The effects of citrulline supplementation on meta-inflammation and insulin sensitivity in type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Abstract

Background This study aimed to examine the effects of l-citrulline (l-CIT) on low-grade inflammation (meta-inflammation) and insulin sensitivity in type 2 diabetes (T2D) patients since it has exhibited hypoglycemic and anti-inflammatory effects in most animal studies. Methods In this double-blind, placebo-controlled randomized clinical trial, 54 patients with T2D referred to specialized clinics of Tabriz University of Medical Sciences were assigned to l-CIT group (receiving orally one 3 g sachet of l-CIT daily before breakfast) or placebo group (receiving orally one 3 g sachet of microcrystalline cellulose daily before breakfast) for eight weeks. Serum levels of fasting blood glucose, hemoglobin A1c (HbA1c), CIT, monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), and toll-like receptor 4 (TLR-4) were determined. The quantitative insulin sensitivity check index (QUICKI) and homeostatic model assessment of β-cell function (HOMA-B) index were estimated at the baseline and post-intervention. Results No significant difference was observed between the studied parameters at the baseline. l-CIT supplementation significantly reduced not only serum concentrations of fasting blood glucose but also HbA1c, serum IL-6 and TLR-4 levels in the l-CIT group (p < 0.05). Additionally, at the end of the study serum levels of CIT increased significantly in l-CIT group compared to the baseline and placebo group. Fasting blood glucose concentrations and HbA1c significantly decreased after the intervention compared to the placebo. There was no significant difference in serum IL-6, TLR-4, MCP-1 levels, as well as QUICKI and HOMA-B index between the two groups, even after adjusting for baseline variables and confounders. Conclusions Our findings revealed that, although l-CIT supplementation significantly reduced fasting blood glucose concentrations, HbA1c and increased serum levels of CIT. It seems it could not significantly improve insulin sensitivity and meta-inflammation biomarkers. Additional studies with longer duration and different doses of l-CIT are required. Trial registration The protocol of this clinical trial is registered at the Iranian Registry of Clinical Trials (registration no: IRCT20100209003320N16 at www.irct.ir)

A unique profile of gut microbiota associated with metabolic syndrome: a remote island most afflicted by obesity in Japan

“…In contrast, citrulline, which was signi cantly reduced in serum of MUO compared to MHO in the present study, appears to play a role in arterial dilation and glucose homeostasis 42 . A randomized double-blind-placebo controlled study revealed that citrulline supplementation was able to markedly reduce value of fasting blood glucose and HbA1c in humans 43 . Lastly, concentration of betaine in serum, a naturally occurring methyl donor, which was signi cantly decreased in the MUO compared to MHO, is known to associate with metabolically-bene cial pro le in Asian men with mild fatty liver disease 44 .…”

Profile of gut microbiota and serum metabolites associated with metabolic syndrome in a remote island most afflicted by obesity in Japan

“…In contrast, citrulline, which was significantly reduced in serum of MUO compared to MHO in the present study, appears to play a role in arterial dilation and glucose homeostasis 39 . A randomized double-blind-placebo controlled study revealed that citrulline supplementation was able to markedly reduce value of fasting blood glucose and HbA1c in humans 40 . Lastly, concentration of betaine in serum, a naturally occurring methyl donor, which was significantly decreased in the MUO compared to MHO, is known to associate with metabolically-beneficial profile in Asian men with mild fatty liver disease 41 .…”

Carotid Artery Disease in Subjects with Type 2 Diabetes: Risk Factors and Biomarkers

“…It was shown that the disturbances of the L-arginine-NO-L-citrulline pathway in diabetes and metabolic syndrome are closely related to inflammation and oxidative stress [ 64 ]—the hallmarks of diabetic vascular complications [ 36 ]. At the same time, it was demonstrated that L-citrulline supplementation increases NO levels [ 65 ], improves insulin resistance, and decreases HbA1c and concentrations of inflammatory markers in patients with T2D [ 66 , 67 ]. The abnormalities of L-citrulline metabolism in diabetes, along with the mechanisms of their relationship with vascular disease, merit further research.…”