Can Magnesium L-Threonate (MagTein) Really Make you Smarter?
What is Magnesium Threonate and What is it Supposed to do?
Magnesium threonate belongs to a class of supplements known as nootropics or smart drugs. If the whole health supplements market abounds in half-truths, unsubstantiated claims and huge leaps of logic, then nootropics are in a league of their own. The claims about strange botanical extracts, or fungus pastes, which will either 'excite your synaptic receptors' or have an 'inhibitory, calming effect' (both appear to be equally desirable), are not just unsubstantiated, most of the time they don't make any kind of sense.
The evidence for Magnesium threonate is very different. It is actually based on proper neuroscience, by a team in MIT, and published in a peer review journal. And not just any journal, but in the very prestigious Neuron!
So what is magnesium threonate? And could it really be the amazing pill which will make you smarter, improve your memory, and stop your brain deteriorating with age?
Magnesium Threonate Facts at a Glance
- Magnesium threonate (MgT) consists of an mg2+ ion chelated to threonine, a vitamin C metabolite.
- It is claimed that the chelation increases its bioavailability, and that it can increase brain Mg2+ levels, unlike other supplements.
- Studies in rats showed that elevated Mg2+ modify signalling through the NMDA receptor in the hippocampus and increase the numbers of synaptic connections.
- Magnesium threonate supplementation improved the performance in working and normal spacial memory of young and aged rats.
- All the available data on the efficacy of MgT is in rats. A human trial with a very small number of people was started in 2012, but the results haven't been published yet.
Magnesium is an Essential Mineral, and it Does Act in the Brain
Magnesium L-threonate is simply a form of magnesium ions chelated to a fairly simple organic molecule, threonine, a metabolite of vitamin C. It is also marketed under the name MagTeinTM (for which a patent is pending). The claims about the ability of the substance to make you smarter come from two angles.
- That elevating magnesium brain levels improves cognitive function
- That chelating Mg2+ to threonine can in fact increase magnesium brain levels, in a way that other supplements can't.
The fact that Magnesium is an essential mineral is not in dispute. It takes part in hundreds of enzymatic reactions and is important for the functioning of pretty much every system in the body including the central nervous system (see more about this below).
The big question is: how many people are actually deficient in magnesium? And if you don't have a deficiency, will pumping more of the stuff into your brain actually bring any benefits?
Do we Really Need More Magnesium?
This is one of the Big Lies I see in supplement marketing copy everywhere. They write about all the important functions of a nutrient. Then they immediately jump to the conclusion that more is better. No matter how important a chemical is, the body needs a certain amount of it, and then giving it more is useless at best, and could be actually harmful.
It is actually quite complicated to detect a magnesium deficiency. A lot of the mineral is stored in bones, and blood levels fluctuate in any one person and are not a reliable indicator of overall levels.
Well the data from the MIT seems to suggest that getting more magnesium into the brains of normal rats (and yes it is all animal studies) does make them smarter. The assumption is that rats fed a normal lab rat diet are already getting the magnesium that rats need.
So what is the evidence for MagTein, and are there any problems with? But before we get into that, here's a little primer on synapses, neurotransmitters, and how learning in the brain is thought to happen:
Synapses, Neurotransmitters, and Synaptic Plasticity
Synapses are the gaps between nerve endings. The axon of one nerve cell does not actually touch the dendrites of another, there is a little gap between them. Electrical impulses cannot jump across the synapse, so for the nerve impulse to continue on its transmission, it has to be converted into a chemical signal, a neurotransmitter.
There are many different neurotransmitters, some are simple amino acids like glycine or glutamate. Acetylcholine and GABA are also examples of neurotransmitters. They are found in vesicles in the presynaptic neurone. When the neurone is excited, they are released into the synapse, and on the other side they bind to receptors. This causes either an electrical impulse in the post-synaptic neurone (excitation) or a block of further transmission (inhibition) depending on the neurotransmitter and the receptor.
But synapses are far more than just obstacles in the smooth transmission of nerves. They are at the centre of encoding memories and learning. Their ability to transmit a nerve signal can be varied, for example by increasing the number of neurotransmitter vesicles, or the number of receptors. This is known as synaptic plasticity, and is fundamental to at least some forms of memory.
Are you interested in taking a 'smart drug'?
A Brief History of Synaptic Plasticity, NMDA, and LTP
1949 - In his book on behaviour Donald Hebb introduces Hebb's rule, which states the if a presynaptic neurone repeatedly stimulates a postsynaptic neurone, the synaptic connection between them will become stronger. Or..."Cells that fire together, wire together" as the rule is commonly known.
1966 - Terje Lomo working in Per Anderson's lab in Norway discover long-term potentiation (LTP) in rabbit hippocampus. He discovers a long-lasting (months) enhancement in the synaptic connection of neurones that are activated synchronously. LTP is generally considered to be one of the major mechanisms resulting in learning and memory.
1999 - A team from Princeton university publish their work on creating a 'smart mouse'. Since NMDA receptors were generally believed to act as 'coincidence detectors', detecting when neurone when activated synchronously, they tested the effects of increasing the number of NMDA 2B receptors in transgenic mice. The mice showed significant improvements in learning and memory. The authors concluded "Our results suggest that genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible."
2004 - A study published in Neuron by a team from MIT established the important function of magnesium in blocking the NMDA receptors during uncorrelated activity. Magnesium seems to enhance synaptic plasticity by blocking background noise.
2010 - The same MIT team publishes another paper in Neuron showing that rats fed on a diet supplemented with magnesium threonate have an elevated brain magnesium levels. The MgT fed rats showed improved synaptic connections, and performed better in tests of working and long term memory.
The Author of the Neuron Papers Talks about Magnesium
But what about Human Magnesium Threonine Trials?
The 2010 Neuron paper testing magnesium threonate in rats is very promising. Fist of all it showed that dietary MgT can increase magnesium levels in cerebro-spinal fluid. From the magnesium supplements tested in the paper (magnesium chloride, citrate, and gluconate) it was the only one that achieved an effect on brain magnesium.
The paper also showed that elevated magnesium levels improved NMDA receptor signalling, and increase the number of synapses in the hippocampus. This is highly significant because synapse density decreases with age, which could be one of the causes of age-related decline in cognitive functions.
The functional tests were done on young and aged rats, and in both cases animals receiving MgT in the diet did significantly better on memory tests.
The animal studies are highly suggestive, but they are only animal studies. Of course rats are a well established model for human brain function, and frequently phenomena observed in rat brains also hold true for human brains. However, you don't really know how something works in humans until you test it in humans.
At the moment there doesn't seem to be any published magnesium threonate human studies that show that the supplement can enhance cognition or memory. A small trial including 50 people was apparently started in 2012, but it hasn't been published yet. Even if it does reproduce the rat data, the number of trial subjects is so small, that many people doubt if the results will have any meaning.
Magnesium threonate does appear to have a lot more solid scientific basis to claiming that it can enhance cognition and memory, and might prevent, and even reverse age-related decline. However, until human trial data is published, it is impossible to say that it does what it claims.