Orange Juice And Sugar Intervention Study

Not Applicable

Completed

Conditions: Metabolic Syndrome
Type2 Diabetes Mellitus
Cardiovascular Risk Factor
Insulin Sensitivity

Registration Number: NCT03527277

Lead Sponsor: University of California, Davis

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 56

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Fasting Low Density Lipoprotein Cholesterol (LDL-C)	4 weeks	Absolute change of plasma LDL-C concentration (4 week value - 0 week value)
Postprandial Low Density Lipoprotein Cholesterol (LDL-C)	4 weeks	Absolute change of plasma postprandial LDL-C concentration (4 week value - 0 week value)
Fasting Apolipoprotein B (apoB)	4 weeks	Absolute change of plasma apoB concentration (4 week value - 0 week value)
Postprandial Apolipoprotein B (apoB)	4 weeks	Absolute change of plasma postprandial apoB concentration (4 week value - 0 week value)
Fasting Uric Acid	4 weeks	Absolute change of plasma uric acid concentration (4 week value - 0 week value)
Postprandial Uric Acid	4 weeks	Absolute change of plasma postprandial uric acid concentration (4 week value - 0 week value)
Fasting Apolipoprotein CIII (apoCIII)	4 weeks	Absolute change of fasting plasma apoCIII concentration (4 week value - 0 week value)
Postprandial Apolipoprotein CIII (apoCIII)	4 weeks	Absolute change of plasma postprandial apoCIII concentration (4 week value - 0 week value)
Postprandial Triglyceride	4 weeks	Absolute change of plasma postprandial triglyceride concentration (4 week value - 0 week value)
Hepatic Triglyceride	4 weeks	Absolute change of % hepatic triglyceride (4 week value - 0 week value)
Matsuda Insulin Sensitivity Index (ISI)	4 week	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).
Total Glucose Uptake During Hyperinsulinemic Euglycemic Clamp	4 weeks	Peripheral insulin sensitivity is assessed as the total glucose uptake during a 3-hour constant rate insulin infusion and a variable rate glucose infusion that is adjusted to maintain glucose levels at baseline levels. A greater amount of glucose uptake during clamp indicates greater insulin sensitivity than lower amount of insulin sensitivity. Therefore, a decrease in total glucose uptake during clamp at 4 weeks compare with clamp at 0 week indicates a decrease of peripheral insulin sensitivity.
Postprandial de Novo Lipogenesis	4 weeks	Absolute change of 11.5-hour AUC %fractional rate postprandial de novo lipogenesis DNL (4 week value - 0 week value)

Secondary Outcome Measures

Name	Time	Method
Fasting Triglyceride	4 weeks	Absolute change of plasma fasting triglyceride concentration (4 week value - 0 week value)
3-(3'-Hydroxy-4'-Methoxyphenyl)Hydracrylic	4 weeks	Absolute change of total 24-hour urinary 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic (4 week value - 0 week value)
Hesperetin-3'-O-glucuronide	4 weeks	Absolute change of total 24-hour urinary hesperetin-3'-O-glucuronide (4 week value - 0 week value)Urine concentration hesperetin-3'-O-glucuronide
Hesperetin-3',7-0-diglucuronide	4 weeks	Absolute change of total 24-hour urinary hesperetin-3',7-0-diglucuronide (4 week value - 0 week value)
p-Hydroxyhippuric Acid	4 weeks	Absolute change of total 24-hour urinary p-Hydroxyhippuric acid (4 week value - 0 week value)
3-(4'-Methoxyphenyl)Propionic Acid-3'-O-glucuronide	4 weeks	Absolute change of total 24-hour urinary 3-(4'-methoxyphenyl)propionic acid-3'-O-glucuronide (4 week value - 0 week value)
Hesperetin-7-O-glucuronide	4 weeks	Absolute change of total 24-hour urinary hesperetin-7-O-glucuronide (4 week value - 0 week value)
Naringin-7-O-glucuronide	4 weeks	Absolute change of total 24-hour urinary naringen-7-O-glucuronide (4 week value - 0 week value)
Oral Glucose Tolerance Test (OGTT) Glucose 3-hour Area Under the Curve (AUC)	4 week	Absolute change in OGTT 3-hour AUC glucose concentration (4-week value - 0-week value)
Oral Glucose Tolerance Test (OGTT) Insulin 3-hour Area Under the Curve	4 week	Absolute change in OGTT 3-hour AUC insulin concentration (4-week value - 0-week value)
Fasting de Novo Lipogenesis	4 weeks	Absolute change of fasting percentage fractional rate fasting de novo lipogenesis DNL (4 week value - 0 week value)

Trial Locations

Locations (1): University of California, Davis
🇺🇸
Davis, California, United States
University of California, Davis
🇺🇸Davis, California, United States