Erythritol for Blood Clot Prevention and Inflammation

(EASI Trial)

Overseen By Marinelle Nunez, B.S.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Davis

Must not be taking: Hyperlipidemia, Hypertension, Diabetes meds

Disqualifiers: Cardiovascular disease, Cancer, Pregnancy, others

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two sweeteners, erythritol and aspartame, affect blood clot prevention and inflammation. Participants will consume beverages sweetened with either erythritol or aspartame for two weeks each to determine any differences in their effects. It is ideal for individuals with a BMI (body mass index) of 27 or higher who have not experienced issues like blood clots or heart problems and are willing to avoid certain medications and lifestyle habits during the study. As an unphased trial, this study provides a unique opportunity to contribute to understanding the health impacts of common sweeteners.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that erythritol, a sugar substitute, might raise the risk of blood clots. Some studies found that consuming erythritol could make platelets, which help blood clot, more active, potentially increasing the chance of clot formation. A few reports even suggest a link between erythritol and a higher risk of heart attacks.

In contrast, aspartame, another sugar substitute, is generally considered safe and is often used in diet sodas and other sugar-free products. Health authorities like the FDA have approved it for many years. While some people report mild side effects like headaches, strong evidence does not connect aspartame to serious health issues.

For those considering joining a clinical trial involving these sweeteners, understanding these risks is important. Always consult a healthcare provider if there are concerns about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Erythritol is unique because it offers a novel approach to preventing blood clots and inflammation by using a natural sweetener instead of traditional medications like anticoagulants or anti-inflammatory drugs. Unlike these standard treatments, which often come with significant side effects, erythritol is a sugar alcohol that could potentially reduce risks with its safer profile. Researchers are excited about this treatment because it targets the condition through a dietary intervention, providing a potentially safer and more accessible option for managing blood clots and inflammation.

What evidence suggests that this trial's treatments could be effective for blood clot prevention and inflammation?

This trial will compare the effects of erythritol and aspartame on blood clot prevention and inflammation. Research has shown that erythritol, a sugar substitute, might raise the risk of blood clots. Studies have found that consuming erythritol can increase the activity of platelets, the tiny blood cells that help form clots. This heightened activity can lead to more blood clots, potentially raising the risk of heart attacks or strokes. These findings suggest a possible risk linked to erythritol consumption. Participants in this trial will receive either an erythritol-sweetened beverage or an aspartame-sweetened beverage as a control. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

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

Unwilling to forego the use of marijuana during the study

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Aspartame
• Erythritol

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10334259/

The artificial sweetener erythritol and cardiovascular event risk Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of ...

2. ahajournals.org ahajournals.org/doi/10.1161/ATVBAHA.124.321019

Ingestion of the Non-Nutritive Sweetener Erythritol, but Not ... Our studies show ingestion of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity and thrombosis potential in ...

3. cnn.com cnn.com/2024/08/08/health/erythritol-blood-clotting-wellness

Erythritol: Sweetener in stevia linked to blood clots, study ... “What we're seeing with erythritol is the platelets become super responsive: A mere 10% stimulant produces 90% to 100% of a clot formation,” ...

4. lerner.ccf.org lerner.ccf.org/news/article/?title=New+study+compares+effects+of+artificial+sweetener+erythritol+and+sugar&id=d177e14f9e80d5ac45a329c97f65b12208a2fed3

New study compares effects of artificial sweetener erythritol ... A side effect of artificial sweetener erythritol was increased potential for blood clotting compared to sugar, Cleveland Clinic researchers

5. nih.gov nih.gov/news-events/nih-research-matters/erythritol-cardiovascular-events

Erythritol and cardiovascular events These results suggest that consuming erythritol can increase blood clot formation. This, in turn, could increase the risk of heart attack or stroke.

6. healthline.com healthline.com/health-news/artificial-sweetener-erythritol-blood-clot-risk

Artificial Sweetener Erythritol May Raise the Risk of Blood ... A recent study presents evidence of a connection between the artificial sweetener erythritol and an increased risk of blood clots.

7. prevention.com prevention.com/health/a43122126/sugar-substitute-erythritol-heart-attack-stroke-study/

Study: Sugar Substitute Erythritol May Cause Heart Attack ... A new study found that the sugar substitute erythritol is linked to an increased risk of blood clots and heart attack. Here's what we know.