Summary
Researchers examined whether beverages sweetened with high-fructose corn syrup (HFCS) or sucrose have different metabolic effects in humans by conducting a double-blind, NIH-funded study involving 75 healthy adults. Participants consumed either HFCS-sweetened, sucrose-sweetened, or aspartame-sweetened control beverages—three servings per day providing 25% of daily energy needs—for 16 days, with metabolic testing performed before and after the intervention during controlled inpatient stays. Both sugar-sweetened beverages, regardless of whether the sweetener was sucrose or HFCS, produced clear signs of metabolic harm: hepatic fat increased, insulin sensitivity declined, and lipids, lipoproteins, and uric acid levels rose, even after adjusting for small changes in body weight. Sucrose increased liver fat relative to baseline and to aspartame, while HFCS showed a similar, though slightly smaller, increase. Measures of insulin sensitivity (Matsuda ISI and Predicted M ISI) declined after both HFCS and sucrose intake, but not after aspartame. Importantly, no metabolic outcome differed significantly between sucrose and HFCS, contradicting the idea that HFCS is uniquely harmful. Overall, just two weeks of consuming sugar-sweetened beverages—whether sweetened with sucrose or HFCS—was enough to impair liver fat metabolism, worsen insulin sensitivity, and elevate circulating cardiometabolic risk markers.
PMID: 34265055
PMCID: PMC8530743
DOI: 10.1210/clinem/dgab508
Abstract
Context
Studies in rodents and humans suggest that high-fructose corn syrup (HFCS)–sweetened diets promote greater metabolic dysfunction than sucrose-sweetened diets.
Objective
To compare the effects of consuming sucrose-sweetened beverage (SB), HFCS-SB, or a control beverage sweetened with aspartame on metabolic outcomes in humans.
Methods
A parallel, double-blinded, NIH-funded study. Experimental procedures were conducted during 3.5 days of inpatient residence with controlled feeding at a research clinic before (baseline) and after a 12-day outpatient intervention period. Seventy-five adults (18-40 years) were assigned to beverage groups matched for sex, body mass index (18-35 kg/m2), and fasting triglyceride, lipoprotein and insulin concentrations. The intervention was 3 servings/day of sucrose- or HFCS-SB providing 25% of energy requirement or aspartame-SB, consumed for 16 days. Main outcome measures were %hepatic lipid, Matsuda insulin sensitivity index (ISI), and Predicted M ISI.
Results
Sucrose-SB increased %hepatic lipid (absolute change: 0.6 ± 0.2%) compared with aspartame-SB (-0.2 ± 0.2%, P < 0.05) and compared with baseline (P < 0.001). HFCS-SB increased %hepatic lipid compared with baseline (0.4 ± 0.2%, P < 0.05). Compared with aspartame-SB, Matsuda ISI decreased after consumption of HFCS- (P < 0.01) and sucrose-SB (P < 0.01), and Predicted M ISI decreased after consumption of HFCS-SB (P < 0.05). Sucrose- and HFCS-SB increased plasma concentrations of lipids, lipoproteins, and uric acid compared with aspartame-SB. No outcomes were differentially affected by sucrose- compared with HFCS-SB. Beverage group effects remained significant when analyses were adjusted for changes in body weight.
Conclusion
Consumption of both sucrose- and HFCS-SB induced detrimental changes in hepatic lipid, insulin sensitivity, and circulating lipids, lipoproteins and uric acid in 2 weeks.
Sigala DM, Hieronimus B, Medici V, Lee V, Nunez MV, Bremer AA, Cox CL, Price CA, Benyam Y, Chaudhari AJ, Abdelhafez Y, McGahan JP, Goran MI, Sirlin CB, Pacini G, Tura A, Keim NL, Havel PJ, Stanhope KL. Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. J Clin Endocrinol Metab. 2021 Oct 21;106(11):3248-3264. doi: 10.1210/clinem/dgab508. PMID: 34265055; PMCID: PMC8530743.