Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial

Highlights

• Magnesium is involved in the pathophysiology of some psychologic disorders including effective disorder such as depression.

• In the majority of studies a significant relationship has been observed between magnesium deficiency and depression.

• The result of 20-y follow-up study showed that magnesium intake may have an effect on the risk of developing depression.

• When the patients suspected of depression are evaluated, it is recommended that they are evaluated their serum magnesium status.

Abstract

Objectives

The aim of this study was to determine the effect of magnesium supplementation on the depression status of depressed patients suffering from magnesium deficiency.

Methods

Sixty depressed people suffering from hypomagnesemia participated in this trial. The individuals were randomly categorized into two groups of 30 members; one receiving two 250-mg tablets of magnesium oxide (MG) daily and the other receiving placebo (PG) for 8 wk. The Beck Depression Inventory-II was conducted and the concentration of serum magnesium was measured.

Results

At the end of intervention, 88.5% of the MG and 48.1% of the PG (P = 0.002) had a normal level of magnesium. The mean changes of serum magnesium were significantly different across the two groups. After the intervention, the mean Beck score significantly declined. However, in the MG, this reduction was more significant than in the PG (P = 0.02), so that the mean changes in this group experienced 15.65 ± 8.9 reduction, but in the PG, it declined by 10.40 ± 7.9.

Conclusions

Daily consumption of 500 mg magnesium oxide tablets for ≥8 wk by depressed patients suffering from magnesium deficiency leads to improvements in depression status and magnesium levels. Therefore, assessment of the magnesium serum and resolving this deficiency positively influence the treatment of depressed patients.

Introduction

Magnesium is the second intracellular cation and the fourth major element in the body [1]. Given the complex function that this element plays in our body, it is considered an important element for human health [2]. This element is an important coenzyme for many enzymes involved in the transfer of phosphate and energy metabolism. Additionally, magnesium has major roles in stabilizing genes, DNA replication, synthesis of protein and nucleic acids, and metabolism of macronutrients [3].

Furthermore, by regulating and transferring some ions, including potassium and calcium, through pumps and channels, magnesium also is effective in neuro-transmission [4]. Accordingly, it is involved in the pathophysiology of some neurologic diseases including migraine, Alzheimer's and Parkinson's diseases, and attention-deficit/hyperactivity disorder [2], [5]. In recent years, the role of this element in the incidence of depression, due to its effect on N-methyl-d-aspartate's (NMDA) nonselective ionotropic channels in the brain, has gained a great deal of attention [6]. These glutamate-dependent channels have important roles in neurotransmission and neuronal plasticity. Thus magnesium is involved in learning, memory, and mood of individuals [7]. NMDA channels are excited by glutamate neurotransmitter and cause entrance of sodium and calcium into the cell. Once sodium is introduced and the intracellular space is depolarized, entrance of calcium is accelerated. Calcium, then, by exciting enzymatic paths including kinase protein and synthesis of nitric oxide, plays an important role in the pathophysiology of depression [8], [9]. However, magnesium is the natural antagonist of calcium [10], whereby inhibiting NMDA ionotropic channels, it prevents entrance of calcium into the cell, thereby inhibiting the activation of its subsequent enzymatic cascade [9], [11], [12].

In many studies, the level of dietary magnesium in relation to depression has been investigated. Although the obtained results are controversial, in the majority of studies a significant relationship has been observed between deficiency of the consumed magnesium and incidence of depression [13], [14], [15]. The result of a 20-y follow-up study showed that magnesium intake may have an effect on the risk for developing depression [16].

A deficiency in dietary magnesium can be accounted for by various factors such as the soil of agricultural lands and new agricultural techniques including genetic manipulation [17], [18]. Another factor is the water being consumed. According to a study, given the amounts of minerals, drinking water can provide 8% of daily magnesium required by individuals [19]. Additionally, an unhealthy diet that contains a high consumption of processed foods and refined grains can result in hypomagnesemia in long term [2]. Therefore, although major sources of magnesium, including dark green leafy vegetables, grains, and nuts are available [20], hypomagnesemia is still seen in many metabolic diseases [21]. Among depressed people, incidence of hypomagnesemia has been estimated to be as high as 13.7% [22]. This figure is almost three times the value of nondepressed individuals (4.6%) [23].

Although the conventional treatment of depression is administration of antidepressants including selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, and tricyclic antidepressants [24], not completing the treatment due to complications caused by these medications, such as headache and nausea, vomiting, restlessness, and drowsiness [25] as well as relapse of the depression or manic periods in about 60% of individuals, highlights the necessity of researching and investigating complementary treatments [26]. Furthermore, studying the effect of food supplements and nutrients such as magnesium on this disease can play an important role in the prevention and treatment of this problem.

The question is to what extent the condition of patients suffering from depression as well as a lack of magnesium can be improved in terms of depression mitigation by resolving the deficiency of magnesium. Accordingly, this research was designed and conducted with the aim of examining the effect of magnesium supplementation on the status of depression in those suffering from magnesium deficiency.