{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:24:44Z","timestamp":1790515484181,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Chronic diseases adversely affect quality of life (QOL). The ketogenic diet (KD) may improve the QOL. Objective: The aim of this systematic review was to summarize the available evidence of randomized controlled trials (RCTs) to establish the effect of KD on the QOL in adults with chronic diseases. Methods: Reporting followed PRISMA guidelines. We included randomized controlled trials (RCTs) conducted on adults with chronic disease including an intervention group that received KD and a control group, and where QOL was reported as outcome. We searched PubMed, APA PsycInfo, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and Clinicaltrials.gov, and the references of the included articles and previous relevant reviews, without language or time restrictions. We critically appraised included studies and narratively synthesized their findings. Results: Nine RCTs were included. The risk of bias was low, except of allocation concealment and blinding. In patients with cancer: one RCT found an improvement in overall QOL, another reported improved physical component summary, and one found no superiority of KD in all QOL domains. In patients with neurological disorders: improved QOL was reported in Alzheimer\u2019s disease patients, whereas no difference in mental and physical health QOL was noted in patients with multiple sclerosis. In patients with obesity and type II diabetes: one RCT reported superiority of energy-restricted KD in improving role functioning, mental health, health perceptions, and pain compared with guideline-based diet, whereas in another RCT, high and low carbohydrate diets achieved comparable improvements. Among patients with knee osteoarthritis, no differences between KD and low-fat groups were noted. Dietary compliance with the KD, reported in three studies, was shown to be high. Side effects were mostly noted during the first weeks of intervention, and adverse events were not markedly different with KD and the comparison diet. Conclusions: The evidence from RCTs investigating the effect of KD on QOL in adults with chronic disease is inconclusive. The promising effect noted in some included studies and the low rates of adverse events and side effects encourage future investigations in this regard.<\/jats:p>","DOI":"10.3390\/nu13124463","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T22:06:10Z","timestamp":1639519570000},"page":"4463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effect of Ketogenic Diet on Quality of Life in Adults with Chronic Disease: A Systematic Review of Randomized Controlled Trials"],"prefix":"10.3390","volume":"13","author":[{"given":"Myriam","family":"Abboud","sequence":"first","affiliation":[{"name":"Department of Health, College of Natural and Health Sciences, Zayed University, Dubai 19282, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1993-6656","authenticated-orcid":false,"given":"Fatme","family":"AlAnouti","sequence":"additional","affiliation":[{"name":"Department of Health, College of Natural and Health Sciences, Zayed University, Abu Dhabi 144534, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evridiki","family":"Georgaki","sequence":"additional","affiliation":[{"name":"Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4923-484X","authenticated-orcid":false,"given":"Dimitrios","family":"Papandreou","sequence":"additional","affiliation":[{"name":"Department of Health, College of Natural and Health Sciences, Zayed University, Abu Dhabi 144534, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Reynolds, R., Dennis, S., Hasan, I., Slewa, J., Chen, W., Tian, D., Bobba, S., and Zwar, N. (2018). A systematic review of chronic disease management interventions in primary care. BMC Fam. Pract., 19.","DOI":"10.1186\/s12875-017-0692-3"},{"key":"ref_2","unstructured":"Dawson, A., Saenz, C., Reis, A., and Bolan, G. (2016). Chronic Disease Prevention and Health Promotion. Public Health Ethics: Cases Spanning the Globe, Springer International Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/pmrj.12444","article-title":"Exergaming for Quality of Life in Persons Living with Chronic Diseases: A Systematic Review and Meta-analysis","volume":"13","author":"Cugusi","year":"2021","journal-title":"PM&R"},{"key":"ref_4","unstructured":"World Health Organization (2014). Global Status Report on Noncommunicable Diseases 2014, World Health Organization."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0891-4222(94)00028-8","article-title":"Quality of life: Its definition and measurement","volume":"16","author":"Felce","year":"1995","journal-title":"Res. Dev. Disabil."},{"key":"ref_6","unstructured":"World Health Organization (1998). Programme on Mental Health: WHOQOL User Manual, World Health Organization."},{"key":"ref_7","unstructured":"Fallowfield, L. (2021, October 06). What is Quality of Life. Available online: http:\/\/www.bandolier.org.uk\/painres\/download\/What%20is%202009\/What_is_QOL.pdf."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/0885-3924(94)90129-5","article-title":"Quality of life: Concepts and definition","volume":"9","author":"Cella","year":"1994","journal-title":"J. Pain Symptom Manag."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1177\/1742395307081504","article-title":"Multiple chronic diseases and quality of life: Patterns emerging from a large national sample, Australia","volume":"3","author":"Walker","year":"2007","journal-title":"Chronic Illn."},{"key":"ref_10","unstructured":"Murray, C.J., Lopez, A.D., and World Health Organization (1996). The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020: Summary, World Health Organization."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.1001\/jama.291.21.2616","article-title":"The global burden of chronic diseases: Overcoming impediments to prevention and control","volume":"291","author":"Yach","year":"2004","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s11065-004-8158-5","article-title":"Quality of life of caregivers","volume":"14","author":"Glozman","year":"2004","journal-title":"Neuropsychol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1177\/105477389500400404","article-title":"Well-being of caregivers of spouses with Parkinson\u2019s disease","volume":"4","author":"Berry","year":"1995","journal-title":"Clin. Nurs. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/mds.870130108","article-title":"Living with a person who has Parkinson\u2019s disease: The spouse\u2019s perspective by stage of disease. Parkinson\u2019s Study Group","volume":"13","author":"Carter","year":"1998","journal-title":"Mov. Disord. Off. J. Mov. Disord. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.yebeh.2016.10.001","article-title":"Changes in quality of life as a result of ketogenic diet therapy: A new approach to assessment with the potential for positive therapeutic effects","volume":"66","author":"Bruce","year":"2017","journal-title":"Epilepsy Behav."},{"key":"ref_16","first-page":"395","article-title":"Cancer patients\u2019 preferences for communicating clinical trial quality of life information: A qualitative study","volume":"12","author":"Brundage","year":"2003","journal-title":"Qual. Life Res. Int. J. Qual. Life Asp. Treat. Care Rehabil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.metabol.2014.08.001","article-title":"Using positron emission tomography to study human ketone body metabolism: A review","volume":"63","author":"Bouteldja","year":"2014","journal-title":"Metab. Clin. Exp."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/ejcn.2013.116","article-title":"Beyond weight loss: A review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets","volume":"67","author":"Paoli","year":"2013","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.plefa.2003.09.007","article-title":"The therapeutic implications of ketone bodies: The effects of ketone bodies in pathological conditions: Ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism","volume":"70","author":"Veech","year":"2004","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1017\/S0317167100013676","article-title":"Ketogenic diet","volume":"40","author":"Dhamija","year":"2013","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S1474-4422(08)70092-9","article-title":"The ketogenic diet for the treatment of childhood epilepsy: A randomised controlled trial","volume":"7","author":"Neal","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.seizure.2011.03.008","article-title":"Low glycemic index diet in children and young adults with refractory epilepsy: First Italian experience","volume":"20","author":"Coppola","year":"2011","journal-title":"Seizure"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.yebeh.2011.02.018","article-title":"Dietary therapies for epilepsy: Future research","volume":"22","author":"Kessler","year":"2011","journal-title":"Epilepsy Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.jand.2017.02.003","article-title":"A Nutritional Perspective of Ketogenic Diet in Cancer: A Narrative Review","volume":"118","author":"Oliveira","year":"2018","journal-title":"J. Acad. Nutr. Diet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/jhn.12587","article-title":"A systematic review of the use of ketogenic diets in adult patients with cancer","volume":"31","author":"Sremanakova","year":"2018","journal-title":"J. Hum. Nutr. Diet. Off. J. Br. Diet. Assoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101346","DOI":"10.1016\/j.eujim.2021.101346","article-title":"Effects of a low-carbohydrate ketogenic diet on reported pain, blood biomarkers and quality of life in patients with chronic pain: A pilot randomised clinical trial rationale, study design and protocol","volume":"45","author":"Field","year":"2021","journal-title":"Eur. J. Integr. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.neulet.2015.07.034","article-title":"How does the ketogenic diet induce anti-seizure effects?","volume":"637","author":"Rho","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5157645","DOI":"10.1155\/2018\/5157645","article-title":"Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health","volume":"2018","author":"Miller","year":"2018","journal-title":"J. Nutr. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1177\/0883073813487595","article-title":"Ketogenic diets and pain","volume":"28","author":"Masino","year":"2013","journal-title":"J. Child Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13643-020-01542-z","article-title":"PRISMA-S: An extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews","volume":"10","author":"Rethlefsen","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jclinepi.2021.03.001","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"134","author":"Page","year":"2021","journal-title":"J. Clin. Epidemiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3389\/fpubh.2016.00159","article-title":"Use Your Words Carefully: What Is a Chronic Disease?","volume":"4","author":"Bernell","year":"2016","journal-title":"Front. Public Health"},{"key":"ref_33","unstructured":"GACD (2021, October 06). Non-Communicable Diseases: Key Facts and Figures. Available online: https:\/\/www.gacd.org\/about\/what-we-do\/what-are-ncds\/key-facts-and-figures."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"702802","DOI":"10.3389\/fnut.2021.702802","article-title":"Ketogenic Diets and Chronic Disease: Weighing the Benefits Against the Risks","volume":"8","author":"Crosby","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Higgins, J.P., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. (2019). Cochrane Handbook for Systematic Reviews of Interventions, John Wiley & Sons.","DOI":"10.1002\/9781119536604"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1080\/01635581.2020.1803930","article-title":"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","volume":"73","author":"Augustus","year":"2021","journal-title":"Nutr. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/joim.12501","article-title":"Long-term effects of very low-carbohydrate and high-carbohydrate weight-loss diets on psychological health in obese adults with type 2 diabetes: Randomized controlled trial","volume":"280","author":"Brinkworth","year":"2016","journal-title":"J. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5367","DOI":"10.1038\/s41467-021-25667-4","article-title":"A randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes","volume":"12","author":"Durrer","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11060-020-03417-8","article-title":"Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): A randomized, mixed methods, feasibility study","volume":"147","author":"Marson","year":"2020","journal-title":"J. Neuro-Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12937-020-00596-y","article-title":"Does a ketogenic diet have beneficial effects on quality of life, physical activity or biomarkers in patients with breast cancer: A randomized controlled clinical trial","volume":"19","author":"Khodabakhshi","year":"2020","journal-title":"Nutr. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13195-021-00783-x","article-title":"Randomized crossover trial of a modified ketogenic diet in Alzheimer\u2019s disease","volume":"13","author":"Phillips","year":"2021","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Cohen, C.W., Fontaine, K.R., Arend, R.C., Soleymani, T., and Gower, B.A. (2018). 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, 10.","DOI":"10.3390\/nu10091187"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/07315724.2020.1734988","article-title":"A Modified MCT-Based Ketogenic Diet Increases Plasma \u03b2-Hydroxybutyrate but Has Less Effect on Fatigue and Quality of Life in People with Multiple Sclerosis Compared to a Modified Paleolithic Diet: A Waitlist-Controlled, Randomized Pilot Study","volume":"40","author":"Lee","year":"2021","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/pm\/pnz022","article-title":"The Effect of Low-Carbohydrate and Low-Fat Diets on Pain in Individuals with Knee Osteoarthritis","volume":"21","author":"Strath","year":"2020","journal-title":"Pain Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1097\/MCO.0000000000000596","article-title":"Lessons learned from recent clinical trials of ketogenic diet therapies in adults","volume":"22","author":"McDonald","year":"2019","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.mehy.2006.07.043","article-title":"Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma-hydroxybutyrate (GHB)?","volume":"68","author":"Brown","year":"2007","journal-title":"Med. Hypotheses"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0149-7634(94)90031-0","article-title":"Gamma-hydroxybutyrate: An overview of the pros and cons for it being a neurotransmitter and\/or a useful therapeutic agent","volume":"18","author":"Cash","year":"1994","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/cob.12203","article-title":"A systematic review of reviews: Exploring the relationship between obesity, weight loss and health-related quality of life","volume":"7","author":"Kolotkin","year":"2017","journal-title":"Clin. Obes."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12955-019-1092-2","article-title":"Inflammation and quality of life in later life: Findings from the health, well-being and aging study (SABE)","volume":"17","author":"Duim","year":"2019","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12955-014-0141-0","article-title":"Chronic inflammation and quality of life in older adults: A cross-sectional study using biomarkers to predict emotional and relational outcomes","volume":"12","author":"Nowakowski","year":"2014","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Shingler, E., Perry, R., Mitchell, A., England, C., Perks, C., Herbert, G., Ness, A., and Atkinson, C. (2019). Dietary restriction during the treatment of cancer: Results of a systematic scoping review. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5931-7"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.molmet.2019.06.026","article-title":"Ketogenic diet in the treatment of cancer-Where do we stand?","volume":"33","author":"Weber","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1093\/nutrit\/nuaa113","article-title":"Ketogenic diet and cognition in neurological diseases: A systematic review","volume":"79","author":"Amayra","year":"2021","journal-title":"Nutr. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-nutr-071816-064916","article-title":"\u03b2-Hydroxybutyrate: A Signaling Metabolite","volume":"37","author":"Newman","year":"2017","journal-title":"Annu. Rev. Nutr."},{"key":"ref_55","unstructured":"Martin, C., Preedy, V., and Rajendram, R. (2021). Factors Affecting Neurological Aging, Academic Press."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1900\/RDS.2016.13.217","article-title":"Blood Ketones: Measurement, Interpretation, Limitations, and Utility in the Management of Diabetic Ketoacidosis","volume":"13","author":"Dhatariya","year":"2016","journal-title":"Rev. Diabet. Stud. RDS"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Castro-Barquero, S., Ruiz-Le\u00f3n, A.M., Sierra-P\u00e9rez, M., Estruch, R., and Casas, R. (2020). Dietary Strategies for Metabolic Syndrome: A Comprehensive Review. Nutrients, 12.","DOI":"10.3390\/nu12102983"},{"key":"ref_58","unstructured":"Nieman, D. (2019). Nutritional Assessment, McGraw-Hill. [7th ed.]."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1093\/advances\/nmaa073","article-title":"To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease","volume":"11","author":"Grammatikopoulou","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fnut.2020.00020","article-title":"Consumer Reports of \u201cKeto Flu\u201d Associated With the Ketogenic Diet","volume":"7","author":"Bostock","year":"2020","journal-title":"Front. Nutr."},{"key":"ref_61","first-page":"e9639","article-title":"Advantages and Disadvantages of the Ketogenic Diet: A Review Article","volume":"12","author":"Batch","year":"2020","journal-title":"Cureus"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4463\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:47:50Z","timestamp":1760168870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,14]]},"references-count":61,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["nu13124463"],"URL":"https:\/\/doi.org\/10.3390\/nu13124463","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,14]]}}}