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

Trial Summary

What is the purpose of this trial?

Background: Artificial sweeteners like sucralose are found in many foods and drinks. Sucralose might affect hormones and cause health changes. Objective: To see if sucralose changes how medicines are absorbed and processed, how hormones are secreted, gut bacteria, and how fat cells are metabolized. Eligibility: People ages 18-60 who: * Are black or Hispanic * Weigh more than 110 pounds * Have a body mass index of 25-40 * Do not have a condition that requires drug treatment Design: Participants will be screened with: * Medical history * Physical exam * Blood, heart, and urine tests Participants must not eat or drink anything with artificial sweeteners throughout the study. Over 7 days, Participants will answer questions, and give daily urine samples and 1 stool sample. Participants will repeat these throughout the study. Overnight Visit 1: participants will fast starting the night before. They will get breakfast at the visit. The visit includes: * An IV will be placed in the arm. Participants will get 2 tablets of medicines. Blood will be drawn several times over 24 hours. * A piece of fat tissue may be taken from the abdomen (biopsy). * Participants will have a sweet drink. Blood samples will be taken over 2 hours. Then participants will be randomly assigned to take either a sucralose capsule or placebo. They will take it twice a day for 2 weeks. They will complete two 24-hour food diaries. Overnight Visit 2 repeats Visit 1 except the biopsy. Then participants will take the capsules for another 2 weeks. Overnight Visit 3 repeats Visit 1. Participants may be contacted by phone within 4 weeks after they finish.

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.

What data supports the effectiveness of the treatment Sucralose for healthy subjects?

Research shows that sucralose is safe for use as a non-caloric sugar alternative, but there is no direct evidence of its effectiveness as a treatment for health conditions in healthy subjects. ^{1 2 3 4 5}

Is sucralose safe for human consumption?

Research shows that sucralose is safe for human consumption. Studies have found no adverse effects on health, even with repeated or long-term exposure at typical intake levels. It is approved globally as a non-caloric sugar alternative. ^{5 6 7 8 9}

How does sucralose differ from other treatments for this condition?

Sucralose is unique because it is a non-caloric artificial sweetener primarily used in foods and beverages, and it is being studied for its effects on healthy individuals rather than treating a specific condition. Unlike other treatments, it is not a medication but a sugar substitute that may influence insulin levels and gut microflora. ^{5 6 10 11 12}

Research Team

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

Principal Investigator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Eligibility Criteria

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

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

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.

I have taken blood sugar medications or antibiotics in the last 3 months.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A digestive tolerance study of maltitol after occasional and regular consumption in healthy humans. [2012]

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

Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. [2022]

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

Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. [2022]

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

A Novel Urinary Biomarker Approach Reveals Widespread Exposure to Multiple Low-Calorie Sweeteners in Adults. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Critical review of the current literature on the safety of sucralose. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Repeated dose study of sucralose tolerance in human subjects. [2022]

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

Widespread sucralose exposure in a randomized clinical trial in healthy young adults. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Tiered intake assessment for low- and no-calorie sweeteners in beverages. [2023]

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

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

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

Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. [2018]

11. Netherlands pubmed.ncbi.nlm.nih.gov

An overview of the safety of sucralose. [2016]

12. Egypt pubmed.ncbi.nlm.nih.gov

A Single 48 mg Sucralose Sip Unbalances Monocyte Subpopulations and Stimulates Insulin Secretion in Healthy Young Adults. [2021]