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This study will focus on acute effects of added sugars on brain health in a specific age group (30-64 years old). We will provide participants two meals (one meal containing 16 g of added sugars and the other containing 61 g of added sugars) and examine blood vessel function and brain structure using a MRI.
Cardiometabolic risk factors are strongly influenced by lifestyle-related environmental factors including the consumption of an unhealthy Western diet (WD). Added sugars (i.e., caloric sweeteners added to food during processing or preparation) have become a major component of the WD that are especially high in added fructose. Americans currently consume more calories from added sugars than is recommended by the American Heart Association (AHA), leading to an increased risk of cardiovascular disease (CVD), which in turn shares common risk factors with age-related memory loss and dementia. Whereas glucose is used as an immediate energy source or stored as glycogen, fructose is associated with the delayed production of triglycerides (TGs) and uric acid. Previous studies have shown that a single high-sugar meal can increase TGs in the blood 150-180 minutes after meal consumption. Increased blood TGs promote release of harmful substances that contribute to the reduction in blood vessel function and may also impact brain blood vessel function; however, these effects are not well established in humans. Our preliminary data has shown a positive association between high added sugars and plasma TG and uric acid concentration, which has been associated with reduced blood vessel function. However, the direct effects of acute added sugar intake on brain blood vessel function is currently unknown. We have also observed that high blood TGs are associated with reduced microstructural integrity of the hippocampus, a brain structure important for memory and other thinking abilities. Therefore, the purpose of this study is to establish a causal link between high added sugar consumption and reduced brain blood vessel function and microstructural integrity. We propose to examine the acute effects of high TGs and uric acid from a single high-sugar meal on brain blood vessel function and brain integrity. To test this hypothesis, we will conduct a randomized-controlled crossover trial of a high-sugar meal vs. a low-sugar meal. This project has the potential to identify future risk of dementia and other memory-related brain diseases caused from repetitive acute insults from high added sugar consumption and will help us inform the public to make better dietary choices.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Added Sugar Meal | Experimental | Participants will be provided a meal low in added sugars. |
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| High Added Sugar Meal | Experimental | Participants will be provided a meal high in added sugars. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low Added Sugar Meal | Other | Consumption of a single 1,250 kcal meal containing 16 g of added sugars (5% of total energy) |
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| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in cerebrovascular reactivity at 3 hours post-consumption of each meal | % change in total cerebral perfusion measured using pseudo-continuous arterial spin labeling in response to 3-minutes of hypercapnia (+9 mmHg increase in PETCO2) | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
| Change from baseline in hippocampal stiffness after 3 hours post-consumption of each meal | Magnetic Resonance Elastography (MRE) of the brain to assess hippocampal viscoelastic properties while the head will be vibrated using the Resoundant acoustic driver system | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
| Change from baseline in hippocampal damping ratio at 3 hours post-consumption of each meal | Magnetic Resonance Elastography (MRE) of the brain to assess hippocampal viscoelastic properties while the head will be vibrated using the Resoundant acoustic driver system | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
| Change from baseline in uric acid at 3 hours post-consumption of each meal | Blood biomarker of uric acid (e.g. serum uric acid) | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
| Change from baseline in triglycerides at 3 hours post-consumption of each meal | Blood biomarker of triglycerides (e.g. serum triglycerides) | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in hippocampal cerebrovascular reactivity at 3 hours post-consumption of each meal | % change in total cerebral perfusion measured using pseudo-continuous arterial spin labeling in response to 3-minutes of hypercapnia (+9 mmHg increase in PETCO2) | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Martens, PhD | University of Delaware | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Delaware | Newark | Delaware | 19713 | United States |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Apr 18, 2024 | |
| Reset | Sep 12, 2024 | |
| Release | Apr 29, 2026 | |
| Reset | May 21, 2026 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Apr 18, 2024 | Sep 12, 2024 | |||
| Apr 29, 2026 |
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| High Added Sugar Meal | Other | Consumption of a single 1,250 kcal meal containing 61 g of added sugars (20% of total energy) |
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| Change from baseline in oxidative stress at 3 hours post-consumption of each meal | Blood biomarker of oxidative stress (e.g. superoxide) | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
| Changes from baseline in resting cerebral blood flow at 3 hours post-consumption of each meal | Total cerebral perfusion measured using pseudo-continuous arterial spin labeling | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
| Change from baseline in other lipid profile at 3 hours post-consumption of each meal | Blood biomarkers of lipid profile (e.g. cholesterol, HDL, LDL, and VLDL) | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
| Change from baseline in blood pressure at 3 hours post-consumption of each meal | Blood pressure measures at baseline and every half hour until post-consumption of meal | Over 2 weeks, at baseline and 3 hours post-consumption of each meal (low and high added sugar), separated by a 1-week washout |
| May 21, 2026 |