Key result
Acute oral tetrahydrobiopterin (BH4) improved flow-mediated dilatation by approximately 45% in older sedentary men (P<0.01) but had no effect in young sedentary or older habitually trained men.
Why the study?
Does acute oral tetrahydrobiopterin improve endothelium-dependent dilatation in healthy men of varying age and exercise habits?
RCT (n=31)
Does acute oral tetrahydrobiopterin improve endothelium-dependent dilatation in healthy men of varying age and exercise habits?
Effect estimate: 45% improvement
Absolute Event Rate: 1% vs 0.57%
p-value: p=<0.01
Acute oral BH4 improves endothelium-dependent dilatation in older sedentary men but not in young sedentary or older habitually exercising men, suggesting BH4 bioactivity is a key mechanism in age-related endothelial dysfunction.
Hypothesis-generating for BH4 in sedentary older men; leaves open effects on outcomes or other populations.
Endothelium-dependent dilatation (EDD) is impaired with ageing in sedentary, but not in regularly exercising adults. We tested the hypotheses that differences in tetrahydrobiopterin (BH(4)) bioactivity are key mechanisms explaining the impairment in EDD with sedentary ageing, and the maintenance of EDD with ageing in regularly exercising adults. Brachial artery flow-mediated dilatation (FMD), normalized for local shear stress, was measured after acute oral placebo or BH(4) in young sedentary (YS) (n = 10; 22 +/- 1 years, mean +/- s.e.m.), older sedentary (OS) (n = 9; 62 +/- 2), and older habitually aerobically trained (OT) (n = 12; 66 +/- 1) healthy men. At baseline, FMD was approximately 50% lower in OS versus YS (1.12 +/- 0.09 versus 0.57 +/- 0.09 (Deltamm (dyn cm(-2))) x 10(-2), P < 0.001; 1 dyn = 10(-5) N), but was preserved in OT (0.93 +/- 0.08 (Deltamm (dyn cm(-2))) x 10(-2)). BH4 administration improved FMD by approximately 45% in OS (1.00 +/- 0.10 (Deltamm (dyn cm(-2))) x 10(-2), P < 0.01 versus baseline), but did not affect FMD in YS or OT. Endothelium-independent dilatation neither differed between groups at baseline nor changed with BH4 administration. These results suggest that BH4 bioactivity may be a key mechanism involved in the impairment of conduit artery EDD with sedentary ageing, and the EDD-preserving effect of habitual exercise.
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Eskurza et al. (2005) conducted an RCT in Healthy men (sedentary and habitually exercising) (n=31). Tetrahydrobiopterin (BH4) vs. Placebo / Baseline was evaluated on Brachial artery flow-mediated dilatation (FMD), normalized for local shear stress (45% improvement, p=<0.01). Acute oral tetrahydrobiopterin (BH4) improved flow-mediated dilatation by approximately 45% in older sedentary men (P<0.01) but had no effect in young sedentary or older habitually trained men.
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