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

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 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: NCT 01363791.