Erythritol for Blood Clot Prevention and Inflammation

(EASI Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of California, Davis

Must not be taking: Hyperlipidemia, Hypertension, Diabetes meds

Disqualifiers: Cardiovascular disease, Cancer, Pregnancy, others

Trial Summary

What is the purpose of this trial?

This trial involves participants drinking beverages sweetened with either erythritol or aspartame for a short period. The study focuses on people at high risk for heart problems. Researchers aim to see if erythritol causes changes in the blood that could lead to heart issues, compared to aspartame. Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms.

Will I have to stop taking my current medications?

Yes, if you are currently using medications for high cholesterol, high blood pressure, diabetes, or any other medication that might affect the study results, you will need to stop taking them to participate in this trial.

What data supports the effectiveness of the treatment Erythritol for Blood Clot Prevention and Inflammation?

The research indicates that erythritol may increase the risk of blood clots, as it was associated with higher platelet reactivity and thrombosis potential, which could be counterproductive for blood clot prevention. ^{1 2 3 4 5}

Is erythritol safe for human consumption?

Erythritol is generally considered a safe sugar substitute, but some studies suggest it may increase the risk of heart-related events and blood clotting. More research is needed to fully understand its long-term safety. ^{1 2 3 4 6}

How does erythritol differ from other treatments for blood clot prevention and inflammation?

Erythritol is unique because it is a sugar alcohol that may help reduce inflammation and improve vascular function, particularly in patients with diabetes, without the caloric impact of traditional sugars. Unlike standard blood clot prevention treatments, erythritol is primarily known as a sweetener and may offer additional metabolic benefits. ^{1 2 6 7 8}

Research Team

Eligibility Criteria

This trial is for adults with a BMI of 27 kg/m2 or higher who don't exercise strenuously, aren't pregnant or lactating, and have no major dietary restrictions. It's not for those who drink lots of sugar or alcohol, use certain medications, have had serious cardiovascular issues, are on weight loss drugs or diets, consume erythritol regularly, use anti-inflammatory drugs or marijuana, smoke tobacco, or have had recent surgery.

Inclusion Criteria

Your body mass index (BMI) is 27 or higher.

Exclusion Criteria

Unwilling to forego the use of marijuana during the study

I am taking or might take medication for high cholesterol, high blood pressure, or diabetes.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants consume beverages sweetened with erythritol or aspartame in a randomized crossover design

4 weeks

Multiple visits for beverage consumption and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Treatment Details

Interventions

• Aspartame (Other)
• Erythritol (Other)

Trial Overview The study tests the effects of drinks sweetened with erythritol versus aspartame on blood clotting and inflammation. Participants will try each sweetener in their beverages for two weeks in a random order to see how it affects their body.

Participant Groups

Group I: Erythritol-sweetened beverage Experimental Treatment 1 Intervention

1-gram erythritol/kg body weight/day, divided into three beverage servings and fruit-flavored with Kool-Aid® unsweetened drink mix.

Group II: Aspartame-sweetened beverage Placebo Group 1 Intervention

Control 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.

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Rakesh Dixit

University of California, Davis

Chief Executive Officer since 2024

PhD in Biochemistry and Molecular Biology from the University of California, Davis

Suresh Mahabhashyam

University of California, Davis

Chief Medical Officer since 2020

MD from Bangalore Medical College

Findings from Research

D-allulose significantly lowered glucose and insulin levels compared to tap water, suggesting it may be a beneficial alternative sweetener for managing blood sugar levels, although Bayesian analysis indicated no significant difference in insulin response.

Erythritol reduced ghrelin levels compared to tap water, which could help with appetite regulation, while both sweeteners showed no adverse effects on blood lipids, uric acid, or inflammation markers, indicating their safety as sugar substitutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Effects and Safety Aspects of Acute D-allulose and Erythritol Administration in Healthy Subjects. Teysseire, F., Bordier, V., Budzinska, A., et al.[2023]

In a pilot study with 24 participants, consuming 36 g/day of erythritol for 4 weeks significantly improved endothelial function in patients with type 2 diabetes, indicating potential cardiovascular benefits.

Chronic erythritol consumption also reduced central pulse pressure and showed a trend towards decreased aortic stiffness, suggesting it may be a beneficial sugar substitute for managing diabetes-related vascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study. Flint, N., Hamburg, NM., Holbrook, M., et al.[2021]

A systematic review and meta-analysis of 29 studies found that aspartame consumption does not significantly affect key metabolic parameters such as blood glucose, insulin levels, cholesterol, triglycerides, or body weight, suggesting it does not provide metabolic benefits for diabetes or obesity.

The analysis indicated that aspartame does not alter energy intake compared to control or sucrose, reinforcing the idea that it may not be beneficial for weight management or metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trials. Santos, NC., de Araujo, LM., De Luca Canto, G., et al.[2023]

A study involving over 4,000 patients found that higher circulating levels of erythritol, a common artificial sweetener, are linked to an increased risk of major adverse cardiovascular events (MACE), such as heart attacks and strokes.

Erythritol was shown to enhance platelet reactivity and thrombosis formation in laboratory studies, and ingestion in healthy volunteers led to sustained increases in plasma erythritol levels, raising concerns about its long-term safety and potential cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The artificial sweetener erythritol and cardiovascular event risk. Witkowski, M., Nemet, I., Alamri, H., et al.[2023]

Erythritol is absorbed in a dose-dependent manner and is metabolized into erythronate, while xylitol shows very low absorption and is not metabolized into erythronate, indicating different metabolic pathways for these sweeteners.

The study involved 17 healthy participants who received varying doses of erythritol and xylitol, highlighting the need for further research to understand the health implications of erythritol's metabolization into erythronate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption and Metabolism of the Natural Sweeteners Erythritol and Xylitol in Humans: A Dose-Ranging Study. Bordier, V., Teysseire, F., Senner, F., et al.[2022]

A study using bidirectional Mendelian randomization found no causal link between erythritol, a low-calorie sweetener, and an increased risk of coronary artery disease (CAD), suggesting it may be safe for cardiovascular health.

The analysis indicated that erythritol might be associated with a decrease in body mass index (BMI), which could be beneficial for weight management in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythritol as a potential causal contributor to cardiometabolic disease: A Mendelian randomization study. Khafagy, R., Paterson, AD., Dash, S.[2023]

Erythritol significantly reduces dental plaque weight and the adherence of harmful bacteria like S. mutans to teeth, which helps in preventing dental caries.

Compared to other sweeteners like xylitol and sorbitol, erythritol shows superior efficacy in improving oral health, making it a promising alternative for dental care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythritol Is More Effective Than Xylitol and Sorbitol in Managing Oral Health Endpoints. de Cock, P., Mäkinen, K., Honkala, E., et al.[2020]

In a study with C57BL/6J mice, erythritol significantly reduced body weight and improved glucose tolerance when given in a high-fat diet, indicating its potential as a beneficial sugar substitute for metabolic health.

Erythritol also enhanced the production of short-chain fatty acids and improved immune responses, suggesting it may help combat obesity-related metabolic disorders by modulating innate immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythritol Ameliorates Small Intestinal Inflammation Induced by High-Fat Diets and Improves Glucose Tolerance. Kawano, R., Okamura, T., Hashimoto, Y., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Metabolic Effects and Safety Aspects of Acute D-allulose and Erythritol Administration in Healthy Subjects. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Metabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trials. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

The artificial sweetener erythritol and cardiovascular event risk. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Absorption and Metabolism of the Natural Sweeteners Erythritol and Xylitol in Humans: A Dose-Ranging Study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Erythritol as a potential causal contributor to cardiometabolic disease: A Mendelian randomization study. [2023]

7. Egypt pubmed.ncbi.nlm.nih.gov

Erythritol Is More Effective Than Xylitol and Sorbitol in Managing Oral Health Endpoints. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Erythritol Ameliorates Small Intestinal Inflammation Induced by High-Fat Diets and Improves Glucose Tolerance. [2023]