Data on Magnesium and Mood

According to nutritionist Blake Graham, all vitamins and minerals are involved in one or more biochemical pathways and/or physiological actions which influence the function of the human brain. Most vitamin and mineral deficiencies result in psychiatric symptoms in a significant number of people, and in people with psychiatric diagnoses these deficiencies are often associated with more severe symptoms and poorer outcome from conventional treatment.

Vitamin and mineral deficiencies may act as an exacerbating factor secondary to malnutrition, alcoholism, etc. or may be a primary causative factor. Either way, optimisation of nutrient levels is in each patients best interest. 

Magnesium deficiency can cause depression, behaviour and personality changes, apathy, irritability and anxiety. (Wacker WE. 1968 & Freyre AV. 1970 & Rasmussen HH. 1989)

Magnesium is required by over 300 chemical reactions in humans. (Shils ME. 1999) Individuals with low cerebrospinal fluid levels of magnesium tend to have lower cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin, indicating lower central nervous system serotonin levels. (Banki CM. 1985 & Banki CM. 1986) An animal study in which magnesium deficiency was induced in cows found magnesium deficiency was associated with reduced dopamine levels in the cerebral cortex and cerebellum and lower norepinephrine in the corpus striatum. (McCoy MA. 2000) The relevance of these findings to human magnesium deficiency is unclear. In humans, magnesium deficiency impairs the cardiovascular response to stress, while stress also increases magnesium requirements. (Seelig MS. 1994) Magnesium deficiency also leads to impaired glutamatergic transmission via NMDA-receptors (Siwek M. 2005) and an increase in the lactate to pyruvate ratio (RA Buist. 1985), both of which are relevant to psychiatric conditions.

Studies of plasma/serum magnesium levels in psychiatric patients have been mixed. In one study, plasma magnesium levels were significantly lower than controls and increased as patients showed clinical improvement. (Frizel D. 1969) Three other studies reported lower plasma levels than controls (Zieba A. 2000) (Kirov GK. 1990) (Frizel D. 1969), one study reported no differences (Manser WW. 1989) and three others found higher levels of plasma or serum magnesium in non-medicated depressed patients. (Widmer J. 1992) (Cade JF. 1964) (Hasey GM. 1993) Only 1% of magnesium in the human body is present in extracellular fluids (e.g. plasma/serum), making plasma/serum magnesium levels an unreliable marker for magnesium status. (Mann. 2000) A group of researchers examining plasma magnesium levels in psychiatric patients found no correlation between low plasma magnesium and increased anxiety levels. (Kirov GK. 1994) However 22.4% and 10.4% of patients had levels below and above the laboratory reference range respectively. There was a strong tendency for more disturbed and excitable patients to fall into either the abnormally low or high groups, suggesting a possible significance of impaired magnesium homeostasis.

Two studies found patients with major depression and affective disorders, respectively, showed no significant differences in RBC magnesium levels as compared to healthy controls. (Kamei K. 1998) (Ramsey TA. 1979) Another study reported 45 depressed patients had lower RBC magnesium levels than 31 controls (Rybakowski J. 1989), while another found higher levels of RBC magnesium in non-medicated depressed patients. (Widmer J. 1992) A study of more than 200 patients with depression and/or chronic pain documented 75% had below normal magnesium levels in white blood cells. (Shealy CN. 1990)

Cerebrospinal fluid (CSF) levels of magnesium were found to be lower in patients with major depression (n = 16) and adjustment disorder (n = 10), as compared with controls. (Banki CM. 1985) This research group also found that it was the psychiatric patients with a history of suicide attempts which had low CSF magnesium levels, pulling down the group average. Differences between depressed patients with no history of suicide attempts and healthy controls were insignificant. Another study by this same research group of 275 drug-free psychiatric patients confirmed both of these findings. (Banki CM. 1986) Levine and colleagues found an elevated Ca/Mg ratio in the CSF of depressed patients. (Levine J. 1999)

In her paper Vitamins, Minerals and Mood, Dr. Bonnie Kaplan states: “… low magnesium levels were reported in 15 adult inpatients with schizophrenia and 10 with depression in comparison with healthy controls but not in 6 patients who were manic (Kirov & Tsachev,1990). Some studies have examined the potential efficacy of magnesium as an adjunctive therapy for patients with bipolar disorder. Heiden et al. (1999) administered intravenous magnesium sulphate to 10 patients with severe treatment-resistant mania.

“Even though the patients were still being treated with lithium (n =10), haloperidol (n = 5), and/or clonazepam (n = 10) for the duration of the study, medication dosages could be decreased significantly with the addition of magnesium sulphate to the treatment regimens. Hence, this is apparently another example of medication augmentation with micronutrient supplementation, in addition to the folic acid study cited above (Coppen & Bailey, 2000). Of the 10 patients, 7 also showed “marked improvement” in the Clinical Global Impression Scale (Guy, 1976). In treating patients with mania, Giannini, Nakoneczie, Melemis, Ventresco, and Condon (2000) compared the effects of verapamil in combination with magnesium oxide to a verapamil–placebo combination.

“Manic symptoms decreased significantly in the group receiving verapamil–magnesium oxide ( p = .02), and at the same time,serum magnesium levels rose significantly in this group ( p = .04).

“Nine female patients with severe rapid-cycling bipolar disorder were treated in an open trial with either a magnesium compound or lithium for up to 32 weeks (Chouinard, Beauclair, Geiser, &Etienne, 1990). The magnesium had clinical effects equivalent to those of lithium in more than half the patients; 7 of the 9 (77.8%)patients showed a significant positive response”  (Kaplan, 2007).

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Banki CM, Vojnik M, Papp Z, Balla KZ, Arato M. Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts. Biol Psychiatry. 1985 Feb;20(2):163-71.

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Chouinard, G., Beauclair, L., Geiser, R., & Etienne, P. (1990). A pilot study of magnesium aspartate hydrochloride (Magnesiocard) as a mood stabilizer for rapid cycling bipolar affective disorder patients. Progress in Neuropsychopharmacology Biology and Psychiatry, 14, 171–180.

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Hasey GM, D’Alessandro E, Cooke RG, Warsh JJ. The interface between thyroid activity, magnesium, and depression: a pilot study. Biol Psychiatry. 1993 Jan 15;33(2):133-5.

Heiden, A., Frey, R., Presslich, O., Blasbichler, T., Smetana, R., & Kasper,S. (1999). Treatment of severe mania with intravenous magnesium sulphate as a supplementary therapy. Psychiatry Research, 89, 239–246.

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McCoy MA, Young PB, Hudson AJ, Davison G, Kennedy DG. Regional brain monoamine concentrations and their alterations in bovine hypomagnesaemic tetany experimentally induced by a magnesium-deficient diet. Res Vet Sci. 2000 Dec;69(3):301-7.

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Shealy CN, et al. Magnesium deficiency in depression and chronic pain. Magnesium Trace Elem 1990;9:333.

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Widmer J, Bovier P, Karege F, Raffin Y, Hilleret H, Gaillard JM, Tissot R. Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months. Neuropsychobiology. 1992;26(4):173-9.

Young SN, Ghadirian AM. Folic acid and psychopathology. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(6):841-63.

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