title: Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials.
abstract: OBJECTIVE
  In the absence of consistent clinical evidence, there are concerns that fructose contributes to non-alcoholic fatty liver disease (NAFLD). To determine the effect of fructose on markers of NAFLD, we conducted a systematic review and meta-analysis of controlled feeding trials.
  
  
  METHODS
  We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library (through 3 September 2013). We included relevant trials that involved a follow-up of ≥ 7 days. Two reviewers independently extracted relevant data. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean difference (SMD) for intrahepatocellular lipids (IHCL) and mean difference (MD) for alanine aminotransferase (ALT). Inter-study heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic).
  
  
  RESULTS
  Eligibility criteria were met by eight reports containing 13 trials in 260 healthy participants: seven isocaloric trials, in which fructose was exchanged isocalorically for other carbohydrates, and six hypercaloric trials, in which the diet was supplemented with excess energy (+21-35% energy) from high-dose fructose (+104-220 g/day). Although there was no effect of fructose in isocaloric trials, fructose in hypercaloric trials increased both IHCL (SMD=0.45 (95% confidence interval (CI): 0.18, 0.72)) and ALT (MD=4.94 U/l (95% CI: 0.03, 9.85)).
  
  
  CONCLUSIONS
  Few trials were available for inclusion, most of which were small, short (≤ 4 weeks), and of poor quality.
  
  
  CONCLUSIONS
  Isocaloric exchange of fructose for other carbohydrates does not induce NAFLD changes in healthy participants. Fructose providing excess energy at extreme doses, however, does raise IHCL and ALT, an effect that may be more attributable to excess energy than fructose. Larger, longer and higher-quality trials of the effect of fructose on histopathological NAFLD changes are required.
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Department of Human Biology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Chiu
authors.affiliation: 1] Department of Pathology and Molecular Medicine, Faculty of Health Sciences, Hamilton, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada [3] The Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Sievenpiper
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada [3] Department of Clinical Epidemiology & Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: R J
authors.initials: RJ
authors.lastname: de Souza
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada.
authors.forename: A I
authors.initials: AI
authors.lastname: Cozma
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Mirrahimi
authors.affiliation: 1] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada [2] Department of Undergraduate Medical Education (MD Program), Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: A J
authors.initials: AJ
authors.lastname: Carleton
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Ha
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Heart and Stroke Foundation of Ontario, Toronto, ON, Canada [3] American Heart Association, Dallas, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Di Buono
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada.
authors.forename: A L
authors.initials: AL
authors.lastname: Jenkins
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada [3] Keenan Research Center of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada [4] Division of Endocrinology, St Michael's Hospital, Toronto, ON, Canada [5] Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: L A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada [3] Keenan Research Center of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada [4] Division of Endocrinology, St Michael's Hospital, Toronto, ON, Canada [5] Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: T M S
authors.initials: TM
authors.lastname: Wolever
authors.affiliation: 1] Department of Pathology and Molecular Medicine, Faculty of Health Sciences, Hamilton, ON, Canada [2] Division of Clinical Chemistry and Immunology, Hamilton Regional Laboratory Medicine Program, Hamilton, ON, Canada.
authors.forename: A C
authors.initials: AC
authors.lastname: Don-Wauchope
authors.affiliation: 1] Department of Clinical Epidemiology & Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada [2] The Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [3] Child Health Evaluative Sciences (CHES), The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Beyene
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada [3] College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: C W C
authors.initials: CW
authors.lastname: Kendall
authors.affiliation: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [2] Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael's Hospital, Toronto, ON, Canada [3] Keenan Research Center of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada [4] Division of Endocrinology, St Michael's Hospital, Toronto, ON, Canada [5] Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: D J A
authors.initials: DJ
authors.lastname: Jenkins
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D016208:Databases, Factual; D005632:Fructose / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000473:pathology*; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic
chemical_list: D005632:Fructose; D000410:Alanine Transaminase