Trial Outcomes & Findings for Orange Juice And Sugar Intervention Study (NCT NCT03527277)

NCT ID: NCT03527277

Last Updated: 2025-11-10

Results Overview

Absolute change of 4-h post-dinner AUC plasma triglyceride concentration (4 week value - 0 week value)

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 56 participants
• Primary outcome timeframe: 4 weeks
• Results posted on: 2025-11-10

Participant Flow

Participant milestones

Measure	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 Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice	Sugar-sweetened beverage Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)
Overall Study STARTED	31	25
Overall Study COMPLETED	25	24
Overall Study NOT COMPLETED	6	1

Reasons for withdrawal

Measure	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 Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice	Sugar-sweetened beverage Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)
Overall Study Withdrawal by Subject	5	0
Overall Study Withdrawn by PI due to veins not suitable for multiple blood draws	0	1
Overall Study Withdrawn by PI due to dietary miscompliance	1	0

Baseline Characteristics

Orange Juice And Sugar Intervention Study

Baseline characteristics by cohort

Measure	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice	Sugar-sweetened beverage n=24 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Total n=49 Participants Total of all reporting groups
Age, Continuous	22.8 years STANDARD_DEVIATION 3.8 • n=5 Participants	24.8 years STANDARD_DEVIATION 7.1 • n=20 Participants	23.8 years STANDARD_DEVIATION 5.7 • n=40 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=20 Participants	21 Participants n=40 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	13 Participants n=20 Participants	28 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	4 Participants n=20 Participants	9 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	20 Participants n=20 Participants	40 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=20 Participants	1 Participants n=40 Participants
Race (NIH/OMB) Asian	16 Participants n=5 Participants	15 Participants n=20 Participants	31 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	8 Participants n=20 Participants	16 Participants n=40 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=20 Participants	1 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Region of Enrollment United States	25 participants n=5 Participants	24 participants n=20 Participants	49 participants n=40 Participants
Body Mass Index	23.8 kg/meters^2 STANDARD_DEVIATION 3.6 • n=5 Participants	24.0 kg/meters^2 STANDARD_DEVIATION 3.3 • n=20 Participants	23.9 kg/meters^2 STANDARD_DEVIATION 3.4 • n=40 Participants
Systolic blood pressure	110.8 mmHg STANDARD_DEVIATION 11.0 • n=5 Participants	111.0 mmHg STANDARD_DEVIATION 11.4 • n=20 Participants	110.9 mmHg STANDARD_DEVIATION 11.1 • n=40 Participants
Diastolic Blood Pressure	71.0 mmHg STANDARD_DEVIATION 7.5 • n=5 Participants	69.7 mmHg STANDARD_DEVIATION 8.3 • n=20 Participants	70.4 mmHg STANDARD_DEVIATION 7.9 • n=40 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of plasma LDL-C concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Fasting Low Density Lipoprotein Cholesterol (LDL-C)	5.8 mg/dl Standard Deviation 7.5	5.5 mg/dl Standard Deviation 5.3

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. Unable to collect week 4 postprandial samples from one participant in the Sucrose Group

Absolute change of plasma postprandial LDL-C concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=22 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Postprandial Low Density Lipoprotein Cholesterol (LDL-C)	6.7 mg/dl Standard Deviation 5.6	5.9 mg/dl Standard Deviation 4.8

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of plasma apoB concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Fasting Apolipoprotein B (apoB)	3.4 mg/dl Standard Deviation 7.5	2.9 mg/dl Standard Deviation 4.6

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. Unable to collect post-dinner blood samples from one participant in the sucrose group during the 4-week intervention trial.

Absolute change of plasma postprandial apoB concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=22 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Postprandial Apolipoprotein B (apoB)	4.3 mg/dl Standard Deviation 5.9	3.7 mg/dl Standard Deviation 4.5

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of plasma uric acid concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Fasting Uric Acid	0.11 mg/dl Standard Deviation 0.60	-0.92 mg/dl Standard Deviation 0.85

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. Unable to collect post-dinner blood samples from one participant in the sucrose group during the 4-week intervention trial.

Absolute change of post-dinner 4-hour AUC plasma uric acid concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=22 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Postprandial Uric Acid	0.40 mg/dl x 4 h Standard Deviation 1.9	-3.3 mg/dl x 4 h Standard Deviation 2.6

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of fasting plasma apoCIII concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Fasting Apolipoprotein CIII (apoCIII)	0.60 mg/dl Standard Deviation 0.92	0.40 mg/dl Standard Deviation 1.03

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. Unable to collect post-dinner blood samples from one participant in the sucrose group during the 4-week intervention trial.

Absolute change of plasma postprandial apoCIII concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=22 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Postprandial Apolipoprotein CIII (apoCIII)	0.38 mg/dl Standard Deviation 0.85	0.64 mg/dl Standard Deviation 0.93

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. Unable to collect post-dinner blood samples from one participant in the sucrose group during the 4-week intervention trial.

Absolute change of 4-h post-dinner AUC plasma triglyceride concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=22 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Postprandial Triglyceride	53.5 mg/dl x 4 h Standard Deviation 56.9	41.8 mg/dl x 4 h Standard Deviation 61.3

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. One participant in the Orange Juice Group was not able to attend the intervention MRI appointment.

Absolute change of % hepatic triglyceride (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=24 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Hepatic Triglyceride	0.26 % fat in liver Standard Deviation 0.53	0.05 % fat in liver Standard Deviation 0.86

PRIMARY outcome

Timeframe: 4 week

Population: This analysis includes participants enrolled after a coronavirus disease 2019 (COVID)-related protocol modification, who completed a 3-hour OGTT. These participants (n=39) did not undergo hyperinsulinemic euglycemic clamps. Final data collection and analysis for this population are complete. One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

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).

Outcome measures

Measure	Sugar-sweetened beverage n=17 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=21 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Matsuda Insulin Sensitivity Index (ISI)	-0.40 units on a scale Standard Deviation 0.98	-0.35 units on a scale Standard Deviation 1.0

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. Unable to collect post-dinner blood samples from one participant in the sucrose group during the 4-week intervention trial.

Absolute change of 8-hour area under the curve (AUC) percentage fractional rate postprandial de novo lipogenesis DNL (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=22 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Postprandial de Novo Lipogenesis	22.3 %fractional rate x 8 h Standard Deviation 16.2	8.3 %fractional rate x 8 h Standard Deviation 12.3

PRIMARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. Unable to collect post-dinner blood samples from one participant in the sucrose group during the 4-week intervention trial.

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)

Outcome measures

Measure	Sugar-sweetened beverage n=6 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=4 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
M Value During Hyperinsulinemic Euglycemic Clamp	0.2 %fractional rate Standard Deviation 0.9	-0.2 %fractional rate Standard Deviation 1.9

SECONDARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of plasma fasting triglyceride concentration (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Fasting Triglyceride	6.4 mg/dl Standard Deviation 14.0	-3.5 mg/dl Standard Deviation 21.2

SECONDARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of total 24-hour urinary 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
3-(3'-Hydroxy-4'-Methoxyphenyl)Hydracrylic	-336 ng Standard Deviation 12414	23322 ng Standard Deviation 32654

SECONDARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of total 24-hour urinary hesperetin-3'-O-glucuronide (4 week value - 0 week value)Urine concentration hesperetin-3'-O-glucuronide

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Hesperetin-3'-O-glucuronide	4 ng Standard Deviation 95	5550 ng Standard Deviation 6502

SECONDARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. Invalid results obtained for this outcome in one participant in the sucrose group.

Absolute change of total 24-hour urinary hesperetin-3',7-0-diglucuronide (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=22 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Hesperetin-3',7-0-diglucuronide	-3 ng Standard Deviation 10	3797 ng Standard Deviation 4955

SECONDARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of total 24-hour urinary p-Hydroxyhippuric acid (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
p-Hydroxyhippuric Acid	-770 ng Standard Deviation 9212	20347 ng Standard Deviation 26775

SECONDARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of total 24-hour urinary 3-(4'-methoxyphenyl)propionic acid-3'-O-glucuronide (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
3-(4'-Methoxyphenyl)Propionic Acid-3'-O-glucuronide	-198 ng Standard Deviation 876	23124 ng Standard Deviation 25954

SECONDARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of total 24-hour urinary hesperetin-7-O-glucuronide (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Hesperetin-7-O-glucuronide	-2 ng Standard Deviation 18	9556 ng Standard Deviation 11081

SECONDARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. Invalid results obtained for this outcome in one participant in the sucrose group.

Absolute change of total 24-hour urinary naringen-7-O-glucuronide (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=22 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Naringin-7-O-glucuronide	-284 ng Standard Deviation 851	3286 ng Standard Deviation 4453

SECONDARY outcome

Timeframe: 4 week

Population: This analysis includes participants enrolled after a COVID-related protocol modification, who completed a 3-hour OGTT. These participants (n=39) did not undergo hyperinsulinemic euglycemic clamps. Final data collection and analysis for this population are complete. One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change in OGTT 3-hour AUC glucose concentration (4-week value - 0-week value)

Outcome measures

Measure	Sugar-sweetened beverage n=17 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=21 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Oral Glucose Tolerance Test (OGTT) Glucose 3-hour Area Under the Curve (AUC)	25.6 mg/dl x 3 hours Standard Deviation 80.1	46.8 mg/dl x 3 hours Standard Deviation 56.2

SECONDARY outcome

Timeframe: 4 week

Population: This analysis includes participants enrolled after a COVID-related protocol modification, who completed a 3-hour OGTT. These participants (n=39) did not undergo hyperinsulinemic euglycemic clamps. Final data collection and analysis for this population are complete. One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change in OGTT 3-hour AUC insulin concentration (4-week value - 0-week value)

Outcome measures

Measure	Sugar-sweetened beverage n=17 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=21 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Oral Glucose Tolerance Test (OGTT) Insulin 3-hour Area Under the Curve	0.1 microUnit/ml x 3 hours Standard Deviation 105.4	74.7 microUnit/ml x 3 hours Standard Deviation 114.9

SECONDARY outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change of fasting percentage fractional rate fasting de novo lipogenesis DNL (4 week value - 0 week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Fasting de Novo Lipogenesis	0.6 %fractional rate Standard Deviation 1.7	0.9 %fractional rate Standard Deviation 1.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 week

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change serum insulin concentration (4-week value - 0-week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Fasting Insulin	0.38 microUnit/ml Standard Deviation 2.32	-0.31 microUnit/ml Standard Deviation 1.80

OTHER_PRE_SPECIFIED outcome

Timeframe: glucose

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Absolute change in fasting plasma glucose concentration (4-week value - 0-week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Fasting Glucose	0.3 mg/dl Standard Deviation 4.7	1.5 mg/dl Standard Deviation 3.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Change in body weight (4-week value - 0-week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Body Weight	-0.5 kg Standard Deviation 0.7	-0.5 kg Standard Deviation 1.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Change in systolic blood pressure (4-week value - 0-week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Systolic Blood Pressure	-4.2 mmHg Standard Deviation 10.6	-2.9 mmHg Standard Deviation 10.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria.

Change in diastolic blood pressure (4-week value minus 0-week value)

Outcome measures

Measure	Sugar-sweetened beverage n=23 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=25 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Diastolic Blood Pressure	-1.0 mmHg Standard Deviation 7.7	-2.3 mmHg Standard Deviation 7.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks

Population: One participant was excluded due to extreme values that deviated from the mean by more than 2 standard deviations across multiple outcomes. The exclusion was based on protocol-defined criteria. DEXA analyzer not available to scan 2 participants in orange juice group and 1 participant in sucrose group during baseline trial.

%body fat

Outcome measures

Measure	Sugar-sweetened beverage n=21 Participants Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)	Naturally-sweetened orange juice n=23 Participants Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice
Body Fat	-0.5 percentage of body fat Standard Deviation 1.0	-0.9 percentage of body fat Standard Deviation 0.7

Adverse Events

Naturally-sweetened orange juice

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sugar-sweetened beverage

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Naturally-sweetened orange juice n=25 participants at risk Naturally-sweetened orange juice Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Naturally-sweetened orange juice: Commercially-available ready-to-serve refrigerated orange juice	Sugar-sweetened beverage n=24 participants at risk Sugar-sweetened beverage Form: Beverage Daily dosage: 25% of daily energy requirement Frequency: Divided into 3 servings/day Duration: 4 weeks Sugar-sweetened beverage: Sugar-sweetened water flavored with Kool-Aid (TM)
Gastrointestinal disorders stomachache	12.0% 3/25 • Number of events 3 • Adverse events for each participant were collected for 6 weeks.	0.00% 0/24 • Adverse events for each participant were collected for 6 weeks.

Additional Information

Kimber Stanhope

University of California, Davis

Phone: 5302190914

Email: klstanhope@ucdavis.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place