Meta Information
ID:magnesium-l-threonate
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/condition/renal-impairment
Target name:
Renal Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The kidneys are responsible for excreting excess magnesium; in renal impairment, magnesium can accumulate to toxic levels, causing severe cardiovascular and neurological complications.
Actionable advice:
Magnesium supplements should not be used, or used only under strict medical supervision, by those with moderate to severe kidney disease.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Here we detail her clinical course, including the unique challenges of treating eclampsia and PRES in the setting of magnesium toxicity.
Label source:
PubMed: Posterior Reversible Encephalopathy Syndrome and Eclampsia in the Setting of Magnesium Toxicity: A Case Report. (PMID 37948545)
Action type:
avoid
Target id:
/class/chelating-antibiotics
Target name:
Chelating Antibiotics (Tetracyclines, Quinolones)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
4
Description:
Magnesium binds to tetracycline and fluoroquinolone antibiotics in the gut, forming non-absorbable complexes that severely reduce the antibiotic's effectiveness.
Actionable advice:
Magnesium should be taken at least 2 hours before or 4 hours after these types of antibiotics.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Clinical studies demonstrated that two classes of antibacterials (tetracyclines and fluoroquinolones) are susceptible to clinically relevant DDIs with antacids through this mechanism. Countermeasures against this type of DDI include spacing out the dosing interval - taking antacid either 4 hours before or 2 hours after administration of these antibacterials.
Label source:
PubMed: Drugs (2011)
Source url:
Exact phrase from label:
Tetracyclines form insoluble complex molecules by metal ion chelation with various antacids; tetracycline absorption may be decreased by more than 90% by this interaction. Of the new class of quinolone antibiotics, the absorption of ciprofloxacin and ofloxacin is reduced by 50 to 90% in the presence of aluminium- and magnesium hydroxide-containing antacids.
Label source:
PubMed: Clinical pharmacokinetics (1990)
Source url:
Exact phrase from label:
Chelation interactions with multivalent cations can result in inactivation of the fluoroquinolone with ramifications in vitro and in vivo. Chelation interactions have been reported to occur in between 22 and 76% of patients prescribed fluoroquinolones. Concurrent administration of magnesium-aluminum antacids and sucralfate has the greatest effect on the bioavailability of quinolones followed by iron, calcium and zinc.
Label source:
PubMed: Drug safety (1995)
Action type:
separate
Target id:
/intervention/bisphosphonates
Target name:
Bisphosphonates
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Magnesium can bind to bisphosphonate drugs (e.g., for osteoporosis), significantly reducing their absorption and efficacy.
Actionable advice:
Magnesium doses and bisphosphonate medications should be separated by at least 2 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate; and to take calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations at a different time of the day
Label source:
FDA label: Risedronate (Actonel)
Action type:
separate
Target id:
/intervention/levothyroxine
Target name:
Levothyroxine
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
4
Description:
Magnesium can interfere with the absorption of thyroid hormone medication in the gastrointestinal tract, potentially reducing its effectiveness.
Actionable advice:
Magnesium is best taken at least 4 hours after levothyroxine.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sucralfate, antacids and Antacids proton pump inhibitors may cause hypochlorhydria, affect (e.g., aluminum & magnesium intragastric pH, and reduce levothyroxine absorption.
Label source:
FDA label: Levothyroxine (Synthroid)
Action type:
separate
Target id:
/class/chelating-minerals
Target name:
Other Divalent Minerals (Calcium, Zinc, Iron)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Magnesium competes with other divalent minerals like calcium, zinc, and iron for the same absorption pathways in the small intestine, reducing the absorption of all involved.
Actionable advice:
Magnesium and high-dose calcium, zinc, or iron supplements should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
The interaction between Fe, Ca, and Mg with other trace elements is orchestrated by some key proteins, especially DMT1 and DCYTB. The former has been implicated in the intestinal transport of Fe, Cu, Zn, and Cd, whereas the latter is able to change the oxidation state of both Fe and Cu ions
Label source:
Action type:
separate
Target id:
/class/proton-pump-inhibitors
Target name:
Proton Pump Inhibitors
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Long-term use of PPIs can impair active magnesium absorption in the intestine, leading to a deficiency (hypomagnesemia) that may require supplementation.
Actionable advice:
If on long-term PPI therapy, monitor magnesium levels and consider supplementation as advised by your doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.
Label source:
Action type:
monitor
Target id:
/class/diuretics
Target name:
Diuretics (Water Pills)
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Many diuretics, particularly loop and thiazide types, increase the excretion of magnesium through the kidneys, potentially leading to deficiency over time.
Actionable advice:
Magnesium status should be monitored, and supplementation may be warranted if these diuretics are taken long-term.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The effects of diuretics on renal handling of potassium and magnesium can result in depletion of these electrolytes.
Label source:
PubMed: Diuretics and potassium/magnesium depletion. Directions for treatment. (PMID 3551599)
Action type:
monitor
Target id:
/class/calcium-channel-blockers
Target name:
Calcium Channel Blockers
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Magnesium has mild calcium channel blocking properties and can enhance the blood pressure-lowering and heart rate-slowing effects of these medications, potentially leading to hypotension.
Actionable advice:
This is best used with caution, and it is a good idea to monitor blood pressure when taking calcium channel blockers concurrently.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
NORVASC is a type of medicine known as a calcium channel
blocker (CCB).
Label source:
Action type:
monitor
Target id:
/class/viscous-fibers
Target name:
Viscous Fibers (e.g., Psyllium)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Gel-forming fibers can trap magnesium in the gut, forming a matrix that prevents its absorption into the bloodstream.
Actionable advice:
Magnesium is best taken at least 2 hours before or after consuming viscous fiber supplements.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Magnesium absorption was reduced with ingestion of intact psyllium (50 g/kg diet) for 4 weeks but this reduced absorption was increased with lower viscous psyllium preparations.
Label source:
PubMed: Bioscience, biotechnology, and biochemistry (2004)
Source url:
Exact phrase from label:
Dietary factors impairing Mg2+ up-take include high doses of other minerals, partly fermentable fibres (e.g., hemicellulose), non-fermentable fibres (e.g., cellulose, lignin), phytate and oxalate, whereas proteins, medium-chain-triglycerides, and low- or indigestible carbohydrates (e.g., resistant starch, oligosaccharides, inulin, mannitol and lactulose) enhance Mg2+ uptake.
Label source:
PubMed: Current nutrition and food science (2017)
Source url:
Exact phrase from label:
Because dietary fibers and some associated substances, such as phytate, have in vitro mineral-binding capacities, they have been thought to impair absorption of minerals such as calcium, iron and zinc, although magnesium absorption seems to be less affected.
Label source:
PubMed: The Journal of nutrition (2003)
Action type:
separate
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Magnesium can reduce the absorption of digoxin, a heart medication; separately, low magnesium levels can increase the risk of digoxin toxicity.
Actionable advice:
Magnesium and digoxin doses should be separated by at least 2 hours, and magnesium levels should be kept adequate.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Digoxin reduced the resting heart rate, but not the heart rate during exercise.
Label source:
Action type:
separate
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1.5
Hours after target:
null
Description:
Magnesium L-threonate is unique in its ability to cross the blood-brain barrier, where it can promote relaxation and support neural pathways involved in sleep and memory consolidation.
Actionable advice:
It is generally best taken 1-2 hours before bedtime to support sleep quality and cognitive function.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
administering a more permeable magnesium salt, such as magnesium threonate, is seen as the preferred option in more chronic neurological conditions, with positive results having been achieved in experimental models of Alzheimer's disease.
Label source:
PubMed: Magnesium research (2016)
Source url:
Exact phrase from label:
Since brain atrophy during aging is strongly associated with both cognitive decline and sleep disorder, we evaluated the efficacy of MMFS-01 in its ability to reverse cognitive impairment and improve sleep.
Label source:
PubMed: Journal of Alzheimer's disease : JAD (2016)
Source url:
Exact phrase from label:
emerging research suggests that dietary and supplementation protocols focused on certain foods, nutrients, and biochemical compounds with sleep-promoting properties can act as subsidiary sleep aids in complementing these behavioral changes.
Label source:
PubMed: Nutrition reviews (2026)
Action type:
separate
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
informational
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Taking magnesium with food can help reduce the risk of gastrointestinal side effects such as diarrhea or stomach upset, which can occur with higher doses.
Actionable advice:
It is generally best taken with a small meal or snack to improve gastrointestinal tolerance.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Biochemical and clinical evidence indicated that excessive ingestion of magnesium was an important cause of chronic diarrhea in 15 of the 359 patients with chronic diarrhea (4.2 percent), if not the only cause.
Label source:
PubMed: The New England journal of medicine (1991)
Source url:
Exact phrase from label:
In 1997, the US Institute of Medicine (IOM) dietary reference intakes (DRI) Committee established a magnesium (Mg) tolerable upper intake level (UL) for adults of 350 mg/d from supplemental intake alone. Diarrhea was the limiting factor.
Label source:
PubMed: Advances in nutrition (Bethesda, Md.) (2023)
Source url:
Exact phrase from label:
Our study also showed that, compared to the other Mg sources tested, the Mg-MS microencapsulation technology reduced adverse side effects commonly associated with Mg supplementation, specifically with regard to increased intestinal motility and sensations of gastric heaviness following oral administration.
Label source:
PubMed: Nutrients (2024)
Action type:
informational_none
Target id:
/dietary/phytate-rich-foods
Target name:
High-Phytate Meal (Grains, Legumes)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Phytic acid, found in whole grains, legumes, and nuts, can bind to magnesium in the gut, forming an insoluble complex that modestly reduces its absorption.
Actionable advice:
For maximum absorption, it is best taken at least 2 hours away from meals very high in unprocessed grains or legumes.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
FA is known as a dietary inhibitor that chelates minerals and trace elements, limiting their bioavailability and reducing their absorption.
Label source:
PubMed: [The role of phytates in human nutrition]. (PMID 37801451)
Action type:
separate
Target id:
/class/benzodiazepines
Target name:
Benzodiazepines
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to its effects on the central nervous system via NMDA receptor modulation, magnesium may enhance the sedative effects of benzodiazepines and other CNS depressants.
Actionable advice:
This is best used with caution, keeping in mind the potential for increased drowsiness when combined with sedative medications.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Magnesium (Mg2+) is a key regulatory ion of N-methyl-ᴅ-aspartate (NMDA) receptors, including conferring them to function as coincidence detectors for excitatory synaptic transmission.
Label source:
Action type:
informational_none
Target id:
/class/potassium-sparing-diuretics
Target name:
Potassium-Sparing Diuretics
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Some potassium-sparing diuretics (e.g., amiloride, triamterene) can also reduce magnesium excretion, slightly increasing the risk of high magnesium levels (hypermagnesemia).
Actionable advice:
It is a good idea to check magnesium levels if using concurrently, especially with any degree of kidney impairment.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
In conclusion, magnesium increases tachycardia cycle length and AH interval in patients with dual AVN physiology through a dominant effect on the slow AVN pathway.
Label source:
Action type:
monitor
Target id:
/biomarker/rbc-magnesium
Target name:
RBC Magnesium Test
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Supplementing with magnesium will directly increase measured levels of magnesium in red blood cells, which is the intended therapeutic effect and not a true interference.
Actionable advice:
It is generally best to let a healthcare provider know about magnesium supplementation when interpreting RBC magnesium test results.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
A magnesium RBC test measures the amount of magnesium inside your red blood cells. This test may be better at finding low magnesium levels than a regular magnesium blood test.
Label source:
Action type:
monitor