Dr. Ron’s Research Review – June 26, 2013

© 2013

This week’s research review focuses on magnesium-L-threonate.

L-Threonate is a metabolite of Vitamin C that is currently being investigated for some vitamin C-like properties as well as its ability to greatly enhance mineral uptake.

In human, dramatic increase (100%–300%) in blood Mg2+ via intravenous infusion of MgSO4 corresponds to elevation in cerebrospinal fluid Mg2+ only by 10%–19%. (McKee, Brewer et al. 2005)

An unpublished study compared the bioavailability of four commercially available Mg2+ compounds (magnesium-chloride, -citrate, -glycinate, and -gluconate) with magnesium-L-threonate and magnesium-gluconate. Both MgT and magnesium-gluconate in milk have higher bioavailability (evaluated by absorption, excretion, and retention rate of magnesium). (X.Z., F. Mao, Y. Shang, N.A., and G.L., unpublished data) (Slutsky, Abumaria et al. 2010)

Dr. Ron


An article by Kelly C. Heim, Ph.D. for Pure Encapsulations contains a chart comparing different forms of magnesium. (Heim 2012)


Figure 1. Evaluation of magnesium concentration in the cerebrospinal fluid following administration of different magnesium compounds.


Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala

         (Abumaria, Yin et al. 2011) Download

Anxiety disorders, such as phobias and posttraumatic stress disorder, are among the most common mental disorders. Cognitive therapy helps in treating these disorders; however, many cases relapse or resist the therapy, which justifies the search for cognitive enhancers that might augment the efficacy of cognitive therapy. Studies suggest that enhancement of plasticity in certain brain regions such as the prefrontal cortex (PFC) and/or hippocampus might enhance the efficacy of cognitive therapy. We found that elevation of brain magnesium, by a novel magnesium compound [magnesium-l-threonate (MgT)], enhances synaptic plasticity in the hippocampus and learning and memory in rats. Here, we show that MgT treatment enhances retention of the extinction of fear memory, without enhancing, impairing, or erasing the original fear memory. We then explored the molecular basis of the effects of MgT treatment on fear memory and extinction. In intact animals, elevation of brain magnesium increased NMDA receptors (NMDARs) signaling, BDNF expression, density of presynaptic puncta, and synaptic plasticity in the PFC but, interestingly, not in the basolateral amygdala. In vitro, elevation of extracellular magnesium concentration increased synaptic NMDAR current and plasticity in the infralimbic PFC, but not in the lateral amygdala, suggesting a difference in their sensitivity to elevation of brain magnesium. The current study suggests that elevation of brain magnesium might be a novel approach for enhancing synaptic plasticity in a regional-specific manner leading to enhancing the efficacy of extinction without enhancing or impairing fear memory formation.

Enhancement of learning and memory by elevating brain magnesium

         (Slutsky, Abumaria et al. 2010) Download

Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed magnesium compound (magnesium-L-threonate, MgT) leads to the enhancement of learning abilities, working memory, and short- and long-term memory in rats. The pattern completion ability was also improved in aged rats. MgT-treated rats had higher density of synaptophysin-/synaptobrevin-positive puncta in DG and CA1 subregions of hippocampus that were correlated with memory improvement. Functionally, magnesium increased the number of functional presynaptic release sites, while it reduced their release probability. The resultant synaptic reconfiguration enabled selective enhancement of synaptic transmission for burst inputs. Coupled with concurrent upregulation of NR2B-containing NMDA receptors and its downstream signaling, synaptic plasticity induced by correlated inputs was enhanced. Our findings suggest that an increase in brain magnesium enhances both short-term synaptic facilitation and long-term potentiation and improves learning and memory functions.


Abumaria, N., B. Yin, et al. (2011). "Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala." J Neurosci 31(42): 14871-81. [PMID: 22016520]

Heim, K. C. (2012). "Nourishing the brain with magnesium: A new approach to cognitive performance." from http://www.pureencapsulations.com/education-research/newscaps/newscap-05-15-12.

McKee, J. A., R. P. Brewer, et al. (2005). "Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in humans with acute brain injury undergoing prolonged induced hypermagnesemia." Crit Care Med 33(3): 661-6. [PMID: 15753761]

Slutsky, I., N. Abumaria, et al. (2010). "Enhancement of learning and memory by elevating brain magnesium." Neuron 65(2): 165-77. [PMID: 20152124]