Research & Education

Magnesium in Mental Health

In the functional and integrative medicine world, most health care practitioners are well-aware of the need for supplemental magnesium in their practices. The current RDA for magnesium is between 300 and 420 mg/day for most people; however, on average, more than one-half of Americans over the age of four consume less than the estimated average requirement (EAR). That is a scary statistic; magnesium deficiency has been linked to an increased risk of cardiometabolic- and bone-related conditions, as well mental and neurological disorders, including headache, stress, traumatic brain injury, seizure, and Parkinson’s and Alzheimer’s diseases. Because only 1% of the body’s magnesium is stored in blood serum (99% stored in bones and soft tissues), it is difficult to assess magnesium status, and abnormal serum magnesium levels “may be the most underdiagnosed serum electrolyte abnormality in clinical practice today”.

There are various forms of supplemental magnesium that play specific roles and impart specific functions in the body depending on a condition or need. For example, magnesium citrate is commonly used as a stool softener for those who may face chronic constipation or IBS-C; too much may cause diarrhea. Magnesium glycinate is an easily absorbable form that may be helpful for general muscle cramping and fatigue. Both of these forms of magnesium are more bioavailable than the oxide and sulfate forms.

Magnesium Threonate and Brain Health

This article’s aim is to explain the roles and benefits of magnesium L-threonate, a chelated magnesium mineral bound to threonic acid, for promoting mental health and cognitive function. Magnesium L-threonate is a superior form of magnesium at passing through the blood-brain-barrier, as it is able to transport Mg ions across the lipid membranes of brain cells. Magnesium ions regulate calcium ion flow in neuronal calcium channels, helping to regulate neuronal nitric oxide (NO) production. In cases of magnesium deficiency, neuronal requirements for magnesium may not be met, causing neuronal damage, which could manifest as memory loss, depression, anxiety and more. Growing evidence suggests that magnesium plays an essential role in neurological conditions, and magnesium L-threonate is a preferred option.

Clincally-supported evidence from both human and animal studies shows that supplemental magnesium L-threonate (MgT) is an effective micronutrient for improving working, attention and episodic memory, executive cognitive function, and reducing overall stress and anxiety. In an animal model of chronic neuropathic pain, oral MgT administration for 2 weeks prevented and restored short-term memory deficits associated with neuropathic pain by regulating TNF-𝜶 expression in the hippocampus and reversing N-methyl-D-aspartic acid (NMDA) receptor dysfunction. A study published in Neuropsychiatric Disease & Treatment demonstrated MgT therapy to significantly increase magnesium concentrations in the cerebrospinal fluid, attenuating dopamine neuronal loss and motor deficits in an animal model of Parkinson’s disease. Furthermore, in aging Alzheimer’s-diseased mice, MgT in combination with environmental enrichment synergistically improved spatial memory and recognition via restoring the NMDA signaling pathway and hippocampal synaptic plasticity. Compared with magnesium chloride and magnesium sulphate, MgT more significantly decreased depression-related behaviors by bolstering cholinergic pathways and dampening oxidative burden in healthy animal models. In the Journal of Cellular Physiology, long-term (12 month) MgT supplementation potentiated neural stem cell proliferation within the hippocampus of young and aged mice.

Magnesium in Clinical Practice

Magnesium is abundant in both plant and animal-based foods. Pumpkin seeds (or pepitas), spinach, Swiss chard, and beet greens are excellent sources, while seeds, nuts, and legumes such as soybeans, sesame seeds, black beans, cashews, and sunflower seeds are very good sources. For patients who do not consume sufficient amounts of these foods, such as those who follow a standard American diet full of processed and refined foods (only 16% of magnesium found in whole wheat remains in refined flour), magnesium threonate supplementation may be necessary to replete magnesium insufficiency, especially in the presence of a declined neurocognitive state and related symptoms. Magnesium can be further depleted by stress, excessive alcohol intake, and certain medications; therefore addressing these factors (in addition to proper supplementation) is critical in order to help increase magnesium levels within the brain and body for helping to prevent disease onset and/or delay progression. 

By Caitlin Higgins, MS, CNS, LDN