Non-Nutritive Sweetener Consumption and Glucose Homeostasis in Older Adults With Prediabetes

NCT ID: NCT05337098

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-18
• Study Completion Date: 2026-02-28

Brief Summary

Animal and observational research in humans suggest that specific types of non-nutritive sweeteners (NNS) may impair glycemic control. However, whether NNS consumption impacts glucose homeostasis in middle-aged/older adults with prediabetes is unknown, and potential mechanisms by which this could occur have yet to be identified. The overall objective of this R21 proposal is to establish proof-of-concept for alterations in glucose homeostasis following intake of sucralose, but not aspartame, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS.

Detailed Description

Observational research has linked intake of non-nutritive sweeteners (NNS), which are consumed daily by ~50% of middle-aged/older U.S. adults, with increased risk of type 2 diabetes (T2D). This risk may be exacerbated by advancing age, which is associated with low-grade chronic inflammation and increased risk of T2D. Current T2D prevention recommendations related to NNS usage are unclear and confusing; use as an alternative to added sugar intake is suggested but long-term NNS use is discouraged despite minimal research to support this recommendation. Animal and observational human studies suggest detrimental effects of some NNS on glucose homeostasis. Longer-term human studies largely demonstrate null findings. Differences in study design and a lack of rigor in existing research contribute to inconclusive findings. In addition, NNS are often studied as a single entity yet types of NNS vary in their absorption and metabolism (e.g., the two most commonly consumed NNS, sucralose and aspartame). Whether NNS consumption impacts glucose homeostasis in middle-aged/older adults with prediabetes is unknown, and potential mechanisms by which this could occur have yet to be identified. The overall objective of this R21 proposal is to establish proof-of-concept for alterations in glucose homeostasis following intake of sucralose, but not aspartame, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS. We will investigate changes in inflammatory markers as potential mechanisms by which sucralose intake influences glucose homeostasis. Following a 2-week eucaloric lead-in diet, 30 middle-aged/older adults (40+ yrs) with prediabetes will be randomly assigned to 1 of 3 controlled feeding conditions for 6 weeks (10 participants per group): sucralose, aspartame, or a control group (no NNS). Standardized diets will be matched for macronutrients (50% carbohydrate, 35% fat, 15% protein) and other variables to avoid the potential confounds of weight change and dietary factors which may influence study outcomes (e.g., added sugars). All groups will receive identical diets, other than the additional NNS for the two NNS groups. 24-hr glycemic control using continuous glucose monitoring and insulin sensitivity and beta cell function via oral glucose tolerance test (OGTT), serum endotoxin, and inflammatory cytokines, including C-reactive protein, will be measured before and following the 6-week dietary treatment period. This research may have clinical practice and policy implications by informing U.S. dietary guidelines and guidelines for T2D prevention, which devote minimal attention to NNS and provide unclear guidance on NNS use due largely to a lack of rigorously-designed controlled feeding trials.

Conditions

Continuous Glucose Monitoring; Oral Glucose Tolerance; Insulin Sensitivity; Inflammatory Markers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Aspartame

Controlled feeding study. Dosage of aspartame will follow 25% of the acceptable daily intake (equivalent to 12.5 mg/kg for aspartame). This amount represents 750 mg/day of aspartame for a 60 kg adult.

Group Type: ACTIVE_COMPARATOR

Non-Nutritive Sweetener Intake and impact on glucose homeostasis

Intervention Type: OTHER

Provision of either aspartame, sucralose, or control with no non-nutritive sweeteners to a controlled feeding study to determine impacts on glucose homeostasis.

Sucralose

Controlled feeding study. Dosage of sucralose will follow 25% of the acceptable daily intake (equivalent to 1.25 mg/kg for sucralose). This amount represents 75 mg/day of sucralose for a 60 kg adult.

Group Type: ACTIVE_COMPARATOR

Non-Nutritive Sweetener Intake and impact on glucose homeostasis

Intervention Type: OTHER

Provision of either aspartame, sucralose, or control with no non-nutritive sweeteners to a controlled feeding study to determine impacts on glucose homeostasis.

No NNS

Controlled feeding study with no non-nutritive sweeteners.

Group Type: SHAM_COMPARATOR

Non-Nutritive Sweetener Intake and impact on glucose homeostasis

Intervention Type: OTHER

Provision of either aspartame, sucralose, or control with no non-nutritive sweeteners to a controlled feeding study to determine impacts on glucose homeostasis.

Interventions

Non-Nutritive Sweetener Intake and impact on glucose homeostasis

Provision of either aspartame, sucralose, or control with no non-nutritive sweeteners to a controlled feeding study to determine impacts on glucose homeostasis.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age 40+ years
• Prediabetic (fasting glucose concentration of 100-125 mg/dL, 2-hour oral glucose tolerance test glucose concentration of 140-199 mg/dL, or a HbA1c value of 5.7% to 6.4%)
• Weight stable for previous 6 months (±2 kg)
• BMI <40 kg/m2
• Sedentary to recreationally active
• No plans to gain/lose weight or change physical activity level
• Willing to pick up food daily and consume foods provided for an 8-week period
• Verbal and written informed consent
• Approval by Medical Director
• Consume less than one serving of non-nutritive sweetener per week

Exclusion Criteria

• BMI >40 kg/m2
• Diabetes or diabetes medication
• Antibiotic, prebiotic or prebiotic use in prior 3 months
• Uncontrolled hypertension (blood pressure (BP) > 159/99 mmHg)
• Diagnosed inflammatory bowel disease
• Past or current heart diseases, stroke, respiratory disease, endocrine or metabolic disease, or hematological-oncological disease
• Vegetarian or vegan
• Pregnant or plans to become pregnant
• Breastfeeding
• Food allergies or aversions, Phenylketonuria (PKU)
• Estrogen or testosterone usage

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Virginia Polytechnic Institute and State University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Valisa Hedrick, PhD

Role: PRINCIPAL_INVESTIGATOR

Virginia Polytechnic Institute and State University

Locations

Virginia Tech

Blacksburg, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Valisa Hedrick, PhD

Role: CONTACT

vhedrick@vt.edu

540-231-7983

Elaina Marinik, PhD

Role: CONTACT

emarinik@vt.edu

540-231-0923

Facility Contacts

Valisa Hedrick, PhD

Role: primary

Other Identifiers

1R21AG075344-01

Identifier Type: NIH

Identifier Source: org_study_id

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