Short‐term L‐Citrulline supplementation and macro‐ and micro‐vascular function in old adults

Abstract

Aging is an independent cardiovascular risk factor that exhibits impaired vascular function and aging itself is associated with a decline in nitric oxide (NO) bioavailability, an essential signaling molecule involved in vascular function. L‐Citrulline (L‐Cit) supplementation, and the subsequent conversion to L‐Arginine (L‐Arg), is an effective approach to augment substrate for endothelial NO production, potentially improving vascular function. However, the effect of L‐Cit supplementation in old adults is not well understood. Therefore, this study evaluated the effect of short‐term oral L‐Cit supplementation on flow mediated‐dilation (FMD) and reactive hyperemia, indicators of macro‐ and microvascular function, respectively. Eleven old adults (72±5 yrs) underwent 7‐day L‐Cit supplementation (6g per day). %FMD assessments were performed pre‐ and post‐L‐Cit supplementation in both the brachial (BA) and popliteal (PA) arteries in addition to the measurement of reactive hyperemia area under the curve (RH AUC) for 60s following FMD cuff release. Plasma L‐Cit and L‐Arg concentrations were measured to confirm L‐Cit absorption and conversion, respectively. The ratio of L‐Arg to plasma asymmetric dimethylarginine (ADMA) was calculated as a biomarker of NO‐bioavailability. L‐Cit supplementation improved plasma L‐Cit and L‐Arg concentrations (+269%; p=0.002; +74%; p=0.0008, respectively). Although plasma ADMA levels increased post‐treatment (0.51±0.02 vs 0.56±0.02uM/l, p=0.04), the L‐Arg/ADMA ratio was also significantly greater (273±30 vs 419±50; p=0.004). In contrast, there was no effect on either brachial or popliteal %FMD (BA 2.6±0.7 vs 3.4±0.7%; PA: 6.9±2.4 vs 6.6±2.0%, respectively) or RH AUC (BA: 537±124 vs 453±93ml; PA: 612±52 vs 706±81ml, respectively). In conclusion, despite the clear pharmacological efficacy of 7 days of L‐Cit supplementation, in terms of raising NO‐substrate bioavailability, neither macro‐ nor microvascular function was altered in old adults.