Background

Elevated plasma asymmetrical dimethylarginine (ADMA) is suggested to contribute to hyperhomocyst(e)ine (Hcy)-related vascular dysfunction in patients with peripheral artery disease (PAD). The present trial investigated if Hcy-lowering therapy with vitamin-B (vit-B) and folic acid affects plasma concentrations of ADMA in patients with PAD and hyperhomocyst(e)inemia.

Patients and Methods

49 subjects (15 women, 34 men) with PAD and fasting plasma total Hcy concentrations >15 µmol/l were randomized to receive either oral vit-B and folic acid therapy (n = 27) or placebo (n = 22) for six weeks. Fasting venous blood samples were monitored for plasma total Hcy, vit-B12 and folate, ADMA, symmetric dimethylarginine (SDMA), L-arginine (L-ARG) and high sensitivity C-reactive protein (hs-CRP).

Results

After six weeks, plasma Hcy concentrations were decreased and concentrations of vit-B12 and folate elevated in patients with vitamin supplementation (all P < 0.05 vs. baseline) and unchanged in the placebo group. Dimethylarginine plasma concentrations were not affected by treatment. hs-CRP correlated with ADMA plasma concentrations (r=0.29; P < 0.01).

Conclusion

The lack of vit-B and folic acid therapy on plasma concentrations of ADMA renders a role of extracellular methylarginines unlikely to be involved in the pathophysiology of hyperhomocyst(e)inemia and its complications.

Condensed Abstract

We investigated if Hcy-lowering therapy with vitamin-B and folic acid over 6 weeks affects plasma concentrations of ADMA in patients with PAD and hyperhomocyst(e)inemia. Vitamin supplementation decreased Hcy and increased vit-B12, folate and had no effect on ADMA. These results render a role of extracellular methylarginines unlikely for hyperhomocyst(e)ine-dependent complications in PAD.