Magnesium Part 2: Critical Micronutrient for Brain Health

In Part 1 of this series, we established the importance of sufficient magnesium for optimal body function.  Topics included possible signs of deficiency, breaking down the different forms of the mineral and the correct way to read a product label to ensure we supplement optimally. 

Today we begin Part 2 focusing on how magnesium in the brain requires its own analysis and specific form a critically important aspect of our discussion. This directly relates to research and treatment for pre-Alzheimer’s Disease, concussion & trauma and the management of exercise-induced stress and cortisol suppression.

From a practical standpoint, magnesium in the brain is important for the following:

• Energy Production
• Memory and Learning
• Resilience to Stress
• Positive impact on Neurotransmitters, including Dopamine and Serotonin
• It helps the brain cope with injury and inflammation (including Concussion and Trauma)
• It affects Mood as well as Anxiety and Depression (covered in a future article)

How Does it Do So Much?

Whether in our body or in our brain, magnesium acts like a ‘facilitator’ having a helping hand in several different biological mechanisms. Therefore, even a slight alteration in the amount present can have profound effects on how we feel and perform. Let us look at some of the above examples to better understand this.

Memory and Alzheimer’s Disease

Our memory system is made up of synapses which are connectors between individual neurons in our brain. These synapses code our memory and allow our neurons to communicate with one another.

The term ‘density’ refers to the strength of a synapse in your brain. As an example, a skill you can mindlessly perform would be an incredibly dense connection. While a piece of knowledge or skill you are struggling to learn would be a low-density connection.

This is where things get interesting.  What if a nutritional modification, like magnesium, were able to meaningfully impact synaptic density?  One could argue that the highest standard it could possibly meet is to produce a change to the symptoms of pre-Alzheimer’s disease.

Also known as Pre-AD, this term is used to describe the early stages of Alzheimer’s Disease which can include one or more of the following:

• Dementia
• Mild cognitive impairment, or MCI*
• Loss of memory and more advanced cognitive impairment

* Note: this is also used to describe a separate condition that occurs before Alzheimer’s Disease; it is sometimes used interchangeably with Pre-AD

Many of the symptoms associated with pre-AD are due in part to a loss of synaptic density in the brain.  This disease wreaks havoc on the neural network, severing these memory connectors and in effect, stealing the mind of the affected person.  For anyone who has witnessed the onset of this condition it can only be described as gut-wrenching. 

Positively, new research on a special form of Magnesium provided improvements to cognitive function for those affected with pre-AD, specifically: MCI (Mild Cognitive Impairment).

Enter Magnesium

Published in the Journal of Alzheimer’s Disease, researchers gave 44 patients with cognitive impairment Magnesium L-threonate (we will talk about the importance of threonate later) at 1.5 grams/day at 50-70kg; or 2 grams at 70-100kg, for 12 weeks. (1)

At the end of the trial, they found marked improvements in cognitive ability compared to the placebo group which “reversed the equivalent of 9 years of brain aging”! The higher magnesium got in the subject’s blood, the more their cognitive function improved!

These results were quite simply astonishing! Even more so, consider that currently there are ZERO effective drugs for the treatment of Alzheimer’s disease. To see a reversal of cognitive impairment of this magnitude is impressive and gives the patient and their family hope that they can offer some resistance to the debilitating effects of this awful condition.

Effectively Delivering Mg Across the Blood Brain Barrier

This is the interesting thing about science and research. They are never constant and can change with a different research approach and/or supplemental form.  For example, when it pertains to published research on magnesium, you find conclusions that state Mg does “nothing” for the brain. Case closed, right?

Obviously no and thank goodness for that!  These tests all fail to show results due to something you might remember from our first article: the use of the incorrect type of magnesium.  For years, the only forms available were Oxide, Chloride and Citrate and even though they are “magnesium” they simply cannot help your brain! 

Before explaining why, an easy way to understand this is to compare magnesium to automotive fuel.  Diesel is a type of fuel and powers some powerful engines.  Yet how well would it work if you used it in a gasoline engine?  Or a plane engine?  Not so well!  Imagine a study headline that read: “Diesel is an ineffective fuel” simply due to the researcher using it to try and power an incompatible motor?  The analogy, as odd as it may sound is bang on. Your brain is protected by something call the Blood Brain Barrier (BBB for short) and it stops solutes from gaining access to the brain and interfering with our neurons.  The stops those forms of magnesium used in the study from gaining access to the brain.  So just how does our body deliver this crucial mineral to our grey matter?

The key difference lies with how your body stores Magnesium (L-Threonate).  It is unique because Threonate is found in your cerebral spinal fluid (CSF); thus, helping to transport it across the blood-brain barrier. Specifically, it does so via GLUT-1 transporters, and gets it into your hippocampal neurons via GLUT-3.  What is this significance to this?  Your hippocampus is most important for memory, which is what makes this so cool and gives insight into how this was able to help those pre-AD patients.

Moreover, the two base ingredients – Threonate and Magnesium – must be bound to be effective.  This 2010 study found that Threonate treatment without Mg²⁺ and Mg²⁺ treatment without threonate (in multiple forms of Mg²⁺-chloride, -citrate, -glycinate, and –gluconate) failed to increase short or long-term memory ability.(4)

This was a crucial finding which leads to another remarkable Alzheimer’s related study which combines Mg²⁺ with Vitamin C and D (aka: Magtein®).  Conducted at Stanford University, researchers gave 15 adults with ‘probable’ AD this patented form of Magnesium L-Threonate. 

Remarkably, the 15 patients with ‘probable Alzheimer’s disease’ had profound improvements to their cognitive score, known as MMSE, which returned them to ABOVE the ‘cognitive decline mark’! (5)

Why was this 1800mg blend of Magnesium L-Threonate, Vitamin C and Vitamin D so effective?  Research shows that deficiencies in vitamins C & D prevent us from properly metabolizing magnesium in the brain, thus adding to the effectiveness of the formula! With that in mind, when ATP Labs formulated their product, MindMag they used this SAME Magtein®, supplying your brain with Mg-L-Threonate, Vitamin C and D.

This is a critically important aspect – look for the Trademark on the label – you do not want to use the “diesel” form of magnesium when your goal is to power your rocket fueled brain!

Resilience to Stress

Magnesium can reduce your perception of stress, but also lessen the neurological side effects of stress.  These are the actual biological consequences that your brain goes through if you are constantly stressed out!  One way it does this is by lessening the response of neurotransmitters released when

For example, when you feel stressed your brain will release catecholamines; these are neurotransmitters like dopamine and norepinephrine which help you cope with that stressful stimulus.  Their effects include increasing your heart rate, causing perspiration, dilating your pupils, vasodilation and so on.

This is a necessary response.  However, spending a large quantity of time in this elevated state will deplete micronutrients and eventually cause you to burn out and crash. In fact, one of the reasons for fatigue during exercise is due to a depletion of these catecholamines! (2)

So what ‘brain magnesium’ does is it makes this response more efficient; it prevents the excessive response of these catecholamines so that you can cope with stress for longer without experiencing the same level of burn out.

Mg Threonate: Link to Overtraining & Recovery from Exercise

We know that hard training elevates stress and cortisol.  Your ability to recover is ultimately dependent on how fast you can lower that stress post workout. To understand how magnesium in your central nervous system supports this I must first show you an extended view of this stress response to exercise – it does get a bit deep - so please stay with me! 

Our body has two primary modes which are (supposed to be) ‘automatic’: the parasympathetic state (“rest & digest”) and the sympathetic system (“fight or flight”).  A stressor like lifting heavy weights or pushing your cardiovascular system to the max, triggers our “sympathetic mode” and initially does the following:

• Activates the hypothalamic-pituitary- adrenal (HPA) axis and the autonomic nervous system.
• Activating these systems leads to release of catecholamines (like we discussed earlier), and a release of corticotropin-releasing factor (CRF) and vasopressin (AVP) from the hypothalamus of your brain.
• This leads to a release of adrenocorticotropic hormone (ACTH), which ultimately stimulates the release of glucocorticoids and cortisol from the adrenal cortex - this is designed to give you energy and amp you up. All the things we love about a hard training session!!

We also know that we cannot spend too much time in this state; we become catabolic, our sex hormones are impaired, sleep disrupted, our immune system is compromised, we suffer from poor digestion, and we do not recover. Exercise-induced stress can be just as debilitating as someone under work, life, or financial stress.  The longer it goes on unchecked we remain tilted to the sympathetic state triggering those negative effects. 

Thus, lowering this stress response ASAP after training should always be a major goal.  In other words, we need to switch from our “fight or flight” sympathetic state back into the calm “rest & digest” mode. 

Here is a critical element: One thing neurological magnesium does is decrease the release of ACTH. (3)  This means that the eventual release of cortisol is blunted, and your body can start recovering faster!  While other forms of Mg can support stress response, Magnesium Threonate is specific to support the brains role in this process.

Cause and Effect: Low Mg leads to Increased Cortisol levels and Perception of Stress

You will not find any existing research on magnesium threonate for recovery from training because this is all very new and nuanced. That said, this is an area that I feel the research will eventually catch up to my own observations as I will use an analogy to set the stage. 

Athletes often share their “feeling the playoff atmosphere” in sport. There was no better example than the Raptors championship. Remember Jurassic Park???  The noise of the crowd and extra energy from the players.  Highs were higher, lows were lower with tension ratcheting up as the game drew closer to the end.  From the players to the fans watching, it was safe to say that those hi-stakes elicited a higher than normal stress response!

While that may seem beyond the realm of experience for most people, it does deliver the point that I want to make.  No matter how much you ride your bike at home or do your workouts in the basement, being “live” in a virtual spin-class or lifting with other in a gym triggers the mind motivating you to push even harder.  Nobody wants to be the first to quit!

Where does that “motivation” come from? This is a stress response and as discussed earlier, those neurotransmitters that produce those catecholamines need support to limit the crash and support mood and focus later in the day. 

You could apply this exact same concept to exams in school, high-stakes deadlines at work or some other incredibly stressful series of events.  If you must increase your training volume trying to peak for a fitness show, weightlifting competition or something like CrossFit Sanctionals or other high volume events help your CNS cope with the demand and support it with Magnesium L-Threonate.  With stakes that high, having that extra support can be very helpful!

Magnesium: Concussions and Trauma

Our body functions best in a balanced state.  In our brain, this takes on an even greater significance with the operation of our neurons and synapses.  Remember: these are the memory pathways that control our ability to perform an activity “without thinking”.  

Glutamate is one such important excitatory neurotransmitter in your brain, but like everything in biology, too much of this is NOT a good thing. Excessive glutamate at ‘NMDA’ receptors (N-methyl-D-aspartate) is associated with memory and learning impairments, psychosis and with something known as ‘excitotoxic’ brain injury.  This condition is synonymous with concussions and mood disorders including depression.

Following a concussion, excess amounts of glutamate are being released in response to the injury. This allows huge amounts of Calcium ions to flow into the cell which disturb the balance that is required for healthy neurons and brain function. The end result is an energy mismatch - where the brain requires MORE energy than usual to cope with all the glutamate/Ca2+ (and consequential damage) but this is happening at a time when there is LESS energy compared to baseline (because of the trauma). This energy mismatch contributes to fatigue, headaches, and all the side effects of a concussion. (6)

Exactly how does Magnesium help?  It serves as a lineman would in football, protecting the QB, or in this case blocking off the calcium channel in the NMDA receptor. For glutamatergic excitatory signaling to occur (and Ca2+ influx) the Mg would need to be removed.  Its presence thereby suppresses signaling, reducing the negative effects triggered by the excessive glutamate present post-concussion. 

What happens if an individual is already operating below optimal magnesium levels in the brain?  Theoretically, we would be more susceptible to a worse outcome, since ‘our QB is already out in the open ready to be sacked.’ (7)  Interestingly, there is a 50% drop in brain magnesium post-concussion which can persist for 5 days. (8) Thus, if you are already deficient, this drop could be even more problematic.

So, can supplemental magnesium really make a difference here?

To date, the only type of supplemental magnesium used to in clinical settings of post trauma or concussion in humans is Magnesium Sulphate which does not access the brain.  As was shown in the 2010 Alzheimer’s study (mentioned earlier in this article) only the L-threonate form was able to significantly improve memory function with its positive effects on neurons and synapses.

The closest study we have to magnesium L-Threonate is a where participants were given 125-300 mg of magnesium (glycinate and taurinate) with each meal and at bedtime. They did find improvements to traumatic brain injury and other accompanying symptoms (9) which is positive, albeit not as powerful as the impact of the Threonate form which is free to access the brain independent of the GLUT-1 process. 

Based on these two studies (and a heaping amount of pre-clinical data showing Mg supports other mechanisms of concussion) it is fair to infer that increasing magnesium levels in the brain can help with concussion recovery. Form matters – inorganic forms simply do not help – so be very careful to read your labels and opt for Threonate in matters of the brain, mental stress and/or memory and a combination of Glycinate and Malate for a good overall balance for your body.

We are not Quite Done Yet! 

In two separate articles, we have covered Magnesium ALMOST from A to Z.  In our final article, we will uncover the last area that Magnesium can help: Anxiety, Depression and Mood.  While the scientific research does somewhat lag, there is enough research and some surprising findings that I hope you will be eager to review. 

References

• Liu G, Weinger JG, Lu ZL, Xue F, Sadeghpour S. 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. 2016;49(4):971‐ doi:10.3233/JAD-150538
• Cordeiro LMS, Rabelo PCR, Moraes MM, et al. Physical exercise-induced fatigue: the role of serotonergic and dopaminergic systems. Braz J Med Biol Res. 2017;50(12): e6432. Published 2017 Oct 19. doi:10.1590/1414-431X20176432
• Cuciureanu MD, Vink R. Magnesium and stress. In: Vink R, Nechifor M, editors. Magnesium in the Central Nervous System [Internet]. Adelaide (AU): University of Adelaide Press; 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507250/
• Qifeng Sun, Jason G. Weinger, Fei Mao, Guosong Liu, Regulation of structural and functional synapse density by L-threonate through modulation of intraneuronal magnesium concentration, Neuropharmacology, 2016. https://doi.org/10.1016/j.neuropharm.2016.05.006.
• Natalie L Rasgon, MD, Ph. D, The Use of Magnesium L-Threonate for the Enhancement of Learning and Memory in People with Mild to Moderate Dementia. Stanford University. ClinicalTrials.gov Identifier: NCT02210286
• Sen AP, Gulati A. Use of magnesium in traumatic brain injury. Neurotherapeutics. 2010;7(1):91-99. doi: 10.1016/j.nurt.2009.10.014
• Xue W, You J, Su Y, Wang Q. The Effect of Magnesium Deficiency on Neurological Disorders: A Narrative Review Article. Iran J Public Health. 2019;48(3):379-387.
• Cernak I, Savic VJ, Kotur J, Prokic V, Veljovic M, Grbovic D. Characterization of plasma magnesium concentration and oxidative stress following graded traumatic brain injury in humans. J Neurotrauma. 2000;17(1):53–68.
• Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362-70. doi: 10.1016/j.mehy.2006.01.047. Epub 2006 Mar 20. PMID: 16542786.