Magnesium

Magnesium (chemical or element symbol Mg) is an essential mineral in the human body. It plays a key role in DNA and RNA synthesis and in the production of ATP. It is a cofactor in more than 300 enzyme systems. Muscle and bone comprise 90% of the body's magnesium content. A serum value of 75–95 mmol/L is considered normal but some research would indicate that serum levels less than 85 mmol/l should be considered deficient. An individual may be profoundly deficient in total body or intracellular Mg, yet have a serum value within normal range.

Deficiency
Symptoms of magnesium deficiency include loss of appetite, nausea, vomiting, fatigue, and weakness. As magnesium deficiency worsens, numbness, tingling, muscle contractions and cramps, seizures, personality changes, abnormal heart rhythms, and coronary spasms can occur. Severe magnesium deficiency can result in hypocalcemia or hypokalemia (low serum calcium or potassium levels, respectively) because mineral homeostasis is disrupted.

Magnesium deficiency disrupts the HPA axis and increases susceptibility to physiological damage produced by stress. Deficiency can promote activation of the N-methyl-D-aspartic acid (NMDA) receptor which triggers inflammatory pathways and cortisol release.

People with gastrointestinal disorders and chronic fatigue syndrome are at higher risk of magnesium deficiency.

Deficiency increases the risk of osteoporosis. Magnesium supplementation may help prevent migraine.

Forms of administration
Magnesium may be taken as an oral supplement but may not be well absorbed. Magnesium oxide and citrate are poorly absorbed forms compared to glycinate and orotate. Magnesium malate is another popular form. Other forms of magnesium administration include transdermal magnesium and intramuscular magnesium sulphate injections.

Magnesium is hypotonic. Administration can cause water to flow into cells in the local area where it is applied, which can cause a temporary stinging sensation.

Chronic fatigue syndrome
In 1991, Cox et al., performed a randomized, double-blind, placebo-controlled trial of 20 United Kingdom chronic fatigue syndrome (CFS) patients finding that the subjects with CFS had lower red blood cell magnesium than healthy controls. Patients treated with intramuscular magnesium sulphate for six weeks had higher self-reported energy levels, better emotional state and less pain on the Nottingham health profile when compared to placebo.

In contrast, three subsequent case‐report studies, two in the UK (Clague et al., 1992 and Hinds et al., 1994 ), and one in the Netherlands (Swanink et al., 1995 ), did not find magnesium deficiency in CFS trial subjects.

X-MEN
A 2014 study found magnesium transporter issues were linked to chronic Epstein-Barr virus infection, decreased Natural killer cell function, and neoplasia (sometimes-cancerous growths). This disorder, termed 'X-MEN' (for X-linked, EBV, and neoplasia) was identified as a recessive, X-linked disorder that would therefore be many times more common in men. Due to magnesium's role as a 'second messenger', this magnesium transporter disorder also would result in a primary immunodeficiency that would worsen with age. Patients also have impaired T-cell activation and decreased natural killer (NK) cell function due to a decreased expression of "the NK stimulatory receptor 'natural-killer group 2, member D' (NKG2D)." Although T-cells are affected, there is no direct evidence of B-cell effects in X-MEN disease.

Since chronic Epstein-Barr virus infection has been associated with chronic fatigue syndrome, this error in magnesium transport may be worth considering in male patients, especially with slow onset and history of childhood infection.

Mast cell activation disorder
Magnesium is a cofactor in the production of diamine oxidase. It is an enzyme that breaks down histamine, which is released by mast cells.

Migraine
Magnesium has been shown to be effective for headaches and for migraine prevention. https://journals.lww.com/clinicalpain/Fulltext/2009/06000/Foods_and_Supplements_in_the_Management_of.15.aspx

Notable studies

 * 1991, Red blood cell magnesium and chronic fatigue syndrome - (Abstract)
 * 1994, Normal red cell magnesium concentrations and magnesium loading tests in patients with chronic fatigue syndrome - (Abstract)
 * 1997, Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue - (Abstract)
 * 2006, Increase of free Mg2+ in the skeletal muscle of chronic fatigue syndrome patients - (Full text)

Learn more

 * PubMed - magnesium and CFS
 * National Institutes of Health: Office of Dietary Supplements
 * Magnesium-Linus Pauling Institute Micronutrient Information Center