THE EFFECTS OF CROCIN SUPPLEMENTATION ON MENTAL HEALTH PARAMETERS, METABOLIC AND GENETIC PROFILES IN PATIENTS UNDER METHADONE MAINTENANCE TREATMENT, A RANDOMIZED CLINICAL TRIAL

Background and Aim : Previous evidence has demonstrated that mental and metabolic disturbances were present in patients under methadone maintenance treatment (MMT). Crocin is a dietary supplement might improve mental and physical health in these patients. This investigation was designed to determine the effect of crocin supplementation on mental health parameters, metabolic and genetic profiles in patients under MMT. Methods : This randomized, double-blind, placebo-controlled, clinical trial was conducted among 60 patients under MMT. Participants were randomly allocated to receive either 30 mg/day crocin (2 plus crocin tablet, 15 mg BID) (n=30) or placebo (2 tablets per day, 15 mg BID) (n=30), one hour after taking food, for 8 weeks. Fasting blood samples were taken at baseline and the end of the trial to evaluate metabolic and genetic variables. HOMA-IR, QUICKI, FPG, lipid profiles, hs-CRP, NO, TAC, GSH and MDA concentrations were assessed at baseline and after the 8-week intervention. Depression was determined using BDI-21. Anxiety measured by BAI-21 was assessed at baseline and after the 8-week intervention. Gene expressions of TNF-α, TGF-β, VEGF, LDLR and PPAR-γ were assessed by quantitative RT-PCR in peripheral blood mononuclear cells (PBMCs). Results : Crocin administration significantly decreased Beck Depression Inventory index (P=0.01) and Beck Anxiety Inventory score (P=0.008) compared with the placebo. In addition, crocin administration resulted in a significant reduction in fasting glucose (P=0.003), insulin levels (P=0.01), insulin resistance (P=0.008), triglycerides (P=0.001), VLDL- (P=0.001) and total cholesterol levels (P=0.03), and a significant increase in insulin sensitivity (P=0.003) compared with the placebo. Additionally, crocin intake was associated with a significant reduction in high sensitivity C-reactive protein (P<0.001) and malondialdehyde (P=0.001), and a significant rise in total antioxidant capacity levels (P=0.01) compared with the placebo. Also, Crocin supplementation up-regulated PPAR- (P=0.01) and LDLR (P=0.003), and down-regulated gene expression of TNF- (P<0.001) in PBMCs of subjects with MMT, but did not affect gene expression of TGF- and VEGF.Conclusion : The findings of this clinical trial indicate that taking crocin for 8 weeks by patients under MMT had beneficial effects on their mental health and improved their metabolic profiles and gene expression. Crocin could be introduced as an adjunct to MMT program in clinical guidelines for withdrawal protocols since it enhances quality of life and diminishes MMT program side effects.

Keywords:

Crocin , mental health , metabolic profiles , methadone maintenance treatment