{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:41:44Z","timestamp":1788831704055,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"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>This prospective observational trial investigated effects and safety of periodic fasting in subjects with and without type 2 diabetes mellitus (T2DM). The primary end point was set as the change of fatty liver index (FLI) as a surrogate parameter of non-alcoholic fatty liver disease (NAFLD). Six-hundred and ninety-seven subjects (38 with T2DM) were enrolled. A baseline FLI \u2265 60 (the threshold for fatty liver) was found in 264 subjects (37.9%). The mean duration of fasting was 8.5 \u00b1 4.0 days (range 6\u201338). FLI decreased significantly (\u221214.02 \u00b1 11.67; p &lt; 0.0001), with a larger effect in individuals with T2DM (\u221219.15 \u00b1 11.0; p &lt; 0.0001; p = 0.002 compared to non-diabetic subjects). Body mass index (BMI) decreased by \u22121.51 \u00b1 0.82 kg\/m2, and 49.9% of the subjects lost \u22655% body weight. After fasting, nearly half of the 264 subjects with FLI \u2265 60 (highest risk category) shifted to a lower category. The improvement of FLI correlated with the number of fasting days (r = \u22120.20, p &lt; 0.0001) and with the magnitude of BMI reduction (r = 0.14, p = 0.0001). Periodic fasting with concomitant weight reduction leads to significant rapid improvement of FLI in subjects with and without T2DM.<\/jats:p>","DOI":"10.3390\/nu11112601","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T05:18:26Z","timestamp":1572499106000},"page":"2601","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Effects of Periodic Fasting on Fatty Liver Index\u2014A Prospective Observational Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Stefan","family":"Drinda","sequence":"first","affiliation":[{"name":"Buchinger Wilhelmi Clinic, 88662 \u00dcberlingen, Germany"},{"name":"Clinic St. Katharinental, Department of Rheumatology, 8253 Diessenhofen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Grundler","sequence":"additional","affiliation":[{"name":"Buchinger Wilhelmi Clinic, 88662 \u00dcberlingen, Germany"},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2013Universit\u00e4t zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Neumann","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0245-2046","authenticated-orcid":false,"given":"Nico","family":"Steckhan","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2013Universit\u00e4t zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Department of Internal and Complementary Medicine, Immanuel Hospital Berlin, 14109 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Michalsen","sequence":"additional","affiliation":[{"name":"Department of Internal and Complementary Medicine, Immanuel Hospital Berlin, 14109 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francoise","family":"Wilhelmi de Toledo","sequence":"additional","affiliation":[{"name":"Buchinger Wilhelmi Clinic, 88662 \u00dcberlingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Glen, J., Floros, L., Day, C., Pryke, R., and Grp, G.D. (2016). Non\u2013alcoholic fatty liver disease (NAFLD): Summary of NICE guidance. BMJ Brit. Med. J., 354.","DOI":"10.1136\/bmj.i4428"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global Epidemiology of Nonalcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1365-2036.2011.04724.x","article-title":"Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults","volume":"34","author":"Vernon","year":"2011","journal-title":"Aliment. Pharm. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1136\/gut.2009.205088","article-title":"Disease progression of non\u2013alcoholic fatty liver disease: A prospective study with paired liver biopsies at 3 years","volume":"59","author":"Wong","year":"2010","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Calzadilla Bertot, L., and Adams, L.A. (2016). The Natural Course of Non-Alcoholic Fatty Liver Disease. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050774"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1111\/jgh.13264","article-title":"Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis","volume":"31","author":"Ballestri","year":"2016","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1007\/s00125-010-1663-6","article-title":"The impact of liver fat vs. visceral fat in determining categories of prediabetes","volume":"53","author":"Kantartzis","year":"2010","journal-title":"Diabetologia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.soard.2017.09.527","article-title":"Nonalcoholic fatty liver disease in patients with different baseline glucose status undergoing bariatric surgery: Analysis of intraoperative liver biopsies and literature review","volume":"14","author":"Souto","year":"2018","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1056\/NEJMra1011035","article-title":"Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease REPLY","volume":"371","author":"Shulman","year":"2014","journal-title":"New Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.cld.2013.09.009","article-title":"The Role of Diet and Nutritional Intervention for the Management of Patients with NAFLD","volume":"18","author":"Barrera","year":"2014","journal-title":"Clin. Liver Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1002\/hep.23535","article-title":"Increased Fructose Consumption Is Associated with Fibrosis Severity in Patients with Nonalcoholic Fatty Liver Disease","volume":"51","author":"Abdelmalek","year":"2010","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kahl, S., Strassburger, K., Nowotny, B., Livingstone, R., Kluppelholz, B., Kessel, K., Hwang, J.H., Giani, G., Hoffmann, B., and Pacini, G. (2014). Comparison of liver fat indices for the diagnosis of hepatic steatosis and insulin resistance. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094059"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., and Tiribelli, C. (2006). The Fatty Liver Index: A simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol., 6.","DOI":"10.1186\/1471-230X-6-33"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.dld.2017.01.147","article-title":"AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions","volume":"49","author":"Lonardo","year":"2017","journal-title":"Digest. Liver Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.jhep.2018.08.011","article-title":"Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease","volume":"69","author":"Wong","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4254\/wjh.v9.i16.715","article-title":"Non-alcoholic fatty liver disease: An expanded review","volume":"9","author":"Benedict","year":"2017","journal-title":"World J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/hep.23276","article-title":"Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis","volume":"51","author":"Promrat","year":"2010","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1053\/j.gastro.2015.04.005","article-title":"Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis","volume":"149","author":"Friedman","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1136\/gutjnl-2016-312431","article-title":"Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease","volume":"66","author":"Rotman","year":"2017","journal-title":"Gut"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1053\/j.gastro.2012.04.001","article-title":"The diagnosis and management of non\u2013alcoholic fatty liver disease: Practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology","volume":"142","author":"Chalasani","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1056\/NEJM200105033441801","article-title":"Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance","volume":"344","author":"Tuomilehto","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cardona\u2013Morrell, M., Rychetnik, L., Morrell, S.L., Espinel, P.T., and Bauman, A. (2010). Reduction of diabetes risk in routine clinical practice: Are physical activity and nutrition interventions feasible and are the outcomes from reference trials replicable? A systematic review and meta-analysis. BMC Public Health, 10.","DOI":"10.1186\/1471-2458-10-653"},{"key":"ref_23","first-page":"444","article-title":"Fasting therapy for treating and preventing disease\u2014Current state of evidence","volume":"20","author":"Michalsen","year":"2013","journal-title":"Forsch Komplementmed"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1089\/acm.2005.11.601","article-title":"Incorporation of fasting therapy in an integrative medicine ward: Evaluation of outcome, safety, and effects on lifestyle adherence in a large prospective cohort study","volume":"11","author":"Michalsen","year":"2005","journal-title":"J. Altern. Complement. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1007\/s00125-011-2204-7","article-title":"Reversal of type 2 diabetes: Normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol","volume":"54","author":"Lim","year":"2011","journal-title":"Diabetologia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.bbalip.2015.01.013","article-title":"Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice","volume":"1851","author":"Baumeier","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wilhelmi de Toledo, F., Grundler, F., Bergouignan, A., Drinda, S., and Michalsen, A. (2019). Safety, health improvement and well\u2013being during a 4 to 21\u2013day fasting period in an observational study including 1422 subjects. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0209353"},{"key":"ref_28","first-page":"434","article-title":"Fasting therapy\u2014An expert panel update of the 2002 consensus guidelines","volume":"20","author":"Buchinger","year":"2013","journal-title":"Forsch Komplementmed"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.dsx.2018.03.016","article-title":"Non-alcoholic fatty liver disease and associated dietary and lifestyle risk factors","volume":"12","author":"Rayyan","year":"2018","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"922","DOI":"10.2337\/dc13-2195","article-title":"Diabetes prevention in the real world: Effectiveness of pragmatic lifestyle interventions for the prevention of type 2 diabetes and of the impact of adherence to guideline recommendations: A systematic review and meta-analysis","volume":"37","author":"Dunkley","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1055\/s-0043-101700","article-title":"Effects of A One-Week Fasting Therapy in Patients with Type-2 Diabetes Mellitus and Metabolic Syndrome\u2014A Randomized Controlled Explorative Study","volume":"125","author":"Li","year":"2017","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_32","first-page":"379","article-title":"Fasting: The history, pathophysiology and complications","volume":"137","author":"Kerndt","year":"1982","journal-title":"West. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Peng, L., Wang, J., and Li, F. (2011). Weight reduction for non\u2013alcoholic fatty liver disease. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD003619.pub3"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3945\/ajcn.110.007674","article-title":"Short\u2013term weight loss and hepatic triglyceride reduction: Evidence of a metabolic advantage with dietary carbohydrate restriction","volume":"93","author":"Browning","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.diabres.2019.03.032","article-title":"Differential effects of gender and patient background diversity on the changes in metabolic and biophysical profiles in people with type-2 diabetes from different ethnicities who fast during Ramadan (H1439): A prospective study from Qatar","volume":"152","author":"Dabbous","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.nutr.26.061505.111258","article-title":"Fuel metabolism in starvation","volume":"26","author":"Cahill","year":"2006","journal-title":"Annu Rev. Nutr"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.cmet.2016.12.022","article-title":"Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics","volume":"25","author":"Puchalska","year":"2017","journal-title":"Cell Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1111\/liv.12769","article-title":"Ketone body production is differentially altered in steatosis and non-alcoholic steatohepatitis in obese humans","volume":"35","author":"Mannisto","year":"2015","journal-title":"Liver Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrd.2015.9","article-title":"Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23","volume":"15","author":"Degirolamo","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.cmet.2018.07.003","article-title":"Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat Content but Is Dependent upon Capacity for \u03b2 Cell Recovery","volume":"28","author":"Taylor","year":"2018","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"260","DOI":"10.14740\/gr685w","article-title":"Association of the Nonalcoholic Hepatic Steatosis and Its Degrees with the Values of Liver Enzymes and Homeostasis Model Assessment\u2014Insulin Resistance Index","volume":"8","author":"Cruz","year":"2015","journal-title":"Gastroenterol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Van den Berg, E.H., Amini, M., Schreuder, T.C., Dullaart, R.P., Faber, K.N., Alizadeh, B.Z., and Blokzijl, H. (2017). Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: A large Dutch population cohort. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171502"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Mameli, C., Krakauer, N.Y., Krakauer, J.C., Bosetti, A., Ferrari, C.M., Moiana, N., Schneider, L., Borsani, B., Genoni, T., and Zuccotti, G. (2018). The association between a body shape index and cardiovascular risk in overweight and obese children and adolescents. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0190426"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0140-6736(17)33102-1","article-title":"Primary care\u2013led weight management for remission of type 2 diabetes (DiRECT): An open\u2013label, cluster\u2013randomised trial","volume":"391","author":"Lean","year":"2018","journal-title":"Lancet"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/11\/2601\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:30:28Z","timestamp":1760189428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/11\/2601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,30]]},"references-count":44,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["nu11112601"],"URL":"https:\/\/doi.org\/10.3390\/nu11112601","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,30]]}}}