Magnesium Supplementation Reduces the Symptoms of People Suffering With Mental Anxiety

and Depression Disorders

Background

Magnesium is an essential macronutrient for the human body in order to maintain

homeostasis, which pertains to an exceedingly long list of functional processes. Not being the

main enzyme itself for these physiological reactions, magnesium holds the function as a

cofactor for hundreds of different enzymes, primarily for energy production in the form of ATP

and in the production of nucleic acids as well. Primarily found in the bone, about one third of

magnesium can be found within blood serum from where it manages homeostasis and may be

transported interbetween cerebrospinal fluid and the blood.1 This is crucial because it’s from this

transporting mechanism that maintenance occurs to secure magnesium concentrations in the

brain. Daily recommended intake for adults is 400 mg per day for adults (0.30–0.35 mEq/kg).

When this intake amount is not reached on a constant day to day basis, magnesium deficiency

occurs over time leading to reduced levels in the brain as well. This effect can then cascade into

affective disorders, cardiac arrhythmias, neuromuscular hyperexcitability, anxiety, apathy, and

depression. This essential nutrient is also responsible for other particular functions such as cell

membrane adhesion, transmembrane electrolyte flux, structure of cellular components, binding

to enzyme active sites like competing with calcium for its binding sites, can cause

conformational changes during catalytic processes, promote the aggregation of multi-enzyme

complexes, or a mixture of several mechanisms.2 Thus, among the long list of enzymatic

reactions magnesium influences, whether directly or indirectly, there have been many studies in

which researchers have hypothesized and concluded that mental health is one of the affected

areas of serum levels. Particularly in the case of this review, where claims have been directed

toward the association of magnesium deficiencies and people affected with mental disorders

such as anxiety and depression.

Methods

Various studies and trials were researched and reviewed using PubMed and UNF

OneSearch databases. Keywords included magnesium and anxiety, or magnesium and

depression. Also, included in the research were articles using randomized controlled clinical

trials, one of such being double-blind and placebo-controlled, in addition to a longitudinal study,

empirical, quantitative, cross-sectional study, and review research articles. Inclusions for the

randomized clinical trial (RCT) included: 18 years of age or older; no change in treatment plan

for depression for previous 2 months and going forward (including no current treatment, stable

use of antidepressant medication, or ongoing nonpharmacologic therapy); and a patient Health

Questionnaire-9 (PHQ-9) score of 5–19.3 Exclusions for this same trial included: Schizophrenia,

bipolar disease, active delirium, dementia, kidney disease, myasthenia gravis, or GI disease;

pregnant or trying to get pregnant; planned surgery in the following 3 months; taking a

medication known to interact with magnesium; and unwilling to stop taking non-study

magnesium supplements for duration of the study. Inclusions for the double-blind, placebo-

controlled RCT included: serum magnesium deficiency (serum levels <1.8 mg/dL in men and

<1.9 mg/dL in women); depression with PHQ-9 score greater than 11; and between 20 to 60

years old.4 Exclusions for this trial were a little different as well as they include: cancer or

malignancy evidence; pregnancy; multimineral/multivitamin supplement consumption over past

3 months; death of a relative, loss of job, or divorce over past 6 months; history of treatment for

depression; consumption of any antidepressants, tranquilizers, diuretics, and laxatives over past

3 months; hypertension diagnosis; diabetes; cardiovascular, hepatic, or renal disease; thyroid

disorders; anemia; and cancer.

Main Findings

After reviewing multiple clinical trials and reviews, many of the researchers report a

similar conclusion with magnesium deficiencies having a significant association with higher risk
of depression and anxiety. Beginning with researchers Jacka FN et. al., this group conducted a

cross-sectional study to examine the association between magnesium intake and depression

and anxiety in a large community sample, which involved data from 2461 men and 3247

women, for a total of 5708 people.5 These adults were separated to be either in the middle aged

group consisting of 46-49 years olds, or the older group consisting of 70-74 year olds. Over the

course of one year, magnesium intake was measured from their own dietary consumption that

was self-chosen, then recorded with a self administered food frequency questionnaire. This

questionnaire recorded the amount of food units eaten, portion size of foods, number of meals

in a day, and timing of these meals. Anxiety and depression symptoms were also self

administered using the Hospital Anxiety and Depression Scale (HADS) that produces scores

ranging from 0-21, where a score greater or equal to 8 classifies a person with case-level

anxiety/depression. A linear regression analyses was used to evaluate the association with

anxiety/depression and magnesium intake. Results revealed significant inverse relationships

with both anxiety and magnesium deficiency, as well as depression and magnesium deficiency.

Although the association regarding depression and Mg showed a much stronger association

when adjusted both scores with related socioeconomic and lifestyle factors.

Another study conducted by researchers Yary et. al. set out to report the association

between magnesium intake and the incidence of depression specifically in men over the course

of 20 years. Although this study did not report on anxiety, depression is many times associated

with anxiety in patients. Thus, the groups were randomly selected and separated where the first

cohort group consisted of 1166 men 54 years old and the second cohort included 1516 men

with ages being 42, 48, 54, or 60.6 At baseline the Human Population Laboratory Depression

Scale was used to assess depression symptoms and participants used a 4-day food recording

software program called Nutrica® to record magnesium concentrations among other nutrients.

Then over the course of 20 years, the association between depression and tertiles of

magnesium, which is how researchers discerned between final Mg intake groupings, these were
tested by Cox's proportional hazard's regression model. By the end of the study, researchers

found participants who were in the lowest tertile of the three, consisting of 347.5±36.2 mg/day,

had the highest chance of being diagnosed with clinical depression. Also, an inverse association

between magnesium intake and the risk of depression was revealed when the middle and

highest tertiles of magnesium intake were combined in comparison to the lowest tertile, thus

meaning the magnesium intakes above 414.3±16.2 mg/day.6

Then, researchers Tarleton et. al. conducted a randomized clinical trial to test whether

magnesium chloride supplementation will improve depressive symptoms.3 112 adults with mild-

to-moderate depression displaying a depression test score of 5-19 were participants, with 38%

being men and 62% women. There was a group of 55 who were given immediate treatment and

a group of 57 given delayed treatment, being called that because these people were 5.1 years

older. Over a course of 6 weeks, one of these groups was the control receiving no treatment

while the other group received 248 mg of elemental magnesium per day in magnesium chloride

tablet form. After the first 6 week period passed, the groups switched treatments. Throughout

the course of 12 weeks, Patient Health Questionnaire-9 (PHQ-9) assessments of depression

symptoms were completed every 2 weeks thru phone calls and then baseline scores were

compared with each 6 week period end score. Researchers found consumption of magnesium

chloride for 6 weeks resulted in significant improvement in PHQ-9 scores of -6.0 points, as well

as significant improvement in Generalized Anxiety Disorders-7 scores of -4.5 points.

Finally, a RCT conducted by Rajizadeh et. al. similarly set aim to determine the effect of

magnesium supplementation on the depression status of depressed patients suffering from

magnesium deficiency.4 Here 60 randomly chosen magnesium deficient participants with a

depression score greater 11 were used in this trial and having an age range of 20-60 years old.

Separated in two, the magnesium treatment group consisted of 26 people who received 500 mg

magnesium oxide tablets daily and a placebo-receiving group that consisted of 27 participants.

Trial period was a short 8 weeks, with a clinic visitation after every 4 weeks where testing was
done. Beck Depression Inventory-II was used to measure depression status where a

questionnaire gives the final score and degree of depressive status and gives a score ranging

from a scale 0 to 63. Also, 5 mL of venous blood was drawn at the beginning and end of the

study to determine serum magnesium concentration. By the end of the trial, both magnesium

receiving treatment group (MG) and placebo group revealed a decrease in depression scores,

however MG still revealed a significantly greater difference. Also, magnesium levels in the blood

were raised in MG but overall only 88.5% of participants reached a normal, healthy serum level

with these treatments.

Discussion and Conclusion

All in all, evidence continues to show the inverse relationship between a deficiency in

magnesium with depression and anxiety. Magnesium supplementation reveals to be of benefit

for people suffering these health disorders, due to previous studies. However, more research

may need to be done in order to conclude a healthy and beneficial dosage amount in order to

recommend patients within the dietetic practice, as well as which form to take the magnesium.

Some forms like magnesium chloride tablets influenced depression/anxiety scores differently

than magnesium oxide tablets, as well as those studies performed using recorded dietary intake

alone. Such studies, with recorded dietary intake as the means of evidence may need to be

repeated and adjusted in order to attain more stability in the proven statistics of their numbers,

as recording accurate numerical information of magnesium intake is more difficult when

attaining it from various foods. Also, longer trial periods should be conducted in order to achieve

greater accuracy. In conclusion, the results of these studies join together to show that

magnesium supplements may have real and true implications in prevention and treatment of

depression and anxiety.

References

1. Młyniec K, Davies CL, Gómez de Agüero Sánchez I, Pytka K, Budziszewska B, Nowak

G. Essential elements in depression and anxiety. part I. Pharmacological reports : PR.

2014;66(4):534-544.

2. Swaminathan R. Magnesium metabolism and its disorders. The Clinical biochemist.

Reviews / Australian Association of Clinical Biochemists. 2003;24(2):47-66.

http://www.ncbi.nlm.nih.gov/pubmed/18568054.

3. Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C. Role of magnesium

supplementation in the treatment of depression: A randomized clinical trial. PLoS One.

2017;12(6):e0180067. doi: 10.1371/journal.pone.0180067.

4. Rajizadeh A, M.Sc, Mozaffari-Khosravi H, Ph.D, Yassini-Ardakani M, M.D, Dehghani A,

Ph.D. Effect of magnesium supplementation on depression status in depressed patients

with magnesium deficiency: A randomized, double-blind, placebo-controlled trial.

Nutrition. 2017;35:56-60. doi: 10.1016/j.nut.2016.10.014.

5. Jacka FN, Overland S, Stewart R, Tell GS, Bjelland I, Mykletun A. Association between

magnesium intake and depression and anxiety in community-dwelling adults: The

hordaland health study. Aust N Z J Psychiatry. 2009;43(1):45-52. doi:

10.1080/00048670802534408.

6. Yary T, Lehto SM, Tolmunen T, et al. Dietary magnesium intake and the incidence of

depression: A 20-year follow-up study. Journal of Affective Disorders. 2016;193:94-98.

doi: 10.1016/j.jad.2015.12.056.