Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

J Am Heart Assoc. 2015 Sep 10;4(9):e001700. doi: 10.1161/JAHA.114.001700.


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.

Methods and 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.

Clinical trials registration: URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT01363791.

Keywords: lipids; meta‐analysis; nutrition.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Apolipoprotein B-100 / blood
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Chi-Square Distribution
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Controlled Clinical Trials as Topic
  • Dietary Carbohydrates / administration & dosage*
  • Dietary Carbohydrates / adverse effects
  • Dyslipidemias / blood*
  • Dyslipidemias / diagnosis
  • Dyslipidemias / epidemiology
  • Energy Intake
  • Fructose / administration & dosage*
  • Fructose / adverse effects
  • Humans
  • Lipids / blood*
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / epidemiology
  • Risk Factors
  • Time Factors
  • Triglycerides / blood


  • APOB protein, human
  • Apolipoprotein B-100
  • Biomarkers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Dietary Carbohydrates
  • Lipids
  • Triglycerides
  • Fructose

Associated data

  • ClinicalTrials.gov/NCT01363791