Magnesium Threonate vs. Magnesium Glycinate: Clinical Comparison
For cognitive enhancement and neurological health, magnesium threonate is superior due to its unique ability to cross the blood-brain barrier and increase brain magnesium levels, while magnesium glycinate is the better choice for general supplementation, sleep support through muscle relaxation, and patients with sensitive stomachs who need to avoid laxative effects. 1, 2, 3
Key Mechanistic Differences
Magnesium Threonate (Brain-Specific Benefits)
Magnesium threonate uniquely elevates cerebrospinal fluid magnesium levels and directly increases intraneuronal magnesium concentration through glucose transporters (GLUTs), a mechanism not shared by other magnesium compounds. 4
This formulation specifically upregulates NR2B-containing NMDA receptors, boosts mitochondrial membrane potential, and increases functional synapse density in neurons—effects that are unique to threonate and not observed with other magnesium anions. 4
In clinical trials, magnesium threonate (1 g/day for 21 days) significantly improved deep sleep score, REM sleep score, behavior upon awakening, mental alertness, mood, energy, and daytime productivity compared to placebo. 2
A study in 109 healthy Chinese adults demonstrated significant improvements in all five subcategories of "The Clinical Memory Test" and overall memory quotient scores after 30 days of supplementation, with older participants showing greater benefits. 5
Magnesium Glycinate (General Supplementation)
Organic magnesium salts including magnesium glycinate have superior bioavailability compared to inorganic forms like magnesium oxide or hydroxide, making them preferred for general supplementation. 1
Magnesium glycinate causes significantly fewer gastrointestinal side effects (diarrhea, bloating) compared to magnesium citrate or oxide due to its excellent absorption and lack of osmotic laxative effect. 1
Animal studies show magnesium glycinate effectively increases muscle tissue magnesium levels, though brain penetration is less pronounced than with threonate. 3
Clinical Decision Algorithm
Choose Magnesium Threonate When:
Primary goal is cognitive enhancement, memory improvement, or prevention of age-related cognitive decline. 5, 4
Patient has documented sleep architecture problems (reduced deep sleep or REM sleep) rather than simple insomnia. 2
Patient needs improved mental alertness, mood stabilization, or enhanced daytime productivity. 2
Neurological health optimization is the priority (neuroprotection, synapse density). 4
Choose Magnesium Glycinate When:
Patient has a sensitive stomach or history of diarrhea with magnesium supplements. 1
Primary goal is general magnesium supplementation for deficiency correction without laxative effects. 1
Patient needs muscle relaxation support or has muscle cramps/tension. 3
Cost is a significant consideration (glycinate is typically less expensive than threonate). 1
Patient requires long-term daily supplementation for cardiovascular or metabolic health. 1
Dosing Recommendations
Magnesium Threonate
Standard dose: 1-2 g/day of magnesium L-threonate (providing approximately 144-288 mg elemental magnesium), typically divided into morning and evening doses. 2, 5
The maximum studied dose is 3000 mg/day (providing ~250 mg elemental magnesium), which corresponds to the tolerable upper limit for supplemental magnesium. 6
Take at consistent times daily; evening dosing may optimize sleep benefits. 2
Magnesium Glycinate
Start with 200-400 mg elemental magnesium daily (typically 1000-2000 mg magnesium glycinate), divided into 1-2 doses. 1
For sleep support specifically, take the full dose 1-2 hours before bedtime to maximize muscle relaxation effects. 1
Maximum daily supplemental magnesium from any readily dissociable salt should not exceed 350 mg elemental magnesium to avoid osmotic diarrhea. 1
Critical Safety Considerations (Both Forms)
Absolute Contraindications
Both forms are absolutely contraindicated when creatinine clearance is <20 mL/min due to life-threatening hypermagnesemia risk. 1, 7
Avoid in patients with known hypermagnesemia (>2.2 mEq/L). 8
Do not use in patients with severe cardiac conduction abnormalities without cardiology consultation. 8
Relative Contraindications and Cautions
Use reduced doses with close monitoring when creatinine clearance is 30-60 mL/min. 7
Exercise extreme caution between creatinine clearance 20-30 mL/min; consider avoiding unless life-threatening emergency. 7
Monitor calcium levels closely, as patients are at increased risk of developing hypocalcemia after magnesium supplementation. 8
Check baseline renal function before initiating any magnesium supplementation. 1, 7
Monitoring Protocol
Initial Assessment (Day 0)
Check serum magnesium, potassium, calcium, and comprehensive metabolic panel including creatinine clearance. 7
Assess for volume depletion; correct with IV saline if present before starting supplementation. 7
Early Follow-Up (2-3 Weeks)
Recheck magnesium level after starting supplementation. 7
Assess for side effects: diarrhea, abdominal distension, nausea (more common with glycinate at high doses). 7
Evaluate subjective response to therapy (cognitive function for threonate, sleep quality for either). 2, 5
Maintenance Monitoring (Every 3 Months)
Monitor magnesium levels quarterly once dose is stable. 7
More frequent monitoring required if high GI losses, renal disease, or concurrent medications affecting magnesium (diuretics, PPIs, calcineurin inhibitors). 7
Common Pitfalls to Avoid
Never assume magnesium supplementation is safe without checking renal function first—this is the most critical error leading to life-threatening hypermagnesemia. 1, 7
Do not use magnesium citrate or oxide when the goal is neurological support; these forms have poor brain penetration compared to threonate. 4
Avoid switching from glycinate to oxide without warning patients about increased diarrhea risk due to osmotic effects. 1
Do not overlook concurrent hypokalemia—magnesium deficiency causes refractory hypokalemia that will not respond to potassium supplementation until magnesium is corrected. 7
Never give magnesium supplements to patients with suspected bowel obstruction or severe gastrointestinal disease. 9
Drug Interactions Requiring Dose Adjustment
Patients on digoxin require 30-50% dose reduction of digoxin when starting magnesium supplementation and close monitoring of digoxin levels. 8
Bisphosphonates, fluoroquinolones, and tetracyclines should be separated from magnesium by at least 2-4 hours to avoid chelation and reduced absorption. 8
Concurrent use with other QT-prolonging medications requires ECG monitoring and maintaining magnesium >2 mg/dL. 8