Magnesium
Magnesium (Glycinate/Threonate)
Magnesium is an essential macromineral involved in over 300 enzymatic reactions in the human body, with glycinate and threonate being premium chelated forms chosen for superior bioavailability and tolerability. Magnesium glycinate is widely used for stress reduction, sleep improvement, muscle relaxation, and correcting deficiency, while magnesium L-threonate is uniquely valued for cognitive enhancement due to its ability to cross the blood-brain barrier and raise cerebrospinal fluid magnesium levels. Subclinical magnesium deficiency is highly prevalent in Western populations due to poor diet, stress, and soil depletion, making supplementation broadly relevant.
Mechanism of Action
Magnesium acts as a cofactor for ATP synthesis, DNA replication, and protein synthesis, and serves as a physiological calcium channel antagonist, regulating neuromuscular excitability and vascular smooth muscle tone. It modulates NMDA glutamate receptor activity by acting as a voltage-dependent channel blocker, which underlies its neuroprotective and anxiolytic properties, and regulates HPA axis activity to dampen cortisol-driven stress responses. Magnesium L-threonate specifically elevates synaptic magnesium concentrations in the brain, enhancing synaptic plasticity, long-term potentiation, and dendritic spine density in hippocampal and prefrontal regions.
Evidence by Health Goal(17 goals)
Dosing Protocols
30-60 minutes before bed
Magnesium glycinate provides roughly 14% elemental magnesium by weight; a 400mg glycinate capsule yields ~56mg elemental Mg. For magnesium L-threonate, the clinically studied dose is 1.5-2g of the compound (providing ~144mg elemental Mg) split across morning and evening doses. Start at the lower end to assess gastrointestinal tolerance. Therapeutic repletion of deficiency may require 300-400mg elemental Mg daily for several weeks.
Safety & Side Effects
Magnesium glycinate and threonate are among the safest supplement forms available, with a well-established tolerability profile in healthy adults at recommended doses; however, individuals with chronic kidney disease (CKD stage 3 or worse) should use caution or avoid supplementation due to risk of magnesium accumulation and hypermagnesemia. The tolerable upper intake level for supplemental magnesium is set at 350mg elemental Mg/day by most health authorities, though this refers primarily to laxative effects rather than systemic toxicity in those with normal renal function.
Possible Side Effects
- !Loose stools or diarrhea at doses exceeding 350mg elemental magnesium (less common with glycinate/threonate than oxide forms)
- !Gastrointestinal cramping or nausea, particularly when taken on an empty stomach
- !Excessive sedation or grogginess the following morning at high doses
- !Headache during initial supplementation, typically transient
- !Hypotension in sensitive individuals, particularly at high doses combined with antihypertensive medications
- !Hypermagnesemia (nausea, muscle weakness, bradycardia) with chronic high-dose use in individuals with impaired renal function
- !Mild fatigue or lethargy during the initial days of supplementation as the body adjusts
Interactions
- -Reduces absorption of certain antibiotics (fluoroquinolones, tetracyclines) — take magnesium at least 2 hours apart
- -May enhance hypotensive effects of antihypertensive medications, increasing risk of low blood pressure
- -Can potentiate the effects of calcium channel blockers, warranting dose monitoring
- -High-dose zinc supplementation (>142mg/day) may impair magnesium absorption — avoid co-administration
- -May reduce absorption of bisphosphonates (e.g., alendronate) — separate administration by at least 2 hours
Cost & Where to Buy
Magnesium glycinate from reputable brands (Thorne, Doctor's Best) typically runs $15-25/month. Magnesium L-threonate (Magtein-branded) commands a significant premium at $30-45/month due to patented sourcing. Generic glycinate from bulk suppliers can be found for $10-15/month. Third-party tested brands cost more but offer greater confidence in elemental magnesium content accuracy.
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