Magnesium Deficiency

Magnesium can play an important therapeutic and preventive role in several conditions such as diabetes, osteoporosis, bronchial asthma, preeclampsia, migraine, and cardiovascular diseases.

Several studies have shown its usefulness in neurological and psychiatric diseases and magnesium supplements may help reduce symptoms of depression, particularly in people with magnesium deficiency.

What is Magnesium?

Magnesium is an essential mineral that plays an important role in many bodily functions, including mood regulation. In addition, it is the fourth most abundant cation in the body. It has several other functions in the human body including its role as a cofactor for more than 300 enzymatic reactions.

It regulates many fundamental functions in the body, such as muscle contraction, neuromuscular conduction, glycemic control, myocardial contraction, and blood pressure. Magnesium also plays a vital role in energy production, active transmembrane transport for other ions, synthesis of nuclear materials, and bone development.

It maintains ionic gradients (keeping intracellular sodium and calcium low and potassium high), cellular and tissue integrity, mitochondrial oxidative phosphorylation (ATP production and activation), and DNA, RNA, and protein synthesis and integrity.

Magnesium Mechanism of Action

A group of studies investigated several microelements, including serum magnesium, in depressed patients vs. healthy controls and it was observed that patients suffering from depression have low levels of serum magnesium. Magnesium plays a crucial role in the function of neurotransmitters (chemicals that transmit signals in the brain).

  • NMDA receptor function: Here, magnesium (Mg+2) acts as a natural blocker of NMDA (N-methyl-D-aspartate) receptors, which are involved in the regulation of mood and help in treating depression. By blocking NMDA receptors, magnesium may help regulate neurotransmitter release and reduce excitotoxicity, which is associated with depression.
  • Serotonin synthesis: Magnesium is also involved in the synthesis of serotonin, which is a neurotransmitter that plays a key role in regulating mood. Low levels of magnesium may lead to decreased serotonin levels, which can contribute to depression and anxiety disorders.
  • GABA function: Magnesium is involved in the regulation of GABA (that is gamma-aminobutyric acid), an inhibitory neurotransmitter that helps calm the nervous system. Dysregulation of GABA has been implicated in anxiety and depression, and clinical observations show that magnesium may help support GABA function.
  • Glutamate receptor: Magnesium is an antagonist at the glutamate receptor. Glutamate is one of the key neurotransmitters involved in the regulation of mood. IV dosage of ketamine which is used for treatment-resistant depression (a form of major depressive disorder), is also a powerful glutamate receptor antagonist.
  • Dopamine receptor: Magnesium has a key role in influencing the hypothalamic-pituitary-adrenal (HPA) axis, which is involved in the production of stress hormones. Chronic stress can dysregulate dopamine signaling, and magnesium may help mitigate the effects of stress on dopamine receptors. In addition to this, magnesium also has anti-inflammatory properties, and inflammation can also impact dopamine receptor function. By reducing inflammation, magnesium may indirectly support dopamine receptor function.
  • Acetylcholine receptor: Effects of magnesium (Mg2+) on acetylcholine (ACh)-evoked secretory responses and calcium (Ca2+) mobilization. Mg2+ can influence ACh-evoked secretory responses possibly by controlling both Ca2+ influx and release in pancreatic acinar cells. It indirectly supports ACh receptor function. Acetylcholine acts on both Nicotinic acetylcholine receptors (nAChRs) and Muscarinic acetylcholine receptors (mAChRs) in the brain, and these receptors are involved in various aspects of mood regulation.

Natural Sources of Magnesium

Magnesium is found in a variety of nutrient-dense foods, including whole grains, nuts, seeds, legumes, and several fruits and vegetables, such as avocados, bananas, chia seeds, fatty fish, tofu, etc.

  • Avocados: Avocados are a nutritious fruit and one of the tasty sources of magnesium. One avocado provides approximately 58 mg of magnesium, which is 14% of the DV.
  • Nuts: Nuts are considered to be good sources of magnesium, including almonds, cashews, and Brazil nuts.
  • Legumes: Legumes are rich in nutrients, such as lentils, beans, chickpeas, peas, and soybeans.
  • Tofu: It is one of the staple foods in vegetarian diets due to its high protein content. It is made by pressing soybean milk into soft white curds, also known as bean curd.
  • Seeds: Many seed varieties contain high amounts of magnesium for example flax, pumpkin, and chia seeds. Pumpkin seeds are a good source.
  • Whole grains: like wheat, oats, and barley, are excellent sources of many nutrients, including magnesium.
  • Some fatty fish: fatty fish, are high in magnesium. These include salmon, mackerel, and halibut.
  • Bananas: Bananas are rich in magnesium, with 37 mg of magnesium, or 9% of the DV, in one large banana.
  • Leafy greens: It has significant amounts of magnesium including kale, spinach, collard greens, turnip greens, and mustard greens.

What is Magnesium Deficiency?

Magnesium deficiency is also known as hypomagnesemia. It is a condition when the body does not have sufficient magnesium, which affects many important body functions. There can be multiple reasons behind magnesium deficiency, like excessive loss through urine, conditions that impair absorption, and many other reasons.

Studies show that individuals with low intakes of magnesium suffer from magnesium deficiency, and deficiency of this micronutrient induces changes in biochemical pathways that can increase the risk of illness and, in particular, chronic degenerative diseases.

Magnesium deficiency is seen frequently in alcoholics and diabetic patients, in whom a combination of factors contributes to its pathogenesis. It is observed that hypomagnesemia produces a wide variety of clinical presentations, including neuromuscular irritability, cardiac arrhythmias, and increased sensitivity to digoxin.

Does Magnesium Deficiency Cause Depression?

Magnesium is essential to ensure the correct functioning of all human cells, which includes neurons; in addition to this, it is involved in many other processes, like in hundreds of enzymatic reactions, intracellular transmission, myelination process, synapse formation, and maintenance as well as in the regulation of serotoninergic, dopaminergic and cholinergic transmission. Therefore magnesium is considered to be an essential element, which is necessary to maintain neurons healthy and viable.

From the above section, it can be easily concluded that magnesium deficiency is linked to depression because it plays a crucial role in brain function and mood regulation. A deficiency in magnesium can disrupt the hypothalamic-pituitary-adrenal (HPA) axis, the body’s central stress response system. This disruption can lead to an increase in cortisol levels, which in turn disrupt the neurotransmitter function, leading to mood imbalances.

Clinically it is proven that people with depression often have lower magnesium levels. Some research also suggests that magnesium supplementation may alleviate depressive symptoms, particularly in those with low magnesium levels or treatment-resistant depression.

Magnesium Deficiency Causes

Hypomagnesemia is a relatively common occurrence in clinical medicine. Still, in most cases, magnesium deficiency is undiagnosed because serum magnesium does not reflect intracellular magnesium, the latter making up more than 99% of total body magnesium.

Because of chronic diseases, medication decreases in food crop magnesium contents, and the availability of refined and processed foods, the vast majority of people in modern societies are at risk for magnesium deficiency.

Furthermore, a magnesium supplement is taken by certain individuals worldwide to prevent suboptimal magnesium deficiency, especially if trying to obtain an optimal magnesium status to prevent chronic disease.

While diet is the starting point to increase magnesium intake levels in general, it may not be enough for some people with mental health conditions, because of two main reasons:

  • Modern-day food cultivation: Modern-day farming processes have depleted magnesium and other minerals from the soil, and the techniques used in food processing can deplete magnesium levels by up to 80%.
  • Biochemical individuality: Factors such as genetics, metabolism, health conditions, and more can influence how much magnesium a person needs for healthy functioning. Those with psychiatric symptoms like anxiety, depression, and insomnia may need more magnesium than they can feasibly get from their food.

The recommended daily intake of magnesium varies by age group and individual requirements may vary based on factors like health status and activity level. It’s always a good idea to consult with a healthcare provider for personalized recommendations.

Recommended Doses of Magnesium

  • Infants (0-6 months): 30 mg
  • Infants (7-12 months): 75 mg
  • Children (1-3 years): 80 mg
  • Children (4-8 years): 130 mg
  • Children (9-13 years): 240 mg (male) / 240 mg (female)
  • Adolescents (14-18 years): 410 mg (male) / 360 mg (female)
  • Adults (19-30 years): 400 mg (male) / 310 mg (female)
  • Adults (31+ years): 420 mg (male) / 320 mg (female)

Pregnant and lactating women have higher magnesium needs:

  • Pregnant adolescents: 400 mg
  • Pregnant adults: 350-360 mg
  • Lactating adolescents: 360-400 mg
  • Lactating adults: 310-320 mg

Some of the causes that contribute to Magnesium deficiency are mentioned below:

  • Inadequate dietary intake: A diet low in magnesium-rich foods such as leafy greens, nuts, seeds, and whole grains can lead to deficiency.
  • Gastrointestinal (GI) diseases: Conditions like Crohn’s disease, celiac disease, and chronic diarrhea can impair magnesium absorption in the gut.
  • Alcoholism: Chronic alcohol consumption can interfere with magnesium absorption and increase urinary excretion.
  • Older age: Older adults are at higher risk due to reduced magnesium absorption and increased excretion.
  • Type 2 diabetes: Insulin resistance and certain diabetes medications can increase magnesium loss through urine.
  • Medications: Some medications, such as diuretics, proton pump inhibitors, and certain antibiotics, can increase magnesium excretion.
  • High calcium or vitamin D intake: Excessive intake of calcium or vitamin D supplements can interfere with magnesium absorption.
  • Chronic stress: It can lead to magnesium depletion due to increased urinary excretion.
  • Other medical conditions: Conditions like hyperthyroidism, kidney disease, and pancreatitis can increase magnesium loss.
  • Low dietary intake of other nutrients: Deficiencies in vitamin D, vitamin K, and potassium can affect magnesium levels.

Alcohol and Magnesium Deficiency

Studies show that individuals with excessive alcohol consumption have significantly low levels of magnesium in their bodies. It damages many biological functions leading to deficiency through increased urinary excretion and impaired absorption caused due to disruption in the gastrointestinal system.

This depletion in magnesium levels due to alcohol can make the situation go worse. It can cause many physical and mental health issues such as anxiety, depression, and sleep disturbances.

Reducing alcohol intake and consuming magnesium-rich foods like leafy greens, nuts, and seeds, and magnesium supplements can help mitigate some of the adverse effects of alcohol consumption and improve overall health and well-being.

How to Test for Magnesium Deficiency?

Magnesium deficiency is diagnosed with a blood test. Typically a healthcare provider uses a magnesium fact sheet and blood tests, including a blood test, to evaluate magnesium levels, which can impact blood flow. Magnesium tests are an essential part of this evaluation process.

The results obtained from the tests are then compared to a reference range of values that describe high and low values for magnesium that are considered normal. The reference range for magnesium is generally described as follows:

  • Adults: 1.8 to 2.6 milligrams per deciliter (mg/dL)
  • Children: 1.7 to 2.2 mg/dL

However, this method may not always accurately reflect magnesium levels because most of the body’s magnesium is stored in bones and soft tissues, not in the blood.

Apart from lab tests, Convenient and confidential at-home testing options for magnesium deficiency are also available. It includes home test kits and online assessment tools. These methods offer a practical way to monitor magnesium levels and can help in identifying potential deficiencies.

  • Home test kits: It generally involves a finger prick blood sample, which is sent to a laboratory for analysis. Even though test kits can give an idea about magnesium levels, choosing a trustworthy and reliable test kit is crucial for obtaining accurate results.
  • Online assessment tools: It utilizes modified questionnaires to identify individuals at risk or who have the above-mentioned risk factors. While they can provide some indication of deficiency, online assessment tools may not be entirely accurate, and therefore a healthcare professional should be consulted for a definitive diagnosis.

Physical Symptoms of Magnesium Deficiency

  • Muscle spasms and cramps
  • Muscle contraction and tremors
  • Fatigue and weakness
  • Numbness and tingling
  • Irregular heartbeat
  • Seizures
  • Nausea and vomiting
  • Mood changes

Psychiatric Symptoms of Magnesium Deficiency

  • Anxiety
  • Depression
  • Irritability
  • Insomnia
  • Restlessness
  • Poor stress tolerance
  • Apathy

Psychiatric Illness Exacerbated by Magnesium Deficiency

  • Depression
  • Anxiety disorders
  • Bipolar disorder
  • Schizophrenia
  • ADHD (Attention-Deficit/Hyperactivity Disorder)
  • Alzheimer’s disease
  • Dementia

Medical Illness Exacerbated by Magnesium Deficiency

  • Hypertension (high blood pressure)
  • Cardiovascular disease
  • Type 2 diabetes
  • Osteoporosis
  • Migraines
  • Muscle disorders
  • Asthma
  • Preeclampsia

Consequences of Magnesium Deficiency

Magnesium is a significant mineral for various physiological functions, and its deficiency can lead to a variety of health issues.

The following are some consequences of magnesium deficiency:

  • Fatigue and Weakness: One of the most common symptoms of magnesium deficiency is chronic fatigue and weakness due to its role in energy production at the cellular level.
  • Bone Health: Magnesium is important for bone formation and calcium metabolism. Deficiency could lead to individuals having weaker bones and an increased risk of osteoporosis; a medical condition characterized by weakened bones that could lead to bone fractures.
  • Gastrointestinal Issues: Early signs of magnesium deficiency could lead to gastrointestinal issues like nausea and vomiting.
  • Neuromuscular Symptoms: Magnesium has a crucial role in muscle function. Its deficiency could result in involuntary muscle contractions, spasms, and cramps.
  • Tremors and Seizures: Tremors and seizures are neuromuscular symptoms. Severe magnesium deficiency could result in detrimental tremors and seizures.
  • Cardiovascular Issues: Magnesium is crucial for maintaining a healthy and stable heart rhythm. Deficiency could lead to irregular heartbeats. Low magnesium levels could contribute to high blood pressure, which increases the risk of cardiovascular diseases.
  • Metabolic Problems: Magnesium deficiency is linked to impaired insulin function and could lead to insulin resistance, resulting in type 2 diabetes. Magnesium is responsible for the regulation of calcium and potassium levels in the body. Its deficiency could result in low levels of these minerals, causing further complications.
  • Mental Health Disorders: Magnesium is important for neurotransmitter function. Its deficiency has been proven to be linked to increased risk of anxiety, depression, and other mood disorders. Low levels of magnesium could result in mental confusion, irritability, and even hallucinations in severe cases.

Magnesium Deficiency Treatment

Treating magnesium deficiency is crucial for leading a healthy and balanced lifestyle. Following are some treatment options individuals with a magnesium deficiency could opt for:

  • Dietary Changes: Intake of magnesium-rich foods such as leafy greens (spinach, kale), nuts and seeds (almonds, pumpkin seeds), whole grains (brown rice, quinoa), legumes (beans, lentils), and fruits (avocado, bananas) could alleviate some of the symptoms of magnesium deficiency.
  • Magnesium Supplements: It is suggested to take magnesium supplements under the guidance of a healthcare professional. Multiple forms like magnesium oxide, magnesium citrate, magnesium glycinate, and magnesium chloride are available.
  • Topical Magnesium: Usage of magnesium oil or lotions on the skin is beneficial. This could be a proficient way to absorb magnesium transdermally, bypassing potential gastrointestinal absorption issues.
  • Intravenous (IV) Magnesium Therapy: Healthcare professionals may administer magnesium intravenously to rapidly increase magnesium levels in severe cases of deficiency or when oral supplementation is not viable.
  • Addressing Underlying Causes: Identifying and treating underlying medical conditions that contribute to magnesium deficiency is crucial. These could be gastrointestinal disorders, kidney disease, or medications that interfere with magnesium absorption.
  • Lifestyle Modifications: Reducing alcohol and caffeine consumption is imperative, as these could increase urinary excretion of magnesium. Practicing relaxation techniques for stress management such as meditation, yoga, or deep breathing exercises could be beneficial, as chronic stress can decrease magnesium levels. Exercising daily could also help alleviate some of the symptoms of magnesium deficiency as physical activity can help regulate magnesium metabolism and improve overall health as well as lifestyle.

Supplements for Magnesium Deficiency

There are two main factors to consider while undergoing magnesium supplementation:

  • Bioavailability: It indicates how much magnesium can be absorbed by the gut.
  • Access to the brain: Effective forms of magnesium must have the ability to cross the protective blood-brain barrier surrounding the brain.

There are two most commonly prescribed forms of magnesium – magnesium oxide and citrate – have the lowest bioavailability of the various forms, which means that they are more likely to pass through the gut and cause loose stools and diarrhea, so they are best used to relieve constipation. Magnesium salts like carbonate and sulfate have similar issues with absorption.

Magnesium forms that have better bioavailability and the ability to cross the blood-brain better, make them better treatment options for symptoms of anxiety and depression.

Daily supplementation with 248 mg of elemental magnesium as four 500 mg tablets of magnesium chloride per day leads to a significant decrease in depression and anxiety symptoms regardless of age, gender, baseline severity of depression, or use of antidepressant medications.

While the cross-over design of this trial is robust in controlling for internal biases, it would be reassuring to see the results replicated in larger clinical trials that test long-term efficacy and provide additional data on subgroups.

However, this efficacy trial showed magnesium supplements may be a fast, safe, and easily accessible alternative, or adjunct, to starting or increasing the dose of antidepressant medications.

  • Magnesium Taurate: It contains an amino acid called taurine, which has a calming, neuroprotective, and anti-inflammatory effect on the brain and can help relieve depression symptoms.
  • Magnesium Threonate: Studies show that back in time it was used in mental health conditions and has evidence that it can cross the blood-brain barrier.
  • Magnesium Glycinate: Glycine is an essential amino acid and has an important neurotransmitter function in the brain. It was observed that Glycine supplementation can improve the quality of sleep, making this form of magnesium a good choice for those with insomnia.
  • Magnesium Malate: This is one of the better-absorbed forms of magnesium, which increases both serum and muscle levels of magnesium. Based on data, magnesium taurate, and glycinate are more effective on anxiety and other mental health disorders.

Toxicity from Magnesium Supplementation

Magnesium toxicity is commonly caused by the overuse of magnesium-containing medication, supplementation, or under-excretion of magnesium by the kidneys.

While magnesium toxicity is rare in the general population, there is a subset of patients at risk of developing this pathology. The magnesium concentration in cells is much higher than that in plasma, so patients having a high rate of cellular hemolysis are also at risk.

The toxic effects of magnesium are inherently linked to the levels (mEq/liters) that are found in the serum. As magnesium levels rise, different symptoms start to manifest, and the fatality of those symptoms is proportional to the levels of magnesium found, fatality increases if magnesium level increases.

Levels that are greater than 2.2 mEq/L (or greater than 1.1 mmol/L) are diagnostic for hypermagnesemia. Minor side effects seen early on in hypermagnesemia include flushed skin, nausea or vomiting, and generalized muscle weakness.

However, as magnesium levels increase, the muscle weakness progresses to loss of deep tendon reflexes and, eventually, flaccid paralysis that can cause respiratory compromise.

Further complications include those in the cardiovascular system, beginning with hypotension and bradycardia. If magnesium levels remain uncorrected, this can lead to a complete heart block and, subsequently, cardiac arrest.

Factors that increase the risk for Magnesium toxicity:

  • Patients with chronic kidney disease
  • Patients on dialysis
  • Patients undergoing cancer treatment
  • Women receiving preeclampsia treatment

The treatment of magnesium toxicity begins with the discontinuation of all magnesium-containing supplements and medication to ease the symptoms of hypermagnesemia. In severe cases, intravenous calcium gluconate can be used to displace and neutralize the effects of magnesium.

However, definitive treatment requires a reduction of magnesium levels within the body. In patients with normal kidney function, this is achievable through intravenous diuretics. For patients with impaired kidney function, dialysis treatment is very necessary.

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