Benzoates - an Obesogenic Endocrine Disrupting Chemical
Condition: Obesity; Metabolic Syndrome
MeSH terms: Metabolic Syndrome
Study type: Interventional

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.
    

Intervention name(s): Benzoic acid washout and exposure
Intervention type(s): Other
Intervention description(s): see above
Intervention MeSH terms: Benzoic Acid
Intervention model: Single Group Assignment
Intervention model description: Pre/post exposure comparison
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: benzoic acid; endocrine disrupting chemicals; leptin; metabolic rate