Sugary to Non-Sugary Beverage Switch for Obesity

(SUB-POP Trial)

Overseen By Trisha Copeland, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Must not be taking: Weight affecting

Disqualifiers: T2D, Cardiovascular disease, Cancer, others

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

Compensation: Varies

Number of Visits: 18

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether swapping sugary drinks for calorie-free alternatives can aid in weight reduction and health improvement. It includes four groups: one will replace sugary drinks with water, another with sucralose-sweetened beverages, a third with aspartame-sweetened drinks, and the last will initially continue with their usual sugary drinks. The trial seeks adults who consume at least one sugary drink daily and have a BMI (a measure of body fat based on height and weight) between 25 and 45. As an unphased study, this trial provides a unique opportunity to contribute to understanding the health impacts of reducing sugary drink consumption.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on medication that may affect weight or other study outcomes. It's best to discuss your specific medications with the trial team.

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

A previous study identified aspartame as one of the most researched food additives, and the FDA reports no safety concerns when used correctly. However, the International Agency for Research on Cancer (IARC) recently stated it might possibly cause cancer in humans, but this remains under investigation.

Research on sucralose shows health experts generally consider it safe. Some studies mention it might affect metabolism, such as raising blood sugar in people with obesity who don't usually consume artificial sweeteners, but no strong evidence links it to cancer or other major health issues.

Studies on replacing sugary drinks with water demonstrate it can aid weight loss. Drinking more water instead of sugary drinks is a safe and effective way to reduce calorie intake.

Overall, these findings suggest that both aspartame and sucralose are safe when consumed within recommended limits, and switching to water is a safe choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores novel ways to tackle obesity by replacing sugary drinks with alternatives like aspartame-sweetened beverages, sucralose-sweetened beverages, and plain water. Unlike traditional diet plans that might focus on calorie counting or meal replacements, this approach zeroes in on beverage choices, which can be a significant source of excess calories. This trial is unique in its stepwise approach: initially substituting sugary drinks with artificially sweetened options before transitioning to water only. This method might offer a more sustainable and gradual change for individuals looking to reduce sugar intake and manage weight effectively.

What evidence suggests that this trial's treatments could be effective for obesity?

This trial will compare strategies for reducing sugary drink consumption. Participants in one arm will switch from sugary drinks to those with aspartame. Research has shown that aspartame can aid in weight loss. One study found that people who drank beverages with aspartame lost more weight and maintained it better than those who did not. However, some long-term studies suggest that aspartame might lead to increased fat storage over time.

Another arm will involve switching to sucralose-sweetened beverages. For sucralose, results are mixed. Some research suggests it could cause weight gain and increase hunger. Overall, evidence does not consistently show that sucralose aids in weight loss.

Participants in another arm will switch to water, a reliable choice. Studies indicate that replacing sugary drinks with water can lead to weight loss and help maintain it. Water is often recommended as a healthy alternative to sugary drinks. ^{3 6 7 8 9}

Who Is on the Research Team?

Deirdre Tobias, ScD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 20-69 with obesity who drink at least one sugary beverage daily and are willing to change their drinking habits. They must have a smartphone, be able to use an app, and not plan to move from the Boston area within a year. People with diabetes, PKU, recent or current pregnancy, weight-affecting medications, or major illnesses cannot join.

Inclusion Criteria

I am between 20 and 69 years old.

You have a body mass index (BMI) between 25 and 45.

I can use a smartphone and am willing to download an app for the study.

Exclusion Criteria

I am not on medication that could change my weight or affect the study.

Pregnant in the past 12 months, currently breastfeeding, or planning to become pregnant during the study period

I have been diagnosed with Phenylketonuria (PKU).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of four beverage groups and receive at-home monthly deliveries of beverages for 6 months.

6 months

In-person clinic visits at baseline, 6 months

Observational

Participants switch to water only for a final 6-month observational period.

6 months

In-person clinic visit at 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aspartame ASBs
• Maintain SSBs (Control)
• Substitute Water
• Sucralose ASBs

Trial Overview The study is testing if replacing sugary drinks (like soda) with water or artificially-sweetened beverages helps reduce body weight in overweight individuals. Participants will be randomly assigned to one of four groups: some get an app plus non-sugary drinks delivered; others maintain their usual intake.

How Is the Trial Designed?

Group I: Substitute Water Experimental Treatment 3 Interventions

Instruction/guidelines to eliminate SSBs and replace with water (months 0-12)

Group II: Substitute Sucralose ASBs (participants randomized through 8/31/2023) Experimental Treatment 3 Interventions

Instruction/guidelines to eliminate SSBs and replace, where possible with beverages artificially sweetened with sucralose (months 0-6); then switch to water only (months 6-12)

Group III: Substitute Aspartame ASBs (participants randomized through 8/31/2023) Experimental Treatment 3 Interventions

Instruction/guidelines to eliminate SSBs and replace, where possible with beverages artificially sweetened with aspartame (months 0-6); then switch to water only (months 6-12)

Group IV: Substitute ASBs (participants randomized on or after 9/1/2023) Experimental Treatment 3 Interventions

Instruction/guidelines to eliminate SSBs and replace, where possible with beverages artificially sweetened with choice of non-nutritive sweeteners such as sucralose or aspartame

Group V: Maintain SSBs (Control) Active Control 3 Interventions

Instruction to maintain baseline intake of SSBs (months 0-6); then switch to water only (months 6-12)

Aspartame ASBs is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Aspartame for:

• Food additive
• Sweetener

Approved in United States as Aspartame for:

• Food additive
• Sweetener

Approved in Canada as Aspartame for:

• Food additive
• Sweetener

Approved in Japan as Aspartame for:

• Food additive
• Sweetener

Approved in China as Aspartame for:

• Food additive
• Sweetener

Approved in Switzerland as Aspartame for:

• Food additive
• Sweetener

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study involving 60 healthy volunteers with overweight/obesity, non-nutritive sweeteners (S&SE) significantly reduced insulin levels after a carbohydrate-rich meal compared to sucrose, indicating potential benefits for glycaemic control.

While some S&SE blends affected cholesterol levels and appetite sensations, they did not lead to significant differences in overall energy intake or cause serious gastrointestinal issues, suggesting they may be a safe alternative to sugar.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of acute consumption of beverages containing plant-based or alternative sweetener blends on postprandial appetite, food intake, metabolism, and gastro-intestinal symptoms: Results of the SWEET beverages trial. Almiron-Roig, E., Navas-Carretero, S., Castelnuovo, G., et al.[2023]

Replacing sugar-sweetened beverages (SSB) with water can significantly reduce energy intake from beverages, lowering the percentage of energy from 17% to 11% for those consuming one SSB per day, based on data from 19,718 US adults.

This substitution not only improved Healthy Beverage Index scores by 9% to 21% but also predicted a decrease in obesity prevalence, suggesting that drinking water instead of SSB can be an effective strategy for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modeling the Effect of Replacing Sugar-Sweetened Beverage Consumption with Water on Energy Intake, HBI Score, and Obesity Prevalence. Duffey, KJ., Poti, J.[2019]

The STOP Sugars NOW trial is a randomized controlled trial involving 80 overweight or obese adults, aiming to compare the effects of non-nutritive sweetened beverages (NSBs) and water as replacements for sugar-sweetened beverages (SSBs) on glucose tolerance and gut microbiota diversity.

Preliminary results indicate that the trial is designed to provide high-level evidence on the safety and efficacy of NSBs in reducing sugar intake, which could influence clinical guidelines and public health policies regarding beverage consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study. Ayoub-Charette, S., McGlynn, ND., Lee, D., et al.[2023]

Observational studies suggest that nonnutritive sweeteners (NNSs) might lead to weight gain due to mechanisms related to cravings and addictive behaviors, but interventional studies indicate that replacing sugar-sweetened beverages with NNS can reduce caloric intake and promote modest weight loss.

The effectiveness of NNS for weight reduction may vary based on an individual's baseline diet, dietary changes, and adherence to a comprehensive weight loss program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The paradox of artificial sweeteners in managing obesity. Roberts, JR.[2022]

In a study of 203 adults over 12 months, replacing sugar-sweetened beverages (SSBs) with artificially sweetened beverages (ASBs) or unsweetened beverages (USBs) did not significantly change serum triglyceride to HDL cholesterol ratios, indicating similar safety profiles for these alternatives.

Participants with higher central adiposity who replaced SSBs with ASBs or USBs experienced less weight gain compared to those who continued consuming SSBs, suggesting that ASBs and USBs can be effective in managing weight in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Beverages on Cardiometabolic Risk Factors, Body Composition, and Sweet Taste Preference: A Randomized Controlled Trial. Ebbeling, CB., Feldman, HA., Steltz, SK., et al.[2021]

The review highlights that while artificial sweeteners (ASBs) are often marketed for weight control, the actual consumption of diet beverages is lower than that of sugar-sweetened beverages (SSBs), with those trying to lose weight consuming the most ASBs.

Current evidence suggests that replacing SSBs with ASBs may lower obesity risk, but more experimental studies are needed to fully understand the long-term benefits and risks of frequent ASB consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet beverages and the risk of obesity, diabetes, and cardiovascular disease: a review of the evidence. Pereira, MA.[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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9301525/

The effect of aspartame and sucralose intake on body ... Results showed that aspartame ingestion significantly increased body weight and fat mass mainly due to an increase in energy efficiency.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7817779/

The Impact of Artificial Sweeteners on Body Weight Control ... Consistently, mice studies and human crossover trials in lean and obese individuals have shown no significant effects of artificial sweeteners ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0002916523175897

The effect of aspartame as part of a multidisciplinary weight ... The aspartame group lost significantly more weight overall (P = 0.028) and regained significantly less weight during maintenance and follow-up (P = 0.046) than ...

4. nature.com nature.com/articles/s41366-023-01336-y

Long-term aspartame and saccharin intakes are related to ... Results suggest that long-term intakes of aspartame, saccharin, or diet soda may increase AT deposition and risk of incident obesity independent of diet ...

5. who.int who.int/news/item/15-05-2023-who-advises-not-to-use-non-sugar-sweeteners-for-weight-control-in-newly-released-guideline

WHO advises not to use non-sugar sweeteners for weight ... "Replacing free sugars with NSS does not help with weight control in the long term. People need to consider other ways to reduce free sugars ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8227014/

Aspartame—True or False? Narrative Review of Safety ... This narrative review investigates the existing literature on the use of aspartame and its possible effects on the human body to refine current knowledge.

7. who.int who.int/news/item/14-07-2023-aspartame-hazard-and-risk-assessment-results-released

Aspartame hazard and risk assessment results released IARC classified aspartame as possibly carcinogenic to humans (IARC Group 2B) and JECFA reaffirmed the acceptable daily intake of 40 mg/kg body weight.

8. fda.gov fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food

Aspartame and Other Sweeteners in Food Aspartame is one of the most studied food additives in the human food supply. FDA scientists do not have safety concerns when aspartame is used ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2161831325000857

The Effects of Aspartame on Glucose, Insulin, and Appetite ... This work identified 100 experiments investigating the effects of aspartame consumption on glucose, insulin and other appetite-regulating hormone responses.