Meta Information
ID:3-hydroxyanthranilic-acid
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:
Kidney impairment can lead to the accumulation of 3-HAA and its downstream metabolite, the neurotoxin quinolinic acid, to dangerous levels.
Actionable advice:
This should be strictly avoided with any degree of kidney disease.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
its metabolism via the kynurenine pathway is potently increased in the course of CKD... Their accumulation in the course of CKD may induce oxidative cell damage which stimulates inflammatory processes.
Label source:
Kynurenine-pathway-in-CKD review, PMC8862190. Supports KP upregulation/metabolite accumulation in kidney impairment (3-HAA/quinolinic acid not named specifically; review level).
Action type:
avoid
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 effects of supplemental 3-HAA on fetal development are unknown, and altering the kynurenine pathway, which is critical for neurodevelopment, poses a significant theoretical risk.
Actionable advice:
This should be strictly avoided during pregnancy.
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:
Precautionary: kynurenine-pathway metabolites (e.g., NMDA-active quinolinic acid) are relevant to neurodevelopment, so supplementing a KP metabolite in pregnancy carries a theoretical risk. FLAG: the cited PMC8862190 is a CKD review and does not address pregnancy/fetal development.
Label source:
Class inference
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 3-HAA or its metabolites pass into breast milk. Due to the potential for neurotoxic effects from downstream metabolites, it should be avoided.
Actionable advice:
It 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:
Action type:
avoid
Target id:
/intervention/vitamin-b6
Target name:
Vitamin B6 (P-5-P)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin B6 is a critical cofactor for enzymes that balance the kynurenine pathway. Deficiency can unfavorably shunt metabolism towards the production of the neurotoxin quinolinic acid from 3-HAA's precursors.
Actionable advice:
Adequate Vitamin B6 intake or co-supplementation should be maintained to prevent metabolic imbalance.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We found increased neuroexcitatory QA/KA ratio in both plasma and CSF of PD participants associated with peripheral and cerebral inflammation and vitamin B6 deficiency.
Label source:
PubMed: Parkinson's disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction. (PMID 40287426)
Action type:
informational_none
Target id:
/intervention/iron-bisglycinate
Target name:
Iron
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The enzyme that metabolizes 3-HAA (3-hydroxyanthranilate 3,4-dioxygenase) is iron-dependent. Iron deficiency can impair its clearance, leading to accumulation.
Actionable advice:
Adequate iron status should be confirmed before and during use, and it should not be taken if iron deficient.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We have found that Fe2+, which is required for enzymatic activity, can equilibrate freely, albeit slowly, with the enzyme during the course of the enzyme reaction even in the presence of saturating 3-hydroxanthranilate.
Label source:
PubMed: Beef kidney 3-hydroxyanthranilic acid oxygenase. Purification, characterization, and analysis of the assay. (PMID 1387)
Action type:
avoid
Target id:
/condition/chronic-systemic-inflammation
Target name:
Chronic Systemic Inflammation
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Inflammatory states strongly upregulate the kynurenine pathway. Adding supplemental 3-HAA could overload this pathway, potentially increasing the production of the neurotoxic metabolite quinolinic acid.
Actionable advice:
Use is best avoided during periods of high systemic inflammation (e.g., elevated hs-CRP).
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Impaired kidney function and increased inflammatory process occurring in the course of Chronic Kidney Disease (CKD) contribute to the development of complex amino-acid alterations... its metabolism via the kynurenine pathway is potently increased.
Label source:
PMC8862190. Supports inflammation-driven kynurenine-pathway induction; that added 3-HAA increases quinolinic acid specifically is an extrapolation.
Action type:
avoid
Target id:
/class/chemotherapy-radiation
Target name:
Cytotoxic Cancer Therapies (Chemotherapy & Radiation)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
As a potent antioxidant, 3-HAA may interfere with the efficacy of cancer treatments that rely on generating reactive oxygen species to destroy malignant cells.
Actionable advice:
This is best avoided during and around periods of chemotherapy or radiation therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
However, rare uterine sarcomas, including malignant mixed mullerian tumors (MMMT), have also been reported.
Label source:
Action type:
avoid
Target id:
/intervention/levodopa
Target name:
Levodopa
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Metabolites of the kynurenine pathway, including 3-HAA, may compete with Levodopa for transport across the blood-brain barrier or exert effects on dopaminergic neurons, potentially altering medication efficacy.
Actionable advice:
Use is best avoided when taking Levodopa for conditions like Parkinson's disease.
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: large neutral amino acids compete with levodopa for blood-brain-barrier transport (cited PMC1032296 confirms LNAA-levodopa competition). FLAG: 3-HAA is a kynurenine metabolite, not an LNAA, so the transport-competition link is only analogical; direct 3-HAA/levodopa data are lacking.
Label source:
Class inference
Action type:
avoid
Target id:
/intervention/nmn
Target name:
NMN (Nicotinamide Mononucleotide)
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
3-HAA is a precursor to NAD+ via the de novo synthesis pathway. Co-administration with NMN (from the salvage pathway) may provide a multi-pronged approach to boosting NAD+ levels.
Actionable advice:
Can be taken at the same time as NMN to potentially enhance NAD+ synthesis.
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:
Biochemical inference: 3-HAA is an intermediate of the de novo NAD+ synthesis pathway while NMN feeds the salvage pathway, so co-use could be complementary for raising NAD+. Established biochemistry (cited PMC5398323 confirms KP->NAD+ de novo route but not the combination).
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/nr
Target name:
NR (Nicotinamide Riboside)
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
3-HAA is a precursor to NAD+ via the de novo synthesis pathway. Co-administration with NR (from the salvage pathway) may provide a multi-pronged approach to boosting NAD+ levels.
Actionable advice:
Can be taken at the same time as NR to potentially enhance NAD+ synthesis.
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:
Biochemical inference: 3-HAA (de novo NAD+ pathway) and NR (salvage pathway) feed NAD+ by complementary routes. Established biochemistry; cited PMC5398323 supports the de novo route only, not the NR combination.
Label source:
Class inference
Action type:
informational_none
Target id:
/class/serotonergic-agents
Target name:
Serotonergic Medications (SSRIs, SNRIs, TCAs, Triptans)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Supplementing a kynurenine pathway metabolite could theoretically alter the complex balance between the kynurenine and serotonin pathways in the brain, though direct clinical interactions are not established.
Actionable advice:
This is best used with caution, and it is worth monitoring for mood changes when taking serotonergic medications.
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: tryptophan is shared between the kynurenine and serotonin pathways (cited PMC5398323 notes the KP controls Trp availability for serotonin synthesis), so loading a KP metabolite could theoretically shift that balance. Extrapolated, not directly studied.
Label source:
Class inference
Action type:
monitor
Target id:
/intervention/copper
Target name:
High-Dose Copper Supplements
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In the presence of transition metals like copper, 3-HAA can act as a pro-oxidant, generating potentially harmful reactive oxygen species.
Actionable advice:
High-dose standalone copper supplements are generally best not taken concurrently.
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 redox chemistry: 3-hydroxyanthranilic acid autoxidizes in the presence of transition metals (copper, iron) to generate hydrogen peroxide/ROS, acting as a pro-oxidant. (Original citation was a non-authoritative bu.edu PDF, discarded; the chemistry itself is well-documented.)
Label source:
Class inference
Action type:
avoid
Target id:
/class/photosensitizing-agents
Target name:
Photosensitizing Medications or Substances
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Other metabolites in the kynurenine pathway are known photosensitizers. While not strongly established for 3-HAA itself, there is a theoretical risk of increased sun sensitivity.
Actionable advice:
Extra sun protection may help if this is taken alongside other photosensitizing agents.
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:
Theoretical: some kynurenine-pathway metabolites are UV chromophores, raising a speculative photosensitivity concern for 3-HAA. FLAG: the cited PMC3399400 covers UV-induced KP changes in skin but does NOT establish 3-HAA as a photosensitizer - low-evidence/theoretical.
Label source:
Class inference
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:
The kynurenine pathway exhibits a diurnal rhythm, and its role in NAD+ synthesis may be most beneficial when aligned with the start of the active circadian phase.
Actionable advice:
Consider taking in the morning to align with natural metabolic rhythms.
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: NAD+ biosynthesis (NAMPT/NAD+) shows circadian oscillation, so timing a NAD+-pathway precursor to the active phase is a rational heuristic. FLAG: the cited PMC5398323 has no circadian content - the NAD+ circadian-rhythm basis is established elsewhere, not in that paper.
Label source:
Class inference
Action type:
informational_none