Meta Information
ID:urolithin-a
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/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The safety of Urolithin A supplementation during pregnancy has not been established through clinical research.
Actionable advice:
Urolithin A supplementation should be avoided completely during pregnancy.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
NatMed Pro Monograph: Pomegranate
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is unknown if Urolithin A or its metabolites are excreted into breast milk or what their effects on a nursing infant might be.
Actionable advice:
Urolithin A supplementation should be avoided completely while breastfeeding.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
NatMed Pro Monograph: Pomegranate
Action type:
avoid
Target id:
/class/ugt1a1-substrates
Target name:
UGT1A1 Substrates
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Urolithin A may inhibit the UGT1A1 enzyme, which is responsible for metabolizing certain drugs. This could increase the concentration and potential for side effects of medications like some statins (atorvastatin) or chemotherapy agents (irinotecan).
Actionable advice:
It is important to consult a physician before use when taking medications metabolized by the UGT1A1 enzyme.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Urolithin A UGT1A1 inhibition is reported only in separate in vitro work that is NOT cited here; the cited house-paper (PMID 35584623, a muscle-function RCT) contains no pharmacokinetic/UGT1A1 data. Insufficient basis as cited - flagged for a proper PK source or removal.
Action type:
informational_none
Target id:
/intervention/exercise
Target name:
Exercise
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Urolithin A promotes the clearing of damaged mitochondria (mitophagy), while exercise stimulates the creation of new, healthy mitochondria (biogenesis). This combination creates a powerful 'remove and replace' cycle for cellular and muscle health.
Actionable advice:
Regular Urolithin A supplementation is best combined with a consistent exercise routine for enhanced benefits.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Furthermore, UA-induced calcium elevation activates mitochondrial biogenesis via UNC-43/CAMK2D and SKN-1/NFE2L2/Nrf2 pathways, which are both essential for healthspan and lifespan extension.
Label source:
PubMed: Autophagy (2025)
Source url:
Exact phrase from label:
A single dose of exercise augmented the expression of citrate synthase (+43%, p < 0.05) and corrected the over-assembly of autophagosomes (-64%, p < 0.05). In patient muscle cells, UA treatment stimulated autophagic flux, increased the expression of OxPhos proteins (+15%-47%, p < 0.05) and improved maximal oxygen consumption (+84%, p < 0.05).
Label source:
PubMed: Journal of cachexia, sarcopenia and muscle (2025)
Action type:
informational_none
Target id:
/condition/hepatic-impairment
Target name:
Hepatic Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Urolithin A is metabolized by the liver via glucuronidation and sulfation. In cases of severe liver disease, its clearance may be impaired, although specific clinical data is lacking.
Actionable advice:
It is important to consult a physician before using Urolithin A for those with significant liver disease.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Using UPLC-MS/MS analysis, the metabolites might be urolithin A 3-O-glucuronide, urolithin A 3-sulfate, and urolithin A-sulfate glucuronide.
Label source:
PubMed: Evidence-based complementary and alternative medicine : eCAM (2023)
Source url:
Exact phrase from label:
Urolithin aglycons were observed in rumen and feces, and glucuronide and sulfate derivatives were detected in plasma and urine. Sulfate derivatives were the main metabolites detected in plasma, while glucuronide derivatives were the main ones in urine.
Label source:
PubMed: Journal of agricultural and food chemistry (2012)
Source url:
Exact phrase from label:
To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues).
Label source:
PubMed: Molecular nutrition & food research (2022)
Action type:
informational_none
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
As a polyphenol metabolite, Urolithin A may have theoretical mild antiplatelet effects. While not clinically established, this could potentially increase bleeding risk when combined with blood-thinning medications.
Actionable advice:
This is best used with caution, and it is worth monitoring for any signs of increased bruising or bleeding when taking anticoagulant or antiplatelet drugs.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties.
Label source:
Action type:
monitor
Target id:
/class/ampk-activators
Target name:
AMPK Activators
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Urolithin A's primary action of mitophagy is complementary to the effects of AMPK activators (like metformin or berberine), which also promote autophagy and mitochondrial biogenesis, potentially leading to synergistic effects on cellular rejuvenation.
Actionable advice:
Consider combining with AMPK activators for a potentially enhanced effect on mitochondrial health.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: urolithin A induces mitophagy (supported by PMID 35584623), which is complementary to AMPK activators (metformin, berberine) that also promote autophagy/mitochondrial biogenesis. The UA-mitophagy half is evidenced; the AMPK-activator synergy is class-level.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/nmn
Target name:
NMN (Nicotinamide Mononucleotide)
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
By improving mitochondrial quality through mitophagy, Urolithin A may create a more efficient cellular environment for NAD+ precursors like NMN to support energy production and sirtuin activity.
Actionable advice:
Taking Urolithin A may improve the cellular machinery that utilizes NAD+ precursors.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: urolithin A improves mitochondrial quality via mitophagy (PMID 35584623), which could complement NAD+ precursors like NMN. UA-mitophagy is evidenced; the NMN synergy is class-level, not studied.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/nr
Target name:
Nicotinamide Riboside (NR)
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
By clearing dysfunctional mitochondria, Urolithin A may enhance the cell's ability to effectively use NAD+ precursors like NR, leading to better support for cellular energy and repair pathways.
Actionable advice:
Taking Urolithin A may improve the cellular machinery that utilizes NAD+ precursors.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
UA administration has been shown to induce mitophagy and mitochondrial function in pre-clinical models of aging and disease.
Label source:
Action type:
informational_none
Target id:
/circadian/wake
Target name:
Waking Up
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
1
Description:
Taking Urolithin A in the morning may better align with the natural circadian rhythms of mitochondrial quality control processes, including mitophagy, potentially enhancing its biological effect.
Actionable advice:
A daily dose of Urolithin A is generally best taken in the morning.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Speculative: the cited house-paper (PMID 35584623) contains no circadian or dosing-time data, and there is no established circadian-timing recommendation for urolithin A. Insufficient basis.
Action type:
informational_none
Target id:
/condition/renal-impairment
Target name:
Renal Impairment
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The kidneys are involved in the clearance of Urolithin A metabolites. While no kidney toxicity has been reported, caution is warranted in individuals with severe renal impairment.
Actionable advice:
Consulting a physician before use may help for those with severe kidney disease.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
urine contained only trace conjugated urolithin A.
Label source:
PubMed: Molecules (Basel, Switzerland) (2026)
Source url:
Exact phrase from label:
On average, glucuronidated urolithins accounted for 85% of the total excreted amount. Urolithin A 3/8-glucuronide was the main metabolite, comprising 54% (JPSP) and 57% (HJPSP) of total urolithin excretion over 72 h.
Label source:
PubMed: Food & function (2026)
Source url:
Exact phrase from label:
a complex combination of urolithin-conjugated forms was observed in nonhydrolyzed urine, confirming an extensive phase II metabolism after absorption.
Label source:
PubMed: Journal of agricultural and food chemistry (2012)
Action type:
informational_none
Target id:
/class/antibiotics-long-term
Target name:
Antibiotics (Long-term Use)
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
This interaction affects natural production, not the supplement. Long-term antibiotic use can destroy the gut bacteria that convert dietary precursors (ellagitannins) into Urolithin A, making supplementation a more reliable method to achieve consistent levels.
Actionable advice:
If on long-term antibiotics, be aware your natural production of Urolithin A is likely compromised.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Established urolithin-A biology: UA is produced by gut bacteria from dietary ellagitannins/ellagic acid, so long-term antibiotics that disrupt the microbiome can reduce endogenous UA production (this concerns natural production, not the supplement). Well-documented; cited house-paper does not itself address it.
Label source:
Class inference
Action type:
informational_none
Target id:
/class/immunosuppressants
Target name:
Immunosuppressants
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Urolithin A modulates mitochondrial function (mitophagy), a process critical for proper immune cell activity and memory. This could theoretically interfere with the intended action of immunosuppressant medications, though this is not clinically proven.
Actionable advice:
It is a good idea to talk to a specialist before using Urolithin A while on immunosuppressive therapy.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Speculative/overstated: the cited house-paper (PMID 35584623) reports reduced CRP but nothing on immune-cell mitophagy or interference with immunosuppressant drugs. No adequate basis for an interaction claim as cited.
Action type:
informational_none