tuneTypical Dose
1-2
Supplement
L-threonate
Magnesium L-threonate
Evidence TierCWADA PROHIBITED
watchEffect Window
3-12 weeks
lockCompliance
WADA PROHIBITED
Overview
Clinical Summary
L-threonate is a small molecule, salt, or polymer used for targeted metabolic or digestive effects. It is used to influence specific pathways rather than general nutrition.
Evidence varies widely by compound. Some have controlled human data for specific outcomes such as lipid markers, glycemic response, or symptom relief, while others are supported mainly by mechanistic studies. Minority uses include inflammation modulation and antioxidant effects. Dose, formulation, and safety constraints often determine whether measurable benefits occur.
A magnesium delivery form with potential CNS-relevant effects on cognitive and sleep-related neural processes.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Improved selected cognitive test outcomes
- Improved subjective sleep/daytime function in some adults
Secondary Outcomes
- Mixed objective sleep effects
- Product/formula dependency
Safety
Contraindications and Interactions
Contraindications
- Significant renal impairment
- Pregnancy/lactation without supervision
- Under age 18 without supervision
Side effects
- Mild GI upset
- Possible loose stools
- Occasional daytime drowsiness
Interactions
- Other magnesium supplements
- Sedative/CNS depressant stacks
- Oral drugs requiring absorption spacing
Avoid if
- Severe renal dysfunction
- No endpoint-tracking plan
- Poor tolerance to magnesium formulations
Evidence
Study-level References
l-threonate-SRC-001Randomized double-blind placebo-controlled trial
Sourceopen_in_newLiu G, et al. Efficacy and safety of MMFS-01 for treating cognitive impairment in older adults. J Alzheimers Dis. 2016;49(4):971-990. PMID:26519439
Population: Older adults (50-70 years) with cognitive impairment
Dose protocol: MMFS-01 for 12 weeks
Key findings: Significant improvement in overall cognitive ability
Notes: Product is magnesium-L-threonate based rather than isolated single ingredient
Paper content
Significant improvement in overall cognitive ability
l-threonate-SRC-002Randomized, double-blind, placebo-controlled trial.
Sourceopen_in_newHausenblas HA, Lynch T, Hooper S, Shrestha A, Rosendale D, Gu J. Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial. Sleep Med X. 2024;8:100121. doi:10.1016/j.sleepx.2024.100121. PMID:39252819.
Population: Adults aged 35 to 55 with self-assessed sleep problems.
Dose protocol: 1 g/day magnesium L-threonate for 21 days
Key findings: Improved subjective sleep/daytime metrics, selected objective improvements
Notes: Short duration and mixed subjective/objective endpoint interpretation
Paper content
This 21-day randomized placebo-controlled trial tested 1 g per day of magnesium L-threonate in 80 adults aged 35 to 55 with self-reported sleep problems. The MgT group showed significant improvements in deep sleep scores, REM sleep, and activity measures compared to placebo. Subjective improvements included better mood, energy, alertness, and productivity. The study adds a second independent RCT endpoint for MgT beyond the earlier Liu 2016 cognitive trial, supporting both sleep and daytime functioning benefits. The short duration and self-report measures are limitations.
l-threonate-SRC-003Randomized double-blind placebo-controlled trial
Sourceopen_in_newLopresti AL, Smith SJ. Magtein effects on cognitive performance and sleep quality in adults: randomized placebo-controlled trial. Front Nutr. 2026;12:1729164. PMID:41601871
Population: Adults 18-45 with dissatisfied sleep (n=100)
Dose protocol: 2 g/day Magtein for 6 weeks
Key findings: Improved cognition and some sleep-related outcomes
Notes: Sponsor involvement, subjective-objective sleep discrepancy
Paper content
Improved cognition and some sleep-related outcomes
l-threonate-SRC-004Double-blind placebo-controlled trial
Sourceopen_in_newZhang C, et al. Magnesium L-threonate-based formula improves brain cognitive functions in healthy adults. Nutrients. 2022;14(24):5235. PMID:36558392
Population: Healthy adults (18-65 years, n=109)
Dose protocol: 2 g/day Magtein-based formula for 30 days
Key findings: Improved memory quotient and subdomain scores
Notes: Multi-component formulation
Paper content
Improved memory quotient and subdomain scores
l-threonate-SRC-005Randomized, double-blind, placebo-controlled, longitudinal superiority trial
Sourceopen_in_newWu S, Jin T, Ma B, Ji Y, Huang X, Wang P, Liu X, Krylov BV, Liu X, Ma K. Oral application of magnesium-L-threonate enhances analgesia and reduces the dosage of opioids needed in advanced cancer patients. Cancer Med. 2023;12(4):4343-4351. doi:10.1002/cam4.4922. PMID:36703238.
Population: Adults with advanced cancer and clinically meaningful cancer pain who were using oral opioids.
Dose protocol: Magnesium L-threonate (L-TAMS) 1.5 to 2.0 g/day versus placebo for 90 days in advanced cancer patients.
Key findings: Significantly lower daily morphine dose escalation from day 30 onward (9.85 mg/d versus 20.49 mg/d). Reduced opioid-induced constipation.
Notes: First RCT of MgT for opioid-sparing in cancer pain. Mechanism likely involves NMDA receptor modulation reducing central sensitization and opioid tolerance.
Paper content
This double-blind randomized oncology trial tested once-daily oral magnesium L-threonate as an adjunct to opioid therapy for 12 weeks in 83 adults with advanced cancer pain. The main signal was opioid sparing rather than lower raw pain scores. Morphine-equivalent dose escalation became significantly lower in the L-TAMS group by day 30 and remained lower through days 60 and 90. Constipation outcomes also favored L-TAMS strongly, with adjusted Wexner scores separating from day 7 onward. By contrast, average VAS pain intensity, breakthrough cancer pain frequency, PHQ-9, and GAD-7 outcomes did not show clear between-group improvement. This makes the study useful as supportive-care evidence for opioid tolerance and opioid-related constipation in a specific cancer population, not as a broad analgesic or mood claim for magnesium L-threonate.