Magnesium L-Threonate

Pharmacological Actions
Magnesium L-threonate is primarily investigated for its effects on brain health due to its ability to cross the blood-brain barrier, a feature not as pronounced in other magnesium forms. The following actions are supported by various studies:

Cognitive Enhancement: Research suggests Magnesium L-threonate can improve memory, learning, and overall cognitive function. A study involving 109 healthy Chinese adults aged 18-65, published in Nutrients in 2022, found that a daily dose of 2 grams of a Magnesium L-threonate-based formula (Magtein®PS) for 30 days significantly improved scores in all categories of "The Clinical Memory Test" compared to a placebo group A Magtein®, Magnesium L-Threonate, -Based Formula Improves Brain Cognitive Functions in Healthy Chinese Adults. Another randomized, double-blind, placebo-controlled trial with 50 adults aged 50-70, as noted in a 2018 Metagenics review, showed a 13.1% improvement in working memory at week 6 with 1.5-2 grams daily, with effects approaching significance by week 12 (source).
Neuroprotection: Animal studies, such as a 2020 study on zebrafish published in BMC Neuroscience, indicate Magnesium L-threonate may protect against brain cell death and preserve cognitive function under hypoxic conditions (source). While promising, human data is limited.
Sleep Improvement: Emerging evidence suggests it may enhance sleep quality, particularly deep sleep. A study mentioned in Verywell Health observed improved deep sleep with 1,000 milligrams daily, supporting memory retention and learning, though details on study duration and population were not specified (source).
Potential Mental Health Benefits: Research indicates possible benefits for anxiety and depression, potentially due to its influence on gamma-aminobutyric acid (GABA) neurotransmitters. A study reported improved stress and anxiety levels with Magnesium L-threonate compared to placebo, but these findings are preliminary and require further human studies (source).

The time to observe these effects varies, with cognitive improvements typically noted after 30 days to 12 weeks of consistent supplementation, based on the aforementioned studies.
Pharmacokinetics
Pharmacokinetic data for Magnesium L-threonate, particularly in humans, is limited, which complicates precise assessments of half-life and bioavailability.

Half-life: Specific half-life data for Magnesium L-threonate was not found in the reviewed literature. However, a study on calcium L-threonate, published in Acta Pharmacologica Sinica in 2011, reported a mean plasma half-life of approximately 2.5 hours for L-threonate, which may provide an indirect comparison (source). Given the structural similarities, this might suggest a similar range, but confirmation for Magnesium L-threonate is needed.
Bioavailability: The European Food Safety Authority (EFSA) concluded in a 2024 opinion that magnesium is bioavailable from Magnesium L-threonate, based on a dissociation study, two rat studies, and one human trial (source). The human trial (Liu et al., 2016; Krieger, 2013, unpublished) showed a 41% increase in urinary magnesium and a 4.9% increase in plasma magnesium at week 6 with doses of 1.5-2 grams daily. However, exact bioavailability percentages were not quantified, and sources like Healthline and product descriptions claim high bioavailability, especially for brain uptake, without specific figures (source).

Dosages
Dosage recommendations are derived from clinical studies and safety assessments:

Common Dosages: Studies typically use 1.5-2 grams per day of Magnesium L-threonate. For instance, the Chinese study used 2 grams daily, and product labels like Life Extension's Neuro-Mag provide 2,000 mg (approximately 144 mg elemental magnesium) per serving. The EFSA opinion notes that 3,000 mg daily provides about 250 mg of magnesium, aligning with the upper limit for supplemental magnesium (source).
Minimum Effective Dose: Based on cognitive benefit studies, the minimum effective dose appears to be around 1.5 grams daily, as seen in the working memory improvement study.
Maximum Safe Dose: The EFSA panel considers 3,000 mg/day safe for adults, excluding pregnant and lactating women, corresponding to 250 mg of magnesium, which aligns with the tolerable upper intake level (UL) for supplemental magnesium from readily dissociable salts.

Safety and Toxicity
Safety assessments are crucial for understanding the risk profile:

Safe Range: Up to 3 grams daily is deemed safe based on the EFSA opinion, with no significant safety concerns at this level, considering the magnesium and L-threonate content.
LD50: Specific LD50 data for Magnesium L-threonate is not available in the literature. For magnesium in general, toxicity is rare with oral supplements due to renal excretion, but high doses can lead to hypermagnesemia, especially in renal impairment. Animal studies, such as those cited in the EFSA report, did not provide human LD50 values.
When It Starts to Become Too Dangerous: Exceeding recommended doses can cause gastrointestinal side effects like diarrhea, nausea, and abdominal cramping, as noted in WebMD (source). Serious effects such as irregular heartbeat, low blood pressure, confusion, and coma are rare and typically associated with very high doses, particularly in individuals with kidney issues. The EFSA opinion suggests that intakes beyond 3 grams daily should be monitored, especially given the lack of extensive long-term human data.

Comparative Analysis
To organize the data, the following table summarizes key study findings on human trials:

Study Reference	Population	Dose (g/day)	Duration	Key Findings
Zhang et al., 2022, Nutrients A Magtein®, Magnesium L-Threonate, -Based Formula...	109 healthy Chinese adults, 18-65 years	2	30 days	Significant cognitive test improvements, especially in older participants
Metagenics Review, 2018, citing Liu et al., 2016 ([Science Review: Magnesium L-Threonate	Metagenics Institute	50 adults, 50-70 years, memory issues	1.5-2	13.1% working memory improvement at week 6, approached significance at week 12
Verywell Health, citing sleep study	Not specified	1	Not specified	Improved deep sleep, supporting memory retention and learning