Fructose-containing sugars and metabolic risk: a systematic review and meta-analysis

Abstract

Background: Fructose-containing sugars are widely consumed, yet their metabolic effects remain debated. Objective: This meta-analysis aimed to evaluate the impact of different fructose-containing sugars on glycaemic control, lipid profiles, and uric acid levels in adults. Methods: A total of 17 study codes from seven clinical trials were included, with intervention durations rang-ing from 7 h to 49 days. Interventions were classified as fructose, fructose-glucose mixtures (F/G), honey, or sucrose. Comparators varied and included unsweetened beverages, artificial sweeteners, and habitual diets. Meta-analyses using random-effects models assessed outcomes including fasting blood glucose (FBG), serum insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL-c), and uric acid. Effect sizes were reported as Hedges’ g. Results: Fructose-glucose mixtures intake significantly increased FBG (Hedges’ g = 0.474, P = 0.002) and serum insulin (Hedges’ g = 0.592, P < 0.001), while fructose, honey, and sucrose showed no significant effects. Monosaccharide intake modestly increased insulin (P = 0.006). Fructose and sucrose alone did not affect TC, but their combined intake resulted in a significant increase (Hedges’ g = 0.412, P = 0.009). No significant changes were observed in LDL-c, VLDL-c, or pooled metabolic outcomes. Fructose intake was strongly associated with increased uric acid (Hedges’ g = 1.628, P < 0.001), and pooled analysis of fructose, F/G, and honey also showed a significant increase (Hedges’ g = 0.550, P = 0.028). Conclusion: The short-term consumption of added sugars – fructose, sucrose, and F/G mixtures – had minimal effects on FBG, insulin, triglycerides (TG), non-esterified fatty acids (NEFAs), high-density lipoprotein cholesterol (HDL-c), and VLDL-c. However, significant increases in TC and LDL-c were observed, particularly with fructose and sucrose, indicating adverse effects on lipid metabolism. Some fructose interventions, especially those using high-fructose corn syrup, also showed marked increases in uric acid. While acute metabolic changes were limited, these findings suggest that regular intake of added sugars may elevate cardiometabolic risk. Long-term studies are warranted to clarify chronic effects and inform dietary guidelines.