Wednesday, January 15, 2014

Zinc supplements in mental health

Zinc is a trace mineral which is necessary for a variety of metabolic functions in the body.  The neuropharmacology of zinc certainly includes NMDA-blockade effects, as well as a probable collection of other effects such as increasing BDNF expression. 

There is evidence that zinc supplements could be helpful to treat depression.  Here is a brief review of some pertinent studies:
In this very simple Polish study published in 2003, 14 patients with unipolar depression were randomized to receive either antidepressant + placebo, or antidepressant  + 25 mg zinc, for 12 weeks.  Both groups improved, but the zinc group had about 40% greater symptom reduction than the placebo group.  I appreciate the fact that in this paper, the complete set of data was shown, for each individual patient in the study.  This allows one to do a custom analysis of the data:  in this case, for example, there were several patients who appeared to be treatment-resistant in the placebo group,  and it was interesting to look at the results with these patients excluded, since they would otherwise skew the results in favor of the zinc group.  But even with this adjustment, the zinc group still had a significant, clinically relevant improvement compared to placebo.
This study done in 2009 looked at imipramine+ 25 mg/d zinc vs imipramine+placebo, for 12 weeks, in 60 unipolar depressed patients.  Here they found that for treatment resistant patients, the zinc group improved significantly more than the placebo group.  In effect, the zinc caused the treatment resistant group to respond as though it was no longer treatment resistant!   Yet, in this study, the zinc did not further improve symptoms in patients who were not treatment resistant.
Another simple 12-week study, done in Iran, of 25 mg/d added zinc or placebo, in 44 patients with major depression.  It was quite recent, from 2013.   The zinc group once again improved substantially more than the placebo group.   The study stands out in looking carefully at dietary intakes of various nutrients in all of the patients, to control for various dietary confounds.
another replication, from 2013
A 2013 meta-analysis, which concluded that zinc supplements have a clinically relevant effect in depression.
Another meta-analysis, from 2012.  Again it affirms the possible usefulness of zinc, not only for treatment of depression, but for prevention as well. 
This meta-analysis looked at zinc in treating ADHD, and the conclusions were largely negative.  There have been a few studies suggesting benefit, but these results seem not to be consistent enough to make a recommendation.  It is tempting to consider a trial of zinc augmentation as a deliberate trial for a an individual though, given the negligible risk.

Here is a link to my previous posting about zinc, which outlines some other uses in psychiatry, such as in eating disorders.  Also my other posting reviews some information about toxicity risks.
This interesting study showed that high dose zinc supplements (corresponding to about 60 mg/d in humans) given to rats actually led to a reduction in zinc levels in the hippocampus, and an impairment in memory performance.  The mechanism may be that higher serum zinc levels reduces synaptic release of zinc, through a negative feedback mechanism.  The article can be taken as a warning that more is not necessarily better!  The low-dose zinc supplemented group in this study did better, corresponding to a human dose of about 15 mg/d.

In conclusion, I think zinc supplementation is a reasonable, safe, evidence-based augmentation strategy for treating or preventing depression.  Most of the studies used 25 mg elemental zinc; I think this is a reasonable dose for an initial 12-week trial.  After this point, if continued zinc supplementation is to be used, I would suggest bringing the dose down to the 15-20 mg per day range, to rule out toxicity risks.  

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