Lack of Effect of Vitamin E on l-Arginine-Responsive Endothelial Dysfunction in Patients with Mild Hypercholesterolaemia and Coronary Artery Disease

Abstract

1. Dietary supplementation with vitamin E reduces ischaemic events in patients with established coronary artery disease and improves endothelial function in cholesterol-fed rabbits. We examined whether such dietary supplementation with vitamin E improves endothelial function in patients with mild hypercholesterolaemia and coronary artery disease. 2. Twenty patients (total cholesterol 6.8 +/- 1.1 mmol/l, mean +/- SD) with angiographically documented coronary artery disease were randomly allocated to receive placebo (n = 10) or vitamin E, 400 i.u. daily, (n = 10) for 8 weeks. Endothelium-dependent and independent vasodilatation within forearm vasculature was assessed by brachial artery infusion of acetylcholine (co-infused with saline vehicle and L-arginine) and nitroprusside before and after supplementation. 3. Plasma concentrations of vitamin E increased from 32.9 +/- 3.8 to 69.1 +/- 11.8 mumol/l (means +/- SE) in the vitamin E-supplemented group (P < 0.01) but did not change significantly in the placebo group. Lipid profiles remained similar before and after supplementation in both groups. Forearm blood flow responses to acetylcholine (7.5 and 15 micrograms/min) and nitroprusside (3 and 10 micrograms/min) were similar before and after supplementation in both groups. Acute intra-arterial administration of L-arginine (10 mg/min) augmented the response to acetylcholine (15 micrograms/min) in both groups before and after supplementation to a similar degree (mean augmentation: 60 +/- 18%, P < 0.01). 4. Acute administration of L-arginine reverses endothelial dysfunction in forearm vasculature of patients with mild hypercholesterolaemia and coronary artery disease but supplementation with vitamin E (400 i.u. daily) for 8 weeks does not reverse L-arginine-responsive endothelial dysfunction.

Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia

“…In addition, vitamin E has improved endothelium-dependent [NO dilator function in the cholesterol-fed hypercholesterolaemic rabbit [14,15]. However, studies in several clinical situations [16][17][18][19], and a previous study of ours in normolipidaemic subjects [20], failed to find improvement in endothelial function after vitamin E administration. The purpose of the present study was to examine the effect of vitamin E administration on basal and stimulated function of the [NO dilator system in subjects with hypercholesterolaemia.…”

Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults

“…That being said, we cannot exclude the possibility that other antioxidants (e.g., allopurinol, vitamin E, glutathione, ␤-carotene, and/or superoxide dismutase) may have produced improvements in Q max and V O 2 max . Present experimental findings, however, are mixed regarding the effect of vitamin E (and, even more so, ␤-carotene) on cardiovascular function (7,9,15). Even combinations of antioxidants (normally ascorbic acid, vitamin E, and ␤-carotenes), when given orally at physiological doses, show conflicting results on cardiovascular outcomes (17,30).…”

The role of nitric oxide in cardiovascular diseases

“…In animal studies, a-tocopherol prevents the endothelial dysfunction associated with both atherosclerosis and hypercholesterolaemia (Keaney Jr et al, 1993;Andersson et al, 1994), although this was dependent upon the dose given. In contrast, most patients based studies have generally failed to demonstrate beneficial effects (McDowell et al, 1994;Chowienczyk et al, 1998;Elliott et al, 1995), although there are some exceptions (Heitzer et al, 1999a). The mechanism by whichã-tocopherol exerts its effects in animals is unclear, but is thought that it may aid the endothelium to resist the effects of oxLDL (Keaney Jr et al, 1993;Cathcart et al, 1988) and thus preserving the function of eNOS.…”