A common dietary supplement that has rapid and lasting antidepressant effects

This 2012 Italian rodent study found that a common dietary supplement had rapid and lasting antidepressant effects:

“Remarkably, L-acetylcarnitine displayed a clear-cut antidepressant effect already after 3 and 7 d[ays] of daily dosing. No tolerance was developed to the action of L-acetylcarnitine. The drug was even more effective after 21 d[ays], and the effect persisted for at least 2 w[ee]k[s] after drug withdrawal.”

The researchers studied stressed mice and rats to determine that:

  1. An effect of the stress was to epigenetically change the hippocampus part of the limbic system to produce less of an important molecule – type 2 metabotropic glutamate (mGlu2).
  2. A reduction of the mGlu2 molecule decreased the hippocampus’ regulation of the glutamate neurotransmitter.
  3. Under-regulation of glutamate, in turn, caused symptoms of depression.

L-acetylcarnitine reversed the stress-induced underlying causes by acetylating histone proteins that control the transcription of the brain-derived neurotrophic factor (BDNF) and mGlu2 receptors in the hippocampus and prefrontal cortex.


A commentary on this research, Next generation antidepressants, had a Figure 1 that showed possible mechanisms for the effects of L-acetylcarnitine. Epigenetic histone modifications seem to be more easily reversible than epigenetic DNA methylation.


“Currently, depression is diagnosed only by its symptoms,” Nasca says. “But these results put us on track to discover molecular signatures in humans that may have the potential to serve as markers for certain types of depression.”

It’s tempting to extrapolate this study to humans and test whether depression symptoms could be effectively treated with some multiple of a normal L-acetylcarnitine dietary supplement dose of 500 mg at $.25 a day. To cure stress-induced illnesses in humans, though, causes of stress should be removed or otherwise addressed.

http://www.pnas.org/content/110/12/4804.full “L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors”

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