Sucralose for Healthy Subjects

Overseen By Paule V Joseph, C.R.N.P.

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

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

Must be taking: Digoxin, Midazolam

Must not be taking: Antibiotics, Oral contraceptives

Disqualifiers: Diabetes, Glaucoma, Cardiac abnormalities, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how sucralose, a common artificial sweetener, might affect the body's absorption and processing of medicines, hormone levels, gut bacteria, and fat metabolism. Participants will take either sucralose or a placebo in capsule form to identify any noticeable changes. The study seeks Black or Hispanic individuals who weigh over 110 pounds, have a body mass index (BMI) between 25 and 40, and do not need medication for existing health conditions. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current medications, as the trial excludes anyone currently using prescription or non-prescription medications, herbal medications, and oral contraceptives, with some exceptions like vitamins.

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

Research has shown that sucralose is generally safe to consume. The FDA reviewed over 110 studies to assess potential harmful effects and determined it is safe for people, including children and those with diabetes. Although some studies have raised questions about long-term effects, these remain under investigation. For short-term use, such as in this study, most people tolerate sucralose well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about sucralose as a treatment because, unlike most standard sweeteners that contribute to calorie intake, sucralose is a non-caloric sweetener. It is unique due to its stability at high temperatures, making it versatile for cooking and baking without losing sweetness. Additionally, sucralose doesn't affect blood sugar levels, which could make it a safer option for those managing diabetes. These features make sucralose stand out as a potentially healthier alternative to traditional sweeteners.

What evidence suggests that sucralose might be an effective treatment for changes in medicine absorption and hormone secretion?

This trial will compare the effects of sucralose with a placebo. Research has shown that sucralose might affect how the body manages sugar. Studies have found that people using sucralose had lower insulin sensitivity, meaning their bodies didn't respond as well to insulin, the hormone that helps control blood sugar. Sucralose has also been linked to changes in gut bacteria and metabolism. These findings suggest that sucralose could influence how medicines are absorbed and processed in the body. While sucralose is generally considered safe when used in moderation, these studies highlight possible effects on metabolism that require further investigation. ^{1 3 6 7 8}

Who Is on the Research Team?

Paule V Joseph, C.R.N.P.

Principal Investigator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Are You a Good Fit for This Trial?

This study is for Black or Hispanic adults aged 18-60, with a BMI of 25-40 and weighing over 110 pounds. They must be healthy without any conditions needing medication, not consume much artificial sweetener, and agree to avoid certain foods during the trial.

Inclusion Criteria

I can avoid grapefruit, certain vegetables, and quinine drinks during the study.

I am a woman who identifies as Hispanic and/or Black.

I weigh more than 110 pounds.

Exclusion Criteria

Unable or unwilling to cooperate with study procedures

I am not currently taking any medication, except possibly vitamins or other exceptions approved by the study.

GI history, at the discretion of the investigators

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Run-in

Participants avoid all non-nutritive sweeteners for 7 days

1 week

Daily monitoring

Treatment Period 1

Participants are randomized to take sucralose or placebo capsules for 14 days

2 weeks

Overnight Visit 1 and 2

Treatment Period 2

Continuation of sucralose or placebo capsules for another 14 days

2 weeks

Overnight Visit 3

Follow-up

Participants may be contacted by phone to monitor safety and effectiveness after treatment

4 weeks

Phone contact

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Sucralose

Trial Overview The SweetMeds Study is testing if sucralose affects how the body absorbs and processes medicines. Participants will take either sucralose capsules or a placebo twice daily for four weeks while their hormone levels, gut bacteria, fat metabolism, and drug absorption are monitored.

How Is the Trial Designed?

Group I: Study Arm 1 Experimental Treatment 1 Intervention

Participants will receive sucralose capsules (approximately 4mg/kg/day) by mouth for 28 days.

Group II: Study Arm 2 Placebo Group 1 Intervention

Participants will receive placebo capsules by mouth for 28 days.

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2,103

Recruited

2,760,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Lead Sponsor

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

A 3-month study involving 128 subjects with type 2 diabetes found that high doses of sucralose (667 mg daily) had no significant impact on glycemic control, as measured by HbA1c and fasting plasma glucose levels.

Sucralose was well-tolerated and showed no clinically meaningful differences in safety compared to a placebo, indicating it does not adversely affect glucose homeostasis in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. Grotz, VL., Henry, RR., McGill, JB., et al.[2022]

A 12-week study on male Sprague-Dawley rats showed that administration of Splenda (containing sucralose) led to a significant reduction in beneficial gut bacteria, such as bifidobacteria and total anaerobes, which are important for gut health.

The study also found that Splenda increased fecal pH and enhanced the expression of drug metabolism enzymes (P-glycoprotein and cytochrome P-450), potentially limiting the effectiveness of other orally administered medications, even at doses within the FDA's acceptable daily intake for sucralose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Abou-Donia, MB., El-Masry, EM., Abdel-Rahman, AA., et al.[2018]

A single sip of sucralose significantly increased serum insulin levels in healthy young adults during an oral glucose tolerance test, indicating a potential impact on insulin response.

Sucralose consumption also caused an imbalance in monocyte subpopulations, increasing classical monocytes by 7% and decreasing nonclassical monocytes by 63%, suggesting that sucralose may alter immune cell profiles and their surface molecule expressions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single 48 mg Sucralose Sip Unbalances Monocyte Subpopulations and Stimulates Insulin Secretion in Healthy Young Adults. Gómez-Arauz, AY., Bueno-Hernández, N., Palomera, LF., et al.[2021]

In a study involving 18 healthy young adults who claimed to be nonconsumers of low-calorie sweeteners (LCSs), over one-third had detectable levels of sucralose in their urine, indicating unrecognized exposure to LCSs.

Despite counseling participants to avoid LCSs, nearly half were still exposed to sucralose after the trial, suggesting that dietary instructions alone are ineffective and that non-dietary sources may contribute significantly to LCS exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Widespread sucralose exposure in a randomized clinical trial in healthy young adults. Sylvetsky, AC., Walter, PJ., Garraffo, HM., et al.[2023]

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]

In a study involving 12 healthy volunteers, maltitol, an indigestible bulking sweetener, was found to cause diarrhea more frequently than sucrose, but only at high doses (threshold dose of 93 g), indicating it can be tolerated without severe digestive symptoms at lower amounts.

Both occasional and regular consumption of maltitol did not lead to significant digestive issues compared to sucrose, suggesting it can be safely consumed in moderation without causing severe gastrointestinal discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A digestive tolerance study of maltitol after occasional and regular consumption in healthy humans. Ruskoné-Fourmestraux, A., Attar, A., Chassard, D., et al.[2012]

In two tolerance studies involving a total of 85 healthy adult volunteers, sucralose was administered in varying doses up to 10 mg/kg without any adverse effects or clinically detectable changes in health markers over the duration of the studies.

Sucralose was well tolerated even at higher doses (up to 500 mg/day for 13 weeks), and there were no indications of harmful effects on health, suggesting it is safe for frequent or long-term consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated dose study of sucralose tolerance in human subjects. Baird, IM., Shephard, NW., Merritt, RJ., et al.[2022]

A study involving 26 patients (13 with IDDM and 13 with NIDDM) found that a single high dose of sucralose did not significantly affect short-term glucose levels or insulin response compared to a placebo.

The results suggest that sucralose is safe for short-term use in individuals with diabetes, as it does not adversely impact blood glucose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. Mezitis, NH., Maggio, CA., Koch, P., et al.[2022]

A comprehensive review of the literature indicates that sucralose, a non-caloric sweetener, is safe for consumption, with studies showing no significant adverse effects on growth, reproduction, or overall health in both animals and humans.

Research has consistently shown that the intake levels of sucralose across various population groups, including children with special dietary needs, remain well below the acceptable daily intake, supporting its safety as a sugar alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical review of the current literature on the safety of sucralose. Magnuson, BA., Roberts, A., Nestmann, ER.[2022]

A comprehensive review of existing studies confirms that sucralose, a non-nutritive sweetener found in SPLENDA products, is safe for consumption in food and beverages.

An independent investigation into Granulated SPLENDA No Calorie Sweetener further supports its safety for intended use, reinforcing the overall conclusion about sucralose's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of the safety of sucralose. Grotz, VL., Munro, IC.[2016]

The study estimates the maximum potential intake of low- and no-calorie sweeteners (LNCS) like aspartame and sucralose across various age groups, using data from the US and UK, and finds that all intake estimates remain below the acceptable daily intake levels, supporting their safety in beverages.

The research demonstrates that a refined budget method for assessing LNCS intake is effective and can prioritize which sweeteners may need more detailed evaluations, ensuring consumer safety across different populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiered intake assessment for low- and no-calorie sweeteners in beverages. Tran, NL., Barraj, LM., Hearty, AP., et al.[2023]

A study analyzing urine samples from 436 adults found that over 96% had detectable levels of at least one low-calorie sweetener (LCS), indicating widespread exposure in the population.

The research revealed that self-reported consumption of low-calorie sweetened beverages significantly underestimated actual LCS exposure, with only 6% reporting consumption compared to 92% identified through urinary biomarkers, suggesting that current methods of assessing LCS intake may be inadequate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Urinary Biomarker Approach Reveals Widespread Exposure to Multiple Low-Calorie Sweeteners in Adults. Logue, C., Dowey, LRC., Verhagen, H., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10971371/

Sucralose: From Sweet Success to Metabolic Controversies ... observed lower insulin sensitivity and acute insulin response in healthy subjects given a 200 mg sucralose pill for four weeks, although there ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0002916522029641

Sucralose decreases insulin sensitivity in healthy subjects RESULTS. Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of −17.7% (− ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11250074/

Unveiling the profound influence of sucralose on metabolism ... The document comprehensively examines in vivo studies, revealing sucralose's implications on insulin resistance, gut microbiota, and metabolic syndrome.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03407079

Effects of Sucralose on Drug Absorption and Metabolism ... Sucralose might affect hormones and cause health changes. Objective: To see if sucralose changes how medicines are absorbed and processed, how hormones are ...

5. healthline.com healthline.com/nutrition/sucralose-good-or-bad

Sucralose (Splenda): Good or Bad? Sucralose is an artificial sweetener that is generally considered safe when enjoyed in moderation. However, research on its long-term effects has turned up ...

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

Aspartame and Other Sweeteners in Food To determine the safety of sucralose, the FDA reviewed more than 110 studies designed to identify possible toxic effects, including studies on ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7584803/

The hidden hazardous effects of stevia and sucralose ... The adverse effects of sucralose can be attributed to the fact that sucralose is not metabolized by the intestinal bacteria, not absorbed or transported ...

8. kentscientific.com kentscientific.com/new-research-with-mice-reveals-the-dangers-of-sweeteners/?srsltid=AfmBOor_kQ6ZMEhiCgg-6BZvrRvbJm5o1Gubg0HKNs--KQHziFPjwuLu

New Research with Mice Reveals the Dangers of ... Sucralose Suppresses the Immune System, Increases Cancer Risk. Sucralose, a zero-calorie sweetener that is 600 times sweeter than sugar, may be ...