Magnesium is an essential mineral for the body which is naturally present in many foods, such as nuts and seeds, leafy greens, whole grains, and legumes. It is required for more than 300 biochemical reactions in the human body that support protein synthesis, muscle health and function, cellular energy generation, bone health, blood glucose regulation, cardiovascular health, and brain function and cognitive health. 

Magnesium intake in the U.S. has been decreasing over the past century, from about 500 mg per day to between 175 mg and 225 mg per day, potentially driven by increased processed food consumption and water and soil demineralization. Magnesium may be further depleted with excessive alcohol consumption, gastrointestinal and cardiovascular disorders, osteoporosis, diabetes, and certain medications. When dietary magnesium is suboptimal, supplementation may be considered. It is available in different forms, including magnesium oxide, citrate, glycinate, malate, chloride, gluconate, and L-threonate. 

Magnesium and brain health

In terms of brain health, magnesium plays an important role in nerve signal transmission and the integrity of the blood-brain barrier (BBB), which supports the homeostasis of the central nervous system. The BBB protects the brain from pathogens and toxins by regulating the passage of particles between the blood and the CNS. Magnesium is also essential for the maintenance of ionic homeostasis in the brain, where it acts as a calcium antagonist, regulating the balance of ions in neurons and promoting healthy nerve function. Magnesium also supports the major excitatory and inhibitory neurotransmission pathways, such as gamma-aminobutyric acid and glutamate. 

The role of magnesium L-threonate in cognitive health

Magnesium L-threonate is formed by chelating magnesium to threonic acid, a metabolite of ascorbic acid found naturally in foods and in the human body. It is a highly bioavailable form of magnesium that has the potential to cross the BBB. Magnesium L-threonate acts as an ionophore, which is a substance that can transport ions across cell membranes. As such, it is able to transport magnesium ions across lipid membranes, including those of brain cells. This enables it to cross the BBB, supporting magnesium status in the brain and throughout the nervous system, and promoting cognitive function, memory, and overall brain health.

In 2010, scientists from the Massachusetts Institute of Technology, Tsinghua University in China, Tel Aviv University, and the University of Toronto collaborated in the development of magnesium L-threonate. According to their animal-model study, MgT supplementation effectively increased magnesium status in the brain, which in turn supported learning and memory functions by promoting the activation of the N-methyl-D-aspartate receptors, leading to increased synaptic density. The authors concluded that MgT may play a role in supporting learning abilities, working memory, and short- and long-term memory. 

Further empirical evidence indicates that magnesium L-threonate may play an important role in supporting memory and cognition in humans. For example, a randomized double-blind study (n = 44) found that U.S. adults (between the ages 50 and 70) supplemented with 1.5 g to 2 g (depending on their weight) of MgT for 12 weeks showed improved overall cognitive ability and reduced cognitive fluctuation. Another randomized double-blind study (n = 109) found that healthy individuals ages 18 to 65 supplemented with 2 g of MgT per day for 30 days showed improvement in all five categories of a memory test and in overall memory scores. Older participants showed greater improvement than younger ones. 

A human clinical trial (n = 15) investigated the effect of a twelve-week MgT supplementation in individuals with mild to moderate dementia. Using brain imaging, cognitive testing, and blood draws, this study found that there was a significant improvement in regional cerebral metabolism and in overall cognitive function. The effect of MgT supplementation was also examined in a subpopulation of adults with moderate attention deficit disorder. In this pilot study (n = 15), participants (ages 18 to 55) supplemented with MgT (500 mg in the morning and evening) for 12 weeks showed significant improvements in clinician- and self‐reported ADHD symptoms, executive functioning and visual scanning measures, and increased IQ scores by 5% to 12%.

Further randomized clinical research on the effects of magnesium L-threonate on cognitive function may be warranted, especially in populations with different neuropathologies. However, current evidence suggests an important role for this unique form of magnesium in cognitive health. 

Learn more about magnesium: 

Magnesium Deficiency: How It Relates to Poor Mood and Mental Health

Is There a Link Between Magnesium Status and Healthy Cognition?

Can Magnesium L-Threonate Support Stress?

By Antonia Toupet, PhD