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 ∼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.

Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

“…Older humans and rodents exhibit impaired EDD in conduit arteries as well as cerebral arteries Csiszar et al 2007a;Blackwell et al 2004;Modrick et al 2009;Hatake et al 1990;Eskurza et al 2004;Celermajer et al 1994). It has been shown previously that lifelong CR can prevent the age-related decline in EDD in the aorta (Csiszar et al 2009), but the effect of CR on resistance artery EDD has not been studied.…”

Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults

“…FMD was calculated as the percent change in brachial artery diameter from baseline (i.e., in the 2-min period before cuff inflation) to the peak increase after cuff release, using a five-point moving average (12,17). Shear rate (4 ϫ brachial artery MBV/brachial artery diameter) area under the curve was used to quantify the stimulus for FMD.…”

“…Moreover, it is not surprising that aging, which is a primary risk factor for the development of cardiovascular disease and atherosclerosis (29,36), is associated with marked endothelial dysfunction. Specifically, in response to stimulation of the vascular endothelium via pharmacological substances, such as acetylcholine, or physiological stimuli, such as increases in vascular shear stress, a reduced endothelium-dependent vasodilatory response occurs in healthy older adults compared with healthy young adults (7,11,12,41). As low levels of brachial artery flow-mediated dilation (FMD), a commonly used method to assess endothelium-dependent vasodilation, are predictive of increased cardiovascular morbidity and mortality in older adults (45), identification of methods/ therapies that increase brachial artery FMD in this population are of biomedical importance.…”

Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults

“…During the 30 days before the final visit, all subjects ingested 500 mg/day of ascorbic acid (time-release capsules, Goldline Laboratories, Miami, FL). The rationale for these doses and methods of administration has been described previously (2,11,12), and the acute dose has been shown to reduce oxidative stress in both young and older adults (2) and restore flow-mediated dilatation in sedentary older men (12). Blood was sampled at three time points for determination of plasma concentration of ascorbic acid and oxidized low-density lipoproteins, a systemic marker of oxidative stress (36): before and following the intravenous ascorbic acid administration, and following the 30-day oral administration.…”