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Magnesium is a crucial macronutrient that is indispensable for the proper functioning of all bodily systems. Insufficient intake of this nutrient primarily impacts the nervous system, leading to a decline in cognitive abilities, headaches, psychological disorders, and cardiac issues. We elucidate the effects of magnesium deficiency on the nervous system and offer preventive measures to mitigate such deficiencies.
The mechanisms of magnesium’s impact on the nervous system
Magnesium serves as a crucial co-factor for over 300 enzymes involved in essential reactions throughout the body, including energy and carbohydrate metabolism, protein and nucleic acid synthesis, and regulation of vascular tone. It is present in all tissues, with a significant proportion, around 98%, located inside cells, particularly in bone tissue, while less than 2% is found in the extracellular space.
The nervous system is especially vulnerable to changes in magnesium levels, and its deficiency can cause a range of neurological manifestations, from reduced stress resistance and headaches to the development of psychopathologies and brain degeneration.
Magnesium contributes to the normal functioning of the nervous system through several mechanisms. These include:
- Participation in the synthesis of ATP, which provides energy for neurons and other cells, by aiding in the production of ATP in the mitochondria.
- Control of the influx of calcium into neurons. Magnesium ions block the calcium channels of glutamate NMDA receptors on the surface of nerve cells. A deficiency of magnesium can result in the hyperactivity of NMDA receptors, which allows too much calcium to enter nerve cells, causing damage and neuronal death. This hyperactivation of NMDA receptors is observed in many neurological disorders and psychopathologies, such as migraines, Alzheimer’s disease, stroke, anxiety disorders, and depression.
- Regulation of the hypothalamic-pituitary-adrenal axis (HPA), which is the foundation of the neuroendocrine system responsible for mood, emotions, and stress response. Magnesium deficiency leads to HPA overstimulation, resulting in hormonal and behavioral disorders and the development of pathological anxiety.
- Reduction of the level of pro-inflammatory cytokines, which cause neuroinflammation and neuronal death.
- Sustains the physiological impact of brain-derived neurotrophic factor, a protein that supports the growth and survival of nerve cells.
In addition, magnesium aids in promoting the wellbeing and variety of the microbiota. The gut-brain axis interconnects the gastrointestinal tract, gut microbes, and the central nervous system. A healthy and diverse microbiome contributes to the proper functioning of the brain, decreases the possibility of developing mental disorders, and lowers the risk of dementia.
Two medical terms are associated with magnesium deficiency in the body: hypomagnesemia and magnesium deficit. Hypomagnesemia is diagnosed when the level of magnesium in the blood serum is <0.7 mmol/L. The term “magnesium deficit” means that the intracellular magnesium depot is depleted. Blood analysis may be insufficient to detect magnesium deficiency because it does not reflect the magnesium content in tissues. A comprehensive diagnosis requires an assessment of symptoms and determination of magnesium content in other biosubstrates (urine, hair, nails, saliva).
Tests that determine the magnesium level in erythrocytes and plasma are more accurate than those that determine it in blood serum. Plasma, unlike blood serum, contains formed elements and proteins. A magnesium level in plasma or erythrocytes of less than 0.8 mmol/L is a provocateur of chronic diseases.
Magnesium deficiency and stress
There exists a reciprocal association between stress and magnesium deficiency. Prolonged stress causes magnesium deficiency. When an individual experiences stress, it triggers the sympathetic-adrenal system and the adrenal cortex produces adrenaline and noradrenaline actively. The excessive release of these hormones causes magnesium to be released from cells and eliminated through urine. The lack of magnesium, in turn, reduces an individual’s ability to resist stress.
Chronic stress, in combination with magnesium deficiency, may lead to psychophysiological syndrome – a malfunction of the autonomic nervous system which causes pathological anxiety, insomnia, and disruptions in the functioning of the heart and respiratory organs.
For children, chronic stress has a detrimental impact on their well-being. Persistent emotional strain places an immense burden on their undeveloped psyche. The ramifications of chronic stress in children may include neurotic disorders, headaches, asthma, neurodermatitis, enuresis, and stuttering. If the stress level surpasses a child’s adaptive capabilities, it may cause malfunctions in the adrenal glands and the immune system.
When children experience emotional tension and are deficient in magnesium, it can worsen the effects of stress on their bodies. This deficiency can lead to a decrease in cognitive function, convulsive seizures, impaired coordination, and increased blood pressure.
However, restoring a normal magnesium status can alleviate these symptoms and enable the child to manage stress without adverse physical or mental health consequences. One of the mechanisms behind magnesium’s ability to reduce stress and depression is the activation of B6-dependent proteins that help maintain the normal functioning of the nervous system.
Magnesium deficiency can trigger headaches.
Magnesium deficiency contributes to the development of headaches and migraines, including menstrual migraines that occur due to fluctuations in estradiol levels during menstruation. Cluster headaches can also be triggered by magnesium deficiency, and their attacks can be extremely painful, sometimes leading to suicidal behavior.
The level of intracellular nitrogen is regulated by magnesium, and elevated nitrogen levels can lead to the development of pain syndrome. Normalizing magnesium levels can reduce the frequency, duration, and severity of headache attacks.
The relationship between magnesium deficiency and psychopathologies
Researchers from the University of Pennsylvania conducted a meta-analysis that revealed an inverse relationship between the risk of depression and dietary intake of magnesium. Additionally, individuals with obsessive-compulsive disorder (OCD), which is characterized by intrusive and frightening thoughts that originate beyond a person’s control, exhibit deficiencies in magnesium, zinc, and iron.
In a study conducted by a team of Russian scientists on 62 patients with various psychopathologies, such as clinical depression, personality disorders, schizotypal disorders, and schizophrenia, it was found that most of the patients had low levels of magnesium in their red blood cells, despite having a normal or nearly normal level of magnesium in their blood plasma.
The magnesium levels in the blood plasma and red blood cells of patients with schizophrenia were within the normal range, which was an unusual finding. The researchers attributed this to the fact that individuals with schizophrenia typically have a disabled status and tend to remain at home, which reduces their exposure to stress that could deplete magnesium stores.
For the majority of participants, a deficiency in magnesium was associated with more severe symptoms of anxiety and depression. Administering magnesium and vitamin B6 supplements improved the patients’ mental state.
There appears to be a connection between magnesium deficiency and suicidal behavior. Low magnesium and zinc levels were discovered in the hippocampus tissues of individuals who had committed suicide, as well as overactive NMDA receptors. The limbic system, which regulates emotions, includes the hippocampus. Dysfunctions in the limbic system can result in psychiatric disorders.
The magnesium deficiency and Alzheimer’s disease
A decrease in synaptic density leading to Alzheimer’s dementia is caused by a low concentration of magnesium in the brain.
Synapses are specialized structures that enable communication between neurons in the nervous system. Although the formation of new synapses continues throughout life, the bulk of their development occurs by the end of puberty, and the number of surviving synapses, known as “synaptic density,” remains relatively stable in adulthood. However, various nervous system pathologies, including neurodegeneration of the brain, can disrupt this stability.
Magnesium levels in the brain have a significant impact on synapses, with a deficiency leading to their death. In individuals with Alzheimer’s disease, the magnesium level in the hippocampus is 18% lower than that of healthy individuals. Increasing magnesium concentration by 15% has been shown to increase synaptic density by 50%.
Low magnesium status and complications during pregnancy
The requirement for magnesium increases by at least 1.5 times during pregnancy since it is utilized by both the mother’s body and the developing fetus.
A deficiency in magnesium during gestation can lead to premature birth, neurological complications in the pregnant woman, and damage to the central nervous system of the fetus.
Magnesium deficiency results in increased neuromuscular activity, causing excessive muscle contractions that can trigger premature labor due to abnormal uterine contractility. Administering magnesium-containing drugs beginning at the 25th week of gestation significantly reduces the risk of premature birth.
Having a normal magnesium status in the mother can help protect the fetal brain from damage, which can occur due to disruption of utero-placental blood flow. Insufficient blood supply to the fetus can lead to hypoxia, increased permeability of cell membranes, and an influx of calcium into neurons, which can destroy fetal nerve cells.
Magnesium preparations are utilized in the treatment of eclampsia, a severe form of gestosis characterized by high blood pressure, headaches, severe convulsions, and loss of consciousness. This condition is the third leading cause of maternal mortality.
Seizures that occur during pregnancy can have serious consequences, including maternal death from cerebral hemorrhage, asphyxia, and pulmonary edema. Additionally, the fetus is at risk of oxygen deprivation, which can be fatal.
Magnesium plays a crucial role in maintaining normal blood pressure, cerebral circulation, and uteroplacental blood flow by suppressing the production of thromboxane A2, which constricts blood vessels. It also helps to prevent seizures and increases the level of calcitonin, which is necessary to maintain normal bone density and protect against destruction.
Using magnesium to treat eclampsia can significantly reduce the risk of maternal mortality by 50% and lower the likelihood of pneumonia and other serious complications. Magnesium-containing drugs are more effective than other anticonvulsants for the prevention and treatment of eclampsia.
Magnesium deficiency is a determinant of severe stroke
Stroke is a severe medical condition that results from a disruption in blood supply to the brain, causing death of nerve cells. During the acute phase, around one-third of patients succumb, and within a year, mortality rises to 50%. It is the primary cause of disability.
The main culprits of stroke are hypertension and atherosclerosis. The risk of the disease is higher in individuals with insulin resistance, type 2 diabetes, endothelial dysfunction, and lipid metabolism disorders. Furthermore, chronic magnesium deficiency is a significant contributor to the disruption of blood supply to the brain.
A plasma magnesium level below 0.76 mmol/L is a predictor of stroke, heart attack, and mortality from these diseases.
During the acute phase of a stroke, there is an excessive production of glutamate, the primary excitatory neurotransmitter in the brain. Under normal conditions, the body regulates glutamate levels by reducing its synthesis in response to feedback signals when too much glutamate is produced. However, during a stroke, the damaged nerve networks cause uncontrolled glutamate production, leading to the overstimulation of NMDA receptors, calcium overload in neurons, swelling, and ultimately, brain cell death.
The intensity of this mechanism is directly linked to the level of magnesium in the bloodstream: people with inadequate magnesium levels are at a higher risk of significant nerve cell destruction and heart attack fatality.
Magnesium deficiency can lead not only to a severe form of stroke but also to other diseases that can contribute to its occurrence:
- Individuals with low magnesium levels are at an increased risk of developing type 2 diabetes and insulin resistance. Hypomagnesemia is commonly observed in individuals with diabetes, and magnesium deficiency is present in around one-third of them. Elevated blood sugar levels and hyperinsulinemia, which are common in diabetes, can deplete magnesium stores in the body and decrease cell sensitivity to insulin. Replenishing magnesium levels to normal can help reduce insulin resistance and improve diabetes management.
- Insufficient levels of magnesium can lead to the accumulation of calcium in cells, which may lead to the development of vascular complications and an increase in blood pressure, known as hypertension.
- Atherosclerosis is often observed in patients with a magnesium deficiency. The intake of magnesium-containing drugs can help to improve lipid metabolism and reduce cholesterol levels.
- Magnesium has anticoagulant properties, and its deficiency increases platelet activity and the risk of thrombosis.
The relationship between recurrent depression and stroke is bidirectional. Depression can contribute to the development of stroke by elevating blood pressure, cholesterol levels, and disrupting heart function, thereby increasing the likelihood of thrombosis. Conversely, stroke can cause depressive disorder, which is a common complication.
Magnesium supplements are frequently employed in the management of post-stroke depression since they are as efficient in reducing anxiety and irritability as antidepressants.
Prevention of magnesium deficiency
The Recommended Dietary Allowance (RDA) for adults between 19-51+ years is 400-420 mg daily for men and 310-320 mg for women. During pregnancy, about 350-360 mg daily intake is required, and during lactation, 310-320 mg.
Foods that are rich in magnesium include pumpkin seeds, cocoa, sesame seeds, bran, and nuts, but they contain a lot of phytic acid which reduces the bioavailability of magnesium. Green leafy vegetables are the most reliable source of magnesium.
The main preventative measure for cerebral ischemia is maintaining normal blood pressure. Reducing high blood pressure lowers the risk of the first stroke by 32% and recurrent stroke by 30%. Magnesium intake with food affects blood pressure levels: every 100 mg of magnesium intake reduces diastolic blood pressure by 3.22 mmHg.
Magnesium is poorly absorbed in diets that are high in fat and with frequent alcohol consumption. Hypomagnesemia is observed in one-third of alcoholics. Alcoholism leads to calcium dysfunction, promoting rapid excretion of magnesium through urine.
Alcohol consumption not only lowers the level of magnesium in the body but also vitamin B6. Combined therapy with magnesium and pyridoxine is indicated:
- In chronic alcoholism and delirium tremens.
- In alcohol intoxication. Magnesium and B6 normalize brain function in alcohol poisoning.
- For people who quit drinking. Magnesium in combination with pyridoxine reduces cravings for alcohol, as well as for drugs and nicotine.
Magnesium citrate is considered the most bioavailable pharmacological form of magnesium, with a bioavailability of 33%, which can increase to 40-50% when combined with vitamin B6.
While magnesium preparations have shown positive effects, they should only be prescribed by a healthcare professional after evaluating the individual’s magnesium status and overall health indicators. It’s important to note that magnesium supplements have contraindications, and improper dosage selection can lead to side effects. It’s crucial to avoid excess magnesium intake, which can be equally dangerous as magnesium deficiency, causing symptoms such as nausea, vomiting, breathing problems, and cardiovascular complications.
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