{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:54:51Z","timestamp":1781862891821,"version":"3.54.5"},"reference-count":80,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health [Ricerca Corrente]"},{"name":"Research and Educational Centre of Environmental Health and Radiation Protection","award":["REC-IMI"],"award-info":[{"award-number":["REC-IMI"]}]},{"name":"Research and Educational Centre of Environmental Health and Radiation Protection","award":["KK.01.1.1.02.0007"],"award-info":[{"award-number":["KK.01.1.1.02.0007"]}]},{"name":"European Union\u2014Next Generation EU","award":["643-02\/23-01\/00016"],"award-info":[{"award-number":["643-02\/23-01\/00016"]}]},{"name":"European Union\u2014Next Generation EU","award":["533-03-23-0006"],"award-info":[{"award-number":["533-03-23-0006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Obesity is a chronic endocrine\u2013metabolic disorder. The risk of comorbidities increases with a higher body mass index (BMI), particularly when BMI \u2265 35.0 kg\/m2. Common complications include insulin resistance, type 2 diabetes, dyslipidemia, and chronic low-grade inflammation, which collectively impair DNA stability by promoting the formation of genotoxic species. Methods: This non-randomised, quasi-experimental clinical intervention study included 53 participants (both sexes) with a BMI \u2265 35.0 kg\/m2, who were assigned to parallel experimental or control streams based on clinical needs and institutional eligibility. During a three-week intervention, the experimental group received a hospital-supervised very-low-calorie diet (VLCD; ~600 kcal\/day) under continuous medical monitoring. Conversely, the control group followed a standard reduced-calorie diet (SRD) of 1500 kcal\/day in a free-living home environment. Before and after the intervention, primary, oxidative, and permanent DNA damage were measured using alkaline, FPG-modified comet (peripheral blood mononuclear cells), and cytokinesis-block micronucleus cytome assays (phytohaemagglutinin-stimulated binucleated lymphocytes), alongside anthropometric and biochemical tracking. Results: Within-group evaluations revealed that both dietary regimens improved several metabolic health indicators, notably modulating insulin resistance, lipid profiles, and leukocyte counts. However, participants in the VLCD stream experienced significantly greater downward changes in body weight, BMI, and absolute lipid values. Crucially, the VLCD intervention was associated with a highly significant within-group reduction in parameters of permanent chromosomal damage, effectively halving the frequencies of micronuclei and nuclear buds, independent of baseline variations, in adjusted multivariate regression models. Conversely, the home-based SRD regimen demonstrated no measurable impact on permanent genomic damage. Neither diet induced a significant change in repairable primary or oxidative DNA lesions over this short timeframe. Conclusions: These exploratory findings suggest that strict calorie restriction can rapidly stabilise genome stability in advanced clinical settings, warranting future randomised controlled trials with long-term longitudinal follow-up to assess permanent risk reductions. Due to structural baseline variations in age, chronic comorbidities, and compliance environments between the cohorts, direct comparative superiority cannot be definitively established.<\/jats:p>","DOI":"10.3390\/nu18121985","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:18:43Z","timestamp":1781860723000},"page":"1985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Caloric Restriction on DNA Damage: A Comparison of Very Low-Calorie and Standard Reduced-Calorie Diets in Obesity\u2014Non-Randomised, Quasi-Experimental Clinical Intervention Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9837-7185","authenticated-orcid":false,"given":"Mirta","family":"Mili\u0107","sequence":"first","affiliation":[{"name":"Division of Toxicology, Institute for Medical Research and Occupational Health (IMROH), 10001 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"O\u017evald","sequence":"additional","affiliation":[{"name":"Neuropsychiatric Hospital Dr. Ivan Barbot of Popova\u010da, 44317 Popova\u010da, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Mannocci","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Sciences and Quality of Life, University San Raffaele, 00166 Rome, Italy"},{"name":"Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-6717","authenticated-orcid":false,"given":"Stefano","family":"Bonassi","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Sciences and Quality of Life, University San Raffaele, 00166 Rome, Italy"},{"name":"Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrvoje","family":"Rada\u0161evi\u0107","sequence":"additional","affiliation":[{"name":"Andrija \u0160tampar Teaching Institute of Public Health, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Nikoli\u0107","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Institute for Medical Research and Occupational Health (IMROH), 10001 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragan","family":"Bo\u017ei\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Special Hospital for Extended Treatment of Duga Resa, 47250 Duga Resa, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidija","family":"Duh","sequence":"additional","affiliation":[{"name":"Special Hospital for Extended Treatment of Duga Resa, 47250 Duga Resa, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6325-7394","authenticated-orcid":false,"given":"Martina","family":"Matovinovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Faculty of Kinesiology, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3596-8383","authenticated-orcid":false,"given":"Martina","family":"Bituh","sequence":"additional","affiliation":[{"name":"Laboratory for Food Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","unstructured":"World Health Organisation (2025). 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