Laura Hosch

N00405108
Zinc intake and supplementation may impact the risk of depression in adults
Introduction

Depression is a common mental disorder. Any person can suffer or become depressed; depression

is unbiased. With the rise of depression rates throughout the world, scientists have been tasked to address

the issue and understand and identify not only the cause but, potential solutions. Many factors such as

age, genetics, non-biological factors, as well as dietary factors can cause depression. 1 Micronutrients such

as folate, vitamin B12, and D found in sources such as fortified cereals, red meat, etc. are known to

influence depression: additionally, the mineral, zinc, is found in similar sources and co-deficiencies

between the micronutrients commonly occur.¹ Zinc, a trace element, is involved in over 300 enzymatic

processes in the human body. One role of zinc is to regulate cellular function. Mostly found in the

regions of the brain related to emotions: the hippocampus, the olfactory bulb, the frontal cortex, and the

amygdala; it has been linked to serotonergic, dopaminergic, and glutamatergic systems. 1,2 These are

nerves that are acted upon and release the affiliated neurotransmitters/hormones. Notedly,

pharmaceutical interventions target inhibiting the N-methyl-D-aspartate (NMDA) receptor to combat

depressive disorder. Overstimulation of NDMA increases Ca 2+ influx known to cause psychiatric

disorders.3 NMDA is modulated by zinc and zinc deficiency increases activity, which is known to cause a

depressive state.² Studies conducted have contradicted each other on the efficacy of zinc treatment for

depression suggesting more research needs to be conducted. The purpose of this paper is to determine the

impact zinc intake and supplementation may have on depression in adults and if it may be used as a

treatment option. In a generation where prescription drug treatments are not always desired, finding

alternative solutions to depression is crucial to for people who are resistant to prescription drug use.

Methods
 All studies used were found on the databases, CINAHL and Science Direct. Through these

databases, the keywords used were: zinc, depression, depressive disorder, NDMA, and depression

treatment. Studies included were prospective cohort, longitudinal, cross-sectional, and epidemiologic

studies. From the yielded search results, the inclusion criteria included both men and women, aged 18 and

older, with both a history and non-history of depression; also included were experiments that used animal

testing. Inclusion criteria also allowed subjects that had been treated prior to the research with

prescription medication. Whether through supplementation or diet, the evaluation and/or addition of zinc

to diagnose or treat is the primary inclusion factor.

Depression and Zinc Deficiencies

Zinc can be found in food sources such as oysters, red meat, fortified breakfast cereals, and

oatmeal. However, there are many other great sources making it readily available to most populations.

Approximately 25% of the world’s population is at risk for zinc deficiency, with a total of 35-40% of

adults aged 60 or older consuming low or inadequate zinc. 4 Studies have found a link between low zinc

intake/plasma levels and depression but, without other variables controlled, understanding its true impact

is limited. Jung and colleagues found in a prospective cohort study conducted on 1,514 men and women

ages 60-84, 18.7% were zinc deficient and 15.7% had depressive symptoms. 4 The group adjusted its

findings to take in account other factors that can contribute to depression such as inadequate sleep and

other deficiencies such as B12 and D. Even with these adjustments, the researchers found deficient zinc

plasma was associated with a high risk of depression. 4 It is worth noting that Lung and his team found

zinc intake was lower in women due to dietary habits (low red meat consumption), but plasma levels

were similar to those in male subjects. They concluded a zinc deficiency sensitivity by aging women is

most likely due to low levels of oestrogen that promote serotonin signaling where zinc is thought to be a

serotonin upregulator.4 Ultimately, the conclusion was an increase in dietary zinc can help to combat zinc

deficient plasma levels and improve depressive symptoms. Similarly, in a cross-sectional, epidemiologic

study conducted by Maserejian, Hall, and McKinlay, found men and women with low zinc intake was
attributed to low socioeconomic status. Women displayed a significant association between low zinc

intake and depressive symptoms.5 A strong limitation to their study due to its observational nature, the

relationships between insufficient zinc and depressive symptoms did not take in account other factors that

affect depression as Jung and colleagues research did. The connection has been repeatedly made between

low zinc intake in women but, the same nexus has not made with men. 5,6 In a prospective cross-sectional

study by Soili M. Lehto and team, 2,682 Finnish men were recruited for baseline testing during the years

1984 and 1989 for zinc intake using a four day food record and to receive a diagnosis of unipolar

depressive disorder or not. Twenty years later, only 2.7% received a diagnosis of depression during the

duration of the study. The team observed that when taking in account all other factors that can attribute to

a depression diagnosis, zinc intake was not associated with an increased risk for depression. 6 From the

evidence, low zinc intake and deficiency is a possible indicator of depression risk in women, but not in

men.4,5,6

Depression and Supplemental Zinc

While many people may self-diagnose their depression, those that seek clinical diagnosis often

are looking for treatment. Zinc, found heavily in the central nervous system, is particularly dense in the

hippocampus. In depressed individuals, the hippocampus has been seen to be reduced in volume which

might lead to reduced neurogenesis.7 Ding and associates found in an animal study on male mice placed

under chronic restraint stress (CRS), that zinc levels in the hippocampus increased while zinc serum

levels were decreased.7 The significance of this is: at increased intracellular Zn 2+ due to a rise in

corticosterone (stress) results in the generation of reactive oxygen species (ROS) and decreased

production of adenosine triphosphate (ATP) in cells, which can lead to a defective hippocampus. 7 High

levels of zinc in the hippocampus can cause depressive symptoms in animals under CRS. Action to

reverse depressive symptoms in the mice used a co-treatment of zinc and imipramine, a tricyclic

antidepressant, that increased zinc serum levels and reduced zinc status in the hippocampus. The

implications suggest that low dosage zinc can be used to enhance the effect of imipramine doses,
increasing the success of treating depression. Similarly, Dou and his team found that zinc and folic acid

supplemented together with paroxetine, an antidepressant treatment, improved depressive behavior in

male rats.8 The pair increased up regulation of NDMA in comparison to the down regulation seen through

the two coupled with paroxetine, suggesting that folic acid and zinc, combined by themselves, can be

used to slow and prevent the development of depression. 8 Decreased NDMA mRNA within the frontal

cortex of the brain was seen in depressed-model mice and an up regulation showed improved symptoms.

Discussion and Conclusion

While zinc clearly plays a role in the proper functioning of the brain, it insufficient intake and

deficiency also is linked to depressive and other psychiatric disorders. Researchers have shown zinc

helps to treat depressive symptoms in adult women, but there has been little connection between zinc

intake/supplementation and the prevention or treatment in adult men. This is an indicator that zinc can be

used to treat women and that their male counterparts will not see the same advantages from the same

preparation.

It is also important to consider the role depression plays in appetite, as one of the main symptoms

of depression is the decrease in pleasure seeking behavior. 3 Low serum zinc levels could possibly be

caused by lack of appetite and not necessarily an issue that existed prior to the depressive symptoms

occurring. This fact does not negate, however, that increased zinc serum levels does improve depressive

symptoms when dietary intake is increased or supplementation is used. 3-8 Zinc coupled with prescription

antidepressant did show an increase in effectiveness in the prescriptions, in contrast, there is also data that

shows the combination of zinc and folic acid with paroxetine decreased its efficacy. 8

NDMA, when over stimulated, can cause depressive symptoms and when down-regulated can

also cause the same symptoms. Studies have shown that direct targeting of NDMA receptors can sharply

increase antidepressant effects.3 Zinc has been shown to inhibit NDMA by binding to its receptor on one
of its subunits causing its antidepressant effects. 2 In contrast, zinc has also increased NDMA mRNA to

decrease depressive symptoms as well. 8

In conclusion, it is important that research on zinc and its impact on depressive disorders

continues. Because depression is multifaceted, independent studies should be conducted individually on

men and women as it is clear that the mechanism of action varies between the sexes which might be due

to underlying hormonal conditions. Zinc appears to have potential in the correction of neurological

imbalances both alone and combined with prescription anti-depressants. It would seem necessary, if

NDMA receptor was the target of treatment, that treating physicians know whether the receptor needs to

be up or down regulated; continued research will help pass along a concise course of action. Continued

studies can also help guide physicians in helping treat patients that seek their support for depression

whether dietary or supplementary zinc can be used as treatment.

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