Effect of fructose instead of glucose or sucrose on cardiometabolic markers: a systematic review and meta-analysis of isoenergetic intervention trials.

CONTEXT Free, or added, sugars are considered important determinants in the pandemics of obesity and associated chronic diseases, and fructose has emerged as the sugar of main concern. OBJECTIVE The aim of this review was to assess the evidence of the effects of isoenergetic replacement of fructose or high-fructose corn syrup (HFCS) for glucose or sucrose on cardiometabolic markers in controlled dietary intervention trials. DATA SOURCES The electronic databases PubMed/MEDLINE, the Cochrane Library, and Embase were searched from 1980 to May 5, 2020. STUDY SELECTION Studies were eligible if they measured at least one of the following outcomes: total cholesterol, low- and high-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A1, apolipoprotein B, systolic blood pressure, diastolic blood pressure, fasting glucose, and body weight. DATA EXTRACTION For each outcome, the mean values and the corresponding measure of dispersion were extracted after the intervention or control diet. DATA ANALYSIS Fixed-effects and random-effects models were used to pool study-specific estimates. Between-study heterogeneity was assessed by the χ2 test and the I2 statistic and publication bias by the Egger test and funnel plots. RESULTS Twenty-five studies involving 1744 volunteers were identified. No significant effects were found when fructose or HFCS was substituted for glucose, except for a slight decrease in diastolic blood pressure when fructose was substituted for glucose. Similarly, no effects were found when fructose or HFCS was substituted for sucrose, except for a small increase, of uncertain clinical significance, of apolipoprotein B when HFCS was substituted for sucrose. CONCLUSIONS Isoenergetic substitution of fructose or HFCS for glucose or sucrose has no significant effect on most of the cardiometabolic markers investigated; however, some results were affected by residual between-study heterogeneity and studies with high or unclear risk of bias. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42016042930.