It is not known whether consumption of excessive amounts of sugar can increase risk factors for cardiovascular disease or diabetes in the absence of increased food (caloric) intake and weight gain, nor whether the negative effects of sugar consumption are made worse when accompanied by weight gain. This study will investigate the effects of excess sugar when consumed with an energy-balanced diet that prevents weight gain, and the effects of excess sugar when consumed with a diet that can cause weight gain. The results will determine whether excess sugar consumption and excess caloric intake that lead to weight gain have independent and additive effects on risk factors for cardiovascular disease or diabetes, and will have the potential to influence dietary guidelines and public health policy.
Recent studies have demonstrated that consuming high fructose corn syrup (HFCS)- or sucrose-sweetened beverages increased lipid/lipoprotein risk factors for cardiovascular disease (CVD) in healthy adults compared with iso-caloric amounts of glucose or low-fat milk. The longest of these studies, which utilized a 6-month intervention, also showed increased liver and muscle TG and increased visceral adipose deposition. Neither of these studies found differences in weight gain between subjects consuming HFCS/sucrose beverages compared with control beverages. These results suggest that it is not just excess calories and weight gain that mediate the effects of dietary sugar/fructose on the development of metabolic disease; rather, dietary sugar per se is also a contributor. However, it is not known whether consumption of excessive amounts of sugar can increase risk factors for metabolic disease in the absence of positive energy balance and weight gain, nor whether the adverse effects of sugar consumption are exacerbated by weight gain. This study will compare the contribution of sugar with the contribution of energy level to the increases in risk factors for metabolic disease induced by consumption of HFCS-sweetened beverages under energy-balanced or ad libitum conditions. The investigators will measure risk factors and processes associated with metabolic disease in 4 groups of young, healthy adults who will consume 1) 0%, 2) or 25% of energy requirement as HFCS-sweetened beverages for 8 weeks with an energy-balanced diet for 6 weeks; 3) 0%, or 4) 25% of energy requirement as HFCS-sweetened beverages for 8 weeks with an ad libitum diet for 6 weeks. All diets, formulated to achieve a comparable macronutrient intake (55% energy as carbohydrate, 35% fat, 15% protein) among all 4 experimental groups, will be provided to the subjects throughout the entire study. The investigators hypothesize that under energy balanced (EB) condition that prevent body weight gain, consumption of HFCS-sweetened beverages will result in adverse metabolic effects compared with aspartame-sweetened beverages. Consumption of HFCS-sweetened beverages with the ad libitum (AL) diet will result in increased energy intake and body weight gain compared with aspartame-sweetened beverages, and will also result in adverse metabolic effects that are more marked than with consumption of HFCS-sweetened beverages with the energy-balanced diet. These results will demonstrate that consumption of HFCS-sweetened beverages increases risk for metabolic disease both directly, via the adverse effects of fructose on lipid and carbohydrate metabolism, and indirectly, via the effects of HFCS-sweetened beverages to promote excess energy intake and body weight gain. These findings will have the potential to influence dietary guidelines and public health policy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
36
High fructose corn syrup provided as 15% HFCS/85% water (weight/weight) fruit-flavored beverage
Aspartame provided as 0.04% aspartame/99.96% water (weight/weight), fruit-flavored beverage
Provided in quantities that equal energy requirement. Formulated such that the overall macronutrient intake; including beverage; equal 45%/5% energy requirement at complex/simple carbohydrate, 35% energy requirement as fat, 15% energy requirement as protein.
Provided in quantities that exceed energy requirement by approximately 25%. Formulated such that the overall macronutrient intake; including beverage; equals approximately 45%/5% energy requirement at complex/simple carbohydrate, 35% energy requirement as fat, 15% energy requirement as protein.
University of California, Davis
Davis, California, United States
Clinical Research Center
Sacramento, California, United States
Touro University California Translational Research Clinic and Student Health Clinic
Vallejo, California, United States
Change of de novo lipogenesis: palmitate tracer-to-tracee ratios by gas chromatography-mass spectrometry.
Blood samples are collected during 26-h isotopic acetate infusion. Blood samples are processed for determination of palmitate tracer-to-tracee ratios by gas chromatography-mass spectrometry.
Time frame: 22 hours at Baseline and 4-week Intervention
Change of endogenous glucose production measured by standard dilution techniques
Blood samples are collected during isotopic glucose infusion, and endogenous glucose production (glucose appearance) is measured by standard dilution techniques.
Time frame: 7 hours at Baseline and 4-week Intervention
Change of whole body insulin sensitivity
A variable 20% glucose infusion is adjusted to maintain euglycemia during insulin infusion in order to determine insulin-mediated glucose uptake.
Time frame: 3 hours at Baseline and 4-week Intervention
Change of liver lipid
Quantified from magnetic resonance imaging
Time frame: Baseline, 4-week Intervention and 8-week intervention
Change of fat oxidation
Fat oxidation is calculated from measures of oxygen consumption and carbon dioxide production by indirect calorimetry.
Time frame: 17 hours at Baseline and 4-week Intervention
Change of Very low density lipoprotein (VLDL)-triglyceride (TG) kinetics
During overnight fasting VLDL-TG kinetics will be determined using a prime constant infusion of isotopic glycerol. During the meal-feeding protocol, the washout kinetic enrichment of isotopic glycerol in the TG will be used to estimate VLDL-TG with a non-steady modeling approach.
Time frame: 22 hours at Baseline and 4-week Intervention
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