Global Ingredient Risk Index Metabolic

Urolithin A

Urolithin A (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one)

Also known as: urolithin A, Mitopure, UA, ellagitannin metabolite

25 მარ 2026

LOW RISK 3.0/10 How?

This ingredient is classified as unclassified risk (GIRI score: 3.0/10).

Known Safety Concerns

Limited long-term human safety data beyond 3 months
FDA GRAS status pending -- relatively new supplement ingredient
Produced by only ~40% of people from diet -- direct supplementation bypasses gut microbiome
Rare: GI discomfort in Phase 1 trials

Contraindications

Limited long-term human safety data beyond 3 months
FDA GRAS status pending -- relatively new supplement ingredient

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Information not yet available for this ingredient profile.

Urolithin A is a gut microbiome-derived metabolite from ellagitannins (pomegranate, walnuts) that induces mitophagy — selective removal of dysfunctional mitochondria. Sold as the branded ingredient Mitopure. Phase 1 trials show safety at 250-1000 mg/day. Long-term safety data is limited. FDA GRAS notification filed.

Scientific Name: Urolithin A (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one)

Information not yet available for this ingredient profile.

SETI Score 50/100

Risk Level High risk

Scientific Confidence Low

Evidence Strength Limited

Key Benefit Metabolic

Key Safety Concern Limited long-term human safety data beyond 3 months

Evidence Reviewed 10 PubMed studies

Scientific Confidence Low

Based on study quality, consistency, and recency

Executive Summary — Ingredient Assessment

SETI Score 50/100

Risk Level High risk

Evidence Strength Limited

Main Benefit Metabolic

Main Safety Concern Limited long-term human safety data beyond 3 months

Ingredient Urolithin A

Scientific name Urolithin A (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one)

Scientific Evidence Overview

10 studies reviewed
0 high-quality studies (meta-analysis or RCT)
Main clinical benefit observed: Metabolic
Evidence consistency: High consistency across studies (100%)

Safety Signals

Limited long-term human safety data beyond 3 months
FDA GRAS status pending -- relatively new supplement ingredient
Produced by only ~40% of people from diet -- direct supplementation bypasses gut microbiome
Rare: GI discomfort in Phase 1 trials

Evidence Strength Limited

Final Scientific Assessment

The available scientific evidence for Urolithin A indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.

Ingredient Urolithin A

Evidence reviewed 10 peer-reviewed studies (last 10 years)

Scientific name Urolithin A (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one)

50 /100

Total SETI Score

High risk

Evidence quality	10/40
Evidence consistency	20/20
Safety signals	0/20
Study recency	10/10
Evidence transparency	10/10

Evidence Summary

10 studies reviewed
0 high-quality studies (meta-analysis or systematic review)
0 studies identified benefits or no safety concern (GREEN)
10 studies reported limited or advisory safety evidence (YELLOW)

Evidence Policy

Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.

Last updated: 25 მარ 2026, 17:56

Evidence Distribution

10 Other / unclassified

Observational / other LOW evidence YELLOW
Trihexyl phosphate exposure disrupts mitophagy and activates mtDNA-cGAS-STING signaling to drive pyroptosis and steroidogenic impairment in Leydig cells. ↗

PMID 41875563 ↗

Journal J Hazard Mater

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41875563/

Dai Y et al.. Trihexyl phosphate exposure disrupts mitophagy and activates mtDNA-cGAS-STING signaling to drive pyroptosis and steroidogenic impairment in Leydig cells.. J Hazard Mater. 2026. PMID:41875563.
Observational / other LOW evidence YELLOW
Urolithin A From Gut Metabolite to Therapeutic Agent: Bioavailability, Mechanisms, and Translational Insights. ↗

PMID 41866331 ↗

Journal J Food Sci

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41866331/

Yuan H et al.. Urolithin A From Gut Metabolite to Therapeutic Agent: Bioavailability, Mechanisms, and Translational Insights.. J Food Sci. 2026. PMID:41866331.
Observational / other LOW evidence YELLOW
Potential impact of urolithin A on pathways relevant to sleep health: a mini review. ↗

PMID 41859662 ↗

Journal Front Nutr

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41859662/

Pinaffi-Langley ACDC et al.. Potential impact of urolithin A on pathways relevant to sleep health: a mini review.. Front Nutr. 2026. PMID:41859662.
Observational / other LOW evidence YELLOW
Beyond Supportive Care: Mitochondria as a Strategic Therapeutic Avenue in Acute Pancreatitis. ↗

PMID 41854947 ↗

Journal Dig Dis Sci

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41854947/

Chooklin S et al.. Beyond Supportive Care: Mitochondria as a Strategic Therapeutic Avenue in Acute Pancreatitis.. Dig Dis Sci. 2026. PMID:41854947.
Observational / other LOW evidence YELLOW
Urolithin A Attenuates Aging-Induced Liver Injury by Inhibiting Nur77 Ubiquitination and Degradation. ↗

PMID 41837341 ↗

Journal J Agric Food Chem

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41837341/

Xiao J et al.. Urolithin A Attenuates Aging-Induced Liver Injury by Inhibiting Nur77 Ubiquitination and Degradation.. J Agric Food Chem. 2026. PMID:41837341.
Observational / other LOW evidence YELLOW
The interplay between mitophagy andu00a0ferroptosis in Alzheimer's disease: Mechanisms and therapeutic implications. ↗

PMID 41823685 ↗

Journal J Alzheimers Dis

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41823685/

Liu A et al.. The interplay between mitophagy andu00a0ferroptosis in Alzheimer's disease: Mechanisms and therapeutic implications.. J Alzheimers Dis. 2026. PMID:41823685.
Observational / other LOW evidence YELLOW
Impaired mitophagy contributes to osteogenesis and mineralization disorders in fibrous dysplasia. ↗

PMID 41803635 ↗

Journal Autophagy

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41803635/

Ling Z et al.. Impaired mitophagy contributes to osteogenesis and mineralization disorders in fibrous dysplasia.. Autophagy. 2026. PMID:41803635.
Observational / other LOW evidence YELLOW
Urolithin 9-dehydroxylase from Enterocloster bolteae JCM 12243(T) catalyzing regiospecific dehydroxylation of urolithins. ↗

PMID 41797252 ↗

Journal Enzyme Microb Technol

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41797252/

Katasho A et al.. Urolithin 9-dehydroxylase from Enterocloster bolteae JCM 12243(T) catalyzing regiospecific dehydroxylation of urolithins.. Enzyme Microb Technol. 2026. PMID:41797252.
Observational / other LOW evidence YELLOW
FUNDC1-dependent mitophagy determines axon regeneration capacity. ↗

PMID 41795666 ↗

Journal Autophagy

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41795666/

Li W et al.. FUNDC1-dependent mitophagy determines axon regeneration capacity.. Autophagy. 2026. PMID:41795666.
Observational / other LOW evidence YELLOW
Neuroprotective effects of Urolithin A and B in an intracerebroventricular streptozotocin-induced Alzheimer's-like model in rats. ↗

PMID 41794870 ↗

Journal BMC Pharmacol Toxicol

Year 2026

Study type Observational / other

Evidence strength LOW evidence

PubMed link https://pubmed.ncbi.nlm.nih.gov/41794870/

Salari MT et al.. Neuroprotective effects of Urolithin A and B in an intracerebroventricular streptozotocin-induced Alzheimer's-like model in rats.. BMC Pharmacol Toxicol. 2026. PMID:41794870.

Q × L × D × S × 10 = 3.0 / 10

The GIRI Score is the product of four independently computed evidence components, each normalised to 0–1, then scaled to 0–10. Every component is derived exclusively from peer-reviewed references and regulatory data — no editorial judgement is applied.

0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.

Method: Q = number of approved references ÷ 10 (capped at 1.0)

50%

Limited — mostly case reports or animal studies

Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.

Benefit

Risk

50%

Mixed or neutral — roughly equal benefit and risk signals

Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.

50%

One or more monitoring-level safety signals active

Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.

0Q × 5L × 5D × 5S = 3.0 / 10

Final GIRI Score for Urolithin A. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.

Full methodology & data sources

The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.

References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.

LOW RISK 3.0/10

Based on available regulatory signals and scientific evidence, this ingredient presents a low safety concern under normal conditions of use.

LOW
0–3.0

MODERATE
3.0–5.5

HIGH
5.5–7.5

CRITICAL
7.5–10

3.0

The score pin shows exactly where this ingredient falls on the fixed risk scale.

What drove the Low classification for Urolithin A

A score of 3.0 places this ingredient in the Low band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.

0 approved references.

Limited — mostly case reports or animal studies (Level 4–5).

Neutral or mixed — benefit and risk signals roughly balanced.

No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.

No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).

How are the Low / Moderate / High / Critical thresholds defined?

The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:

Level	Score	Meaning
LOW	0.0 – 2.9	Sparse or predominantly beneficial evidence. No active safety alerts.
MODERATE	3.0 – 5.4	Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups.
HIGH	5.5 – 7.4	Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended.
CRITICAL	7.5 – 10	Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision.

Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.

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Urolithin A

Safety Profile

Known Safety Concerns

Contraindications

Interactions

Evidence and Scientific Findings

Ingredient Overview

Biological and Chemical Classification

Mechanism of Action

Clinical Evidence of Effectiveness

Pharmacokinetics

Recommended Dosage

SETI — Scientific Evidence Transparency Index

Executive Summary — Ingredient Assessment

Evidence Summary

Evidence Policy

Evidence Distribution

Score Transparency

Risk Level Classification

What drove the Low classification for Urolithin A

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