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The Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation

Not Applicable
Recruiting
Conditions
Platelet Aggregation, Spontaneous
Vascular Thrombosis
Interventions
Other: Erythritol
Other: Aspartame
Registration Number
NCT05967741
Lead Sponsor
University of California, Davis
Brief Summary

The purpose is to conduct a dietary intervention study in which human participants will consume beverages sweetened with erythritol or aspartame, each for 2 weeks, in a randomized crossover design

Detailed Description

There is a strong correlation between plasma erythritol concentrations and adverse cardiovascular events in high risk individuals. It has also been demonstrated that consumption of dietary erythritol leads to high levels of plasma erythritol. There is in vitro evidence that erythritol at comparable concentrations promotes platelet activation. However, there is no direct evidence that links human consumption of erythritol with the onset of platelet activation and adhesion leading to inflammation. The investigators seek to fill this evidence gap by conducting a randomized crossover dietary intervention study in which human participants will consume beverages sweetened with erythritol or aspartame, each for two weeks.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
24
Inclusion Criteria
  • BMI ≥ 27 kg/m2
Exclusion Criteria
  • • History of blood clot, transient ischemic attack (TIA), stroke, angina, heart attack, or peripheral vascular disease, or current cancer diagnosis.

    • Pregnant or lactating women
    • Current, prior (within 12 months), or anticipated use of medications for treatment of hyperlipidemia, high blood pressure or diabetes, or any medication that in the opinion of the investigators will confound results.
    • Unwilling to forego the use of anti-inflammatory medication during study.
    • Unwilling to forego the use of marijuana during the study.
    • Use of tobacco.
    • Strenuous exerciser (>4 hours/week at a level more vigorous than walking).
    • Surgery or medication for weight loss.
    • Diet exclusions: Food allergies or dietary restrictions that may undermine compliance to dietary protocol, routine ingestion of more than 2 sugar-sweetened beverages or 2 alcoholic beverage/day. Unwillingness to consume artificial or noncaloric sweeteners. Habitual consumption (>10 gram/day) of beverage or foods that contain erythritol. Recent or current weight loss diet.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Erythritol-sweetened beverageErythritol1-gram erythritol/kg body weight/day, divided into three beverage servings and fruit-flavored with Kool-Aid® unsweetened drink mix.
Aspartame-sweetened beverageAspartameControl beverages will be made from a noncaloric aspartame-sweetened, fruit-flavored drink mix at the concentration needed to match the sweetness (\~3 mg aspartame/kg/day) and flavoring of the erythritol beverages on a per volume basis.
Primary Outcome Measures
NameTimeMethod
Platelet aggregation in response to physiologic agonist, assessed as aggregation/min6 weeks

The change in aggregation/min induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

Platelet-leukocyte interaction, assessed as platelet/leukocyte aggregate size by fluorescence mean intensity6 weeks

Change in platelet/leukocyte aggregate size, an index of platelet-leukocyte interaction, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

P-selectin, a platelet surface marker, assessed as percentage of P-selectin positive cells6 weeks

Change in percentage of P-selectin positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as median fluorescence intensity6 weeks

Change in median fluorescence intensity of PAC-1, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as percentage of PAC-1 positive cells6 weeks

Change in percentage of PAC-1 positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

P-selectin, a platelet surface marker, assessed as median fluorescence intensity6 weeks

Change in median fluorescence intensity of P-selectin, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

Annexin V, a platelet surface marker, assessed as percentage of annexin V positive cells6 weeks

Change in percentage of annexin V positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

Platelet reactivity to physiologic agonist, assessed as change in median fluorescence intensity6 weeks

The change in median fluorescence intensity induced by physiologic agonists, an index of platelet reactivity, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

Annexin V, a platelet surface marker, assessed as median fluorescence intensity6 weeks

Change in median fluorescence intensity of annexin V, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

Platelet aggregation in response to physiologic agonist, assessed as percent of maximum aggregation6 weeks

The change in % maximum aggregation induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

Secondary Outcome Measures
NameTimeMethod
Plasma concentration of sICAM16 weeks

Change in plasma sICAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage

Plasma concentration of E-Selectin6 weeks

Change in plasma E-Selectin in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage

Plasma concentration of sVCAM16 weeks

Change in plasma sVCAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage

Plasma concentration of D-dimer6 weeks

Change in plasma D-dimer in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage

Plasma concentration of Fibrinogen6 weeks

Change in plasma fibrinogen in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage

Plasma concentration of Platelet factor 46 weeks

Change in plasma platelet factor 4 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage

Plasma concentration of Prothrombin fragment 1+26 weeks

Change in plasma prothrombin fragment 1+2 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage

Plasma concentration of Plasmin-antiplasmin complex6 weeks

Change in plasma plasmin-antiplasmin complex in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage

Plasma concentration of Lp(a)6 weeks

Change in plasma Lp(a) in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage

Trial Locations

Locations (1)

Ragle Human Nutrition Research Center, University of California, Davis

🇺🇸

Davis, California, United States

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