Meta Information
ID:magnesium-malate
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 (Kidney Disease)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Impaired kidney function prevents the effective excretion of excess magnesium, leading to a high risk of accumulation and toxic levels (hypermagnesemia), which can cause serious cardiac and neurological complications.
Actionable advice:
Magnesium supplements should not be used by those with kidney disease unless specifically prescribed and monitored by a physician.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Severe symptomatic hypermagnesemia is a rare clinical problem that predominantly results from excess exogenous magnesium intake in patients with renal failure.
Label source:
PubMed: Clinical nephrology (2000)
Source url:
Exact phrase from label:
Hypermagnesemia typically arises from excessive magnesium intake or reduced renal excretion; however, it also occurs in patients with normal kidney function.
Label source:
PubMed: Electrolyte & blood pressure : E & BP (2023)
Source url:
Exact phrase from label:
Physiological oral magnesium supplementation (5 mg/kg/day) is easy and can be carried out in the diet or with magnesium salts, with practically only one contra-indication: overt renal failure.
Label source:
PubMed: Magnesium research (1994)
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:
6
Description:
Magnesium ions bind to tetracycline and fluoroquinolone antibiotics in the gastrointestinal tract, forming insoluble complexes that prevent their absorption and severely reduce their effectiveness.
Actionable advice:
Magnesium should be taken at least 2 hours before or 6 hours after these 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:
Fluoroquinolones (FQs) are a widespread class of broad-spectrum antibiotics prescribed as a first line of defense, and, in some cases, as the only treatment against bacterial infection. However, when administered orally, reduced absorption and bioavailability can occur due to chelation in the gastrointestinal tract (GIT) with multivalent metal cations acquired from diet, coadministered compounds (sucralfate, didanosine), or drug formulation.
Label source:
PubMed: Pharmaceutics (2021)
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., alendronate) in the gut, significantly reducing their absorption and effectiveness in treating bone density loss.
Actionable advice:
Magnesium doses and bisphosphonates 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:
/condition/myasthenia-gravis
Target name:
Myasthenia Gravis
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Magnesium can inhibit the release of acetylcholine at the neuromuscular junction, which can worsen muscle weakness in patients with myasthenia gravis.
Actionable advice:
Magnesium supplementation should not be used by those with myasthenia gravis, except under strict medical supervision.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Magnesium is known to act at the neuromuscular junction by inhibiting the presynaptic release of acetylcholine and desensitizing the postsynaptic membrane.
Label source:
PubMed: Acute Respiratory Failure Induced by Magnesium Replacement in a 62-Year-Old Woman with Myasthenia Gravis. (PMID 26504451)
Action type:
avoid
Target id:
/intervention/levothyroxine
Target name:
Levothyroxine
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Magnesium can form insoluble complexes with levothyroxine in the gut, impairing its absorption and potentially leading to reduced therapeutic effect.
Actionable advice:
Magnesium and levothyroxine doses should be separated by at least 4 hours.
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:
/intervention/calcium-citrate
Target name:
High-Dose Calcium Supplements
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
High doses of calcium and magnesium compete for the same absorption pathways in the intestine, which can reduce the absorption of both minerals if taken together.
Actionable advice:
High-dose calcium and magnesium supplements should be separated by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The ratio of calcium-to-magnesium intake (Ca:Mg) may be important for bone due to their competitive absorption.
Label source:
PubMed: The Journal of nutrition (2023)
Source url:
Exact phrase from label:
Intestinal interactions between Mg and calcium or phosphate have been demonstrated in both humans and animals. The nature of these interactions cannot be readily explained by data currently available.
Label source:
PubMed: The Journal of nutrition (1991)
Source url:
Exact phrase from label:
OBJECTIVE: In view of the widespread use of magnesium (Mg) as a nutritional supplement, we investigated whether Mg would affect the absorption of calcium (Ca) as the intestinal absorption sites for Mg and Ca differ.
Label source:
PubMed: Journal of the American College of Nutrition (1994)
Action type:
separate
Target id:
/intervention/vitamin-d
Target name:
Vitamin D
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Magnesium is an essential cofactor for the metabolism and activation of Vitamin D, and Vitamin D in turn can enhance the intestinal absorption of magnesium.
Actionable advice:
Adequate intake of both Vitamin D and magnesium is a good idea for optimal status of both nutrients.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Magnesium assists in the activation of vitamin D, which helps regulate calcium and phosphate homeostasis to influence the growth and maintenance of bones. All of the enzymes that metabolize vitamin D seem to require magnesium, which acts as a cofactor in the enzymatic reactions in the liver and kidneys.
Label source:
PubMed: Role of Magnesium in Vitamin D Activation and Function. (PMID 29480918)
Action type:
informational_none
Target id:
/class/proton-pump-inhibitors
Target name:
Proton Pump Inhibitors (PPIs)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Long-term use of PPIs can significantly reduce the absorption of dietary and supplemental magnesium, increasing the risk of deficiency; supplementation helps counteract this effect.
Actionable advice:
If using PPIs for an extended period, monitor magnesium levels and consider supplementation.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(5.1)
• Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer • Acute Interstitial Nephritis: Observed in patients taking PPIs.
Label source:
Action type:
monitor
Target id:
/class/diuretics
Target name:
Loop and Thiazide Diuretics
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Loop and thiazide diuretics increase the urinary excretion of magnesium, which can lead to depletion over time; supplementation helps counteract this common side effect.
Actionable advice:
If taking these diuretics long-term, consider regular magnesium supplementation and monitor levels.
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/gabapentinoids
Target name:
Gabapentin
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Magnesium can decrease the absorption of gabapentin from the gut, potentially reducing its effectiveness for nerve pain or seizures.
Actionable advice:
Magnesium supplements and gabapentin doses 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:
/condition/heart-block
Target name:
Heart Block
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Magnesium can slow atrioventricular (AV) conduction in the heart, which may exacerbate pre-existing heart block, particularly at high doses.
Actionable advice:
It is important to consult a cardiologist before taking magnesium supplements for those with a history of heart block.
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:
informational_none
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 buffer its potential laxative effect and improve gastrointestinal tolerance, which is a common issue with magnesium supplements.
Actionable advice:
Magnesium malate is generally best taken with a meal to minimize potential stomach upset or diarrhea.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Supplementation with MagSRT™, a timed-release dimagnesium malate supplement containing vitamins B6, B12, and folate, for at least 30 days significantly improved magnesium status symptoms and increased RBC magnesium with minimal gastrointestinal symptoms.
Label source:
PubMed: Journal of the American College of Nutrition (2018)
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)
Source url:
Exact phrase from label:
This formulation conforms to the physiological mechanism of magnesium absorption throughout the digestive tract, allowing high absorption, and may improve gastrointestinal tolerance in long-term use.
Label source:
PubMed: Biological trace element research (2018)
Action type:
informational_none
Target id:
/circadian/wake
Target name:
Morning / Daytime
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
4
Description:
The malate (malic acid) component is involved in the Krebs cycle for cellular energy (ATP) production, making this form of magnesium potentially more suitable for daytime use to support energy levels.
Actionable advice:
Magnesium malate is generally best taken in the morning or early afternoon to align with its potential energizing effects.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Results demonstrated that Mg-malate supplementation significantly increased Mg levels in skeletal muscle and whole-brain tissue, correlating with enhanced neuromuscular performance.
Label source:
PubMed: Biological trace element research (2026)
Source url:
Exact phrase from label:
Among 14 verified protein targets, four were Krebs cycle enzymes, fumarate hydratase (FH), malate dehydrogenase-2 (MDH2), dihydrolipoamide acetyltransferase (DLAT) in pyruvate dehydrogenase complex (PDHC) and dihydrolipoamide S-succinyltransferase (DLST) in a-ketoglutarate dehydrogenase complex (KGDHC).
Label source:
PubMed: The Prostate (2019)
Source url:
Exact phrase from label:
We propose that the biological function of Citric Acid Cycle 2.1 in muscles is to accelerate recovery of ATP; whereas in white tissue adipocytes our testing of the theoretical concept led to the storage of energy as lipids.
Label source:
PubMed: Heliyon (2023)
Action type:
informational_none
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Magnesium can cause vasodilation and has a mild blood pressure-lowering effect, which can be additive with antihypertensive medications, potentially increasing the risk of hypotension.
Actionable advice:
It is a good idea to check blood pressure when starting magnesium supplementation while on blood pressure medication.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
This review investigates the anti-hypertensive potential of M. oleifera and its bioactive constituents, including moringin, phenolic acids, flavonoids, astragalin, and minerals, which have been identified for their vasodilatory, antioxidant, and angiotensin-converting enzyme (ACE) inhibitory properties.
Label source:
PubMed: An insight review on the potential anti-hypertensive effects of Moringa oleifera. (PMID 40882528)
Action type:
monitor
Target id:
/intervention/zinc
Target name:
High-Dose Zinc Supplements
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Very high doses of zinc can interfere with magnesium absorption and balance; this is less of a concern at typical supplemental doses but spacing is still prudent for optimal absorption.
Actionable advice:
For optimal absorption, high-dose zinc and magnesium supplements are best separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
OBJECTIVE: Both zinc (Zn) and magnesium (Mg) are widely used as nutritional supplements and the possibility was considered that Zn may interfere with the absorption of Mg, similar to previously reported results [1,2] obtained with the same dose of supplemental Zn on the absorption of calcium (Ca).
Label source:
PubMed: Inhibitory effects of zinc on magnesium balance and magnesium absorption in man. (PMID 7836627)
Action type:
separate
Target id:
/intervention/iron-bisglycinate
Target name:
Iron Supplements
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Magnesium can modestly decrease the absorption of non-heme iron supplements when taken at the same time by competing for absorption pathways.
Actionable advice:
To maximize iron absorption, take iron supplements at least 2 hours apart from magnesium.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Mean +/- SEM for deltaAUC due to experimental iron ingestion followed by treatment with Mg(OH)2, 78 +/- 23 micromol(hr)/L, was significantly less than that followed by no treatment, 144 +/- 33 micromol(hr)/L (p = 0.03 by signed rank test).
Label source:
PubMed: Academic emergency medicine : official journal of the Society for Academic Emergency Medicine (1998)
Source url:
Exact phrase from label:
Ca is able to inhibit the divalent metal transporter 1 (DMT1) in a dose-dependent manner to reduce Fe absorption and low Mg concentrations can exacerbate Fe deficiency.
Label source:
PubMed: Biological trace element research (2025)
Source url:
Exact phrase from label:
Administration of MgOH does not affect iron absorption in humans after a supratherapeutic dose of iron when the ratio of MgOH to elemental iron is 5:1.
Label source:
PubMed: Annals of emergency medicine (1999)
Action type:
separate
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:
Potassium-sparing diuretics can also reduce the amount of magnesium excreted by the kidneys, creating a small risk of elevated magnesium levels (hypermagnesemia) when combined with high-dose supplements.
Actionable advice:
Caution may help, and magnesium levels are worth monitoring, when combining high doses with these medications, especially with kidney issues.
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:
/dietary/phytate-rich-foods
Target name:
Phytate-Rich Foods (Grains, Legumes, Nuts)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Phytic acid, present in plant seeds, grains, and legumes, can bind to magnesium in the gut and form insoluble complexes, slightly reducing its bioavailability.
Actionable advice:
Magnesium supplements are generally best not taken with exceptionally high-phytate meals if absorption is a primary concern.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The addition of phytic acid lowered fractional apparent magnesium absorption from 32.5 +/- 6.9% (no added phytic acid) to 13.0 +/- 6.9% (1.49 mmol added phytic acid; P < 0.0005) and from 32.2 +/- 12.0% (no added phytic acid) to 24.0 +/- 12.9% (0.75 mmol added phytic acid; P < 0.01).
Label source:
PubMed: The American journal of clinical nutrition (2004)
Source url:
Exact phrase from label:
Phytate binds avidly to and can reduce gastrointestinal absorption of the phosphate anion and many macrominerals and trace elements including iron, zinc, calcium, and magnesium.
Label source:
PubMed: Clinical journal of the American Society of Nephrology : CJASN (2024)
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)
Action type:
avoid