Effects of a Food Preservative on Glucose Homeostasis

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.