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Greater Understanding of How High Fructose Corn Syrup Enhances Metabolic Risk Factors

MedicalResearch.com Interview with:

Kimber L. Stanhope PhD RD
Department of Molecular Biosciences
School of Veterinary Medicine
University of California

Dr. Bettina Hieronimus PhD
Institute of Child Nutrition
Max Rubner-Institut,
Federal Research Institute of Nutrition and Food

MedicalResearch.com: What is the background for this study?  

Response: Sugar consumption is associated with increased body weight and other metabolic diseases. Fructose in particular seems to be detrimental to health as it causes higher increases in blood lipids compared to glucose.

Our study assessed the effects of sugar consumption on cardiometabolic risk factors. We compared the effects of consuming glucose, two different doses of fructose or high fructose corn syrup (HFCS) with a non-caloric sweetener. Our subjects were healthy young individuals who drank three sweetened beverages per day over the course of two weeks.

MedicalResearch.com: What are the main findings?

Response: Our finding was unexpected because fructose is metabolized differently from glucose, with the important difference being where. Most of the fructose we consume is metabolized in the liver immediately after it is absorbed from the gut. This is because the enzyme responsible for how much fructose is pulled out of the blood by the liver is always turned on, even when the liver is well-stocked with energy and glycogen and doesn’t need anymore. Therefore, a big dose of fructose leads to an overload of fructose in the liver that ramps up uric acid and fat production and leads to increases in downstream risk factors. In contrast, the enzyme responsible for how much glucose is pulled out of the blood by the liver is only turned on when the liver needs energy. Therefore, a big dose of glucose does not overload the liver, rather most of the glucose gets used by the entire body. So, what we expected to find was a consistent pattern in which fructose, the sugar that leads to the greatest fructose overload in the liver, leads to the highest increases in risk factors, with HFCS second and glucose third. To find that HFCS caused the highest increases in some risk factors, including those that many scientists believe are the most predictive of heart disease, was surprising. To demonstrate statistically that this effect was due to a synergy between fructose and glucose when co-ingested as HFCS, was novel.

The two doses (17.5 and 25% of energy requirement) of fructose and HFCS that were consumed by our subjects were higher than the amount of added sugar consumed by the average American (~15% of daily energy). However, the added sugar intake reported by participants in the National Health and Nutrition Examination Survey suggest that about 40% of the adults in this country compared to the US average sugar consumption consume more than 17% of their daily energy as added sugar (Wang, JAMA IM, 2014 LINK: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1899558). Furthermore, our published results document that HFCS has a linear dose response effect of risk factors, with even a 10% dose causing increases in risk factors compared to pre-study levels (Stanhope AJCN, 2015 LINK: https://academic.oup.com/ajcn/article/101/6/1144/4564534).

MedicalResearch.com: What should readers take away from your report?

Response: The biggest take away for us was the unexpected finding that certain blood risk factors were more increased when the subjects consumed high fructose corn syrup compared to the same amount of pure fructose. Nevertheless, we do not want these novel findings to distract consumers from what we already knew—the excessive amounts of sugar added to our processed foods are not good for you, whatever the type.   

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: The findings in our study where unexpected and not an aim of the study and they need to be confirmed in the future. Future research should consider our proposed interaction mechanism and put emphasis on postprandial glucose levels and possible non-enzymatic glycation. This can be assessed by testing established markers like HbA1c, fuctoseamine or LDL-particle glycation.

Independent of sugar, our study is another example that food and food compounds have to be studied in real-life applications. While the assessment of individual food components is essential in understanding specific mechanisms, these studies can only tell us so much. Interactions and cross talks between food components are important to consider. These Interactions make our field highly complex and challenging but that is what fascinates me about nutrition.

MedicalResearch.com: Is there anything else you would like to add? 

Response: Considering all we know about the detrimental effects sugar has on health it is surprising how little is done to limit the use of sugar in foods and food products. Our study puts further emphasis on the need to implement public health strategies to restrict sugar consumption. 


Synergistic effects of fructose and glucose on lipoprotein risk factors for cardiovascular disease in young adults Bettina Hieronimus ValentinaMedici Andrew A.Bremer VivienLee Marinelle V.NunezcDesiree M.Sigala Nancy L.Keim Peter J.Havel Kimber L.Stanhope


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Sep 29, 2020 @ 11:28 am

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