The Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation

Platelet Aggregation, Spontaneous Clinical Trial

— EASI  

Official title:

Randomized Controlled Clinical Trial to Gauge the Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05967741
• Other study ID #: 2030510
• Status: Recruiting
• Phase: N/A
• Start date: July 20, 2023
• Est. completion date: June 2024

Study information

• Verified date: September 2023
• Source: University of California, Davis
• Contact: Kimber L. Stanhope, Ph.D.
• Phone: 5302190914
• Email: klstanhope[@]ucdavis.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Inflammation
• Platelet Aggregation, Spontaneous
• Thrombosis
• Vascular Thrombosis

Intervention

Other:
• Erythritol
Erythritol is a naturally occurring and non-nutritive sugar alcohol that is classified as generally recognized as safe (GRAS)
• Aspartame
Aspartame consists of two amino acids, phenylalanine and aspartic acid, and a methyl group. It does not have metabolic effects and has served as the blinded control beverage in the investigators' completed NIH-funded clinical trials.

Locations

Country	Name	City	State
United States	Ragle Human Nutrition Research Center, University of California, Davis	Davis	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Davis

Country where clinical trial is conducted

United States, 

References & Publications (1)

Witkowski M, Nemet I, Alamri H, Wilcox J, Gupta N, Nimer N, Haghikia A, Li XS, Wu Y, Saha PP, Demuth I, Konig M, Steinhagen-Thiessen E, Cajka T, Fiehn O, Landmesser U, Tang WHW, Hazen SL. The artificial sweetener erythritol and cardiovascular event risk. Nat Med. 2023 Mar;29(3):710-718. doi: 10.1038/s41591-023-02223-9. Epub 2023 Feb 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma concentration of glucose	Change in plasma fasting glucose in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage	6 weeks
Other	Plasma concentration of triglyceride	Change in plasma fasting triglyceride in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage	6 weeks
Other	Plasma concentration of cholesterol	Change in plasma fasting cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage	6 weeks
Other	Plasma concentration of low density lipoprotein cholesterol	Change in plasma fasting low density lipoprotein cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage	6 weeks
Other	Plasma concentration of high density lipoprotein cholesterol	Change in plasma fasting high density lipoprotein cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage	6 weeks
Other	Plasma concentration of apolipoprotein B	Change in plasma fasting apolipoprotein B in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage	6 weeks
Other	Plasma concentration of apolipoprotein CIII	Change in plasma fasting apolipoprotein CIII in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage	6 weeks
Other	Plasma concentration of uric acid	Change in plasma fasting uric acid in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage	6 weeks
Primary	P-selectin, a platelet surface marker, assessed as median fluorescence intensity	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	6 weeks
Primary	P-selectin, a platelet surface marker, assessed as percentage of P-selectin positive cells	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	6 weeks
Primary	PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as median fluorescence intensity	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	6 weeks
Primary	PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as percentage of PAC-1 positive cells	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	6 weeks
Primary	Annexin V, a platelet surface marker, assessed as median fluorescence intensity	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	6 weeks
Primary	Annexin V, a platelet surface marker, assessed as percentage of annexin V positive cells	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	6 weeks
Primary	Platelet reactivity to physiologic agonist, assessed as change in median fluorescence intensity	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	6 weeks
Primary	Platelet aggregation in response to physiologic agonist, assessed as aggregation/min	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	6 weeks
Primary	Platelet aggregation in response to physiologic agonist, assessed as percent of maximum aggregation	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	6 weeks
Primary	Platelet-leukocyte interaction, assessed as platelet/leukocyte aggregate size by fluorescence mean intensity	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	6 weeks
Secondary	Plasma concentration of E-Selectin	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	6 weeks
Secondary	Plasma concentration of sVCAM1	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	6 weeks
Secondary	Plasma concentration of sICAM1	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	6 weeks
Secondary	Plasma concentration of D-dimer	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	6 weeks
Secondary	Plasma concentration of Platelet factor 4	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	6 weeks
Secondary	Plasma concentration of Fibrinogen	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	6 weeks
Secondary	Plasma concentration of Prothrombin fragment 1+2	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	6 weeks
Secondary	Plasma concentration of Plasmin-antiplasmin complex	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	6 weeks
Secondary	Plasma concentration of Lp(a)	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	6 weeks