Orange Juice And Sugar Intervention Study

Specific Aims: There is considerable epidemiological evidence that demonstrates associations
between added sugar/sugar-sweetened beverage consumption and increased risk for or prevalence
of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes (T2D), metabolic
syndrome, and gout. Especially concerning is recent evidence from National Health and
Nutrition Examination Survey III that demonstrates that there is increased risk of CVD
mortality with increased intake of added sugar across quintiles (Yang, 2014). Even the US
mean added sugar intake, 15% of daily calories, was associated with an 18% increase in risk
of CVD mortality over 15 years. The results from the investigator's recently completed study
(1R01 HL09133) corroborate these findings (Stanhope, 2015). They demonstrate that
supplementing the ad libitum diets of young adults with beverages containing 0, 10, 17.5 or
25% of daily energy requirement (Ereq) as high fructose corn syrup (HFCS) affects
lipid/lipoprotein risk factors for CVD in a dose response manner. Specifically, levels of
nonHDL-cholesterol(C), LDL-C, apolipoprotein B (apoB), and postprandial triglycerides (TG)
increased linearly over a 2-week period with increasing doses of HFCS. Furthermore, even the
participants consuming the 10% Ereq dose exhibited increased levels of these risk factors
compared to baseline.

These and similar results have helped to lead to reductions in soda consumption in this
country, and new dietary guidelines and FDA food labeling requirements to promote reductions
in added sugar consumption. However, there are gaps in knowledge about other sugar-containing
foods that lead to public confusion concerning healthier options for soda, and impede further
progress in implementing public health policies that will promote further reductions in soda
consumption. One such food is naturally-sweetened fruit juice. The amount of sugar in fruit
juice is comparable to the amount in soda. Because of this, a consumer seeking answers on the
internet will find many articles in which experts state or suggest that the effects of
consuming fruit juice are as detrimental as or even worse than those of soda. However, in
contrast to soda, fruit juice contains micronutrients and bioactives that may promote health.
Therefore the consumer can also find numerous articles on the internet where the health
benefits of fruit juice and these bioactives are extolled. There are a limited number of
clinical dietary intervention studies that have directly compared the metabolic effects of
consuming fruit juice and sugar-sweetened beverage, and their results are not conclusive.
Thus we will pursue the following Specific Aims:

1. Specific Aim 1: To compare the weight-independent effects of consuming 25%Ereq as orange
juice or sugar-sweetened beverages for 4 weeks on risk factors for CVD and other chronic
disease in normal weight and overweight men and women.

2. Specific Aim 2: To mechanistically compare the weight-independent effects of consuming
25%Ereq as orange juice or sugar-sweetened beverages on metabolic processes associated
with the development of CVD and T2D in normal weight and overweight men and women.

3. Specific Aim 3: To relate the changes assessed under Specific Aims 1 and 2 to the
changes in the urinary levels of metabolites and catabolites of the main flavanones in
orange juice, hesperetin and naringenin.

Inclusion Criteria: men and pre-menopausal women Body mass index: 20-35 kg/m2 Body weight >
than 50 kg Self-reported stable body weight during the prior six months

Exclusion Criteria:

Fasting glucose >125 mg/dl Evidence of liver disorder (AST or ALT >200% upper limit of
normal range) Evidence of kidney disorder (>2.0 mg/dl creatinine) Evidence of thyroid
disorder (out of normal range) Systolic blood pressure consistently over 140 mmHg or
diastolic blood pressure over 90 mmHg Triglycerides > 400 mg/dl LDL-C > 160 mg/dl in
combination with Chol:HDL > 4 Hemoglobin < 10 g/dL Pregnant or lactating women 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, 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
Veins that are assessed by the 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 magnetic resonance imaging Any
other condition that, in the opinion of the investigators, would put the subject at risk