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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether non-nutritive sweeteners, such as sucralose and aspartame, affect blood sugar balance in individuals with prediabetes. Researchers aim to determine if sucralose alters sugar metabolism, while aspartame does not, compared to a diet without sweeteners. The trial targets individuals over 40 with prediabetes who rarely consume non-nutritive sweeteners. Participants will follow a specific diet plan for 8 weeks. As an unphased trial, this study provides a unique opportunity to contribute to understanding dietary impacts on prediabetes.

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.

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

Research has shown that sucralose is generally safe for consumption. Studies have found no harm, even for individuals with diabetes. However, some concerns exist about a potential link to a higher risk of heart problems.

Aspartame has undergone thorough study, with over 100 studies supporting its safe use in foods. Although considered safe, some research suggests a possible link between artificial sweeteners like aspartame and a higher risk of type 2 diabetes.

Health authorities, such as the FDA, have approved both sucralose and aspartame for use in foods, indicating they are generally safe to consume in usual amounts. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about exploring the impact of non-nutritive sweeteners (NNS) like sucralose and aspartame on prediabetes because these sweeteners offer a no-calorie alternative to sugar, which could help manage blood sugar levels without adding extra calories. Unlike standard treatments that often involve medication or significant dietary changes, these sweeteners can be easily incorporated into everyday diets, potentially offering a simpler, more accessible approach to managing prediabetes. By investigating how these sweeteners affect blood sugar and insulin levels, researchers hope to understand whether they could be a helpful tool in preventing the progression to type 2 diabetes.

What evidence suggests that non-nutritive sweetener intake might affect glucose homeostasis in prediabetes?

This trial will compare the effects of different non-nutritive sweeteners on blood sugar management in individuals with prediabetes. Research has shown that sucralose, one of the sweeteners tested in this trial, might reduce the body's responsiveness to insulin, which is crucial for controlling blood sugar. Specifically, one study found that people who consumed sucralose experienced about a 17.7% decrease in insulin responsiveness, potentially affecting blood sugar management. In contrast, aspartame, another sweetener in this trial, has shown mixed results in studies, with no clear evidence of altering blood sugar levels. Aspartame might not significantly impact blood sugar control in people with prediabetes. While these sweeteners are often used to cut calories, their effects on blood sugar can differ. ^{1 2 4 6 7}

Who Is on the Research Team?

Valisa Hedrick, PhD

Principal Investigator

Virginia Polytechnic Institute and State University

Are You a Good Fit for This Trial?

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 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: 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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