High-fructose corn syrup (HFCS) has been speculated to have stronger negative metabolic effects than sucrose. However, given the current equivocality in the field, the aim of the present study was to determine the impact of HFCS use compared to sucrose on anthropometric and metabolic parameters. We searched PubMed, Scopus, Cochrane Central and web of sciences, from database inception to May 2022. A random effects model and the generic inverse variance method were applied to assess the overall effect size. Heterogeneity analysis was performed using the Cochran Q test and the I2 index. Four articles, with 9 arms, containing 767 participants were included in this meta-analysis. Average HFCS and sucrose usage equated to 19% of daily caloric intake. Combined data from three studies indicated that HFCS intake does not significantly change the weight (weighted mean difference (WMD): −0.29 kg, 95% CI: −1.34, 0.77, I2 = 0%) when compared to the sucrose group. Concordant results were found for waist circumstance, body mass index, fat mass, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Moreover, overall results from three studies indicated a significant increase in CRP levels (WMD: 0.27 mg/l, 95% CI: 0.02, 0.52, I2 = 23%) in the HFCS group compared to sucrose. In conclusion, analysis of data from the literature suggests that HFCS consumption was associated with a higher level of CRP compared to sucrose, whilst no significant changes between the two sweeteners were evident in other anthropometric and metabolic parameters.
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