The effect of L-citrulline supplementation on glycemic status, meta-inflammation and obesity indices in type 2 diabetes patients: A randomized controlled clinical trial

Abstract

Background: Diabetes mellitus is the most common metabolic disease and a major cause of death in the world. L-citrulline- a non-essential alpha-amino acid- is a precursor of L-arginine and nitric oxide. Results of animal studies have indicated positive effects of L-citrulline on inflammatory and metabolic pathways of type 2 diabetes. Therefore, this study was designed to determine the effect of L-citrulline supplementation on glycemic status, meta-inflammation and obesity indices in patients with type 2 diabetes.

Methods: In this double-blind randomized controlled clinical trial, 45 patients with type 2 diabetes 23 in the L-citrulline group (receiving a 3-gram sachet of L-citrulline) and 22 in the placebo group (receiving a 3-gram sachet of microcrystalline cellulose) before breakfast for eight weeks. All subjects were asked to follow a healthy diet. Demographic and 3-day food record questionnaires were completed and anthropometric indices were measured at the beginning and end of the study. At the beginning and end of the study, intravenous fasting blood sample was taken and serum levels of glycemic indices (FBS, HbA1c), meta-inflammation markers (monocyte chemoattractant protein 1 (MCP-1) and toll-like receptor 4 (TLR-4)) in whole blood and obesity indices were assessed.

Results: At the end of the study, L-citrulline supplementation significantly reduced serum concentrations of glucose (P = 0.016) and hemoglobin A1c (P = 0.001) compared with the placebo group. There was no significant difference in anthropometric measurements and obesity indices (weight, BMI and waist circumference, waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR)) compared with the placebo group. Despite a decrease in serum concentrations of TLR-4 (P = 0.002) in the L-citrulline group, the difference between the two groups was not statistically significant and L-citrulline supplementation could not significantly reduce serum levels of MCP-1 compared with placebo.

Conclusion: Our findings indicate that L-citrulline supplementation significantly improved glucose profile without any statiticaly significant improvement in meta-inflammation status and obesity indices in patients with type 2 diabetes. As other inflammatory factors have not been investigated in this study, further clinical trials are required with larger sample size, longer period considering pro- and anti-inflammatory factors.

Keywords: L-citrulline, type 2 diabetes, meta-inflammation, glycemic status