l-Citrulline Supplementation: Impact on Cardiometabolic Health

Abstract

Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations. In this review, we examine the impact of supplementing this important urea cycle intermediate on cardiovascular and metabolic health outcomes and identify future directions for investigating its therapeutic impact on cardiometabolic health.

Aspartic acid supplementation ameliorates symptoms of diabetic kidney disease in mice

“…However, oral Arg supplementation is largely ineffective due to gastrointestinal and hepatic extraction of Arg. Alternatively, oral Citrulline supplementation consistently increases the bioavailability of Arg and NO in plasma and tissue [24]. Most of the orally administered Citrulline is removed from circulation by the kidneys, and it is efficiently converted into Arg [25].…”

Serum Metabolomic Patterns in Young Patients with Ischemic Stroke

“…Nitric oxide (NO) is a gas-signal molecule with various physiological functions, including regulating the balance of blood ow and oxygen demand and neurovascular coupling in the brain [22][23]. Endogenous NO was mainly generated from the citrulline-arginine-NO pathway [24]. Previous studies have shown that L-citrulline supplementation increased the bioavailability of L-arginine and promoted NO synthesis [24].…”

The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: a clinical review

“…L-citrulline is non-essential amino acid that found in abundance in watermelon. Potential beneficial effects on cardio-metabolic health [119,120] have been reported. In a recent study, 22 patients with flow mediated dilation of the brachial artery (< 5.5%) were recruited take 800 mg/day of L-citrulline for 8 weeks.…”