Effect of Folic Acid and Vitamins B6 and B12 on Microcirculatory Vasoreactivity in Patients With Hyperhomocysteinemia

Abstract

Objective: Hyperhomocysteinemia (HHcy) has been identified as an independent risk factor for atherosclerotic vascular disease. The effect of high-dose folic acid or combination vitamin therapy for the treatment of HHcy on the microcirculation is unknown. The purpose of this study was to evaluate the effect of a combination of folic acid, vitamin B6, and vitamin B12 on endothelium-dependent and endothelium-independent vasoreactivity in patientswith HHcy. Methods: Baseline cutaneous microvascular vasoreactivity was measured in 20 patients with HHcy and 18 patients with normohomocysteinemia (NHcy). Laser Doppler scan imaging before and after iontophoresis of 1% acetylcholine chloride (endothelium-dependent response) and 1% sodium nitroprusside (endothelium-independent response) was performed for the measurement of forearm skin vasodilatation. Patients were then treated with 10 mg folic acid, 100 mg vitamin B6, and 1 mg vitamin B12 orally once a day for 6 months. Follow-up fasting serum homocysteine and cutaneous Laser Doppler scan imaging before and after iontophoresis were performed at 1, 2, 3, and 6 months. Statistical analysis was performed using Fisher's exact test, paired t test, and Wilcoxon matched-pairs signed-ranks test, with significance set at P < .05. Results: The HHcy group was older than the NHcy group (70.89 ± 1.95 vs 61.78 ± 2.73 years, P = .02). Otherwise the groups were similar in terms of race, tobacco use, comorbid diseases, and serum lipoproteins. Over the 6-month period, fasting serum homocysteine levels decreased significantly in both the NHcy group (10.40 ± 0.59 µmol/L vs 8.97 ± 0.84 µmol/L, P = .01) and the HHcy group (19.80 ± 1.06 µmol/L vs 13.40 ± 0.86 µmol/L, P = .0002). There were no statistically significant changes in endothelium-independent vasoreactivity (voltage change from baseline) in either group. Endothelium-independent vasore activity decreased over the 6-month period in the HHcy group (0.20 ± 0.04 V vs 0.11 ± 0.03 V, P = .03). Subanalysis of HHcy with diabetes or age greater than 65 years both showed worsening trends in endothelium-independent vasoreactivity ( P = .05 for both groups). There were no statistically significant changes in endothelium-independent vasoreactivity in the NHcy group. Conclusions: High doses of folic acid and vitamins B6 and B12 lower fasting serum homocysteine levels in patients with HHcy. Older and diabetic patients with HHcy tend to do worse possibly because of long-term fixed microvascular insult secondary to multiple sustained comorbidities.