L-citrulline as a nitric oxide–modulating therapeutic adjunct to exercise: effects on vascular function, arterial stiffness, and cardiometabolic health in postmenopausal and older women

Abstract

Postmenopausal women face increased risks of vascular dysfunction, loss of lean muscle mass, and reduced physical performance due to age-related hormonal and metabolic changes. These factors contribute to heightened cardiovascular risk and physical frailty. L-citrulline, a non-essential amino acid and precursor to nitric oxide (NO), has emerged as a potential therapeutic agent for improving vascular and muscular health. When combined with structured exercise, L-citrulline may enhance NO bioavailability, improve endothelial function, increase muscle perfusion, and potentiate exercise-induced adaptations. This review synthesizes current evidence on the combined impact of L-citrulline supplementation and exercise on endothelial function, arterial stiffness, leg muscle function, lean mass, and strength in postmenopausal women. Findings from preclinical and clinical studies suggest that this combined intervention can reduce arterial stiffness, enhance leg muscle strength, increase lean body mass, and improve overall physical function, potentially via NO-mediated vasodilation, the mechanistic target of rapamycin signaling, improved mitochondrial function, and reduced oxidative stress. These effects are especially relevant in postmenopausal populations at risk for cardiovascular disease and sarcopenia. While early results are promising, further high-quality randomized controlled trials are needed to confirm these benefits, establish optimal dosing strategies, and determine long-term clinical relevance.