title: The ecologic validity of fructose feeding trials: supraphysiological feeding of fructose in human trials requires careful consideration when drawing conclusions on cardiometabolic risk.
abstract: BACKGROUND
  Select trials of fructose overfeeding have been used to implicate fructose as a driver of cardiometabolic risk.
  
  
  OBJECTIVE
  We examined temporal trends of fructose dose in human controlled feeding trials of fructose and cardiometabolic risk.
  
  
  METHODS
  We combined studies from eight meta-analyses on fructose and cardiometabolic risk to assess the average fructose dose used in these trials. Two types of trials were identified: (1) substitution trials, in which energy from fructose was exchanged with equal energy from other carbohydrates and (2) addition trials, in which energy from fructose supplemented a diet compared to the diet alone.
  
  
  RESULTS
  We included 64 substitution trials and 16 addition trials. The weighted average fructose dose in substitution trials was 101.7 g/day (95% CI: 98.4-105.1 g/day), and the weighted average fructose dose in addition trials was 187.3 g/day (95% CI: 181.4-192.9 g/day).
  
  
  CONCLUSIONS
  Average fructose dose in substitution and addition trials greatly exceed national levels of reported fructose intake (49 ± 1.0 g/day) (NHANES 1977-2004). Future trials using fructose doses at real world levels are needed.
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto , Toronto, ON , Canada ; Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital , Toronto, ON , Canada.
authors.forename: Vivian L
authors.initials: VL
authors.lastname: Choo
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto , Toronto, ON , Canada ; Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital , Toronto, ON , Canada ; Division of Endocrinology and Metabolism, Department of Medicine, St. Michael's Hospital , Toronto, ON , Canada.
authors.forename: John L
authors.initials: JL
authors.lastname: Sievenpiper
keywords: HFCS; cardiometabolic risk; dose; fructose; meta-analysis