The role of magnesium in the brain  

Magnesium is required for over 300 enzymatic reactions in the human body, positively supporting neurological, cardiovascular, and musculoskeletal health. Regarding brain health, magnesium is needed for optimal ionic homeostasis, normal nerve signal transmission, and major excitatory/inhibitory neurotransmission pathways. Magnesium is required to maintain the blood-brain barrier (BBB), which protects the brain against toxins and pathogens and bidirectionally controls the passage of molecules from the blood and the central nervous system. Magnesium may also promote the normal function of brain-derived neurotrophic factor (BDNF), which contributes to neuronal plasticity and is required for normal learning and memory. Furthermore, magnesium may lower the adverse effects of oxidative stress and promote healthy inflammatory responses in the brain. 

Due to magnesium’s pivotal role in brain health, magnesium is suggested to support a more balanced mood and mental health. This may help to explain why a systematic review and meta-analysis of six observational studies (n = 19,137) concluded that individuals with magnesium deficiency (hypomagnesemia) had an overall 1.3-fold increased risk of depression. 

What causes suboptimal magnesium status? 

According to epidemiological studies, magnesium intake in the U.S. has significantly decreased from 500 mg to a range of 175 mg to 225 mg per day. Individuals who follow a Western‑style diet consume less than 30% to 50% of the Recommended Daily Allowance (RDA) for magnesium, which is 320 mg to 420 mg daily for adults. Magnesium insufficiency is common in the U.S. due to the wide use of demineralized water and soil and the increased consumption of processed foods. Magnesium is also depleted by stress, excessive alcohol consumption, gastrointestinal disorders, diabetes, and certain medications. 

Magnesium deficiency, or hypomagnesemia, is characterized by serum magnesium levels below 1.46 mg/dL (normal levels are between 1.46 and 2.68 mg/dL). Hypomagnesemia is reported to have a prevalence of 2.5% to 15% in the general population. However, it can be under-recognized or under-reported, as it is typically asymptomatic until serum magnesium concentration is less than 1.2 mg/dL. Signs and symptoms include mild tremors, generalized weakness, cardiac ischemia, and may result in death.

Magnesium and certain medications  

A variety of medications can cause magnesium loss or hypomagnesemia, including proton pump inhibitors (PPIs). PPIs can be prescribed or taken over the counter and are used for individuals with occasional or chronic heartburn. PPIs are designed to lower gastric acidity, resulting in an unwanted outcome of reducing the absorption of essential vitamins and minerals, including magnesium. The authors of a cross-sectional study (n = 16,881) proposed that one potential hypothesis for why they found an association between PPIs and depression in adults is due to PPI-induced hypomagnesemia.  

PPIs are intended for short-term use of 14 days, up to three times per year. The Food and Drug Administration (FDA) stated there is little risk of hypomagnesemia when PPIs are used according to the directions on the label. However, studies show that 40% to 60% of PPI use is inappropriately misused or overused for unnecessarily long periods. A systematic review of global trends and practices identified 28 million PPI users in 23 countries, indicating that nearly one-quarter of adults worldwide use a PPI. Among those taking a PPI, 25% used PPIs for over one year, and 28% used PPIs for over three years. 

Clinical insights 

According to the FDA, hypomagnesemia has been reported in adult patients taking PPIs for at least three months, but most cases occurred after PPI use for one year. One-quarter of cases required discontinuing PPI treatment under medical supervision plus magnesium supplementation to reestablish healthy magnesium status. Once discontinuing the PPI, the median time required for magnesium to normalize was one week. Interestingly, if the individual restarted the PPI, the median time to develop hypomagnesemia again was two weeks. (Note: If you are concerned about your magnesium status with certain medication use, talk with a healthcare provider immediately. Do not discontinue the medication without medical supervision.)  

It is well known that magnesium can help support balanced mood and mental health due to its various roles in the brain. In addition to promoting magnesium status through supplementation or dietary sources (green leafy vegetables, legumes, nuts, seeds, and whole grains), one may want to consider what other lifestyle or dietary factors may cause magnesium insufficiency or deficiency.  

Learn more about magnesium: 

The Link Between Magnesium Status and Healthy Cognition 

The Connection Between Magnesium and Vitamin B6 to Support a Normal Stress Response 

Explore Magnesium Status and Cardiometabolic Health

Magnesium for Healthy Blood Sugar Support  

By Danielle Moyer Male, MS, CNS, LDN