Life Extension Magazine®
As our brains age, we lose connections between brain cells called synapses.1
Loss of synapses is associated with brain shrinkage which is a structural predictor of cognitive decline.1-3
Preclinical studies show that by increasing brain magnesium concentrations, synaptic density (number) and plasticity (ability to adapt to stimuli) are enhanced.4-7
Regular magnesium intake, however, does not increase brain levels much because many forms of this mineral fail to efficiently cross the blood-brain barrier.6,8-10
MIT researchers developed a novel form called magnesium L-threonate that changes all that. It is easily absorbed and does cross the blood-brain barrier.8,11,12
Taken orally, magnesium L-threonate has the ability to significantly boost brain magnesium levels. This enables it to improve synaptic density and plasticity, and thus help reverse these aspects of brain aging.8,10,13,14
The effects are striking. In a human study, volunteers who took magnesium L-threonate had a reversal in measures of brain age of more than 9 years.13
Magnesium’s Brain Impact
The mineral magnesium works throughout the body as a cofactor required for normal functioning of hundreds of enzymes.15,16
Magnesium's role in the brain is especially critical. It protects synapses, the communication connection points between brain cells.10
In order to learn, or access memory, the brain's synapses require plasticity, the ability to adapt and change in response to stimuli.17
Decreased synaptic plasticity is a major contributor to cognitive decline in older adults.1
Animal studies show that increasing brain levels of magnesium:7,8,10-12,18
- Increases the total number of synapses,
- Improves synaptic plasticity,
- Stimulates the growth of new brain cells, and
- Improves learning and memory.
Reaching the Brain
The majority of the U.S. population are not getting enough magnesium in their diet.19 And very little magnesium from supplements enters the brain.8,20
A clinical study found that increasing blood magnesium levels by approximately 160%, changed magnesium levels in cerebrospinal fluid by only 15%.21
As a result, taking standard oral magnesium can provide bodily benefits but may not significantly improve brain function.8
There is a way around this problem. Researchers developed a specific form of magnesium that elevates levels of magnesium in the brain.8,10 It is called magnesium L-threonate (MgT).
In a rodent study, MgT raised cerebrospinal fluid levels of magnesium by approximately 15% and successfully increased synaptic density, an effect also observed in a separate cell culture study.7
Improving Memory
In this study, the effect on rodents' cognitive ability was dramatic.
Aged rats given magnesium L-threonate had enhanced learning ability, with improvements in short-term and long-term memory.8
Magnesium L-threonate was also tested in two studies utilizing a mouse model of Alzheimer's. In both studies, it prevented the loss of synapses associated with the disease and maintained or improved memory.10,12
Another mouse study showed that magnesium L-threonate stimulated growth of new brain cells in brain areas central to memory and learning. Growth of these cells typically slows or stops in older animals, but magnesium L-threonate restricted this decline.18
What You Need to Know
Magnesium-L-Threonate Takes Years Off Your Brain Age
- Magnesium helps prevent brain aging and the loss of synapses seen with cognitive decline.
- In animal studies, magnesium L-threonate crossed the blood-brain barrier and boosted brain magnesium levels to a vastly greater degree than other forms.
- In animal models and human trials, magnesium L-threonate improved cognitive function. In one human study, it reversed cognitive measures of brain age by a remarkable nine years.
Human Trial
To test the cognitive benefits of magnesium L-threonate in humans, scientists conducted a randomized, placebo-controlled trial.13
Volunteers aged 50-70 years old were given either a placebo or 1,500-2,000 mg of magnesium L-threonate (depending on body weight) daily for 12 weeks. The participants all had some impairment in executive functioning, the ability to plan, adapt, focus, and make decisions.
Compared to placebo subjects, those receiving magnesium L-threonate showed improved cognitive abilities after six weeks.
A further 20% improvement from baseline was observed after 12 weeks 13 including significantly increased performance speed for executive function and cognitive processing.
The treatment group's composite scores for all tests combined increased significantly compared to their baseline scores and compared to the placebo group's scores at weeks six and twelve.13
All subjects were assigned a "brain age" by comparing their cognition test scores with normal scores for people the same age. At the start of the trial, the participants' chronological ages averaged 57.8 years. Their brain ages averaged a much older 68.3 years.13
After six weeks, those who took magnesium L-threonate had improved their brain age by an astounding nine years and by the end of the study the number was further improved to 9.4 years.13
Overall, taking magnesium L-threonate:13
- Improved memory and executive function,
- Improved cognitive abilities and speed,
- Reduced fluctuations in cognitive function (cognitive function being worse on some days than others is an early warning sign of mild cognitive impairment), and
- Reversed measures of brain age.
These improvements are consistent with the greater synaptic density and plasticity shown in preclinical studies of magnesium L-threonate.5,10,12,14,18,22
In another clinical study, scientists tested magnesium L-threonate in patients with mild to moderate dementia. Even at this more advanced stage of cognitive decline, magnesium L-threonate led to improvements in cognition and executive function.23
Whether taken in a capsule, powder, or gummy form, magnesium L-threonate shows potential to delay or reverse some measured aspects of brain aging.
Potential ADHD Benefits
Based on magnesium L-threonate's brain benefits, researchers wondered whether it could also improve neuropsychiatric conditions.
In a pilot study, they gave magnesium L-threonate to 15 adults with moderate ADHD (attention deficit hyperactivity disorder) for up to 12 weeks.24
Almost half the participants displayed clinical improvements.24
Summary
Magnesium supports youthful brain function, and it is needed for functioning of brain synapses, vital for complex tasks such as learning and memory.
Unlike other forms magnesium L-threonate increases brain levels by a significant amount.
This enables it to boost synaptic density and plasticity.
A clinical study found that magnesium L-threonate reversed measures of brain age in people by nine years.
If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.
References
- Available at: https://lpi.oregonstate.edu/mic/health-disease/cognitive-function-in-brief#:~:text=Cognition%20basically%20means%20using%20your,problem%20solving%2C%20and%20multitasking). Accessed September 28, 2023.
- Temido-Ferreira M, Coelho JE, Pousinha PA, et al. Novel Players in the Aging Synapse: Impact on Cognition. J Caffeine Adenosine Res. 2019 Sep 1;9(3):104-27.
- Subramanian J, Savage JC, Tremblay M. Synaptic Loss in Alzheimer's Disease: Mechanistic Insights Provided by Two-Photon in vivo Imaging of Transgenic Mouse Models. Front Cell Neurosci. 2020;14:592607.
- Maier JAM, Locatelli L, Fedele G, et al. Magnesium and the Brain: A Focus on Neuroinflammation and Neurodegeneration. Int J Mol Sci. 2022 Dec 23;24(1).
- Zhou H, Liu G. Regulation of density of functional presynaptic terminals by local energy supply. Mol Brain. 2015 Jul 17;8:42.
- Yamanaka R, Shindo Y, Oka K. Magnesium Is a Key Player in Neuronal Maturation and Neuropathology. International Journal of Molecular Sciences. 2019;20(14):3439.
- Sun Q, Weinger JG, Mao F, et al. Regulation of structural and functional synapse density by L-threonate through modulation of intraneuronal magnesium concentration. Neuropharmacology. 2016 Sep;108:426-39.
- Slutsky I, Abumaria N, Wu LJ, et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010 Jan 28;65(2):165-77.
- Barbagallo M, Veronese N, Dominguez LJ. Magnesium in Aging, Health and Diseases. Nutrients. 2021 Jan 30;13(2).
- 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 Sep 13;7:65.
- Sadir S, Tabassum S, Emad S, et al. Neurobehavioral and biochemical effects of magnesium chloride (MgCl2), magnesium sulphate (MgSO4) and magnesium-L-threonate (MgT) supplementation in rats: A dose dependent comparative study. Pak J Pharm Sci. 2019Jan;32(1(Supplementary)):277-83.
- Huang Y, Huang X, Zhang L, et al. Magnesium boosts the memory restorative effect of environmental enrichment in Alzheimer's disease mice. CNS Neurosci Ther. 2018 Jan;24(1):70-9.
- 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. 2016;49(4):971-90.
- 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. 2011Oct 19;31(42):14871-81.
- Workinger JL, Doyle RP, Bortz J. Challenges in the Diagnosis of Magnesium Status. Nutrients. 2018 Sep 1;10(9).
- Uwitonze AM, Razzaque MS. Role of Magnesium in Vitamin D Activation and Function. J Am Osteopath Assoc. 2018 Mar 1;118(3):181-9.
- Mateos-Aparicio P, Rodríguez-Moreno A. The Impact of Studying Brain Plasticity. Front Cell Neurosci. 2019;13:66.
- Jia S, Liu Y, Shi Y, et al. Elevation of Brain Magnesium Potentiates Neural Stem Cell Proliferation in the Hippocampus of Young and Aged Mice. J Cell Physiol. 2016 Sep;231(9):1903-12.
- Al Alawi AM, Majoni SW, Falhammar H. Magnesium and Human Health: Perspectives and Research Directions. Int J Endocrinol. 2018;2018:9041694.
- Kim YJ, McFarlane C, Warner DS, et al. The effects of plasma and brain magnesium concentrations on lidocaine-induced seizures in the rat. Anesth Analg. 1996 Dec;83(6):1223-8.
- McKee JA, Brewer RP, Macy GE, et al. 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. 2005 Mar;33(3):661-6.
- Slutsky I, Sadeghpour S, Li B, et al. Enhancement of synaptic plasticity through chronically reduced Ca2+ flux during uncorrelated activity. Neuron. 2004 Dec 2;44(5):835-49.
- Wroolie TE, Watson K, Chen K, et al. Open Label Trial of Magnesium L-Threonate in Patients with Dementia. Innov Aging. 2017 Jul Jun 30;1(Suppl 1):170. doi: 10.1093/geroni/igx004.661. eCollection 2017 Jul.
- Surman C, Vaudreuil C, Boland H, et al. L-Threonic Acid Magnesium Salt Supplementation in ADHD: An Open-Label Pilot Study. J Diet Suppl. 2021;18(2):119-31.