavenging process, can be reduced by vitamin C resulting in a higher level of the vitamin C radical (semidehydroascorbate free radical). An increase of the vitamin C radical, however, is assumed to exert prooxidative effects. AIM OF THE STUDY: To elucidate whether supplementation of vitamin E and exhaustive exercise lead to an increase of the vitamin C radical in human plasma. METHODS: A placebo controlled, cross over study with 13 male volunteers was carried out. After an 8 day supplementation period with 500 I.U. D-alpha-tocopherol, the subjects performed two exhaustive treadmill runs. Blood samples were collected at rest, 0, 0.25, 1, 3, 24 and 48 h after exercise. Serum was separated and concentrations of D-alpha-tocopherol and ascorbic acid were determined by HPLC. Vitamin C radical levels in plasma were assessed by electron paramagnetic resonance (EPR). RESULTS: Vitamin E and C both showed a tendency to decrease between 3 h and 24 h after exercise. Vitamin C radical level remained stable during the whole period. Neither vitamin E supplementation nor exercise had any influence on the plasma concentration of the vitamin C radical. CONCLUSIONS: Vitamin E supplementation under conditions of mild oxidative stress does not result in an increased vitamin C radical concentration.

A randomised, placebo-controlled study comparing two formulations of dimenhydrinate with respect to efficacy in motion sickness and sedation.

It is known that sedation by H1 antihistaminic drugs can be reduced or avoided if slow release formulations are used for their administration, probably because of a slower increase of the drug concentration in plasma and brain. The aim of this study was to compare two different formulations of dimenhydrinate (CAS 523-87-5), a single fast release tablet with three chewing gums (divided dose principle), with regard to their efficacy in a motion sickness model and their detrimental effect on vigilance and central nervous system (CNS) performance. Caloric stimulation of the eardrum (air at 44 degrees C) was used to induce the symptoms of motion sickness in 24 symptomatic volunteers in a three-way cross-over design comparing three chewing gums (Superpep forte, chewed for 30 min each) containing 20 mg dimenthydrinate each with a 50 mg dimenhydrinate tablet and placebo. During caloric stimulation the following parameters were measured in order to compare efficacy: Quantitative analysis of sodium excretion by sweat (main target parameter), subjective well being (vertigo) by visual analogue scales (VAS) and frequency of binocular nystagmus by computer nystagmography. Unwanted effects on vigilance and CNS performance were measured by means of the N1-P2 peak to peak amplitudes of auditory evoked potentials (AEPs) as an objective, quantitative parameter of vigilance and the latency to correct responses and the number of correct responses (complex choice reaction task) in the oculodynamic test (ODT) as parameters of complex choice reaction ability. As a main efficacy result sodium excretion by sweat was markedly reduced by the chewing gums and by the tablet. The differences to placebo were highly significant (chewing gums vs. placebo p < 0.0001, tablet vs. placebo p < 0.0001). There was no relevant and no significant difference between both medications (p = 0.308). The secondary efficacy parameters, frequency of binocular nystagm and the VAS vertigo were markedly reduced by both medications in comparison to placebo, i.e. both medications were markedly effective. In both cases, however, this result failed statistical significance. The unwanted depressing effects on vigilance and CNS performance of the chewing gums were less pronounced than that of tablets. The N1/P2 peak-to-peak amplitudes of the AEPs were significantly reduced by both the chewing gums and the tablets. The effect of the tablets was, however, larger than that of the chewing gums. This highly significant (tablet vs. chewing gums, p = 0.0003) difference shows that the tablet had a larger depressing effect on vigilance (greater sedation). In line with this result, the number of correct responses in the ODT was markedly and significantly reduced by the tablet (p = 0.0027) but not significantly by the chewing gums (p = 0.8140). The difference between the tablet and the chewing gums was highly significant (p = 0.0052). The complex choice reaction time was markedly and nearly significantly (p = 0.0558) prolonged by the tablet whereas the chewing gums produced only a very small and insignificant prolongation. That the objective measurements of vigilance and CNS performance showed significantly larger detrimental effects of the tablet than of the chewing gums is probably a consequence of a faster increase of the dimenhydrinate concentration in the CNS after administration of the tablet in comparison to the divided dose principle of the chewing gums.