Magnesium

Magnesium is an essential mineral in maintaining overall health and well-being.  Magnesium serves as a cofactor for hundreds of enzymatic reactions contributing to energy production, muscle and nerve function, and bone health. 

Found abundantly in various dietary sources such as nuts, seeds, leafy greens, and whole grains, magnesium intake is crucial for meeting daily recommended levels. While the recommended dietary allowance (RDA) varies depending on age, gender, and specific health conditions, supplementation may be warranted in cases of deficiency or certain medical indications. 

Understanding the significance of magnesium levels through laboratory testing is essential for assessing nutritional status and guiding supplementation strategies. Interpreting test results involves analyzing reference ranges and recognizing clinical implications associated with both high and low levels of magnesium. 

Additionally, exploring related biomarkers and natural approaches to support magnesium levels, including dietary modifications, lifestyle adjustments, and targeted supplementation, offers a comprehensive perspective on optimizing overall health and well-being.

Definition and Function

Definition: What is Magnesium?

Magnesium is an essential mineral that serves as a critical cofactor for numerous enzymatic reactions within the body.  It is a vital cofactor for over 300 enzyme systems, serving crucial roles in energy generation, glycolysis, and oxidative phosphorylation.

The human body contains about 25 grams of magnesium, making it the fourth most abundant mineral in the human body.  Magnesium is primarily found in bones (50-60% of the body’s total magnesium), and the rest is found in muscles and soft tissues. [6., 12.]

Magnesium exists in various forms, with magnesium ions (Mg2+) being the biologically active form responsible for its physiological functions.

Mg2+, the magnesium ion, facilitates ATP and ADP chelation which is essential for mitochondrial function.  Cellular transport of magnesium relies on carrier-mediated systems, coupling with sodium and bicarbonate transport. 

Hormonal factors like β-agonists and insulin influence magnesium transport, impacting intracellular concentration and enzyme activity. 

Magnesium deficiency affects DNA and RNA synthesis, adenylate cyclase activation, and potassium transport, contributing to muscle cramps, hypertension, and cardiovascular dysfunctions. 

Although intestinal absorption, primarily in the distal jejunum and ileum, involves passive and active transport, renal reabsorption accounts for magnesium homeostasis. Vitamin D enhances intestinal magnesium absorption to some extent, and magnesium reabsorption in the kidney is regulated mainly through the loop of Henle and proximal convoluted tubule.  [2.]

Excessive alcohol intake and certain medications can exacerbate magnesium depletion, highlighting the importance of maintaining adequate magnesium levels for overall health.

Functions of Magnesium: What Does Magnesium Do In The Body?

Magnesium, as a critical cofactor for over 300 enzymes, has many diverse functions in the human body.  This list provides an overview, with a focus on the essential roles of magnesium for cellular health, which ultimately affects the well-being of the organism.  

• Magnesium serves as a required cofactor for over 300 enzyme systems in the body.
• It plays a crucial role in energy generation, including both anaerobic and aerobic processes such as glycolysis and oxidative phosphorylation.
• Magnesium facilitates the chelation of ATP and ADP, vital for mitochondrial function and phosphate transfer reactions.
• Cellular transport of magnesium involves carrier-mediated systems, with efflux coupled to sodium transport and influx linked to sodium and bicarbonate transport.
• Hormonal factors like β-agonists, growth factors, and insulin influence magnesium transport and intracellular concentration.
• Magnesium is essential for DNA and RNA synthesis, maintaining an adequate supply of purine and pyrimidine nucleotides during cell proliferation.
• It activates adenylate cyclase, a crucial enzyme in signal transduction pathways, impacting hormone and neurotransmitter regulation.
• Magnesium regulates sodium, potassium-ATPase activity, facilitating potassium transport and maintaining intracellular potassium levels.
• Its presence modulates calcium channels, preventing intracellular calcium rise and consequent muscle cramps, hypertension, and vasospasms.
• Magnesium depletion is associated with various diseases affecting cardiovascular, neuromuscular function, malabsorption syndromes, diabetes mellitus, renal wasting syndromes, and alcoholism.

Magnesium and Brain Health  [2.]

Low serum magnesium levels are linked to various neurological disorders such as migraine, depression, epilepsy, and Parkinson's disease, underscoring its critical role in brain function.

Magnesium modulates the excitability of N-methyl-D-aspartate (NMDA) receptors which is essential for synaptic transmission, neuronal plasticity, and learning.  It does this by inhibiting excessive receptor activation and subsequent calcium influx.

Additionally, magnesium regulates γ-aminobutyric acid (GABA) receptors, promoting neuronal hyperpolarization and counteracting NMDA receptor hyperexcitability, thereby contributing to overall neuronal stability.

In conditions like epilepsy, magnesium deficiency may exacerbate seizures due to heightened NMDA receptor activity, while in stroke, low magnesium levels may worsen excitotoxicity and impair vasodilation, although clinical trials investigating magnesium's efficacy in stroke treatment have yielded mixed results.

While magnesium has not been implicated in the pathogenesis of ADHD, lower levels are commonly found in children with ADHD than in those without the diagnosis.  [4.]  Magnesium is also being explored as a therapeutic tool in ADHD.  

Moreover, magnesium plays a role in other brain pathologies such as traumatic brain injury, spinal cord injury, and neurodegenerative diseases like Alzheimer's, where its deficiency may exacerbate oxidative stress, lipid peroxidation, and neuronal cell death, highlighting its potential as a therapeutic target for various neurological disorders.

Magnesium and Cardiovascular Health  [8.]

Magnesium plays a crucial role in cardiovascular health through various mechanisms. 

In vascular medicine, it promotes vascular smooth-muscle relaxation by inhibiting calcium influx, thus lowering blood pressure and reducing triglycerides while increasing high-density lipoprotein (HDL) levels. Additionally, magnesium inhibits cholesterol synthesis and promotes HDL production, offering protective effects against atherosclerosis and hypertension. 

Hypomagnesemia has been associated with proinflammatory responses and endothelial dysfunction, contributing to arterial plaque formation and vascular mineralization. Animal studies have shown that magnesium supplementation can reduce atherosclerotic plaque formation and vascular calcification.

Moreover, magnesium supplementation has demonstrated potential benefits in reducing the risk of atrial fibrillation post-coronary artery bypass grafting, lowering blood pressure, and decreasing carotid intima-media thickness (CIMT), a marker of atherosclerosis. 

Studies have also suggested a potential role of magnesium in stroke prevention, with higher dietary intake associated with a lower risk of ischemic stroke. However, clinical trials investigating magnesium's efficacy in stroke treatment have yielded mixed results, with challenges in timely administration.  [8.]

Dietary Sources of Magnesium  [9.]

Animal-Based Sources of Magnesium:

‍

• Salmon, Atlantic, farmed, cooked, 3 ounces: 26 mg
• Milk, 1 cup: 24–27 mg
• Halibut, cooked, 3 ounces: 24 mg
• Chicken breast, roasted, 3 ounces: 22 mg
• Beef, ground, 90% lean, pan broiled, 3 ounces: 20 mg

Plant-Based Sources of Magnesium:

• Pumpkin seeds, roasted, 1 ounce: 156 mg
• Chia seeds, 1 ounce: 111 mg
• Almonds, dry roasted, 1 ounce: 80 mg
• Spinach, boiled, ½ cup: 78 mg
• Cashews, dry roasted, 1 ounce: 74 mg
• Peanuts, oil roasted, ¼ cup: 63 mg
• Cereal, shredded wheat, 2 large biscuits: 61 mg
• Soymilk, plain or vanilla, 1 cup: 61 mg
• Black beans, cooked, ½ cup: 60 mg
• Edamame, shelled, cooked, ½ cup: 50 mg
• Peanut butter, smooth, 2 tablespoons: 49 mg
• Potato, baked with skin, 3.5 ounces: 43 mg
• Rice, brown, cooked, ½ cup: 42 mg
• Yogurt, plain, low fat, 8 ounces: 42 mg
• Breakfast cereals, fortified with 10% of the DV for magnesium, 1 serving: 42 mg
• Oatmeal, instant, 1 packet: 36 mg
• Kidney beans, canned, ½ cup: 35 mg
• Banana, 1 medium: 32 mg
• Raisins, ½ cup: 23 mg
• Bread, whole wheat, 1 slice: 23 mg
• Avocado, cubed, ½ cup: 22 mg
• Broccoli, chopped and cooked, ½ cup: 12 mg
• Rice, white, cooked, ½ cup: 10 mg
• Apple, 1 medium: 9 mg
• Carrot, raw, 1 medium: 7 mg

Recommended Intake And Supplementation of Magnesium

RDA of Magnesium: How Much Magnesium Should I Get a Day?  [6.]

The RDA, or Recommended Dietary Allowance, of Magnesium depends on factors including age and gender. 

The RDA for men ages 19-30 is  400 mg and for men 31 and older is 420 mg a day.  For women, the RDA for ages 19-30 is 300 mg and for women ages 31 and older the RDA is 320 mg a day.  

In pregnancy the recommendation rises to 350-360 mg a day, and is set at 310-320 mg a day in lactation.  

Indications for Supplementation: Should I Take a Magnesium Supplement? [6.]

This question should be discussed with a licensed healthcare provider, who can recommend individualized testing and a supplementation plan, as well as long-term monitoring.   

General indications for magnesium supplementation may include: 

• Symptoms of severe magnesium depletion:some text
  • Hypocalcemia, a prominent manifestation of magnesium deficiency in humans
  • Resistance to pharmacological doses of vitamin D, affecting vitamin D metabolism and action
• Neuromuscular hyperexcitability may occur, presenting as:some text
  • Latent tetany, observed through positive Chvostek's and Trousseau's signs
  • Spontaneous carpal-pedal spasm
  • Frank, generalized seizures
• Cardiovascular Symptoms:some text
  • Increased urinary thromboxane concentration
  • Elevated angiotensin II-induced plasma aldosterone levels
  • Changes in blood pressure
  • Cardiac complications such as electrocardiographic changes and arrhythmias
  • Sensitivity to cardiac glycosides
  • Atrial and ventricular premature systoles
  • Atrial fibrillation
  • Ventricular tachycardia and fibrillation
• Association with Atheromatous Disease:some text
  • Epidemiological studies suggest lower cardiovascular death rates in areas with increased water hardness (due to high calcium and magnesium content)
  • Animals on low magnesium diets develop arterial wall degeneration, calcification, hypertriglyceridemia, hypercholesterolemia, and atherosclerosis
• Hypertension:some text
  • Low dietary intake of magnesium associated with increased incidence of hypertension
  • Some intervention studies show positive effects of magnesium supplements on blood pressure, while others do not
  • Low serum magnesium concentrations observed in hypertensive patients
• Skeletal Growth and Osteoporosis:some text
  • Magnesium plays a role in bone and mineral homeostasis
  • Magnesium deficiency may be a risk factor for postmenopausal osteoporosis
  • Some studies suggest a positive effect of magnesium supplementation on bone mineral density
• Diabetes Mellitus:some text
  • Magnesium depletion linked to insulin resistance and impaired insulin secretion
  • Experimental studies show a decrease in insulin sensitivity with magnesium depletion
  • Elderly individuals with diabetes may experience magnesium depletion due to glycosuria-induced renal magnesium wasting
• Increased Risk of Deficiency in the Elderly:some text
  • Elderly people often have relatively low dietary intakes of magnesium
  • Aging affects magnesium metabolism, leading to decreased absorption and increased urinary excretion, increasing the risk of magnesium depletion

Magnesium Supplement Forms

Magnesium supplements are offered in many different forms according to the substrate used to bind magnesium.  Some of these provide additional health benefits above magnesium.

Magnesium Citrate:

• Well-absorbed form of magnesium due to its high bioavailability
• Known for its effectiveness in relieving constipation as it can act as a laxative
• May cause diarrhea if taken in excessive amounts
• Suitable for individuals with low stomach acid or those seeking a gentle form of magnesium supplementation

Magnesium Glycinate:

• Magnesium bound to glycine, an amino acid, which enhances its absorption and bioavailability
• Less likely to cause gastrointestinal discomfort or laxative effects compared to other forms
• May provide additional support for healthy sleep
• Suitable for individuals with digestive issues or those prone to diarrhea

Magnesium Oxide:

• Contains a high percentage of elemental magnesium but has low bioavailability
• Often used as a laxative due to its ability to draw water into the intestines
• Not recommended for individuals seeking optimal absorption or those prone to gastrointestinal issues

Magnesium Taurate:

• Magnesium bound to taurine, an amino acid, which may improve cardiovascular health and support heart function
• Taurine may enhance magnesium's ability to cross cell membranes, potentially improving absorption
• Suitable for individuals looking to support heart health or those with cardiovascular concerns

Magnesium Malate:

• Magnesium combined with malic acid, a compound naturally found in fruits
• Malic acid may support energy production and alleviate muscle pain and fatigue
• Often chosen by individuals seeking to improve energy levels or manage fibromyalgia symptoms

Magnesium L-Threonate:

• Unique form of magnesium that may have enhanced ability to cross the blood-brain barrier
• Promoted for cognitive support and brain health, potentially improving memory and cognitive function
• Suitable for individuals interested in supporting brain health or cognitive function

Magnesium Chloride:

• Contains magnesium combined with chloride, a form often found in seawater or salt lakes
• May be used in topical applications like magnesium oil or bath salts for skin absorption
• Suitable for individuals with sensitive digestive systems or those preferring topical magnesium supplementation

Magnesium Sulfate (Epsom Salt):

• Often used in baths for relaxation and muscle soreness relief
• Absorbed through the skin rather than taken orally
• Suitable for individuals seeking muscle relaxation or stress relief through topical application

Testing Options for Magnesium

Lab Tests and Sample Type

Testing magnesium levels involves several methods, each with its advantages and limitations. 

Serum magnesium concentration is commonly assessed but might not accurately reflect intracellular magnesium availability because serum magnesium is tightly regulated.  [1., 3., 6.]

However, experimental dietary magnesium depletion consistently lowers serum magnesium levels, indicating its sensitivity to magnesium status changes.  [6.]

Intracellular magnesium assessment, crucial for enzyme activation within cells, includes evaluation of various tissues like red blood cells, skeletal muscle, and lymphocytes. 

Urine magnesium testing may also be done, which is often either ordered as a 24 hour urine collection test or as a spot or random urine assessment.  

Some specialized companies off magnesium testing as part of a comprehensive nutritional assessment.  

Preparation for Lab Testing

This test commonly requires a venipuncture.  Fasting is typically required.  

Urine testing requires a urine sample, and may require 24 hour collection.

Interpreting Test Results

Reference Range for Magnesium

The Reference Range for magnesium testing will depend on the sample type and lab company used.  It is essential to consult with the ordering lab company for their recommended reference ranges and interpretation.  

Typical reference ranges for serum magnesium are given as:  [10.]

Normal findings:

Adult: 1.3-2.1 mEq/L or 0.65-1.05 mmol/L (SI units)

Child: 1.4-1.7 mEq/L

Newborn: 1.4-2 mEq/L

Possible critical values:

< 0.5 mEq/L or >3 mEq/L

Clinical Significance of High Levels of Magnesium  [11.]

High magnesium levels, known as hypermagnesemia, are typically rare unless induced by magnesium administration or kidney dysfunction. The kidneys play a crucial role in regulating plasma magnesium levels within a narrow range. 

Usually asymptomatic at mild elevations (<3 mEq/L or 3.6 mg/dL), symptoms may arise when levels exceed 4 mEq/L (4.8 mg/dL). 

Hypermagnesemia is primarily observed in conditions such as kidney impairment, excessive magnesium intake orally, intravenously, or via enema, and increased gastrointestinal absorption due to issues like constipation or gastrointestinal diseases. 

Moreover, hypermagnesemia exacerbates its own effects by enhancing magnesium absorption in the gut, leading to a further rise in magnesium levels. The causes, symptoms, and management of hypermagnesemia are important considerations in clinical practice.

Clinical Significance of Low Levels of Magnesium  [5.]

Low magnesium levels are more commonly discovered.  Causes of low magnesium, or hypomagnesemia, include:

Decreased Intake:

• Starvation
• Alcohol use disorder
• Anorexia nervosa
• Terminal cancer
• Critically ill patients on total parenteral nutrition

Medications:

• Loop and thiazide diuretics
• Proton pump inhibitors
• Aminoglycoside antibiotics
• Amphotericin B
• Pentamidine
• Digitalis
• Chemotherapeutic drugs (cisplatin, cyclosporine)
• Antibodies targeting EGF receptors (cetuximab, matuzumab, panitumumab)
• Laxative abuse

Redistribution from Extracellular to Intracellular Compartment:

• Treatment of diabetic ketoacidosis with insulin
• Refeeding syndrome
• Correction of metabolic acidosis
• Acute pancreatitis
• Ethanol withdrawal syndrome

Gastrointestinal and Renal Losses:

• Acute and chronic diarrhea (Crohn's disease, ulcerative colitis)
• Hungry bone syndrome
• Gastric bypass surgery
• Genetic disorders (Gitelman syndrome, Bartter syndrome, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, EAST syndrome)
• Renal malformations and early-onset diabetes mellitus due to HNF1-beta mutation
• Post-kidney transplant complications
• Recovery from acute tubular necrosis
• Postobstructive diuresis

 Natural Ways to Optimize Magnesium Levels

Include Magnesium-Rich Foods:  [9.]

• Leafy green vegetables (spinach, kale, Swiss chard)
• Nuts and seeds (almonds, pumpkin seeds, sunflower seeds)
• Legumes (black beans, chickpeas, lentils)
• Whole grains (brown rice, quinoa, oats)
• Avocado
• Bananas
• Dark chocolate

• Berries (blueberries, raspberries, strawberries)
• Figs
• Kiwi
• Prunes
• Choose fortified cereals and plant-based milk alternatives (fortified with magnesium)
• Include tofu and tempeh in meals

Enjoy Magnesium-Boosting Beverages:  [9.]

• Consume mineral water high in magnesium content

Include Magnesium in Snacks:  [9.]

• Snack on magnesium-rich options like trail mix with nuts and seeds
• Have a serving of yogurt with almonds or fruit

Diversify Protein Sources:  [9.]

• Include fish (salmon, mackerel) which provide magnesium
• Incorporate lean meats like chicken and turkey

Moderate Consumption of Caffeine and Alcohol: [5.]

• Limit intake of caffeine-containing beverages like coffee and tea
• Moderate alcohol consumption, as excessive alcohol can interfere with magnesium absorption

Choose Nutrient-Dense Foods:  [5., 9.]

• Focus on whole, unprocessed foods to ensure adequate magnesium intake
• Opt for a balanced diet with a variety of fruits, vegetables, whole grains, and protein sources

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