Pretreatment with vitamin C prevented the acute impairment of flow-mediated dilatation induced by oral methionine in healthy subjects (2.8% vs -0.7% at 4 hours; P=0.02).
RCT (n=17)
random order
Does vitamin C prevent acute impairment of vascular endothelial function induced by oral methionine in healthy volunteers?
Vitamin C pretreatment prevents the acute impairment of vascular endothelial function associated with elevated homocysteine concentrations, supporting an oxidative stress mechanism.
Absolute Event Rate: 2.8% vs -0.7%
p-value: p=0.02
BACKGROUND: Hyperhomocysteinemia is a major and independent risk factor for vascular disease. The mechanisms by which homocysteine promotes atherosclerosis are not well understood. We hypothesized that elevated homocysteine concentrations are associated with rapid onset endothelial dysfunction, which is mediated through oxidant stress mechanisms and can be inhibited by the antioxidant vitamin C. METHODS AND RESULTS: We studied 17 healthy volunteers (10 male and 7 female) aged 33 (range 21 to 59) years. Brachial artery diameter responses to hyperemic flow (endothelium dependent), and glyceryltrinitrate (GTN, endothelium independent) were measured with high resolution ultrasound at 0 hours (fasting), 2 hours, and 4 hours after (1) oral methionine (L-methionine 100 mg/kg), (2) oral methionine preceded by vitamin C (1g/day, for 1 week), and (3) placebo, on separate days and in random order. Plasma homocysteine increased (0 hours, 12.8+/-1.4; 2 hours, 25.4+/-2.5; and 4 hours, 31. 2+/-3.1 micromol/l, P<0.001), and flow-mediated dilatation fell (0 hours, 4.3+/-0.7; 2 hours, 1.1+/-0.9; and 4 hours, -0.7+/-0.8%) after oral L-methionine. There was an inverse linear relationship between homocysteine concentration and flow-mediated dilatation (P<0. 001). Pretreatment with vitamin C did not affect the rise in homocysteine concentrations after methionine (0 hours, 13.6+/-1.6; 2 hours, 28.3+/-2.9; and 4 hours, 33.8+/-3.7 micromol/l, P=0.27), but did ameliorate the reduction in flow-mediated dilatation (0 hours, 4. 0+/-1.0; 2 hours, 3.5+/-1.2 and 4 hours, 2.8+/-0.7%, P=0.02). GTN-induced endothelium independent brachial artery dilatation was not affected after methionine or methionine preceded by vitamin C. CONCLUSIONS: We conclude that an elevation in homocysteine concentration is associated with an acute impairment of vascular endothelial function that can be prevented by pretreatment with vitamin C in healthy subjects. Our results support the hypothesis that the adverse effects of homocysteine on vascular endothelial cells are mediated through oxidative stress mechanisms.
Chambers et al. (1999) conducted an RCT in Healthy volunteers (n=17). Vitamin C pretreatment followed by oral methionine vs. Oral methionine alone and placebo was evaluated on Flow-mediated dilatation at 4 hours (p=0.02). Pretreatment with vitamin C prevented the acute impairment of flow-mediated dilatation induced by oral methionine in healthy subjects (2.8% vs -0.7% at 4 hours; P=0.02).
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