Benzoates - an Obesogenic Endocrine Disrupting Chemical
| Status: | Recruiting |
|---|---|
| Conditions: | Obesity Weight Loss, Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 30 |
| Updated: | 2/3/2018 |
| Start Date: | July 1, 2017 |
| End Date: | July 2019 |
| Contact: | David N Collier, MD, PhD |
| Email: | collierd@ecu.edu |
| Phone: | 252 744 4994 |
Benzoic Acid in Beverages: Establishing a Link Between Urinary Metabolites, Metabolic Dysregulation and Weight Loss Failure
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.
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.
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.
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.
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
We found this trial at
1
site
Greenville, North Carolina 27834
Phone: 252-744-4994
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