Objectives We aimed to quantify the effect of fructose in isocaloric exchange for other carbohydrates on total cholesterol (TC), LDL cholesterol (LDL-C), and (HDL-C) in adult humans.

Methods We searched PubMed, Embase and the Cochrane Library database up to December 2012 for human controlled feeding trials of isocaloric oral fructose exchange for other carbohydrates on cholesterol lasting ≥2 weeks. Weighted mean differences were calculated for changes from baseline cholesterol concentrations by using generic inverse variance random-effects models even where there was no evidence of between-study heterogeneity because these models give more conservative summary effectestimates in the presence of undetected residual heterogeneity than fixed-effects models. The Heyland Methodological Quality was used to assess study quality. Subgroup analyses and meta-regression were conducted to explore possible influence of study characteristics. Funnel plots and Egger’s linear regression test were conducted to detect publication bias.

Results Twenty-four trials (with a total of 474 subjects) were included in our meta-analysis. In an overall pooled estimate, fructose exerted no effect on TC, LDL-C and HDL-C. Meta-regression analysis indicated that fructose dose was positively correlated with the effect sizes of TC and LDL-C (TC regression coefficient = 0.16; 95% CI: 0.05, 0.27, P = 0.006; LDL-C regression coefficient = 0.14; 95% CI: 0.03, 0.26, P = 0.018). Subgroup analyses showed that isocaloric fructose exchange for carbohydrates could significantly increase TC by 12.97 mg/dL (95%CI: 4.66, 21.29; P = 0.002) and LDL-C by 11.59 mg/dL (95%CI: 4.39, 18.78; P = 0.002) at>100 g fructose/d but had no effect on TC and LDL-C when fructose intake was ≤100 g/d. Funnel plots and Egger’s test indicated no significant publication bias in the meta-analyses of TC, LDL cholesterol, and HDL cholesterol.

Conclusions The meta-analysis showed that very high fructose intake (>100 g/d) could lead to significantly increase in serum LDL-C and TC. This effect seems not to be dose-dependent when fructose is given at moderate or high dose of fructose (<100 g). Larger, longer and higher-quality human controlled feeding trials are needed to confirm these results.