07/16/13: Magnesium: The mind mineral‡

Magnesium: The mind mineral

By James Greenblatt, M.D. and Kelly Heim, Ph.D.

Magnesium is required for more than 300 biochemical reactions in the body. It ranks fourth as the most abundant mineral in the body, and second to potassium, is the most prevalent intracellular mineral. Its roles in brain function are diverse—it is essential for the neurotransmission that orchestrates mood, cognition, memory, sleep, relaxation and overall emotional well-being.1 However, as the magnesium content of soil, water and the American food supply have declined considerably over the last 100 years, moderate deficiencies have become increasingly prevalent.2 According to the 1999–2000 National Health and Nutrition Examination Survey, two thirds of American men and women fail to consume the recommended dietary intakes of 320 and 420 mg, respectively.3 In addition, accumulating evidence suggests that magnesium deficiency ramifies to many aspects of emotional wellness.1

An evolving body of scientific evidence, dating back to the 1920s, substantiates magnesium status as an important consideration in psychiatric care. In 1921, researchers documented significant mood benefits in 220 out of 250 patients receiving supplemental magnesium.4 More rigorous studies over the last 50 years have associated repletion of magnesium with positive changes in mood, healthy eating behavior, balanced stress responses and sleep quality.1,5-7 As healthy levels of this mineral may support the efficacy of other modalities, supplements are widely utilized in integrative psychiatry.1,8

Neurotransmitters and receptors: Supporting both sides of a neuronal conversation

The neurological mechanisms of this nutrient are diverse and include interactions with neurotransmitters and receptors. Neurotransmitters are synthesized by one neuron and released into the synapse, the space between two neurons, and are recognized by another neuron via a receptor. Magnesium facilitates many of these molecular conversations.1,8-9 Known as neurotransmission, these exchanges mediate all aspects of brain function.

Magnesium is a cofactor for the biosynthesis of dopamine and serotonin, neurotransmitters that maintain healthy mood, behavior, appetite, cognitive function, sleep patterns and stress responses.1,8,10 Patients with adequate magnesium levels tend to exhibit healthy amounts of these chemical messengers in the cerebrospinal fluid.11 Supplementation has produced significant support for mood, sleep and cognition, even when baseline levels are not assessed.1 This data is valuable because magnesium levels in the body are not easy to measure—only 1% of the body’s stores circulate in the bloodstream, and serum values do not reflect tissue levels.1

Magnesium also supports neurotransmission by interacting with receptors on the postsynaptic neuron. The most clearly defined example is the glutamate receptor, or the NMDA receptor. Glutamate is an excitatory neurotransmitter involved in mood regulation. To exerts its effects, glutamate must attach itself to this receptor. Too much activation occurs easily, so the brain has a device to keep it within healthy limits. This device is magnesium, which binds the same receptor, but instead of activating it, it serves as a gatekeeper.1 In doing so, it keeps glutamate-mediated stimulation within a healthy range.9 Neurobiologists ascribe many neurological benefits of magnesium to this unique molecular mechanism.1,9

Magnesium and healthy stress management: A reciprocal relationship

Mental health is contingent on healthy management of daily stress. At the molecular level, stress evokes changes in both neurotransmitters and hormones. The relationship between stress and magnesium is reciprocal—while this nutrient maintains healthy responses to life’s daily adversities, stress itself affects the body’s retention of magnesium.8 Everyday stress can activate the hypothalamic-pituitary-adrenal (HPA) axis, stimulating the release of cortisol. By acting at both the pituitary and adrenal levels, magnesium helps to maintain homeostasis of the entire axis. For example, in the pituitary gland, magnesium modulates the release of ACTH, a hormone that travels to the adrenal glands to stimulating cortisol release.12 Simultaneously, magnesium acts in the adrenal gland to maintain a healthy response to the ACTH. In turn, cortisol release is kept within a normal range.13

Magnesium supplements

When bound to an organic molecule, such as citrate, gluconate or glycine, magnesium is easily absorbed. Absorption is particularly efficient if the body’s levels are low. Magnesium glycinate is often preferred by patients with digestive sensitivities to magnesium. Additional ways to maximize bioavailability include:

  • Taking 2 or more divided doses throughout the day
  • Taking with meals containing carbohydrates (Fine et al)
  • Ensuring adequate intake of vitamins D3 and B6 (Rude et al)
  • Avoiding excessive phosphorus intake

New delivery options provide convenient alternatives to capsules. Magnesium liquid delivers magnesium citrate, providing 215 mg elemental magnesium, along with vitamin B6 in a great-tasting liquid. For sleep-related applications, GlyMag-Z is a convenient packet that delivers magnesium in combination with glycine, a relatively short-acting neurotransmitter that supports relaxation for occasional sleeplessness. When taken daily on a continual basis, supplementation with any of these forms can provide powerful support for mood, relaxation, cognitive performance, healthy stress management and sleep quality.14


  1. Szewczyk B, Poleszak E, Sowa-Kućma M, et al. Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action. Pharmacol Rep (2008) 60(5):588-9.
  2. Bear FE. Variations in vegetable mineral content. Soil Science Society of America Journal. (1991) 55(5).
  3. Moshfegh, A., et al. What We Eat in America. NHANES 2005-2006: Usual Intakes from Food and Water Compared to 1997 Dietary Reference Intakes for Vitamin D, Calcium, Phosphorus, and Magnesium. US Department of Agriculture, Agricultural Research Service (2009).
  4. Weston PG. Magnesium as a sedative. Am J Psychiatry (1921) 22(1):637–8.
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  8. Greenblatt, J. The Breakthrough Depression Solution. Sunrise River Press (2011) pp. 132-135.
  9. Poleszak E, Wlaź P, Wróbel A, et al. NMDA/glutamate mechanism of magnesium-induced anxiolytic-like behavior in mice. Pharmacol Rep (2008) 60(5):655-63.
  10. Cardoso CC, Lobato KR, Binfaré RW, et al. Evidence for the involvement of the monoaminergic system in the antidepressant-like effect of magnesium. Prog Neuropsychopharmacol Biol Psychiatry (2009) 33(2):235-42.
  11. Banki CM, Vojnik M, Papp Z, et al. Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts. Biol Psychiatry (1985) 20(2):163-71.
  12. Sartori SB, Whittle N, Hetzenauer A, Singewald N. Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment. Neuropharmacology (2012) 62(1):304-12.
  13. Held K, Antonijevic IA, Künzel H, et al. Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacopsychiatry (2002) 35(4):135-43.
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