Nurturing the Brain – Part 11, Magnesiumby Sara Adaes, PhD | July 26, 2017
Magnesium is everywhere—it does not occur free in nature, but in combination with other elements it is the eighth-most abundant chemical element in the Earth’s crust and the third-most abundant element in seawater; it is even the ninth-most abundant in the Milky Way! In the human body, magnesium is the fourth most abundant ion and the eleventh most abundant element by mass, being stored in bones, muscles, and soft tissues.
Magnesium is fundamental for health: it is essential to all cells and to the function of hundreds of enzymes, including enzymes that synthesize DNA and RNA, and enzymes involved in cellular energy metabolism, many of which are vital. Magnesium is involved in virtually every major metabolic and biochemical process in our cells and it plays a critical role in the physiology of basically every single organ.
Low plasma levels of magnesium are common and are mostly due to poor dietary intake, which has lowered significantly in the last decades. Magnesium can be found in high quantities in foods containing dietary fiber, including green leafy vegetables, legumes, nuts, seeds, and whole grains. But although magnesium is widely distributed in vegetable and animal foods, some types of food processing can lower magnesium content up to 90%. Also, the soil used for conventional agriculture is becoming increasingly deprived of essential minerals. In the last 60 years, the magnesium content in fruit and vegetables has decreased by around 20–30%.
Symptomatic magnesium deficiency due to low dietary intake in healthy people is not very frequent, but a consistently poor dietary supply of magnesium has insidious effects. Magnesium deficiency alters biochemical pathways and increases the risk of a wide range of diseases over time, including hypertension and cardiovascular diseases, metabolic diseases, osteoporosis, and migraine headaches.
In the brain, magnesium is an important regulator of neurotransmitter signaling—particularly the main neurotransmitters glutamate and GABA—by modulating the activation of NMDA glutamate and GABAA receptors. It also contributes to the maintenance of adequate calcium levels in the cell by regulating the activity of calcium channels.
These physiological roles make magnesium an essential element in important neuronal processes. Magnesium participates in mechanisms of synaptic transmission, neuronal plasticity, and consequently, learning and memory. Accordingly, increased levels of magnesium in the brain have been shown to promote multiple mechanisms of synaptic plasticity that enhance different forms of learning and memory, as well as delay age-related cognitive decline. Increased levels of magnesium in the brain have also been linked to an increased proliferation of neural stem cells, indicating that it may promote the generation of new neurons (neurogenesis) in adulthood. This is an important feature because neurogenesis is a key mechanism in the brain’s structural and functional adaptability, in cognitive flexibility, and in mood regulation.
Magnesium supplementation has also been shown to modulate the neuroendocrine system and to improve sleep quality by promoting slow wave (deep) sleep, which, among many other functions, is also important for cognition and memory consolidation.
Furthermore, magnesium may enhance the beneficial effects of exercise in the brain, since it has been shown to increase the availability of glucose in the blood, muscle, and brain, and diminish the accumulation of lactate in the blood and muscles during exercise.
But just as increasing magnesium levels can be beneficial, magnesium deficiency can have serious harmful effects.
Magnesium has important roles in the regulation of oxidative stress, inflammatory processes and modulation of brain blood flow. In circumstances of magnesium deficiency, all of these functions can potentially be dysregulated, laying the ground for neurological disorders. Also, in a context of low magnesium availability in the brain, NMDA glutamate receptors, which are excitatory, may become excessively activated, and GABAA receptors, which are inhibitory, may become insufficiently activated; this can lead to neuronal hyperactivity and to a condition known as glutamate excitotoxicity. This causes an excessive accumulation of calcium in neurons, which in turn leads to the production of toxic reactive oxygen species and, ultimately, to neuronal cell death.
Magnesium deficiency has been associated with several neurological and psychiatric diseases, including migraines, epilepsy, depression, schizophrenia, bipolar disorder, stress, and neurodegenerative diseases. Magnesium supplementation has shown beneficial effects on many of these conditions, as well as in post-stroke, post-traumatic brain injury, and post-spinal cord injury therapies. This therapeutic action is likely due to the blocking of NMDA glutamate receptors and decreasing excitotoxicity, reducing oxidative stress and inflammation, and increasing blood flow to the brain, all of which are determinants of the outcome of these conditions.
There are multiple benefits to be obtained from magnesium, both from a health promotion and disease prevention/management perspective. The recommended daily intake of magnesium is 320 mg for females and 420 mg for males. Too much magnesium from food sources has no associated health risks in healthy individuals because the kidneys readily eliminate the excess. However, there is a recommended upper intake level for supplemental magnesium, since it can cause gastrointestinal side effects. So, keep it below 350 mg/day.
Chen HY, et al (2014). Magnesium enhances exercise performance via increasing glucose availability in the blood, muscle, and brain during exercise. PLoS One, 9(1):e85486. doi: 10.1371/journal.pone.0085486
de Baaij JH, et al (2015). Magnesium in man: implications for health and disease. Physiol Rev, 95(1):1-46. doi: 10.1152/physrev.00012.2014
Held K, et al (2002). Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacopsychiatry, 35(4):135-43. doi: 10.1016/j.pbb.2004.01.006
Jia S, et al (2016). Elevation of Brain Magnesium Potentiates Neural Stem Cell Proliferation in the Hippocampus of Young and Aged Mice. J Cell Physiol, 231(9):1903-12. doi: 10.1002/jcp.25306
National Institutes of Health, Office of Dietary Supplements. Magnesium Fact Sheet for Health Professionals
Slutsky I, et al (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010 Jan 28;65(2):165-77. doi: 10.1016/j.neuron.2009.12.026
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