Zinc is an essential micronutrient which is responsible for the different biological roles. Some of these functions are involvement in some enzymes activation, gene expression, synthesis and release of insulin, and cardiovascular homeostasis. The amount of zinc stored in the adults’ body is 2-3 grams; most of which, is in skeletal muscle and bone. Only 0.1% of the total zinc pool is present in plasma. The plasma levels of zinc are used to evaluate the nutritional status of zinc.
In the present study, mean serum zinc concentration in the group receiving zinc supplements increased by 6.5 µg/dL. However, this increment was not significant compared with placebo. Mean serum zinc concentrations at baseline were 100 ±15 and 106 ±17 µg/dl in the zinc and placebo groups, respectively. These amounts were similar to the mean serum zinc concentrations in healthy adults in Shiraz 104 ±18 µg/dL, and Ahvaz 111 ± 18 µg/dL, respectively. Some studies have shown the low serum zinc levels in depressed patients which are resistant to treatment .Other studies have also shown that low serum zinc levels are normalized during treatment with antidepressants which is consistent with our findings. In the present study, the mean dietary zinc intake in patients with major depression was about 6.5-7 mg per day. While in the study of Ghasemi and colleagues, the mean dietary zinc intake in men and women were 15.8 ± 11 and 14.7 ± 11 mg/day, respectively . The less zinc intake in these patients may be due to some antidepressants and lack of appetite as one of the symptoms of depression. Serum zinc level was normal in the current study. Therefore, despite the low intakes of zinc, we can infer that the increased serum zinc up to normal levels may be due to antidepressants. The antidepressants may stimulate releasing zinc from the body's stores such as muscles and bones. Also, zinc supplementation on these patients has restored the zinc pools.
Studies on dietary factors and their relation to depression have shown that consumption of meals containing high amounts of carbohydrates cause insulin release. Insulin causes glucose entrance into the cells, and on the other hand make more amino acids such as tryptophan to cross the blood - brain barrier. This may increase neurotransmitter levels, especially serotonin, in the brain which can lead to improved mood . Amino acid tryptophan can be converted to serotonin in the body and can cause sleep and mental calmness . Tyrosine amino acid can be synthesized from the amino acid phenylalanine and may enter into the biochemical pathways of dopamine and norepinephrine . Dietary omega-3 fatty acids are provided from some especial plant and animal sources (especially some marine animals). Omega-3 fatty acids are involved in regulating corticotropin factor, stimulating the serotonergic pathway, preventing neuronal apoptosis, improving blood flow to the brain and regulating gene expression . Folate and B12 deficiency are associated with depression. About 10 to 30% of depressed patients have low serum folate levels and their response to antidepressants is weak. Early vitamin B12 deficiency leads to depression. This is due to the reduced synthesis of S-Adenosyl Methionine . S-Adenosyl Methionine is associated with mood. The low concentrations in cerebrospinal fluid of depressed patients have been observed and it was found that increasing its plasma concentrations have improved the depressive symptoms . So far, clinical trials published in this field have not assessed the mentioned dietary confounding factors. However, the present study was the first experiment which evaluated the effects of dietary confounding factors in patients with depression. As shown in the results, the effects of dietary factors on depression during the study were similar between the two groups. In cases where there was statistical difference between the two groups, the confounding effects were adjusted using ANCOVA.
In the present study, zinc supplementation significantly decreased the Beck depression scores compared with the placebo. Findings of this research were similar to the study by Nowak and colleagues on 20 patients with major depression. Nowak supplemented the antidepressants with 25 milligrams of zinc in one group and the other group was given a placebo with antidepressants. Beck depression scale at baseline and the second, sixth and twelfth weeks were measured. Nowak showed that reduction in Beck scores at week 6 and 12 in the group receiving the supplement were significant compared with placebo.
In a study on patients with major depression, Siwek and colleagues gave imipramine combined with 25 mg zinc supplement to one group and placebo combined with imipramine to another group. Siwek findings revealed no significant change in depression scores of the two groups. However, zinc supplementation significantly reduced the rate of depression in patients resistant to medication and may facilitate treatment with antidepressants. One of the possible causes of the differences in the results of Siwek study with ours may be due to different type of antidepressant medication prescribed.
Antidepressants may exert their effect through the zinc-containing neurons. Zinc is located in the presynaptic vesicles of neurons of the cortex, amygdala, hippocampus, and spinal cord. These neurons are mainly glutaminergic. The majority of zinc-containing neurons in the spinal cord is gamma-amino butyric acidergic or GAB Aergic and partly Glycinergic; perhaps zinc inhibits glutamate receptors such as N-Methyl-D-Aspartic (NMDA) .
Another hypothesis in this field is the role of the protein Brain-Derived Neurotrophic Factor (BDNF). Some recent studies have shown that the BDNF may be involved in mechanism of zinc antidepressant effect. Chronic high doses of zinc increases BDNF gene expression in the cerebral cortex of rats, while a low dose of zinc may increase BDNF gene expression in hippocampus .
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