Magnesium L-Threonate vs Glycinate for the Brain

Short answer: Threonate is the only form with cognition data: it raised brain magnesium in rats, and one small, company-funded trial in 44 older adults found better test scores. Glycinate is well absorbed, cheaper and gives more magnesium per dose, but has not been tested directly for sleep or thinking. Keep supplemental magnesium within 350 mg a day.

Neither form is proven to improve memory or sleep in people. If your interest is cognition, threonate has preliminary evidence; if you want to correct low magnesium intake at a lower cost, glycinate is the more efficient choice.

The upper limit for magnesium from supplements is 350 mg a day for adults. Ask a doctor or pharmacist before starting either form, especially if you have kidney disease or take medication. This page compares only these two forms. For what magnesium does in the brain, food sources and other forms, see our main guide to magnesium and brain health.

Threonate vs glycinate at a glance

Magnesium L-threonate: the evidence for cognition

Researchers at MIT and Tsinghua University developed magnesium L-threonate (MgT) because, they reported, ordinary supplements raised blood magnesium without a matching rise in the brain. They screened several compounds in nerve-cell cultures and chose L-threonate, a breakdown product of vitamin C, as the carrier. The carrier’s value lies in transport; it has no known effects of its own on the brain.

In rats (Slutsky 2010), oral MgT raised magnesium in the fluid around the brain and spinal cord. Treated rats had more synaptic markers in the hippocampus, did better on learning and memory tests, and showed stronger long-term potentiation, a cellular mechanism of learning. Aged rats also improved on a pattern-completion task. These are animal results and do not show what the supplement does in people.

The one human trial (Liu 2016) was randomized, double-blind and placebo-controlled. It enrolled 44 adults aged 50 to 70 with self-reported memory and concentration complaints, anxiety and sleep problems. They took the MgT formulation MMFS-01 (1.5 or 2 g a day by body weight, about 108–144 mg of elemental magnesium) or placebo for 12 weeks.

The MgT group (n = 23) improved more than placebo (n = 21) on a composite score across four cognitive domains (p = 0.003). The clearest changes were in executive function and working memory. Using a model based on normative test data, the authors estimated that “brain age” improved by about 9 years. Sleep and anxiety improved as much on placebo.

The trial was small. Neurocentria, the company developing MgT, funded it and wrote the paper. The nine-year “brain age” figure is a modeled estimate, not a biological measurement, and we found no independent replication.

Magnesium glycinate: absorption and glycine

Magnesium glycinate (bisglycinate) is magnesium bound to two molecules of the amino acid glycine. The glycine protects the magnesium from binding to phytates, oxalates and other compounds in the gut. In a 60-day trial, an amino-acid chelate of magnesium was absorbed better than magnesium oxide (Walker et al., 2003). Chelated forms are generally well tolerated, although any magnesium supplement can cause loose stools at higher doses.

That makes glycinate a practical way to correct low intake. About 48 percent of US adults get less magnesium from food than the Estimated Average Requirement (Rosanoff et al., 2012).

Glycine is also active in the nervous system. It is a calming (inhibitory) neurotransmitter, mainly in the brainstem and spinal cord, and NMDA receptors need it alongside glutamate to work.

Evidence for glycine and sleep comes from small studies by one Japanese group. Bannai (2012) cut volunteers’ sleep by 25 percent for three nights. Those given 3 grams of glycine before bed reported less next-day fatigue and did better on a vigilance test. The same group reports earlier studies in which glycine improved subjective sleep quality in poor sleepers.

A glycinate dose providing 200 mg of elemental magnesium contains about 1,200 mg of glycine, less than half the 3,000 mg used in those studies. Proposed calming and anti-stress effects have not been tested for magnesium glycinate in trials we could find.

Which form to choose

Choose threonate if cognition is your interest. It is the only form with evidence for raising brain magnesium (in rats) and improving cognitive scores (in one small trial of adults aged 50–70 with memory complaints). That evidence is preliminary, and memory changes deserve a check with a doctor rather than self-treatment. Threonate supplies little elemental magnesium, so it does little for low overall intake.

Choose glycinate if you need more magnesium overall. At about 14 percent elemental magnesium by weight, it delivers more magnesium per gram than threonate (8 percent). It also costs less (see cost below).

For sleep, the case for glycinate is indirect. Small trials of magnesium in older adults found better sleep, but they used magnesium oxide (Abbasi et al., 2012) or effervescent tablets (Held et al., 2002). Glycine has its own small studies. No trial has tested magnesium glycinate for sleep, and in the threonate trial sleep improved equally on placebo. Ongoing insomnia is worth discussing with a doctor. For other ways food affects sleep, see sleep and diet.

For anxiety, neither form has been tested. Boyle, Lawton, and Dye (2017) reviewed 18 studies and found evidence suggestive of a benefit of magnesium on subjective anxiety in anxiety-prone people, but rated its quality as poor. None tested glycinate. Magnesium is not a substitute for anxiety treatment prescribed by a doctor. Our page on diet and anxiety covers the wider evidence.

Combining both: No interaction between the two forms is known, but no trial has tested the combination. If you combine products, add up the elemental magnesium from all of them and stay within the 350 mg/day upper limit unless a doctor advises otherwise.

Supplements work best on top of a diet rich in pumpkin seeds, almonds, dark leafy greens, legumes and whole grains. Those foods also feature in the Mediterranean diet, the best-supported overall dietary pattern for brain health.

Doses used in studies, and safety

The Liu et al. (2016) trial used 1.5 g of threonate compound a day for people weighing 50–70 kg and 2 g a day for 70–100 kg, about 108–144 mg of elemental magnesium. We found no other human cognition trials. We found no trials of magnesium glycinate for sleep or cognition. Higher doses are not better.

• The upper limit (UL) for magnesium from supplements and medicines (not food) is 350 mg a day for adults. Above this, diarrhea, nausea and cramping become more likely. Take doses above the UL only under medical supervision. If you combine products, add up the elemental magnesium in each.
• People with kidney disease should not take magnesium supplements without a doctor’s advice, because magnesium can build up to dangerous levels.
• Magnesium reduces the absorption of some antibiotics (tetracyclines, fluoroquinolones) and bisphosphonates. Ask a doctor or pharmacist before starting any supplement, especially if you are pregnant, breastfeeding, taking medication or have a health condition.

Cost

A 30-day supply of threonate (2,000 mg compound a day) typically costs $25 to $45 USD. Branded Magtein products sit at the higher end; generic versions cost less, though quality and consistency may vary. A 30-day supply of glycinate providing 200 to 400 mg of elemental magnesium a day typically costs $10 to $20 USD, so glycinate usually costs 40 to 60 percent less. Both together cost about $35 to $65 USD a month.

Does glycinate cross the blood-brain barrier?

Supplement marketing often says so, but this is misleading. All forms raise blood magnesium, which affects brain magnesium to some degree. There is no published evidence that glycinate raises brain or spinal-fluid magnesium beyond what blood levels alone would explain. Threonate’s claim rests on rat data and has not been measured directly in humans.

Magnesium oxide is not a cheap substitute for either. It had a fractional absorption of about 4 percent in one study (Firoz and Graber, 2001), although it was the form used in the Abbasi et al. (2012) insomnia trial.

Frequently Asked Questions

Is Magtein the same as magnesium L-threonate?

Magtein is a branded, patented form of magnesium L-threonate linked to the team behind the Slutsky et al. (2010) study. The Liu et al. (2016) trial tested MMFS-01, a formulation containing it. Generic products contain the same compound but may differ in purity, manufacturing standards or fillers.

How long does magnesium L-threonate take to work?

In the Liu et al. (2016) trial, the composite cognitive score had improved by week six and stayed improved at week twelve. No other human trial shows how long effects take.

Is magnesium L-threonate safe long-term?

Long-term safety has not been studied. In the 12-week trial, side effects possibly related to the product were more common on placebo than on MgT. The trial doses (about 108–144 mg/day) sit below the 350 mg/day upper limit. People with kidney disease should consult their doctor before use.

Can magnesium glycinate cause daytime drowsiness?

It has not been reported as a common effect, but no glycinate trial has measured it. If it happens, ask a pharmacist about timing.

Sources

• Slutsky, I., Abumaria, N., Wu, L. J., Huang, C., Zhang, L., Li, B., … & Liu, G. (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron, 65(2), 165-177. doi:10.1016/j.neuron.2009.12.026

• Liu, G., Weinger, J. G., Lu, Z. L., Xue, F., & Sadeghpour, S. (2016). Efficacy and safety of MMFS-01, a synapse density enhancer, for treating cognitive impairment in older adults: a randomized, double-blind, placebo-controlled trial. Journal of Alzheimer’s Disease, 49(4), 971-990. doi:10.3233/JAD-150538

• Bannai, M., Kawai, N., Ono, K., Nakahara, K., & Murakami, N. (2012). The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Frontiers in Neurology, 3, 61. doi:10.3389/fneur.2012.00061

• Walker, A. F., Marakis, G., Christie, S., & Byng, M. (2003). Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnesium Research, 16(3), 183-191. PMID:14596323

• Rosanoff, A., Weaver, C. M., & Rude, R. K. (2012). Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutrition Reviews, 70(3), 153-164. doi:10.1111/j.1753-4887.2011.00465.x

• Boyle, N. B., Lawton, C., & Dye, L. (2017). The effects of magnesium supplementation on subjective anxiety and stress — a systematic review. Nutrients, 9(5), 429. doi:10.3390/nu9050429

• Firoz, M., & Graber, M. (2001). Bioavailability of US commercial magnesium preparations. Magnesium Research, 14(4), 257-262. PMID:11794633

• Abbasi, B., Kimiagar, M., Sadeghniiat, K., Shirazi, M. M., Hedayati, M., & Rashidkhani, B. (2012). The effect of magnesium supplementation on primary insomnia in elderly: a double-blind placebo-controlled clinical trial. Journal of Research in Medical Sciences, 17(12), 1161-1169. PMID:23853635

• Held, K., Antonijevic, I. A., Künzel, H., Uhr, M., Wetter, T. C., Golly, I. C., Steiger, A., & Murck, H. (2002). Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacopsychiatry, 35(4), 135-143. doi:10.1055/s-2002-33195