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Benzoates - an Obesogenic Endocrine Disrupting Chemical

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

Tracking Information
First Submitted Date  ICMJE June 13, 2017
First Posted Date  ICMJE June 19, 2017
Last Update Posted Date March 24, 2023
Actual Study Start Date  ICMJE July 1, 2017
Actual Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Benzoates - an Obesogenic Endocrine Disrupting Chemical
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Pre/post exposure comparison
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Obesity
  • Metabolic Syndrome
Intervention  ICMJE Other: Benzoic acid washout and exposure
see above
Study Arms  ICMJE 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 15, 2017)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 1, 2021
Actual Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 30 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03190785
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Current Responsible Party David Nash Collier, East Carolina University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE East Carolina University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account East Carolina University
Verification Date March 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP