In patients with PAOD and hyperhomocysteinemia, 8 weeks of L-arginine significantly improved flow-dependent vasodilation (10.2% vs placebo 8.9%), whereas B vitamins had no significant effect.
RCT (n=27)
Double-blind
assigned
Does oral treatment with B vitamins or L-arginine improve endothelium-dependent vasodilation in patients with peripheral arterial occlusive disease and hyperhomocyst(e)inemia?
L-arginine, but not B vitamins, improves endothelial function in patients with PAOD and hyperhomocysteinemia, suggesting that ADMA and oxidative stress drive the dysfunction rather than homocysteine alone.
Absolute Event Rate: 10.2% vs 8.9%
p-value: p=n.s. for B vitamins
OBJECTIVES: Hyperhomocyst(e)inemia is a risk factor for atherosclerotic vascular disease, and it is associated with endothelial dysfunction. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of NO, possibly secondary to accumulation of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) and increased oxidative stress. We investigated whether oral treatment with B vitamins or L-arginine normalizes endothelium-dependent, flow-dependent vasodilation (FDD) in patients with peripheral arterial occlusive disease (PAOD) and hyperhomocyst(e)inemia. METHODS: 27 patients with PAOD and hyperhomocyst(e)inemia were assigned to oral treatment with combined B vitamins (folate, 10 mg; vitamin B-12, 200 microg; vitamin B-6, 20 mg/day), L-arginine (24 g/day) or placebo, for 8 weeks in a double-blind fashion. FDD was determined by high-resolution ultrasound in the radial artery. RESULTS: Vitamin B supplementation significantly lowered plasma homocyst(e)ine concentration from 15.8+/-1.8 to 8.7+/-1.1 micromol/l (P<0.01). However, B vitamins had no significant effect on FDD (baseline, 7.8+/-0.7%, B vitamins, 8.3+/-0.9%, placebo 8.9+/-0.7%; P=n.s.). In contrast, L-arginine treatment did not affect homocyst(e)ine levels, but significantly improved FDD (10.2+/-0.2%), probably by antagonizing the impact of elevated ADMA concentration (3.8+/-0.3 micromol/l) and reducing the oxidative stress by lowering urinary 8-iso-prostaglandin F(2alpha) (baseline, 76.3+/-7.1 vs. 62.7+/-8.3 pmol/mmol creatinine after 8 weeks). CONCLUSIONS: Oral supplementation with combined B vitamins during 8 weeks does not improve endothelium-dependent vasodilation in PAOD patients with hyperhomocyst(e)inemia, whereas L-arginine significantly improved endothelial function in these patients. Thus, accumulation of ADMA and increased oxidative stress may underlie endothelial dysfunction under hyperhomocyst(e)inemic conditions. These findings may have importance for evaluation of homocyst(e)ine-lowering therapy.
K. Sydow (Sat,) conducted a rct in Peripheral arterial occlusive disease (PAOD) and hyperhomocyst(e)inemia (n=27). L-arginine or combined B vitamins vs. Placebo was evaluated on Endothelium-dependent, flow-dependent vasodilation (FDD) (p=n.s. for B vitamins). In patients with PAOD and hyperhomocysteinemia, 8 weeks of L-arginine significantly improved flow-dependent vasodilation (10.2% vs placebo 8.9%), whereas B vitamins had no significant effect.
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