The Effectiveness and Safety of Pomegranate (Punica granatum L.) Juice Powder in Patients with Diabetic Nephropathy, a Double-Blinded Randomized Clinical Trial
Abstract
Diabetic nephropathy affects more than 40 % of diabetic patients and is the major cause of death in this population. Current medications, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, sodium-glucose cotransporter-2 inhibitors, calcitriol, etc., represent limitations both in terms of maximum efficacy and adverse effects. Animal studies exist regarding the nephroprotective effects of Punica granatum L. (Pomegranate) extract. The present study aims to assess the safety and efficacy of pomegranate juice in patients with diabetic nephropathy. Freeze-dried pomegranate juice powder was purchased from Shaanxi Tianxingjian Co. and filled in 500 ± 5 mg capsules. The intervention group (n= 23) received 4 capsules of pomegranate daily for 8 weeks; while the placebo group (n= 23) received identical-looking capsules similarly. All patients received maximum tolerated doses of ACEI /ARB, Statin, and fixed doses of Empagliflozin for the last 6 months. Fasting blood sugar, serum creatinine, blood urea nitrogen, aspartate transaminase, alanine transaminase, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, urine albumin, and urine albumin-creatinine ratio were measured at baseline and the end of the 4th and 8th weeks. Among all of the investigated parameters, urine albumin-creatinine ratio, and urine albumin were significantly reduced (p < 0.001) in the intervention group after 4 and 8 weeks as compared with the baseline and the placebo group. Other investigated parameters represent no differences in none of the groups. No adverse reaction was reported during the study. Previous studies suggest that pomegranate possesses anti-inflammatory properties by inhibiting interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-α, and transforming growth factor-β. This is the first clinical trial study investigating the efficacy of pomegranate in diabetic nephropathy, suggesting a promising role for this formulation as a supplement for patients receiving standard treatment, since it remarkably reduced the indicators of diabetic nephropathy.
Coccheri S. Approaches to the prevention of cardiovascular complications and events in diabetes mellitus. Drugs 2007;67:997-1026.
Fallahzadeh MK, Dormanesh B, Sagheb MM, Roozbeh J, Vessal G, et al. Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic patients with overt nephropathy: a randomized, double-blind, placebo-controlled trial. American J Kidney Dis 2012;60:896-903.
Gross JL, De Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, et al. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 2005;28:164-176.
Papale M, Di Paolo S, Vocino G, Rocchetti MT, Gesualdo L. Proteomics and diabetic nephropathy: what have we learned from a decade of clinical proteomics studies? J Nephrol 2014;27:221-228.
Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870-878.
Balakumar P, Chakkarwar VA, Kumar V, Jain A, Reddy J, et al. Experimental models for nephropathy. J Renin-Angiotensin-Aldosterone Syst 2008;9:189-195.
Declèves AE, Sharma K. New pharmacological treatments for improving renal outcomes in diabetes. Nat Rev Nephrol 2010;6:371-380.
Ting RZ, Luk AO, Chan JC. Treatment and landmark clinical trials for renoprotection. Diabetes and the Kidney 2011;170:184-95.
Yamazaki T, Mimura I, Tanaka T, Nangaku M. Treatment of diabetic kidney disease: current and future. Diabetes Metab J 2021;45:11-26.
Shahin DH, Sultana R, Farooq J, Taj T, Khaiser UF, et al. Insights into the uses of traditional plants for diabetes nephropathy: a review. Curr Issues Mol Biol 2022;44:2887-2902.
Dragoș D, Manea MM, Timofte D, Ionescu D. Mechanisms of herbal nephroprotection in diabetes mellitus. J Diabetes Res 2020;2020:5710513.
Ibn Sina (Avicenna). Kitab al-Qanon fi al-Tibb (Canon of medicine). Senior Press Superintendent, Jamia Hamdard Printing Press. New Delhi 1998.
Gurukar A, Nandini CD, Mahadevamma S, Salimath PV. Ocimum sanctum and Morus alba Leaves and Punica granatum Seeds in Diet Ameliorate Diabetes-Induced Changes in Kidney. J Pharm Res 2012;5:4729-4733.
Ansari R, Karimzade I, Nimrouzi M, Ezatzadegan S, Hosseini MM, et al. Safety and efficacy of a polyherbal formulation from traditional Persian medicine in patients with calcium kidney stones: A randomized, double-blinded clinical trial. J Res Med Sci 2024;29:12.
Halonen JI, Erhola M, Furman E, Haahtela T, Jousilahti P, et al. The Helsinki declaration 2020: Europe that protects. Lancet Planet Health 2020;4:e503-e505.
Movahedinia A, Heydari M. Antioxidant activity and total phenolic content in two alga species from the Persian Gulf in Bushehr province, Iran. Int J Sci Res 2014;3:954-958.
Slinkard K, Singleton VL. Total phenol analysis: automation and comparison with manual methods. Am J Enol Vitic 1977;28:49-55.
Chang CC, Yang MH, Wen HM, Chern JC. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal 2002;10:178-182.
Ismail T, Sestili P, Akhtar S. Pomegranate peel and fruit extracts: a review of potential anti-inflammatory and anti-infective effects. J Ethnopharmacol 2012;143:397-405.
Asgary S, Sahebkar A, Afshani MR, Keshvari M, Haghjooyjavanmard S, et al. Clinical evaluation of blood pressure lowering, endothelial function improving, hypolipidemic and anti‐inflammatory effects of pomegranate juice in hypertensive subjects. Phytother Res 2014;28:193-199.
Yan Huan YH, Peng KeJun PK, Wang QiuLin WQ, Gu ZhengYi GZ, Lu YaoQin LY, et al. Effect of pomegranate peel polyphenol gel on cutaneous wound healing in alloxan-induced diabetic rats. Chin Med J (Engl) 2013;126:1700-1706
Rao NK, Nammi S. Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats. BMC complement Alternat Med 2006;6:1-6.
Rock W, Rosenblat M, Miller-Lotan R, Levy AP, Elias M,et al. Consumption of wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities. J Agric Food Chem 2008;56:8704-8713.
Esmaillzadeh A, Tahbaz F, Gaieni I, Alavi-Majd H, Azadbakht L. Concentrated pomegranate juice improves lipid profiles in diabetic patients with hyperlipidemia. J Med Food 2004;7:305-308.
Esmaillzadeh A, Tahbaz F, Gaieni I, Alavi-Majd H, Azadbakht L. Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. Int J Vitam Nutr Res 2006;76:147-151.
Jandari S, Hatami E, Ziaei R, Ghavami A, Yamchi AM. The effect of pomegranate (Punica granatum) supplementation on metabolic status in patients with type 2 diabetes: A systematic review and meta-analysis. Complement Ther Med 2020;52:102478.
Laurindo LF, Barbalho SM, Marquess AR, Grecco AI, Goulart RD, et al. Pomegranate (Punica granatum L.) and metabolic syndrome risk factors and outcomes: A systematic review of clinical studies. Nutrients 2022;14:1665.
Moneim AE, Dkhil MA, Al-Quraishy S. Studies on the effect of pomegranate (Punica granatum) juice and peel on liver and kidney in adult male rats. J Med Plants Res 2011;5:5083-5088.
Singh AP, Singh AJ, Singh N. Pharmacological investigations of Punica granatum in glycerol-induced acute renal failure in rats. Indian J Pharmacol 2011;43:551-556.
Tugcu V, Kemahli E, Ozbek E, Arinci YV, Uhri M, et al. Protective effect of a potent antioxidant, pomegranate juice, in the kidney of rats with nephrolithiasis induced by ethylene glycol. J Endourol 2008;22:2723-2232.
Ankita P, Deepti B, Nilam M. Flavonoid rich fraction of Punica granatum improves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals. Pharm Biol 2015;53:61-71.
Douglas K, O'Malley PG, Jackson JL. Meta-analysis: the effect of statins on albuminuria. Ann Int Med 2006;145:117-124.
Lee TM, Su SF, Tsai CH. Effect of pravastatin on proteinuria in patients with well-controlled hypertension. Hypertension 2002;40:67-73.
Toblli JE, Bevione P, Di Gennaro F, Madalena L, Cao G, et al. Understanding the mechanisms of proteinuria: therapeutic implications. Int J Nephrol 2012;2012:546039.
Bianchi S, Bigazzi R, Caiazza A, Campese VM. A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease. Am J Kidney Dis 2003;41:565-570.
Virgen-Carrillo CA, Martínez Moreno AG, Valdés Miramontes EH. Potential hypoglycemic effect of pomegranate juice and its mechanism of action: a systematic review. J Med Food. 2020;23:1-1.
| Issue | Vol 10, No 4, 2025 -In Press- | |
| Section | Research Article(s) | |
| Keywords | ||
| Diabetic nephropathy Punica granatum Clinical trial Urine albumin | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |


