The beneficial effects of crocin supplementation on metabolic and genetic parameters in type 2 diabetic patients under metformin treatment: A randomized double-blind controlled clinical trial

Abstract

Background and objective

Since it has been demonstrated that inflammation and oxidative stress (OS) are important in the etiology and complexity of type 2 diabetes mellitus (T2DM), antioxidant treatment is recognized as an effective approach for managing the progression of the disease. The current study was conducted to assess the effects of crocin administration on metabolic and genetic indices in T2DM patients who were receiving metformin.

Materials and methods

Sixty T2DM patients, receiving metformin, were included in our randomized double-blind placebo-controlled clinical trial. Patients were divided into two groups (n = 30) and received either 15 mg/day crocin supplementation or a placebo twice a day for 12 weeks. Fasting blood was obtained at the beginning and end of the intervention to assess glycemic index, lipid content, indicators of inflammation, and OS. Patients’ peripheral blood mononuclear cells (PBMC) were analyzed for gene expression associated with OS and inflammation using real-time polymerase chain reaction (real-time PCR).

Results

Crocin intake significantly decreased fasting plasma glucose (P < 0.001), HbA₁c (P = 0.002), serum insulin levels (P = 0.03), and insulin resistance (P < 0.001), while significantly enhanced insulin sensitivity (P < 0.001) compared with the placebo. These improvements were also found to be statistically significant in comparison to the baseline values in the crocin group. Moreover, a significant reduction in triglyceride levels (P = 0.04), VLDL-cholesterol (P = 0.04), high-sensitivity C-reactive protein (P < 0.001), malondialdehyde (P = 0.046), and significant enhancement of plasma glutathione (P = 0.008) were found in the intervention group compared to the placebo group. Additionally, the level of high-sensitivity C-reactive protein in the intervention group decreased compared to baseline while it increased in the placebo group. Crocin significantly lowered TOS (P < 0.05); however, at the end of the trial there was no significant difference between the two groups. Eventually, crocin supplementation induced AMP-activated protein kinase (P = 0.002) and glucose transporter type 4 (P = 0.02), while downregulating nuclear factor kappa B gene expression levels (P = 0.04) of PBMC compared to the placebo.

Conclusion

Overall, crocin supplementation was demonstrated to have ameliorative effects on glycemic indices as well as cardio-metabolic risk.