Reducing Artificial Sweeteners for Diabetes in Pregnancy

Overseen By Allison C Sylvetsky, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: George Washington University

Must not be taking: Metformin, GLP-1 agonists

Disqualifiers: Tobacco, Alcohol, Gastrointestinal disorders, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

324 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial excludes participants who are taking medications that affect body weight, body composition, insulin resistance, or lipid profiles, so you may need to stop such medications to participate.

What data supports the effectiveness of the treatment for reducing artificial sweeteners in managing diabetes during pregnancy?

While there is no direct evidence about reducing artificial sweeteners, studies show that dietary changes, like calorie restriction, can help manage blood sugar levels in pregnant women with gestational diabetes. This suggests that modifying diet, including reducing artificial sweeteners, might also be beneficial. ^{1 2 3 4 5}

Is it safe to reduce artificial sweeteners during pregnancy?

The safety of reducing artificial sweeteners during pregnancy is not fully established. While some artificial sweeteners are generally recognized as safe, there are concerns about potential risks, such as metabolic changes in the mother and child, and possible associations with preterm birth. Pregnant women should use these products with caution and consult healthcare providers for personalized advice. ^{6 7 8 9 10}

How is the NNS Restriction Intervention treatment different from other treatments for diabetes in pregnancy?

The NNS Restriction Intervention is unique because it focuses on reducing the intake of artificial sweeteners (like Splenda and Stevia) during pregnancy, which is not a standard approach for managing diabetes in pregnancy. This treatment is based on concerns that these sweeteners may affect metabolism and health outcomes in both the mother and the baby, unlike traditional diabetes treatments that focus on managing blood sugar levels directly. ^{6 7 10 11 12}

What is the purpose of this trial?

The effects of consuming non-nutritive sweeteners (NNS) during pregnancy and lactation on infant obesity and cardiometabolic disease risk are not well understood. In this project, pregnant women who frequently consume NNS will be randomly assigned to an NNS-restriction intervention (NNS restriction during pregnancy and lactation or during lactation only) or a control group (no NNS restriction) to determine whether NNS consumption during pregnancy and/or lactation affects infant body composition, maternal blood sugar during pregnancy, and the infants' gut microbiome and metabolome. The results of this study have the potential to shape recommendations around NNS consumption during pregnancy and lactation, thereby potentially improving maternal and infant metabolic health and reducing the global burden of obesity and cardiometabolic disease.

Eligibility Criteria

This trial is for pregnant women who often use non-nutritive sweeteners (NNS). They will be studied to see if avoiding NNS during pregnancy and breastfeeding affects their baby's risk of obesity and other health issues, as well as the mother's blood sugar levels.

Inclusion Criteria

Pregnant

Singleton pregnancy

Able to read English at a 5th grade level

Exclusion Criteria

I have been diagnosed with a major illness like cancer or heart disease.

Tobacco or drug use during pregnancy

Pre-existing diabetes or GDM in a previous pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants are randomly assigned to an NNS-restriction intervention or a control group to assess the effects of NNS consumption during pregnancy and/or lactation.

Pregnancy and lactation period

Follow-up

Participants are monitored for maternal and infant outcomes, including glucose tolerance, body composition, and gut microbiome.

6 months postpartum

Treatment Details

Interventions

• NNS Restriction Intervention

Trial Overview The study compares two groups: one that restricts NNS intake during pregnancy and lactation, and a control group with no restrictions. The impact on infant body composition, maternal glucose levels, and both the mother's and infant’s gut health are being observed.

Participant Groups

Group I: Control (Group 1) Active Control 1 Intervention

Participants in this arm will continue their usual consumption of NNS throughout pregnancy and lactation without any intervention. They will not receive any specific NNS-restriction intervention.

Group II: NNS Restriction in Lactation (Group 2) Active Control 2 Interventions

Participants in this arm will maintain their usual NNS consumption during pregnancy but will receive an intervention to restrict NNS intake during lactation.

Group III: NNS Restriction in Pregnancy and Lactation (Group 3) Active Control 1 Intervention

Participants in this arm will receive an intervention to restrict NNS intake both during pregnancy and lactation.

Who Is Running the Clinical Trial?

George Washington University

Lead Sponsor

Trials

263

Recruited

476,000+

Children's Hospital Los Angeles

Collaborator

Trials

257

Recruited

5,075,000+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Findings from Research

In a study of 121 women with a median BMI of 32.6 kg/m2, those who perceived a high risk of developing type-2 diabetes (T2DM) and had better access to healthy foods experienced greater weight loss after 3 months, highlighting the importance of environmental factors in weight management.

Continuous energy restriction (CER) led to better improvements in dietary quality compared to intermittent energy restriction (IER) after 12 months, suggesting that adherence to dietary changes may be more effective with a consistent approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight Loss Barriers and Dietary Quality of Intermittent and Continuous Dieters in Women with a History of Gestational Diabetes. Gray, KL., Clifton, PM., Keogh, JB.[2021]

A clinical trial involving 215 women with gestational diabetes showed that following specific nutrition practice guidelines led to less insulin use and better control of glycated hemoglobin levels in diabetes clinic settings compared to usual care.

Women receiving care under the nutrition practice guidelines had a lower proportion of elevated glycated hemoglobin levels (8.1%) compared to those in the usual care group (13.6%), suggesting that these guidelines may improve management of gestational diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of gestational diabetes mellitus nutrition practice guidelines implemented by registered dietitians on pregnancy outcomes. Reader, D., Splett, P., Gunderson, EP.[2022]

In a study involving 12 obese pregnant women with gestational diabetes, calorie restriction to approximately 1200 kcal/day led to a significant reduction in mean glucose levels and fasting plasma insulin after one week, indicating improved metabolic control.

The calorie-restricted group also showed increased levels of beta-hydroxybutyrate and urine ketones, suggesting a shift towards fat metabolism, while the control group maintained stable metabolic parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic effects of 1200-kcal diet in obese pregnant women with gestational diabetes. Magee, MS., Knopp, RH., Benedetti, TJ.[2019]

Women with diet-controlled gestational diabetes who followed a low-carbohydrate diet (below 42%) experienced significant reductions in postprandial glucose levels and required less insulin therapy compared to those on a high-carbohydrate diet (over 45%).

The low-carbohydrate group also had a significantly lower incidence of large for gestational age (LGA) infants and fewer cesarean deliveries due to complications related to macrosomia, indicating better overall perinatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of carbohydrate restriction in patients with diet-controlled gestational diabetes. Major, CA., Henry, MJ., De Veciana, M., et al.[2022]

In a pilot study involving 43 women with gestational diabetes, those on a very low energy diet (VLED) gained significantly less weight (5.9 kg) compared to those on a low energy diet (LED) who gained 12.0 kg, suggesting that VLED may be more effective for managing weight during pregnancy.

Both VLED and LED resulted in similar maternal and infant outcomes, with a low incidence of complications and a majority of infants being appropriate-for-gestational age, indicating that either diet can be safely used in managing gestational diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIMER: A Clinical Study of Energy Restriction in Women with Gestational Diabetes Mellitus. Tsirou, E., Grammatikopoulou, MG., Nigdelis, MP., et al.[2021]

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]

About 30% of pregnant women are consuming non-nutritive sweeteners (NNSs) like Splenda and Stevia, which are often used to reduce sugar intake and prevent health issues like diabetes and heart disease.

Research indicates that NNS consumption during pregnancy may lead to negative outcomes for offspring, such as increased risk of obesity and metabolic issues, but there are currently no specific guidelines for pregnant women regarding NNS intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consumption of non-nutritive sweeteners during pregnancy. Palatnik, A., Moosreiner, A., Olivier-Van Stichelen, S.[2020]

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]

Maternal intake of non-nutritive sweeteners (NNS) during pregnancy is linked to higher BMI z-scores and body fat in children from birth to 18 years, with the strongest associations observed as children age.

Specifically, children whose mothers were in the highest quartile of NNS intake showed significant increases in BMI z-scores and body fat measures at various stages of childhood, suggesting a potential long-term impact on obesity risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of maternal non-nutritive sweetener intake during pregnancy with offspring body mass index and body fat from birth to adolescence. Plows, JF., Aris, IM., Rifas-Shiman, SL., et al.[2023]

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]

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]

Recent randomized clinical trials (RCTs) on nonnutritive sweeteners (NNSs) found that most types, particularly artificial ones like sucralose and aspartame, generally do not affect blood glucose or insulin levels, indicating limited efficacy for glycaemic control.

Some studies did show an acute insulin response to sucralose, suggesting that certain NNSs may have specific effects, but overall, more research is needed to clarify their impact on glycaemic control and to explore different types of NNSs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent evidence for the effects of nonnutritive sweeteners on glycaemic control. Ahmad, SY., Azad, MB., Friel, J., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Weight Loss Barriers and Dietary Quality of Intermittent and Continuous Dieters in Women with a History of Gestational Diabetes. [2021]

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

Impact of gestational diabetes mellitus nutrition practice guidelines implemented by registered dietitians on pregnancy outcomes. [2022]

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

Metabolic effects of 1200-kcal diet in obese pregnant women with gestational diabetes. [2019]

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

The effects of carbohydrate restriction in patients with diet-controlled gestational diabetes. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

TIMER: A Clinical Study of Energy Restriction in Women with Gestational Diabetes Mellitus. [2021]

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

Consumption of non-nutritive sweeteners during pregnancy. [2020]

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

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

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

Associations of maternal non-nutritive sweetener intake during pregnancy with offspring body mass index and body fat from birth to adolescence. [2023]

10. England pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

Non-nutritive sweeteners for diabetes mellitus. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Recent evidence for the effects of nonnutritive sweeteners on glycaemic control. [2020]