| 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. |