What is magnesium threonate?

What is Magnesium Threonate?

Magnesium threonate (also known as magnesium L-threonate or L-TAMS) is a specific magnesium compound that uniquely crosses the blood-brain barrier to elevate brain magnesium levels, thereby enhancing cognitive function through increased synaptic density and neuroplasticity. 1, 2

Chemical Composition and Formulation

• Magnesium threonate consists of magnesium bound to L-threonic acid, creating a salt form (L-Threonic acid Magnesium salt or L-TAMS) that has superior brain bioavailability compared to other magnesium compounds 2, 3
• It is available as a medical food ingredient (marketed as Magtein®) and is included in formulations containing phosphatidylserine, vitamins C and D, and other cofactors 1, 4
• The compound is found naturally in cerebrospinal fluid (CSF), and oral administration elevates CSF threonate levels 2

Mechanism of Action

The threonate component is essential and acts through glucose transporters (GLUTs) to directly increase intraneuronal magnesium concentration, which distinguishes it from other magnesium salts that cannot achieve the same neurological effects 2:

• Threonate specifically elevates intracellular magnesium in neurons, while other common magnesium anions (sulfate, oxide, chloride) fail to produce equivalent results 2
• Elevated neuronal magnesium increases NMDA receptor (specifically NR2B-containing) density and signaling 2, 3, 5
• This leads to upregulation of synaptic proteins (synaptophysin, synaptobrevin), increased functional presynaptic release sites, and enhanced synaptic plasticity 2, 3
• The compound boosts mitochondrial membrane potential and increases both structural and functional synapse density 2
• Magnesium threonate activates the ERK/CREB signaling pathway, which promotes adult hippocampal neurogenesis 6

Clinical Effects on Cognition

Human clinical trials demonstrate that magnesium threonate-based formulations significantly improve memory and cognitive function across all age groups, with older adults showing more pronounced benefits 4:

• In a double-blind, placebo-controlled study of 109 healthy Chinese adults (ages 18-65), subjects receiving 2g/day of a magnesium threonate-based formula showed significant improvements in all five subcategories of standardized memory testing plus overall memory quotient scores after 30 days 4
• Animal studies show enhancement of learning abilities, working memory, short-term and long-term memory, and pattern completion ability in both young and aged rats 3
• The compound enhances retention of fear extinction without impairing or erasing original fear memories, suggesting potential applications in anxiety disorders and PTSD 5
• In Alzheimer's disease mouse models, magnesium threonate ameliorates cognitive deficits by attenuating impaired adult hippocampal neurogenesis 6

Regional Brain Specificity

A critical distinction is that magnesium threonate produces region-specific effects in the brain, enhancing synaptic plasticity preferentially in the prefrontal cortex and hippocampus rather than uniformly across all brain regions 5:

• Elevation of brain magnesium increases NMDAR signaling, BDNF expression, and synaptic plasticity in the prefrontal cortex but not in the basolateral or lateral amygdala 5
• This regional specificity explains why the compound can enhance extinction learning (PFC-dependent) without affecting fear memory formation (amygdala-dependent) 5

Distinction from Standard Magnesium

Magnesium threonate should not be confused with standard magnesium supplements used for systemic magnesium deficiency 7, 8:

• Standard magnesium formulations (magnesium sulfate, magnesium oxide) are used for treating hypomagnesemia, eclampsia prevention, cardiac arrhythmias, and electrolyte disturbances 7, 8
• These conventional forms have poor brain penetration and are ineffective for cognitive enhancement 2, 3
• Magnesium oxide, commonly prescribed for hypomagnesemia in conditions like short bowel syndrome, has poor absorption and may worsen diarrhea 7

Clinical Context

Magnesium threonate represents a neurologically-targeted formulation designed specifically for cognitive enhancement rather than systemic magnesium repletion 1, 2:

• It is classified as a medical food requiring medical supervision, particularly in formulations designed for patients with methylation pathway deficiencies 1
• The compound's unique ability to elevate brain magnesium makes it fundamentally different from magnesium used in emergency medicine for cardiac arrest, eclampsia, or electrolyte replacement 7