Magnesium L-threonate is the magnesium salt of a naturally occurring
vitamin C metabolite L-threonic acid. Magnesium, a divalent cation, is
important for neuronal activity as it is a co-factor for enzymes present
in the neurons or glial cells.1,2
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Magnesium and Cognitive Health
Two observational studies found that individuals with a diet rich in
magnesium have a lower risk of cognitive decline:
- 86% reduced risk in an Australian cohort of 1,400 elderly people
between 60-72 years of developing mild cognitive impairment (MCI)
in men (p=0.008).3 - 74% reduced risk in 1,081 Japanese men and women older than
60 years of developing vascular dementia and 37% reduced risk of
developing all-cause-dementia.4
Mechanism of Action
Magnesium regulates the opening of N-methyl-D-aspartate receptor
(NMDAR) in the brain. This receptor plays a critical role in cognitive
function and is the target of various neurological treatments.5
Structurally, NMDAR is made up of two glycine-binding NR1 subunits,
and two of four glutamate-binding NR2 subunits: NR2A, NR2B, NR2C,
and NR2D (Figure 1).
Research Highlights
- Magnesium L-threonate administered at 1.5 or 2 grams daily
in addition to vitamins C and D showed improvement in
measures of cognitive and executive function in older adults
compared to those given placebo and vitamins.12 - Aged animals given magnesium L-threonate showed
improvement in spatial memory (memory in relation to
environment) and spatial orientation; these improvements
declined with discontinuation of magnesium L-threonate.11 - Magnesium L-threonate has been shown to upregulate
expression of the NR2B subunit of the NMDA receptor in
cultured hippocampal neurons.10 This action is thought to
enhance memory by increasing long-term potentiation
(i.e., synaptic efficiency), which is critical for learning.9
Long-Term Potentiation
Out of the four NR2 subunits, NR2B is of prime importance because
it confers greater synaptic plasticity which helps to create and retain
memories. However, the number of NR2B subunits have been shown
to decrease with age in animals.6 Overexpression of the NR2B subunit
enhanced memory in transgenic rats and mice compared to wild-type
littermates.7 NR2B is also thought to influence memory formation by
increasing the long-term potentiation (LTP) through the activation of
calcium/calmodulin dependent protein kinase II (CaMKII) (Figure 2).8
Long-term potentiation is long lasting increase in synaptic efficacy,
which is critical for learning and memory.9
Magnesium L-Threonate Enhances Spatial Memory in Animals
Magnesium L-threonate upregulated the expression of NR2B subunit in cultured hippocampal neurons.10 Compared to control, rats treated with magnesium L-threonate had:
- Increased NR2B subunit expression in the hippocampus by 60% (p<0.001)
- Upregulated the activation of CaMKII by 92% (p<0.01)
- Enhanced the magnitude of LTP by 52% in the hippocampal slices
(p<0.0001).11
This increase in NR2B subunit expression and magnitude of LTP by magnesium L-threonate translates into enhanced hippocampus dependent memory. In this study, spatial working memory, memory regarding one’s environment, and spatial orientation, were assessed at day 0 and day 24 by T maze. At day 0, rats in both groups made 30% fewer correct choices, but at day 24 aged rats treated with magnesium L-threonate made about 15% more correct choices than untreated rats (p<0.05). Interestingly, the improvement in spatial memory of aged rats declined within 12 days of stopping the treatment but improved when the treatment was reinitiated.
Magnesium L-Threonate Improves Memory in Older Adults
The effect of magnesium L-threonate on memory was studied in a randomized double-blind placebo controlled study with 50 men and women between 50-70 years of age with self-reported complaints of memory and concentration.
Subjects were treated with 1.5-2 g/day of magnesium L-threonate, along with 200 IU of vitamin D and 30 mg of vitamin C for 12 weeks. Working memory and capacity to store and process information, measured by digit span test, improved by 13.1% at week 6 compared to placebo (p=0.023). However, this effect on working memory approached significance at week 12, which was the end of the study (p=0.064).12
Conclusion
Preclinical studies demonstrate that magnesium L-threonate may increase synaptic plasticity through increasing the expression of one of the NMDA receptor subunits. In vivo and clinical study results show that magnesium L-threonate positively influences cognitive measures of memory. More clinical studies are underway to further evaluate effects of magnesium L-threonate on memory and other dimensions of cognition.
