Zinc is one of the most important and ubiquitous minerals in the body, for many reasons. Most of us probably think of it for immune function, and it is important for that. Deficiency symptoms include brittle nails and hair, hair loss, poor skin healing, poor appetite, taste and smell, slow growth, infertility including impotence and lack of menses, and gut symptoms including gas, bloating, diarrhea, and nausea. It’s also critical for DNA transcription, or the process by which your body turns on and off various genes.

But zinc is also very important for mental emotional health, even though it isn’t one of the primary cofactors necessary to produce neurotransmitters. It has been linked to depression and anxiety, as well as attention problems, poor sleep, and many other mental and emotional conditions.

Metallothionein, Heavy Metals, and Oxidative Stress

Thioneins are a family of proteins that transport metals. As soon as they’ve bound a metal, they become metallothioneins (MT). The primary job of MT is to transport zinc and copper throughout the body—two minerals that act like a see-saw to one another. This may be due to competitive inhibition: they both use the same transporter, and therefore if there’s too much of one of them, there’s not enough space left for the other.

MT transports other metals too, both minerals and heavy metals. It has a particularly high affinity for cadmium, probably because zinc and cadmium are in the same group of the periodic table (which means they participate in similar chemical reactions). Each MT can bind up to seven atoms of either cadmium or zinc. In this way, MT can protect the body against heavy metal toxicity.

The most abundant amino acid in MT is cysteine (you might know the NAC version). These are terrific antioxidants, and they can thus bind to free radicals, protecting the body from oxidative stress.

Production of MT depends upon a feedback mechanism: higher levels of dietary metals (particularly of zinc) trigger increased production of MT. The opposite is also true: zinc deficiency leads to decreased levels of MT.

What this means is, the more zinc you have, the more MT you have—and aside from MT’s function of transporting zinc around the body for its various physiological functions (as well as copper, selenium, or other essential minerals), it also protects against heavy metal toxicity and oxidative stress. Both of these have been associated with mental and emotional disorders in and of themselves.

Zinc and Protection Against Excitotoxicity

Zinc also has a modulating effect upon the NMDA receptors, which are responsible for learning and memory. Specifically, zinc tends to raise the threshold required to stimulate them, and make them more liable to close, once open. This is protective against overstimulation, which can lead to excitotoxicity, neuronal inflammation and damage.

One possible cause of excitotoxicity, therefore, may be zinc deficiency.

Zinc and Maintenance of the Blood Brain Barrier (BBB)

The blood-brain barrier is an extra, very tight layer of protection against toxic chemicals in the brain. While there are many possible causes of disruption of the BBB such as gut inflammation, low essential fatty acids, poor antioxidant status, and low magnesium, zinc also plays an important role.

This is because zinc metallothionein itself helps to protect the BBB—and in return, the BBB helps to maintain zinc levels inside the brain as well. Disruption of this system can set up the brain for pathological changes.

Zinc and Neurotransmitter Levels

Even though zinc itself isn’t one of the primary cofactors necessary for neurotransmitter production, it is still critically important to the process.

One reason for this is because P5P, or activated vitamin B6, is such a ubiquitous cofactor in production of serotonin, dopamine, GABA, and glycine. And zinc is a cofactor required for the conversion of inactive Vitamin B6 to P5P (along with magnesium and Vitamin B2). Therefore, even if Vitamin B6 levels are adequate, if you’re taking the inactivated form and you’re deficient in zinc, you still might end up low in all of those neurotransmitters.

Also, one critical cofactor for the enzyme that converts dopamine into norepinephrine (dopamine beta-hydroxylaze) uses copper as a cofactor—and again, because copper and zinc tend to be a see-saw, low zinc will likely mean excessive copper. Too much copper can lead to overactivity of that enzyme, and too little dopamine with too much norepinephrine.

Zinc is also involved in modulating proteins involved with the reuptake of neurotransmitters. Because of this, it also can act as a natural serotonin reuptake inhibitor—which is a problem if you’re low in zinc, as this would translate to low serotonin also.

In addition to being necessary for GABA production (indirectly, by activating Vitamin B6), this study also shows that zinc directly modulates GABA release as well, at least in the amygdala (the part of the brain most associated with fear).

Low Levels of Zinc

Zinc is found in many different whole foods, and is particularly high in turkey, mustard greens, oysters, pumpkin seeds, soy beans, tuna, ginger root, peas, cashews, sunflower seeds, pecans, tahini, crab, peanuts, red meat, beans, whole grains, and dairy. Dietary deficiency is only likely if you’re eating a highly processed, standard American diet, and are not on a good multivitamin.

However, certain conditions can also contribute to zinc depletion. Exposure to excessive heavy metals, for example, may cause competitive inhibition with metallothionein, and lead to zinc deficiency. High copper, which can be genetic or acquired, will also lead to zinc deficiency. Pyroluria, either genetic or acquired, is another potential cause for deficiency.

Assuming none of these apply to you, except for brief periods of acute illness, it’s best not to exceed about 30 mg of zinc per day unless you are also taking copper, to offset the possibility of inducing a copper deficiency with excess zinc supplementation.

How Zinc Influences Mental Health