{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:26:24Z","timestamp":1783995984935,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"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>Atherosclerotic cardiovascular diseases are preferential targets of healthy diet and preventive medicine partially through strategies to improve lipid profile and counteract oxidative metabolites. Ninety individuals with cardiovascular disease (CVD) risk factors were randomized (1:1:1 ratio) to three arms, according to a four-week run-in, eight-week intervention, and four-week follow up study, testing the effects of a lactofermented Annurca apple puree (lfAAP), compared to unfermented apple puree (AAP) or probiotic alone (LAB) on plasma lipid profile and trimethylamine-N-oxide (TMAO) levels. By comparing the treatments, data indicated for the subjects tested with lfAAP a higher variation of the following serum parameters, in respect to the other treatment groups: high density lipoprotein cholesterol (HDL-C), +61.8% (p = 0.0095); and TMAO levels, \u221263.1% (p = 0.0042). The present study would suggest lfAAP as an effective functional food for beneficial control of plasma HDL-C and TMAO levels.<\/jats:p>","DOI":"10.3390\/nu11010122","type":"journal-article","created":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T03:22:31Z","timestamp":1547090551000},"page":"122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Lactofermented Annurca Apple Puree as a Functional Food Indicated for the Control of Plasma Lipid and Oxidative Amine Levels: Results from a Randomised Clinical Trial"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0251-9936","authenticated-orcid":false,"given":"Gian Carlo","family":"Tenore","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cardarelli, Via Antonio Cardarelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Buonomo","sequence":"additional","affiliation":[{"name":"Coop. Samnium Medica, Viale C. Colombo, 18, 82037 Benevento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"D\u2019Avino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cardarelli, Via Antonio Cardarelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Ciampaglia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Maisto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Schisano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Bocchino","sequence":"additional","affiliation":[{"name":"UCCP (Unit\u00e0 Complessa Cure Primarie), Via Manzoni, San Giorgio del Sannio, 82100 Benevento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ettore","family":"Novellino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, Via D. 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Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.foodchem.2012.02.082","article-title":"Binding of polyphenols to plant cell wall analogues-Part 1: Anthocyanins","volume":"134","author":"Padayachee","year":"2012","journal-title":"Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1016\/j.foodchem.2012.07.004","article-title":"Binding of polyphenols to plant cell wall analogues-Part 2: Phenolic acids","volume":"135","author":"Padayachee","year":"2012","journal-title":"Food Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bbagen.2005.06.004","article-title":"Non-covalent interaction between procyanidins and apple cell wall material. Part III: Study on model polysaccharides","volume":"1725","author":"Bouchet","year":"2005","journal-title":"Bba-Gen Subj."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0141-8130(01)00155-6","article-title":"Interactions between apple cell walls and native apple polyphenols: Quantification and some consequences","volume":"29","author":"Renard","year":"2001","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_8","first-page":"1905","article-title":"Role of nutrition in preventing cancer","volume":"53","author":"Beliveau","year":"2007","journal-title":"Can. Fam. Physician"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16095","DOI":"10.3748\/wjg.v20.i43.16095","article-title":"Probiotics in dietary guidelines and clinical recommendations outside the European Union","volume":"20","author":"Ebner","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.copbio.2016.11.010","article-title":"Health benefits of fermented foods: Microbiota and beyond","volume":"44","author":"Marco","year":"2017","journal-title":"Curr. Opin. Biotech."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ray, R.C., and Ward, O.P. (2006). Microbial Biotechnology in Horticulture, CRC Press.","DOI":"10.1201\/9781482280432"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0168-1605(01)00709-7","article-title":"Impact of small scale fermentation technology on food safety in developing countries","volume":"75","author":"Motarjemi","year":"2002","journal-title":"Int. J. Food Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.foodres.2017.09.031","article-title":"Fruits and vegetables, as a source of nutritional compounds and phytochemicals: Changes in bioactive compounds during lactic fermentation","volume":"104","author":"Remize","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1007\/s00217-001-0450-5","article-title":"Nutritional improvement of beans (Phaseolus vulgaris) by natural fermentation","volume":"214","author":"Granito","year":"2002","journal-title":"Eur. Food Res. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1021\/jf034980t","article-title":"Effect of fermentation and autoclaving on dietary fiber fractions and anti nutritional factors of beans (Phaseolus vulgaris L.)","volume":"52","author":"Sanfiz","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/09637480120057585","article-title":"Studies on tape ketan-an Indonesian fermented rice food","volume":"52","author":"Siebenhandl","year":"2001","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.foodchem.2012.10.112","article-title":"Nutraceutical potential of polyphenolic fractions from Annurca apple (M. pumila Miller cv Annurca)","volume":"140","author":"Tenore","year":"2013","journal-title":"Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1002\/jsfa.8016","article-title":"Annurca (Malus pumila Miller cv. Annurca) apple as a functional food for the contribution to a healthy balance of plasma cholesterol levels: Results of a randomized clinical trial","volume":"97","author":"Tenore","year":"2017","journal-title":"J. Sci. Food Agric."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0308-8146(00)00306-X","article-title":"\u2018Annurca\u2019 apple fruit, a southern Italy apple cultivar: Textural properties and aroma composition","volume":"73","author":"Testoni","year":"2001","journal-title":"Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1002\/jsfa.3343","article-title":"Synbiotic potential of carrot juice supplemented with Lactobacillus spp. and inulin or fructooligosaccharides","volume":"88","author":"Nazzaro","year":"2008","journal-title":"J. Sci. Food Agric."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.jff.2018.02.020","article-title":"Effect of artichoke fermentation by probiotic strain Lactobacillus paracasei LMG P-22043 and of digestion process on polyphenols and antioxidant activity","volume":"45","author":"Garbetta","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.aca.2016.07.016","article-title":"Quantification of glycine betaine, choline and trimethylamine N-oxide in seawater particulates: Minimisation of seawater associated ion suppression","volume":"938","author":"Beale","year":"2016","journal-title":"Anal. Chim. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Little, R.J.A., and Rubin, D.B. (2002). Statistical Analysis with Missing Data, John Wiley & Sons, Inc.","DOI":"10.1002\/9781119013563"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/biostatistics\/kxh001","article-title":"Analyzing incomplete longitudinal clinical trial data","volume":"5","author":"Molenberghs","year":"2004","journal-title":"Biostatistics"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"O\u2019Kelly, M., and Ratitch, B. (2014). Clinical Trials with Missing Data: A Guide for Practitioners, John Wiley & Sons, Inc.","DOI":"10.1002\/9781118762516"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1177\/1740774512450098","article-title":"Including all individuals is not enough: Lessons for intention-to-treat analysis","volume":"9","author":"White","year":"2012","journal-title":"Clin. Trials"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1001\/jama.2013.879","article-title":"Reporting of patient-reported outcomes in randomized trials: The CONSORT PRO extension","volume":"309","author":"Calvert","year":"2013","journal-title":"J. Am. Med. Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S0014-5793(00)01211-4","article-title":"Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase","volume":"468","author":"Day","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Crozier, A. (2007). Plant Secondary Metabolites: Occurrence, Structure and Role in the Human Diet, Blackwell Publishing Ltd.","DOI":"10.1002\/9780470988558"},{"key":"ref_30","first-page":"814","article-title":"Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: A prognostic marker for incident cardiovascular events beyond traditional risk factors","volume":"38","author":"Li","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1111\/bph.13959","article-title":"Trimethylamine N-oxide: Breathe new life","volume":"175","author":"Subramaniam","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.nut.2015.05.006","article-title":"TMAO: A small molecule of great expectations","volume":"31","author":"Ufnal","year":"2015","journal-title":"Nutrition"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature09922","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"ref_34","first-page":"320","article-title":"Formation of methylamines from ingested choline and lecithin","volume":"225","author":"Zeisel","year":"1983","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cmet.2012.12.011","article-title":"Trimethylamine-N-Oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation","volume":"17","author":"Bennett","year":"2013","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.cmet.2014.10.006","article-title":"gamma-Butyrobetaine Is a proatherogenic intermediate in gut microbial metabolism of L-Carnitine to TMAO","volume":"20","author":"Koeth","year":"2014","journal-title":"Cell Metab."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lyu, M., Wang, Y.F., Fan, G.W., Wang, X.Y., Xu, S.Y., and Zhu, Y. (2017). Balancing herbal medicine and functional food for prevention and treatment of cardiometabolic diseases through modulating gut microbiota. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.02146"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6485","DOI":"10.1021\/jf902107d","article-title":"Interaction between phenolics and gut microbiota: Role in human health","volume":"57","author":"Selma","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.resmic.2006.07.004","article-title":"Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota","volume":"157","author":"Lee","year":"2006","journal-title":"Res. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1136\/gutjnl-2015-309957","article-title":"High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome","volume":"65","author":"Pellegrini","year":"2016","journal-title":"Gut"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev.mi.39.100185.001023","article-title":"Bacterial reduction of trimethylamine oxide","volume":"39","author":"Barrett","year":"1985","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Baugh, M.E., Steele, C.N., Angiletta, C.J., Mitchell, C.M., Neilson, A.P., Davy, B.M., Hulver, M.W., and Davy, K.P. (2018). Inulin supplementation does not reduce plasma trimethylamine n-oxide concentrations in individuals at risk for type 2 diabetes. Nutrients, 10.","DOI":"10.3390\/nu10060793"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1039\/C8FO00962G","article-title":"Impact of short-term flavanol supplementation on fasting plasma trimethylamine N-oxide concentrations in obese adults","volume":"9","author":"Angiletta","year":"2018","journal-title":"Food Func."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s11094-017-1600-9","article-title":"Comparative assessment of the prebiotic activity of some pectin polysaccharides","volume":"51","author":"Islamova","year":"2017","journal-title":"Pharm. Chem. J."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chung, W.S.F., Meijerink, M., Zeuner, B., Hoick, J., Louis, P., Meyer, A.S., Wells, J.M., Flint, H.J., and Duncan, S.H. (2017). Prebiotic potential of pectin and pectic oligosaccharides to promote anti-inflammatory commensal bacteria in the human colon. FEMS Microbiol. Ecol., 93.","DOI":"10.1093\/femsec\/fix127"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Vieira, A.T., Teixeira, M.M., and Martins, F.S. (2013). The role of probiotics and prebiotics in inducing gut immunity. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00445"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/1\/122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:24:30Z","timestamp":1760185470000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/1\/122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,9]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["nu11010122"],"URL":"https:\/\/doi.org\/10.3390\/nu11010122","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,9]]}}}