Magnesium is a vital mineral that is essential for numerous bodily functions, playing a key role in various biochemical and physiological processes. Its deficiency is a serious health concern, as it can lead to a wide range of issues affecting the nervous system, muscles, bones, heart, metabolism, and overall well-being. Despite its importance, the clinical significance of hypomagnesemia is often underappreciated due to subtle symptoms, lack of routine screening and the overlap with other conditions, making it difficult to diagnose early and address effectively.
This article examines the role of magnesium in the body, the causes of magnesium deficiency and how to identify it.
Role of magnesium in our body
Magnesium (Mg) is a co-factor for over 300 enzymes in the human body, making it an essential mineral for regulating a wide variety of biochemical reactions.1 Notably, approximately 90% of total body magnesium is stored in the muscles and bones, with around 27% found in the muscles and 63% in the bones. Most of this magnesium is bound, with only a small fraction (10%) being free. In the serum, magnesium is primarily bound to proteins, with around 32% bound to albumin. The remaining 55% exists in its free form, which is biologically active and available to participate in enzymatic processes.2 At birth, the human body contains approximately 760 mg of magnesium, and this amount increases to around 5 grams by 4 to 5 months of age. The total magnesium content in the body varies between 20 and 28 grams in adults, with the majority of it stored intracellularly.3
Some of the key functions of magnesium include:
1. Maintaining Ionic Gradients:2
Magnesium helps regulate ionic gradients like low levels of intracellular sodium and calcium levels while promoting high potassium levels inside the cell. This is vital for maintaining cellular function and electrical activity, particularly in nerve and muscle cell
2. Cellular and Tissue Integrity:2
Magnesium contributes to the structural integrity of cell membranes and tissues. It helps to stabilize cell membranes and protects against oxidative stress, ensuring proper cellular function and preventing damage.
3. Mitochondrial Oxidative Phosphorylation:2
Magnesium plays a pivotal role in mitochondrial function, supporting ATP production and activation, which is essential for energy generation in cells.
4. DNA, RNA and Protein Synthesis: 2
Magnesium is integral to the synthesis and stabilization of DNA and RNA, which are vital for cellular growth, replication and repair. It also plays a crucial role in protein synthesis, helping enzymes catalyze the formation of amino acid chains.
5. Neurological Function:1
Magnesium helps to regulate nerve transmission and muscle contraction, contributing to normal brain function, mood regulation and preventing excessive nerve excitability.
6. Bone Health:1
Magnesium helps to regulate calcium levels in bones and teeth, contributing to bone mineralization and strength, supporting skeletal health.
7. Blood Sugar Regulation:1
Magnesium aids in the regulation of insulin and blood sugar levels, playing a role in reducing the risk of developing type 2 diabetes.
8. Cardiovascular Health: 1
Magnesium is essential for maintaining a healthy heart rhythm and regulating blood pressure. It helps prevent arrhythmia (irregular heartbeats) and supports overall cardiovascular health.
9. Immune System Support:1
Magnesium plays a crucial role in modulating immune responses. It helps in regulating the production of inflammatory markers and supports the functioning of immune cells. A sufficient magnesium level is essential for a well-balanced immune system, aiding the body’s defense against infections and promoting overall health.
Therefore, magnesium consumption is essential for overall health. The average daily magnesium intake recommended to meet the nutrient requirements of nearly all healthy individuals, based on age is as follows:
Therefore, magnesium consumption is essential for overall health. The average daily magnesium intake recommended to meet the nutrient requirements of nearly all healthy individuals, based on age is as follows:
Birth to 6 months: 30 mg
7–12 months: 75 mg
1–3 years: 80 mg
4–8 years: 130 mg
9–13 years: 240 mg
14–18 years (Male): 410 mg: (Female): 360 mg
19–30 years (Male): 400 mg: (Female): 310 mg
31–50 years (Male): 420 mg: (Female): 320 mg
51+ years (Male): 420 mg: (Female): 320 mg4
During pregnancy, the recommended intake of magnesium is around 360–400 mg per day, while during lactation, it is around 320–360 mg per day.4
What is Magnesium Deficiency?
The normal serum magnesium levels are typically between 1.46 and 2.68 mg/dL, which indicates the optimal amount of magnesium circulating in the blood for proper bodily function. ‘Magnesium deficiency or Hypomagnesemia’ is a condition characterized by low levels of magnesium in the blood, specifically when the serum magnesium level falls below 1.46 mg/dL. In most cases, symptoms do not appear until magnesium levels fall below 1.2 mg/dL (0.5 mmol/L). At this point, the deficiency becomes more pronounced and the body starts to show signs of magnesium insufficiency.5
Causes of Magnesium Deficiency
Magnesium deficiency can result from various factors including inadequate dietary intake, gastrointestinal and renal losses, certain medications and metabolic conditions.
1. Inadequate Dietary Intake:6
Diets low in magnesium can contribute to deficiency, particularly in individuals consuming processed foods with minimal magnesium content.
2. Alcoholism:7
Chronic alcohol consumption is a well-recognized cause of magnesium deficiency due to multiple contributing factors like poor dietary intake of magnesium, increased urinary magnesium excretion, gastrointestinal disturbances such as vomiting and diarrhea, and alcohol-induced renal magnesium wasting.
3. Calcium Administration and Vitamin D intake:7
Excessive calcium intake or intravenous calcium administration can induce magnesium deficiency by altering magnesium homeostasis. Both hypocalcemia (low calcium levels) and hypercalcemia (high calcium levels) can influence magnesium levels, but hypercalcemia is more likely to cause magnesium deficiency due to its effects on kidney function and magnesium homeostasis. Calcium supplementation may lead to magnesium deficiency by competing for absorption in the intestines. Similarly, excessive vitamin D intake can intensify magnesium depletion by enhancing calcium absorption, which may also raise the risk of arterial calcification.2
4. Stress:8
Subclinical or moderate magnesium deficiency, if prolonged, can contribute to inflammatory stress and various physiological disturbances. Magnesium plays a crucial role in regulating inflammatory pathways and its deficiency has been linked to increased oxidative stress, elevated levels of pro-inflammatory cytokines (such as TNF-α and IL-6) and heightened stress responses.
5. Aging and Magnesium Deficiency:9
Hypomagnesemia is more common in elderly individuals due to their reduced dietary intake, diminished intestinal absorption, increased urinary magnesium excretion and drug interactions that contribute to magnesium loss.
6. Gastrointestinal (GI) Causes:
Since magnesium is primarily absorbed in the intestines, any condition that disrupts its absorption or increases its loss through the GI tract can lead to deficiency. These include protein-calorie malnutrition, failure of gastrointestinal absorption, long-term administration of magnesium-free iv fluids or total parenteral nutrition (TPN) without adequate magnesium supplementation, chronic diarrhea & steatorrhea, short bowel syndrome & bowel fistulas, continuous removal of gastric contents via nasogastric tubes, rare genetic disorders like primary familial magnesium malabsorption. 10
7. Renal (Kidney-Related) Causes:10
The kidneys play a crucial role in magnesium balance. Certain renal conditions can cause excessive magnesium loss through urine including Bartter’s & Gitelman’s Syndrome, increased urination following the relief of a urinary obstruction (Post-Obstructive Diuresis), Post-Acute Tubular Necrosis (ATN), Renal Transplantation (due to altered kidney function or immunosuppressive medications), Interstitial Nephropathy.
8. Drug-Induced Magnesium Wasting:
Certain medications can interfere with renal magnesium reabsorption, increasing urinary magnesium excretion. These include Diuretics (Loop & Thiazide Diuretics), Aminoglycoside Antibiotics (e.g., Gentamicin, Amikacin), Cisplatin, Pentamidine, Foscarnet, Proton pump inhibitors, Amphotericin B, Digitalis, Cyclosporine, Cetuximab, Matuzumab, Panitumumab. (5,10)
9. Diabetes Mellitus:10
Magnesium deficiency is frequently observed in diabetic patients, especially those with poor glycemic control. High blood glucose levels cause osmotic diuresis (excessive urination), leading to increased magnesium excretion. Insulin resistance may also further impair cellular magnesium uptake.
Signs and Symptoms of Magnesium Deficiency
A deficiency in magnesium can cause a wide range of signs and symptoms. These can vary from mild to severe, depending on the degree of deficiency.
Early signs 4
Loss of appetite
Nausea
Vomiting
Fatigue
Weakness
Moderate magnesium deficiency 4
Numbness
Tingling
Muscle contractions and cramps
Seizures
Personality changes
Abnormal heart rhythms
Coronary spasms
Severe magnesium deficiency 4
Hypocalcemia (low calcium levels)
Hypokalemia (low potassium levels)
1. Metabolic and Electrolyte Imbalances:11
a. Altered glucose metabolism: Increased insulin resistance, higher risk of type 2 diabetes.
b. Electrolyte imbalances: Can cause hypokalemia (low potassium levels) and hypocalcemia (low calcium levels) due to disrupted mineral regulation.
2. Cardiovascular Complications:11
a. Arrhythmias, including:
Atrial tachycardia and fibrillation
Supraventricular and ventricular arrhythmias
Torsades de Pointes (a life-threatening arrhythmia
b. Myocardial infarction (heart attack)
c. Atherosclerosis: Increased arterial stiffness and plaque buildup, raising cardiovascular disease risk.
d. Hypertension (high blood pressure)
3. Neuromuscular Hyperexcitability:11
a. Tremors and fasciculations (muscle twitching)
b. Tetany (involuntary muscle contractions)
c. Seizures and convulsions
d. Neuropsychiatric changes, including:
Apathy
Depression
Psychosis
Vertigo
Nystagmus (involuntary eye movements)
Athetoid and choreiform movements (involuntary, writhing, or jerky movements)
e. Migraine headaches
f. Asthma (reactive airway dysfunction)
g. Impaired exercise performance
4. Bone and Kidney Effects:11
a. Osteoporosis: Increased bone fragility due to impaired calcium and vitamin D metabolism.
b. Kidney stones: Magnesium plays a role in preventing calcium oxalate stone formation.
5. Other Complications:11
a. Rhabdomyolysis: Breakdown of muscle tissue, leading to kidney damage.
b. Hemolysis: Destruction of red blood cells.
c. Enhanced apoptosis: Increased programmed cell death, which may contribute to neurodegenerative and cardiovascular diseases.
d. Enhanced digoxin sensitivity: Increased risk of toxicity in patients taking digoxin for heart conditions
Laboratory Tests
In a patient suspected of having hypomagnesemia, the following should be checked.
1. Serum Magnesium Levels:12 A low serum magnesium level suggests a deficiency, but it is not always a reliable marker, as only about 1% of the body’s magnesium is found in the blood. (Normal value ranges can indeed vary slightly between different laboratories due to factors like testing methods, equipment, and population differences).
2. Red Blood Cell Magnesium Test: 12 This test measures magnesium concentration in red blood cells and may give a better reflection of magnesium status in the body than serum levels.
3. Urinary Magnesium Excretion: 12 A 24-hour urine test can be done to check magnesium excretion. Low urinary magnesium excretion may indicate magnesium deficiency.
4. Electrocardiogram (ECG):13 The ECG findings seen with magnesium deficiency often resemble those seen in hypokalemia, as both conditions can affect cardiac conduction. Common ECG abnormalities associated with magnesium deficiency include prolonged PR interval, prolonged QT interval, increased QRS duration and ST-segment abnormalities.
Additionally, similar to hypokalemia, magnesium deficiency increases the risk of arrhythmias, especially in patients taking cardiac glycosides (e.g., digoxin). This is because magnesium plays a key role in maintaining normal electrolyte balance and cardiac function. A deficiency in magnesium can enhance the toxic effects of cardiac glycosides, leading to arrhythmias. Therefore, correcting magnesium deficiency is essential in patients receiving such medications to prevent complications.
5. Additional Testing:
a. Calcium and Potassium Levels: Deficiencies in magnesium can also cause imbalances in calcium and potassium levels. These are often measured to support the diagnosis.
b. Parathyroid Hormone (PTH) Levels: Low magnesium can lead to increased PTH secretion, which can further contribute to calcium imbalances.
Conclusion
Magnesium is a fundamental mineral involved in numerous physiological functions, from maintaining cellular integrity to regulating neuromuscular and cardiovascular health. Magnesium deficiency can be challenging to diagnose due to its non-specific symptoms. The symptoms often overlap with other conditions, which can make it difficult to pinpoint magnesium deficiency as the cause. Left untreated, it can lead to severe metabolic imbalances, cardiovascular disorders, neuromuscular dysfunction and long-term complications such as osteoporosis and insulin resistance.
Recognizing the risk factors, early symptoms and potential complications of magnesium deficiency is crucial for both healthcare providers and the general population. Routine monitoring, dietary adjustments and appropriate supplementation can help to prevent and manage this condition effectively. By increasing awareness and prioritizing magnesium intake, we can significantly enhance overall health and well-being, reducing the burden of associated chronic diseases.
References:
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