title: Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.
abstract: BACKGROUND
  Debate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease (low-density lipoprotein cholesterol [LDL]-C, apolipoprotein B, non-high-density lipoprotein cholesterol [HDL-C]), and metabolic syndrome (triglycerides and HDL-C), we conducted a systematic review and meta-analysis of controlled feeding trials.
  
  
  RESULTS
  MEDLINE, EMBASE, CINHAL, and the Cochrane Library were searched through July 7, 2015 for controlled feeding trials with follow-up ≥7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids (LDL-C, apolipoprotein B, non-HDL-C, triglycerides, and HDL-C) 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. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) 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 on LDL-C, non-HDL-C, apolipoprotein B, triglycerides, or HDL-C in isocaloric trials. However, in hypercaloric trials, fructose increased apolipoprotein B (n=2 trials; mean difference = 0.18 mmol/L; 95% CI: 0.05, 0.30; P=0.005) and triglycerides (n=8 trials; mean difference = 0.26 mmol/L; 95% CI: 0.11, 0.41; P<0.001). The study is limited by small sample sizes, limited follow-up, and low quality scores of the included trials.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT01363791.
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.).
authors.forename: Laura
authors.initials: L
authors.lastname: Chiavaroli
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada (R.J.S., V.H., J.B.).
authors.forename: Russell J
authors.initials: RJ
authors.lastname: de Souza
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada (R.J.S., V.H., J.B.).
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ha
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.).
authors.forename: Adrian I
authors.initials: AI
authors.lastname: Cozma
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) School of Medicine, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada (A.M.).
authors.forename: Arash
authors.initials: A
authors.lastname: Mirrahimi
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.).
authors.forename: David D
authors.initials: DD
authors.lastname: Wang
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) School of Dentistry, University of Minnesota, Minneapolis, MN (M.Y.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Undergraduate Medical Education (MD Program), Faculty of Medicine, University of Toronto, ON, Canada (A.J.C.).
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Carleton
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Heart and Stroke Foundation of Ontario, Toronto, ON, Canada (M.D.B.) American Heart Association, Dallas, TX (M.D.B.).
authors.forename: Marco
authors.initials: M
authors.lastname: Di Buono
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.).
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Jenkins
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Division of Endocrinology, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., T.S.W., D.A.J., J.L.S.) Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Medicine, Faculty of Medicine, University of Toronto, ON, Canada (L.A.L., T.S.W., D.A.J.).
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Division of Endocrinology, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., T.S.W., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Medicine, Faculty of Medicine, University of Toronto, ON, Canada (L.A.L., T.S.W., D.A.J.).
authors.forename: Thomas M S
authors.initials: TM
authors.lastname: Wolever
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada (R.J.S., V.H., J.B.).
authors.forename: Joseph
authors.initials: J
authors.lastname: Beyene
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada (C.C.K.).
authors.forename: Cyril W C
authors.initials: CW
authors.lastname: Kendall
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Division of Endocrinology, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., T.S.W., D.A.J., J.L.S.) Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Medicine, Faculty of Medicine, University of Toronto, ON, Canada (L.A.L., T.S.W., D.A.J.).
authors.forename: David J A
authors.initials: DJ
authors.lastname: Jenkins
authors.affiliation: Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, ON, Canada (L.C., R.J.S., V.H., A.I.C., A.M., M.Y., A.L.J., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Division of Endocrinology, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., T.S.W., D.A.J., J.L.S.) Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada (L.A.L., D.A.J., J.L.S.) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada (L.C., A.I.C., D.D.W., M.D.B., L.A.L., T.S.W., C.C.K., D.A.J., J.L.S.) Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada (J.L.S.).
authors.forename: John L
authors.initials: JL
authors.lastname: Sievenpiper
mesh_terms: D053299:Apolipoprotein B-100 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018849:Controlled Clinical Trials as Topic; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000009:adverse effects; D050171:Dyslipidemias / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D002149:Energy Intake; D005632:Fructose / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008055:Lipids / Q000097:blood*; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology; D012307:Risk Factors; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004040:Dietary Carbohydrates; D008055:Lipids; D014280:Triglycerides; D005632:Fructose
keywords: lipids; meta‐analysis; nutrition