Scientists have been surprised by the discovery that magnesium plays an essential role in supporting brain plasticity, which is the sign of a youthful, flexible brain primed for optimal learning, memory, and cognitive function.1
The good news is that raising brain magnesium levels has been proven to restore critical brain plasticity and improve cognitive function.1 In a just-published landmark human study, researchers showed that they could reverse brain aging by as much as nine to 14 years in magnesium supplemented people.2
Scientists at the Massachusetts Institute of Technology (MIT) found a novel way of overcoming the problem of getting magnesium loaded into the brain due to poor absorption.1
These researchers tested a unique compound called magnesium-L-threonate and found it boosted brain magnesium levels by an approximate 15%.1
When comparing various forms of magnesium, they found that magnesium-L-threonate had the highest bioavailability and brain magnesium-loading ability.
As a result, studies show that magnesium-L-threonate improves brain plasticity, leading to direct and significant improvements in memory, learning, and cognition.3
The Foundation of Learning and Memory
The human brain is capable of forming new connections between neurons. When we take in new information, an electro-chemical signal is sent across the space between neurons (called the synaptic space). This ability of the brain to form new connections or neural pathways to communicate with each other is often referred to as brain plasticity.
Think of it as the ability to learn a new skill, like a dance move. Our brains generate new neural pathways or “wires” to master the particular skill. On the contrary, when these “wires” become faulty or deteriorate, memories start fading and individuals can forget simple things like names or phone numbers.
Brain plasticity is now understood to be the very foundation of learning and memory.4 This means that changes in memory (including the formation of new memories and learning of new concepts) requires changes in those synaptic connections, hence the term, plasticity.
As you are reading this article, your brain is forming and reforming new neural connections.
With aging, we lose brain plasticity, which results in a loss of cognitive function.5 That’s why a young person, with an active, flexible brain, easily latches on to new ideas and simply thinks faster than an older person whose brain has lost plasticity and is more fixed in its patterns.
As recently as a decade ago, scientists thought that loss of vital brain plasticity was inevitable due to age.
But they were wrong.
Recent studies have shown that increasing brain magnesium levels can reverse deteriorating brain plasticity. The result is considerable restoration of cognitive function both in healthy adults and in those with neurodegenerative diseases.1,6-8
What You Need to Know: Magnesium Improves Brain Plasticity
- Brain plasticity, the ability to remodel connections between brain cells, is the physical foundation of memory and cognition.
- Loss of memory and cognitive function in old age and in neurodegenerative diseases is the result of lost brain plasticity.
- Studies show that raising brain magnesium levels restores lost plasticity and improves cognitive function in aging animals and in models of neurodegenerative diseases.
- But conventional magnesium supplements fail to significantly raise brain magnesium levels.
- A novel form of magnesium, magnesium-L-threonate, has been developed, which is capable of rapid absorption and superior delivery to brain tissue, raising brain magnesium levels by up to 15%.
- Animal studies reveal marked and significant improvements in memory, learning, and cognition with magnesium-L-threonate supplementation, and lab studies show corresponding improvements in synaptic structures that correlate with improved brain plasticity.
- New human data shows promising results in older adults with cognitive impairment after supplementing with magnesium-L-threonate.
- Regular supplementation with magnesium-L-threonate is essential for anyone concerned about age-related loss of cognitive function or neurodegenerative diseases.
The Magnesium Connection
Magnesium is absolutely critical for maintaining healthy brain plasticity. This is because magnesium regulates how brain cells form those critical connections that are the foundation of learning and memory.
In fact, magnesium ions control tiny electrical switches (technically, “ion channels”) in brain cells.9 The more signals that these electrical switches transmit, the stronger the connections between cells, and the stronger the formation of the resulting memory. Thus, magnesium concentrations are an essential part of brain plasticity-the ability to add, remove, or revise cell-to-cell connections to regulate learning and memory.
Numerous studies demonstrate the dangerous impact of insufficient magnesium on brain health.9,10 Lab studies show us that depriving brain cells of sufficient magnesium impairs their ability to participate in optimal plasticity.10,11 In animals and humans, we are now able to see that this loss of plasticity leads directly to a poorer performance on tests of memory.12,13
The reason memory is impacted is because low levels of magnesium create decreases in the strengthening of connections between brain cells that lead to memory formation.10
In addition to impacting memory, chronically low calcium and magnesium levels in the diet have also been shown to correlate with a high incidence of neurodegenerative diseases.14
Basic lab studies have shown that boosting magnesium concentrations at excitatory synapses can enhance brain plasticity.15 In brain cells cultured from the hippocampus (the part of the brain where we store and retrieve memories), these changes led to more permanent enhancements of brain plasticity, demonstrating long-lasting improvement.15 (It is important to note that the levels of magnesium needed to improve plasticity are well within the normal physiological range, not exceedingly high.)
Studies in diabetic rats provide further support for magnesium’s ability to reverse losses in brain plasticity and restore cognitive function.11
Like diabetic humans, these rats have a high risk of developing Alzheimer’s disease. Researchers found that elevating brain magnesium levels with injected magnesium protected learning and memory in diabetic rats with spontaneous Alzheimer’s-like symptoms. Elevating brain magnesium levels also reversed impairments in synaptic function and long-term potentiation (the cellular equivalent of learning).11
These studies make it clear that elevating brain levels of magnesium helps to improve cognition by improving plasticity (the ability to make connections between brain cells) and long-term potentiation (the strengthening of those connections).
But, one of the biggest challenges that researchers have encountered is delivering sufficient amounts of magnesium into the brain. Fortunately, scientists at the Massachusetts Institute of Technology (MIT) have found a solution.
A Breakthrough Form of Magnesium
Scientists at MIT set out to find a better-absorbed form of magnesium that also could boost concentrations of the mineral in the brain.1 After testing numerous compounds, they found what they were looking for in a unique compound called magnesium-L-threonate. This is a complex of magnesium along with threonic acid, a breakdown product of vitamin C.1,16
Figure 1 shows the dramatic results of treating rats with magnesium-L-threonate (MgT) compared with untreated control animals and with those supplemented with two other forms of magnesium.1 Only magnesium-L-threonate proved capable of significantly raising magnesium levels in spinal fluid, which is a measure of brain magnesium.
Magnesium-L-threonate’s effects were even more remarkable on short- and long-term memory performance in live rats (Figure 2). Compared with the other forms of magnesium, the animals that were supplemented with magnesium-L-threonate demonstrated significantly greater memory retention over 10 minutes and 12 hours (Refer to Figure 2 charts on next page).1
In addition to short- and long-term memory improvements, rats supplemented with magnesium-L-threonate demonstrated enhanced learning abilities and enhanced working memory, which are essential for normal cognitive function.1
And in aged rats, supplemented animals were better at pattern completion (ability to retrieve memories based on incomplete information) compared with control animals.1
Microscopic examination of brain tissue explained the reason for these dramatic improvements. As expected, the rats supplemented with magnesium-L-threonate had higher densities of synaptic proteins associated with memory formation, especially in the hippocampus. These findings correlated with the animals’ improved memory performance on testing.1
In addition, the magnesium increased the number of release sites at the presynaptic nerve endings, but reduced their overall probability of releasing neurotransmitters. This reconfiguration enabled synapses to more finely tune their transmissions, resulting in greater plasticity. The synapses were, in effect, “trained” to respond only to the “right” stimuli, producing improved memories in the live animals.1
Finally, the increase in brain magnesium levels enhanced long-term potentiation, which is the process that refers to the strengthening of connections between brain cells based on recent patterns of activity that is associated with enhanced learning and memory.1,10
New Findings for Post-Traumatic Stress Disorder
While Alzheimer’s is the most urgent demonstration of restoration of brain plasticity by magnesium-L-threonate, it is far from the only potential application for this supplement.
Researchers also found that magnesium-L-threonate has beneficial effects for those suffering from post-traumatic stress disorder (PTSD). 6
Sometimes when our brains form connections, they aren’t good ones. For example, certain objects or events linked with a previous danger triggers fear memories. In healthy people, these fear memories fade in time as the object triggering them is experienced in a safe environment. (Perhaps this is the likely scientific explanation for the phrase “time heals all wounds.”)
For example, if you experienced a house fire, hearing fire engines could reproduce the feelings of fear experienced from the fire itself. In time, that feeling will fade when the triggering event is experienced in a safe environment.
Unfortunately, in people who suffer from post-traumatic stress disorder, that fear response does not fade with time. This is likely due to the fact that post-traumatic stress disorder induces a sharp reduction in brain plasticity.21-24
Exciting research has demonstrated that magnesium-L-threonate can help speed up this recovery process in people suffering from post-traumatic stress disorder.
Scientists studied magnesium-L-threonate in rats with conditioned fear responses (the animal equivalent of post-traumatic stress disorder). Amazingly, the magnesium-L-threonate treatment helped the fear memory fade with time, without impacting the original memory.6,25
Research shows that magnesium-L-threonate enhances brain plasticity in specific regions of the brain most affected by traumatic events. 6 Because of these dramatic results, scientists are suggesting that magnesium could be a novel supplement for those suffering from post-traumatic stress disorder, anxiety, or depression.6,25
What Is Magnesium?
Magnesium, the fourth most abundant mineral in the body, is known to be a co-factor for more than 300 reactions catalyzed by enzymes, including those essential for energy release from food and conversion to cellular work through formation of adenosine triphosphate, or ATP, in mitochondria. Magnesium is also required for the synthesis of DNA and RNA.27
Magnesium is especially important in all of our bodies’ electrical and electrochemical activities, including muscle contractions, heart rhythm, nerve conduction, and brain cell activity.27
The most common disturbance of magnesium in our bodies is hypomagnesemia, or low blood magnesium levels, which is widely recognized as a cause of seizures, hypertension, stroke, migraine headaches, attention deficit hyperactivity disorder, and metabolic conditions such as insulin resistance and type II diabetes.27
In addition to all of these known functions, magnesium has been found to be the controlling and essential factor in regulating synaptic plasticity in the brain, which is the physical process that underlies what we perceive as learning and memory.1
Recent Human Study
A remarkable human study on magnesium-L-threonate was released late in 2015 with compelling results that corroborate and extend all of the previous laboratory findings.2
Men and women aged 50 to 70, who reported cognitive problems (e.g., memory and concentration) were enrolled in the study. They were randomly assigned to receive either placebo or a supplement containing magnesium-L-threonate. Subjects took 1.5 grams per day of the supplement if they weighed less than 154 pounds, and 2 grams per day if they weighed more.
Subjects were evaluated before starting the supplement and again at weeks six and 12 (end of the study). At each evaluation, subjects participated in a series of tests of cognitive function, while blood and urine tests were performed to calculate total body magnesium status.2
By 12 weeks, lab results showed that magnesium-L-threonate was effective at loading magnesium into the body, as well as into cells (red blood cells were used because it is impossible to safely sample brain cells in humans).2
This form of magnesium was shown to be effective at loading magnesium into the brain and at enhancing brain function. This was made clear by results of cognitive testing. Already by week six, supplemented subjects demonstrated significantly increased speed in tests of executive function (e.g., reasoning, problem-solving, and planning). By week 12, that increased speed reached an approximate 20% improvement over baseline, while placebo recipients experienced no significant change.2
There was also a significant 13.1% improvement in supplemented subjects’ working memory (the memory we use, for example, to remember where we put things) and a significant 37.6% improvement in episodic memory (for example, the ability to put new faces and names together). And composite scores of overall cognitive ability rose significantly from baseline and compared with placebo at both weeks six and 12.2
Tellingly, magnesium loading into red blood cells was significantly correlated with enhancement in overall cognitive ability in supplemented patients. This was a strong validation of earlier animal studies in which raising brain magnesium levels boosted cognitive function.1
An unexpected benefit was also demonstrated when the researchers examined fluctuations in cognitive performance over time. Such a fluctuation is known to be an early sign of impending cognitive impairment.2,26 Not only did supplemented patients experience less cognitive fluctuation, but the changes that they did experience were primarily positive (performing better than usual).
All of these data provide impressive support for the use of magnesium-L-threonate to improve cognitive function. But the real shocker comes with an analysis of this study’s subjects in the context of normal brain aging.
The researchers compared results of their study with data from a second study of cognitively normal subjects. They determined that cognitive performance fell about 1.04% per year in the cognitive normal subjects. Researchers established that baseline performance in the first study was about 10% lower than that of age-matched controls. But after 12 weeks of supplementation, the average increase in performance was 10.3%, essentially restoring performance to that of age-matched people without cognitive decline.2
A still more remarkable finding became evident when researchers used the normal cognition study to assign a “brain age” to each of their own study subjects. Using this calculation, for example, a 50-year-old with a 10% worse performance on cognitive testing would have a brain age equivalent to that of a cognitively normal 60-year-old (approximately 1% function loss per year).2
Using that calculation, the researchers found that even though the average chronological age of subjects who completed their study was 57.8 years, their average brain age at baseline was 68.3 years. But by 12 weeks, the brain age of the supplemented subjects had fallen by an average of 9.4 years, while that of placebo recipients fell by less than a year.2
In other words, supplementation with magnesium-L-threonate resulted in an effective reversal of brain age to near normal. The brain age reversal in subjects who had significant increases in red blood cell magnesium was still higher, at 14.6 years, moving those individuals into a brain age in fact younger than their actual age in years!
The loss of brain plasticity is at the heart of age-related loss of cognitive function. As our brains lose flexibility, we lose the ability to learn new concepts, to make sharp judgments, and to develop new skills.
Loss of brain plasticity is implicated in both the “natural” loss of brain function with aging and with accelerated cognitive decline as seen in Alzheimer’s and other neurodegenerative diseases.
Restoring brain plasticity has become a major focus of neuroscientists aiming to slow or eliminate the loss of brain function over time.
Studies show that boosting brain magnesium levels dramatically renews the ability of brain cells and, in animals, to form new memories and discriminate between existing ones. But conventional magnesium supplements are inadequately delivered to brain tissue, challenging our ability to effectively raise brain magnesium levels.
The development of magnesium-L-threonate appears to have shattered that barrier. Studies show that this compound enters brain tissue more effectively than other magnesium preparations, and is significantly more effective at restoring memory functions and brain plasticity in numerous animal models, including those of Alzheimer’s disease.
Recent new human data on magnesium-L-threonate shows promising results in older adults with cognitive impairment. Those interested in preventing cognitive decline and in restoring active, flexible brains should consider daily supplementation with magnesium-L-threonate. No other magnesium preparation comes close to its performance.
Repinted with kind permission of LifeExtension
- Slutsky I, Abumaria N, Wu LJ, et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010;65(2):165-77.
- Liu G, Weinger JG, Lu ZL, et al. Efficacy and safety of MMFS-01, a synapse density enhancer, for treating cognitive impairment in older adults: a randomized, double-blind, placebo-controlled trial. J Alzheimers Dis. 2015;49(4):971-90.
- Mickley GA, Hoxha N, Luchsinger JL, et al. Chronic dietary magnesium-L-threonate speeds extinction and reduces spontaneous recovery of a conditioned taste aversion. Pharmacol Biochem Behav. 2013;106:16-26.
- Mahncke HW, Bronstone A, Merzenich MM. Brain plasticity and functional losses in the aged: scientific bases for a novel intervention. Prog Brain Res. 2006;157:81-109.
- Wang D, Jacobs SA, Tsien JZ. Targeting the NMDA receptor subunit NR2B for treating or preventing age-related memory decline. Expert Opin Ther Targets. 2014;18(10):1121-30.
- Abumaria N, Yin B, Zhang L, et al. Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala. J Neurosci. 2011;31(42):14871-81.
- Basheer MP, Pradeep Kumar KM, Sreekumaran E, et al. A study of serum magnesium, calcium and phosphorus level, and cognition in the elderly population of South India. Alexandria J Med.
- Li W, Yu J, Liu Y, et al. Elevation of brain magnesium prevents and reverses cognitive deficits and synaptic loss in Alzheimer’s disease mouse model. J Neurosci. 2013;33(19):8423-41.
- Palacios-Prado N, Chapuis S, Panjkovich A, et al. Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36. Nat Commun. 2014;5:4667.
- Danysz W, Parsons CG. The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer’s disease: preclinical evidence. Int J Geriatr Psychiatry. 2003;18(Suppl 1):S23-32.
- Xu ZP, Li L, Bao J, et al. Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer’s model. PLoS One. 2014;9(9):e108645.
- Murphy T, Dias GP, Thuret S. Effects of diet on brain plasticity in animal and human studies: mind the gap. Neural Plasticity. 2014;2014:32.
- Bilbo SD, Smith SH, Schwarz JM. A lifespan approach to neuroinflammatory and cognitive disorders: a critical role for glia. J Neuroimmune Pharmacol. 2012;7(1):24-41.
- Taniguchi R, Nakagawasai O, Tan-no K, et al. Combined low calcium and lack magnesium is a risk factor for motor deficit in mice. Biosci Biotechnol Biochem. 2013;77(2):266-70.
- Slutsky I, Sadeghpour S, Li B, et al. Enhancement of synaptic plasticity through chronically reduced Ca2+ flux during uncorrelated activity. Neuron. 2004;44(5):835-49.
- Available at: http://www.fda.gov/downloads/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/UCM400322. Accessed February 26, 2016.
- Li W, Yu J, Liu Y, et al. Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer’s disease mouse model. Mol Brain. 2014;7:65.
- Yu J, Sun M, Chen Z, et al. Magnesium modulates amyloid-beta protein precursor trafficking and processing. J Alzheimers Dis. 2010;20(4):1091-106.
- Bisel BE, Henkins KM, Parfitt KD. Alzheimer amyloid beta-peptide A-beta25-35 blocks adenylate cyclase-mediated forms of hippocampal long-term potentiation. Ann N Y Acad Sci. 2007;1097:58-63.
- Yu X, Guan PP, Guo JW, et al. By suppressing the expression of anterior pharynx-defective-1alpha and -1beta and inhibiting the aggregation of beta-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice. Faseb j. 2015;29(12):5044-58.
- Chao LL, Tosun D, Woodward SH, et al. Preliminary evidence of increased hippocampal myelin content in veterans with posttraumatic stress disorder. Front Behav Neurosci. 2015;9:333.
- Cominski TP, Jiao X, Catuzzi JE, et al. The role of the hippocampus in avoidance learning and anxiety vulnerability. Front Behav Neurosci. 2014;8:273.
- Powers MB, Medina JL, Burns S, et al. Exercise augmentation of exposure therapy for PTSD: rationale and pilot efficacy data. Cogn Behav Ther. 2015;44(4):314-27.
- Wingo AP, Almli LM, Stevens JJ, et al. DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression. Nat Commun. 2015;6:10106.
- Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=9415df25-4759-4d28-a789-5945ea5355d1&cKey=a899d2d6-6d4e-4201-8d26-6a3c82145103&mKey=%7b081F7976-E4CD-4F3D-A0AF-E8387992A658%7d#. Accessed February 29, 2016.
- Palop JJ, Chin J, Mucke L. A network dysfunction perspective on neurodegenerative diseases. Nature. 2006;443(7113):768-73.
- Grober U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015;7(9):8199-226.