Orange Juice And Sugar Intervention Study (OASIS)

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

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Cardiovascular Risk Factor; Insulin Sensitivity; Type2 Diabetes Mellitus
• Intervention / Treatment: Other: Naturally-sweetened orange juice; Other: 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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Davis, California, United States, 95616
      • University of California, Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Low Density Lipoprotein Cholesterol (LDL-C)	Absolute change of plasma LDL-C concentration (4 week value - 0 week value)	4 weeks
Postprandial Low Density Lipoprotein Cholesterol (LDL-C)	Absolute change of plasma postprandial LDL-C concentration (4 week value - 0 week value)	4 weeks
Fasting Apolipoprotein B (apoB)	Absolute change of plasma apoB concentration (4 week value - 0 week value)	4 weeks
Postprandial Apolipoprotein B (apoB)	Absolute change of plasma postprandial apoB concentration (4 week value - 0 week value)	4 weeks
Fasting Uric Acid	Absolute change of plasma uric acid concentration (4 week value - 0 week value)	4 weeks
Fasting Apolipoprotein CIII (apoCIII)	Absolute change of fasting plasma apoCIII concentration (4 week value - 0 week value)	4 weeks
Postprandial Apolipoprotein CIII (apoCIII)	Absolute change of plasma postprandial apoCIII concentration (4 week value - 0 week value)	4 weeks
Hepatic Triglyceride	Absolute change of % hepatic triglyceride (4 week value - 0 week value)	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).	4 week
Postprandial Uric Acid	Absolute change of post-dinner 4-hour AUC plasma uric acid concentration (4 week value - 0 week value)	4 weeks
Postprandial Triglyceride	Absolute change of 4-h post-dinner AUC plasma triglyceride concentration (4 week value - 0 week value)	4 weeks
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)	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)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Triglyceride	Absolute change of plasma fasting triglyceride concentration (4 week value - 0 week value)	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)	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	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)	4 weeks
p-Hydroxyhippuric Acid	Absolute change of total 24-hour urinary p-Hydroxyhippuric acid (4 week value - 0 week value)	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)	4 weeks
Hesperetin-7-O-glucuronide	Absolute change of total 24-hour urinary hesperetin-7-O-glucuronide (4 week value - 0 week value)	4 weeks
Naringin-7-O-glucuronide	Absolute change of total 24-hour urinary naringen-7-O-glucuronide (4 week value - 0 week value)	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)	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)	4 week
Fasting de Novo Lipogenesis	Absolute change of fasting percentage fractional rate fasting de novo lipogenesis DNL (4 week value - 0 week value)	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Insulin	Absolute change serum insulin concentration (4-week value - 0-week value)	4 week
Fasting Glucose	Absolute change in fasting plasma glucose concentration (4-week value - 0-week value)	glucose
Body Weight	Change in body weight (4-week value - 0-week value)	4 weeks
Systolic Blood Pressure	Change in systolic blood pressure (4-week value - 0-week value)	4 weeks
Diastolic Blood Pressure	Change in diastolic blood pressure (4-week value minus 0-week value)	4 weeks
Body Fat	%body fat	4 weeks

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Touro University, California
• Investigators: Principal Investigator: Kimber L Stanhope, Ph.D., University of California, Davis

Publications and helpful links

General Publications

• Yang Q, Zhang Z, Gregg EW, Flanders WD, Merritt R, Hu FB. Added sugar intake and cardiovascular diseases mortality among US adults. JAMA Intern Med. 2014 Apr;174(4):516-24. doi: 10.1001/jamainternmed.2013.13563.
• Stanhope KL, Medici V, Bremer AA, Lee V, Lam HD, Nunez MV, Chen GX, Keim NL, Havel PJ. A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults. Am J Clin Nutr. 2015 Jun;101(6):1144-54. doi: 10.3945/ajcn.114.100461. Epub 2015 Apr 22.

Helpful Links

• Learn more or sign up for the study here!

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): May 28, 2023
• Study Completion (Actual): May 28, 2023

Study Registration Dates

• First Submitted: April 10, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 17, 2018

Study Record Updates

• Last Update Posted (Estimated): November 7, 2025
• Last Update Submitted That Met QC Criteria: October 21, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: uric acid; orange juice; low density lipoprotein cholesterol; apolipoprotein B; triglyceride; de novo lipogenesis; hepatic glucose production; sugar-sweetened beverage; hepatic triglyceride; whole body insulin sensitivity
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Nutritional and Metabolic Diseases; Metabolic Syndrome; Insulin Resistance; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Beverages; Sugar-Sweetened Beverages
• Other Study ID Numbers: 1167030; R01HL137716 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Final dataset will include data collected specifically for the study and data provided during screening in the medical history form. This includes some demographic information and data regarding family history of disease. We will make data and demographic information available to other investigators upon request. The dataset will be stripped of all unique identifiers and subject characteristics and prepared in accordance with all HIPAA regulations prior to release for sharing. Study outcome results will be submitted to ClinicalTrials.gov no later than one year after the trial's primary completion date.
• IPD Sharing Time Frame: One year after the end of study--January 31, 2025

IPD Sharing Access Criteria

We will make data and demographic information available to investigators who submit an outline with:

1. Hypotheses/aims
2. Assurance that the data will be stored on secured computer
3. Assurance that access will be limited to those named in the proposal
4. Commitment to destroy/return the data after analyses are completed
5. Guarantee that the grant and the primary investigators will be acknowledged in any publications arising from these data.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No