title: Effects of sodium benzoate, a widely used food preservative, on glucose homeostasis and metabolic profiles in humans.
abstract: Sodium benzoate is a widely used preservative found in many foods and soft drinks. It is metabolized within mitochondria to produce hippurate, which is then cleared by the kidneys. We previously reported that ingestion of sodium benzoate at the generally regarded as safe (GRAS) dose leads to a robust excursion in the plasma hippurate level [1]. Since previous reports demonstrated adverse effects of benzoate and hippurate on glucose homeostasis in cells and in animal models, we hypothesized that benzoate might represent a widespread and underappreciated diabetogenic dietary exposure in humans. Here, we evaluated whether acute exposure to GRAS levels of sodium benzoate alters insulin and glucose homeostasis through a randomized, controlled, cross-over study of 14 overweight subjects. Serial blood samples were collected following an oral glucose challenge, in the presence or absence of sodium benzoate. Outcome measurements included glucose, insulin, glucagon, as well as temporal mass spectrometry-based metabolic profiles. We did not find a statistically significant effect of an acute oral exposure to sodium benzoate on glucose homeostasis. Of the 146 metabolites targeted, four changed significantly in response to benzoate, including the expected rise in benzoate and hippurate. In addition, anthranilic acid, a tryptophan metabolite, exhibited a robust rise, while acetylglycine dropped. Although our study shows that GRAS doses of benzoate do not have an acute, adverse effect on glucose homeostasis, future studies will be necessary to explore the metabolic impact of chronic benzoate exposure.
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: belinda.lennerz@childrens.harvard.edu.
authors.forename: Belinda S
authors.initials: BS
authors.lastname: Lennerz
authors.affiliation: Massachusetts General Hospital, Boston MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: vafai@molbio.mgh.harvard.edu.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Vafai
authors.affiliation: Massachusetts General Hospital, Boston MA 02114, USA. Electronic address: nigel.delaney@post.harvard.edu.
authors.forename: Nigel F
authors.initials: NF
authors.lastname: Delaney
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: clary@broadinstitute.org.
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: adeik@broadinstitute.org.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Deik
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: kpierce@broadinstitute.org.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Pierce
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: david.ludwig@childrens.harvard.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Ludwig
authors.affiliation: Massachusetts General Hospital, Boston MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: vamsi@hms.harvard.edu.
authors.forename: Vamsi K
authors.initials: VK
authors.lastname: Mootha
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004032:Diet; D005260:Female; D005520:Food Preservatives / Q000008:administration & dosage / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000097:blood; D006626:Hippurates / Q000097:blood; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D055442:Metabolome; D050177:Overweight; D020160:Sodium Benzoate / Q000008:administration & dosage* / Q000378:metabolism*; D055815:Young Adult; D062367:ortho-Aminobenzoates / Q000097:blood
chemical_list: D000927:Anticonvulsants; D001786:Blood Glucose; D005520:Food Preservatives; D006626:Hippurates; D007328:Insulin; D062367:ortho-Aminobenzoates; D005934:Glucagon; D005947:Glucose; D020160:Sodium Benzoate; C030514:hippuric acid; D005998:Glycine; C006368:aceturic acid
keywords: Benzoate; Diabetes; Hippurate; Preservative; Tryptophan