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Consequences of fructose consumption not so sweet

PIONEERING STUDIES by nutritional biologist Kimber Stanhope conducted with the Clinical and Translational Science Center (CTSC) are revealing new information about the metabolic effects of sugar consumption, and point to a possible cause-and-effect relationship between fructose intake and cardiovascular disease. Stanhope anticipates that findings from a study she conducted in 2005, and an ongoing investigation that will continue through 2015, may provide important new information for revised nutritional guidelines for safe upper limits of sugar consumption. 

Research studies that Stanhope and her colleagues have published in scientific journals attracted the attention of CBS television’s 60 Minutes program. Producers at 60 Minutes dispatched a news crew to the CTSC Clinical Research Center (CCRC) at the Sacramento VA Medical Center to observe research subjects participating in Stanhope’s current study. 

The earlier research, also conducted at the CCRC, compared the effects of consuming high levels of glucose or fructose, constituting 25 percent of each participant’s energy intake. In that closely controlled study, 32 overweight subjects between 40 and 72 years of age lived during a two-week baseline period at the CCRC and participated in numerous experimental procedures while they consumed weight maintaining diets high in complex carbohydrate. They subsequently returned to their homes for eight weeks and drank either a glucose- or fructose-sweetened beverage with each meal. They then returned for another carefully administered two-week period at the CCRC, during which all the same experimental procedures were repeated and they consumed weight-maintaining diets that included the glucose- or fructose-sweetened beverages. 

“Study participants who drank fructose had increased lipid levels, decreased insulin sensitivity and increased levels of the fat that surrounds visceral organs, and they exhibited increased denovo lipogenesis – the process by which the liver turns sugar into fat,” said Stanhope, a registered dietitian and associate project scientist in the School of Veterinary Medicine’s Department of Molecular Biosciences. 

“None of these changes were seen in the group that drank the glucose-sweetened beverages. The study is important because it shows very clear metabolic differences between glucose and fructose. That difference had not been well documented in humans until this study,” Stanhope added. 

The current study, even more ambitious, encompasses 200 subjects aged 18 to 40, who range from normal weight to overweight. Participants are organized into eight research study groups to compare the effects of commonly consumed sugars – high-fructose corn syrup (HFCS) and sucrose – with those of glucose and fructose. Participants each begin with three days of baseline study at the CCRC, followed by a 12-day outpatient period and conclude with a return visit to the CCRC. Even though the study is still under way, initial results were published in the Journal of Clinical Endocrinology and Metabolism in October 2011. “Early results from the first 48 subjects showed very clearly that beverages sweetened with high-fructose corn syrup increased lipids – risk factors for cardiovascular disease – comparably to fructose and significantly more than glucose does. That is important because these results – even more directly than our first study – suggest that the association between high-sugar diets and cardiovascular disease may specifically be due to cause and effect,” Stanhope said. “Two weeks after giving the subjects high-fructose corn syrup, we saw an increase in the risk factors for cardiovascular disease, specifically LDL cholesterol and apolipoprotein-B.” 

Stanhope’s collaborators on these studies include principal investigator Peter Havel, a UC Davis professor of molecular biosciences and nutrition; Nancy Keim at the USDA Western Human Nutrition Research Center; and Lars Berglund, John McGahan and Valentina Medici of the UC Davis School of Medicine. Throughout the studies, CCRC’s research nursing team managed all subject care activity and implemented the protocol. “Our nurses assessed eligibility, collected and processed more than 200 blood specimens for serial blood sampling, conducted oral glucose tolerance tests and heparin trials, collected and processed urine samples, dispensed study beverages as outlined in the protocol, and ensured safety and protocol adherence,” said registered nurse and CCRC Associate Director Nicole Mullen. The CCRC’s nurse practitioner prepared drafts of physician orders and nursing flow sheets that mirrored the IRB-approved protocol; gathered medical histories from subjects and conducted physical exams; conveyed information to study physicians; and performed the gluteal adipose tissue biopsies. 

“Our exercise physiologist conducted DEXA scans, measured total body water using a bioimpedance spectroscopy device, conducted metabolic testing, and compiled data for the principal investigator monthly,” Mullen added. Further, the CCRC’s dietitian supervised meal preparation and trained the study staff in food-handling safety and labeling regulations. 

Stanhope credits the CTSC staff and the CCRC facilities for contributing to the success of her studies. 

“The reasons we were able to show the differences so clearly are partly related to how carefully the study was controlled using the CCRC facilities,” Stanhope said. She is preparing grant proposals for two more studies that she plans to also conduct at the CCRC. 

The project described is supported by the National Center for Research Resources through grant #UL1RR024146 and the National Center for Advancing Translational Sciences, National Institutes of Health.