The European Food Standards Agency (EFSA) has reviewed the data relating to this mineral and has authorised 8 health claims at dosages of over 55mg. Specific to brain function are the health claims that magnesium contributes to normal functioning of the nervous system and magnesium contributes to the maintenance of psychological function.
The proposed dose relating to magnesium in the formulation is 60mg. The EU Reference Nutrient Value is 375mg. The UK Expert Group on Vitamins and Minerals in their document Safe Upper Limits for Vitamins and Minerals considers 750mg from supplements as acceptable to contribute to a daily intake of 1400mg.
There is evidence that demonstrates depression and anxiety contribute to insomnia and that there is also a bidirectional effect (1-3).
60% of cases of clinical depression are considered to be treatment-resistant depression (TRD) and brain magnesium has been found low in TRD using phosphorous nuclear magnetic resonance spectroscopy, an accurate means for measuring magnesium. (4) Taurine and glycine are also found to be low in TRD and are each important in regulating magnesium homeostasis. A 1921 study first showed success in TRD cases, but a 2008 randomized clinical trial showed magnesium as effective as the tricyclic anti-depressant imipramine in treating depression in diabetics, without any of the side effects of imipramine (5). Intravenous and oral magnesium in specific protocols have been reported to rapidly terminate TRD safely and without side effects (6). Benefits of IV magnesium treatment of TRD have been found to be extremely rapid and unequivocally strong and are suggested for treatment initiation. (7)
Depression-inducing severe loss of IQ, memory and attention in children due to loss of neuronal Mg has been reported in conditions of exceptional stress. Stress worsened mental health by Mg depletion, but was minimized with magnesium supplementation. (8) Memory loss, IQ loss and attention deficits associated with onset of severe depression appeared completely reversible upon magnesium treatment in a case report (9). In familial depression with low IQ, poor memory and concentration, vitamin B6, magnesium, zinc and manganese deficiencies were common in diets of families of depressives (10). Test anxiety in students resulted in increased losses of magnesium in the urine. (11)
Magnesium is an essential cofactor for many enzymatic reactions, especially those that are involved in energy metabolism and neurotransmitter synthesis (12). Although the effect of magnesium on neural function and sleep behaviors is not fully understood, magnesium has an essential role in ion channels conductivity, such as N-Methyl-D-aspartic acid (NMDA) receptor, and unilateral entrance of potassium channels. (13). Therefore, magnesium as a natural antagonist of NMDA and agonist of GABA and seems to play a critical role in sleep regulation.
Inadequate intake of magnesium has been linked to sleep disorders. Results of the study by Abbasi et al (14) about the role of magnesium in sleep regulation are consistent with Dralle and Bodeker study (15), which showed that there is an association between magnesium supplementation and REM, muscle tone, and gross body movements in infants. Results of Dralle and Bodeker also suggested that there is a relationship between serum magnesium level and active sleep, likewise between serum magnesium level and quiet sleep. In their study magnesium supplementation increased the quiet sleep and decreased the active sleep. Also, the results of the Abbasi study are consistent with Murck and Steiger study in which the most important effects of Mg2+ supplementation were an increment in spindle power during non-rapid eye movement (NREM) and a change in delta power in the in the third sleep cycle (16). A study conducted by Held et al. to analyze magnesium supplementation effects on sleep EEG, plasma ACTH, cortisol, AVP, renin, angiotensin II, and aldosterone in the elderly, showed that the most important Mg2+ supplementation effect in healthy elderly subjects was short wave sleep (SWS) increment (17). Also, the results are consistent with Rondanelli et al. study, to investigate the effects of combined melatonin, magnesium, and zinc supplementation, which showed that the supplementation resulted in total score improvement of Pittsburg questionnaire compared to placebo, and suggested that treatment has beneficial effects on capability of recovering body activities through sleep (18). The study of Rodriguez et al., which dealt with magnesium supplementation in the treatment of depression in diabetic elderly subjects, reported a significant difference in serum magnesium level in supplement group compared to placebo group (19).
In general, studies show that magnesium deficiency affects circadian cycle, melatonin reduction, and sleep disorders (20,21). Morton and James suggested that the N-acetyltransferase (NAT) activity is increased after magnesium injection. Moreover, magnesium increases NAT activity in pineal gland in vitro, suggesting that the pineal gland, not another place of the body, is the affect site (22). These findings suggest a possible magnesium deficiency role in reduced NAT activity and reduced melatonin production.
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2. Taylor DJ; Lichstein KL; Durrence HH et al. Epidemiology of insomnia, depression, and anxiety. SLEEP 2005;28(11): 1457-1464.
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5. Barragan-Rodriguez L et al. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type II diabetes; a randomised equivalent trial. Magnes Res 2008, 21, 218-23
6. Enya M et al depressive state and paraesthesia dramatically improved by intravenous magnesium sulphate in Gitelman’s syndrome. InternMed 2004; 43; 218-23
7. Eby GA et al. Magnesium for treatment resistant depression; a review and hypothesis. Med Hypothes 2010, 74, 649-60
8. Papadopol V et al. Magnesium and some psychological features into groups of pupils. Magnes Res 2001, 14, 27-32
9. Eby GA et al rapid recovery from major depression using magnesium treatment. Med Hypotheses 2006, 67, 362-70
10. Reading CM. family tree connection; how your past can shape your future health. A lesson in Orthomolecular medicine J Orthomol Med 1988, 3, 123-34
11. Grases G et al . Anxiety and stress amongst science students. Study of calcium and magnesium alterations. Mag Res 2006, 19, 102-6
12. Morris ME. Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: Neurological symptoms. Magnes Res. 1992;5:303–13.
13. Chollet D, Franken P, Raffin Y, Malafosse A, Widmer J, Tafti M. Blood and brain magnesium and their correlation with sleep quality. Am J Physiol Regul Integr Comp Physiol. 2000;279:R2173–8.
14. Abbasi B, Kimiagar M, Sadeghniiat K, Shirazi MM, Hedayati M, Rashidkhani B. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences. 2012 Dec;17(12):1161.
15. Dralle D, Bodeker RH. Serum magnesium level and sleep behavior of newborn infants. Eur J Pediatr. 1980;134:239–43.
16. Murck H, Steiger A. Mg2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men-possible therapeutic implications. Psychopharmacology (Berl) 1998;137:247–52.
17. Held K, Antonijevic IA, Kunzel H, Uhr M, Wetter TC, Golly IC, et al. Oral Mg2+ supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacopsychiatry. 2002;35:135–43.
18. Rondanelli M, Opizzi A, Monteferrario F, Antoniello N, Manni R, Klersy C. The effect of melatonin, magnesium, and zinc on primary insomnia in long-term care facility residents in Italy: A double-blind, placebo-controlled clinical trial. J Am Geriatr Soc. 2011;59:82–90.
19. Barragan-Rodriguez L, Rodriguez-Moran M, Guerrero-Romero F. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: A randomized, equivalent trial. Magnes Res. 2008;21:218–23.
20. Durlach J, Pages N, Bac P, Bara M, Guiet-Bara A. Biorhythms and possible central regulation of magnesium status, phototherapy, darkness therapy and chronopathological forms of magnesium depletion. Magnes Res. 2002;15:49–66.
21. Durlach J, Pages N, Bac P, Bara M, Guiet-Bara A, Agrapart C. Chronopathological forms of magnesium depletion with hypofunction or with hyperfunction of the biological clock. Magnes Res. 2002;15:263–8 22. Morton DJ, James MF. Effect of magnesium ions on rat pineal N-acetyltransferase (EC 2.3.1.5) activity. J Pineal Res. 1985;2:387–91.
