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

NCT05211726 | Completed Results

• 2 other identifiers: 1760500P20GM113125
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This study will focus on improving brain health through dietary modification of added sugars in middle aged adults (50- 64 years old). Participants will be fed two 10-day diets (one diet containing 5% of total energy from added sugars and one diet containing 25% of total energy from added sugars) and examine blood vessel function, hippocampus structure using a MRI, and memory performance.

Conditions

Aging; Healthy Diet

Keywords

added sugars; arterial stiffness; cerebrovascular function; cognitive function

Outcome Measures

Primary Outcomes (8)

• Arterial Compliance (m^2 Kilopascal^-1)

  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.

  Day 10 of the diet

• Cerebrovascular Reactivity (Percent Increase in Cerebral Perfusion Normalized to the Increase in PETCO2

  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.

  Day 10 of the diet

• Hippocampal Stiffness (kPa)

  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')

  Day 10 of the diet

• Hippocampal Damping Ratio (Unitless Ratio)

  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'

  Day 10 of the diet

• Revised Hopkins Verbal Learning Test (HVLT-R) Total Recall Memory

  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).

  Day 10 of the diet

• Revised Brief Visuospatial Memory Test (BVMT-R) Total Recall Score

  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).

  Day 10 of the diet

• Seated Systolic Blood Pressure (mmHg)

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

  Day 10 of diet

• Seated Diastolic Blood Pressure (mmHg)

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

  Day 10 of diet

Secondary Outcomes (4)

• Carotid-femoral Pulse Wave Velocity (CFPWV) (m/Seconds)

  Day 10 of the diet

• Pattern Comparison Processing Speed Test (Raw/Computed Score)

  Day 10 of the diet

• Flanker Test (Raw/Computed Score)

  Day 10 of the diet

• Triglycerides (mg/dL)

  Day 10 of the diet

Other Outcomes (3)

• Inflammatory Cytokines (%)

  Day 10 of the diet

• Sleep Quality (%)

  Day 10 of the diet

• Oxidative Stress

  Day 10 of the diet

Study Arms (2)

Low Added Sugar Diet

EXPERIMENTAL

Subjects will be provided with a diet that is low in added sugars.

Other: Low Added Sugar Diet

High Added Sugar Diet

EXPERIMENTAL

Subjects will be provided with a diet that is high in added sugars.

Other: High Added Sugar Diet

Interventions

Low Added Sugar Diet OTHER

Consumption of 10 days of a diet low in added sugars (5% of total caloric intake)

Low Added Sugar Diet

High Added Sugar Diet OTHER

Consumption of 10 days of a diet high in added sugars (25% of total caloric intake)

High Added Sugar Diet

Eligibility Criteria

• Age: 50 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• ability to provide informed consent;
• men and postmenopausal women aged 50-64 years;
• habitual intake of added sugars ≤15% of total calories;
• systolic BP \< 130 mmHg; diastolic BP \< 90 mmHg;
• body mass index (BMI) \<30 kg/m2 and % body fat \< 25% for men and \< 33% for women;
• fasting triglycerides \< 200 mg/dl (\< 2.3 mmol/L);
• LDL cholesterol \<160 mg/dl (4.14 mmol/L);
• fasting plasma glucose \<126 mg/dl (\<7.0 mmol/L) and hemoglobin A1C \< 6.5% at screening;
• weight stable in the prior 6 months (≤ 2 kg weight change);
• blood chemistries indicative of normal liver enzymes and renal function (estimated glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) prediction equation must be \>60 ml/min/1.73 m\^2).

You may not qualify if:

• current use of medications or supplements known to lower blood triglycerides or cholesterol (e.g., fibrates, statins, high dose niacin, high dose omega-3 supplement);
• chronic clinical diseases (e.g., coronary artery/peripheral artery/cerebrovascular diseases, heart failure, diabetes, chronic kidney disease requiring dialysis, neurological or autoimmune conditions affecting cognition (e.g. Alzheimer's disease or other form of dementia, Parkinson's disease, epilepsy, multiple sclerosis, large vessel infarct);
• major psychiatric disorder (e.g. schizophrenia, bipolar disorder);
• major depressive disorder (PHQ-9 ≥ 10);
• current or past (i.e., last 3 months) use of anti-hypertensive or other cardiovascular-acting medications known to influence vascular function and/or arterial stiffness;
• current medication use likely to affect central nervous system (CNS) functions (e.g. long active benzodiazepines);
• concussion within last 2 years and ≥ 3 lifetime concussions;
• heavy alcohol consumption (defined by the Centers for Disease Control and Prevention and United States Department of Agriculture as ≥8 drinks/week for women and ≥15 drinks/week for men).
• claustrophobia, metal implants, pacemaker or other factors affecting feasibility and/or safety of MRI scanning;
• recent major change in health status within previous 6 months (i.e., surgery, significant infection or illness);
• current smoking within the past 3 months;
• High degree of physical activity as defined by ≥ 25 leisure metabolic equivalent (MET)-hours/week, within the past 3 months.

Sponsors & Collaborators

• University of Delaware: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

University of Delaware

Newark, Delaware, 19713, United States

Location

Results Point of Contact

• Title: Christopher Martens
• Organization: University of Delaware

cmartens@udel.edu

302-831-7270

Study Officials

• Christopher Martens, Ph.D.

  University of Delaware

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A single-blind, randomized-crossover, controlled feeding study. Participants will be provided with 10-days each of a research diet containing low sugar (LS; 5% of energy from added sugars) vs. high sugar (HS; 25% of energy from added sugars) in a random order, separated by a 2-week washout.

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: January 27, 2022
• Study Start: January 11, 2022
• Primary Completion: May 3, 2024
• Study Completion: May 3, 2024
• Last Updated: June 12, 2025
• Results First Posted: June 12, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)