No effect of acute tetrahydrobiopterin (BH4) supplementation on vascular dysfunction in the old.

ABSTRACT

As a deficiency in tetrahydrobiopterin (BH4), a cofactor for endothelial nitric oxide synthase, has been implicated in the age-related decline in vascular function, this study aimed to determine the impact of acute BH4 supplementation on flow-mediated vasodilation (FMD) in old adults. Two approaches were used 1) A multiday, double-blind, placebo-controlled, crossover design measuring, FMD [ΔFMD (mm), %FMD (%)] and shear rate area under the curve (SR AUC) in nine old subjects (73 ± 8 yr) with either placebo (placebo) or BH4 (≈10 mg/kg, post), and 2) a single experimental day measuring FMD in an additional 13 old subjects (74 ± 7 yr) prior to (pre) and 4.5 h after ingesting BH4 (≈10 mg/kg). With the first experimental approach, acute BH4 intake did not significantly alter FMD (ΔFMD 0.17 ± 0.03 vs. 0.13 ± 0.02 mm; %FMD 3.3 ± 0.61 vs. 2.9 ± 0.4%) or SR AUC (30,280 ± 4,428 vs. 37,877 ± 9,241 s-1) compared with placebo. Similarly, with the second approach, BH4 did not significantly alter FMD (ΔFMD 0.09 ± 0.02 vs. 0.12 ± 0.03 mm; %FMD 2.2 ± 0.6 vs. 2.9 ± 0.6%) or SR AUC (37,588 ± 6,753 vs. 28,996 ± 3,735 s-1) compared with pre. Moreover, when the two data sets were combined, resulting in a greater sample size, there was still no evidence of an effect of BH4 on vascular function in these old subjects. Importantly, both plasma BH4 and 7,8-dihydrobiopterin (BH2), the oxidized form of BH4, increased significantly with acute BH4 supplementation. Consequently, the ratio of BH4/BH2, recognized to impact vascular function, was unchanged. Thus, acute BH4 supplementation does not correct vascular dysfunction in the old.NEW & NOTEWORTHY Despite two different experimental approaches, acute BH4 supplementation did not affect vascular function in older adults, as measured by flow-mediated vasodilation. Plasma levels of both BH4 and BH2, the BH4 oxidized form, significantly increased after acute BH4 supplementation, resulting in an unchanged ratio of BH4/BH2, a key determining factor for endothelial nitric oxide synthase coupling. Therefore, likely due to the elevated oxidative stress with advancing age, acute BH4 supplementation does not correct vascular dysfunction in the old.