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Natalie Brasch

Magnesium and Depression

Depression is a neuropsychiatric disorder characterized by symptoms that interfere with a persons
ability to eat, sleep, maintain a career, and find general enjoyment in daily activities (Eby & Eby, 2010;
Nordqvist, 2009). 25% of Americans are expected to develop depression at some point in life (Eby & Eby,
2010). Most likely, the cause of depression is a combination of genetic, biochemical, psychological, and
environmental factors. Because all of these factors can be affected by combinations of nutrients in the diet,
dietary changes have the potential to influence depression (Bjelland et al., 2009; Nordqvist, 2009). Currently,
Americans eat more processed food than in years past. During food processing, magnesium is removed, while
additives like calcium and glutamate are commonly incorporated (Eby & Eby, 2010; Aazami et al., 2012). This
combination of decreased magnesium and increased calcium may serve to harm the brain (Eby & Eby, 2010).
Magnesium, an essential mineral in the human body, is connected with brain biochemistry and is crucial
to several biological processes. Magnesium influences systems related to the pathophysiology of mood
disorders such as depression (Chung et al., 2009; Derom et al., 2012; Derom et al., 2013; Bria et al., 2012;
Nowak et al., 2013). Inadequate brain magnesium has been shown to reduce serotonin levels (Eby & Eby,
2010). Magnesium also regulates the entry of calcium into the neuron by serving as a voltage-dependent
blocker of the N-methyl-D-aspartate channel (Derom et al., 2012, Derom et al., 2013; Aazami et al., 2012).
Magnesium deficiency may deregulate brain cell synaptic function, especially in the presence of too much
calcium, leading to neuron swelling and death (Nowak et al., 2013). These events collectively stimulate the onset of depression and other mood disorders (Derom et al., 2013; Nowak et al., 2013). Given depressions high
rate of incidence, combined with current dietary trends towards processed foods, research examining the role of
diet in depression is continuing.

Previous studies assessing the relationship between magnesium and

depression have generated inconsistent results. Researchers have hypothesized that an inverse association
exists between serum magnesium levels and depression, and between magnesium intake and depression
(Derom et al., 2012; Chung et al., 2009; Bria et al., 2012; Aazami et al., 2012; Bjelland et al., 2009).
Researchers have observed that depression severity declines with magnesium supplementation, and that
magnesium can be used as an effective treatment for depression (Eby & Eby, 2010; Bria et al., 2012; Derom et

al., 2013; Nowak et al., 2013). However, the role of magnesium in treating depression not yet fully understood
(Eby & Eby, 2010; Nowak et al., 2013). If a clear relationship is established between magnesium levels and
depression severity or treatment outcome, future research can better direct the use of magnesium to treat and
prevent depression onset.
Literature Review
Serum magnesium and depression
Research has indicated that serum magnesium levels, as well as serum calcium/magnesium ratio, are
involved in processes associated with mood disorders (Chung et al., 2009). High, normal, and low serum
magnesium levels have been detected in patients with depression (Eby & Eby, 2010; Bria et al., 2012). Bria et
al., in Italy in 2012, tested 123 untreated outpatient participants during a major depressive episode to determine
the relationship of serum magnesium levels and depression severity (Bria et al., 2012). A colorimetric assay was
used to measure total plasma magnesium levels, and depression severity was determined by a trained physician
using the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale. Subjects were then treated
with antidepressants using a variety of treatment strategies, and reassessed for severity of depression and
anxiety after 3 months. No significant correlation existed between baseline plasma magnesium levels and initial
depression or anxiety scores (Bria et al., 2012). Their results contrast with those of an earlier study assessing
magnesium levels in healthy participants (Chung et al., 2009). Chung et al. associated high serum magnesium
levels with lower depression scores in 112 healthy adult women ages 21-72. Lower scores on depression and
stress scales were also associated with the middle tertile of serum calcium/magnesium ratio. Participants with
the highest Ca/Mg ratio had higher scores on the Hospital Anxiety Depression Scale and the Modified Brief
Encounter Psychosocial Instrument Stress Scale, and higher risk of depressive mood disorder (Chung et al.,
2009). Their results support the prediction that depression is associated with lower serum magnesium levels,
and an elevated serum Ca/Mg ratio. Magnesium levels and Ca/Mg ratio, then, may be involved in the
mechanism for depressive mood or stress perception in healthy adult women (Chung et al., 2009).
Magnesium intake and depression
The association between magnesium intake and depression remains unclear. Bjelland et al., in Western
Norway, observed that magnesium intake was inversely associated with standardized depression scores in

5708 middle-aged and elderly participants in a cross-sectional study (Bjelland et al., 2009). Dietary intake was
measured using a self-administered food frequency questionnaire, and depression and anxiety were selfreported using the Hospital Anxiety and Depression Scale. The extent to which magnesium intake reflected
depression severity was comparable to low education and low physical activity levels as indicators of
depression, both of which are current established risk factors for depression (Bjelland et al., 2009). A later
cross-sectional study of 402 participants in Malaysia paralleled these results (Aazami et al., 2012). Aazami et
al. assessed the relationship between magnesium intake and depression symptoms in post-graduate students.
A self-administered depression questionnaire was used to measure depressive symptoms over 12 months, and
dietary magnesium intake was assessed using a food frequency questionnaire. An inverse relationship was
observed between magnesium levels and depressive symptoms. From these results, Aazami et al. inferred that
long-term magnesium intake may serve to modulate depressive symptoms (Aazami et al., 2012). In Spain in
2012, Derom et al. designed a longitudinal study to further evaluate the association between dietary magnesium
intake and depression on-set across an average of 6 years (Derom et al., 2012). Self-reported data was
assessed from 12,939 Spanish university graduates participating in the ongoing Seguimiento Universidad de
Navarra (SUN) Project. Dietary magnesium was determined from food frequency questionnaires, and included
dietary magnesium and magnesium intake from supplements. Depression incidence was defined when
participants were free of depression at baseline, but responded positively during follow-up either to the use of
anti-depressant drugs or to the diagnosis of depression by a physician (Derom et al., 2012). No significant
relationship existed between magnesium intake and depression, in contrast to the cross-sectional studies of
Bjelland et al. and Aazami et al. (Aazami et al., 2012; Derom et al., 2012; Bjelland et al., 2009).
Magnesium in depression treatment
Current anti-depressant drugs include selective serotonin reuptake inhibitors, monoamine oxidase
inhibitors, and tricyclic anti-depressants, among others (Eby & Eby, 2010; Nordqvist, 2009). These medications
can lead to undesirable side-effects, including headaches, nausea, insomnia, and increased risk for seizures, so
scientists are continually seeking other avenues for depression treatment (Eby & Eby, 2010; Nordqvist, 2009).
Researchers have explored the relationship between plasma magnesium levels and likelihood of responding to
depression treatment, and have attempted to determine the effectiveness of magnesium supplementation in

treating depression (Bria et al., 2012; Barragan-Rodriguez et al., 2012). In their 2012 study, Bria et al.
determined that higher baseline plasma magnesium levels, when adjusted for age and gender, were a predictor
of more positive response to antidepressant treatment after 3 months (Bria et al., 2012). In 2008, BarraganRodriguez et al. assessed the effect of oral magnesium supplementation on newly-depressed elderly patients
with type 2 diabetes and hypomagnesaemia in Mexico (Barragan-Rodriguez et al., 2008). 23 elderly subjects
over the age of 60 with recent depression onset were eligible for the 12-week study. One group received daily
magnesium supplements (50 mL of 5% MgCl2 in water solution) equivalent to 450mg Mg daily, while a second
group received a tricyclic antidepressant, imipramine (Barragan-Rodriguez et al., 2008). Two subjects dropped
out due to unpleasant side effects of imipramine. Results showed that magnesium was as effective in treating
depression as 50g of imipramine daily, and provided a safer and more tolerable alternative to the drug
(Barragan-Rodriguez et al., 2008). These results support the statement that assessment and management of
serum magnesium levels is important in the treatment of depression.
Although several studies link magnesium to depression onset, severity, and treatment, limitations of
previous research could contribute to the noted inconsistent results. Self-reported questionnaires used to
measure magnesium intake and depression symptoms may be vulnerable to error (Derom et al., 2012, Bjelland
et al., 2009). In addition, measuring plasma magnesium levels may misrepresent ionized magnesium, total
body magnesium, or brain magnesium levels (Chung et al., 2009; Bria et al., 2012; Barragan-Rodriguez et al.,
2008; Volpe, 2012). Some isolation of brain magnesium from blood magnesium does occur (Bria et al., 2012).
Bioavailability of magnesium is also important, and depends on other vitamins, such as B6 and D (Aazami et al.,
2012; Bjelland et al., 2009). Measurements of these micronutrients should be taken into account in assessing
magnesium absorption as related to depression. Another limitation to previous research includes blurred
direction of results. In cross-sectional studies, it could be the case that depression causes poor diet, and not
the reverse (Aazami et al., 2012; Bjelland et al., 2009). Finally, limited samples demonstrate results that are
not reflective of the population in its entirety. Samples limited to University graduates and young, healthy
participants might be skewed towards higher magnesium intake as a whole (Derom et al., 2012; Chung et al.,
2009; Aazami et al., 2012). The small sample size tested by Barragan-Rodriguez et al., was further limited to

diabetic depressed elderly participants (Barragan-Rodriguez et al., 2008). Magnesium related to depression
could show a very small effect, so larger and more comprehensive samples are desirable (Derom et al., 2012;
Chung et al., 2009; Aazami et al., 2012; Bjelland et al., 2009; Barragan-Rodriguez et al., 2008)
Future Directions
The extent to which magnesium influences depression, and whether magnesium can be used as
an effective means to treat and prevent depression, should be further investigated. Researchers know
that magnesium is important in neurological pathways involved in mood disorders, and that magnesium
deficiency may lead to brain cell dysfunction inducing depression (Derom et al., 2013). Additional
research should utilize new techniques that measure brain magnesium concentrations, which could be
more accurate than plasma measurements in determining a correlation between hypomagnesaemia and
depression (Bria et al., 2012). The form of magnesium given as a supplement for treating depression
should also be taken into consideration. If given with a high concentration of calcium, magnesium
bioavailability may be disturbed (Nowak et al., 2013). To accurately measure its effectiveness in
depressed subjects, magnesium should be given in a form that is highly biologically available to a test
group, while a control group is given an antidepressant. Longitudinal studies, as opposed to crosssectional analyses, can best recognize a cause-and-effect relationship between dietary intake of
magnesium and depression, and large samples that are not restricted by age group or educational
background will better reflect magnesiums effect on depression in the general population.
There is strong evidence that magnesium contributes to depression, though the mechanism is not
yet fully understood (Nowak et al., 2013). Magnesium deficiency may deregulate brain cell synaptic
function, causing brain system malfunctions that can collectively stimulate the on-set of depression and
other mood disorders (Derom et al., 2013; Nowak et al., 2013).

It is not surprising, then, that

researchers have attempted to determine a potential efficacy of magnesium in the treatment of depression
(Derom et al., 2013).

Additional longitudinal studies should be conducted to more clearly define the

long-term relationship between magnesium and depression, and to further realize important treatment
implications for depression.

Aazami, S., Soleimannejad, K., & Yary, T. (2012). Dietary intake of magnesium may modulate depression.
Biological Trace Element Research, 151: 324-329.
Barragan-Rodriguez, L., Rodriguez-Moram, M., & Guerrero-Romero, F. (2008). Efficacy and safety of oral
magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a
randomized, equivalent trial. Magnesium Research, 21(4): 218-223.
Bjelland, I., Jacka, F. N., Mykleton, A., Overland, S., Stewart, R., & Tell, G. S. (2009). Association
between magnesium intake and depression and anxiety in community-dwelling adults: the
Hordaland health study. Australian and New Zealand Journal of Psychiatry, 43: 45-50.
Bria, P., Buccelletti, F., Camardese, G., Janiri, L., Leone, B., Mattioli, B., Pizi, G., Risio, L. D., Serrani, R.,
& Sgambato, A. (2012). Plasma magnesium levels and treatment outcome in depressed patients.
Nutritional Neuroscience, 15(2): 78-84.
Chung, J. H., Jung, K. I., & Ock, S. M. (2009). Associations of serum Ca and Mg levels with mental health
in adult women without psychiatric disorders. Biological Trace Element Research, 133: 153-161.
Derom M. L., Martinez-Gonzales, J. M., Martinez-Gonzales, M. A., Sayon-Orea, C. (2013). Magnesium
and depression: a systematic review. Nutritional Neuroscience, 16(5): 191-206.
Derom, M. L., Martinez-Gonzalez, M. A., Sayon-Orea, M. C., Bes-Rastrollo, M., Beunza, J. J., & SanchezVillegas, A..(2012). Magnesium intake is not related to depression risk in Spanish university
graduates. The Journal of Nutrition, 142: 1053-1059.
Eby, G. A., & Eby, K. L. (2010). Magnesium for treatment-resistant depression: A review and hypothesis.
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Nordqvist, C. (2009). What is depression? What causes depression? Medical News Today. Accessed November 5, 2013.
Nowak G., Poleszak E., Radziwon-Zaleska, M., Serefko, A., Skalski, M., Szopa, A., & Wlaz, P. (2013).
Magnesium in depression. Pharmacological Reports, 65: 547-554.
Volpe, S. L. (2012). Magnesium. Erdman, J. W., Macdonald, I. A., & Zeisel, S. H. (Ed.s), Present
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