A high methyl donor diet affects physiology and behavior in Peromyscus polionotus

Physiol Behav. 2019 Oct 1:209:112615. doi: 10.1016/j.physbeh.2019.112615. Epub 2019 Jul 9.


Folic acid and other dietary methyl donors are widely supplemented due to their ability to prevent neural tube defects. Dietary methyl donors are also added to other consumables such as energy drinks due to energy-promoting attributes and other perceived benefits. However, there is mounting evidence that indicates developmental exposure to high levels of dietary methyl donors may have deleterious effects. We assessed whether behavior was affected in the social North American rodent species Peromyscus polionotus exposed to a diet enriched with folic acid, Vitamin B12, choline, and betaine/trimethylglycine(TMG). P. polionotus (PO) animals are very social and exhibit little repetitive behavior, particularly compared to their sister species, P. maniculatus. We assayed the effects of dietary methyl-donor supplementation on anxiety-like repetitive and social behaviors by testing young adult animals for novel cage behavior and in social interaction tests. Animals of both sexes exposed to the diet had increased repetitive behaviors and reduced social interactions. Males exposed to the diet became more aggressive compared to their control counterparts. Since methyl-diet animals were larger than control animals, DEXA scans and hormone analyses were performed. Animals exposed to the diet had increased body fat percentages and experienced hormonal changes typically associated with excess fat storage and anxiety-like behavior changes. Therefore, these data suggest the wide use of these dietary supplements makes further investigation imperative.

Keywords: Anxiety-like behavior; Folic acid; Methyl-donor pathway; Peromyscus; Repetitive behavior; Social behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Absorptiometry, Photon
  • Animals
  • Anxiety / psychology
  • Behavior, Animal*
  • Betaine / antagonists & inhibitors
  • Choline / adverse effects
  • DNA Methylation
  • Diet*
  • Female
  • Folic Acid / adverse effects
  • Gonadotropin-Releasing Hormone / metabolism
  • Male
  • Peromyscus / physiology*
  • Social Behavior
  • Vitamin B 12 / adverse effects


  • Gonadotropin-Releasing Hormone
  • Betaine
  • Folic Acid
  • Choline
  • Vitamin B 12