The Impact of Ramadan Fasting on Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein in Overweight and/or Obese and Non-Obese Individuals: A Systematic Review with Meta-Analysis
DOI:
https://doi.org/10.21831/jomassh.v1i1.1042Keywords:
C-reactive protein, inflammation, interleukin-6, intermittent fasting, Ramadan fasting, tumor necrosis factor-αAbstract
Introduction: Ramadan fasting (RF) has been suggested to modulate inflammation. Inflammatory biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) play pivotal roles in various metabolic and immune-related diseases. Given their clinical relevance, this study aims to evaluate the impact of RF on IL-6, TNF-α, and CRP. Methods: A systematic search of the literature evaluating the impact of RF on IL-6, TNF-α, and CRP/high sensitivity CRP (hsCRP) published in PubMed, ScienceDirect, Scopus, and Google Scholar was employed. Study quality was evaluated using the Newcastle-Ottawa Scale. Fixed- or random-effects model meta-analyses were performed using RevMan version 5.4 software. Subgroup analysis was performed based on BMI status, in overweight and/or obese (BMI ≥25) and non-obese (BMI ≥18.5) individuals. Meta-analysis was presented in standardized mean difference (SMD) with 95% confidence interval (CI). Fourteen studies involving 522 participants were finally included. Results: The finding showed that RF significantly reduced IL-6 (SMD = 0.68; 95% CI = 0.50, 0.87; p <0.00001) and TNF-α (SMD = 0.69; 95% CI = 0.34, 1.04; p = 0.0001), with stronger effects in overweight and/or obese individuals for IL-6 (SMD = 0.71; 95% CI = 0.52, 0.90; p <0.00001) and TNF-α (SMD = 0.79; 95% CI = 0.35, 1.23; p = 0.0005). Meanwhile, the reduction of CRP/hsCRP was significant only in non-obese individuals (SMD = 1.03; 95% CI = 0.04, 2.02; p = 0.04). Conclusion: RF may serve as a natural strategy to reduce systemic inflammation, particularly in individuals with elevated BMI. These findings may have clinical relevance for populations at risk of inflammation-related conditions such as obesity and metabolic syndrome. However, the heterogeneity in this meta-analysis requires the interpretation of the results with caution.
Downloads
References
1. Gusev E, Zhuravleva Y. Inflammation: A New Look at an Old Problem. IJMS. 2022;23(9):4596. https://doi.org/10.3390/ijms23094596
2. Germolec DR, Shipkowski KA, Frawley RP, Evans E. Markers of Inflammation. In: DeWitt JC, Rockwell CE, Bowman CC, editors. Immunotoxicity Testing. New York, NY: Springer New York; 2018. p. 57–79. (Methods in Molecular Biology; vol. 1803). https://doi.org/10.1007/978-1-4939-8549-4_5
3. Ridho FM, Agustina AW, Hidayati NN, Pratama MI, Laksono EP. Exploring the Association between Periodontitis and Erectile Dysfunction: A Systematic Review. Indonesian Andrology and Biomedical Journal. 2024;5(1):42–51. https://doi.org/10.20473/iabj.v5i1.56744
4. Ridho FM, Algifnita AO, Pramaztri NN, Laksono EP, Allifiah BPN, Ahmad M. Periodontitis as a Risk Factor of Preeclampsia in Pregnancy: A Scoping Review. International Islamic Medical Journal. 2024;5(2):9–25. https://doi.org/10.33086/iimj.v5i2.5316
5. Ridho FM, Maulidina AAN, Allifiah BPN. Correlation between Salivary Cortisol Levels in Patients with Psychological Stress and Incidence of Recurrent Aphthous Stomatitis: A Scoping Review. Indonesian Journal of Dentistry. 2024;4(1):23. https://doi.org/10.26714/ijd.v4i1.14026
6. Michels N, Van Aart C, Morisse J, Mullee A, Huybrechts I. Chronic inflammation towards cancer incidence: A systematic review and meta-analysis of epidemiological studies. Critical Reviews in Oncology/Hematology. 2021;157:103177. https://doi.org/10.1016/j.critrevonc.2020.103177
7. Manabe I. Chronic Inflammation Links Cardiovascular, Metabolic and Renal Diseases. Circ J. 2011;75(12):2739–48. https://doi.org/10.1253/circj.CJ-11-1184
8. Del Giudice M, Gangestad SW. Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters. Brain, Behavior, and Immunity. 2018;70:61–75. https://doi.org/10.1016/j.bbi.2018.02.013
9. Mohammadian Khonsari N, Baygi F, Tabatabaei-Malazy O, Mohammadpoor Nami S, Ehsani A, Asadi S, et al. Association of normal weight obesity phenotype with inflammatory markers: A systematic review and meta-analysis. Front Immunol. 2023;14:1044178. https://doi.org/10.3389/fimmu.2023.1044178
10. Schmidt FM, Weschenfelder J, Sander C, Minkwitz J, Thormann J, Chittka T, et al. Inflammatory Cytokines in General and Central Obesity and Modulating Effects of Physical Activity. Eckel J, editor. PLoS ONE. 2015;10(3):e0121971. https://doi.org/10.1371/journal.pone.0121971
11. Hirano T. IL-6 in inflammation, autoimmunity and cancer. International Immunology. 2021;33(3):127–48. https://doi.org/10.1093/intimm/dxaa078
12. Jang D in, Lee AH, Shin HY, Song HR, Park JH, Kang TB, et al. The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. IJMS. 2021;22(5):2719. https://doi.org/10.3390/ijms22052719
13. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018 Apr 13;9:754. https://doi.org/10.3389/fimmu.2018.00754
14. Sanvictores T, Casale J, Huecker MR. Physiology, Fasting. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Available from: http://www.ncbi.nlm.nih.gov/books/NBK534877/
15. Rouhani MH, Azadbakht L. Is Ramadan fasting related to health outcomes? A review on the related evidence. J Res Med Sci. 2014;19(10):987–92.
16. Alasmari AA, Alhussain MH, Al-Khalifah AS, Alshiban NM, Alharthi R, Alyami NM, et al. Ramadan fasting model modulates biomarkers of longevity and metabolism in male obese and non-obese rats. Sci Rep. 2024;14(1):28731. https://doi.org/10.1038/s41598-024-79557-y
17. Mohajeri FA, Ahmadi Z, Hassanshahi G, Akrami Mohajeri E, Ravari A, Ghalebi SR. Dose Ramadan Fasting Affects Inflammatory Responses: Evidences for Modulatory Roles of This Unique Nutritional Status via Chemokine Network. Iran J Basic Med Sci. 2013;16(12):1217–22.
18. Al Zunaidy NA, Al-Khalifa AS, Alhussain MH, Althwab SA, Mohammed MA, Faris ME. The effect of Ramadan intermittent fasting on anthropometric, hormonal, metabolic, inflammatory, and oxidative stress markers in pre-and post-menopausal women: a prospective cohort of Saudi women. Front Nutr. 2024;11:1437169. https://doi.org/10.3389/fnut.2024.1437169
19. Tang D, Tang Q, Huang W, Zhang Y, Tian Y, Fu X. Fasting: From Physiology to Pathology. Advanced Science. 2023 Mar;10(9):2204487. https://doi.org/10.1002/advs.202204487
20. Faris MAIE, Jahrami HA, Obaideen AA, Madkour MI. Impact of diurnal intermittent fasting during Ramadan on inflammatory and oxidative stress markers in healthy people: Systematic review and meta-analysis. Journal of Nutrition & Intermediary Metabolism. 2019;15:18–26. https://doi.org/10.1016/j.jnim.2018.11.005
21. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71
22. Stevens GA, Singh GM, Lu Y, Danaei G, Lin JK, Finucane MM, et al. National, regional, and global trends in adult overweight and obesity prevalences. Popul Health Metrics. 2012;10(1):22. https://doi.org/10.1186/1478-7954-10-22
23. Gunaydin C, Bilge SS. Effects of Nonsteroidal Anti-Inflammatory Drugs at the Molecular Level. Eurasian J Med. 2018;50(2):116–21. https://doi.org/10.5152/eurasianjmed.2018.0010
24. Więdłocha M, Marcinowicz P, Krupa R, Janoska-Jaździk M, Janus M, Dębowska W, et al. Effect of antidepressant treatment on peripheral inflammation markers – A meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018;80:217–26. https://doi.org/10.1016/j.pnpbp.2017.04.026
25. Liu JJ, Wei YB, Strawbridge R, Bao Y, Chang S, Shi L, et al. Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis. Mol Psychiatry. 2020;25(2):339–50. https://doi.org/10.1038/s41380-019-0474-5
26. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5. https://doi.org/10.1007/s10654-010-9491-z
27. Sedgwick P, Marston L. How to read a funnel plot in a meta-analysis. BMJ. 2015;351:h4718. https://doi.org/10.1136/bmj.h4718
28. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. https://doi.org/10.1136/bmj.315.7109.629
29. Begg CB, Mazumdar M. Operating Characteristics of a Rank Correlation Test for Publication Bias. Biometrics. 1994;50(4):1088. https://doi.org/10.2307/2533446
30. Ajabnoor GM, Bahijri S, Borai A, Abdulkhaliq AA, Al-Aama JY, Chrousos GP. Health Impact of Fasting in Saudi Arabia during Ramadan: Association with Disturbed Circadian Rhythm and Metabolic and Sleeping Patterns. Dileepan KN, editor. PLoS ONE. 2014;9(5):e96500. https://doi.org/10.1371/journal.pone.0096500
31. Askari VR, Alavinezhad A, Boskabady MH. The impact of “Ramadan fasting period” on total and differential white blood cells, haematological indices, inflammatory biomarker, respiratory symptoms and pulmonary function tests of healthy and asthmatic patients. Allergologia et Immunopathologia. 2016;44(4):359–67. https://doi.org/10.1016/j.aller.2015.10.002
32. Mohammadzade F, Vakili MA, Seyediniaki A, Amirkhanloo S, Farajolahi M, Akbari H, et al. Effect of Prolonged Intermittent Fasting in Ramadan on Biochemical and Inflammatory Parameters of Healthy Men. jcbr. 2017;1(1):38–46. https://doi.org/10.18869/acadpub.jcbr.1.1.38
33. Faris “Mo’ez Al-Islam” E., Kacimi S, Al-Kurd RA, Fararjeh MA, Bustanji YK, Mohammad MK, et al. Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects. Nutrition Research. 2012;32(12):947–55. https://doi.org/10.1016/j.nutres.2012.06.021
34. Faris “Mo’ez Al-Islam” E., Madkour MI, Obaideen AK, Dalah EZ, Hasan HA, Radwan H, et al. Effect of Ramadan diurnal fasting on visceral adiposity and serum adipokines in overweight and obese individuals. Diabetes Research and Clinical Practice. 2019;153:166–75. https://doi.org/10.1016/j.diabres.2019.05.023
35. Madkour MI, Malhab LJB, Abdel-Rahman WM, Abdelrahim DN, Saber-Ayad M, Faris ME. Ramadan Diurnal Intermittent Fasting Is Associated with Attenuated FTO Gene Expression in Subjects with Overweight and Obesity: A Prospective Cohort Study. Front Nutr. 2022;8:741811. https://doi.org/10.3389/fnut.2021.741811
36. Ghashang SK, Suwandi A, Buettner M, Hamdan I, Grassl GA, Gutenbrunner C, et al. Alterations in anthropometric, inflammatory and mental health parameters during Ramadan intermittent fasting in a group of healthy people: a prospective cohort study. Front Nutr. 2024;11:1298281. https://doi.org/10.3389/fnut.2024.1298281
37. Harder-Lauridsen NM, Rosenberg A, Benatti FB, Damm JA, Thomsen C, Mortensen EL, et al. Ramadan model of intermittent fasting for 28 d had no major effect on body composition, glucose metabolism, or cognitive functions in healthy lean men. Nutrition. 2017;37:92–103. https://doi.org/10.1016/j.nut.2016.12.015
38. Lahdimawan A, Handono K, Indra MR, Prawiro SR. Effect of Ramadan Fasting On Classically Activated, Oxidative Stress and Inflammation of Macrophage. iosrphr. 2013;3(4):14–22. https://doi.org/10.9790/3013-034101422
39. Zekri NM, Martati E, Handayani D. The effect of duration of ramadan fasting on food intake, lipid profiles, and pro-inflammatory cytokines (TNF-α and IL-6) in overweight male subjects in Malang, Indonesia. International Journal of ChemTech Research. 2016;9(07):396–403.
40. Mushtaq R, Akram A, Mushtaq R, Khwaja S, Ahmed S. The role of inflammatory markers following Ramadan Fasting. Pak J Med Sci. 2019;35(1):77–81. https://doi.org/10.12669/pjms.35.1.95
41. Ünalacak M, Kara İH, Baltaci D, Erdem Ö, Bucaktepe PGE. Effects of Ramadan Fasting on Biochemical and Hematological Parameters and Cytokines in Healthy and Obese Individuals. Metabolic Syndrome and Related Disorders. 2011;9(2):157–61. https://doi.org/10.1089/met.2010.0084
42. Zouhal H, Bagheri R, Ashtary-Larky D, Wong A, Triki R, Hackney AC, et al. Effects of Ramadan intermittent fasting on inflammatory and biochemical biomarkers in males with obesity. Physiology & Behavior. 2020;225:113090. https://doi.org/10.1016/j.physbeh.2020.113090
43. Ridho FM, Syachputra AJ, Nur’aini AD, Ulfah K, Faqih M, Nurhuda A. Pre-clinical and clinical efficacy of curcumin as an anti-inflammatory agent for periodontitis. A systematic review. Revista Científica Odontológica. 2024;12(4):e222. https://doi.org/10.21142/2523-2754-1204-2024-222
44. Wang T, He C. Pro-inflammatory cytokines: The link between obesity and osteoarthritis. Cytokine & Growth Factor Reviews. 2018;44:38–50. https://doi.org/10.1016/j.cytogfr.2018.10.002
45. Monserrat-Mesquida M, Quetglas-Llabrés M, Capó X, Bouzas C, Mateos D, Pons A, et al. Metabolic Syndrome Is Associated with Oxidative Stress and Proinflammatory State. Antioxidants. 2020;9(3):236. https://doi.org/10.3390/antiox9030236
46. Bou Malhab LJ, Madkour MI, Abdelrahim DN, Eldohaji L, Saber-Ayad M, Eid N, et al. Dawn-to-dusk intermittent fasting is associated with overexpression of autophagy genes: A prospective study on overweight and obese cohort. Clinical Nutrition ESPEN. 2025;65:209–17. https://doi.org/10.1016/j.clnesp.2024.11.002
47. Dastghaib S, Siri M, RahmaniKukia N, Heydari ST, Pasalar M, Zamani M, et al. Effect of 30-day Ramadan fasting on autophagy pathway and metabolic health outcome in healthy individuals. Mol Biol Res Commun. 2025;14(2):115–27. https://doi.org/10.22099/mbrc.2024.50105.1978
48. Prasetya G, Sapwarobol S. Intermittent Fasting During Ramadan Improves Insulin Sensitivity and Anthropometric Parameters in Healthy Young Muslim Men. American Journal of Lifestyle Medicine. 2021;15(2):200–6. https://doi.org/10.1177/1559827618815430
49. Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiological Reviews. 2018;98(4):2133–223. https://doi.org/10.1152/physrev.00063.2017
50. Diep Nguyen T. Adiponectin: Role in physiology and pathophysiology. Int J Prev Med. 2020;11(1):136. https://doi.org/10.4103/ijpvm.IJPVM_193_20
51. Chandrasekar B, Boylston WH, Venkatachalam K, Webster NJG, Prabhu SD, Valente AJ. Adiponectin Blocks Interleukin-18-mediated Endothelial Cell Death via APPL1-dependent AMP-activated Protein Kinase (AMPK) Activation and IKK/NF-κB/PTEN Suppression. Journal of Biological Chemistry. 2008;283(36):24889–98. https://doi.org/10.1074/jbc.M804236200
52. Choi HM, Doss HM, Kim KS. Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases. IJMS. 2020;21(4):1219. https://doi.org/10.3390/ijms21041219
53. Febriza A, Ridwan R, As’ad S, Kasim VN, Idrus HH. Adiponectin and Its Role in Inflammatory Process of Obesity. Mol Cell Biomed Sci. 2019;3(2):60. https://doi.org/10.21705/mcbs.v3i2.
Downloads
Published
How to Cite
Issue
Section
Citation Check
License
Copyright (c) 2025 Fiki Muhammad Ridho, Ridwan Alfatah
This work is licensed under a Creative Commons Attribution 4.0 International License.
