Download Zinc: an Antidepressant The essential mineral for resiliency Zinc is

Zinc: an Antidepressant
The essential mineral for resiliency
Zinc is an essential mineral that may be lacking in modern processed and strict vegetarian diets, as major sources
are meat, poultry, and oysters. While beans and grains also contain zinc depending on the soils in which they are
grown, phytates in grains, legumes, and nuts can interfere with its absorption. Since the body has no special zinc
storage capability, its important to consume a bit of zinc on a regular basis (1).
What does zinc have to do with depression? It turns out that zinc plays a part in modulating the brain and body’s
response to stress all along the way. I’ll review some tried and true information, but excellent new paper brings all the
evidence together and sheds some new light.
300 or more enzymes in our bodies use zinc as a buddy to help them do their thing, making DNA, protein synthesis,
cell division, all hugely important stuff. Zinc is also critical to cell signaling (a major receptor motif, the “zinc finger” is
as famous as the G protein in cell biology circles). The highest amount of zinc in the body is found in our brains,
particularly in a part of our brains called the hippocampus. Zinc deficiency can lead to symptoms of deression, ADHD,
difficulties with learning and memory, seizures (2), aggression, and violence (3).
Back in the day, scientists did all sorts of horrible experiments on rats to see what zinc does in the brain. It is antiinflammatory and anti-depressant on its own, and the combination of zinc plus
modern antidepressant medication made rats more resilient in face of hopeless swimming and being restrained. Zinc
increased the amount of the brain fertilizer BDNF in the hippocampus and reduced rat fighting behavior.
In humans, zinc has been found to be low in the serum of those suffering from depression. In fact, the more
depressed someone is, the lower the zinc level (4). Low zinc also seems to affect inflammation and immunity. The T
cells in our immune system, which hunt and kill infection, don’t work well without zinc and also release more calls for
help (leading to more inflammation, via IL-6 and IL-1) in the case of zinc deficiency. Zinc supplementation has been
shown to have antidepressant effects in humans, and successful treatment with antidepressants will increase serum
zinc levels. That last bit of information tells us that low zinc levels are a biomarker for depression, zinc is not the
whole story. Under conditions of major stress, we tend to get rid of zinc like gangbusters in our urine, sweat, and
saliva.
If we want to get down to the super nitty gritty, we can examine the role of zinc in the hippocampus, which is the part
of the brain central to memory and mood. Antidepressants work (when they do) by increasing the production of the
nerve fertilizer BDNF in the hippocampus, which helps in nerve recovery, adaptation, and repair. Zinc deficiency
leads to decreased zinc in the nerve synapse, which results in an increase in the NMDA receptors. These receptors
respond to glutamate, an excitatory neurotransmitter that can be responsible for toxic effects in the brain if there is
too much. At the same time, the inhibitory (in this case, neuroprotective) neurotransmitter GABA is decreased, along
with BDNF and another nerve growth factor, NGF. The glutamate level in the synapse is higher, so calcium mediated
stimulation of the nerves is primed. Do this too much, and you get "excitotoxicity." This same mechanism is thought
(in acute vs chronic and in differing areas of the brain) to be responsible for seizures, migraines, dementia, anxiety,
depression, and bipolar disorder (and is why pharmaceutical GABA receptor modulators, such as valium and antiseizure medicines, can be effective for certain symptoms of any of those conditions).
To rephrase, zinc is a cog in the machine in pretty much every signal and second messenger system you might have
learned about in molecular biology classes. So that said So there are clear mechanisms by which absolute zinc
deficiency can have a hand in all sorts of bad brain syndromes, and vegetarians, dieters, the elderly, those with
malabsorption or intestinal issues, and the two billion people on the planet who (due to poverty) pretty much subsist
on grains alone (rich in zinc-binding phytates) are all at risk for absolute zinc deficiency.
But the zinc-replete massive meat-eaters can get depression, diabetes, and all the Western diaspora of chronic
disease, of course. Inflammation is the primary driving mechanism behind the whole shebang and may decrease
brain zinc levels all on its own. Pancreatic beta cells, who are on the front lines in diabetes, also run a lot of zincdependent pathways (5)(6). Zinc plays a major role in the inflammatory response, increasing the body’s ability to fight
viruses such as the common cold (7) and, at the same time, starts the domino chain in down-regulating the
inflammatory response. IL-6, an inflammatory cytokine which needs zinc the be born, will activate a protein in the
liver called metallothionein, a protein that holds on to zinc and keeps it in the liver, so that even if you eat a lot of zinc,
it won't be available in your blood or brain for other uses. A lot of biochemical systems work this way—too little zinc
(such as in people born without the ability to absorb it (8) and you get immune dysfunction and vulnerability to
infection, as your protective inflammatory response won't work. But if inflammation gets high enough, it has its own
down regulating systems (sequestering zinc via IL-6 and metallothionein, for example) that cool things off.
Our inflammatory and fight or flight systems were built for acute insults. Viruses, injury, bacterial invasion, angry lion
attacking the camp. When the insults are chronic (unalleviated stress, gallons of inflammatory-promoting omega-6
fatty acids, weird glutens and lectins, chronic depression-causing viral infections such as herpes, HIV, or Epstein
Barr), the whole system becomes dysregulated. What should be up is down. So zinc ought to be in the central
nervous system, helping out with nerve repair and plasticity, and instead it is crusading with the inflammatory
cytokines or stuck with metallothionein in the liver, and your poor hippocampus is shorting out on glutamate and
calcium. Extra zinc might help. As might antidepressants, GABA receptor modulators, and other neuroprotective
chemicals. But those are bailing buckets. What we really need is to correct the problem causing the boat to sink. We
need to reduce the inflammatory insults in the first place.