Non-Nutritive Sweeteners for Prediabetes

Overseen By Elaina Marinik, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Must not be taking: Diabetes medications, Estrogen, Testosterone

Disqualifiers: Diabetes, Heart disease, Stroke, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different non-nutritive sweeteners affect blood sugar control in people with prediabetes. It compares the impact of saccharin, acesulfame potassium, and no sweeteners. The researchers aim to determine if saccharin affects glucose levels differently than acesulfame potassium. Middle-aged or older adults with prediabetes who consume few artificial sweeteners and can follow a controlled diet for eight weeks may find this trial suitable. As an unphased trial, it offers participants the chance to contribute to important research that could enhance dietary recommendations for people with prediabetes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on diabetes medication or have used antibiotics, prebiotics, or probiotics in the last 3 months.

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

Research shows that both acesulfame potassium and saccharin are generally safe for people. Studies have found that consuming up to 15 mg of acesulfame potassium per kilogram of body weight each day is safe. The study under consideration uses only 25% of this amount. Although there are concerns about possible long-term effects, such as a higher risk of type 2 diabetes, more research is needed to confirm these risks.

Saccharin has been used for a long time and is considered safe by major health organizations at tested doses. However, results about its long-term effects, such as the risk of diabetes or heart problems, are mixed. Still, the amounts used in studies remain well within safe limits. The FDA has approved both sweeteners for use in foods.

In summary, while some studies suggest possible risks with long-term use, the trial uses much lower amounts, which are considered safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about exploring non-nutritive sweeteners like acesulfame potassium and saccharin for prediabetes because they offer a different approach from traditional options like lifestyle changes or medications like metformin. Most treatments for prediabetes focus on lowering blood sugar through diet, exercise, or medication. However, these sweeteners can potentially reduce sugar intake without sacrificing taste, offering a novel way to manage blood sugar levels. By replacing regular sugar with these zero-calorie alternatives, there's hope to help prevent the progression of prediabetes into diabetes. This could make managing prediabetes easier and more enjoyable for many people.

What evidence suggests that this trial's treatments could be effective for prediabetes?

This trial will compare the effects of acesulfame potassium and saccharin on blood sugar control in individuals with prediabetes. Research has shown mixed results regarding the impact of these non-nutritive sweeteners on blood sugar. For acesulfame potassium, some studies indicate it doesn't significantly change blood sugar levels compared to sugar or water. However, other research suggests that consuming large amounts of artificial sweeteners might link to a higher risk of developing type 2 diabetes. Regarding saccharin, some studies found no short-term connection between its use and diabetes, but the long-term effects remain unclear. Overall, evidence about how these sweeteners impact blood sugar and diabetes risk remains inconclusive. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for middle-aged and older adults over 40 with prediabetes, who have been weight stable and are not on a special diet or planning to change their physical activity. They should be non-vegetarians without serious health conditions like heart disease or diabetes, not pregnant, and consume less than one serving of artificial sweeteners per week.

Inclusion Criteria

Willing to pick up food daily and consume foods provided for an 8-week period

Your weight has stayed about the same for the past 6 months, give or take 2 kilograms.

You are not planning to change your weight or how much you exercise.

Exclusion Criteria

You have a body mass index (BMI) higher than 40.

Pregnant or plans to become pregnant

I have a history of heart, lung, hormone, blood, or cancer conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Diet

Participants follow a 2-week eucaloric lead-in diet to standardize conditions before treatment

2 weeks

Treatment

Participants are randomly assigned to one of three controlled feeding conditions for 6 weeks: saccharin, acesulfame potassium, or a control group with no NNS

6 weeks

Baseline and follow-up visits for measurements

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurements of glycemic control and inflammatory markers

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acesulfame Potassium
• Saccharin

Trial Overview The study tests the effects of two artificial sweeteners, saccharin and acesulfame potassium, on blood sugar control in people with prediabetes. Participants will follow a specific diet including these sweeteners to see if there's any difference in how their bodies handle glucose compared to a normal diet without these sweeteners.

How Is the Trial Designed?

Group I: Acesulfame Potassium Active Control 1 Intervention

Controlled feeding study. Dosage of acesulfame potassium will follow 25% of the acceptable daily intake (equivalent to 3.75 mg/kg). This amount represents 225 mg/day of acesulfame potassium for a 60 kg adult.

Group II: Saccharin Active Control 1 Intervention

Controlled feeding study. Dosage of saccharin will follow 25% of the acceptable daily intake (equivalent to 3.75 mg/kg). This amount represents 225 mg/day of saccharin for a 60 kg adult.

Group III: No NNS Placebo Group 1 Intervention

controlled feeding study with no non-nutritive sweeteners

Acesulfame Potassium is already approved in European Union, United States for the following indications:

Approved in European Union as Acesulfame Potassium for:

• General-purpose sweetener in foods and beverages

Approved in United States as Acesulfame Potassium for:

• General-purpose sweetener in foods and beverages

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

A systematic review of nine randomized controlled trials involving 979 participants with diabetes found inconclusive evidence regarding the effects of non-nutritive sweeteners (NNS) on important health outcomes like HbA1c levels and body weight, indicating very low certainty in the results.

The studies showed that NNS consumption did not significantly improve or worsen HbA1c levels or body weight compared to sugar, placebo, or other low-calorie sweeteners, and there was a lack of data on adverse events and other health-related impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-nutritive sweeteners for diabetes mellitus. Lohner, S., Kuellenberg de Gaudry, D., Toews, I., et al.[2022]

In a 6-month intervention study with 101 participants, there was a significant increase in non-nutritive sweetener (NNS) consumption, particularly aspartame and total NNS, suggesting that NNS may help reduce sugar-sweetened beverage (SSB) intake.

Despite the increase in NNS consumption, there were no significant changes in weight or body mass index (BMI) among different SSB-NNS change groups, indicating that while NNS can be used to decrease SSB consumption, their impact on weight management may need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Non-Nutritive Sweetener Consumption Patterns in Response to a Sugar-Sweetened Beverage Reduction Intervention. Acero, D., Zoellner, JM., Davy, BM., et al.[2021]

A study of breast milk from 20 lactating women found that nonnutritive sweeteners (NNS) like saccharin, sucralose, and acesulfame-potassium were present in 65% of samples, indicating that nursing infants are often exposed to these substances.

While saccharin is the only NNS detected in breast milk, the safety and potential clinical implications of early exposure to NNS through breastfeeding remain unclear, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonnutritive Sweeteners in Breast Milk. Sylvetsky, AC., Gardner, AL., Bauman, V., et al.[2019]

The newly developed non-nutritive sweetener food frequency questionnaire (NNS-FFQ) shows high reproducibility for measuring total NNS intake and specific sweeteners like erythritol and aspartame, with agreement levels above 95% for most types.

The NNS-FFQ also demonstrates acceptable validity in assessing habitual NNS consumption compared to 24-hour dietary recalls, making it a useful tool for researchers studying NNS intake in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Comparative Reproducibility and Validity of a Non-Nutritive Sweetener Food Frequency Questionnaire. Myers, EA., Passaro, EM., Hedrick, VE.[2019]

Research indicates that certain sweeteners may not significantly impact weight or appetite, suggesting they could be a useful tool for those looking to manage their calorie intake.

However, there are concerns about the long-term effects of these sweeteners on the risk of developing type 2 diabetes, highlighting the need for further studies to understand their safety and metabolic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What we know--and don't--about non-nutritive sweeteners. Dugan, J., Chiu, JW., Shubrook, JH., et al.[2020]

Low- and no-calorie sweeteners (LNCSs) have been affirmed as safe by regulatory agencies worldwide, which can help alleviate concerns about their use in managing caloric intake and obesity.

This review highlights the importance of understanding the biological fate of different LNCSs, including their absorption and metabolism, to better evaluate potential safety concerns and effects on health, such as their impact on gut microflora.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological fate of low-calorie sweeteners. Magnuson, BA., Carakostas, MC., Moore, NH., et al.[2018]

In a study of 532 adults with type 1 diabetes, 68% reported using low-calorie sweeteners (LCS) in the past month, with many believing that LCS improved their glucose control and quality of life.

Despite the positive perceptions of LCS, the study found no significant differences in quality of life scores between recent LCS users and non-users, except for lower physical activity levels among LCS users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the relationship between low-calorie sweetener use and quality of life measures in adults with type 1 diabetes. Akturk, HK., Snell-Bergeon, J., Karakus, KE., et al.[2023]

In a study of patients with diabetes, 96% reported consuming non-nutritive sweeteners (NNS), indicating their widespread use in this population.

NNS consumption was higher among men and those with type 1 diabetes, and it positively correlated with higher levels of glycated hemoglobin, suggesting a potential link to diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevalence of non-nutritive sweeteners consumption in a population of patients with diabetes in Mexico]. Romo-Romo, A., Almeda-Valdés, P., Brito-Córdova, GX., et al.[2018]

Acesulfame potassium (ACE-K), a widely used low and no calorie sweetener, is considered safe for human consumption and has high margins of safety in the aquatic environment, posing negligible risk based on extensive environmental monitoring and risk assessments.

Recent studies indicate that while ACE-K is generally persistent in the environment, wastewater treatment plants may have improved capabilities to biodegrade it, although some reports suggest it can photodegrade into potentially toxic byproducts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of the Environmental Fate and Effects of Acesulfame-Potassium. Belton, K., Schaefer, E., Guiney, PD.[2023]

A 3-month study involving 128 subjects with type 2 diabetes found that high doses of sucralose (667 mg daily) had no significant impact on glycemic control, as measured by HbA1c and fasting plasma glucose levels.

Sucralose was well-tolerated and showed no clinically meaningful differences in safety compared to a placebo, indicating it does not adversely affect glucose homeostasis in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. Grotz, VL., Henry, RR., McGill, JB., et al.[2022]

A study involving 26 patients (13 with IDDM and 13 with NIDDM) found that a single high dose of sucralose did not significantly affect short-term glucose levels or insulin response compared to a placebo.

The results suggest that sucralose is safe for short-term use in individuals with diabetes, as it does not adversely impact blood glucose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. Mezitis, NH., Maggio, CA., Koch, P., et al.[2022]

In a study with 10 healthy participants, consuming non-nutritive sweeteners (NNS) like aspartame and acesulfame-K in diet cola did not significantly affect blood glucose levels compared to glucose alone, indicating their glycaemic inactivity.

The glycaemic response to sucrose-sweetened cola was slightly lower than that of glucose and diet cola, but overall, there were no significant differences in blood glucose rises among the different beverages tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute effects of the non-nutritive sweeteners aspartame and acesulfame-K in UK diet cola on glycaemic response. Solomi, L., Rees, GA., Redfern, KM.[2020]

Citations

1. efsa.onlinelibrary.wiley.com efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2025.9317

Re‐evaluation of acesulfame K (E 950) as food additive - - 2025 Acesulfame K (E 950) was found to be stable under various conditions; at pH lower than 3 with increasing temperatures, it is degraded to a certain amount.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9655943/

Is the Use of Artificial Sweeteners Beneficial for Patients ... The early intake of ACE K was also shown to suppress the taste response to sugar. Furthermore, a large cohort study showed that high artificial sweetener intake ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11233937/

Artificial sweeteners and their implications in diabetes: a review This review thoroughly examines the nuanced relationship between artificial sweeteners and diabetes, addressing their benefits and potential risks.

4. diabetesjournals.org diabetesjournals.org/care/article/46/9/1681/153434/Artificial-Sweeteners-and-Risk-of-Type-2-Diabetes

Artificial Sweeteners and Risk of Type 2 Diabetes in the ... Compared with nonconsumers, higher consumers of artificial sweeteners had higher T2D risk (HR 1.69 [95% CI 1.45–1.97] P-trend <0.001) (Fig. 1).

5. sciencedirect.com sciencedirect.com/science/article/pii/S2161831323000807

The Combined Effects of Aspartame and Acesulfame-K ... The Asp/Ace-K group's blood glucose was nonsignificantly reduced compared with sugar (MD: –1.48 mmol/L; 95% CI: –3.26, 0.3 mmol/L; P = 0.1) and water (MD: –0.08 ...

6. medicalnewstoday.com medicalnewstoday.com/articles/318604

Acesulfame potassium safety and side effects Some people suggest acesulfame potassium side effects include an increased risk of cancer and harm during pregnancy. However, more research is ...

7. fda.gov fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food

Aspartame and Other Sweeteners in Food Text Version of Safe Levels of Sweeteners​​ Aspartame is 50 mg/kg bw/d. Acesulfame potassium (Ace-K) is 15 mg/kg bw/d. Sucralose is 5 mg/kg bw/d. ...