What is the difference between magnesium l-threonate and magnesium glycinate?

Magnesium L-Threonate vs. Magnesium Glycinate: Key Differences

Magnesium glycinate is the preferred choice for general magnesium supplementation due to superior bioavailability and minimal gastrointestinal side effects, while magnesium L-threonate is specifically indicated when targeting brain health, cognitive function, or sleep quality due to its unique ability to cross the blood-brain barrier and elevate brain magnesium levels. 1

Bioavailability and Absorption

• Magnesium glycinate belongs to the class of organic magnesium salts with high bioavailability, making it superior to inorganic forms like magnesium oxide or hydroxide for systemic magnesium repletion 1

• Magnesium L-threonate has unique brain bioavailability - it effectively crosses the blood-brain barrier and elevates cerebrospinal fluid (CSF) magnesium and threonate levels, which other magnesium forms cannot achieve 2

• The bioavailability differences between various organic magnesium compounds (citrate, glycinate, aspartate) for systemic effects are not well-established in clinical trials, but threonate's brain penetration is distinctly superior 1

Mechanism of Action

Magnesium Glycinate

• Functions primarily as a systemic magnesium source for general physiological processes including energy production, enzyme activity, nerve and muscle function, cardiovascular health, and bone maintenance 3

• Well-tolerated with minimal osmotic effects, making it suitable for patients who cannot tolerate gastrointestinal side effects 1

Magnesium L-Threonate

• The threonate component acts through glucose transporters (GLUTs) to directly increase intraneuronal magnesium concentration, a mechanism unique to this form 2

• Elevates expression of NR2B-containing NMDA receptors, boosts mitochondrial membrane potential, and increases functional synapse density in neurons 2

• Upregulates excitatory amino acid transporter (EAAT4) glutamate transporter expression, protecting against hypoxic injury and supporting cognitive function 4

• Activates the ERK/CREB signaling pathway, promoting adult hippocampal neurogenesis and neuronal differentiation 5

Clinical Applications

When to Choose Magnesium Glycinate

• General magnesium deficiency correction in patients with malabsorption, short bowel syndrome, or medication-induced depletion 1

• Patients requiring magnesium supplementation who have gastrointestinal sensitivity, as glycinate causes less diarrhea and bloating than citrate or oxide 1

• Cardiovascular indications including arrhythmia prevention (though IV magnesium sulfate is preferred for acute cardiac emergencies) 6

• Chemotherapy-induced hypomagnesemia for maintenance therapy after IV correction 1

• Starting dose: 320 mg elemental magnesium daily for women, 420 mg for men, which can be increased gradually based on tolerance 1

When to Choose Magnesium L-Threonate

• Cognitive decline or memory impairment - demonstrated efficacy in improving global cognitive abilities in older adults and Alzheimer's disease models 2, 5

• Sleep disorders, particularly when deep sleep and REM sleep are impaired - significantly improves sleep quality, deep sleep score, REM sleep score, and restorative sleep parameters 7

• Mood disturbances - improves grouchiness, mental alertness, energy, and daytime productivity 7

• Neuroprotection following hypoxic injury - reduces cerebral infarction and preserves cognitive function 4

• Typical dosing: 1-2 grams daily of magnesium L-threonate (providing approximately 144-288 mg elemental magnesium), taken for minimum 21-30 days to see cognitive benefits 7, 8

Side Effect Profile

Magnesium Glycinate

• Minimal gastrointestinal effects - well-tolerated with rare diarrhea or bloating 1

• May cause hypocalcemia with prolonged use - monitor calcium levels 1

• Contraindicated when creatinine clearance <20 mL/min due to hypermagnesemia risk 1

Magnesium L-Threonate

• Well-tolerated with no significant adverse effects reported in clinical trials 7, 8

• Does not cause the osmotic diarrhea seen with citrate or oxide forms 7

• Same renal precautions apply - avoid in severe renal impairment 1

Cost and Practical Considerations

• Magnesium glycinate is more widely available and less expensive than L-threonate, making it the practical choice for general supplementation 1

• Magnesium L-threonate is significantly more expensive but justified when specific brain-targeted effects are needed 7, 8

• For constipation, neither form is optimal - magnesium citrate or oxide are preferred due to stronger osmotic effects 1, 6

Clinical Decision Algorithm

Step 1: Identify the primary indication

• If cognitive impairment, memory problems, or sleep quality issues → Choose magnesium L-threonate 7, 5, 8
• If general magnesium deficiency, cardiovascular support, or maintenance therapy → Choose magnesium glycinate 1
• If constipation is the concern → Choose magnesium citrate or oxide instead 1, 6

Step 2: Assess renal function

• Check creatinine clearance - if <20 mL/min, avoid all magnesium supplementation 1
• If 20-30 mL/min, use extreme caution with reduced doses and close monitoring 6

Step 3: Consider gastrointestinal tolerance

• If patient has diarrhea-predominant symptoms → Prefer glycinate or L-threonate over citrate 1
• If constipation is present → Citrate may provide dual benefit 1

Step 4: Determine appropriate dosing

• Glycinate: Start 320-420 mg elemental magnesium daily, increase gradually to 600 mg if needed 1
• L-threonate: 1-2 grams daily (144-288 mg elemental magnesium), continue for minimum 21-30 days before assessing efficacy 7, 8

Step 5: Monitor response

• Check magnesium levels at 2-3 weeks after initiation, then every 3 months once stable 6
• For L-threonate, assess cognitive function and sleep quality at 30 days 7, 8
• Monitor for hypocalcemia with glycinate, particularly in long-term use 1

Common Pitfalls to Avoid

• Do not assume all magnesium forms are interchangeable - threonate's brain-specific effects cannot be replicated by glycinate or other forms 2

• Do not use glycinate when brain-targeted effects are needed - it will not achieve the same CSF magnesium elevation as L-threonate 2

• Do not overlook renal function assessment - hypermagnesemia can be life-threatening in renal impairment 1, 6

• Do not expect immediate results with L-threonate - cognitive and sleep benefits require 21-30 days of consistent use 7, 8

• Do not use L-threonate for acute magnesium deficiency correction - glycinate or IV magnesium sulfate are more appropriate for rapid repletion 1