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

Trial Summary

What is the purpose of this trial?

Animal and observational research in humans suggest that specific types of non-nutritive sweeteners (NNS) may impair glycemic control. However, whether NNS consumption impacts glucose homeostasis in middle-aged/older adults with prediabetes is unknown, and potential mechanisms by which this could occur have yet to be identified. The overall objective of this R21 proposal is to establish proof-of-concept for alterations in glucose homeostasis following intake of saccharin, but not acesulfame potassium, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS.

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.

What data supports the effectiveness of the treatment Acesulfame Potassium and similar non-nutritive sweeteners for prediabetes?

Research shows that non-nutritive sweeteners like acesulfame-K do not significantly affect blood sugar levels, suggesting they might be a safe alternative to sugar for people trying to manage their blood sugar, such as those with prediabetes. ^{1 2 3 4 5}

Are non-nutritive sweeteners like acesulfame potassium and saccharin safe for human consumption?

Non-nutritive sweeteners such as acesulfame potassium and saccharin are considered safe for human consumption by regulatory agencies like the USFDA. However, saccharin is the only one found in breast milk after consumption, and its safety during pregnancy and lactation is not as well established as other sweeteners. ^{6 7 8 9 10}

How does the treatment with Acesulfame Potassium and Saccharin differ from other treatments for prediabetes?

This treatment uses non-nutritive sweeteners, which are low-calorie alternatives to sugar, potentially helping to reduce sugar intake and manage blood sugar levels without adding calories. Unlike traditional treatments that may focus on medication or lifestyle changes, this approach leverages sweeteners like Acesulfame Potassium and Saccharin to support dietary adjustments. ^{4 7 9 11 12}

Eligibility Criteria

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 consume less than one serving of artificial sweetener per week.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

References

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

Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. [2022]

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

Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The acute effects of the non-nutritive sweeteners aspartame and acesulfame-K in UK diet cola on glycaemic response. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Non-nutritive sweeteners for diabetes mellitus. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Assessing the relationship between low-calorie sweetener use and quality of life measures in adults with type 1 diabetes. [2023]

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

What we know--and don't--about non-nutritive sweeteners. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Changes in Non-Nutritive Sweetener Consumption Patterns in Response to a Sugar-Sweetened Beverage Reduction Intervention. [2021]

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

Biological fate of low-calorie sweeteners. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Nonnutritive Sweeteners in Breast Milk. [2019]

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

A Review of the Environmental Fate and Effects of Acesulfame-Potassium. [2023]

11. Mexico pubmed.ncbi.nlm.nih.gov

[Prevalence of non-nutritive sweeteners consumption in a population of patients with diabetes in Mexico]. [2018]

12. Switzerland pubmed.ncbi.nlm.nih.gov

The Comparative Reproducibility and Validity of a Non-Nutritive Sweetener Food Frequency Questionnaire. [2019]