{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:38:06Z","timestamp":1787067486019,"version":"build-2736575974"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 degli studi \"Magna Graecia\" di Catanzaro"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nutr"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a common condition characterized by liver fat accumulation, and it has become a leading cause of liver-related morbidity and mortality worldwide. Currently, no drugs are approved to prevent or treat this condition. Carotenoids, especially lycopene, a potent antioxidant present in tomatoes, have demonstrated potential benefits for liver health in both preclinical and clinical studies. However, the lycopene content differs between tomatoes according to maturity stage. Ripening is an agronomic technique that enhances lycopene content by allowing tomatoes to fully mature on the plant. This study aimed to assess the effect of a carotenoid-rich tomato sauce made from vine-ripened tomatoes (OsteoCol\u00ae, patent N\u00b0:102019000000061 on liver fat in adults with MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 98 patients were enrolled in a double-blind, placebo-controlled clinical trial. The protocol was approved by the local Ethics Committee (124\/2022\/CE). The intervention group consumed the carotenoid-rich tomato sauce (OsteoCol\u00ae), while the control group received a commercial tomato sauce as a placebo for a total of 12\u00a0weeks.<\/jats:p>\n                    <jats:p>The main outcome was the variation in hepatic fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, and transaminases were measured at baseline and after treatment. We also investigated the effect of OsteoCol\u00ae extract on rat hepatoma cells and human hepatocellular carcinoma cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A greater reduction in liver fat content was observed in participants consuming OsteoCol\u00ae compared to those receiving the placebo (CAP score: \u2212\u200933\u2009\u00b1\u200944\u00a0dB\/m vs. \u2212\u200912\u2009\u00b1\u200938\u00a0dB\/m,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014). The percentage reduction in the CAP score was even greater in men, individuals aged 60 and older, those with normal weight\/overweight, and adults with mild hepatic steatosis at baseline. Additionally, in vitro studies on hepatic cell lines supported the clinical findings by demonstrating that OsteoCol\u00ae extract significantly reduced intracellular lipid accumulation through modulation of lipogenesis, \u03b2-oxidation, and cholesterol synthesis pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A functional tomato sauce made from vine-ripened tomatoes reduced liver fat content in adults with MASLD. This carotenoid-rich tomato sauce could serve as a novel nutritional strategy for patients with MASLD.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                      ISRCTN, ISRCTN10483954. Registered 04 June 2025\u2014retrospectively registered,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1186\/ISRCTN10483954\" ext-link-type=\"uri\">https:\/\/doi.org\/10.1186\/ISRCTN10483954<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00394-026-04049-w","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:34:42Z","timestamp":1783074882000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A carotenoid-rich functional tomato sauce (OsteoCol\u00ae) reduces liver fat content in adults with metabolic dysfunction-associated steatotic liver disease: a randomized clinical trial"],"prefix":"10.1007","volume":"65","author":[{"given":"Rosario","family":"Mare","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvelise","family":"Ferro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Maurotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Mazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Castagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Pujia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Rita","family":"Noto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Galluccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Mirarchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Andrea","family":"Giamp\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Moraca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Montalcini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Pujia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"4049_CR1","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.jhep.2024.04.031","volume":"81","author":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO)","year":"2024","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO) (2024) EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 81:492\u2013542","journal-title":"J Hepatol"},{"key":"4049_CR2","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.tem.2024.02.007","volume":"35","author":"L Miao","year":"2024","unstructured":"Miao L, Targher G, Byrne CD, Cao Y, Zheng M (2024) Current status and future trends of the global burden of MASLD. Trends Endocrinol Metab 35:697\u2013707","journal-title":"Trends Endocrinol Metab"},{"key":"4049_CR3","doi-asserted-by":"publisher","first-page":"e573","DOI":"10.1016\/j.cgh.2021.02.030","volume":"20","author":"J Liu","year":"2022","unstructured":"Liu J, Ayada I, Zhang X, Wang L, Li Y, Wen T, Ma Z, Bruno MJ, de Knegt RJ, Cao W et al (2022) Estimating global prevalence of metabolic dysfunction-associated fatty liver disease in overweight or obese adults. Clin Gastroenterol Hepatol 20:e573\u2013e582","journal-title":"Clin Gastroenterol Hepatol"},{"key":"4049_CR4","doi-asserted-by":"publisher","first-page":"S32","DOI":"10.3350\/cmh.2024.0431","volume":"31","author":"ZM Younossi","year":"2025","unstructured":"Younossi ZM, Kalligeros M, Henry L (2025) Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol 31:S32\u2013S50","journal-title":"Clin Mol Hepatol"},{"key":"4049_CR5","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1016\/j.jhep.2024.09.027","volume":"82","author":"Z Li","year":"2025","unstructured":"Li Z, Li Z, Cao D, Hu Y (2025) Is MASLD a real culprit for all-cause mortality? A meta-analysis and preliminary pathophysiology exploration in the real world. J Hepatol 82:e29\u2013e31","journal-title":"J Hepatol"},{"key":"4049_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmr.2024.100018","volume":"77","author":"X Zhang","year":"2025","unstructured":"Zhang X, Lau HC, Yu J (2025) Pharmacological treatment for metabolic dysfunction-associated steatotic liver disease and related disorders: current and emerging therapeutic options. Pharmacol Rev 77:100018","journal-title":"Pharmacol Rev"},{"key":"4049_CR7","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.livres.2025.01.001","volume":"9","author":"JYL Chiang","year":"2025","unstructured":"Chiang JYL (2025) New drug therapies for metabolic dysfunction-associated steatohepatitis. Liver Res 9:94\u2013103","journal-title":"Liver Res"},{"key":"4049_CR8","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1056\/NEJMoa2401943","volume":"391","author":"R Loomba","year":"2024","unstructured":"Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E, Yoneda M, Behling C, Cummings OW, Tang Y et al (2024) Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N Engl J Med 391:299\u2013310","journal-title":"N Engl J Med"},{"key":"4049_CR9","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","volume":"384","author":"PN Newsome","year":"2021","unstructured":"Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling A, Harrison SA, NN9931-4296 Investigators (2021) A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med 384:1113\u20131124","journal-title":"N Engl J Med"},{"key":"4049_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.iliver.2024.100131","volume":"3","author":"P Yadav","year":"2024","unstructured":"Yadav P, Quadri K, Kadian R, Waziri A, Agrawal P, Alam MS (2024) New approaches to the treatment of metabolic dysfunction-associated steatotic liver with natural products. iLIVER 3:100131","journal-title":"iLIVER"},{"key":"4049_CR11","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12040903","volume":"12","author":"C Munteanu","year":"2023","unstructured":"Munteanu C, Schwartz B (2023) The effect of bioactive aliment compounds and micronutrients on non-alcoholic fatty liver disease. Antioxidants 12:903. https:\/\/doi.org\/10.3390\/antiox12040903","journal-title":"Antioxidants"},{"key":"4049_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00494","volume":"11","author":"Y Ferro","year":"2020","unstructured":"Ferro Y, Montalcini T, Mazza E, Foti D, Angotti E, Gliozzi M, Nucera S, Paone S, Bombardelli E, Aversa I et al (2020) Randomized clinical trial: bergamot citrus and wild cardoon reduce liver steatosis and body weight in non-diabetic individuals aged over 50 years. Front Endocrinol 11:494","journal-title":"Front Endocrinol"},{"key":"4049_CR13","doi-asserted-by":"publisher","first-page":"279","DOI":"10.3390\/ph18020279","volume":"18","author":"D Ciobarca","year":"2025","unstructured":"Ciobarca D, Catoi AF, Gavrilas L, Banc R, Miere D, Filip L (2025) Natural bioactive compounds in the management of type 2 diabetes and metabolic (dysfunction)-associated steatotic liver disease. Pharmaceuticals 18:279. https:\/\/doi.org\/10.3390\/ph18020279","journal-title":"Pharmaceuticals"},{"key":"4049_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9080706","volume":"9","author":"M Imran","year":"2020","unstructured":"Imran M, Ghorat F, Ul-Haq I, Ur-Rehman H, Aslam F, Heydari M, Shariati MA, Okuskhanova E, Yessimbekov Z, Thiruvengadam M et al (2020) Lycopene as a natural antioxidant used to prevent human health disorders. Antioxidants 9:706. https:\/\/doi.org\/10.3390\/antiox9080706","journal-title":"Antioxidants"},{"key":"4049_CR15","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1079\/BJN2000284","volume":"85","author":"ME O\u2019Neill","year":"2001","unstructured":"O\u2019Neill ME, Carroll Y, Corridan B, Olmedilla B, Granado F, Blanco I, Van den Berg H, Hininger I, Rousell AM, Chopra M et al (2001) A European carotenoid database to assess carotenoid intakes and its use in a five-country comparative study. Br J Nutr 85:499\u2013507","journal-title":"Br J Nutr"},{"key":"4049_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/nu14030717","volume":"14","author":"R Mare","year":"2022","unstructured":"Mare R, Maurotti S, Ferro Y, Galluccio A, Arturi F, Romeo S, Procopio A, Musolino V, Mollace V, Montalcini T et al (2022) A rapid and cheap method for extracting and quantifying lycopene content in tomato sauces: effects of lycopene micellar delivery on human osteoblast-like cells. Nutrients 14:717. https:\/\/doi.org\/10.3390\/nu14030717","journal-title":"Nutrients"},{"key":"4049_CR17","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.jfca.2003.10.003","volume":"17","author":"E Sahlin","year":"2004","unstructured":"Sahlin E, Savage GP, Lister CE (2004) Investigation of the antioxidant properties of tomatoes after processing. J Food Compos Anal 17:635\u2013647","journal-title":"J Food Compos Anal"},{"key":"4049_CR18","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1002\/jsfa.3622","volume":"89","author":"P G\u00f3mez","year":"2009","unstructured":"G\u00f3mez P, Ferrer M\u00c1, Fern\u00e1ndez-Trujillo JP, Calder\u00f3n A, Art\u00e9s F, Egea-Cortines M, Weiss J (2009) Structural changes, chemical composition and antioxidant activity of cherry tomato fruits (Cv. Micro-Tom) stored under optimal and chilling conditions. J Sci Food Agric 89:1543\u20131551","journal-title":"J Sci Food Agric"},{"key":"4049_CR19","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1089\/jmf.2015.0123","volume":"19","author":"RM Pina-Zentella","year":"2016","unstructured":"Pina-Zentella RM, Rosado JL, Gallegos-Corona MA, Madrigal-Perez LA, Garcia OP, Ramos-Gomez M (2016) Lycopene improves diet-mediated recuperation in rat model of nonalcoholic fatty liver disease. J Med Food 19:607\u2013614","journal-title":"J Med Food"},{"key":"4049_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2022.134799","volume":"405","author":"Y Li","year":"2023","unstructured":"Li Y, Cui Z, Hu L (2023) Recent technological strategies for enhancing the stability of lycopene in processing and production. Food Chem 405:134799","journal-title":"Food Chem"},{"key":"4049_CR21","doi-asserted-by":"publisher","first-page":"967","DOI":"10.3390\/metabo3040967","volume":"3","author":"A Sorrequieta","year":"2013","unstructured":"Sorrequieta A, Abriata LA, Boggio SB, Valle EM (2013) Off-the-vine ripening of tomato fruit causes alteration in the primary metabolite composition. Metabolites 3:967\u2013978","journal-title":"Metabolites"},{"key":"4049_CR22","doi-asserted-by":"publisher","first-page":"2763","DOI":"10.1002\/jsfa.9484","volume":"99","author":"K Sikorska-Zimny","year":"2019","unstructured":"Sikorska-Zimny K, Badelek E, Grzegorzewska M, Ciecierska A, Kowalski A, Kosson R, Tuccio L, Mencaglia AA, Ciaccheri L, Mignani AG et al (2019) Comparison of lycopene changes between open-field processing and fresh market tomatoes during ripening and post-harvest storage by using a non-destructive reflectance sensor. J Sci Food Agric 99:2763\u20132774","journal-title":"J Sci Food Agric"},{"key":"4049_CR23","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/B978-0-323-89779-2.00009-0","volume-title":"Nutraceuticals and Health Care","author":"N Yasmeen","year":"2022","unstructured":"Yasmeen N, Syed Sameer A, Nissar S (2022) Chapter 6\u2014lycopene. In: Kour J, Nayik GA (eds) Nutraceuticals and Health Care. Academic Press, pp 115\u2013134"},{"key":"4049_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.lwt.2020.109323","volume":"127","author":"M Caseiro","year":"2020","unstructured":"Caseiro M, Ascenso A, Costa A, Creagh-Flynn J, Johnson M, Sim\u00f5es S (2020) Lycopene in human health. LWT 127:109323","journal-title":"LWT"},{"key":"4049_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2024.106284","volume":"118","author":"J Bufka","year":"2024","unstructured":"Bufka J, Va\u0148kov\u00e1 L, S\u00fdkora J, K\u0159\u00ed\u017ekov\u00e1 V (2024) Exploring carotenoids: metabolism, antioxidants, and impacts on human health. J Funct Foods 118:106284","journal-title":"J Funct Foods"},{"key":"4049_CR26","doi-asserted-by":"publisher","first-page":"1120254","DOI":"10.3389\/fnut.2023.1120254","volume":"10","author":"X Gao","year":"2023","unstructured":"Gao X, Zhao X, Liu M, Zhao H, Sun Y (2023) Lycopene prevents non-alcoholic fatty liver disease through regulating hepatic NF-kappaB\/NLRP3 inflammasome pathway and intestinal microbiota in mice fed with high-fat and high-fructose diet. Front Nutr 10:1120254","journal-title":"Front Nutr"},{"key":"4049_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8080276","volume":"8","author":"M Rovero Costa","year":"2019","unstructured":"Rovero Costa M, Leite Garcia J, Cristina Vagula de Almeida Silva C, Junio Togneri Ferron A, Valentini Francisqueti-Ferron F, Kurokawa Hasimoto F, Schmitt Gregolin C, Henrique Salome de Campos D, Roberto de Andrade C, Dos Anjos Ferreira AL et al (2019) Lycopene modulates pathophysiological processes of non-alcoholic fatty liver disease in obese rats. Antioxidants 8:276. https:\/\/doi.org\/10.3390\/antiox8080276","journal-title":"Antioxidants"},{"key":"4049_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.phanu.2020.100225","volume":"14","author":"NM Saeed","year":"2020","unstructured":"Saeed NM, Mansour AM, Allam S (2020) Lycopene induces insulin signaling and alleviates fibrosis in experimental model of non-alcoholic fatty liver disease in rats. PharmaNutrition 14:100225","journal-title":"PharmaNutrition"},{"key":"4049_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9010141","volume":"9","author":"R Negri","year":"2020","unstructured":"Negri R, Trinchese G, Carbone F, Caprio MG, Stanzione G, di Scala C, Micillo T, Perna F, Tarotto L, Gelzo M et al (2020) Randomised clinical trial: calorie restriction regimen with tomato juice supplementation ameliorates oxidative stress and preserves a proper immune surveillance modulating mitochondrial bioenergetics of T-lymphocytes in obese children affected by non-alcoholic fatty liver disease (NAFLD). J Clin Med 9:141. https:\/\/doi.org\/10.3390\/jcm9010141","journal-title":"J Clin Med"},{"key":"4049_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/nu11051101","volume":"11","author":"K Christensen","year":"2003","unstructured":"Christensen K, Lawler T, Mares J (2003) Dietary carotenoids and non-alcoholic fatty liver disease among US adults, NHANES 2003(-)2014. Nutrients 11:1101. https:\/\/doi.org\/10.3390\/nu11051101","journal-title":"Nutrients"},{"key":"4049_CR31","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1007\/s00394-018-1678-1","volume":"58","author":"M Xiao","year":"2019","unstructured":"Xiao M, Chen G, Zeng F, Qiu R, Shi W, Lin J, Cao Y, Li H, Ling W, Chen Y (2019) Higher serum carotenoids associated with improvement of non-alcoholic fatty liver disease in adults: a prospective study. Eur J Nutr 58:721\u2013730","journal-title":"Eur J Nutr"},{"key":"4049_CR32","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1159\/000496458","volume":"74","author":"L Wang","year":"2019","unstructured":"Wang L, Ding C, Zeng F, Zhu H (2019) Low levels of serum beta-carotene and beta-carotene\/retinol ratio are associated with histological severity in nonalcoholic fatty liver disease patients. Ann Nutr Metab 74:156\u2013164","journal-title":"Ann Nutr Metab"},{"key":"4049_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/nu16040562","volume":"16","author":"R Donghia","year":"2024","unstructured":"Donghia R, Campanella A, Bonfiglio C, Cuccaro F, Tatoli R, Giannelli G (2024) Protective role of lycopene in subjects with liver disease: NUTRIHEP study. Nutrients 16:562. https:\/\/doi.org\/10.3390\/nu16040562","journal-title":"Nutrients"},{"key":"4049_CR34","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12967-020-02676-3","volume":"19","author":"Y Ferro","year":"2021","unstructured":"Ferro Y, Mazza E, Angotti E, Pujia R, Mirarchi A, Salvati MA, Terracciano R, Savino R, Romeo S, Scuteri A et al (2021) Effect of a novel functional tomato sauce (OsteoCol) from vine-ripened tomatoes on serum lipids in individuals with common hypercholesterolemia: tomato sauce and hypercholesterolemia. J Transl Med 19:19\u201323","journal-title":"J Transl Med"},{"key":"4049_CR35","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1007\/s00394-024-03370-6","volume":"63","author":"E Mazza","year":"2024","unstructured":"Mazza E, Ferro Y, Maurotti S, Micale F, Boragina G, Russo R, Lascala L, Sciacqua A, Gazzaruso C, Montalcini T et al (2024) Association of dietary patterns with sarcopenia in adults aged 50 years and older. Eur J Nutr 63:1651\u20131662","journal-title":"Eur J Nutr"},{"key":"4049_CR36","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1186\/s12967-022-03579-1","volume":"20","author":"Y Ferro","year":"2022","unstructured":"Ferro Y, Pujia R, Mazza E, Lascala L, Lodari O, Maurotti S, Pujia A, Montalcini T (2022) A new nutraceutical (Livogen Plus(R)) improves liver steatosis in adults with non-alcoholic fatty liver disease. J Transl Med 20:377\u2013381","journal-title":"J Transl Med"},{"key":"4049_CR37","doi-asserted-by":"crossref","unstructured":"Expert panel on detection, E. (2001) Executive summary of the third report of the National cholesterol education program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 285:2486\u20132497","DOI":"10.1001\/jama.285.19.2486"},{"key":"4049_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-018-5538-y","volume":"18","author":"IH Danquah","year":"2018","unstructured":"Danquah IH, Petersen CB, Skov SS, Tolstrup JS (2018) Validation of the NPAQ-Short\u2014a brief questionnaire to monitor physical activity and compliance with the WHO recommendations. BMC Public Health 18:601","journal-title":"BMC Public Health"},{"key":"4049_CR39","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1136\/bjsports-2020-102955","volume":"54","author":"FC Bull","year":"2020","unstructured":"Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, Carty C, Chaput J, Chastin S, Chou R et al (2020) World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med 54:1451\u20131462","journal-title":"Br J Sports Med"},{"key":"4049_CR40","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","volume":"18","author":"WT Friedewald","year":"1972","unstructured":"Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499\u2013502","journal-title":"Clin Chem"},{"key":"4049_CR41","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1007\/BF00280883","volume":"28","author":"DR Matthews","year":"1985","unstructured":"Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412\u2013419","journal-title":"Diabetologia"},{"key":"4049_CR42","doi-asserted-by":"publisher","DOI":"10.3390\/ph17111418","volume":"17","author":"M Settino","year":"2024","unstructured":"Settino M, Maurotti S, Tirinato L, Greco S, Coppoletta AR, Cardamone A, Musolino V, Montalcini T, Pujia A, Mare R (2024) Zibibbo grape seeds\u2019 polyphenolic profile: effects on bone turnover and metabolism. Pharmaceuticals 17:1418. https:\/\/doi.org\/10.3390\/ph17111418","journal-title":"Pharmaceuticals"},{"key":"4049_CR43","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/s41596-018-0119-1","volume":"14","author":"A Brodkorb","year":"2019","unstructured":"Brodkorb A, Egger L, Alminger M, Alvito P, Assuncao R, Ballance S, Bohn T, Bourlieu-Lacanal C, Boutrou R, Carriere F et al (2019) INFOGEST static in vitro simulation of gastrointestinal food digestion. Nat Protoc 14:991\u20131014","journal-title":"Nat Protoc"},{"key":"4049_CR44","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1177\/1740774515602688","volume":"13","author":"JM Lachin","year":"2016","unstructured":"Lachin JM (2016) Fallacies of last observation carried forward analyses. Clin Trials 13:161\u2013168","journal-title":"Clin Trials"},{"key":"4049_CR45","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1089\/jmf.2005.8.413","volume":"8","author":"S Xianquan","year":"2005","unstructured":"Xianquan S, Shi J, Kakuda Y, Yueming J (2005) Stability of lycopene during food processing and storage. J Med Food 8:413\u2013422","journal-title":"J Med Food"},{"key":"4049_CR46","unstructured":"Liana Maria A, Diana M, Maria BD, Maria R Monitoring the lycopene content in some fruits and vegetables"},{"key":"4049_CR47","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1080\/01635589809514703","volume":"31","author":"AV Rao","year":"1998","unstructured":"Rao AV, Agarwal S (1998) Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. Nutr Cancer 31:199\u2013203","journal-title":"Nutr Cancer"},{"key":"4049_CR48","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1093\/jn\/138.3.482","volume":"138","author":"ML Failla","year":"2008","unstructured":"Failla ML, Chitchumroonchokchai C, Ishida BK (2008) In vitro micellarization and intestinal cell uptake of cis isomers of lycopene exceed those of all-trans lycopene. J Nutr 138:482\u2013486","journal-title":"J Nutr"},{"key":"4049_CR49","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1017\/S0007114507685201","volume":"98","author":"NZ Unlu","year":"2007","unstructured":"Unlu NZ, Bohn T, Francis DM, Nagaraja HN, Clinton SK, Schwartz SJ (2007) Lycopene from heat-induced cis-isomer-rich tomato sauce is more bioavailable than from all-trans-rich tomato sauce in human subjects. Br J Nutr 98:140\u2013146","journal-title":"Br J Nutr"},{"key":"4049_CR50","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3390\/antiox8070229","volume":"8","author":"LI Elvira-Torales","year":"2019","unstructured":"Elvira-Torales LI, Garcia-Alonso J, Periago-Caston MJ (2019) Nutritional importance of carotenoids and their effect on liver health: a review. Antioxidants 8:229. https:\/\/doi.org\/10.3390\/antiox8070229","journal-title":"Antioxidants"},{"key":"4049_CR51","doi-asserted-by":"publisher","first-page":"5701","DOI":"10.1002\/fsn3.3523","volume":"11","author":"MH Abir","year":"2023","unstructured":"Abir MH, Mahamud AGMSU, Tonny SH, Anu MS, Hossain KHS, Protic IA, Khan MSU, Baroi A, Moni A, Uddin MJ (2023) Pharmacological potentials of lycopene against aging and aging-related disorders: a review. Food Sci Nutr 11:5701\u20135735","journal-title":"Food Sci Nutr"},{"key":"4049_CR52","doi-asserted-by":"publisher","first-page":"10180","DOI":"10.3748\/wjg.v22.i46.10180","volume":"22","author":"W Jiang","year":"2016","unstructured":"Jiang W, Guo M, Hai X (2016) Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat. World J Gastroenterol 22:10180\u201310188","journal-title":"World J Gastroenterol"},{"key":"4049_CR53","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201601083","author":"S Fenni","year":"2017","unstructured":"Fenni S, Hammou H, Astier J, Bonnet L, Karkeni E, Couturier C, Tourniaire F, Landrier J (2017) Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders. Mol Nutr Food Res. https:\/\/doi.org\/10.1002\/mnfr.201601083","journal-title":"Mol Nutr Food Res"},{"key":"4049_CR54","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jnutbio.2019.03.008","volume":"69","author":"J Wang","year":"2019","unstructured":"Wang J, Suo Y, Zhang J, Zou Q, Tan X, Yuan T, Liu Z, Liu X (2019) Lycopene supplementation attenuates western diet-induced body weight gain through increasing the expressions of thermogenic\/mitochondrial functional genes and improving insulin resistance in the adipose tissue of obese mice. J Nutr Biochem 69:63\u201372","journal-title":"J Nutr Biochem"},{"key":"4049_CR55","doi-asserted-by":"publisher","first-page":"360","DOI":"10.3389\/fphys.2018.00360","volume":"9","author":"T Cvitanovic Tomas","year":"2018","unstructured":"Cvitanovic Tomas T, Urlep Z, Moskon M, Mraz M, Rozman D (2018) LiverSex computational model: sexual aspects in hepatic metabolism and abnormalities. Front Physiol 9:360","journal-title":"Front Physiol"},{"key":"4049_CR56","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1002\/hep.30626","volume":"70","author":"A Lonardo","year":"2019","unstructured":"Lonardo A, Nascimbeni F, Ballestri S, Fairweather D, Win S, Than TA, Abdelmalek MF, Suzuki A (2019) Sex differences in nonalcoholic fatty liver disease: state of the art and identification of research gaps. Hepatology 70:1457\u20131469","journal-title":"Hepatology"},{"key":"4049_CR57","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.freeradbiomed.2020.02.025","volume":"152","author":"Z Chen","year":"2020","unstructured":"Chen Z, Tian R, She Z, Cai J, Li H (2020) Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic Biol Med 152:116\u2013141","journal-title":"Free Radic Biol Med"},{"key":"4049_CR58","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/6252426","volume":"2024","author":"MO Shafe","year":"2024","unstructured":"Shafe MO, Gumede NM, Nyakudya TT, Chivandi E (2024) Lycopene: a potent antioxidant with multiple health benefits. J Nutr Metab 2024:6252426","journal-title":"J Nutr Metab"},{"key":"4049_CR59","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/s41575-023-00800-4","volume":"20","author":"ZM Younossi","year":"2023","unstructured":"Younossi ZM, Zelber-Sagi S, Henry L, Gerber LH (2023) Lifestyle interventions in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 20:708\u2013722","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"4049_CR60","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/8861126","author":"B Zanini","year":"2024","unstructured":"Zanini B, Benini F, Marullo M, Simonetto A, Rossi A, Cavagnoli P, Bonalumi A, Marconi S, Pigozzi MG, Gilioli G et al (2024) Mediterranean-oriented dietary intervention is effective to reduce liver steatosis in patients with nonalcoholic fatty liver disease: results from an Italian clinical trial. Int J Clin Pract. https:\/\/doi.org\/10.1155\/2024\/8861126","journal-title":"Int J Clin Pract"},{"key":"4049_CR61","doi-asserted-by":"publisher","DOI":"10.3390\/nu15102265","volume":"15","author":"HR Rocha","year":"2023","unstructured":"Rocha HR, Coelho MC, Gomes AM, Pintado ME (2023) Carotenoids diet: digestion, gut microbiota modulation, and inflammatory diseases. Nutrients 15:2265. https:\/\/doi.org\/10.3390\/nu15102265","journal-title":"Nutrients"},{"key":"4049_CR62","doi-asserted-by":"publisher","DOI":"10.3390\/foods14050794","volume":"14","author":"D Mou","year":"2025","unstructured":"Mou D, Ding D, Pu J, Zhou P, Cao E, Zhang X, Lan J, Ye L, Wen W (2025) Effects of dietary pretreatment with all-trans lycopene on lipopolysaccharide-induced jejunal inflammation: a multi-pathway phenomenon. Foods 14:794. https:\/\/doi.org\/10.3390\/foods14050794","journal-title":"Foods"},{"key":"4049_CR63","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1111\/jgh.12519","volume":"29","author":"K Shi","year":"2014","unstructured":"Shi K, Tang J, Zhu X, Ying L, Li D, Gao J, Fang Y, Li G, Song Y, Deng Z et al (2014) Controlled attenuation parameter for the detection of steatosis severity in chronic liver disease: a meta-analysis of diagnostic accuracy. J Gastroenterol Hepatol 29:1149\u20131158","journal-title":"J Gastroenterol Hepatol"},{"key":"4049_CR64","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.jhep.2016.12.022","volume":"66","author":"T Karlas","year":"2017","unstructured":"Karlas T, Petroff D, Sasso M, Fan J, Mi Y, de Ledinghen V, Kumar M, Lupsor-Platon M, Han K, Cardoso AC et al (2017) Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol 66:1022\u20131030","journal-title":"J Hepatol"}],"container-title":["European Journal of Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00394-026-04049-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00394-026-04049-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00394-026-04049-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:59:20Z","timestamp":1787065160000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00394-026-04049-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":64,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["4049"],"URL":"https:\/\/doi.org\/10.1007\/s00394-026-04049-w","relation":{},"ISSN":["1436-6207","1436-6215"],"issn-type":[{"value":"1436-6207","type":"print"},{"value":"1436-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]},"assertion":[{"value":"4 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Territorial Ethics Committee of the Calabria Region (protocol code number 124\/2022\/CE approved 21 April 2022). Written informed consent was obtained from all participants. The investigation conforms to the principles outlined in the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"189"}}