Benzoates - an Obesogenic Endocrine Disrupting Chemical

• ClinicalTrials.gov Identifier: NCT03190785
• Recruitment Status: Completed
• First Posted: June 19, 2017
• Last Update Posted: March 24, 2023
• Sponsor: East Carolina University
• Information provided by (Responsible Party): David Nash Collier, East Carolina University

Tracking Information

• First Submitted Date: June 13, 2017
• First Posted Date: June 19, 2017
• Last Update Posted Date: March 24, 2023
• Actual Study Start Date: July 1, 2017
• Actual Primary Completion Date: March 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 15, 2017)

Metabolic rate [ Time Frame: measured following 1 week dietary exposure to benzoic acid. ]

Metabolic rate as measured by indirect calorimetry

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 15, 2017)

Leptin levels [ Time Frame: measured following 1 week dietary exposure to benzoic acid ]

Circulating levels of the adipokine leptin will be measured using ELISA

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Benzoates - an Obesogenic Endocrine Disrupting Chemical
• Official Title: Benzoic Acid in Beverages: Establishing a Link Between Urinary Metabolites, Metabolic Dysregulation and Weight Loss Failure

Brief Summary

The benzoic acid derivatives sodium and potassium benzoate are preservatives that are commonly added to food and beverages to inhibit microbial growth and prevent spoilage. In the US the major source of benzoate intake is beverages. Studies have shown that piglets or chicks fed low levels of benzoic acid have greater feed efficiency and gain more weight than control fed animals. It has also been shown that benzoic acid inhibits the release of a key metabolic hormone, leptin, from isolated adipocytes (fat cells). Inadequate leptin levels result in increased appetite, decreased metabolic rate, weight gain, insulin resistance and increased diabetes risk.

The primary aim of the proposed research is to directly determine if benzoate consumption in human volunteers results in lower levels of leptin, decreased metabolic rate and increased insulin resistance. If so this would implicate benzoic acid as an obesogen and would help inform more effective approaches to obesity prevention and treatment. A secondary aim of the study is to establish a connection between benzoate exposure and biomarkers in urine that can be used to help treat obese patients.

Detailed Description

Our hypothesis is that benzoic acid is an obesogenic xenobiotic that attenuates the leptin signaling pathway resulting in lower metabolic rate and hence a propensity to weight loss non-responsiveness.

This hypothesis will be addressed in this pilot project via the following Specific Aims:

Aim 1. Determine if dietary benzoate attenuates leptin levels and metabolic rate in human subjects. Twenty heathy adolescents and young adults (age 18-25 yrs.) who are either overweight (BMI 25-29.9) or obese (BMI ≥ 30) will be studied. Following a 14 day period of avoiding benzoate containing beverages (washout period) subjects will then consume 36 oz./day of benzoate containing beverages (~ 3.9 - 4.5 mg benzoate/kg body weight per day exposure) for 7 days (exposure period). Fasting plasma samples will be collected pre and post-exposure and leptin, adiponectin, insulin and glucose levels will be compared. Indirect calorimetry will be used to compare resting energy expenditure pre-and post-exposure.

Aim 2. Validate the use of urinary hippurate and glycine to assess benzoate exposure. An early morning void urine samples will be collected pre-and post-exposure. Non-targeted NMR-based metabolomics analysis will be used to compare changes in individual subject's urinary metabolome using pre- and post-exposure as the "phenotypic" anchors.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Pre/post exposure comparison

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Obesity
• Metabolic Syndrome

Intervention

Other: Benzoic acid washout and exposure

see above

Study Arms

Experimental: Benzoic acid washout and exposure

All subjects will be in this arm which employs a pre-post exposure design. Subjects will undergo a 2 week washout period where they avoid consumption of benzoate containing beverages. Then there is a 1 week exposure period comprising daily consumption of benzoate containing beverages to result in up to 5 mg/kg per day benzoic acid intake.

Intervention: Other: Benzoic acid washout and exposure

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 15, 2017): 20
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 1, 2021
• Actual Primary Completion Date: March 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Young adult (18-30 yrs)
• Healthy non-smoker
• Either overweight (BMI >25 but <30) or obese (BMI >30)
• Has or can obtain transportation to study site
• Able to provide written consent in English

Exclusion Criteria:

• Metabolic disease

  1. Diabetes mellitus
  2. Hypothyroidism

• Use of medication that may influence metabolism

  1. Anti-hyperglycemic agents
  2. Thyroid hormone
  3. Stimulants for ADD/ADHD
  4. Atypical anti-psychotics
  5. Weight loss medications
• Benzoate sensitivity
• Known pregnancy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 30 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03190785
• Other Study ID Numbers: 17-000376
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: David Nash Collier, East Carolina University
• Original Responsible Party: Same as current
• Current Study Sponsor: East Carolina University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: East Carolina University
• Verification Date: March 2023