Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing

Abstract

Peripheral conduit artery flow-mediated dilatation decreases with ageing in humans. The underlying mechanisms and efficacy of preventive strategies are unknown. Brachial artery flow-mediated dilatation was determined at baseline and after ascorbic acid (vitamin C) intravenous infusion and chronic supplementation (500 mg day(-1) for 30 days) in three groups of healthy men: young sedentary (n= 11; 25 +/- 1 years, mean +/-s.e.m.), older sedentary (n= 9; 64 +/- 2), and older endurance-exercise trained (n= 9; 64 +/- 2). At baseline, flow-mediated dilatation (normalized for the hyperaemic stimulus) was approximately 45% lower in the older (0.015 +/- 0.001) versus young (0.028 +/- 0.004) sedentary men (P < 0.01), but was preserved in older exercising men (0.028 +/- 0.004). Ascorbic acid infusion increased plasma concentrations > 15-fold in all groups and restored flow-mediated dilatation in the sedentary older men (to 0.023 +/- 0.002; P > 0.1 versus other groups), with no effects in the other two groups. Oral ascorbic acid supplementation did not affect flow-mediated dilatation in any group. Brachial artery endothelium-independent dilatation (sublingual nitroglycerin) did not differ among the groups at baseline nor change with ascorbic acid administration. These results provide the first evidence for an important role of oxidative stress in both the impairment in peripheral conduit artery flow-mediated dilatation with sedentary human ageing and the preservation of flow-mediated dilatation with physically active ageing.

Figure 1. Plasma ascorbic acid concentrations

Plasma ascorbic acid concentrations are shown at baseline, after acute ascorbic acid infusion, and after 30 days of ascorbic acid supplementation. Filled bars: young sedentary; open bars: older sedentary; and hatched bars: older endurance trained. Acute = post-infusion; Chronic = end of oral supplementation. * P < 0.0001 versus baseline within the same group; † P < 0.01 versus young within the same condition.

Figure 2. Brachial artery diameters in representative men

Brachial artery diameters are shown before (baseline, A, C and E) and during peak flow-mediated dilatation (B, D and F), in representative young sedentary (A and B), older sedentary (C and D), and older exercise-trained (E and F) men.

Figure 3. Brachial artery diameters before and after the hyperemic stimulus

Brachial artery diameters before (baseline) and during (peak) flow-mediated dilatation in the young sedentary (A), older sedentary (B), and older exercise-trained (C) men. D, mean brachial artery diameters before (baseline) and during (peak) flow-mediated dilatation for the young sedentary, older sedentary, and older exercise-trained groups.

Figure 4. Brachial artery flow-mediated dilatation

Brachial artery flow-mediated dilatation is shown (normalized for the hyperaemic flow stimulus) in young and older sedentary men and older endurance exercise-trained men at baseline, after acute ascorbic acid infusion, and after 30 days of ascorbic acid supplementation. A, percentage change in diameter divided by percentage change in blood flow; B, absolute (mm) change in diameter divided by absolute (ml min⁻¹) change in blood flow. Mean ±s.e.m. values are shown. Filled bars: young sedentary; open bars: older sedentary; and hatched bars: older endurance trained. Acute = postinfusion; Chronic = end of oral supplementation. * P < 0.01 versus young and older trained groups.