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    We know magnesium as a micromineral. But this micromineral is not an ordinary one.

    Magnesium is the fourth most abundant cation forming mineral in the body. It is found in several items of our daily dietary intake, and its deficiency is a rare occurrence. But what’s unique about this mineral is that its deficiency and its signs and symptoms are quite scary and serious, unlike many other minerals.

    Another important aspect of this mineral is that it is not only known for oral magnesium supplementation but also as a medicine. Some emergency conditions such as eclampsia in pregnancy and heart rhythm abnormality use magnesium as the first line of therapy.

    In this article, we will be looking at the health benefits of using Mg supplements, their dosage, side effects, and contraindications. And also see how Mg and its various forms are used as medicines.


    Physiological Roles of Magnesium

    The human body contains almost 25 grams of Mg. More than 60 percent of the total Mg content resides in the bones, and the rest is found in the connective tissue such as skin and joint cavities. Only about 1 percent magnesium is present in the blood serum or extracellular fluid.

    This 1 percent is more crucial than you can imagine. It is involved in various biochemical processes that are essential for life by acting as a mandatory cofactor. More critical and life-saving mechanisms that use Mg include:

    • Synthesis of DNA and RNA
    • Working on the antioxidant agents
    • Mg facilitates the opening of the calcium channels to produce an action potential in contractile cells. This is the major mechanism behind nerve impulse conduction, muscle contraction, the spontaneous heart rhythm, and the functioning of the neuromuscular junctions.
    • Magnesium salts concentrate in the bones with calcium and phosphates and provide strength to the skeleton of the body.
    • Magnesium creates energy by the activation of adenosine triphosphate (ATP) and ensuring the availability of energy for the cellular processes.


    Mg Plays a Central Role in Energy Production

    If Mg does not enter the mitochondria due to its low levels, availability, or impaired transport mechanisms, the energy production in the cell cannot proceed.

    Mg acts as a cofactor for three main and most important enzymes involved in the cellular respiratory processes:

    • Isocitrate dehydrogenase
    • Oxoglutarate Dehydrogenase
    • Pyruvate Dehydrogenase

    Magnesium forms a complex with isocitrate compounds and acts as a stimulator of these enzymes.

    Besides, what we call ATP is Mg-ATP. ATP is the central molecule involved in energy production, use, and transport. But it cannot perform its function without its essential element, magnesium. Until or unless the Mg atom attaches to the ATP molecule, no cell can use and transport energy.

    The channel that transports magnesium ions into the mitochondria is named as MRS2 channel. Research with controlled trials reveals that when these channels are knocked off or impaired in a cell, the level of metabolites associated with the energy production cycle decrease. This shows that energy production is severely impaired in the absence of magnesium.

    Magnesium plays several essential structural roles in the body as well. But its role in the production of energy defines the health benefits of magnesium supplementation for the human body.


    Health Benefits of Taking Magnesium Supplementation

    A systematic review and meta-analysis of various studies establish that oral magnesium supplementation according to the recommended 360 mg/day can have various health benefits for health as well as diseased individuals.

    Magnesium Intake Enhances Brain Health and Function

    The brain constitutes only 2 percent of body weight and uses almost 20 percent of the total energy consumption by the body. This shows the survival-level importance of the energy-producing mechanisms for brain health and functioning.

    Interestingly enough, magnesium intake has brain health roles apart from energy production as well. Research scientist Sara Adaes analyses the role of magnesium levels in nerve conduction and neurotransmitter function. This comprehensive review tells us that magnesium directly facilitates neuronal processes by regulating the activation of N-methyl D-aspartate glutamate (NMDA glutamate) and GABA (gamma-aminobutyric acid) receptors, associated with a lower risk of brain disorders.

    Since Mg is also involved in regulating the ion channels and producing an action potential, the depolarization or activation of brain cells also depends on the availability and normal functioning of magnesium.

    All these mechanisms directly contribute to enhanced memory and learning. Also, patients with neurological disorders such as Parkinson’s exhibit low levels of Mg. Its supplementation may improve cognition and dementia in such patients. This is another test result that indicates the importance of magnesium citrate in normal cognition, memory, and brain health.

    According to Taiwan’s National Health Research Institute (NHRI) Database, individuals who used magnesium oxide supplements were less likely to develop dementia and slowing of cognition with age.

    Magnesium Maintains a Healthy Heartbeat

    Magnesium intake maintains a healthy heartbeat by regulating the neuronal discharge in the pacemaker nodes of the heart. Firstly, the sodium-potassium pump is directly involved in the generation of the action potential. In the same way, calcium channels open and conduct the action potential passively.

    These two ion channels are the backbone of the action potential or the pacemaker current in the heart. Mg directly activates the sodium-potassium pump. At the same time, the calcium channels are counteracted by magnesium. In this way, Mg is not only important in the generation of the action potential but also prevents its overexcitation.

    Magnesium sulfate helps the heart muscle relax by counteracting the calcium channels, which then stimulates the contraction of the heart musculature. So, the whole heartbeat cycle works alongside the normal serum level and working of Mg.

    This also explains the increased risk of irregular heartbeat disorders in individuals with magnesium deficiency. According to a systematic review and meta-analysis of research published in the cardiology research and practice, low levels of Mg in the blood are associated with an increased risk of developing cardiovascular disease along with arrhythmias and atrial fibrillation.

    Anti-inflammatory Effect of Magnesium Supplementation

    Optimum magnesium concentrations help with the normal anti-inflammatory functions of the body. A systematic review and meta-analysis of a study conducted in 2017 with overweight women revealed anti-inflammatory effects of magnesium supplements.

    Biomarkers of inflammation, mainly the C-reactive protein (CRP), significantly reduced at the end of the eight-week study period. Inflammation is the major underlying factor involved in the progression of conditions such as cardiovascular disease, metabolic syndrome, diabetes mellitus, arthritis, and gout.

    Another important observation is the reduction of interleukin-6 levels in the blood after an eight-week supplementation with magnesium sulfate. these observations indicate that maintaining normal Mg levels in the blood can help reduce the risk of various chronic diseases and also help manage them.

    Magnesium Intake helps Improve PMS

    Premenstrual syndrome (PMS) is a major issue among women of child-bearing age. Women who maintain normal magnesium levels with supplements and natural food sources show a lesser intensity of PMS and its major signs such as anxiety, nausea, cramps, and depression.

    Besides, magnesium sulfate has been known to decrease the level of prostaglandins in the blood, which are the main mediators of period pains. Mg is also known as a natural relaxant as it relaxes the uterine muscles and relieves menstrual cramps.

    Some women even experience menstrual migraine episodes, for which, as discussed above, magnesium supplements are effective in various mechanisms. Inadequate dietary magnesium intake actually triggers excessive muscle contractions, which result in muscle cramps and spasms.

    The best form of magnesium supplement for PMS is magnesium glycinate. It absorbs well and does not cause diarrhea. At the same time, it lowers blood pressure which again gives a relaxant effect during menstruation.

    Roles of Magnesium Sulfate in Bone health

    Mg is one of the most important minerals involved in bone strength and health. People with higher magnesium intakes have a high bone mineral density and exhibit a reduced risk of developing osteoporosis at a later age and fractures in general. Because magnesium supplements directly increase bone mineral density.

    Osteoporosis is a major concern in postmenstrual women. And lifestyles such as reduced physical activity and alcoholism increase the risk of this condition in the general population. Research suggests better outcomes with osteoporosis preventive strategies than treatment therapies.

    A major preventive factor here is dietary intervention, especially vitamin d, calcium, and magnesium supplementation.

    Magnesium loss or decreased magnesium dietary intake rapidly results in hypomagnesemia. To maintain normal serum Mg, bones dissolve and release magnesium from the salts. This results in demineralization of bones, resulting in weak bones.

    This, when superimposed with the loss of estrogen in postmenstrual women, increases the risk of fractures and osteoporosis.

    Another mechanism by which magnesium deficiency causes weak bones is by inducing inflammatory cytokines that stimulate the remodeling and dissolving of the skeleton.

     Loss of mineral density in bones is very common in patients with chronic kidney disease. And one reason for this is the loss of Mg in the urine.

    Effect of Magnesium Supplementation in Maintaining Healthy Blood Sugar Levels

    Inadequate levels of dietary magnesium have been associated with insulin resistance and an increased risk of developing type 2 diabetes mellitus. Since type 2 diabetes mellitus roots in insulin resistance with a genetic predisposition and a sedentary lifestyle, its risk can be reduced with some dietary modifications. One of these is taking magnesium supplements daily.

    In addition to improving the response to insulin by the cells, Mg slows down the inflammatory processes going on alongside, which worsens the condition progressively.

    If the disease has already set in, magnesium intake can help with blood sugar control. Besides, magnesium supplements are important in patients with diabetes mellitus because the following cascade lowers the Mg levels in the blood, which can give rise to various conditions:

    When the blood sugar level is high, the kidneys reduce the rates of reabsorption in the tubules and increase urinary excretion to get rid of excess glucose. But along increases the urinary magnesium excretion in poorly controlled diabetes. Reduced levels of Mg predispose the patient to cardiovascular disease and muscle weakness, as discussed before.

    Magnesium supplements improve the response of the cells of the body to insulin and increase the uptake of glucose by the cells, hence improving insulin sensitivity. Patients with diabetes mellitus also have an increased rate of magnesium excretion. it is important to assess magnesium status before prescribing them the right, effective dose.

    Magnesium Citrate can Help Improve Exercise Tolerance

    Magnesium intake has been shown to decrease the biomarkers of muscle damage and injury in the blood. by improving muscle function and performance, magnesium increases tolerance for exercise strenuous physical activity.

    Healthy muscle tissue can get rid of lactic acid, and other muscle waste efficiently and hence tolerates exercise better and for longer.

    A study with almost 3000 women displayed beneficial effects of magnesium in improving muscle mass and power in the subjects who took the supplement.

    Also, by enhancing insulin sensitivity, magnesium increases the use and uptake of glucose by the working muscle cells to produce more energy.

    After a workout, magnesium also helps counteract the stimulant role of calcium. By causing muscle relaxation, magnesium relieves sore muscles.

    Magnesium Promotes Better Sleep and Relieves Anxiety

    Magnesium is directly involved in the neurotransmitter functions in the neural pathways of the brain. The main transmitter that connects with the magnesium balance is GABA. GABA is an inhibitory neurotransmitter, and the same is true for its receptor. These are hence involved in inducing sleep.

    Another mechanism of sleep-induction by magnesium is muscle relaxation. Magnesium supplements relax the muscles of the body and relieve anxiety and depression as well.


    Medicinal Uses of Magnesium

    Mg is a mineral widely used in pharmacy and medicines for the treatment of various diseases and conditions, sometimes in life-saving emergencies.

    Neurological Disorders

    Two major neurological disorders linked with magnesium supplementation are migraine and depression. NMDA receptors and abnormal mitochondrial function have repeatedly shown their connection with pain transmission and cortical spreading depression. And Magnesium is the main regulator of these receptor channels in the brainstem and is involved in the main energy-producing process of the mitochondria.

    A systematic review and meta-analysis involving migraine patients supplemented with magnesium established that normal magnesium levels reduced the frequency of migraine episodes by 20-40 percent.

    Though animal studies suggest a link, patients of epilepsy and Parkinson’s have shown minor differences in the levels of magnesium with the controls in human research. Patients of stroke and Alzheimer’s, however, report lower levels of magnesium and also exhibit better outcomes when supplemented with magnesium.

    Magnesium is used as a Laxative

    Common forms of magnesium that act as osmotic laxatives include magnesium citrate, magnesium hydroxide, magnesium oxide, and magnesium sulfate. These increase the water levels in the stools and thus help the hard stools pass through the gut easily.

    Dietary magnesium intakes in various forms can hence treat constipation without any major side effects.

    Magnesium is used as an Antacid

    Magnesium hydroxide is used along with aluminum hydroxide as an antacid to relieve heartburn due to stomach acid reflux, acid indigestion, and generally upset stomach.

    This combination can safely be used in any condition characterized by increased acid, such as gastric hyperacidity, peptic ulcer, gastritis, esophagitis, or hiatal hernia. Magnesium hydroxide combines and neutralizes the excess acid and alleviates the symptoms.

    Magnesium oxide is another magnesium salt effective against acid indigestion and constipation.

    Intravenous Magnesium is first-line therapy for torsades de pointes

    Torsades de pointes is an abnormality of the electrical rhythm of the heart along with many other conditions such as tinnitus and is exhibited as the prolongation of the QT interval on the ECG.

    Intravenous magnesium therapy is the first-line treatment for a patient who presents with this fatal arrhythmia. Major risk factors for torsades are hypomagnesemia, hypercalcemia, old age, genetics, and some heart stimulant drugs such as digoxin.

    Two grams of magnesium sulfate are administered initially to rectify this emergency. Magnesium inhibits the calcium channels and terminates arrhythmia.

    Magnesium Sulfate acts as a Bronchodilator

    Magnesium sulfate is a natural stimulant that can help relax the airways and help them respire better. Intravenous magnesium sulfate does this by the relaxation of the muscles of the bronchi.

    Intravenous or inhaled magnesium sulfate has shown remarkable results in combating the sudden flares of asthma but has not yet gotten the status of a first-line drug.

    Magnesium Sulfate for Complications of Pregnancy

    Major life-threatening complications of pregnancy are eclampsia and preeclampsia. These conditions are characterized by high blood pressure and renal failure. This fatal emergency can cause the deaths of both the mother and the child.

    Normal serum magnesium concentrations help regulate systolic and diastolic blood pressure and protect against the complications of pregnancy. Pregnant and breastfeeding mothers should consult a physician for safe adjusted doses of magnesium supplements as they usually take many other supplements and medications as well.

    Intravenous magnesium sulfate or magnesium carbonate can help revive a patient with eclampsia immediately. They are afterward prescribed dietary supplements to maintain an adequate intake of magnesium.


    Signs of Magnesium Overdose

    Too much magnesium is not safe, whether as a magnesium supplement or from natural sources. Research and studies are non-concluding. Higher dietary magnesium intakes have been tested, but taking 350 mg of magnesium a day has shown signs and symptoms of magnesium overdose in some individuals.

    Hypermagnesemia is an electrolyte overload disorder that can alter the functioning of the ion channels that produce nerve impulses. The signs and symptoms of excess magnesium include:

    1. Neuronal inhibition and excessive lethargy
    2. Dangerously low blood pressure that a person can lose consciousness and fall
    3. An irregular heartbeat or arrhythmia
    4. Slowed breathing, dyspnea, and coma
    5. Muscle weakness
    6. Urine retention
    7. Nausea, vomiting, and muscle cramps
    8. Excessive gut motility that results in diarrhea
    9. Cardiac arrest or heart block may occur in susceptible individuals


    Signs and Symptoms of Magnesium Deficiency

    Mg deficiency manifests as the following signs and symptoms:

    1. Since magnesium is involved in the major energy-producing processes in the cell, its deficiency can result in weight gain and severe body and muscle weakness.
    2. In the presence of low magnesium levels, calcium channels go unchecked. Their overexcitation can result in dangerous ventricular tachycardia and fibrillation and another condition called torsades.
    3. Magnesium is also involved in the generation of action potentials and depolarization of the ion channels. Magnesium deficiency will result in excessive sleepiness, lethargy, and depression.
    4. Low levels of magnesium have often been associated with an increased risk of developing high blood sugar levels and hence type 2 diabetes mellitus.
    5. Magnesium deficiency can also stimulate the bone cells to release their phosphate and magnesium compounds to maintain a normal serum concentration. This will result in bone weakness and an increased risk of fractures.
    6. Severe muscle weakness will set in. this may also result in tremors and muscle spasms.
    7. Pregnant women with a magnesium deficiency may experience pre-term diabetes and high blood pressure. Assessing magnesium status is of prime importance in pregnancy.


    Who is at Risk of developing Magnesium Deficiency?

    The following groups are at high risk of developing severe magnesium deficiency and should use magnesium supplements with the advice of a physician:

    Type 2 Diabetes Mellitus

    Patients of type 2 diabetes mellitus have an increased rate of urination and reduced reabsorption due to high blood sugar levels. Increased urination takes important minerals and salts, such as magnesium.

    Gastrointestinal Disease

    Any gastrointestinal disorder that impairs adequate magnesium absorption and other minerals and salts from food can also result in magnesium deficiency. Major culprits in such a scenario are Crohn’s disease, enteritis, gluten-sensitive enteropathy, or any inflammatory condition of the intestine. Malabsorption of fat due to any pathology can also result in magnesium loss and deficiency.


    Renal magnesium excretion increases with age, and dietary magnesium intake and absorption decrease. To maintain normal serum magnesium levels, magnesium therapy becomes essential in old age.

    Alcohol Disorder

    People with chronic alcoholism experience a whole syndrome of disorders that collectively result in renal and fecal loss, malabsorption, and loss of function of magnesium in the body.

    These conditions include gastrointestinal problems, poor dietary magnesium intake, vitamin d deficiency, liver problems, renal dysfunction, diarrhea, and steatorrhea (loss of fats and lipids in the feces) resulting from pancreatitis.


    Recommended Dietary Allowance RDA for Magnesium

    The food and nutrition board has published dietary reference intakes for minerals, vitamins, and primary and minor nutrients. The safe recommended dietary allowance for magnesium is as follows:

    Tolerable upper intake level for children aged between 1 and 3 years has been placed below 80 mg/day. For kids ages between 4 and 8 years, the safe magnesium dosage lies below 130 mg/day. For pre-teens or kids below age 13, recommended allowance is below 240 mg/day.

    For adults, as discussed above, magnesium dosages higher than 360 mg/day are not safe. High doses have been tested safely, but the same has shown side effects in some individuals.


    Natural Food Sources of Magnesium

    You can always use magnesium supplementation, but poor dietary intake can always pull you back. Here are some magnesium-rich foods that will help you replenish your serum magnesium concentration and enjoy sound health:

    • Whole grains
    • Green leafy vegetables such as spinach
    • Nuts and legumes
    • Flaxseed and pumpkin seeds
    • Dark chocolate
    • Fatty fish such as salmon
    • Bananas

    Fortified foods are good sources of magnesium chloride and elemental magnesium. A rich, healthy diet consisting of the above sources will provide enough magnesium to maintain a healthy bone mineral density and protect you against heart disease. Controlled trials have also shown that taking more magnesium is associated with a lower risk of stroke and high blood pressure.


    Drug Interactions of Magnesium Supplements

    1. Patients with severe heart problems such as atrial fibrillation and who use digoxin have low levels of magnesium. Digoxin reduces the tubular reabsorption of magnesium in the kidneys and is a risk factor for causing magnesium depletion. Magnesium levels in the serum have to be monitored in such patients. You may want to increase the dose of magnesium supplements in this case.
    2. Taking magnesium supplements can cause the systolic blood pressure to fall too low. This may result in loss of consciousness, and the person may faint and fall.
    3. Magnesium might decrease the absorption of some antibiotics by the body. That’s why these drugs should not be taken too close. Always wait at least 2 hours after taking magnesium supplements.


    The Bottom Line

    Randomized controlled trials have shown the effect of magnesium on inflammatory conditions such as metabolic syndrome and diabetes and cardiovascular disease hypertension. Incorporating Mg supplements in your daily routine can improve your overall health and are associated with a lower risk of developing chronic conditions.

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