Very High Fructose Intake Increases Serum LDL-Cholesterol and Total Cholesterol: A Meta-Analysis of Controlled Feeding Trials

Fructose is widely used as a sweetener in the production of many foods, yet the relation between fructose intake and cholesterol remains uncertain. In this study, we performed a systematic review and meta-analysis of human, controlled, feeding trials involving isocaloric fructose exchange for other carbohydrates to quantify the effects of fructose on serum total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in adult humans. Weighted mean differences were calculated to determine changes from baseline cholesterol concentrations by means of generic, inverse variance, random-effect models. The Hey land Methodological Quality was used to assess the quality of the study. Subgroup analyses and meta-regression were conducted to explore the possible influences of study characteristics. Twenty-four trials (with a total of 474 participants) were included in the meta-analysis. In an overall pooled estimate, it was shown that fructose exerted no effect on HDL-C. Meta-regression analysis indicated that fructose dose was positively correlated with the effect sizes of TC and LDL-C. Subgroup analyses showed that isocaloric fructose exchange for carbohydrates increased TO by 13.0 mg/dL [(95% Cl: 4.7, 21.3); P = 0.002] and LDL-C by 11.6 mg/dL [(95% Cl: 4.4, 18.9); P = 0.0021 at >100 g fructose/d. However, no effect was shown on TC or LDL-C when the fructose intake was :5100 g/d. In conclusion, it was shown that very high fructose intake (>100 g/d) increases serum LDL-C and TC concentrations. Larger, longer, and higher-quality human, controlled, feeding trials are needed to confirm these results.