Stevia for Childhood Obesity

Overseen By Mario Ferruzzi, Ph.D.

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Arkansas Children's Hospital Research Institute

Must not be taking: Antibiotics, Inhalers

Disqualifiers: Obesity, Asthma, Autism, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 to 14 weeks

210 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an 8 to14-week three-arm randomized controlled in children 8 to 12 years old. The main purpose of the study is to evaluate if stevia (as with other sweeteners and consistent with prior research in children and adults) has benefits for weight control and metabolic function relative to caloric sweeteners, and whether it provides benefits in this regard similar to water.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have certain medical conditions or are on medications that might affect the study's outcomes, you may not be eligible to participate.

What data supports the effectiveness of the treatment Stevia for Childhood Obesity?

Research suggests that replacing sugar-sweetened beverages with sugar-free options, like those sweetened with stevia, can help reduce weight gain in children, especially those with higher body weight. ^{1 2 3 4 5}

Is stevia safe for human consumption?

Stevia, a low-calorie sweetener, has been affirmed as safe by several food regulatory and safety authorities worldwide. It is generally recognized as safe (GRAS) by the FDA, and the European Food Safety Authority (EFSA) has also evaluated its safety, setting an acceptable daily intake of 4 mg/kg body weight per day. While there are some concerns about impurities, the overall safety of stevia is not considered to be of concern. ^{6 7 8 9 10}

How does the treatment using stevia-sweetened beverages differ from other treatments for childhood obesity?

The treatment using stevia-sweetened beverages is unique because it offers a plant-based, zero-calorie alternative to sugar, which is significantly sweeter than regular sugar, making it an appealing option for reducing calorie intake in children. Unlike traditional sugar, stevia does not contribute to weight gain and may help manage energy intake, which is crucial in addressing childhood obesity. ^{1 5 10 11 12}

Eligibility Criteria

The Sweet Kids Study is for children aged 8-12 who regularly drink sugary beverages and are either of normal weight or overweight, but not severely obese. They should be willing to try new drinks and not have conditions like diabetes, chronic infections, hormonal diseases, severe asthma, bleeding disorders, certain mental health issues or a recent history of antibiotic use.

Inclusion Criteria

You have a body mass index (BMI) between the 5th and 85th percentile for your age and gender.

You rarely use artificial sweeteners (less than 3 times per week).

My BMI is high, between 35 and less than 40, or it's in the top 15% for my age.

Exclusion Criteria

I have chronic kidney disease.

My child is classified with class 3 obesity.

I have asthma triggered by exercise.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants consume either a sucrose-sweetened beverage, a stevia-sweetened beverage, or a calorie-free flavored water beverage once a day

8 to 14 weeks

Weekly check-ins (virtual or in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of metabolic function and gut microbial communities

4 weeks

Treatment Details

Interventions

• Calorie free flavored water beverage
• Stevia sweetened beverages
• Sucrose sweetened beverage

Trial Overview This study compares the effects of three types of beverages on children's weight and metabolic function over an 8 to14-week period: water flavored without calories, drinks sweetened with stevia (a no-calorie sweetener), and drinks sweetened with regular sugar (sucrose).

Participant Groups

Group I: Stevia sweetened beverage Experimental Treatment 1 Intervention

The stevia-sweetened beverage contains 30.1 mg of steviol equivalents. Participants will be asked to consume the study product once a day for 8 to 14 weeks if they have normal weight or excessive weight, respectively.

Group II: Calorie free flavored water beverage Active Control 1 Intervention

Flavored water. Participants will be asked to consume the study product once a day for 8 to 14 weeks if they have normal weight or excessive weight, respectively.

Group III: Sucrose sweetened beverage Active Control 1 Intervention

Sucrose (i.e. sugar): 25 g sugar (100 Kcal per serving). Participants will be asked to consume the study product once a day for 8 to 14 weeks if they have normal weight or excessive weight, respectively.

Calorie free flavored water beverage is already approved in United States, European Union for the following indications:

Approved in United States as Flavored water for:

• General hydration
• Dietary supplement

Approved in European Union as Flavored water for:

• General hydration
• Dietary supplement

Who Is Running the Clinical Trial?

Arkansas Children's Hospital Research Institute

Lead Sponsor

Trials

141

Recruited

5,025,000+

Cargill

Industry Sponsor

Trials

28

Recruited

3,200+

Findings from Research

Low-calorie sweeteners (LCSs) are commonly found in beverages, with 32% of adult and 19% of child beverage consumption in the U.S. containing them, but there is limited evidence on their long-term effects on health.

While LCS beverages may help adults reduce sugar-sweetened beverage intake and manage weight, prolonged consumption by children is not recommended due to potential adverse effects, and water remains the best beverage choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association. Johnson, RK., Lichtenstein, AH., Anderson, CAM., et al.[2019]

In a study of 477 children over 18 months, replacing one sugary drink per day with a sugar-free drink significantly reduced weight gain, with a greater effect observed in children with a higher BMI, who experienced a reduction in BMI z-score by 0.21 SD compared to 0.05 SD in those with a lower BMI.

Children with a higher BMI showed a lower tendency to compensate for the reduction in sugar intake, only compensating 13% of the removed calories, while those with a lower BMI compensated 65%, suggesting that different compensatory mechanisms may influence weight gain in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Masked Replacement of Sugar-Sweetened with Sugar-Free Beverages on Body Weight Increases with Initial BMI: Secondary Analysis of Data from an 18 Month Double-Blind Trial in Children. Katan, MB., de Ruyter, JC., Kuijper, LD., et al.[2018]

Substituting low- and no-calorie sweetened beverages (LNCSBs) for sugar-sweetened beverages (SSBs) was associated with a small but significant reduction in body weight and improvements in cardiometabolic risk factors, based on a systematic review of 17 randomized clinical trials involving 1733 adults.

In contrast, substituting water for SSBs did not show any significant benefits, suggesting that LNCSBs can be a viable alternative for reducing body weight and improving health outcomes in adults with overweight or obesity, particularly those at risk for diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis. McGlynn, ND., Khan, TA., Wang, L., et al.[2023]

In a study involving 89 children aged 5 to 12, only 24% could distinguish between non-nutritively sweetened and sugar-sweetened beverages, indicating that many children may not notice a difference in taste.

The children showed no preference between non-nutritively sweetened and sugar-sweetened beverages, both scoring similarly on a liking scale, suggesting that non-nutritively sweetened drinks could be a viable alternative to reduce sugar intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can children discriminate sugar-sweetened from non-nutritively sweetened beverages and how do they like them? de Ruyter, JC., Katan, MB., Kas, R., et al.[2019]

In Chile, over half (55.5%) of the analyzed food products contained non-caloric sweeteners (NCSs), with particularly high prevalence in dairy (67.1%) and non-alcoholic beverages (74.3%), indicating a significant shift in product formulation due to new food labeling laws.

The widespread use of NCSs, especially sucralose and steviol glycosides, raises concerns about children's consumption potentially exceeding the acceptable daily intake, as many products targeted at children contain these sweeteners, and there are few NCS-free alternatives available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overuse of Non-caloric Sweeteners in Foods and Beverages in Chile: A Threat to Consumers' Free Choice? Sambra, V., López-Arana, S., Cáceres, P., 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]

Low calorie sweeteners like aspartame and saccharin have undergone extensive safety evaluations by regulatory bodies such as the FDA and EFSA, addressing concerns like cancer risk and effects on weight and metabolism.

Most modern sweeteners, including acesulfame K and sucralose, have been approved as safe through rigorous testing, ensuring they pose no significant health risks when consumed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and regulatory process for low calorie sweeteners in the United States. Roberts, A.[2018]

The EFSA Panel concluded that expanding the specifications for steviol glycosides (E 960) to include 60 identified glycosides is not a safety concern, as they share similar metabolic pathways and can be evaluated based on existing toxicological data.

The acceptable daily intake (ADI) of 4 mg/kg body weight per day applies to all steviol glycosides, but the Panel noted that the presence of up to 5% impurities in the additive could not be fully evaluated, leaving some uncertainty regarding safety if purity is not maintained.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of a proposed amendment of the specifications for steviol glycosides (E 960) as a food additive: to expand the list of steviol glycosides to all those identified in the leaves of Stevia Rebaudiana Bertoni. Younes, M., Aquilina, G., Engel, KH., et al.[2020]

Female Sprague-Dawley rats and C57BL/6J mice showed a strong preference for a high-rebaudioside, low-stevioside extract from stevia, comparable to saccharin, but with less tendency to overdrink, indicating a favorable response to stevia sweeteners.

Mice preferred pure rebaudioside A and a commercial mixture of rebaudioside A and erythritol (Truvia) over other noncaloric sweeteners, suggesting that the sweet taste of stevia is appealing to rodents, unlike some other sweeteners like aspartame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stevia and saccharin preferences in rats and mice. Sclafani, A., Bahrani, M., Zukerman, S., et al.[2022]

Steviol glycoside sweeteners from the Stevia plant are gaining popularity as low- and no-calorie sweeteners due to their plant-based origin, zero calories, and sweetness that is 50-350 times greater than sugar, making them suitable for reducing sugar intake in food and beverages.

Despite being affirmed as safe by various food regulatory authorities, there is still a lack of education about stevia's safety and benefits, which affects its acceptance among health professionals and consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stevia Leaf to Stevia Sweetener: Exploring Its Science, Benefits, and Future Potential. Samuel, P., Ayoob, KT., Magnuson, BA., et al.[2023]

Steviol glycosides (SGs), derived from the Stevia plant, showed a significant reduction in systolic blood pressure in a meta-analysis of nine randomized controlled trials involving 462 participants, suggesting potential cardiovascular benefits for individuals with type 2 diabetes.

While SGs did not significantly impact other key diabetes-related biomarkers like fasting blood glucose or glycated hemoglobin, the overall findings indicate a need for further research to fully understand their effects on human health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Steviol Glycosides on Human Health with Emphasis on Type 2 Diabetic Biomarkers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Bundgaard Anker, CC., Rafiq, S., Jeppesen, PB.[2020]

In a study with 40 C57BL/6J mice, those given stevia extract alongside a high-fat diet showed significantly lower body weight gain and reduced triglyceride levels compared to those given sucrose, indicating stevia's potential anti-obesity effects.

Stevia extract also improved lipid profiles by lowering total cholesterol and increasing levels of beneficial metabolites related to fat metabolism, suggesting it may help manage obesity-related lipid issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stevia rebaudiana Bertoni extract supplementation improves lipid and carnitine profiles in C57BL/6J mice fed a high-fat diet. Park, JE., Cha, YS.[2015]

References

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

Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association. [2019]

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

Impact of Masked Replacement of Sugar-Sweetened with Sugar-Free Beverages on Body Weight Increases with Initial BMI: Secondary Analysis of Data from an 18 Month Double-Blind Trial in Children. [2018]

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

Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis. [2023]

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

Can children discriminate sugar-sweetened from non-nutritively sweetened beverages and how do they like them? [2019]

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

Overuse of Non-caloric Sweeteners in Foods and Beverages in Chile: A Threat to Consumers' Free Choice? [2020]

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

Biological fate of low-calorie sweeteners. [2018]

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

The safety and regulatory process for low calorie sweeteners in the United States. [2018]

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

Safety of a proposed amendment of the specifications for steviol glycosides (E 960) as a food additive: to expand the list of steviol glycosides to all those identified in the leaves of Stevia Rebaudiana Bertoni. [2020]

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

Stevia and saccharin preferences in rats and mice. [2022]

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

Stevia Leaf to Stevia Sweetener: Exploring Its Science, Benefits, and Future Potential. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Steviol Glycosides on Human Health with Emphasis on Type 2 Diabetic Biomarkers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2020]

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

Stevia rebaudiana Bertoni extract supplementation improves lipid and carnitine profiles in C57BL/6J mice fed a high-fat diet. [2015]