The science behind magnesium’s roles in brain health

Magnesium is an essential micromineral that has a role in more than 300 enzymatic systems. Magnesium also acts within specific body tissues and organs. This includes the brain, the highly complex organ that defines humans. It controls movement, intelligence, memory, learning, and in some instances, defines life. When things go wrong with the brain, it can have devastating effects throughout the body. Yet, the brain and how it functions are a mystery to most people.

One of the biggest roles of magnesium in the body is in energy production. Adenosine triphosphate (ATP) is the energy currency of the body. But, for it to be biologically active, ATP must be bound to a magnesium ion, generally to one of the phosphate groups.

Researchers have recently studied magnesium homeostasis on mitochondrial function. One research group looked at MRS2 knock down HeLa cells (the oldest human cell line and most commonly used in scientific research) as an in vitro model for study.1 MRS2 is a mitochondrial magnesium ion channel that controls the influx of magnesium ions into the mitochondrial space. When knocked down, the influx of magnesium ions into the mitochondria is impaired.

The researchers found that compared to control cells, MRS2 knock down cells experienced a suppression of various metabolites that are associated with the energy production cycle—namely malate, citrate, cis-aconitate and succinate. Additionally, using fluorescence techniques they found the ATP levels in MRS2 knock down cells were lower than in control cells. These findings showed that if magnesium cannot get into the cellular mitochondria, energy production is impaired and does not function optimally. In the brain, this might mean energy production is not optimal and, subsequently, may have an impact on cognition.

Other researchers reviewed existing studies and discovered magnesium enhances the activity of three important mitochondrial dehydrogenases involved in energy production.2 Isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase are stimulated directly by a magnesium-isocitrate complex and free magnesium ions. Pyruvate dehydrogenase is indirectly stimulated by magnesium. From this research, scientists can conclude that magnesium is deeply embedded in the role of energy production. These two studies are key to understanding the role of magnesium in energy production.

The brain is one of the largest consumers of energy. Researcher Marcus Raichle, M.D., Ph.D., professor of radiology, neurology, neurobiology and biomedical engineering at Washington University in St Louis, stated that in the average human adult the brain represents only about 2 percent of body weight.3 However, it consumes a disproportionate amount of energy: 20 percent of all energy consumed.

Ensuring that the brain and other parts of the body have the magnesium, calories and other nutrients required for ATP production and conversion will help to optimize those cognitive and other biological process that rely upon that energy.

Magnesium and Neuronal Processes

Recent research suggested magnesium has additional roles in the brain that are not necessarily associated with energy production.

Sara Adaes, Ph.D., research scientist, Neurohacker Collective, reviews the functions of magnesium in the brain in the BrainBlogger blog from the Global Neuroscience Initiative Foundation (GNIF). According to this review, magnesium is a regulator of neurotransmitter signaling in the brain. It is vital to the main neurotransmitters glutamate and gamma-aminobutyric acid (GABA), through modulating the activation of N-methyl-D-aspartate (NMDA) glutamate and GABA Alpha receptors. Via regulation of the activity of calcium channels, magnesium contributes to the maintenance of adequate calcium in brain cells. Thus, this mineral is important to neuronal processes.

Magnesium’s involvement in the mechanics of synaptic transmissions and neuronal plasticity result in its impact on learning and memory. Increased levels of magnesium in the brain have been shown to promote multiple mechanisms of synaptic plasticity that can enhance different forms of learning and memory.

Potential Roles of Magnesium in Brain Decline and Injury

Magnesium might play other, yet-undefined, roles in brain health. A systematic review recently determined that in comparison to healthy and medical illness controls, the magnesium levels in those with Alzheimer’s disease was significantly lower in cerebrospinal fluid and in hair (P<0.05) even though there was no difference in serum magnesium levels.4

Another study found that based upon Taiwan’s National Health Research Institute (NHRI) Database, those that had used magnesium oxide were less likely to develop dementia.5 They further adjusted their data to compensate for various factors including age, gender, geography and economic variation and found that the relationship held. Finally, a group of researcher from India reported that magnesium decline is likely to play a role in the pathogenesis of traumatic brain injuries.6 They found that those who were parenterally administered magnesium sulfate within 12 hours of their injury had a much greater chance of a favorable outcome with no observed significant adverse effects.

Magnesium in the Diet May Not be Enough

From the above studies, magnesium has multiple roles in normal brain health and function. Unfortunately, according to a U.S.-based research team, approximately 50 percent of the U.S. population consumes less than the daily requirement from their diets.7 They further stated that the 2015 Dietary Guidelines Advisory Committee characterized magnesium as a “shortfall nutrient of public health concern.”

This dietary inadequacy is not limited to the United States. Spanish researchers reported from the ANIBES (Anthropometry, Intake and Energy Balance) data that 72 percent of the Spanish population did not meet the European Food Safety Authority (EFSA) recommended intakes of magnesium from their diets.

If the diet is inadequate for magnesium content, a dietary supplement containing magnesium may be warranted to help support normal brain health.

Stephen Ashmead is a senior fellow for Balchem Corp. His area of specialty is in mineral amino acid chelates and their functions.

References

1.         Yamanaka R. et al. “Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress.” Sci Rep. 2016 Jul 26;6:30027. DOI: 10.1038/srep30027.

2.         Pilchova I et al. “The involvement of Mg2+ in regulation of cellular and mitochondrial functions.” Oxid Med Cell Longev. 2017;2017:6797460. DOI: 10.1155/2017/6797460.

3.         Raichle M. “Two views of brain function.” Trends Cogn Sci. 2010 Apr;14(4):180-90. DOI: 10.1016/j.tics.2010.01.008.

4.         Veronese N, Zurlo A, Solmi M. “Magnesium status in Alzheimer's disease: A systematic review.” Am J Alzheimers Dis Other Demen. 2016 May;31(3):208-13. DOI: 10.1177/1533317515602674.

5.         Tzeng N et al. “Magnesium oxide use and reduced risk of dementia: a retrospective, nationwide cohort study in Taiwan Curr Med Res Opin. 2018 Jan;34(1):163-169. DOI: 10.1080/03007995.2017.1385449.

6.         Dhandapani S. et al. “Randomized controlled trial of magnesium sulphate in severe closed traumatic brain injury.” The Indian Journal of Neurotrama. 2008;5(1):27-33.

8.         Costello R et al. “Perspective: The case for an evidence-based reference interval for serum magnesium: the time has come.” Adv Nutr. 2016 Nov 15;7(6):977-993. DOI: 10.3945/an.116.012765.

9.         Olza J et al. “Reported dietary intake, disparity between the reported consumption and the level needed for adequacy and food sources of calcium, phosphorus, magnesium and vitamin D in the Spanish population: findings from the ANIBES study.” Nutrients. 2017;168. DOI:10.3390/nu9020168