Magnesium: The Mighty Mineral!

Magnesium, often referred to as the “mighty mineral,” plays a various role in so many physiological processes within the human body. The human body operates in a state of balance, and all components contributing to this balance play vital roles. Vitamins and minerals play a significant role in maintaining this balance. The deficiency or excess of each element can disrupt the equilibrium and lead to functional impairments.

Magnesium, a substance with crucial physiological properties essential for vital activities, participates in over 300 reactions in the body. It is recognized as the second most abundant cation in terms of intracellular quantity, following potassium as the first.

In the human body, there are approximately 20-28 grams of magnesium. About 50-60% of magnesium content is found in bones, along with calcium and phosphorus, while less than 1% is present in blood serum, and the remainder is distributed in soft tissues.

However, the primary function of magnesium lies not in bones but in the blood and muscular systems, where it constitutes approximately 40%. The symbol for magnesium is represented as “Mg.” Magnesium participates in more than 300 metabolic reactions, including ATP-dependent reactions. ATP, especially in degradation reactions, is associated with magnesium. Magnesium is involved in enzyme activations, mitochondrial ATP synthesis, insulin receptors, and the sodium-potassium (Na-K) pump.

It plays a role in the control of the calcium pump, inhibition of calcium-dependent acetylcholine release in muscle contractions, cardiac pumps, potassium control, myocardial cells, platelet aggregation, and the continuity of endothelial function. It is responsible for the intracellular balance of calcium and potassium. Magnesium is also present in bone mineralization, maintaining its structure, and in nucleic acid structures, contributing to the activation of vitamin D, thiamine, and glutathione.

Table of Contents

The Magnesium Mechanism

Magnesium is a vital mineral involved in over 300 biochemical reactions in the body. It serves as a cofactor for enzymes that are essential for functions such as energy production, DNA and RNA synthesis, muscle contraction, and nerve transmission. This mineral is also a key player in maintaining a proper electrolyte balance, supporting heart health, and regulating blood glucose levels.

Musculoskeletal System and Magnesium

Magnesium plays an active role in the musculoskeletal system. While calcium facilitates muscle contraction, magnesium allows the muscle to relax and unwind. The sarcoplasmic reticulum (SR), an endoplasmic reticulum with a mesh-like structure within muscle fibers, is filled with calcium. When the muscle is going to contract, calcium is released from here, causing the muscle to contract. When the neural stimulus for contraction ends, the released calcium ions are pumped back into the sarcoplasmic reticulum. This process is regulated by magnesium. The essential role of magnesium in muscle relaxation is to pump the used calcium back into the sarcoplasmic reticulum. In the absence of magnesium, muscles cannot relax, leading to the occurrence of cramps.

Magnesium in Calcium-Potassium Balance

Magnesium plays a role in calcium and potassium homeostasis in the body. If magnesium is deficient for any reason, leading to hypomagnesemia, the activity of the magnesium-dependent enzyme “Na-K-ATPase” (a complex enzyme that pumps 3 sodium ions (Na+) out of the cell while taking in 2 potassium ions (K+), linked to magnesium) decreases. As a result, the cell’s potassium retention capacity decreases, and potassium and calcium are excreted in large amounts in the urine.

Cofactor Function in the Enzyme Working System

Magnesium particularly serves as a cofactor in phosphorylation reactions, essential for the functioning of kinase enzymes (hexokinase, protein kinase, creatine kinase). Additionally, it can activate enzymes by binding to them (such as phosphofructokinase). Magnesium achieves enzyme activation by binding to the active portion of the enzyme (like pyruvate kinase, enolase), binding to ligands (ATP-dependent enzymes), causing changes in catabolic processes (Na-K-ATPase), and facilitating the structuring of multi-enzyme complexes.

Effects on the Cardiovascular System

Magnesium is a significant element for the cardiovascular system. Numerous epidemiological and experimental studies associate magnesium deficiency with cardiovascular diseases such as hypertension and atherosclerosis. Its deficiency is a major risk factor for hypertension, heart diseases, and stroke. Magnesium also plays a crucial role in the regulation of blood pressure. Any alteration in the endogenous magnesium levels leads to changes in vascular tone and consequently in arterial blood pressure. Mg is particularly a key component in maintaining the healthy structure of endothelial function, ensuring vasodilation in the blood vessels, controlling blood pressure, regulating cardiac rhythm, preventing inflammatory reactions and platelet accumulation, and reducing ischemic injury caused by excess calcium in the blood vessels.

Role in Glucose Metabolism

Type 2 diabetes is often associated with both extracellular and intracellular magnesium (Mg) deficiencies. Chronic Mg deficiency or clinical hypomagnesemia is common in individuals with type 2 diabetes, especially those with poor glycemic profiles. Insulin and glucose are significant regulators of Mg metabolism.

Intracellular Mg plays a crucial role in the effect of insulin, insulin-mediated glucose uptake, and regulation of vascular tone. Decreased intracellular Mg concentrations lead to defective tyrosine kinase activity and insulin receptor dysfunction.

Low Mg intake and increased Mg loss through urine seem to be crucial mechanisms supporting Mg depletion in individuals with type 2 diabetes. An association has been suggested between plasma Mg levels and the development of type 2 diabetes in the general population. Type 2 diabetes is often accompanied by renal loss of calcium and Mg, although the mechanisms of this loss have not been fully elucidated.

Both hyperglycemia and hyperinsulinemia can increase Mg excretion through urine. Mg excretion through urine has been found to be inversely proportional to fasting serum Mg levels. Therefore, hyperglycemia reduces tubular Mg reabsorption. Good metabolic control is associated with a decrease in urinary Mg loss.

Low dietary Mg intake is closely associated with the development of type 2 diabetes and metabolic syndrome.

Diabetes, with a prevalence of 25-39% among endocrine and metabolic disorders associated with Mg deficiency. The effect of magnesium on glucose metabolism is primarily related to insulin signaling, insulin secretion, and insulin resistance. Mg plays a significant role in glucose and insulin metabolism by transferring phosphate from ATP to proteins, affecting the tyrosine kinase activity of insulin receptors. Additionally, Mg can influence glycogenolysis by releasing glucose-1-phosphate from glycogen phosphorylase b kinase activity. Furthermore, Mg can directly affect glucose transporter protein activities (GLUT4) and help regulate cellular glucose translocation.

Mg and the diabetes cycle

Recent studies have shown an inverse relationship between magnesium intake and the incidence of type 2 diabetes. This finding suggests that increased consumption of magnesium-rich foods such as whole grains, beans, nuts, and green leafy vegetables may reduce the risk of type 2 diabetes.

A meta-analysis of seven prospective cohort studies conducted between 1966 and 2007 investigated the relationship between magnesium intake (from foods and supplements) and the incidence of type 2 diabetes. The incidence of hypomagnesemia in individuals with diabetes ranged from 13.5% to 47.7%.

The prevalence of hypomagnesemia in diabetics is reported to be between 65% and 85%. For diabetic patients, the Magnesium Research Society recommends daily magnesium supplementation between 240 to 480 mg (10-20 mmol). In another study, daily oral magnesium supplementation with 2.5 g magnesium chloride (MgCl2) solution improved insulin sensitivity and metabolic control in type 2 diabetic subjects with reduced serum magnesium levels.

Events resulting in diabetes due to magnesium deficiency

An analysis of 12 different clinical studies included in a review was conducted with diabetic adults of both genders from six different countries, with varying Mg levels and using doses ranging from 250 to 450 mg/day. The results of eight clinical studies confirmed that Mg supplementation reduced fasting serum glucose, two studies showed improvement in oral glucose tolerance, and five showed a decrease in fasting insulin. Regarding HbA1c, only one study showed improvement. Seven studies demonstrated a decrease in HOMA-IR after mineral supplementation.

Conditions Increasing and Decreasing Mg Absorption

Dietary Mg restriction or deficiency, parathyroid hormone, glucagon, calcitonin, vasopressin, aldosterone, and insulin increase the absorption of Mg from the intestines. On the other hand, hypermagnesemia, metabolic acidosis, hypercalcemia, diuretics, antibiotics, chemotherapy drugs, and immunosuppressants reduce Mg absorption. Below are some conditions that decrease magnesium absorption:

Reduced dietary intake
Decreased gastrointestinal absorption (due to vitamin D deficiency)
Mg loss from the gastrointestinal system due to acute diarrhea and vomiting
Chronic diarrhea and fat malabsorption
Celiac disease (generally detected in individuals with celiac disease)
Regional enteritis
Crohn’s disease (may require up to 700 mg/day of Mg)
Resection or small intestine bypass
Laxative use
Increased renal loss (an average of 30% of dietary intake is lost through urine)
Diabetes mellitus/insulin resistance
Kidney excretion resulting from increased urine output due to higher glucose concentrations in the kidneys
Alcoholism
Decreased intake, gastrointestinal problems, vomiting, phosphate depletion, kidney dysfunction, and vitamin D deficiency
Medication-induced
Excessive sweating
Increased requirements (pregnancy and growth)
Elderly individuals: Lower magnesium intake, decreased absorption, increased renal excretion.

Hypomagnesemia

Mg deficiency is often a result of reduced intake, inadequate absorption, and/or increased excretion from the body. Patients with serum Mg concentrations around 0.61 mmol/L (1.5 mg/dL) and 0.75 mmol/L are considered hypomagnesemic. Hypomagnesemia is also defined when serum Mg concentration falls below 0.66 mmol/L (1.6 mg/dL), and clinical symptoms may not be observed until the levels drop below 0.5 mmol/L. This condition is particularly common among hospitalized patients, with a prevalence ranging from 9% to 65%.

Hypomagnesemia is often accompanied by signs of hypocalcemia. The mechanism of hypocalcemia can be explained by impaired PTH release and PTH resistance due to Mg deficiency.

Some conditions that can lead to Mg deficiency include:

Age: Elderly individuals experience more loss due to reduced absorption capacity.
Prolonged consumption of a low-magnesium diet
Consumption of low-magnesium soft drinking water
Regular alcohol intake and chronic alcoholism
Malabsorption conditions (short bowel syndrome/intestinal surgery)
Celiac disease or intestinal resections
Certain medications like diuretics
Parenteral infusions excluding magnesium
Severe diarrhea
Laxative use
Congenital tubule defects
Iatrogenic conditions
Hyperaldosteronism
Hyperparathyroidism
Chemotherapeutic drugs
Diabetes
Excessive sweating
Pregnancy and growth
Excessive release of antidiuretic hormone
Acute bone syndrome
Burns
Stress
Carbohydrates (white sugar, flour)
Coffee
Sodas (cola types, both diet and regular)
Sodium
Calcium (High intake blocks magnesium absorption)

Common symptoms of hypomagnesemia include:

General: Anxiety, numbness, fatigue, agitation, depression, dysmenorrhea, hyperactivity, migraine-type headaches, irritability, speech disorders, low stress tolerance, anorexia, nausea, sleep disorders, impaired athletic performance.
Muscular system: Muscle spasms, cramps in the soles of the feet, leg cramps, carpopedal spasms, back pain, neck pain, urinary spasms, Mg deficiency tetany.
Nervous system: Irritability, migraines, depression, nystagmus, paresthesia, memory weakness, seizures, tremors, vertigo, Parkinson’s.
Gastrointestinal system: Constipation.
Cardiovascular system: Risk of arrhythmia, supraventricular or ventricular arrhythmias, hypertension, coronary spasm, decreased myocardial pump function, digital sensitivity, death from heart disease.
Electrolytes: Hypokalemia, hypocalcemia, sodium retention.
Metabolism: Dyslipoproteinemia (increased blood triglycerides and cholesterol), decreased glucose tolerance, insulin resistance, increased risk of metabolic syndrome, disorders of bone and vitamin D metabolism, PTH resistance, low circulating PTH levels, resistance to vitamin D, low circulating levels of 25(OH)D, recurrence of calcium oxalate stones.
Others: Asthma, chronic fatigue syndrome, osteoporosis, hypertension, altered glucose homeostasis.
Pregnancy: Pregnancy complications (e.g., miscarriage, premature birth, preeclampsia)

In cases of severe symptomatic hypomagnesemia with serum magnesium levels of 1 mEq/L or less and accompanying neuromuscular or neurological symptoms or cardiac arrhythmias, Mg replacement is considered beneficial. Administration of 2 g of magnesium sulfate intravenously over 5 to 10 minutes should be provided, followed by continuous infusion of 4 to 6 g/day for 3 to 5 days if renal function is relatively normal. Addressing the cause of Mg deficiency and implementing specific treatment is crucial to prevent future recurrences.

Replacement therapy may require oral administration of magnesium oxide, magnesium chloride, magnesium citrate, magnesium taurate, magnesium orotate, and other amino acid chelates, as they have high bioavailability.

Hypermagnesemia

Hyperactivity refers to a serum Mg concentration above 2.1 mEq/L (> 2.5 mg/dL). It is commonly observed in patients with kidney disease, those using intravenous Mg, undergoing eclampsia treatment, receiving lithium therapy, and using antacids or magnesium supplements. However, hypermagnesemia is typically iatrogenic. Other less common causes of hypermagnesemia include hypothyroidism and Addison’s disease. Clinical outcomes of hypermagnesemia vary according to serum Mg levels.

Dangerous ranges of serum Mg are given as follows:

0.70–1.0 mmol/L: Considered normal.
2.2–3.5 mmol/L: Nausea, vomiting, facial flushing, urine retention, ileus, and hypotension may occur.
3.9–5.2 mmol/L: Somnolence, absence of deep tendon reflexes, and complete heart block may occur.
6.5 mmol/L: Respiratory depression, paralysis, and complete heart block are possible.
8.7 mmol/L: The patient enters asystole

Symptoms of hypermagnesemia include:

Laxative effect, diarrhea
Dizziness due to severe hypotension
Muscle weakness and deep tendon reflexes
Severe back and pelvic pain
Confusion and loss of consciousness
Respiratory arrest or difficulty breathing
Cardiac arrhythmias leading to cardiac arrest
Other effects: Numbness, confusion, impaired kidney function

Treatment

In mild Mg overdose, magnesium-containing laxatives, antacids, or magnesium supplements should be discontinued, and symptoms of renal failure should be corrected.
In severe Mg overdose, artificial respiratory support may be required, intravenous fluids (saline) may be needed, and calcium gluconate or calcium chloride and hemodialysis may be necessary.

Mg Supplements And Dietary Choices

To meet the daily recommended intake, a need for 300 mg/day of magnesium supplementation is required.

GENDER/AGE
RDA FOR Mg (mg/day)

Females (19-30)

310

Females (31+) (non-pregn.-lactating)

320

Females (19-30) (pregnant)

350

Females (31-50) (pregnant)

360

Males (19-30)

400

Males (31+)
420

https://lpi.oregonstate.edu/mic/minerals/magnesium

This amount should ideally be obtained throughout the day from various sources such as animal, plant, and water (which covers 10% of the daily requirement).

If additional daily Mg supplementation is needed, it is advisable to take Mg in chelate form, meaning it is bound to amino acids. It can be taken on an empty or full stomach, but it is best taken between meals.

Many nutrition experts believe that the ideal Mg intake should be based on body weight (e.g., 4-6 mg/kg/day). Magnesium supplements are available in various forms such as magnesium oxide, magnesium chloride, magnesium citrate, magnesium taurate, magnesium orotate, and other amino acid chelates. Due to their high bioavailability, organic-bound magnesium salts like magnesium citrate, gluconate, orotate, or aspartate are specifically recommended for treating Mg deficiency. It’s crucial to match the right form to the specific symptoms or issues, as different studies discuss different forms and reasons for use.

Supplement Forms

Glycinate: A compound of Mg and the amino acid glycine, it relaxes the nervous system and is effective in depression, anxiety, and sleep disorders. It is also used in patients who have had intestinal resection.

Chloride/taurate: Beneficial in individuals with hypertension and diabetes.

Malate: Supports intracellular energy production and can be used in chronic fatigue and fibromyalgia.

Sulfate: Used in hospitals in IV form; oral use is not highly recommended.

Oxide: Poorly bioavailable; absorbed better than effervescent magnesium oxide tablets.

Hydroxide: Poorly absorbed; used as an antacid.

Citrate: More soluble than oxide, thus significantly better absorbed.

Fumarate: Provides very high bioavailability at low doses.

Citrate with potassium citrate: Used in kidney stone disease.

Orotate: Potentially beneficial in heart failure.

Salicylate: Used in rheumatoid arthritis.

Mandelate: Used as a urinary antiseptic.

Magnesium obtained from magnesium-rich mineral water: Shows a 59% absorption rate.

Transdermal Mg application (gel, oil, cream): A more expensive form compared to oral therapy but has high absorption. Recent studies report absorption through sweat glands.

The amount of Mg in the foods we consume today is significantly lower than it was 50 years ago. The decrease is attributed to factors such as fertilizers, pesticides, chemical applications, and acid rain affecting the Mg content in plants. Approximately 40-60% of in foods is easily absorbed and deposited in tissues. Considering the human body’s daily requirement of 280-350 mg of Mg, the increase in toxin intake should not be overlooked. Therefore, turning to organic farming and safe contents enhances both the quantity and quality of magnesium intake.

According to the United States Food and Nutrition Board, the recommended daily amount of Mg is 420 mg for adult males and 320 mg for adult females.

Magnesium Sources

Examining magnesium sources reveals that green vegetables, nuts with shells, seeds are rich in magnesium as chlorophyll’s primary source. Additionally, fruits, fish, meat, and dairy products contain some amount of magnesium.

Fish, almonds, hazelnuts, peanuts, walnuts, soybeans, asparagus, onions, tomatoes, carrots, celery, leeks, gruyere cheese, bananas, black beans, broccoli, brown rice, cashews, flaxseeds, green vegetables (spinach), seeds (pumpkin, sesame, sunflower), soybeans, soy cheese, and dates, black radish, sunflower, cocoa, tonguefish, and hard water are also rich in Mg.

Hemp seeds are one of the best sources, containing 700 mg of Mg per 100 grams. Pumpkin seeds (535 mg), flaxseeds (392 mg), and Brazil nuts (376 mg) follow as additional high-magnesium sources.

Oxalate and phytate found in some vegetables and grains, similar to iron, make magnesium absorption difficult.

Epidemiological studies show that the majority of the population in Western countries consumes much less magnesium than the recommended amount. This is attributed to the consumption of processed foods, demineralized water, and greenhouse products, as well as agricultural practices using magnesium-deficient soil.

List of Magnesium Food Sources

Food	Milligrams (mg) per serving	Percent DV*
Pumpkin seeds, roasted, 1 ounce	156	37
Chia seeds, 1 ounce	111	26
Almonds, dry roasted, 1 ounce	80	19
Spinach, boiled, ½ cup	78	19
Cashews, dry roasted, 1 ounce	74	18
Peanuts, oil roasted, ¼ cup	63	15
Cereal, shredded wheat, 2 large biscuits	61	15
Soymilk, plain or vanilla, 1 cup	61	15
Black beans, cooked, ½ cup	60	14
Edamame, shelled, cooked, ½ cup	50	12
Peanut butter, smooth, 2 tablespoons	49	12
Potato, baked with skin, 3.5 ounces	43	10
Rice, brown, cooked, ½ cup	42	10
Yogurt, plain, low fat, 8 ounces	42	10
Breakfast cereals, fortified with 10% of the DV for magnesium, 1 serving	42	10
Oatmeal, instant, 1 packet	36	9
Kidney beans, canned, ½ cup	35	8
Banana, 1 medium	32	8
Salmon, Atlantic, farmed, cooked, 3 ounces	26	6
Milk, 1 cup	24–27	6
Halibut, cooked, 3 ounces	24	6
Raisins, ½ cup	23	5
Bread, whole wheat, 1 slice	23	5
Avocado, cubed, ½ cup	22	5
Chicken breast, roasted, 3 ounces	22	5
Beef, ground, 90% lean, pan broiled, 3 ounces	20	5
Broccoli, chopped and cooked, ½ cup	12	3
Rice, white, cooked, ½ cup	10	2
Apple, 1 medium	9	2
Carrot, raw, 1 medium	7	2

*DV = Daily Value.

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