International Journal of Nutrition Sciences

International Journal of Nutrition Sciences

The Effect of Whole Pomegranate Juice (Punica Granatum) on Nutritional and Immunological Status of Hospitalized Covid-19 Patients

Document Type : Original Article

Authors
Zaker Saeedinezhad 1
Mahak Hosseinikia 2
Seyed-Bahman Panahande 3
Marjan Roozbehi 3
Sara Mahmoodi 3
Mohammadreza Sadriirani 3
Bahar Samimi 3
Jose M. Soriano 4
Mehrnaz Abbasi 5
Azizollah Pourmahmoudi 3
1 Department of Internal Medicine, School of Medicine, Yasouj University of Medical Sciences, Yasouj, Iran
2 School of Nutrition and Public Health, Linus Pauling Institute, Oregon State University, OR, USA
3 Department of Nutrition, School of Health and Nutrition, Yasuj University of Medical Sciences, Yasuj, Iran
4 Food and Health Laboratory, Institute of Materials Science, University of Valencia, 46980 Paterna, Spain
5 College of Health Solutions, Arizona State University, Phoenix, Arizona, 85004, USA
10.30476/ijns.2025.105819.1407
Abstract
Background: Pomegranate juice may favorably affect nutritional and immunological status. This study set out to explore the nutritionalimmunological effects of pomegranate juice on hospitalized COVID-19 patients.
Methods: We conducted this study as an exploratory randomized clinical trial recruiting 48 COVID-19 patients. Subjects were randomly allocated to intervention and placebo groups. Intervention participants received 500 mL of whole pomegranate juice as a complementary therapy, and control patients received the same amount of placebo for 2 weeks. Controlling nutritional status (CONUT), prognostic nutritional index (PNI) and albumin to globulin ratio (AGR) scores were measured at baseline and the end of the trial.
Results: Forty three patients completed the study. Cholesterol level significantly decreased (p<0.0001), and albumin (p<0.0001), total protein (p=0.03) and lymphocytes (p=0.04) levels significantly increased in the pomegranate juice group. However, the result remained insignificant regarding CONUT, PNI and AGR.
Conclusion: Our intervention showed that pomegranate juice had no significant effect on nutritional-immunological indicators, including CONUT, PNI and AGR scores. However, it did significantly reduced cholesterol level and increased albumin, total protein and lymphocyte levels. Further studies are needed to determine the long-term effects of pomegranate juice consumption on nutritional-immunological indicators and overall health outcomes.

Highlights

Azizollah Pourmahmoudi (Google Scholar)

 

Keywords
Pomegranate
COVID-19
Nutrition
Immunology
Iran
  1. Ahmadi S, Firoozi D, Masoumi SJ. The Effect of Micronutrients on COVID-19 Disease: A Review of Available Evidences. Int J Nutr Sci. 2022;7:10-18. DOI: 10.30476/IJNS.2022.94162.1169.
  2. Ghadimi Moghadam AK, Masoumi SJ, Nouri M, et al. The Effect of Nutrients Intake with an Emphasis on Immune-Boostings in Patients with COVID-19. Int J Nutr Sci. 2022;7:34-40. DOI: 10.30476/IJNS.2022.94174.1170.
  3. Mehrdad M, Eftekhari MH. Concerns on Obesity during COVID-19 Pandemic. Int J Nutr Sci. 2021;6:111-112. DOI: 10.30476/IJNS.2021.90311.1125.
  4. Rahman S, Montero MTV, Rowe K, Kirton R, Kunik Jr F. Epidemiology, pathogenesis, clinical presentations, diagnosis and treatment of COVID-19: a review of current evidence. Expert Rev Clin Pharmacol. 2021;14:601-21. DOI: 10.1080/17512433.2021.1902303. PMID: 33705239.
  5. Moazzen N, Imani B, Aelami MH, et al. How to boost our immune system against coronavirus infection? Arch Bone Jt Surg. 2020;8:220. DOI: 10.22038%2Fabjs.2020.47559.2330. PMID: 32733978.
  6. Mehrabani D, Masoumi SJ, Masoumi AS, et al. Role of Diet in Mesenchymal Stem Cells’ Function: A Review. Int J Nutr Sci. 2023;8:9-19. DOI: 10.30476/IJNS.2023.97788.1221.
  7. Hedayati A, Homayuon M, Mobaracky A, et al. Lithium Chloride, Ketogenic Diet and Stem Cell Transplantation in Treatment of Bipolar Disorder. Int J Nutr Sci. 2024;9:80-82. DOI: 10.30476/IJNS.2024.99601.1250.
  8. Homayoun M, Mehrabani D, Edalatmanesh MA, et al. The Role of Lithium Chloride in Nutrition and Stem Cell Growth Kinetics: A Review. Int J Nutr Sci. 2021;6:6-13. DOI: 10.30476/IJNS.2021.88801.1104.
  9. Kandylis P, Kokkinomagoulos E. Food applications and potential health benefits of pomegranate and its derivatives. Foods. 2020;9:122. DOI: 10.3390/foods9020122. PMID: 31979390.
  10. Hosseini SE, Mehrabani D, Ghaedi HR. The effect of pomegranate juice on hemogram of male adult rats. Damghan Zool J. 2014;6:25-30.
  11. Hosseini SE, Mehrabani D, Rezaei E. Effects of pomegranate juice on liver enzymes (ALT, ALP, AST) in diabetic and non-diabetic rats. J Anim Physiol Develop. 2014;24:59-64.
  12. Hosseini SE, Rezaei E, Mehrabani D, et al. Effect of pomegranate juice on lipid profile in streptozotocin-induced diabetic adult male rats. J Exp Anim Biol. 2013;2:13-20.
  13. Feng X, Yang Q, Wang C, Tong W, Xu W. Punicalagin exerts protective effects against ankylosing spondylitis by regulating NF-κB-TH17/JAK2/STAT3 signaling and oxidative stress. Biomed Res Int. 2020;2020: 4918239. DOI: 10.1155/2020/4918239. PMID: 33029510.
  14. Tito A, Colantuono A, Pirone L, et al. Pomegranate peel extract as an inhibitor of SARS-CoV-2 spike binding to human ACE2 receptor (in vitro): a promising source of novel antiviral drugs. Front Chem. 2021;9:638187. DOI: 10.3389/fchem.2021.638187. PMID: 33996744.
  15. Suručić R, Tubić B, Stojiljković MP, et al. Computational study of pomegranate peel extract polyphenols as potential inhibitors of SARS-CoV-2 virus internalization. Mol Cell Biochem. 2021;476:1179-93. DOI: 10.1007/s11010-020-03981-7. PMID: 33200379.
  16. Jia H, Neptune E, Cui H. Targeting ACE2 for COVID-19 therapy: opportunities and challenges. Am J Respir Cell Mol Biol. 2021;64:416-25. DOI: 10.1165/rcmb.2020-0322PS. PMID: 33296619.
  17. Wang R, He M, Yue J, et al. CONUT score is associated with mortality in patients with COVID-19: a retrospective study in Wuhan. preprint. 2020. DOI: 10.21203/rs.3.rs-32889/v1.
  18. Kang HW, Seo SP, Kim WT, et al. Prognostic impact of nutritional status assessed by the controlling nutritional status (CONUT) score in patients with surgically treated renal cell carcinoma. Nutr Cancer. 2018;70:886-94. DOI: 10.1080/01635581.2018.1490448. PMID: 30235010.
  19. Chambers KF, Day PE, Aboufarrag HT, et al. Polyphenol effects on cholesterol metabolism via bile acid biosynthesis, CYP7A1: a review. Nutrients. 2019;11:2588. DOI: 10.3390/nu11112588. PMID: 31661763.
  20. Agustini N, Setiawan A, Salni S. Effect Of Pomegranate (Punica granatum L.) Fraction In Reducing Total Blood Cholesterol Levels and Triglyceride in Mice (Mus muscullus L.). Indonesian Environ Manage Sustain. 2020;4:14-22. DOI: 10.26554/ijems.2020.4.1.14-22.
  21. Wu M, Fossali T, Pandolfi L, et al. Hypoalbuminemia in COVID‐19: assessing the hypothesis for underlying pulmonary capillary leakage. J Intern Med. 2021;289:861-72. DOI: 10.1111/joim.13208. PMID: 33411411.
  22. Yousefi M, Sadriirani M, PourMahmoudi A, et al. Effects of pomegranate juice (Punica Granatum) on inflammatory biomarkers and complete blood count in patients with COVID-19: A structured summary of a study protocol for a randomized clinical trial. Trials. 2021;22:246. DOI: 10.1186/s13063-021-05194-9. PMID: 33810808.
  23. Yousefi M, Mahmoodi S, Samimi B, et al. Adjuvant Pomegranate Juice Intake Improves the Inflammatory Status and Clinical Outcomes of Hospitalized COVID-19 Patients: An Exploratory Randomized and Placebo-Controlled Trial​. Complement Ther Med. DOI: 10.1016/j.ctim.2023.102958. PMID: 37271189.
  24. Zhou H, Chao W, Cui L, et al. Controlling Nutritional Status (CONUT) score as immune-nutritional predictor of outcomes in patients undergoing peritoneal dialysis. Clin Nutr. 2020;39:2564-70. DOI: 10.1016/j.clnu.2019.11.018. PMID: 31787366.
  25. Shirakabe A, Hata N, Kobayashi N, et al. The prognostic impact of malnutrition in patients with severely decompensated acute heart failure, as assessed using the Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) score. Heart Vessels. 2018;33:134-44. DOI: 10.1007/s00380-017-1034-z. PMID: 28803356.
  26. Upadhyay J, Tiwari N, Ansari MN. Role of inflammatory markers in corona virus disease (COVID-19) patients: a review. Exp Biol Med (Maywood). 2020;245(15):1368-75. DOI: 10.1177/1535370220939477. PMID: 32635752.
  27. Valero-Mendoza A, Meléndez-Rentería N, Chávez-González M, et al. The whole pomegranate (Punica granatum. L), biological properties and important findings: A review. Food Chem. 2022:100153. DOI: 10.1016/j.focha.2022.100153.
  28. Rezaei E, Hosseini SE, Mehrabani D. Effects of pomegranate juice on insulin and glucose in diabetic and non-diabetic male rats. J Birjand Univ Med Sci. 2013;20:1-8.
  29. Balachandar V, Mahalaxmi I, Kaavya J, et al. COVID-19: emerging protective measures. Eur Rev Med Pharmacol Sci. 2020;24:3422-5. DOI: 10.26355/eurrev_202003_20713. PMID: 32271461.
  30. Khalifa I, Zhu W, Nafie MS, et al. Anti-COVID-19 effects of ten structurally different hydrolysable tannins through binding with the catalytic-closed sites of COVID-19 main protease: An in-silico approach. Preprint. 2020. DOI: 10.20944/preprints202003.0277.v1.
  31. Wang F, Xue Y, Yang J, et al. Hepatoprotective effect of apple polyphenols against concanavalin A-induced immunological liver injury in mice. Chem Biol Interact. 2016;258:159-65. DOI: 10.1016/j.cbi.2016.08.018. PMID: 27567545.
  32. Esmaillzadeh A, Tahbaz F, Gaieni I, et al. Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. Int J Vitam Nutr Res. 2006;76:147-51. DOI: 10.1024/0300-9831.76.3.147. PMID: 17048194.
  33. Binmowyna MN, Alfaris NA, Almnaizel AT, et al. Hypolipidemic and antioxidant effects of the juice and water seed extracts of two pomegranate species in high-cholesterol diet fed rats. J Food Sci Technol. 2020;41:732-40. DOI: 10.1590/fst.31220.
  34. Hashemi MS, Namiranian N, Tavahen H, et al. Efficacy of pomegranate seed powder on glucose and lipid metabolism in patients with type 2 diabetes: a prospective randomized double-blind placebo-controlled clinical trial. J Complement Med Res. 2021;28:226-33. DOI: 10.1159/000510986. PMID: 33302270.
  35. Wu Y, Zhu CP, Zhang Y, et al. Immunomodulatory and antioxidant effects of pomegranate peel polysaccharides on immunosuppressed mice. Int J Biol Macromol. 2019;137:504-11. DOI: 10.1016/j.ijbiomac.2019.06.139. PMID: 31229542.
  36. Kalemba-Drożdż M, Cierniak A, Cichoń I. Berry fruit juices protect lymphocytes against DNA damage and ROS formation induced with heterocyclic aromatic amine PhIP. J Berry Res. 2020;10:95-113. DOI: 10.3233/JBR-190429.
  37. Gavlighi HA, Tabarsa M, You S, et al. Extraction, characterization and immunomodulatory property of pectic polysaccharide from pomegranate peels: Enzymatic vs conventional approach. Int J Biol Macromol. 2018;116:698-706. DOI: 10.1016/j.ijbiomac.2018.05.083. PMID: 29775715.
  38. Saadh M, Almaaytah A, Alaraj M, et al. Punicalagin and zinc (II) ions inhibit the activity of SARS-CoV-2 3CL-protease in vitro. Eur Rev Med Pharmacol Sci. 2021;25:3908-13. DOI: 10.26355/eurrev_202105_25958. PMID: 34109605.
  39. Amin SA, Banerjee S, Gayen S, et al. Protease targeted COVID-19 drug discovery: What we have learned from the past SARS-CoV inhibitors? Eur J Med Chem. 2021;215:113294. DOI: 10.1016/j.ejmech.2021.113294. PMID: 33618158.
  40. Du R, Cooper L, Chen Z, et al. Discovery of chebulagic acid and punicalagin as novel allosteric inhibitors of SARS-CoV-2 3CLpro. Antivir Res. 2021;190:105075. DOI: 10.1016/j.antiviral.2021.105075. PMID: 33872675.
International Journal of Nutrition Sciences
Volume 10, Issue 4 - Serial Number 4
December 2025
Pages 707-714