OASIS: Orange Juice And Sugar Intervention Study

Sponsor

University of California, Davis (Other)

Overall Status

Recruiting

CT.gov ID

NCT03527277

Collaborator

Touro University, California (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Risk Factor Type2 Diabetes Mellitus Insulin Sensitivity Metabolic Syndrome	Other: Naturally-sweetened orange juice Other: Sugar-sweetened beverage	N/A

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:

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.
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.
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 Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized controlled trialRandomized controlled trial

Masking:

Single (Outcomes Assessor)

Masking Description:

All outcomes will be analyzed/assessed by subject identity number, which are assigned prior to randomization to experimental arm.

Primary Purpose:

Basic Science

Official Title:

The Effects of Orange Juice Compared With Sugar-sweetened Beverage on Risk Factors and Metabolic Processes Associated With the Development of Cardiovascular Disease and Type 2 Diabetes

Actual Study Start Date :

Jun 1, 2018

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jan 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naturally-sweetened orange juice Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks	Other: Naturally-sweetened orange juice Commercially-available ready-to-serve refrigerated orange juice
Active Comparator: Sugar-sweetened beverage Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks	Other: Sugar-sweetened beverage Sugar-sweetened water flavored with Kool-Aid (TM)

Arm

Intervention/Treatment

Experimental: Naturally-sweetened orange juice

Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks

Other: Naturally-sweetened orange juice

Commercially-available ready-to-serve refrigerated orange juice

Active Comparator: Sugar-sweetened beverage

Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks

Other: Sugar-sweetened beverage

Sugar-sweetened water flavored with Kool-Aid (TM)

Outcome Measures

Primary Outcome Measures

Low density lipoprotein cholesterol (LDL-C) [4 weeks]
Plasma LDL-C concentration
Apolipoprotein B (apoB) [4 weeks]
Plasma apoB concentration
Uric acid [4 weeks]
Plasma uric acid concentration
de novo lipogenesis (DNL) [4 weeks]
%Fractional rate DNL
Hepatic triglyceride [4 weeks]
%hepatic triglyceride
Endogenous glucose production [4 weeks]
Endogenous glucose production during hyperinsulinemic clamp

Secondary Outcome Measures

Postprandial triglyceride [4 weeks]
Plasma postprandial triglyceride concentration
3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic [4 weeks]
Urine concentration of 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic
hesperetin-3'-O-glucuronide [4 weeks]
Urine concentration hesperetin-3'-O-glucuronide
hesperetin-3'-sulfate [4 weeks]
Urine concentration hesperetin-3'-sulfate
Apolipoprotein CIII (apoCIII) [4 weeks]
Fasting and postprandial plasma apoCIII concentration
non-high density lipoprotein cholesterol (non-HDL-C) [4 weeks]
Plasma non-HDL-C concentration

Other Outcome Measures

Gluconeogenesis [4 weeks]
Determined from glucose isotopomer distribution
Glycogenolysis [4 weeks]
Endogenous glucose production minus gluconeogenesis
Lipolysis [4 weeks]
Determined from glycerol isotopomer distribution
Triglyceride production [4 weeks]
Determined from glycerol isotopomer distribution
Energy expenditure [4 weeks]
Postprandial energy expenditure
Fat oxidation [4 weeks]
Postprandial fat oxidation
Hesperetin-7-O-glucuronide [4 weeks]
Urine concentration hesperetin-7-O-glucuronide
Naringenin-4'-O-glucuronide [4 weeks]
Urine concentration naringenin-4'-O-glucuronide
Naringen-7-O-glucuronide [4 weeks]
Urine concentration naringen-7-O-glucuronide
Fecal microbiota [4 weeks]
Fecal relative bacterial abundance
Insulin [4 week]
fasting and postprandial plasma insulin concentration
glucose [glucose]
fasting and postprandial plasma glucose concentration
Apolipoprotein E (apoE) [4 weeks]
plasma apoE concentration
high sensitivity C reactive protein (CRP) [4 weeks]
plasma CRP concentration
aspartate aminotransferase (AST) [4 weeks]
plasma AST concentration
alanine aminotransferase (ALT) [4 weeks]
plasma ALT concentration
gamma-glutamyl transferase (GGT) [4 weeks]
plasma GGT concentration
oxidized LDL (oxLDL) [4 weeks]
plasma oxLDL concentration
malondialdehyde [4 weeks]
fasting and postprandial plasma malondialdehyde concentration
total antioxidant status [4 weeks]
fasting and postprandial plasma total antioxidant status
soluble vascular cellular adhesion molecule (sVCAM-1) [4 weeks]
plasma sVCAM-1 concentration
monocyte chemotactic protein-1 (MCP-1) [4 weeks]
plasma MCP-1 concentration
nitric oxide metabolite (NOx) [4 weeks]
plasma NOx concentration
Diastolic and systolic blood pressure [4 weeks]
fasting and postprandial blood pressure
Body fat [4 weeks]
%body fat
Visceral fat [4 weeks]
Abdominal visceral fat volume
Subcutaneous fat [4 weeks]
Abdominal subcutaneous fat volume
Physical activity [4 weeks]
Assessed by accelerometer
Eating motivation [4 weeks]
Assessed by 19 questions that are scored on a 5-point scale with 5 describing eating behavior driven by reasons other than hunger (i.e. emotions, social pressure)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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