Randomized Control Trials Impact of curcumin supplementation on expression of inflammatory transcription factors in hemodialysis patients: A pilot randomized, double-blind, controlled study Livia Alvarenga a, * , Roberta Salarolli b , Ludmila F.M.F. Cardozo c , Rhayssa S. Santos d , Jessyca S. de Brito a , Julie Ann Kemp c , Drielly Reis a , Bruna Regis de Paiva c , Peter Stenvinkel e , Bengt Lindholm e , Denis Fouque f , Denise Mafra a, b, c, d a Graduate Program in Medical Sciences, Fluminense Federal University (UFF), Niter oi, Brazil b Graduate Program in Nutrition Sciences, Fluminense Federal University (UFF), Niter oi, Brazil c Graduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niter oi, Brazil d College of Nutrition, Fluminense Federal University (UFF), Niter oi, Brazil e Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Stockholm, Sweden f Department of Nephrology, Centre Hopitalier Lyon Sud, INSERM 1060, CENS, Universit e de Lyon, France article info Article history: Received 30 October 2019 Accepted 6 March 2020 Keywords: Chronic kidney disease Curcumin Inflammation Oxidative stress Turmeric summary Background & aims: Chronic kidney disease (CKD) patients have numerous complications associated with inflammation, which is a potential driver for cardiovascular disease. Curcumin, a compound of the curcuminoid class produced by the Curcuma longa, has been reported to activate nuclear factor erythroid factor 2-related (Nrf2) and inhibit nuclear factor kappa-B (NF-kB). Our aim was to evaluate the effects of curcumin juice on the expression of inflammatory transcription factors in hemodialysis (HD) patients. Methods and results: This double-blind randomized pilot study included 31 HD patients divided into two groups: curcumin group (receiving 100 mL of orange juice with 12 g of carrot and 2.5 g of turmeric after each dialysis session/week for 3 months) and control group (receiving the same juice without curcumin); 14 patients in each arm completed the study. The mRNA expression of Nrf2, NF-kB, NLRP3 inflammasome and IL-1b in peripheral blood mononuclear cells (PBMC; using real-time quantitative polymerase chain reaction, qPCR) and routine biochemistries, food intake and anthropometrics were analyzed. After three months of supplementation, the curcumin group showed a significant decrease in NF-kB mRNA expression (AU) [from 1.08 (0.77e1.38) to 0.52 (0.32e0.95),p ¼ 0.02] and in plasma high sensitivity C- reactive protein (hsCRP) levels [from 3.8 (2.5e6.8) to 2.0 (1.1e3.8) mg/L, p ¼ 0.04]. There was no change in the other evaluated markers. Conclusion: Three months treatment with curcumin in CKD patients undergoing HD resulted in decreased markers of inflammation, NF-kB mRNA expression and hsCRP, suggesting that oral supple- mentation of curcumin may have an anti-inflammatory effect in this patient group. Trial registration: Approved by the Ethics Committee of the Faculty of Medicine/UFF, number: 2.346.933. This study was registered within ClinicalTrials.gov under the number NCT 03475017. © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. 1. Introduction Common clinical complications and comorbidities in patients with chronic kidney disease (CKD), such as diabetes mellitus, hypertension, systemic diseases, immunological disorders, persistent uremia, and poor nutritional status, are associated with increased oxidative stress and inflammation that may contribute to cardiovascular disease (CVD), premature ageing and increased mortality [1e6]. Inflammation and oxidative stress are common features of the uremic phenotype, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant capacity [7e9]. Along with a ROS production increase, the * Corresponding author. E-mail address: liviaalvarenga92@gmail.com (L. Alvarenga). Contents lists available at ScienceDirect Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu https://doi.org/10.1016/j.clnu.2020.03.007 0261-5614/© 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. Clinical Nutrition xxx (xxxx) xxx Please cite this article as: Alvarenga L et al., Impact of curcumin supplementation on expression of inflammatory transcription factors in hemodialysis patients: A pilot randomized, double-blind, controlled study, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2020.03.007