Original title: Acute vitamin B12 supplementation evokes antidepressant response and alters Ntrk-2

Authors: Charlotte Trautmann, Andreas Bock, Christian A. Hübner from the Institute of Human Genetics at Jena University Hospital; Anja Urbach from the Institute of Neurology at Jena University Hospital; Olivia Engmann from the Institute of Human Genetics at Jena University Hospital and the Laboratory of Neuroepigenetics at the University of Zurich and ETH Zurich

Source: DOI: https://doi.org/10.1016/j.neuropharm.2020.108112

Note: This scientific study is freely accessible to everyone and has been translated into German by me. The emphasis is mine.

What was the study about?

It was investigated whether vitamin B12 supplementation has an effect on depression.


  • Vitamin B12 reduces DNA methylation in the Ntrk-2 gene in vitro.
  • A single dose of vitamin B12 improves depression-like behavior in mice 24 hours later.
  • Vitamin B12 reverses the effects of stress on the expression of the Ntrk-2 gene in the prefrontal cortex.


  • Depression is the most common cause of disability worldwide. Although most research on risk factors focuses on stress, there is also a strong link between dietary factors and depression.
  • Chronic vitamin B12 supplementation can reduce the risk of depression and, in animal models, help to reverse the pro-depressive effects of early childhood stress.
  • However, it is still unclear whether a single acute dose of vitamin B12 is sufficient to induce antidepressant effects at the molecular or behavioral level.
  • Based on pharmacological work and CRISPR-dCas9 epigenome editing in Neuro2A cells, we provide in vitro evidence for a link between vitamin B12, gene expression and DNA methylation of the antidepressant-associated gene Ntrk-2 encoding the BDNF receptor TRKB.
  • Using stress induction protocols in C57Bl/6 J mice in combination with behavioral tests and subsequent molecular tissue analysis , we provide in vivo evidence for antidepressant effects of vitamin B12.
  • Acute supplementation with vitamin B12, but not folic acid, selectively altered DNA methylation and Ntrk-2 gene expression in vitro, although DNA methylation and Ntrk-2 gene expression do not correlate in vivo.
  • Importantly, acute vitamin B12 injection improved several behavioral measures in tests of antidepressant activity while reversing the effects of chronic and acute stress on Ntrk-2 levels in vivo, although causality has not yet been established at this stage.
  • Overall, acute vitamin B12 supplementation can reverse the effects of stress on Ntrk-2 gene expression and improve behaviors associated with depression-like behaviors in mice.
  • Our results encourage further investigation of vitamin B12 supplementation as a novel model for antidepressant action.