Citation

Kalkman HO. Int. J. Mol. Sci. 2022; 23(13): e6953.

Copyright

(Copyright © 2022, Molecular Diversity Preservation International)

DOI

10.3390/ijms23136953

PMID

35805959

Abstract

Low levels of n-3 poly-unsaturated fatty acids (n-3 PUFAs) and high levels of n-6 PUFAs in the blood circulation are associated with an increased risk for suicide. Clinical studies indicate that docosahexaenoic acid (DHA, a n-3 PUFA found in fish-oil) displays protective effects against suicide. It has recently been proposed that the activation of the transcription factor NRF2 might be the pharmacological activity that is common to current anti-suicidal medications. Oxidation products from fish oil, including those from DHA, are electrophiles that reversibly bind to a protein 'KEAP1', which acts as the molecular inhibitor of NRF2 and so indirectly promotes NRF2-transcriptional activity. In the majority of publications, the NRF2-stimulant effect of DHA is ascribed to the metabolite 4-hydroxyhexenal (4HHE). It is suggested to investigate whether 4HHE will display a therapeutically useful anti-suicidal efficacy.

Language: en

Keywords

suicide prevention; 4-hydroxyhexenal; docosahexaenoic acid; fish oil; NRF2