The objectives of this proposal are to address the gaps in knowledge regarding the metabolic effects of consuming orange juice, the most frequently consumed fruit juice in this country, compared to sugar-sweetened beverage.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
56
Commercially-available ready-to-serve refrigerated orange juice
Sugar-sweetened water flavored with Kool-Aid (TM)
University of California, Davis
Davis, California, United States
Fasting Low Density Lipoprotein Cholesterol (LDL-C)
Absolute change of plasma LDL-C concentration (4 week value - 0 week value)
Time frame: 4 weeks
Postprandial Low Density Lipoprotein Cholesterol (LDL-C)
Absolute change of plasma postprandial LDL-C concentration (4 week value - 0 week value)
Time frame: 4 weeks
Fasting Apolipoprotein B (apoB)
Absolute change of plasma apoB concentration (4 week value - 0 week value)
Time frame: 4 weeks
Postprandial Apolipoprotein B (apoB)
Absolute change of plasma postprandial apoB concentration (4 week value - 0 week value)
Time frame: 4 weeks
Fasting Uric Acid
Absolute change of plasma uric acid concentration (4 week value - 0 week value)
Time frame: 4 weeks
Postprandial Uric Acid
Absolute change of post-dinner 4-hour AUC plasma uric acid concentration (4 week value - 0 week value)
Time frame: 4 weeks
Fasting Apolipoprotein CIII (apoCIII)
Absolute change of fasting plasma apoCIII concentration (4 week value - 0 week value)
Time frame: 4 weeks
Postprandial Apolipoprotein CIII (apoCIII)
Absolute change of plasma postprandial apoCIII concentration (4 week value - 0 week value)
Time frame: 4 weeks
Postprandial Triglyceride
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Absolute change of 4-h post-dinner AUC plasma triglyceride concentration (4 week value - 0 week value)
Time frame: 4 weeks
Hepatic Triglyceride
Absolute change of % hepatic triglyceride (4 week value - 0 week value)
Time frame: 4 weeks
Matsuda Insulin Sensitivity Index (ISI)
Absolute change of Matsuda ISI (4 week value - 0 week value). The Matsuda Index is a ratio of glucose and insulin levels during oral glucose tolerance test. It is calculated using fasting and mean glucose and insulin measurements, but the units of these measurements cancel out in the formula. A Matsuda value less than 2.5 may indicate insulin resistance, thus a lowering of the Matsuda index is a detrimental outcome. At baseline the Matsuda index in the participants for which it was assessed ranged from 1.4 to 7.8 (mean = 3.7, standard deviation = 1.6).
Time frame: 4 week
Postprandial de Novo Lipogenesis
Absolute change of 8-hour area under the curve (AUC) percentage fractional rate postprandial de novo lipogenesis DNL (4 week value - 0 week value)
Time frame: 4 weeks
M Value During Hyperinsulinemic Euglycemic Clamp
Absolute change of M value (glucose infusion rate during final 30 minute steady state)/ fat free body mass (kg) (4 week value - 0 week value)
Time frame: 4 weeks
Fasting Triglyceride
Absolute change of plasma fasting triglyceride concentration (4 week value - 0 week value)
Time frame: 4 weeks
3-(3'-Hydroxy-4'-Methoxyphenyl)Hydracrylic
Absolute change of total 24-hour urinary 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic (4 week value - 0 week value)
Time frame: 4 weeks
Hesperetin-3'-O-glucuronide
Absolute change of total 24-hour urinary hesperetin-3'-O-glucuronide (4 week value - 0 week value)Urine concentration hesperetin-3'-O-glucuronide
Time frame: 4 weeks
Hesperetin-3',7-0-diglucuronide
Absolute change of total 24-hour urinary hesperetin-3',7-0-diglucuronide (4 week value - 0 week value)
Time frame: 4 weeks
p-Hydroxyhippuric Acid
Absolute change of total 24-hour urinary p-Hydroxyhippuric acid (4 week value - 0 week value)
Time frame: 4 weeks
3-(4'-Methoxyphenyl)Propionic Acid-3'-O-glucuronide
Absolute change of total 24-hour urinary 3-(4'-methoxyphenyl)propionic acid-3'-O-glucuronide (4 week value - 0 week value)
Time frame: 4 weeks
Hesperetin-7-O-glucuronide
Absolute change of total 24-hour urinary hesperetin-7-O-glucuronide (4 week value - 0 week value)
Time frame: 4 weeks
Naringin-7-O-glucuronide
Absolute change of total 24-hour urinary naringen-7-O-glucuronide (4 week value - 0 week value)
Time frame: 4 weeks
Oral Glucose Tolerance Test (OGTT) Glucose 3-hour Area Under the Curve (AUC)
Absolute change in OGTT 3-hour AUC glucose concentration (4-week value - 0-week value)
Time frame: 4 week
Oral Glucose Tolerance Test (OGTT) Insulin 3-hour Area Under the Curve
Absolute change in OGTT 3-hour AUC insulin concentration (4-week value - 0-week value)
Time frame: 4 week
Fasting de Novo Lipogenesis
Absolute change of fasting percentage fractional rate fasting de novo lipogenesis DNL (4 week value - 0 week value)
Time frame: 4 weeks