Oxidative stress and nitrate/nitrite (NOx) status following citrulline supplementation in type 2 diabetes: a randomised, double‐blind, placebo‐controlled trial

Abstract

Background The pathogenesis of diabetes is accompanied by oxidative stress. Citrulline can be considered as a potent antioxidant. The present study aimed to examine the effects of citrulline supplementation on the status of oxidative stress and serum levels of nitrite/nitrate (NOx) in patients suffering from type 2 diabetes (T2DM). Methods The present study comprises a double‐blind placebo‐controlled randomised clinical trial. The study subjects include 54 patients with T2DM chosen from specialised clinics of Tabriz University of Medical Sciences. The patients were allocated to one of the placebo or intervention groups. The patients in the placebo and the intervention group received one sachet of microcrystalline cellulose or l‐citrulline (3 g), respectively, every day for 2 months. Malondialdehyde (MDA), glutathione peroxidase (GPx), total antioxidant capacity (TAC), superoxide dismutase (SOD), serum levels of fasting blood sugar (FBS), citrulline and NOx were assessed before and after the intervention. Results Forty‐five patients completed the trial. Significant decreases were found in serum levels of FBS and MDA. Serum levels of TAC, citrulline and NOx in the intervention group increased compared to those of the placebo group, after adjusting the data for the baseline values and confounders. Differences between and within the two groups were statistically nonsignificant for GPx and SOD at the end of the study. Body mass index and energy intake were not changed significantly after the intervention. Conclusions The results of the present study show the positive effects of citrulline supplementation with respect to attenuating FBS levels and oxidative stress, as well as boosting NOx status, in patients with T2DM.

Metabolic effects of L‐citrulline in type 2 diabetes

“…Cit increases insulin secretion from the pancreatic β cells, 115 improves insulin sensitivity, 155 and has antihyperten sives, [61][62][63] antihyperglycemic, 61 antidyslipidemic, 61,64 and antioxidant 65 effects. In vitro studies indicate that Cit (100 μM) increases insulin release in the presence of 8.3 mM glucose from isolated islets of Wistar rats.…”

“…56,57 Polypharmacy is associated with increased drug side-effects 58 (e.g., higher risk of bone fracture and depression 59 ), lower quality of life, and higher healthcare costs. 60 The therapeutic effects of Cit against oxidative stress, hyperglycemia, hypertension, hypertriglyceridemia, hypercholesterolemia, and insulin resistance have been reported in experimental [61][62][63][64] and clinical studies [65][66][67][68][69][70][71] in both males [61][62][63][64][66][67][68][69][70][71] and females. [67][68][69][70][71] Therefore, Cit can potentially act as a onedrug-multi-target agent in patients with T2D.…”

The Influence of Lifestyle and Treatment on Oxidative Stress and Inflammation in Diabetes

“…Among inflammatory markers, a reduction in CRP was noted among the AP group and a reduction in TNF-α in the PP group, while in terms of oxidative stress markers, reductions in MDA and protein carbonyls were noted in both groups [ 20 ]. Another interesting issue was addressed by Azizi et al [ 64 ], who conducted a study evaluating the effect of alpha-amino acid-citrulline supplementation on oxidative stress and (nitrite/nitrate) NOx in type 2 diabetic patients. At two months, in terms of oxidative stress markers, a marked reduction in serum MDA and fasting blood sugar (FBS) levels and a significant increase in NOx, citrulline and TAC levels were observed compared, to the baseline values, in the citrulline-supplemented group.…”

“…No significant differences were noted with regard to SOD and GSH-Px. In conclusion, citrulline as a precursor of arginine to increase its bioavailability for NO synthesis seems to be a helpful adjunctive therapy, however, further studies are needed [ 64 ].…”

The association between serum Sestrin2 and the risk of coronary heart disease in patients with type 2 diabetes mellitus

“…Oxidative stress, inflammation, endothelial dysfunction, and the release of proinflammatory cytokines are thought to countribute to the pathogenesis of both T2DM and CHD [ 4 ]. More evidence suggests that T2DM and CHD are induced by oxidative stress in greater numbers in recent years [ 5 , 6 ]. Therefore, finding effective antioxidant targets are the focus of the current research.…”