Trial Outcomes & Findings for The Effects of Added Sugar Intake on Brain Blood Flow and Hippocampal Function in Midlife Adults (NCT NCT05211726)

NCT ID: NCT05211726

Last Updated: 2025-06-12

Results Overview

Change in cross-sectional area of the common carotid artery (assessed using ultrasound) per 1 mmHg increase in carotid artery blood pressure (assessed by applanation tonometry). A lower carotid artery compliance is indicative of stiffer elastic arteries.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

44 participants

Primary outcome timeframe

Day 10 of the diet

Results posted on

2025-06-12

Participant Flow

Participants were screened for inclusion in this study at the University of Delaware between January 11, 2022 - January 5, 2024. The study concluded on May 3, 2024.

44 participants were consented and randomized. After baseline testing, but prior to starting the intervention, 5 participants withdrew \[MRI concerns (N=3) or unable to maintain the required time commitment (N=2)\]. 1 participant started the intervention, but was dropped due to a change in medication not-related to the study, thus making this participant ineligible. A total of 38 participants completed both the high and low sugar diet, with a ≥ 2-week washout in between.

Participant milestones

Participant milestones
Measure
Low Sugar, High Sugar Diet
Subjects will be provided with a diet that is low in added sugars followed by a diet that is high in added sugars. 1. Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake) 2. High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
High Sugar, Low Sugar Diet
Subjects will be provided with a diet that is high in added sugars followed by a diet that is low in added sugars. 1. High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake) 2. Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Overall Study
STARTED
20
24
Overall Study
COMPLETED
18
20
Overall Study
NOT COMPLETED
2
4

Reasons for withdrawal

Reasons for withdrawal
Measure
Low Sugar, High Sugar Diet
Subjects will be provided with a diet that is low in added sugars followed by a diet that is high in added sugars. 1. Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake) 2. High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
High Sugar, Low Sugar Diet
Subjects will be provided with a diet that is high in added sugars followed by a diet that is low in added sugars. 1. High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake) 2. Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Overall Study
Withdrawal by Subject
2
3
Overall Study
Protocol Violation
0
1

Baseline Characteristics

The Effects of Added Sugar Intake on Brain Blood Flow and Hippocampal Function in Midlife Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Low Sugar, High Sugar Diet
n=18 Participants
Subjects will be provided with a diet that is low in added sugars followed by a diet that is high in added sugars. 1. Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake) 2. High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
High Sugar, Low Sugar Diet
n=20 Participants
Subjects will be provided with a diet that is high in added sugars followed by a diet that is low in added sugars. 1. High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake) 2. Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Total
n=38 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
18 Participants
n=5 Participants
20 Participants
n=7 Participants
38 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Continuous
57 years
STANDARD_DEVIATION 4 • n=5 Participants
57 years
STANDARD_DEVIATION 4 • n=7 Participants
57 years
STANDARD_DEVIATION 4 • n=5 Participants
Sex: Female, Male
Female
11 Participants
n=5 Participants
13 Participants
n=7 Participants
24 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
7 Participants
n=7 Participants
14 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
18 Participants
n=5 Participants
20 Participants
n=7 Participants
38 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
White
16 Participants
n=5 Participants
18 Participants
n=7 Participants
34 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
18 Participants
n=5 Participants
20 Participants
n=7 Participants
38 Participants
n=5 Participants
Seated systolic blood pressure (mmHg)
116 mmHg
STANDARD_DEVIATION 9 • n=5 Participants
113 mmHg
STANDARD_DEVIATION 10 • n=7 Participants
114 mmHg
STANDARD_DEVIATION 10 • n=5 Participants
Seat diastolic blood pressure (mmHg)
70 mmHg
STANDARD_DEVIATION 8 • n=5 Participants
70 mmHg
STANDARD_DEVIATION 7 • n=7 Participants
70 mmHg
STANDARD_DEVIATION 7 • n=5 Participants
Height (cm)
171.4 cm
STANDARD_DEVIATION 10.6 • n=5 Participants
170.5 cm
STANDARD_DEVIATION 8.0 • n=7 Participants
170.9 cm
STANDARD_DEVIATION 9.2 • n=5 Participants
Body mass (kg)
77.1 kg
STANDARD_DEVIATION 16.4 • n=5 Participants
71.2 kg
STANDARD_DEVIATION 11.4 • n=7 Participants
74.0 kg
STANDARD_DEVIATION 14.2 • n=5 Participants
Body mass index (BMI)
26.0 kg/m^2
STANDARD_DEVIATION 3.4 • n=5 Participants
24.4 kg/m^2
STANDARD_DEVIATION 3.1 • n=7 Participants
25.2 kg/m^2
STANDARD_DEVIATION 3.3 • n=5 Participants

PRIMARY outcome

Timeframe: Day 10 of the diet

Change in cross-sectional area of the common carotid artery (assessed using ultrasound) per 1 mmHg increase in carotid artery blood pressure (assessed by applanation tonometry). A lower carotid artery compliance is indicative of stiffer elastic arteries.

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=38 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=38 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Arterial Compliance (m^2 Kilopascal^-1)
0.824 m^2 kilopascal^-1
Standard Deviation 0.280
0.772 m^2 kilopascal^-1
Standard Deviation 0.201

PRIMARY outcome

Timeframe: Day 10 of the diet

Population: 5 participants did not have a CVR test with a ETCO2 changed by at least 6.5 mmHg. 2 participants did not perform the CVR test (due to discomfortable from the mask or not adequate space in the head coil). MRI was quenched (not working) for 2 participant during both diets.

Cerebrovascular reactivity (CVR) is the relative (percent) change in total cerebral perfusion measured using pseudo-continuous arterial spin labeling per mmHg change in end-tidal carbon dioxide (ETCO2) during a brief period of hypercapnia. Hypercapnia was induced by prospective end-tidal targeting (RespirAct, Thornhill Medical) in which a target change in end-tidal CO2 of +9 millimeters of mercury (mmHg) was set. Data were only analyzed if ETCO2 changed by at least 6.5 mmHg. All data were then normalized to the absolute change in ETCO2.

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=29 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=29 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Cerebrovascular Reactivity (Percent Increase in Cerebral Perfusion Normalized to the Increase in PETCO2
4.035 percent increase in cerebral perfusion n
Standard Deviation 2.486
6.075 percent increase in cerebral perfusion n
Standard Deviation 3.789

PRIMARY outcome

Timeframe: Day 10 of the diet

Population: MRI was quenched (not working) for 2 participant during both diets. The resoundant acoustic driver system did not work for 2 participants during the Low Sugar Diet.

Noninvasive brain imaging using Magnetic Resonance Elastography (MRE) to estimate tissue mechanical properties. Stiffness values are derived from the propagation of shear waves delivered to the head using vibration at 50 Hertz (Hz) from an acoustic driver system (Resoundant, Inc, Rochester MN) and reflects the distribution and organization of neurons, axons, and glial cells. A higher brain stiffness indicates greater tissue integrity. A nonlinear inversion algorithm estimated mechanical properties in the brain from acquired MRE displacement data to map shear modulus, G = G'+iG", where G' is the storage modulus and G'' is the loss modulus. From these parameters, stiffness is calculated, μ = 2\*\|G\|\^2 / (\|G\|+G')

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=36 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=34 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Hippocampal Stiffness (kPa)
3.09473 kPa
Standard Deviation 0.29062
3.04559 kPa
Standard Deviation 0.30600

PRIMARY outcome

Timeframe: Day 10 of the diet

Population: MRI was quenched (not working) for 2 participant during both diets. The resoundant acoustic driver system did not work for 2 participants during the LS diet.

Noninvasive brain imaging using Magnetic Resonance Elastography (MRE) to estimate tissue mechanical properties. Damping Ratio is derived from the propagation of shear waves delivered to the head using vibration at 50Hz from an acoustic driver system (Resoundant, Inc, Rochester MN) and reflects the relative elasticity of the brain tissue. A lower damping ratio indicates greater tissue integrity. A nonlinear inversion algorithm estimated mechanical properties in the brain from acquired MRE displacement data to map shear modulus, G = G'+iG", where G' is the storage modulus and G'' is the loss modulus. From these parameters, damping ratio is calculated, ξ = G"/2\*G'

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=36 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=34 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Hippocampal Damping Ratio (Unitless Ratio)
0.18186 unitless ratio
Standard Deviation 0.02949
0.18794 unitless ratio
Standard Deviation 0.02982

PRIMARY outcome

Timeframe: Day 10 of the diet

The Revised Hopkins Verbal Learning Test (HVLT-R) assesses verbal learning and memory, immediate recall and delayed recall from a list of 12 words. Immediate recall takes place over 3 trials (out of 12 correct responses each) Total recall is the sum of trials 1-3 (out of 36 correct responses). Delayed recall takes place 20-25 minutes after trial 3 and the participant must recall the entire list of words (out of 12 correct responses).

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=38 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=38 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Revised Hopkins Verbal Learning Test (HVLT-R) Total Recall Memory
Trial 1 Recall
7.6 correct responses
Standard Deviation 1.6
7.8 correct responses
Standard Deviation 1.8
Revised Hopkins Verbal Learning Test (HVLT-R) Total Recall Memory
Trial 2 Recall
9.7 correct responses
Standard Deviation 1.7
10.2 correct responses
Standard Deviation 1.5
Revised Hopkins Verbal Learning Test (HVLT-R) Total Recall Memory
Trial 3 Recall
10.9 correct responses
Standard Deviation 1.3
11.1 correct responses
Standard Deviation 1.2
Revised Hopkins Verbal Learning Test (HVLT-R) Total Recall Memory
Total Recall
28.2 correct responses
Standard Deviation 4.0
29.2 correct responses
Standard Deviation 3.9
Revised Hopkins Verbal Learning Test (HVLT-R) Total Recall Memory
Delayed Recall
9.9 correct responses
Standard Deviation 1.9
10.5 correct responses
Standard Deviation 1.7

PRIMARY outcome

Timeframe: Day 10 of the diet

The Revised Brief Visuospatial Memory Test (BVMT-R) assesses visuospatial memory and includes an immediate recall and delayed recall from images. Immediate recall takes place over 3 trials (out of 12 correct responses each) Total recall is the sum of trials 1-3 (out of 36 correct responses). Delayed recall takes place 20-25 minutes after trial 3 and the participant must recall or redraw all the images (out of 12 correct responses).

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=38 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=38 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Revised Brief Visuospatial Memory Test (BVMT-R) Total Recall Score
Trial 1 Recall
5.6 correct responses
Standard Deviation 2.4
6.3 correct responses
Standard Deviation 2.1
Revised Brief Visuospatial Memory Test (BVMT-R) Total Recall Score
Trial 2 Recall
8.0 correct responses
Standard Deviation 2.3
8.9 correct responses
Standard Deviation 2.2
Revised Brief Visuospatial Memory Test (BVMT-R) Total Recall Score
Trial 3 Recall
9.3 correct responses
Standard Deviation 2.0
10.2 correct responses
Standard Deviation 1.8
Revised Brief Visuospatial Memory Test (BVMT-R) Total Recall Score
Total Recall
22.9 correct responses
Standard Deviation 6.3
25.2 correct responses
Standard Deviation 5.5
Revised Brief Visuospatial Memory Test (BVMT-R) Total Recall Score
Delayed Recall
8.9 correct responses
Standard Deviation 2.1
9.9 correct responses
Standard Deviation 1.8

PRIMARY outcome

Timeframe: Day 10 of diet

Seated systolic blood pressure taken with arm at heart level after a 10-minute rest. Results are average of triplicate measurements

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=38 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=38 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Seated Systolic Blood Pressure (mmHg)
115 mmHg
Standard Deviation 10
111 mmHg
Standard Deviation 10

PRIMARY outcome

Timeframe: Day 10 of diet

Seated diastolic blood pressure taken with arm at heart level after a 10-minute rest. Results are average of triplicate measurements

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=38 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=38 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Seated Diastolic Blood Pressure (mmHg)
70 mmHg
Standard Deviation 7
67 mmHg
Standard Deviation 7

SECONDARY outcome

Timeframe: Day 10 of the diet

Population: 1 participant did not have an accessible carotid artery via applanation tonometry for both diets

Carotid-femoral pulse wave velocity (CFPWV) assessed using applanation tonometry of the carotid artery and cuff-based assessment of the femoral pulse wave (SphygmoCor XCEL). CFPWV is calculated as the distance between the carotid and femoral pulse divided by the time-delay between pulses. A higher CFPWV is indicative of stiffer elastic arteries.

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=37 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=37 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Carotid-femoral Pulse Wave Velocity (CFPWV) (m/Seconds)
7.92 m/seconds
Standard Deviation 1.00
7.71 m/seconds
Standard Deviation 1.01

SECONDARY outcome

Timeframe: Day 10 of the diet

National Institute of Health (NIH) Toolbox Pattern Comparison Processing Speed Test Brief, computer-based assessment of processing speed in which participants quickly determine if two visual patterns are the same or different. For age 50-59, raw/computed score has a mean of 41.53 and standard deviation of 19.42 based on a normative dataset (Range = 11.00 - 65.00). For age 60-69, raw/computed score has a mean of 39.44 and standard deviation of 16.39 based on a normative dataset (Range = 7.00 - 64.00). A higher score indicates a better outcome.

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=38 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=38 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Pattern Comparison Processing Speed Test (Raw/Computed Score)
45.50 score on a scale
Standard Deviation 8.20
47.89 score on a scale
Standard Deviation 6.29

SECONDARY outcome

Timeframe: Day 10 of the diet

Brief, standardized assessment of attention and inhibitory control, which are key components of executive function. For age 50-59, raw/computed score has a mean of 8.21 and standard deviation of 1.73 based on a normative dataset (Range = 3.88 - 9.74). For age 60-69, raw/computed score has a mean of 8.16 and standard deviation of 1.60 based on a normative dataset (Range = 3.63 - 9.59). A higher score indicates a better outcome.

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=38 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=38 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Flanker Test (Raw/Computed Score)
8.35 score on a scale
Standard Deviation 0.66
8.52 score on a scale
Standard Deviation 0.55

SECONDARY outcome

Timeframe: Day 10 of the diet

Population: 2 participants had missed blood draws on the High Sugar Diet.

Blood biomarkers triglycerides in mg/dL

Outcome measures

Outcome measures
Measure
High Sugar Diet
n=36 Participants
High Added Sugar Diet: Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)
Low Sugar Diet
n=38 Participants
Low Added Sugar Diet: Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)
Triglycerides (mg/dL)
102.9 mg/dL
Standard Deviation 31.0
91.2 mg/dL
Standard Deviation 28.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 10 of the diet

Biomarkers of inflammation (e.g. cytokines) from peripheral blood mononuclear cells

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 10 of the diet

Sleep quality will be continuously measured for 10 days using an Actiwatch.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 10 of the diet

Blood biomarkers of oxidative stress (e.g. superoxide) using Electron Paramagnetic Resonance

Outcome measures

Outcome data not reported

Adverse Events

Low Sugar Diet

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

High Sugar Diet

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Christopher Martens

University of Delaware

Phone: 302-831-7270

Results disclosure agreements

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