The dose-response effects of consuming high fructose corn syrup-sweetened beverages on hepatic lipid content and insulin sensitivity in young adults

Authors: SIGALA, DESIREE - University Of California, Davis; HIERONIMUS, BETTINA - University Of California, Davis; MEDICI, VALENTINA - University Of California, Davis; LEE, VIVIEN - University Of California, Davis; NUNEZ, MARINELLE - University Of California, Davis; BREMER, ANDREW - University Of California, Davis; COX, CHAD - California State University; PRICE, CANDICE - University Of California, Davis; BENYAM, YANET - University Of California, Davis; ABDELHAFEZ, YASSER - University Of California, Davis; MCGAHAN, JOHN - University Of California, Davis; Keim, Nancy; GORAN, MICHAEL - Children'S Hospital Los Angeles; PARCINI, GIOVANNI - Consiglio Nazionale Delle Ricerche; TURA, ANDREA - Consiglio Nazionale Delle Ricerche; SIRLIN, CLAUDE - University Of California, San Diego; CHAUDHARI, ABHIJIT - University Of California, Davis; HAVEL, PETER - University Of California, Davis; STANHOPE, KIMBER - University Of California, Davis

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/10/2022
Publication Date: 4/15/2022
Citation: Sigala, D.M., Hieronimus, B., Medici, V., Lee, V., Nunez, M.V., Bremer, A.A., Cox, C.L., Price, C.A., Benyam, Y., Abdelhafez, Y., Mcgahan, J.P., Keim, N.L., Goran, M., Parcini, G., Tura, A., Sirlin, C.B., Chaudhari, A.J., Havel, P.J., Stanhope, K.L. 2022. The dose-response effects of consuming high fructose corn syrup-sweetened beverages on hepatic lipid content and insulin sensitivity in young adults. Nutrients. 14(8). Article 1648. https://doi.org/10.3390/nu14081648.
DOI: https://doi.org/10.3390/nu14081648

Interpretive Summary: There is strong scientific evidence that the consumption of sugar-sweetened beverages increases multiple risk factors for chronic disease. However more information is needed to understand what amount of these beverages is associated with detrimental effects, and to identify key changes in physiology that may contribute to these effects. In this study it was determined that fat accumulated in the liver in just two weeks with a dose of high fructose corn syrup (HFCS) as low as 10% of total caloric intake, and at higher HFCS doses of 17.5% and 25% of caloric intake more liver fat accumulated as dose increased. This HFCS dose response of liver fat coincided with measures of poor blood glucose control, also in a dose response manner. These results contribute to the strong and growing body of evidence that increased consumption of sugar-sweetened beverages heightens risk for non-alcoholic fatty liver diseased and type 2 diabetes.

Technical Abstract: Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for 2 weeks on hepatic lipid content and insulin sensitivity in young (18-40 years) adults (BMI 18-35 kg/m2). In a parallel, double-blinded study, participants consumed 3 beverages/day providing 25% (n=28), 17.5% (n=16), 10% (n=18), or 0% (aspartame: n=23) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (P = 0.015) and OGTT glucose and insulin AUCs during OGTT (both P = 0.0004) and for decreases of the Matsuda (P = 0.0087) and Predicted M (P = 0.0027) indices of insulin sensitivity. These dose-response effects strengthen the mechanistic evidence implicating consumption of sugar-SB as a contributor to the metabolic dysregulation that increases risk for nonalcoholic fatty liver disease and type 2 diabetes.