Intervention Summary
Magnesium supplementation to address the documented magnesium deficiency in fibromyalgia and its role in central sensitization. Magnesium is a physiological NMDA receptor antagonist — blocking the receptor channel that drives wind-up and central pain amplification in FM. Additionally serves as a cofactor for >300 enzymatic reactions including ATP synthesis.
Evidence
- RCTs: Magnesium citrate (300mg/day, 8 weeks) reduced tender point count and FIQ scores compared to placebo in FM patients
- Cross-sectional: Low serum Mg correlates with higher pain scores, worse sleep quality, and elevated substance P in FM
- Intracellular Mg: Red blood cell magnesium (a more accurate measure than serum) is consistently low in FM cohorts
- Combination: Magnesium + malic acid combination showed pain reduction in early clinical trials, though replication is needed
Mechanism
- NMDA receptor blockade: Mg2+ sits in the NMDA receptor channel at resting potential, preventing calcium influx. Mg deficiency removes this block, facilitating glutamate excitotoxicity and central sensitization
- ATP cofactor: Mg-ATP is the biologically active form of ATP; Mg deficiency impairs cellular energy production, contributing to the fatigue hallmark of FM
- Calcium channel modulation: Mg competes with Ca2+ at voltage-gated channels, reducing neuronal hyperexcitability
- Sleep architecture: Mg deficiency disrupts sleep quality; supplementation improves sleep onset and slow-wave sleep duration
Clinical Context
Magnesium glycinate or citrate are preferred forms for bioavailability (magnesium oxide is poorly absorbed). Typical dose: 300-600mg elemental Mg/day, divided doses. GI tolerance improves with gradual dose escalation. Serum Mg is an insensitive marker — RBC magnesium or ionized Mg better reflects tissue status. Most FM patients benefit from sustained supplementation rather than short courses.