Folic acid supplementation improves vascular endothelial function, yet not skin blood flow during exercise in the heat, in patients with heart failure

Abstract

Heart failure (HF) patients are susceptible to heat strain during exercise, secondary to blunted skin blood flow (SkBF) responses, which may be explained by impaired nitric oxide (NO)-dependent vasodilation. Folic acid improves vascular endothelial function and SkBF through NO-dependent mechanisms in healthy older individuals and patients with cardiovascular disease. We examined the effect of folic acid supplementation (5 mg/day for 6 wk) on vascular function [brachial artery flow-mediated dilation (FMD)] and SkBF responses [cutaneous vascular conductance (CVC)] during 60 min of exercise at a fixed metabolic heat production (300 ẆHprod) in a 30°C environment in 10 patients with HF (New York Heart Association Class I–II) and 10 healthy controls (CON). Serum folic acid concentration increased in HF [preintervention (pre): 1.4 ± 0.2; postintervention (post): 8.9 ± 6.7 ng/ml, P = 0.01] and CON (pre: 1.3 ± 0.6; post: 5.2 ± 4.9 ng/ml, P = 0.03). FMD improved by 2.1 ± 1.3% in HF ( P < 0.01), but no change was observed in CON postintervention ( P = 0.20). During exercise, the external workload performed on the cycle ergometer to attain the fixed level of heat production for exercise was similar between groups (HF: 60 ± 13; CON: 65 ± 20 external workload, P = 0.52). Increases in CVC during exercise were similar in HF (pre: 0.89 ± 0.43; post: 0.83 ± 0.45 au/mmHg, P = 0.80) and CON (pre: 2.01 ± 0.79; post: 2.03 ± 0.72 au/mmHg, P = 0.73), although the values were consistently lower in HF for both pre- and postintervention measurement intervals ( P < 0.05). These findings demonstrate that folic acid improves vascular endothelial function in patients with HF but does not enhance SkBF during exercise at a fixed metabolic heat production in a warm environment.