Efficacy of the ketogenic diet on mental health and glycemic metrics in oncological care: A systematic review with meta-analysis
Abstract
Background: Cancer and its conventional treatments pose not only a physiological burden but also cause significant psychological distress, including anxiety, depression, and diminished quality of life. The ketogenic diet (KD), a high-fat, very-low-carbohydrate nutritional regimen, has garnered interest in oncology due to its potential to influence tumor metabolism by inducing ketosis and lowering blood glucose. Methods: A comprehensive literature search was conducted across multiple electronic databases (PubMed, MEDLINE, Embase, Cochrane CENTRAL, Web of Science, EBSCO, PsycINFO) from inception until 1 September 2025, following PRISMA guidelines. Randomized controlled trials and non-randomized interventional studies involving adult cancer patients (any type or stage) were included. The intervention was any KD protocol designed to induce nutritional ketosis. Primary outcomes were psychological metrics measured by validated scales and fasting blood glucose. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers. Data were pooled using a random-effects model. Results: Eight studies involving 376 patients with various cancers (e.g., ovarian, endometrial, breast, glioblastoma) were included. The meta-analysis revealed a significant reduction in anxiety scores (HADS-A) favouring the KD group (Mean Difference [MD] = −11.13, 95% CI: −13.88 to −8.38, p < 0.00001). For depression, results were mixed; a significant effect was found on the HADS-D (MD = −11.17, 95% CI: −21.18 to −1.15, p = 0.03) but with high heterogeneity (I2 = 84%), while no significant effect was observed on the PHQ-9 (MD = −10.32, 95% CI: −25.45 to 4.81, p = 0.18). Quality of life showed a non-significant trend towards improvement (MD = −13.52, 95% CI: −32.70 to 5.67, p = 0.17). Metabolically, the KD consistently and significantly reduced fasting blood glucose (MD = −8.73 mg/dL, 95% CI: −12.57 to −4.89, p < 0.00001, I2 = 0%). Conclusion: The ketogenic diet demonstrates a consistent and significant effect on improving metabolic parameters by lowering blood glucose in cancer patients. Its impact on psychological well-being is more specific, showing a robust and significant benefit for alleviating anxiety, inconsistent effects on depression, and a promising, though non-significant, trend for improved quality of life. Registration number: CRD420251160658.
Copyright (c) 2026 Yao Chen, Yongting Pan, Qian Zhao, Minxiao Gu
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
1. Tsenkova M, Brauer M, Pozdeev VI, et al. Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate. Nature Communications. 2025; 16(1). doi: 10.1038/s41467-025-56678-0
2. Wan S, Zhou X, Xie F, et al. Ketogenic diet and cancer: multidimensional exploration and research. Science China Life Sciences. 2025; 68(4): 1010–1024. doi: 10.1007/s11427-023-2637-2
3. Muscogiuri G, Barrea L, Bettini S, et al. European Association for the Study of Obesity (EASO) position statement on medical nutrition therapy for the management of individuals with overweight or obesity and cancer. Obesity Facts. 2025; 18(1): 86–105. doi: 10.1159/000542155
4. Mensah EO, Danyo EK, Asase RV. Exploring the effect of different diet types on ageing and age-related diseases. Nutrition. 2025; 129: 112596. doi: 10.1016/j.nut.2024.112596
5. Zhang M, Zhang Q, Huang S, et al. Impact of ketogenic diets on cancer patient outcomes: a systematic review and meta-analysis. Frontiers in Nutrition. 2025; 12. doi: 10.3389/fnut.2025.1535921
6. Deng Q, Lv R, Zou T. The effects of the ketogenic diet on cancer treatment: a narrative review. European Journal of Cancer Prevention. 2024; 34(4): 291–300. doi: 10.1097/cej.0000000000000918
7. Roichman A, Zuo Q, Hwang S, et al. Microbiome metabolism of dietary phytochemicals controls the anticancer activity of PI3K inhibitors. Cell. 2025; 188(11): 3065–3080.e21. doi: 10.1016/j.cell.2025.04.041
8. Peng H, Fu M, Li J. New perspectives: the impact of ketogenic diet on the immune system. Signal Transduction and Targeted Therapy. 2025; 10(1). doi: 10.1038/s41392-025-02188-w
9. Luo C, Dai Z, He W, et al. Ketogenic diet and β-hydroxybutyrate in osteoporosis: current progress and controversy. Frontiers in Nutrition. 2025; 12. doi: 10.3389/fnut.2025.1508695
10. Fleigle D, Brumitt J, McCarthy E, et al. Polycystic Ovary Syndrome and the Effects of a Ketogenic Diet: A Scoping Review. Nutrients. 2025; 17(17): 2893. doi: 10.3390/nu17172893
11. Gautam R, Maan P, Jyoti A, et al. The Role of Lifestyle Interventions in PCOS Management: A Systematic Review. Nutrients. 2025; 17(2): 310. doi: 10.3390/nu17020310
12. Luong T, Svart M, Gormsen LC, et al. Ketogenic diet in the management of disease. Current Opinion in Clinical Nutrition & Metabolic Care. 2025; 28(6): 477–482. doi: 10.1097/mco.0000000000001158
13. Vranjić P, Vuković M, Blažetić S, et al. Ketogenic Diet and Thyroid Function: A Delicate Metabolic Balancing Act. Current Issues in Molecular Biology. 2025; 47(9): 696. doi: 10.3390/cimb47090696
14. Onyeaka HK, Zambrano J, Longley RM, et al. Use of digital health tools for health promotion in cancer survivors. Psycho-Oncology. 2021; 30(8): 1302–1310. doi: 10.1002/pon.5677
15. Cohen C, Fontaine K, Arend R, et al. Favorable Effects of a Ketogenic Diet on Physical Function, Perceived Energy, and Food Cravings in Women with Ovarian or Endometrial Cancer: A Randomized, Controlled Trial. Nutrients. 2018; 10(9): 1187. doi: 10.3390/nu10091187
16. Cohen CW, Fontaine KR, Arend RC, Gower BA. A Ketogenic Diet Is Acceptable in Women with Ovarian and Endometrial Cancer and Has No Adverse Effects on Blood Lipids: A Randomized, Controlled Trial. Nutrition and Cancer-an International Journal. 2020; 72(4): 584–594. doi: 10.1080/01635581.2019.1645864
17. Khodabakhshi A, Akbari ME, Mirzaei HR, et al. Effects of Ketogenic metabolic therapy on patients with breast cancer: A randomized controlled clinical trial. Clinical Nutrition. 2021; 40(3): 751–758. doi: 10.1016/j.clnu.2020.06.028
18. Alfano CM, Day JM, Katz ML, et al. Exercise and dietary change after diagnosis and cancer‐related symptoms in long‐term survivors of breast cancer: CALGB 79804. Psycho-Oncology. 2008; 18(2): 128–133. doi: 10.1002/pon.1378
19. Augustus E, Granderson I, Rocke KD. The Impact of a Ketogenic Dietary Intervention on the Quality of Life of Stage II and III Cancer Patients: A Randomized Controlled Trial in the Caribbean. Nutrition and Cancer. 2020; 73(9): 1590–1600. doi: 10.1080/01635581.2020.1803930
20. Khodabakhshi A, Akbari ME, Mirzaei HR, et al. Effects of Ketogenic metabolic therapy on patients with breast cancer: A randomized controlled clinical trial. Clinical Nutrition. 2021; 40(3): 751–758. doi: 10.1016/j.clnu.2020.06.028
21. Voss M, Wenger KJ, von Mettenheim N, et al. Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial. European Journal of Nutrition. 2021; 61(1): 477–487. doi: 10.1007/s00394-021-02666-1
22. Rogava M, Aprati TJ, Chi WY, et al. Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation. Nature Cancer. 2024; 5(3): 433–447. doi: 10.1038/s43018-023-00704-x
23. Yang H, Zingaro VA, Lincoff J, et al. Remodelling of the translatome controls diet and its impact on tumorigenesis. Nature. 2024; 633(8028): 189–197. doi: 10.1038/s41586-024-07781-7
24. Murphy S, Rahmy S, Gan D, et al. Ketogenic Diet Alters the Epigenetic and Immune Landscape of Prostate Cancer to Overcome Resistance to Immune Checkpoint Blockade Therapy. Cancer Research. 2024; 84(10): 1597–1612. doi: 10.1158/0008-5472.can-23-2742
25. Richard J, Beauvillain C, Benoit M, et al. Ketogenic diet enhances the anti-cancer effects of PD-L1 blockade in renal cell carcinoma. Frontiers in Endocrinology. 2024; 15. doi: 10.3389/fendo.2024.1344891
26. Xiao YL, Gong Y, Qi YJ, et al. Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential. Signal Transduct Target Ther. 2024; 9(1): 59. doi: 10.1038/s41392-024-01771-x
27. Wei SJ, Schell JR, Chocron ES, et al. Ketogenic diet induces p53-dependent cellular senescence in multiple organs. Science Advances. 2024; 10(20). doi: 10.1126/sciadv.ado1463
28. Duraj T, Kalamian M, Zuccoli G, et al. Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma. BMC Medicine. 2024; 22(1). doi: 10.1186/s12916-024-03775-4
29. Dahlin M, Wheelock CE, Prast-Nielsen S. Association between seizure reduction during ketogenic diet treatment of epilepsy and changes in circulatory metabolites and gut microbiota composition. Ebio Medicine. 2024; 109: 105400. doi: 10.1016/j.ebiom.2024.105400
30. Sharifi M, Saber A, Moludi J, et al. The effects of portfolio moderate-carbohydrate and ketogenic diets on anthropometric indices, metabolic status, and hormonal levels in overweight or obese women with polycystic ovary syndrome: a randomized controlled trial. Nutrition Journal. 2024; 23(1). doi: 10.1186/s12937-024-01056-7
31. Giuliani G, Longo VD. Ketone bodies in cell physiology and cancer. American Journal of Physiology-Cell Physiology. 2024; 326(3): C948–C963. doi: 10.1152/ajpcell.00441.2023
32. Weathers B, Barg FK, Collier A, et al. Perceptions of changes in weight among African American breast cancer survivors. Psycho-Oncology. 2005; 15(2): 174–179. doi: 10.1002/pon.939
33. Calcaterra V, Magenes VC, Massini G, et al. High Fat Diet and Polycystic Ovary Syndrome (PCOS) in Adolescence: An Overview of Nutritional Strategies. Nutrients. 2024; 16(7): 938. doi: 10.3390/nu16070938
34. Mishra A, Giuliani G, Longo VD. Nutrition and dietary restrictions in cancer prevention. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2024; 1879(1): 189063. doi: 10.1016/j.bbcan.2023.189063
