Effects of saffron supplementation on glycemia and inflammation in patients with type 2 diabetes mellitus: A randomized double-blind, placebo-controlled clinical trial study Majid Mobasseri a , Alireza Ostadrahimi b , Aynaz Tajaddini b, c , Samira Asghari d , Meisam Barati e , Moloud Akbarzadeh d , Omid Nikpayam f, g , Jalil Houshyar a , Neda Roshanravan h, * , Naimeh Mesri Alamdari i, ** a Department of Medicine, Endocrine Section, Endocrine Research Center, Tabriz University of Medical Sciences, Iran b Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran c Pharmacology School of Medical Sciences, Faculty of Medicine, The University of New South Wales, Sydney, NSW, 2052, Australia d Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran e Student Research Committee, Department of Cellular and Molecular Nutrition, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran f Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran g Department of Clinical Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran h Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran i Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran article info Article history: Received 21 January 2020 Received in revised form 19 April 2020 Accepted 21 April 2020 Keywords: Inflammation Type 2 diabetes mellitus Saffron TNF-a IL-6 abstract Background: New evidence indicates that overproduction of pro-inflammatory cytokines is responsible for the development of diabetes difficulties. Some herbals such as saffron, may control inflammation and improve the hyperglycemic states in diabetic patients. Therefore, this investigation aimed to assess the effects of saffron supplementation on fasting glucose and inflammatory markers levels in patients with type2 diabetes mellitus (T2DM). Methods: In this randomized double-blind, placebo-controlled clinical trial, 60 T2DM patients were randomly assigned into two groups as saffron and placebo (n ¼ 30) receiving 100 mg/day saffron powder or starch capsules (1 capsule) for a duration of 8 weeks. Fasting blood sample was collected at baseline and at the end of the intervention. Fasting blood glucose (FBG) was immediately analyzed by the auto- analyzer. The serum level of Interleukin 6 (IL-6), Tumor necrosis factor-alpha (TNF-a), and Interleukin- 10 (IL-10) were measured using ELISA assay by laboratory kits. Also, Real-time quantitative reverse transcription (RT-PCR) assay measured the expression level of TNF-a, IL-6, and IL-10 at the mRNA level. Results: Saffron supplementation significantly decreased the FBG levels within 8 weeks compared to placebo (130.93 ± 21.21 vs 135.13 ± 23.03 mg/dl, P ¼ 0.012). Moreover, the serum level of TNF-a notably reduced in the saffron group compared to the placebo group (114.40 ± 24.28 vs 140.90 ± 25.49 pg/ml, P < 0.001). Also, saffron supplementation significantly down-regulated the expressions of TNF-a (P ¼ 0.035) and IL-6 mRNA levels (P ¼ 0.014). Conclusion: In our study, it was indicated that saffron modulates glucose levels as well as inflammation status in T2DM patients through decreasing the expressions levels of some inflammatory mediators. Also, further investigations are necessary to confirm the positive effects of saffron as a complementary therapy for T2DM patients. © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved. 1. Introduction Type 2 diabetes mellitus (T2DM) is considered to be a chronic disease as a defect in glucose metabolism with unidentified * Corresponding author. Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, 5166615573, Iran. ** Corresponding author. E-mail addresses: roshanravann@tbzmed.ac.ir, neda.roshanravan10@gmail.com (N. Roshanravan), mesrialamdari.n@tak.iums.ac.ir (N.M. Alamdari). Contents lists available at ScienceDirect Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx https://doi.org/10.1016/j.dsx.2020.04.031 1871-4021/© 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14 (2020) 527e534