Magnesium L-Threonate: Benefits and Clinical Applications

Many factors in our modern society increase the risk of magnesium deficiency, placing a vast number of individuals at risk of suboptimal levels. An individual’s magnesium level can become depleted from issues such as medication usage, chronic diseases, poor magnesium content in crops and soil, and the increased consumption of refined and processed foods.

Magtein Magnesium L-Threonate
Magtein Magnesium L-Threonate

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Magnesium L-threonate offers a cost effective, safe for long term use, and well tolerated form of magnesium that provides optimum levels. It has been shown to be the only form of magnesium capable of increasing magnesium levels in the brain and cerebrospinal fluid (CSF).

This ability to cross the blood brain barrier (BBB) increases its efficacy for use in many chronic disease states, especially those associated with central nervous system (CNS) dysfunction.

Conditions that respond to Magnesium L-threonate

Magnesium L-Threonate and Pain
Magnesium is useful for treating chronic pain and inflammation that occurs due to the activation of the NMDA receptor during trauma. The NMDA receptor, which is normally not activated, becomes activated during traumatic physical or emotional events.

During periods of excitotoxicity, calcium shuttles through the NMDA receptor and causes increased immune system responses (release of substance P, mast cells, immune cells, oxidative stress). Magnesium works to inhibit calcium influx through the NMDA receptor thereby decreasing oxidative stress as well as decreasing inflammation by blocking substance P. Blocking the NMDA receptor also serves to inhibit cortical spreading depression (CSD).

Magnesium L-Threonate and Migraine
Magnesium is also useful in treating migraine due to its ability to inhibit platelet activation. Platelet activation stimulates the release of serotonin which triggers spasming of blood vessels in the central nervous system (CNS) resulting in migraine.

Magnesium inhibits calcitonin gene related peptide (CGRP) mediated vasodilation, another driver of migraine. Magnesium threonate is especially useful for the treatment of migraine as it is capable of crossing the blood brain barrier (BBB) and providing Mg2+ directly to the affected area.

Magnesium L-Threonate and the Ear
Magnesium helps protect against hearing loss from noise as well as drug ototoxicity by decreasing the oxidative stress created by these stressors. Magnesium is also protective in sudden sensorineural hearing loss due to issues such as viral infections, vascular impairment, CNS disorders, inner ear abnormalities, or immune related mechanisms.

Magnesium provides protection from hearing loss due to its ability to function as a Ca2+ antagonist, vasodilator, antioxidant, and a non-competitive NMDA antagonist. Magnesium threonate, with the ability to enter the CNS, is particularly useful in working with individuals with tinnitus.

Protecting and Repairing the Hippocampus: Learning, Memory, and Emotion

Alzheimer’s disease
Alzheimer’s disease (AD) is associated with a magnesium deficiency in the serum or brain.7 Yu, Guan, Gu (2015) found that magnesium L-threonate enhanced the clearance of amyloid beta, the plaquing seen in AD. They demonstrated that magnesium L-threonate was able to slow the progression of AD.

Magnesium threonate treatment was even effective at preventing synapse loss and memory decline when used in mice with end-stage AD.

It has also demonstrated the ability to be neuroprotective against oxidative stress and hippocampal neuronal apoptosis.

Chemotherapy-induced memory/emotional deficits
Magnesium L-threonate prevented oxaliplatin(OXA)-induced behavioral and synaptic changes in a 2020 study conducted using rats. This study showed that magnesium L-threonate prevented the OXA-induced upregulation of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and nuclear factor-kappaB (NF-кB).

Magnesium L-threonate also downregulated part of the NMDA receptor, the N-methyl-D-aspartate receptor (NR2B) subunit in the hippocampal slices examined. Microglial activation in the hippocampus and medial prefrontal cortex was also observed.

A separate study showed that magnesium L-threonate was useful at preventing neuropathic pain in patients on chemotherapy by preventing magnesium deficiency.

Enhanced synaptic plasticity, learning, memory, and emotion
Zhou, Huang, and Zhang (2020) found that magnesium L-threonate increased brain magnesium levels in rats. The increased brain levels of magnesium was able to enhance learning and memory in the rats studied due to increased synaptic plasticity in the prefrontal cortex and hippocampus. Other effects noted included increases in the following: NMDA receptors signaling, brain-derived neurotropic factor (BDNF) expressions, and density of presynaptic puncta.

Neural stem cell proliferation
Long term (12 month) supplementation with magnesium L-threonate in aged mice was able to stop age-associated decline in neural stem cell proliferation (NSC). The study also demonstrated, in vitro, the association between elevated extracellular magnesium concentrations and NSC self-renewal concluding that key signaling pathways for cell growth and proliferation were potential targets for magnesium supplementation.

Attention Deficit Hyperactivity Disorder
Magnesium L-threonate is recommended for those with ADHD as they often respond quickly with an increased ability to focus, often within 48-72 hours.

Surman et al (2020) found that a 12-week course of supplementation with L-threonic acid magnesium salt (LTAMS) was beneficial for increasing global functioning and cognitive scores in 15 individuals with ADHD. They stated that LTAMS offered clinical benefit for those with ADHD due to the enhanced neurobiological and neurofunctional affects.

Chronic Pain
• Individuals in chronic pain experience heightened amounts of stress/cortisol. This excess cortisol damages areas of the hippocampus. Magnesium L-threonate was shown to be better than magnesium chloride or magnesium sulphate at strengthening the cholinergic system, decreasing oxidative stress, and improving brain function in rats.
• Two-thirds of patients with chronic pain suffer from memory deficits. Chronic use of magnesium L-threonate was able to restore the short-term memory deficits caused by chronic pain in rats. The magnesium L-threonate was protective of the hippocampus, blocking the upregulation of TNF-a and restoring function to this area. Phosphatidyl Serine is also useful in repairing hippocampus but is not as well tolerated as magnesium l-threonate. Magnesium L-threonate is safe to use long term and should be considered in all patients with neuropathic pain and any pain in general.
• Hypoxia is another driver of pain and inflammation observed in clinical practice. Magnesium L-threonate is neuroprotective against the downstream negative inflammatory effects and neuronal degeneration caused by hypoxia.

Intestinal Barrier Dysfunction
Liu et al (2021) studied the effects of magnesium L-threonate on inflammation and memory impairment caused by alcohol abuse in mice. Their study showed that magnesium L-threonate decreased inflammatory cytokines in the serum, colon, and the brain. Intestinal barrier dysfunction improved as well with an enhancement of a healthier microbiota which included an increased presence of Blautia and Akkermansia. Memory was enhanced and the metabolism of amino acids and glutamate was also improved.

Androgen Driven Hair Loss
Dickkopf 1 (DKK-1) is one of the most upregulated genes associated with androgen-potentiated balding. Magnesium L-threonate was shown to inhibit dihydrotestosterone (DHT)-inducible DKK-1 in cultured dermal papilla cells (DPCs). Kwack et al (2010) concluded that magnesium L-threonate provided an effective treatment option for the prevention of androgen-driven balding.

Perimenopausal/menopausal women
Magnesium L-threonate was found to be a novel treatment approach for menopause-related neuronal disorders. It was able to prevent or reverse chronic pain due to neuroinflammation as well as enhance memory/emotional deficits due to impaired synaptic transmission in ovariectomized and aged mice.

Parkinson’s disease
Magnesium deficiency has been associated with an increased incidence of Parkinson’s Disease (PD). A primary concern is supplying magnesium in a form capable of crossing the BBB to increase the levels found in the cerebral spinal fluid (CSF).

Shen et al (2019) were able to increase the level of magnesium in the CSF in mice with PD using magnesium L-threonate. This resulted in reduced motor deficits and decreased dopamine neuron loss in the mice studied.

Supplement Recommendation—Magtein® by Moss Nutrition
Magnesium = 144 mg per serving (from 2,000 mg Magtein®/Magnesium L-Threonate)
Serving size = 3 capsules
• Standard dose = 3 capsules per day (1 with breakfast and 2 with dinner).
• Take 1 hour before bed for those with insomnia.
• In rare instances, magnesium can be overstimulating.
• Magnesium threonate is safe for long term use and is usually well tolerated.
• It can take ~1 hour for absorption to take place across the BBB.

Magtein® is a patented chelate of elemental magnesium and L-threonic acid, a vitamin C metabolite. These combine to form magnesium L-threonate. This is the only supplemental form of magnesium shown to cross the blood BBB and significantly raise magnesium levels in the brain and CSF. Increasing brain magnesium levels helps enable healthy synaptic function, neurotransmitter synthesis and activity. Research has shown that magnesium L-threonate helps support memory, cognitive function, mental acuity, sharpness, and attention.

Hedberg Institute Members can download my magnesium L-threonate protocols by logging in and visiting the Practice Tools page.

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