Potential roles of Citrulline and watermelon extract on metabolic and inflammatory variables in diabetes mellitus, current evidence and future directions: A systematic review.

Diabetes mellitus is a prevalent endocrine disorder worldwide. Citrulline is an α-amino acid, which is abundant in watermelon, and a precursor of arginine and nitric oxide. Decreased bioavailability of nitric oxide is associated with insulin resistance. The present systematic review focused on the existing evidence of citrulline and watermelon extract effects on metabolic and inflammatory parameters in diabetes mellitus.A systematic search of the databases PubMed, Scopus, EMBASE, ProQuest and Google Scholar was conducted for relevant papers published from inception until October 2018. All clinical trials, animal and in vitro studies published in English-language that assessed the role of citrulline and watermelon extract on diabetes mellitus, were eligible. Studies providing inadequate information were excluded.Out of 1262 articles we found, only 8 articles met the inclusion criteria for analysis. In three studies an increase in the synthesis of nitric oxide was reported with citrulline and watermelon extract supplementation. Four studies showed a significant reduction in blood glucose after supplementation with watermelon extract, and two studies reported a decrease in a number of inflammatory biomarkers following citrulline supplementation. Although citrulline intake caused a significant reduction in HOMA-IR in one study, inconsistent results were revealed on the effects of citrulline and watermelon extract on insulin levels and lipid profile.Citrulline and watermelon extract could improve nitric oxide synthesis, glycemic status and inflammation in diabetes mellitus. However, further studies are required to shed light on the underlying mechanisms.