Effects of a Food Preservative on Glucose Homeostasis

The investigators propose to examine the effects of the common food preservative sodium benzoate on blood glucose and related hormones and metabolites. If an effect is demonstrated, patients with increased diabetes risk could be counseled to avoid this preservative.

Study Overview

• Status: Completed
• Conditions: Overweight
• Intervention / Treatment: Other: benzoate containing test drinks; Other: non sodium benzoate containing test drinks

Detailed Description

Soft drink consumption has been repeatedly implicated in the development of type 2 diabetes (T2DM). Interestingly, epidemiology studies have yielded inconsistent results. Some studies identify sugar-sweetened beverages as the culprit, whereas others point towards artificially-sweetened beverages. Beyond differences in methodology, these conflicting reports raise the question whether another ingredient common to both sugar and artificially-sweetened soft drinks, such as a preservative, might play a role.

Benzoate salts are widely used preservatives in products such as sodas, canned goods, and pharmaceuticals. Interestingly, there is published evidence that sodium benzoate and its metabolite hippurate can affect pancreatic islet function and impair glucose tolerance. However, the effects of oral sodium benzoate at concentrations typically used in our diet on glucose homeostasis have not been systematically studied. Here, we propose to close this knowledge gap.

We will recruit 15 healthy, overweight volunteers, age 18-35. Each subject will receive 4 interventions: an oral glucose challenge 1) with and 2) without 0.1% benzoic acid, and a drink of water 3) with and 4) without 0.1% benzoic acid. Blood samples will be analyzed for glucose, insulin, glucagon, and a panel of approximately 300 different metabolites at baseline and serially for 2 hours after each intervention. Factorial analysis of variance will be performed to determine the effects of benzoic acid in the presence and absence of glucose, and interactions between glucose and benzoate. The planned sample size of 15 will provide 80% power to detect an effect-size of 0.16 standard-deviations in outcome measures, and an interaction-effect of 0.33 standard-deviations, with a critical value p=0.05.

If we find through this study that sodium benzoate significantly affects glucose tolerance, the public health implications would be great. High level, frequent consumption might cause diseases associated with insulin resistance, chiefly T2DM. Furthermore, its presence in OGTT testing solutions could provide misleading results.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital
    • Boston, Massachusetts, United States, 02101
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women age 18-35
• BMI 25-30

Exclusion Criteria:

• Diabetes Mellitus (fasting Blood Glucose ≥ 126mg/dl)
• Exercise more than 60 minutes more that 4 times a week
• Major medical illness
• Medications or supplements that can influence glucose metabolism
• Large fluctuations in weight (>5% over the past 6 months)
• Currently following a weight loss program
• Consumption of more than 24 ounces of soda per day (defined as sugar- or artificially sweetened beverages, e.g. colas or fruit punches, excluding hot tea and coffee)
• Allergy or intolerance to sodium benzoate
• Nicotine use
• Illicit substance use
• Women with irregular menstrual cycles, or who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sodium benzoate containing	Other: benzoate containing test drinks; Subjects will consume 500ml of water with 0.5 grams of sodium benzoate, followed by a solution of 75g sugar in 500ml water with 0.5 grams sodium benzoate 3 hours later. Each solution will be consumed over 5 minutes.
Active Comparator: non sodium benzoate containing	Other: non sodium benzoate containing test drinks; Subjects will consume 500ml of water followed by a solution of 75g sugar in 500ml water 3 hours later. Each solution will be consumed over 5 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose area under the curve (AUC)	Plasma glucose will be measured at baseline, 15, 30, 45, 60, 90, and 120 minutes post ingestion of each test solution, and area under the curve will be calculated.	120 minutes post ingestion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin AUC	Serum Insulin will be measured at baseline, 15, 30, 45, 60, 90, and 120 minutes post ingestion of each test solution, and area under the curve will be calculated.	120 minutes
Glucagon AUC	Plasma Glucagon will be measured at baseline, 15, 30, 45, 60, 90, and 120 minutes post ingestion of each test solution, and area under the curve will be calculated.	120 minutes
Metabolite Profiles	Metabolite analysis will be performed on blood samples at baseline, 15, 30, 45, 60, 90, and 120 minutes post ingestion of each test solution, and area under the curve will be calculated.	120 minutes

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Massachusetts General Hospital
• Investigators: Principal Investigator: Vamsi Mootha, MD, Massachusetts General Hospital; Study Director: Belinda S Lennerz, MD, PhD, Boston Children's Hospital; Study Director: Scott Vafai, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: August 10, 2010
• First Submitted That Met QC Criteria: August 10, 2010
• First Posted (Estimate): August 11, 2010

Study Record Updates

• Last Update Posted (Estimate): October 1, 2012
• Last Update Submitted That Met QC Criteria: September 28, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: diabetes; blood sugar; benzoic acid; benzoate; soda; soft drink; preservative
• Additional Relevant MeSH Terms: Body Weight; Overweight
• Other Study ID Numbers: 10-05-0202