Combined Effects of Exercise and Cinnamon Supplementation on Liver Fibrosis and Oxidative Stress in Women with Type 2 Diabetes Mellitus: A Double-Blind, Randomized Clinical Trial

Subject Areas : Exercise Physiology and Performance

Mahdieh Ghasemi ¹ , Ahmad Abdi ^{2 *} , Alireza Barari ³ , khosro jalali ⁴

1 - Department of Physical Education and Sport Science, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
2 - Department of Physical Education and Sport Science, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
3 - Department of Physical Education and Sport Science, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
4 - Assistant Professor,Department of Sport Physiology, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran

Received: 2025-02-26 Accepted : 2025-05-05 Published : 2025-05-15

Keywords: Diabetes Mellitus, Exercise, Cinnamon, Liver Fibrosis,

Abstract :

Background: This double-blind, randomized clinical trial aimed to assess the effects of concurrent exercise and cinnamon supplementation on liver fibrosis (FIB-4 index) and oxidative stress in women with type 2 diabetes mellitus (T2DM).

Methods: Thirty women, aged 35-50 years, diagnosed with T2DM, were randomly assigned to one of four intervention groups: 1) Control (C), 2) Moderate-intensity aerobic exercise + resistance exercise (RME), 3) Cinnamon supplementation (Ci), and 4) Moderate-intensity aerobic exercise + resistance exercise + cinnamon supplementation (RMECi). Participants in the exercise groups performed a combined aerobic and resistance training program five times a week, targeting 400 kcal expenditure per day, while the supplementation groups consumed 1000 mg of cinnamon per day. Fasting blood samples were collected before and after the 8-week intervention to evaluate liver enzymes, FIB-4 index, and markers of oxidative stress (MDA, SOD, GPx, CAT). Statistical analyses, including paired t-tests and ANCOVA, were performed to determine the effects within and between groups.

Results: Results indicated significant reductions in FIB-4, MDA, ALT, and AST in the RME, Ci, and RMECi groups compared to the control group, with the RMECi group showing the most significant improvements. Additionally, antioxidant capacity, as indicated by SOD, GPx, and CAT levels, was enhanced in the intervention groups.

Conclusion: These findings suggest that the combination of exercise and cinnamon supplementation may have synergistic effects on improving liver function and reducing oxidative stress in women with T2DM.

References:


1. Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7(9):851-61. doi:10.1016/S2468-1253(22)00145-4.
2. Davidson KW, Barry MJ, Mangione CM, Cabana M, Caughey AB, Davis EM, et al. Screening for prediabetes and type 2 diabetes: US Preventive Services Task Force recommendation statement. JAMA. 2021;326(8):736-43. doi:10.1001/jama.2021.13606.
3. Sugimoto R, Enjoji M, Kohjima M, Tsuruta S, Fukushima M, Iwao M, et al. High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen‐activated protein kinase. Liver Int. 2005;25(5):1018-26. doi:10.1111/j.1478-3231.2005.01016.x.
4. Bedossa P, Dargère D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003;38(6):1449-57. doi:10.1053/jhep.2003.50471.
5. Abeysekera KW, Valenti L, Younossi Z, Dillon JF, Allen AM, Noureddin M, et al. Implementation of a liver health check in people with type 2 diabetes. Lancet Gastroenterol Hepatol. 2024;9(1):83-91. doi:10.1016/S2468-1253(23)00301-2.
6. Wei Y, Chen P, de Bruyn M, Zhang W, Bremer E, Helfrich W. Carbon monoxide-releasing molecule-2 (CORM-2) attenuates acute hepatic ischemia reperfusion injury in rats. BMC Gastroenterol. 2010;10(1):42. doi:10.1186/1471-230X-10-42.
7. Luangmonkong T, Suriguga S, Mutsaers HA, Groothuis GM, Olinga P, Boersema M. Targeting oxidative stress for the treatment of liver fibrosis. Rev Physiol Biochem Pharmacol. 2018;175:71-102. doi:10.1007/112_2017_28.
8. Ambelu T, Teferi G. The impact of exercise modalities on blood glucose, blood pressure and body composition in patients with type 2 diabetes mellitus. BMC Sports Sci Med Rehabil. 2023;15(1):153. doi:10.1186/s13102-023-00377-9.
9. Syeda UA, Battillo D, Visaria A, Malin SK. The importance of exercise for glycemic control in type 2 diabetes. Am J Med Open. 2023;9:100031. doi:10.1016/j.ajmopen.2023.100031.
10. Merz KE, Thurmond DC. Role of skeletal muscle in insulin resistance and glucose uptake. Compr Physiol. 2011;10(3):785-809. doi:10.1002/cphy.c100072.
11. Coffey VG, Hawley JA. Concurrent exercise training: do opposites distract? J Physiol. 2017;595(9):2883-96. doi:10.1113/JP272731.
12. Zaki S, Sharma S, Vats H. Effectiveness of concurrent exercise training in people with type 2 diabetes: A systematic review and meta-analysis. Physiother Theory Pract. 2024;40(9):2094-115. doi:10.1080/09593985.2023.2251514.
13. Voudouris D, Horianopoulou M, Apostolopoulou Z, Chryssanthopoulos C, Bardopoulou M, Maridaki M, et al. The effects of a short-term combined exercise program on liver steatosis indices and the lipidemic and glycemic profile in NAFLD individuals: A pilot study. Metabolites. 2023;13(10):1074. doi:10.3390/metabo13101074.
14. Ghanbari P, Khajehzadeh S, Sayyed A, Raeisi D, Salehi O. The effect of high intensity interval training with beetroot (Beta vulgaris) juice supplementation on serotonin and dopamine receptors expression, anxiety and depression in middle-aged diabetic rats. Avicenna J Phytomed. 2022;12(6):627.
15. Matacchione G, Gurău F, Baldoni S, Prattichizzo F, Silvestrini A, Giuliani A, et al. Pleiotropic effects of polyphenols on glucose and lipid metabolism: Focus on clinical trials. Ageing Res Rev. 2020;61:101074. doi:10.1016/j.arr.2020.101074.
16. Jamali N, Kazemi A, Saffari-Chaleshtori J, Samare-Najaf M, Mohammadi V, Clark CC. The effect of cinnamon supplementation on lipid profiles in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials. Complement Ther Med. 2020;55:102571. doi:10.1016/j.ctim.2020.102571.
17. Ali MA, Mahmoud SA, Alkhedaide A, Soliman MM, Al-Shafie TA, El-Sayed YS, et al. Boosting effects of Cranberry and Cinnamaldehyde for pioglitazone amelioration of liver steatosis in rat via suppression of HIF-1α/Smad/β-catenin signaling. J Funct Foods. 2022;90:104973. doi:10.1016/j.jff.2022.104973.
18. Azimi P, Ghiasvand R, Feizi A, Hariri M, Abbasi B. Effects of cinnamon, cardamom, saffron, and ginger consumption on markers of glycemic control, lipid profile, oxidative stress, and inflammation in type 2 diabetes patients. Rev Diabetic Stud. 2015;11(3):258. doi:10.1900/RDS.2015.11.258.
19. Hageman PA, Walker SN, Pullen CH, Pellerito P. Test-retest reliability of the Rockport Fitness Walking Test and other fitness measures in women ages 50–69 years. J Geriatr Phys Ther. 2001;24(2):7-11. doi:10.1519/00139143-200124020-00002.
20. American College of Sports Medicine. ACSM's guidelines for exercise testing and prescription. Lippincott Williams & Wilkins; 2013.
21. Zare R, Shams M, Heydari M, Najarzadeh A, Zarshenas M. Analysis of the efficacy of cinnamon for patients with diabetes mellitus type II based on traditional Persian medicine syndrome differentiation: A randomized controlled trial. Shiraz E Med J. 2020;21(7). doi:10.5812/semj.105214.
22. Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7(10):1104-12. doi:10.1016/j.cgh.2009.04.013.
23. Naeiji I, Abdi A. Evaluation of Liver Fibrosis-4 (FIB-4) index and oxidative stress following aerobic training and *Momordica Charantia* L. in men with type 2 diabetes. Res Med. 2022;46(1):24-32.
24. Askari R, Rabani N, Marefati H, Azarnive MS, Pusceddu M, Migliaccio GM. Aerobic-resistance training with royal jelly supplementation has a synergistic effect on paraoxonase 1 changes and liver function in women with MASLD. Medicina. 2025;61(2):349. doi:10.3390/medicina61020349.
25. Abassi W, Ouerghi N, Hammami MB, Jebabli N, Feki M, Bouassida A, et al. High-intensity interval training reduces liver enzyme levels and improves MASLD-related biomarkers in overweight/obese girls. Nutrients. 2025;17(1):164. doi:10.3390/nu17010164.
26. Houghton D, Thoma C, Hallsworth K, Cassidy S, Hardy T, Burt AD, et al. Exercise reduces liver lipids and visceral adiposity in patients with nonalcoholic steatohepatitis in a randomized controlled trial. Clin Gastroenterol Hepatol. 2017;15(1):96-102.e3. doi:10.1016/j.cgh.2016.06.023.
27. Barani F, Afzalpour ME, Ilbiegi S, Kazemi T, Mohammadi Fard M. The effect of resistance and combined exercise on serum levels of liver enzymes and fitness indicators in women with nonalcoholic fatty liver disease. J Sci Res Med Sci. 2014;21(2):188-202.
28. Kim K-S, Lee B-W, Kim YJ, Lee DH, Cha B-S, Park C-Y. Nonalcoholic fatty liver disease and diabetes: part II: treatment. Diabetes Metab J. 2019;43(2):127-43. doi:10.4093/dmj.2019.0004.
29. Ebrahimi-Mamghani M, Arefhosseini S. Comparison of low-calorie diet with and without sibutramine on body weight and liver function of patients with non-alcoholic fatty liver disease. Armaghane Danesh. 2011;16(2):101-10.
30. Nikroo H, Nematy M, Sima H, ATTARZADE HS. The effect of restricted diet with or without aerobic training program on cardio respiratory fitness and anthropometric indices in patients with non-alcoholic steatohepatitis. 2011.
31. Fukai T, Siegfried MR, Ushio-Fukai M, Cheng Y, Kojda G, Harrison DG. Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. J Clin Invest. 2000;105(11):1631-9. doi:10.1172/JCI8761.
32. Touron J, Costes F, Coudeyre E, Perrault H, Richard R. Aerobic metabolic adaptations in endurance eccentric exercise and training: from whole body to mitochondria. Front Physiol. 2021;11:596351. doi:10.3389/fphys.2020.596351.
33. Porter C, Reidy PT, Bhattarai N, Sidossis LS, Rasmussen BB. Resistance exercise training alters mitochondrial function in human skeletal muscle. Med Sci Sports Exerc. 2015;47(9):1922. doi:10.1249/MSS.0000000000000627.
34. Sarmadi B, Musazadeh V, Dehghan P, Karimi E. The effect of cinnamon consumption on lipid profile, oxidative stress, and inflammation biomarkers in adults: An umbrella meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis. 2023;33(10):1821-35. doi:10.1016/j.numecd.2023.06.009.
35. Mirmiranpour H, Huseini HF, Derakhshanian H, Khodaii Z, Tavakoli-Far B. Effects of probiotic, cinnamon, and synbiotic supplementation on glycemic control and antioxidant status in people with type 2 diabetes: a randomized, double-blind, placebo-controlled study. J Diabetes Metab Disord. 2020;19:53-60. doi:10.1007/s40200-020-00511-6.
36. Zhou Q, Lei X, Fu S, Li Z, Chen Y, Long C, et al. Efficacy of cinnamon supplementation on glycolipid metabolism in T2DM diabetes: A meta-analysis and systematic review. Front Physiol. 2022;13:960580. doi:10.3389/fphys.2022.960580.
37. Fernandez T, Vinuela M, Vidal C, Barrera F. Lifestyle changes in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. PLoS One. 2022;17(2):e0263931. doi:10.1371/journal.pone.0263931.
38. Ghalandari K, Shabani M, Khajehlandi A, Mohammadi A. Effect of aerobic training with silymarin consumption on glycemic indices and liver enzymes in men with type 2 diabetes. Arch Physiol Biochem. 2020:1-6. doi:10.1080/13813455.2020.1822044.