The Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation

Official title

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

Overview

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.

Interventions

• Other Erythritol
  Erythritol is a naturally occurring and non-nutritive sugar alcohol that is classified as generally recognized as safe (GRAS)
• Other 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.

Primary outcome measures

• P-selectin, a platelet surface marker, assessed as median fluorescence intensity [Time frame: 6 weeks]
• P-selectin, a platelet surface marker, assessed as percentage of P-selectin positive cells [Time frame: 6 weeks]
• PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as median fluorescence intensity [Time frame: 6 weeks]
• PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as percentage of PAC-1 positive cells [Time frame: 6 weeks]
• Annexin V, a platelet surface marker, assessed as median fluorescence intensity [Time frame: 6 weeks]
• Annexin V, a platelet surface marker, assessed as percentage of annexin V positive cells [Time frame: 6 weeks]
• Platelet reactivity to physiologic agonist, assessed as change in median fluorescence intensity [Time frame: 6 weeks]
• Platelet aggregation in response to physiologic agonist, assessed as aggregation/min [Time frame: 6 weeks]
• Platelet aggregation in response to physiologic agonist, assessed as percent of maximum aggregation [Time frame: 6 weeks]
• Platelet-leukocyte interaction, assessed as platelet/leukocyte aggregate size by fluorescence mean intensity [Time frame: 6 weeks]

Secondary outcome measures (9)

• Plasma concentration of E-Selectin [Time frame: 6 weeks]
• Plasma concentration of sVCAM1 [Time frame: 6 weeks]
• Plasma concentration of sICAM1 [Time frame: 6 weeks]
• Plasma concentration of D-dimer [Time frame: 6 weeks]
• Plasma concentration of Platelet factor 4 [Time frame: 6 weeks]
• Plasma concentration of Fibrinogen [Time frame: 6 weeks]
• Plasma concentration of Prothrombin fragment 1+2 [Time frame: 6 weeks]
• Plasma concentration of Plasmin-antiplasmin complex [Time frame: 6 weeks]
• Plasma concentration of Lp(a) [Time frame: 6 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Basic science

Study locations

United States · 1 center

• Ragle Human Nutrition Research Center, University of California, Davis — Davis

Publications

• 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. PMID 36849732

Identifiers

NCT: NCT05967741 · 2030510

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗