Abstract
Nitric oxide is a gaseous molecule endogenously produced by endothelial cells, which stands out for its vascular tone regulation effects after crossing through the endothelium and diffusing to smooth blood vessel muscle cells. Reduced nitric oxide bioavailability contributes to the development of hypertension, atherosclerosis, worsening endothelial function, arterial stiffness, and ineffective stimulation of smooth muscle relaxation. L-citrulline, an amino acid found in high concentrations in watermelon, may serve as a recycling substrate, increasing L-arginine availability and, consequently, nitric oxide synthesis. By enhancing circulating L-arginine, L-citrulline indirectly improves the synthesis and bioavailability of nitric oxide, promoting smooth muscle vasodilation. Herein, this narrative review critically examines current evidence of the cardiovascular benefits of L-citrulline ingestion obtained exclusively through watermelon consumption, exploring the nutritional and bioactive composition of the edible parts of this fruit and the metabolism and effects of L-citrulline supplementation on vascular and metabolic physiology and proposing directions for future research, such as long-term studies and studies in specific populations. The beneficial effects of oral L-citrulline ingestion through watermelon require additional evidence, but it has already been demonstrated that it does not undergo hepatic metabolism, instead being transported to the kidneys to participate in de novo L-arginine synthesis. The generation of endogenous NO then causes positive biochemical, hemodynamic, and vascular effects, remodeling the physio-pathological conditions of those adults that present risk factors for cardiovascular diseases.