Adverse Metabolic Effects of Dietary Sugar

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 with an energy-balanced diet; 3) 0%, or 4) 25%
of energy requirement as HFCS-sweetened beverages with an ad libitum diet for 8 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.

Inclusion Criteria:

- BMI 22-28 kg/m2

- Self-reported stable body weight during the prior six months

Exclusion criteria:

- Fasting glucose >105 mg/dl

- Evidence of liver disorder [AST (Aspartate Aminotransferase) or ALT (Alanine
Aminotransferase)] >200% upper limit of normal range)

- Evidence of kidney disorder (>2.0mg/dl creatinine)

- Evidence of thyroid disorder (out of normal range)

- Systolic blood pressure consistently over 140mm Hg (mercury) or diastolic blood
pressure over 90mmHg

- Triglycerides > 200mg/dl

- LDL-C > 130mg/dl in combination with Chol:HDL > 4

- Hemoglobin < 8.5 g/dL

- Pregnant or lactating women

- Any other condition that, in the opinion of the investigators, would put the subject
at risk

- Current, prior (within 12 months), or anticipated use of any hypolipidemic or
anti-diabetic agents.

- Use of thyroid, anti-hypertensive, anti-depressant, weight loss medications or any
other medication which, in the opinion of the investigator, may confound study results

- Use of tobacco

- Strenuous exerciser (>3.5 hours/week at a level more vigorous than walking)

- Surgery for weight loss

- Diet exclusions: Food allergies, special dietary restrictions, food allergies, routine
consumption of less than 3 meals/day, routine ingestion of more than 2 sugar-sweetened
beverages or 1 alcoholic beverage/day, unwillingness to consume any food on study menu

- Hydrogen concentration in breath sample following consumption of HFCS-beverage during
screening >50ppm

- Veins that are assessed by the CCRC (Clinical Research Center) R.N.s as being
unsuitable for long-term infusions and multiple blood draws from a catheter.

- Pre-existing claustrophobia or metal implants that preclude MRI