Non-Nutritive Sweetener Consumption for Prediabetes

Overseen By Valisa Hedrick, 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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

30 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on diabetes medication, antibiotics, prebiotics, or probiotics, or if you use estrogen or testosterone.

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 past 3 months.

What data supports the idea that Non-Nutritive Sweetener Consumption for Prediabetes is an effective treatment?

The available research shows mixed results about the effectiveness of non-nutritive sweeteners (NNS) for prediabetes. Some studies suggest that NNS can help reduce body weight and BMI, especially when compared to sugar, which could be beneficial for people with prediabetes. However, other studies indicate that NNS might not have a significant impact on preventing type 2 diabetes, and some even suggest a potential risk. Overall, the evidence is inconsistent, and more well-designed studies are needed to draw firm conclusions. Compared to other sweeteners like fructose, xylitol, and sorbitol, NNS are often used to reduce sugar intake, but their overall impact on blood sugar control and diabetes risk remains unclear. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Non-Nutritive Sweetener Intake for prediabetes?

Some studies suggest that non-nutritive sweeteners (NNS) can help reduce body weight and BMI (body mass index) when used instead of sugar, especially in people with overweight or obesity. However, the evidence is mixed, and more research is needed to determine their impact on preventing or managing prediabetes. ^{1 2 3 4 5}

What safety data exists for non-nutritive sweeteners?

Non-nutritive sweeteners (NNS) have been widely evaluated in scientific literature and reviewed by international regulatory health agencies. The FDA has granted a generally recognized as safe (GRAS) status to several NNS, including aspartame, saccharine, sucralose, neotame, acesulfame-K, and stevia. Despite this, there is inconclusive evidence regarding their benefits and potential risks, especially for susceptible populations like pregnant women, children, and individuals with certain health conditions. While moderate use of NNS may be beneficial for weight management and diabetes, it is recommended to consume them in minimal amounts. The American Dietetic Association supports the safe use of NNS when consumed within federal nutrition guidelines. However, more research is needed to fully understand their long-term health effects. ^{6 7 8 9 10}

Are non-nutritive sweeteners safe for human consumption?

Non-nutritive sweeteners (NNS) are generally recognized as safe by the FDA and other health agencies, but there are some concerns about their use during pregnancy, lactation, and in certain populations like children and people with specific health conditions. While moderate use is considered safe, it's recommended to consume them in minimal amounts as part of a balanced diet. ^{6 7 8 9 10}

Is non-nutritive sweetener intake a promising treatment for prediabetes?

Non-nutritive sweeteners can help reduce sugar intake and may aid in weight loss or maintenance, which is beneficial for managing prediabetes. They provide sweetness without adding calories, potentially helping to control blood sugar levels. However, the evidence is mixed, and more research is needed to confirm their effectiveness in preventing type 2 diabetes. ^{1 2 3 11 12}

How does the treatment of non-nutritive sweetener intake differ from other treatments for prediabetes?

Non-nutritive sweeteners are unique because they provide sweetness without adding calories, which can help reduce sugar intake and potentially aid in weight management. Unlike other treatments that may focus on medication or more drastic dietary changes, these sweeteners offer a way to control calorie and sugar intake without significantly altering the taste of foods and beverages. ^{1 2 3 11 12}

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 sucralose, but not aspartame, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS.

Research Team

Valisa Hedrick, PhD

Principal Investigator

Virginia Polytechnic Institute and State University

Eligibility Criteria

This trial is for middle-aged/older adults over 50 with prediabetes who are relatively inactive, willing to consume provided foods for 8 weeks, and have been weight stable. They should not be consuming much non-nutritive sweetener already (less than one serving per week), must not have plans to change their diet or exercise routine, and cannot be pregnant or planning pregnancy.

Inclusion Criteria

Your body mass index (BMI) is less than 40.

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

You eat less than one serving of artificial sweetener per week.

Exclusion Criteria

My blood pressure is not higher than 159/99 mmHg.

I have a history of heart, lung, blood, hormone, or cancer-related diseases.

I have food allergies or PKU.

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: sucralose, aspartame, or no NNS, for 6 weeks

6 weeks

Follow-up

Participants are monitored for changes in glycemic control, insulin sensitivity, and inflammatory markers after treatment

4 weeks

Treatment Details

Interventions

• Non-Nutritive Sweetener Intake

Trial Overview The study investigates how the consumption of a non-nutritive sweetener called sucralose affects blood sugar control in older adults with prediabetes compared to aspartame and a regular diet without these sweeteners. The goal is to see if sucralose alters glucose levels differently than other options.

Participant Groups

Group I: Sucralose Active Control 1 Intervention

Controlled feeding study. Dosage of sucralose will follow 25% of the acceptable daily intake (equivalent to 1.25 mg/kg for sucralose). This amount represents 75 mg/day of sucralose for a 60 kg adult.

Group II: Aspartame Active Control 1 Intervention

Controlled feeding study. Dosage of aspartame will follow 25% of the acceptable daily intake (equivalent to 12.5 mg/kg for aspartame). This amount represents 750 mg/day of aspartame for a 60 kg adult.

Group III: No NNS Placebo Group 1 Intervention

Controlled feeding study with no non-nutritive sweeteners.

Non-Nutritive Sweetener Intake is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Various Non-Nutritive Sweeteners for:

• General food additive
• Dietary supplement

Approved in United States as Various Non-Nutritive Sweeteners for:

• General food additive
• Dietary supplement

Approved in Canada as Various Non-Nutritive Sweeteners for:

• General food additive
• Dietary supplement

Approved in Japan as Various Non-Nutritive Sweeteners for:

• General food additive
• Dietary supplement

Approved in China as Various Non-Nutritive Sweeteners for:

• General food additive
• Dietary supplement

Approved in Switzerland as Various Non-Nutritive Sweeteners for:

• General food additive
• Dietary supplement

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

Findings from Research

The review of literature on non-nutritive sweeteners (NNS) and their relationship with type 2 diabetes (T2D) shows inconsistent results, with some studies suggesting NNS may increase the risk of T2D while others indicate a neutral or protective effect.

Due to the heterogeneity of the studies and the lack of strong conclusions, there is a need for well-designed research that considers all confounding factors, prompting caution among clinicians who recommend NNS as healthy sugar substitutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-nutritive sweeteners and type 2 diabetes: Should we ring the bell? Daher, MI., Matta, JM., Abdel Nour, AM.[2019]

Nutritive sweeteners like fructose, xylitol, and sorbitol are being explored as alternatives to saccharin for diabetic patients, focusing on their impact on blood glucose control, obesity, and hyperlipidemia.

The review highlights the need to consider both the efficacy of these sweeteners in managing diabetes-related dietary concerns and their potential side effects, ensuring a balanced approach to their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of fructose, sorbitol, or xylitol as a sweetener in diabetes mellitus. Brunzell, JD.[2017]

In Australia, 18.2% of adults and 8.5% of children reported consuming non-nutritive sweeteners (NNS), primarily from sources like soft drinks, tabletop sweeteners, and yogurt.

While NNS consumers among adults had lower free sugar intake, their overall energy intake was similar to non-consumers, suggesting that while NNS can help reduce sugar consumption, they may lead to compensatory increases in energy intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet-Quality and Socio-Demographic Factors Associated with Non-Nutritive Sweetener Use in the Australian Population. Grech, A., Kam, CO., Gemming, L., et al.[2018]

A systematic review of 20 randomized controlled trials involving 2914 participants found that nonnutritive sweeteners (NNS) can lead to significant weight loss compared to sugar, especially in individuals with overweight or obesity on unrestricted diets.

While NNS showed no significant effect compared to placebo or water, they were effective in reducing body weight when compared to sucrose, suggesting that replacing sugar with NNS may be a beneficial strategy for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of nonnutritive sweeteners on body weight and BMI in diverse clinical contexts: Systematic review and meta-analysis. Laviada-Molina, H., Molina-Segui, F., Pérez-Gaxiola, G., et al.[2021]

Short-term studies indicate that substituting non-nutritive sweeteners (NNS) for added sugars may help reduce energy intake and improve glycemic control, but the effects are often modest or negligible.

Long-term observational studies on NNS use and its relationship with obesity or type 2 diabetes are complicated by factors like reverse causality, making it difficult to draw clear conclusions about their effectiveness in reducing added sugar intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-nutritive sweeteners: evidence for benefit vs. risk. Gardner, C.[2014]

Non-nutritive sweeteners (NNS) are commonly used as sugar substitutes, particularly by individuals with diabetes and obesity, but their safety during pregnancy and lactation is still debated.

Concerns have been raised about the potential association of NNS with preterm birth and other metabolic consequences for both mothers and their offspring, highlighting the need for more education and objective information for health professionals and consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non-caloric sweeteners in women of reproductive age - A consensus document]. Bailón Uriza, R., Ayala Méndez, JA., Cavagnari, BM., et al.[2022]

Non-nutritive sweeteners (NNS) are marketed as safe for all ages and may serve as dietary aids for weight loss or diabetes management, but there is insufficient clinical evidence to confirm their effectiveness in promoting weight loss or improving cardiometabolic health.

Despite endorsements of safety from the FDA and some studies, the lack of conclusive research means that both sugar and NNS should be consumed in minimal amounts for optimal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-nutritive sweeteners: review and update. Shankar, P., Ahuja, S., Sriram, K.[2022]

Nonnutritive sweeteners (NNS) like aspartame and sucralose are considered safe by the FDA and are widely used for their intense sweetness and low-calorie content, but evidence supporting their benefits, such as weight loss and safety for diabetics, is inconclusive.

Certain populations, including pregnant women, children, and individuals with diabetes or specific health conditions, may be more vulnerable to potential adverse effects from NNS, highlighting the need for caution and better consumer education regarding their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Artificial sweeteners as a sugar substitute: Are they really safe? Sharma, A., Amarnath, S., Thulasimani, M., et al.[2018]

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]

Nutritive sweeteners like sucrose and fructose are generally recognized as safe by the FDA, but intakes above 25% of total energy can negatively impact dietary quality, especially in children aged 9 to 18, where one in four may exceed this level.

Non-nutritive sweeteners, such as aspartame and sucralose, are also FDA-approved and can be safely consumed below the Acceptable Daily Intake, potentially enhancing the palatability of nutrient-dense foods without increasing obesity risk or causing behavioral disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners. [2022]

Non-nutritive sweeteners (NNSs) can help reduce dietary sugar and calorie intake, making them beneficial for diabetics and those trying to manage their weight.

Contrary to some beliefs, studies show that replacing sugar with NNSs does not increase hunger or food intake, and can actually lead to reduced energy intake and body weight in both children and adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-nutritive sweeteners and obesity. Fernstrom, JD.[2015]

Nonnutritive sweeteners can help reduce overall calorie intake and promote weight loss or maintenance, as controlled studies have shown no change or even a decrease in body weight during their use.

These sweeteners do not affect blood sugar levels in diabetics, making them a safe option for managing carbohydrate consumption and improving metabolic parameters, provided they are not accompanied by increased caloric intake from other sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of nonnutritives weeteners on certain metabolic parameters]. Hidvégi, T.[2018]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Non-nutritive sweeteners and type 2 diabetes: Should we ring the bell? [2019]

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

Use of fructose, sorbitol, or xylitol as a sweetener in diabetes mellitus. [2017]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Diet-Quality and Socio-Demographic Factors Associated with Non-Nutritive Sweetener Use in the Australian Population. [2018]

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

Effects of nonnutritive sweeteners on body weight and BMI in diverse clinical contexts: Systematic review and meta-analysis. [2021]

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

Non-nutritive sweeteners: evidence for benefit vs. risk. [2014]

6. Spain pubmed.ncbi.nlm.nih.gov

[Non-caloric sweeteners in women of reproductive age - A consensus document]. [2022]

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

Non-nutritive sweeteners: review and update. [2022]

8. India pubmed.ncbi.nlm.nih.gov

Artificial sweeteners as a sugar substitute: Are they really safe? [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners. [2022]

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

Non-nutritive sweeteners and obesity. [2015]

12. Hungary pubmed.ncbi.nlm.nih.gov

[The effect of nonnutritives weeteners on certain metabolic parameters]. [2018]