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To update the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease (low\u2010density lipoprotein cholesterol [LDL<\/jats:styled-content>]\u2010C, apolipoprotein B, non\u2010high\u2010density lipoprotein cholesterol [HDL<\/jats:styled-content>\u2010C]), and metabolic syndrome (triglycerides andHDL<\/jats:styled-content>\u2010C), we conducted a systematic review and meta\u2010analysis of controlled feeding trials.<\/jats:p><\/jats:sec>Methods and Results<\/jats:title>MEDLINE<\/jats:styled-content>,EMBASE<\/jats:styled-content>,CINHAL<\/jats:styled-content>, and the Cochrane Library were searched through July 7, 2015 for controlled feeding trials with follow\u2010up \u22657\u00a0days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids (LDL<\/jats:styled-content>\u2010C, apolipoprotein B, non\u2010HDL<\/jats:styled-content>\u2010C, triglycerides, andHDL<\/jats:styled-content>\u2010C) in participants of all health backgrounds. Two independent reviewers extracted relevant data. Data were pooled using random effects models and expressed as mean difference with 95%CI<\/jats:styled-content>. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2<\/jats:sup>statistic). Eligibility criteria were met by 51 isocaloric trials (n=943), in which fructose was provided in isocaloric exchange for other carbohydrates, and 8 hypercaloric trials (n=125), in which fructose supplemented control diets with excess calories compared to the control diets alone without the excess calories. Fructose had no effect onLDL<\/jats:styled-content>\u2010C, non\u2010HDL<\/jats:styled-content>\u2010C, apolipoprotein B, triglycerides, orHDL<\/jats:styled-content>\u2010C in isocaloric trials. However, in hypercaloric trials, fructose increased apolipoprotein B (n=2 trials; mean difference = 0.18\u00a0mmol\/L; 95%CI<\/jats:styled-content>: 0.05, 0.30;P<\/jats:italic>=0.005) and triglycerides (n=8 trials; mean difference = 0.26\u00a0mmol\/L; 95%CI<\/jats:styled-content>: 0.11, 0.41;P<\/jats:italic><0.001). The study is limited by small sample sizes, limited follow\u2010up, and low quality scores of the included trials.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Pooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories (+21% to 35% energy). When isocalorically exchanged for other carbohydrates, fructose had no adverse effects on blood lipids. More trials that are larger, longer, and higher quality are required.<\/jats:p><\/jats:sec>Clinical Trials Registration<\/jats:title>URL<\/jats:styled-content>:https:\/\/www.clinicaltrials.gov\/<\/jats:ext-link>. Unique Identifier:NCT<\/jats:styled-content>01363791.<\/jats:p><\/jats:sec>","DOI":"10.1161\/jaha.114.001700","type":"journal-article","created":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T03:03:28Z","timestamp":1441940608000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta\u2010Analysis of Controlled Feeding Trials"],"prefix":"10.1161","volume":"4","author":[{"given":"Laura","family":"Chiavaroli","sequence":"first","affiliation":[{"name":"Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada"},{"name":"Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell J.","family":"de Souza","sequence":"additional","affiliation":[{"name":"Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada"},{"name":"Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Ha","sequence":"additional","affiliation":[{"name":"Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada"},{"name":"Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian I.","family":"Cozma","sequence":"additional","affiliation":[{"name":"Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada"},{"name":"Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arash","family":"Mirrahimi","sequence":"additional","affiliation":[{"name":"Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada"},{"name":"School of Medicine, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Yu","sequence":"additional","affiliation":[{"name":"Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada"},{"name":"School of Dentistry, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Carleton","sequence":"additional","affiliation":[{"name":"Department of Undergraduate Medical Education (MD Program), Faculty of Medicine, University of Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Di Buono","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada"},{"name":"Heart and Stroke Foundation of Ontario, Toronto, ON, Canada"},{"name":"American Heart Association, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra L.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence A.","family":"Leiter","sequence":"additional","affiliation":[{"name":"Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada"},{"name":"Division of Endocrinology, St. Michael's Hospital, Toronto, ON, Canada"},{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada"},{"name":"Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada"},{"name":"Department of Medicine, Faculty of Medicine, University of Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M. 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