Science

L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychologically fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research.

The studies reviewed suggest a key role of NO in the PVN for the control of erectile function and of both the PVN and the medial preoptic area in male rat sexual behavior. In the PVN NO is synthesized by NO synthase located in the cell bodies of oxytocinergic neurons projecting to extra-hypothalamic brain areas and mediating this sexual response.

In summary, inorganic nitrate supplementation within the CVD cohort shows promise as a potential “therapeutic” with the aim of restoring deficient NO bioavailability, correcting physiological dysfunctions, and recovering exercise capacity/performance and health.

The findings reveal that short-term high-dose NO3−supplementation elevated plasma NO2−concentration and reduced BP during a short isometric contraction and a sustained ischaemic contraction in healthy males. These findings support that NO3−supplementation is an effective nutritional intervention in reducing SBP and MAP in healthy young males during submaximal exercise.

Nitric oxide is a physiological compound of the human body that dilates blood vessels, stimulates hormone release, regulates neurotransmission and acts as a signaling molecule. Nitric oxide is synthesized by NOS-dependent and -independent pathways. Nitric oxide supplementation improves cardiac health, enhances performance during exercise, improves healing, reduces erectile dysfunction, reduces high blood pressure during pregnancy and improves respiratory response.

NO (nitric oxide), formed in the vascular endothelium and derived from a biochemical reaction catalysed by eNOS (endothelial NO synthase), appears to play a role in exercise-induced dilation of blood vessels supplying cardiac and skeletal muscle. Endothelium-dependent, NO-mediated vasodilation is augmented by exercise training. Increases in eNOS gene transcription, eNOS mRNA stability and eNOS protein translation appear to contribute to increased NO formation and, consequently, enhanced NO-mediated vasodilation after training. Enhanced endothelial NO formation may also have a role(s) in the prevention and management of atherosclerosis because several steps in the atherosclerotic disease process are inhibited by NO. A growing body of work suggests that exercise training, perhaps via increased capacity for NO formation, retards atherosclerosis. This has significant implications for human health, given that atherosclerosis is the leading killer in Western society.

In conclusion, dose-dependent effects have been established between dietary NO3 and plasma NO3 and NO2 levels, BP, and vascular health markers. Due to the high NO3 content and other active ingredients in dietary NO3 sources, they may effectively regulate BP and enhance arterial stiffness and endothelial function. Moreover, individuals with HTN may derive greater benefits from these sources. The observed effects are at times on par with or comparable to existing treatments, including dietary and pharmaceutical interventions. Before clinical application, further research is required to validate the long-term safety and adherence to dietary NO3 supplementation.

L-Citrulline supplementation significantly increased plasma L-arginine levels and reduced completion time by 1.5 % (p < 0.05) compared with placebo. Moreover, L-citrulline significantly improved subjective feelings of muscle fatigue and concentration immediately after exercise.

In conclusion, this study has shown that short-term Cit supplementation can reduce blood pressure, speed V̇o2kinetics, and enhance endurance exercise performance. Supplementation with Arg, on the other hand, did not significantly affect these parameters. Therefore, the results of this study suggest that chronic supplementation with Cit might represent a practical, dietary intervention to reduce blood pressure and enhance oxidative metabolism and exercise performance in young healthy adults.

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. Whilel-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), orall-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 recyclingl-arginine. Unlikel-arginine,l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasingl-arginine levels and NO synthesis.

In summary, endogenous NO is generated via two discrete pathways—the NOS-dependent pathway (L-arginine-NO pathway) and NOS-independent pathway (NO3−-NO2−-NO pathway). Supplementation with precursors may improve their bioavailability and NO synthesis to promote relaxation of vascular smooth muscle which may favorably impact blood flow and augment mechanisms contributing to skeletal muscle performance, hypertrophy, and strength adaptations. L-citrulline and/or nitrates show the most promise for improving NO synthesis because they are well-absorbed into systemic circulation, whereas L-arginine is subjected to significant catabolism leading to poor bioavailability following oral intake. There is very limited supportive evidence to recommend L-arginine supplementation to improve strength performance, whereas acute or short-term supplementation with L-citrulline (≥3 g·d−1 L-citrulline or ≥8 g·d−1 CitMal; ~1 h prior) and nitrates (≥400 mg·d−1; ~2 h prior) appear to have beneficial effects on muscular performance, but evidence on their effectiveness is mixed. Overall, the potential for the use of foods and dietary supplements rich in L-citrulline and nitrates is promising for the strength and power athlete, yet more research is warranted. Particularly, further research is required to determine the chronic effects of supplementation and the potential synergistic effects of NO precursors given the growing trend of multi-ingredient “NO boosting” supplements on the market.

In conclusion, dose-dependent effects have been established between dietary NO3 and plasma NO3 and NO2 levels, BP, and vascular health markers. Due to the high NO3 content and other active ingredients in dietary NO3 sources, they may effectively regulate BP and enhance arterial stiffness and endothelial function. Moreover, individuals with HTN may derive greater benefits from these sources. The observed effects are at times on par with or comparable to existing treatments, including dietary and pharmaceutical interventions. Before clinical application, further research is required to validate the long-term safety and adherence to dietary NO3 supplementation.