Synergistic effects of fructose and glucose on lipoprotein risk factors for cardiovascular disease in young adults

Authors: HIERONIMUS, BETTINA - Max Rubner-Institut (MRI); MEDICI, VALENTINA - University Of California, Davis; BREMER, ANDREW - National Institutes Of Health (NIH); LEE, VIVIEN - University Of California, Davis; NUNEZ, MARINELLE - University Of California, Davis; SIGALA, DESIREE - University Of California, Davis; Keim, Nancy; HAVEL, PETER - University Of California, Davis; STANHOPE, KIMBER - University Of California, Davis

Submitted to: Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2020
Publication Date: 9/9/2020
Citation: Hieronimus, B., Medici, V., Bremer, A.A., Lee, V., Nunez, M.V., Sigala, D.M., Keim, N.L., Havel, P.J., Stanhope, K.L. 2020. Synergistic effects of fructose and glucose on lipoprotein risk factors for cardiovascular disease in young adults. Metabolism. 112. Article 154356. https://doi.org/10.1016/j.metabol.2020.154356.
DOI: https://doi.org/10.1016/j.metabol.2020.154356

Interpretive Summary: Consumption of sweeteners containing fructose has increased dramatically in the American diet over the past 3 decades, in parallel with the increasing incidence of obesity and diseases associated with obesity such as cardiovascular disease. Young adults have high consumption of sweeteners in the form of sugar-sweetened beverages. We focused on this age group to determine the effects of consuming large quantities of beverages sweetened with the simple sugars, fructose, glucose, or high fructose corn syrup (HFCS) at levels between 17.5 or 25% of energy needs, over a 2-week period, on measures of cardiovascular risk. We found that fructose alone increased the amount of triglycerides circulating in blood over a 24-hour period. LDL-cholesterol and its associated apolipoprotein, apoB, were elevated when both glucose and fructose were ingested together, namely with HFCS. While fructose alone increased the risk factors, the co-ingestion of fructose and glucose together led to the highest levels of the most recognized risk factor, LDL-cholesterol. Our findings, along with other emerging data regarding sugar-sweetened beverages, suggest that new, feasible strategies to limit the consumption of added sugars in beverages are needed.

Technical Abstract: We compared the effects of consuming fructose or glucose or their combination, high fructose corn syrup (HFCS), on cardiometabolic risk factors. Adults (18–40 years; BMI 18–35 kg/m2) participated in a parallel-armed, double-blinded dietary intervention trial during which beverages sweetened with aspartame or with 25% of energy requirement (ereq) glucose, fructose or HFCS, or with 17·5% ereq fructose or HFCS were consumed for two weeks. Groups were matched for sex, baseline BMI and plasma lipid/lipoprotein concentrations. 24-h serial blood samples were collected during inpatient testing at the beginning and end of study. The primary outcomes were 24h triglyceride AUC and LDL-cholesterol (C), and apolipoprotein (apo)B. We tested for an interaction between fructose and glucose in post hoc analyses. The study was registered with clinicaltrials.gov, identifier NCT01103921. We included 145 subjects (aged 26·0±5·8; body mass index 25·±3·7) who completed the study during the time from October 2008 to February 2014. 24h triglyceride tended to be more increased by fructose (25%: 6·66 mmol/Lx24h 95% CI [1·90 to 11·63], P 0·0013, 17·5%: 6·93 mmol/Lx24h 95% CI [1·64 to 12·12], P 0·0024 versus aspartame) than HFCS (25%: 4·68 mmol/Lx24h 95% CI [-0·18 to 9·55], P 0·066, 17·5%: 4·07 mmol/Lx24h 95% CI [-1·66 to 9·81], P 0·319 versus aspartame). LDL-C tended to be more increased by HFCS (25%: 0·46 mmol/L 95% CI [0·16 to 0·77] , P 0·0002, 17·5%: 0·29 mmol/L 95% CI [-0·06 to 0·64], P 0·289 versus aspartame) than fructose (25%: 0·33 mmol/L 95% CI [0·03 to 0·63], P 0·023, 17·5%: 0·23 mmol/L 95% CI [ 0·09 to 0·55], P 0·156), as was apoB (HFCS-25%: 0·108 g/L 95%CI [0·032 to 0·184], P 0·001, 17·5%: 0·046 g/L 95%CI [-0·035 to 0·127], P 0·571; fructose 25%: 0·072 g/L 95%CI [-0·004 to 0·148], P 0·074, 17·5%: 0·049 g/L 95%CI [-0·040 to 0·137], P 0·604 versus aspartame). The post-hoc analyses showed significant interactive effect of fructose*glucose on LDL-C and apoB (both P<0·01), but not on 24h triglyceride (P 0·340). While sole consumption of fructose led to increases in risk factors, those increases appear to be exacerbated for several risk factors when fructose is co-ingested with glucose. Our findings suggest that HFCS is not less harmful than isocaloric amounts of pure fructose and provide further support for the urgency to implement strategies to limit added sugar consumption.