Neuro(b)log for Patients

How magnesium works in the human body

About 60% of the body's magnesium is stored in bone, 20% in soft tissues and roughly 1% in extracellular fluid; the remainder is distributed among organs and tissues. Magnesium participates in cellular energy metabolism as a cofactor for several hundred enzymatic reactions associated with ATP (adenosine triphosphate), the molecule central to cellular energy production. It also activates synthetases and transferases in ribosomes and is therefore integral to protein synthesis. Insufficient magnesium intake slows the renewal of muscle and liver proteins. During cell division it stabilizes DNA polymerases and other enzymes responsible for DNA replication. Magnesium is required for microtubule synthesis, a functional component of the mitotic spindle that ensures correct chromosome distribution during cell division. Deficiency impairs cell proliferation, slows tissue regeneration and reduces immunity. Rapidly dividing cells in bone marrow or mucosa consume magnesium at higher rates.

Magnesium also regulates muscle contraction and relaxation, helping to prevent cramps and muscle fatigue and improving recovery after physical exertion. For neurologists, magnesium is particularly interesting because it plays an important role in proper nerve impulse transmission, reduces excitability and improves psychological well‑being. Adequate magnesium intake also supports proper calcium handling and contributes to stronger bones.

Magnesium affects cardiovascular function by helping to normalize heart rate, dilate blood vessels and maintain stable blood pressure. Intravenous magnesium supplementation is used in acute settings (for example, certain cardiac arrhythmias) and it also influences the body's acid–base balance.

In one study of patients with chronic heart failure, administration of 6,000 mg magnesium orotate daily for one month (followed by 3,000 mg daily for 11 months) was associated with about a 25% reduction in mortality during the study and symptom improvement in 40% of patients. This effect is attributed to support of RNA and DNA synthesis in cardiac muscle cells. Orotates generally facilitate mineral transport across cell membranes and participate in energy metabolism through ATP binding. Caution and monitoring of serum magnesium are required in patients with kidney disease.

In patients with diabetes, magnesium helps regulate cellular glucose uptake and reduces insulin resistance (type 2 diabetes), thereby supporting normal blood glucose levels. Disturbed balance between blood calcium and its deposition (caused by magnesium deficiency) can lead to kidney stones and soft‑tissue calcification. Magnesium keeps calcium soluble in blood, stimulates calcitonin and suppresses parathyroid hormone; both hormones are essential for hormonal regulation of calcium metabolism. Magnesium supports activation of vitamin D, which improves intestinal calcium absorption, and it binds oxalates, reducing formation of calcium‑oxalate kidney stones.

Conditions associated with hypomagnesemia

Hypomagnesemia can arise from malnutrition, diabetes, hypertension, excessive alcohol use, chronic diarrhea, hyperthyroidism, hypoparathyroidism, hyperaldosteronism and many other conditions. It may also occur as an adverse effect of certain medications (long‑term proton pump inhibitors, diuretics), after bariatric or oncologic surgery, in chronic pancreatitis, cystic fibrosis, celiac disease, etc.

Magnesium deficiency is linked not only to tetany but also to tension‑type headache and migraine, anxiety, internal tremor or shaking, and insomnia.

How magnesium affects mental health

Magnesium modulates the nervous system on multiple levels by acting on biochemical pathways that influence mood, stress resilience and sleep quality.

• Blocks excessive NMDA receptor activation. NMDA receptors bind glutamate and allow calcium ions into the cell; excessive calcium influx causes neuronal damage or cell death. NMDA receptors are crucial for learning, synaptic plasticity and memory. Drugs such as memantine act as NMDA antagonists in dementia; magnesium supports balanced NMDA function.

• Supports GABA synthesis. By promoting production of the inhibitory neurotransmitter GABA (gamma‑aminobutyric acid), magnesium reduces anxiety and nervousness.

• Slows serotonin reuptake. Serotonin, often called the "happiness hormone," has an antidepressant effect and improves mood.

• Increases stress resilience. Magnesium helps regulate the hypothalamic–pituitary–adrenal (HPA) axis, lowering stress hormones such as cortisol and adrenaline.

• Improves sleep quality. By activating the parasympathetic system and relaxing muscles and nerves, magnesium supports melatonin production and prolongs deep sleep phases. Patients report fewer nighttime awakenings, greater restorative sleep and fewer nocturnal cramps. Improvements typically appear within 4–6 weeks of supplementation.

• Supports antidepressant effects. Magnesium has been reported to enhance antidepressant efficacy and to exert partial antidepressant effects on its own by participating in synthesis of neurotransmitters such as serotonin, dopamine, acetylcholine and GABA. For example, in a placebo‑controlled study at the University of Vermont, 126 patients with mild to moderate depression received 248 mg magnesium daily for 6 weeks; after 2 weeks the average PHQ‑9 score fell by 6 points, indicating a faster and stronger antidepressant response with magnesium supplementation.

In migraine sufferers, a significant reduction in attack frequency was observed only after 3 months of regular magnesium use, especially in patients with documented low serum magnesium (also detectable in saliva).

BDNF, magnesium and neuroplasticity

Magnesium acts as a key modulator of brain processes by influencing release and expression of brain‑derived neurotrophic factor (BDNF) and by supporting synaptic plasticity. Through interactions with NMDA receptors and intracellular signaling cascades, magnesium regulates BDNF levels and facilitates learning, memory and regeneration of neural connections.

Research evidence: animal models (rats) show that supplementation with magnesium L‑threonate significantly increases brain magnesium levels, BDNF and the number of synaptic connections in the hippocampus. Clinical studies in humans have found correlations between adequate magnesium intake, higher serum BDNF and improved cognitive performance, particularly in older adults and patients with depression.

Practical application: to support brain function, magnesium L‑threonate is recommended because it crosses the blood–brain barrier more effectively. Other forms such as magnesium citrate or magnesium glycinate have high bioavailability and good gastrointestinal tolerance. Physical exercise itself stimulates BDNF; combining training with adequate magnesium intake produces a cumulative positive effect on neuroplasticity.

Other factors that influence BDNF and neuroplasticity

• Omega‑3 fatty acids (EPA and DHA): support membrane fluidity and complement BDNF effects.

• Sleep: deep sleep phases enhance synaptic network restoration and BDNF production.

• Vitamin D: regulates gene expression of neurotrophic factors including BDNF.

• Stress management: meditation and breathing exercises lower cortisol, which otherwise reduces BDNF.

Magnesium absorption and use

Better solubility is associated with higher absorption and bioavailability of magnesium. Unabsorbed magnesium acts as a laxative, and different magnesium forms can cause digestive (dyspeptic) complaints such as bloating, heartburn and similar symptoms. Organic magnesium compounds therefore tend to have good solubility, for example magnesium orotate, magnesium lactate, and magnesium citrate.

Watch other ingredients that magnesium products may contain. These can include vitamin B6 (pyridoxine), sodium, or potassium, which may increase the total daily intake and raise the risk of exceeding recommended limits, potentially causing adverse effects. Also be cautious with combined supplements during pregnancy because recommended daily intakes for some vitamins and minerals differ from those for non‑pregnant adults.

Practical notes

Possible contraindications for high magnesium intake should be noted. For magnesium lactate, contraindications include severe kidney disease, advanced heart failure, low blood calcium, and allergy. Be aware of drug interactions: absorption is reduced by tetracyclines and some other antibiotics; magnesium can affect absorption of bisphosphonates and thyroid medications.

Magnesium gluconate may interact with diuretics and antibiotics (tetracyclines, quinolones) and with bisphosphonates (osteoporosis drugs). It is also advisable to separate intake of other supplements such as magnesium bisglycinate and calcium, iron, or zinc by at least two hours.

Conclusion

Magnesium is an important biogenic element that can help patients with various complaints. However, like other dietary supplements, it should be used thoughtfully and, if possible, after consulting a physician or pharmacist. In some cases it is appropriate to check serum magnesium and other mineral levels before starting supplementation. In today's climate of lively public discussion and interest in supplements, minerals and vitamins for prevention, health improvement and longevity, all information should be received with caution. This article is not an exhaustive review of the uses, functions and effects of this interesting mineral in the body; it offers my perspective as a neurologist on magnesium supplementation in neurological patients. I also wish to exclude any conflict of interest regarding products from pharmaceutical companies.

"Keep the key to your balance with magnesium — even without it!"

MUDr. Petra Mištríková, MBA

References for further study:

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