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Grade A Evidence

Magnesium

The form matters more than the dose. A clinical guide to matching magnesium to the indication.

Sleep and anxiety (glycinate)Cognitive support (threonate)Muscle pain and fatigue (malate)Cardiovascular (taurate)Constipation (citrate, oxide)Migraine preventionInsulin resistancePMS/PMDD

Evidence highlight

RBC magnesium deficiency is present in up to 60% of type 2 diabetics and 40% of fibromyalgia patients. Serum magnesium is a poor marker — normal serum can coexist with significant intracellular depletion.

Therapeutic dosing

Magnesium glycinate

200-400mg elemental before bed

Best for sleep, anxiety, muscle relaxation; high bioavailability, low laxative effect

Magnesium threonate

1.5-2g/day (delivering ~144mg elemental)

Crosses blood-brain barrier; for cognitive and neurological indications

Magnesium malate

200-400mg elemental/day

For muscle pain, fibromyalgia, fatigue; malic acid supports ATP production

Magnesium citrate

200-400mg elemental/day

Good general bioavailability; laxative effect at higher doses

Magnesium oxide

Not recommended for systemic use

Very poor absorption (~4%); mainly used for short-term constipation only

Drug interactions

Bisphosphonates (e.g., alendronate) — separate by 2+ hours; magnesium reduces absorption

Antibiotics (quinolones, tetracyclines) — separate by 2+ hours; chelation reduces antibiotic absorption

Levothyroxine — separate by 4 hours; may interfere with absorption

Diuretics (loop, thiazide) — may increase magnesium excretion, worsening deficiency

Proton pump inhibitors — long-term use depletes magnesium; supplementation often needed

Contraindications

Severe renal impairment (eGFR <30) — risk of hypermagnesemia

Heart block

Active bowel obstruction (magnesium citrate/oxide)

Labs to monitor

RBC magnesium (more accurate than serum)Serum magnesiumRenal function (before starting in any patient with kidney concerns)

Mechanism of action

Magnesium is a cofactor in over 300 enzymatic reactions, including ATP synthesis, DNA replication, and glucose metabolism. It modulates NMDA receptors (relevant for pain and sleep), regulates HPA axis response, and is required for vitamin D activation — magnesium deficiency can cause apparent vitamin D resistance even with adequate supplementation.

Clinical note

Never use magnesium oxide for anything other than short-term constipation. The 4% absorption rate makes it clinically useless for systemic deficiency. For patients with insomnia, anxiety, or muscle tension, glycinate is the first choice. Always check RBC magnesium, not serum, for a true picture of status.

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