Intermittent Fasting and Its Health Implications: A Systematic Review of Existing Research
DOI:
https://doi.org/10.12775/QS.2025.40.59420Keywords
Intermittent fasting, Time-restricted eating, Alternate day fasting, Metabolic effect, Cardiometabolic health, hormonal chanegesAbstract
Intermittent fasting (IF) strategy, including time-restricted eating (TRE), alternate day fasting (ADF), and other variations, is a dietary approach that alternates between periods of eating and fasting. This review investigates the influence of IF on human health, focusing on metabolic effects, cardiometabolic health, neurocognitive functions, and hormonal changes. IF is believed to help in weight reduction, improve insulin sensitivity, and reduce the risk of type II diabetes mellitus. It may also have positive impact on cardiovascular health by reducing blood pressure and improving lipid profiles. Moreover, IF is believed to have
neuroprotective effects, improve cognitive functions and slow the progression of
neurodegenerative diseases. Hormonal changes during IF are very complex and require careful management in conditions like hypothyroidism and Cushing's syndrome. Despite promising results, more research is needed to fully explore the potential negative outcomes and safety of IF. Choice of exact dietary protocol should be individualized and supervised by a healthcare provider.
References
[1] R. E. Patterson and D. D. Sears, “Metabolic Effects of Intermittent Fasting,” On: Wed, vol. 08, p. 16, 2025, doi: 10.1146/annurev-nutr-071816.
[2] K. Nowosad and M. Sujka, “Effect of Various Types of Intermittent Fasting (IF) on Weight Loss and Improvement of Diabetic Parameters in Human,” DIABETES AND OBESITY, doi: 10.1007/s13668-021-00353-5/Published.
[3] E. Naous, A. Achkar, and J. Mitri, “Intermittent Fasting and Its Effects on Weight, Glycemia, Lipids, and Blood Pressure: A Narrative Review,” Aug. 01, 2023, Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/nu15163661.
[4] B. L. Reddy, V. S. Reddy, and M. H. Saier, “Health Benefits of Intermittent Fasting,” Jul. 02, 2024. doi: 10.1159/000540068.
[5] A. Elias, N. Padinjakara, and N. T. Lautenschlager, “Effects of intermittent fasting on cognitive health and Alzheimer’s disease,” Sep. 01, 2023, Oxford University Press. doi: 10.1093/nutrit/nuad021.
[6] J. Gudden, A. Arias Vasquez, and M. Bloemendaal, “The effects of intermittent fasting on brain and cognitive function,” Sep. 01, 2021, MDPI. doi: 10.3390/nu13093166.
[7] A. Brocchi, E. Rebelos, A. Dardano, M. Mantuano, and G. Daniele, “Effects of Intermittent Fasting on Brain Metabolism,” Mar. 01, 2022, MDPI. doi: 10.3390/nu14061275.
[8] S. Cienfuegos et al., “Effect of Intermittent Fasting on Reproductive Hormone Levels in Females and Males: A Review of Human Trials,” Jun. 01, 2022, MDPI. doi: 10.3390/nu14112343.
[9] B. H. Kim, Y. Joo, M. S. Kim, H. K. Choe, Q. Tong, and O. Kwon, “Effects of intermittent fasting on the circulating levels and circadian rhythms of hormones,” Aug. 01, 2021, Korean Endocrine Society. doi: 10.3803/ENM.2021.405.
[10] K. A. Varady, S. Cienfuegos, M. Ezpeleta, and K. Gabel, :“35 Annual Review of Nutrition Downloaded from www.annualreviews.org. Guest (guest) IP: 195.225.68.157 On: Wed,” vol. 10, no. 10, p. 35, 2025, doi: 10.1146/annurev-nutr-052020
[11] C. A. Rynders, E. A. Thomas, A. Zaman, Z. Pan, V. A. Catenacci, and E. L. Melanson, “Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss”, doi: 10.3390/nu11102442.
[12] V. Pavlou et al., “Effect of Time-Restricted Eating on Weight Loss in Adults With Type 2 Diabetes A Randomized Clinical Trial + Visual Abstract + Supplemental content,” 2023, doi: 10.1001/jamanetworkopen.2023.39337.
[13] Corley BT, Carroll RW, Hall RM, Weatherall M, Parry-Strong A, Krebs JD. Intermittent fasting in type 2 diabetes mellitus and the risk of hypoglycaemia: a randomized controlled trial. Diabet Med 2018;35:588-94.
[14] Kalam F, Gabel K, Cienfuegos S, Wiseman E, Ezpeleta M, Steward M, et al. Alternate day fasting combined with a low- carbohydrate diet for weight loss, weight maintenance, and metabolic disease risk reduction. Obes Sci Pract. 2019;5(6):531–9. https://doi.org/10.1002/osp4.367
[15] Sundfor TM, Svendsen M, Tonstad S. Effect of intermittent versus continuous Energy restriction on weight loss, maintenance and cardiometabolic risk: a randomized 1-year trial. Nutr Metab Cardiovasc Dis. 2018; 28(7):698–706. https://doi.org/10.1016/j.numecd.2018.03.009
[16] Eshghinia S, Mohammadzadeh F. The effects of modified alternate-day fasting diet on weight loss and CAD risk factors in overweight and obese women. J Diabetes Metab Disord. 2013;12(1):4. https://doi.org/10.1186/2251-6581-12-4
[17] Varady KA, Bhutani S, Church EC, Klempel MC. Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults. Am J Clin Nutr. 2009;90(5):1138–43. https://doi.org/10.3945/ajcn.2009.28380
[18] Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab. 2018;27(6):1212–21.e3. https://doi.org/10.1016/j.cmet.2018.04.010
[19] Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G, et al. The effects of intermittent or continuous Energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes. 2011;35(5):714–27. https://doi.org/10.1038/ijo.2010.171
[20] Carter S, Clifton PM, Keogh JB. Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: a randomized noninferiority trial. JAMA Netw Open. 2018;1(3):e180756. https://doi.org/10.1001/jamanetworkopen.2018.0756
[21] Catenacci VA, Pan Z, OstendorfD, Brannon S, Gozansky WS, Mattson MP, et al. A randomized pilot study comparing zerocalorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity. 2016;24(9):1874–83. https://doi.org/10.1002/oby.21581
[22] Klempel MC, Kroeger CM, Varady KA. Alternate day fasting (ADF) with a high-fat diet produces similar weight loss and cardio- protection as ADF with a low-fat diet Metabolism. 2013;62(1):137–43. https://doi.org/10.1016/j.metabol.2012.07.002
[23] Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med. 2007;42(5):665–74. https://doi.org/10.1016/j.freeradbiomed.2006.12.005
[24] Horne BD, Muhlestein JB, May HT, Carlquist JF, Lappe DL, Bair TL, et al. Relation of routine, periodic fasting to risk of diabetes mellitus, and coronary artery disease in patients undergoing coronary angiography. Am J Cardiol. 2012;109(11):1558–62. https://doi.org/10.1016/j.amjcard.2012.01.379
[25] Horne BD, May HT, Anderson JL, Kfoury AG, Bailey BM, McClure BS, et al. Usefulness of routine periodic fasting to lower risk of coronary artery disease in patients undergoing coronary angiography. Am J Cardiol. 2008;102(7):814–9. https://doi.org/10.1016/j.amjcard.2008.05.021
[26] Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan MI. Chronic alternate-day fasting results in reduced diastolic compliance and diminished systolic reserve in rats. J Card Fail. 2010;16(10):843–53. https://doi.org/10.1016/j.cardfail.2010.05.007
[27] Varela A, Marina Prendes MG, Testoni G, Vazquez N, Astudilla C, Cerruti S, et al. Influence of fasting on the effects of ischemic preconditioning in the ischemic reperfused rat heart. Arch Physiol Bio-chem. 2002;110(3):189–96. https://doi.org/10.1076/apab.110.3.189.8291
[28] Sheikh A, Mawani M, Mahar SA. Impact of Ramadan fast ing on thyroid status and quality of life in patients with primary hypothyroidism: a prospective cohort study from Karachi, Pakistan. Endocr Pract 2018;24:882-8.
[29] Jakubowicz, D.; Barnea, M.; Wainstein, J.; Froy, O. Effects of caloric intake timing on insulin resistance and hyperandrogenism in lean women with polycystic ovary syndrome. Clin. Sci. 2013, 125, 423–432
[30] Kumar S, Kaur G. Intermittent fasting dietary restriction regimen negatively influences reproduction in young rats: a study of hypothalamo-hypophysial-gonadal axis. PLoS One 2013;8:e52416.
[31] Martin B, Pearson M, Kebejian L, Golden E, Keselman A, Bender M, et al. Sex-dependent metabolic, neuroendocrine, and cognitive responses to dietary energy restriction andexcess. Endocrinology 2007;148:4318-33.
[32] Hua L, Feng B, Huang L, Li J, Luo T, Jiang X, et al. Time-restricted feeding improves the reproductive function of female mice via liver fibroblast growth factor 21. Clin Transl Med 2020;10:e195.
[33] Li, C.; Xing, C.; Zhang, J.; Zhao, H.; Shi, W.; He, B. Eight-hour time-restricted feeding improves endocrine and metabolic profiles in women with anovulatory polycystic ovary syndrome. J. Transl. Med. 2021, 19, 148.
[34] Harvie, M.N.; Pegington, M.; Mattson, M.P.; Frystyk, J.; Dillon, B.; Evans, G.; Cuzick, J.; Jebb, S.A.; Martin, B.; Cutler, R.G.; et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: A randomized trial in young overweight women. Int. J. Obes. 2011, 35, 714–727.
[35] Duan, W.; Guo, Z.; Jiang, H.; Ware, M.; Mattson, M.P. Reversal of Behavioral and Metabolic Abnormalities, and Insulin Resistance Syndrome, by Dietary Restriction in Mice Deficient in Brain-Derived Neurotrophic Factor. Endocrinology 2003, 144, 2446 -2453. https://doi.org/10.1210/en.2002-0113
[36] Stranahan, A.M.; Lee, K.; Martin, B.; Maudsley, S.; Golden, E.; Cutler, R.G.; Mattson, M.P. Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice. Hippocampus 2009, 19, 951–961.
[37] Lee, J.; Duan, W.; Mattson, M.P. Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J. Neurochem. 2002, 82, 1367–1375. https://doi.org/10.1046/j.1471-4159.2002.01085.x
[38] Han, R.; Liu, Z.; Sun, N.; Liu, S.; Li, L.; Shen, Y.; Xiu, J.; Xu, Q. BDNF Alleviates Neuroinflammation in the Hippocampus of Type1 Diabetic Mice via Blocking the Aberrant HMGB1/RAGE/NF-κB Pathway. Aging Dis. 2019, 10, 611–625.
[39] Kempuraj, D.; Thangavel, R.; Natteru, P.A.; Selvakumar, G.P.; Saeed, D.; Zahoor, H.; Zaheer, S.; Iyer, S.S.; Zaheer, A. Neuroinflammation Induces Neurodegeneration. J. Neurol. Neurosurg. Spine 2016, 1, 1003.
[40] Yuen, A.W.; Sander, J. Rationale for using intermittent calorie restriction as a dietary treatment for drug resistant epilepsy. Epilepsy Behav. 2014, 33, 110–114. https://doi.org/10.1016/j.yebeh.2014.02.026
[41] Zhou, J.; Blundell, J.; Ogawa, S.; Kwon, C.H.; Zhang, W.; Sinton, C.; Powell, C.M.; Parada, L.F. Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice. J. Neurosci. 2009, 29, 1773–1783. https://doi.org/10.1523/JNEUROSCI.5685-08.2009
[42] Mammana, S.; Bramanti, P.; Mazzon, E.; Cavalli, E.; Basile, M.S.; Fagone, P.; Petralia, M.C.; McCubrey, J.A.; Nicoletti, F.; Mangano, K. Preclinical evaluation of the PI3K/Akt/mTOR pathway in animal models of multiple sclerosis. Oncotarget 2018, 9, 8263–8277. https://doi.org/10.18632/oncotarget.23862
[43] Dello Russo, C.; Lisi, L.; Feinstein, D.L.; Navarra, P. mTOR kinase, a key player in the regulation of glial functions: Relevance for the therapy of multiple sclerosis. Glia 2013, 61, 301–311. https://doi.org/10.1002/glia.22433
[44] Lan, A.-P.; Chen, J.; Zhao, Y.; Chai, Z.; Hu, Y. mTOR Signaling in Parkinson’s Disease. Neuromol. Med. 2017, 19, 1–10. https://doi.org/10.1007/s12017-016-8417-7
[45] Jiang, J.; Jiang, J.; Zuo, Y.; Gu, Z. Rapamycin protects the mitochondria against oxidative stress and apoptosis in a rat model of Parkinson’s disease. Int. J. Mol. Med. 2013, 31, 825–832. https://doi.org/10.3892/ijmm.2013.1280
[46] Arumugam, T.; Phillips, T.M.; Cheng, A.; Morrell, C.H.; Mattson, M.P.; Wan, R. Age and energy intake interact to modify cel stress pathways and stroke outcome. Ann. Neurol. 2010, 67, 41–52. https://doi.org/10.1002/ana.21798
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Copyright (c) 2025 Jagoda Kubicka, Martyna Grabowska, Karolina Grabowska, Aleksandra Wiśniewska, Jakub Dąbek, Wiktoria Kosucka, Dominik Balik, Joanna Lara, Anna Kwaśniewska, Karolina Kaszyńska
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