Urolithin A
Urolithin A scored 6.8 / 10 (👍 Worth trying) on the BioHarmony scale as a Substance → Exogenous Metabolite.
What It Is
Urolithin A is a postbiotic metabolite naturally produced by gut bacteria from dietary ellagitannins (found in pomegranates, walnuts, and berries). It selectively induces mitophagy via the PINK1/Parkin pathway, clearing damaged mitochondria and stimulating their replacement with healthy ones. However, only ~40% of people efficiently produce urolithin A from food, making direct supplementation the primary access route for the majority. Type: Postbiotic / Exogenous Metabolite Current status: FDA GRAS since 2018 (GRN 000791). Available as Mitopure (Timeline brand) and generic supplements, though generic quality is highly variable (6/10 generic products failed lab testing per SuppCo 2025).
Dosing & Protocols
Dosing information is summarized from published research and community reports. This is not a prescribing guide. Consult a healthcare provider before starting any protocol.
Routes & Forms
| Route | Form | Clinical Range | Community Range |
|---|---|---|---|
| oral | capsule / powder (Mitopure) | 250-1000mg/day 8 human RCTs, all industry-funded (Amazentis/Timeline) | 500-1000mg/day Community consensus on 500mg minimum; 1000mg for noticeable effects |
Protocols
Standard daily Clinical
- Dose
- 500-1000mg/day oral (Mitopure)
- Frequency
- daily with breakfast
- Duration
- ongoing
Biomarker changes at 4 weeks. Functional outcomes require 2-4 months.
Budget entry Clinical
- Dose
- 500mg/day oral
- Frequency
- daily
- Duration
- minimum 4 weeks for biomarker shift
Minimum dose used in RCTs. Cost-conscious entry point.
Use-Case Specific Dosing
| Use Case | Dose | Notes |
|---|---|---|
| Mitochondrial | 500-1000mg/day | Primary mechanism; acylcarnitine and mitophagy gene expression shifts at 4 weeks |
| Muscle Growth | 500mg/day | +12% hamstring strength in one trial; inconsistent across studies |
| Anti Inflammatory | 500-1000mg/day | CRP, TNF-alpha, IFN-gamma reductions observed |
How this score is calculated →
Upside (1.45 / 5.00)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Efficacy | 25% | 2.5 | 0.625 | |
| Breadth of Benefits | 15% | 2.8 | 0.420 | |
| Evidence Quality | 25% | 2.5 | 0.625 | |
| Speed of Onset | 10% | 2.5 | 0.250 | |
| Durability | 10% | 1.5 | 0.150 | |
| Bioindividuality Upside | 15% | 2.5 | 0.375 | |
| Total | 2.445 |
Upside Rationale
Efficacy (2.5/5.0) Mitochondrial biomarkers reliably improve across trials (acylcarnitine reductions, mitophagy gene expression). But functional outcomes are borderline: +12% hamstring strength in one trial, VO2max trend at p=0.058, +33m 6MWT within-group only. The 2025 systematic review concluded "insufficient evidence" for functional benefits.
Breadth of Benefits (2.8/5.0) Mitochondrial function, muscle strength/endurance, anti-inflammatory (CRP, TNF-alpha), immune remodeling (CD8+ expansion). All mechanistically linked to mitophagy. Three distinct systems.
Evidence Quality (2.5/5.0) 8 human RCTs is a decent count. But ALL funded by Amazentis (manufacturer). No independent replication of any flagship finding. Industry-bias penalty -1.0. Base 3.5 - 1.0 = 2.5.
Speed of Onset (2.5/5.0) Biomarker changes at 4 weeks. Functional outcomes require 2-4 months.
Durability (1.5/5.0) No washout data published. Significant evidence gap.
Bioindividuality Upside (2.5/5.0) The 40/30/30 metabotype split means most people can't produce it naturally (the selling point). But community shows only 30-35% report meaningful subjective effects. Fit, young adults least likely to notice.
Downside (0.31 / 5.00)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Safety Risk | 30% | 1.2 | 0.360 | |
| Side Effect Profile | 15% | 1.2 | 0.180 | |
| Financial Cost | 5% | 3.5 | 0.175 | |
| Time/Effort Burden | 5% | 1.2 | 0.060 | |
| Opportunity Cost | 5% | 2.0 | 0.100 | |
| Dependency / Withdrawal | 15% | 1.0 | 0.150 | |
| Reversibility | 25% | 1.0 | 0.250 | |
| Total | 1.275 | |||
| Harm subtotal × 1.4 | 1.316 | |||
| Opportunity subtotal × 1.0 | 0.335 | |||
| Combined downside | 1.651 | |||
| Baseline offset (constant) | −1.340 | |||
| Effective downside penalty | 0.311 |
Downside Rationale
Safety Risk (1.2/5.0) GRAS since 2018. Endogenous metabolite. NOAEL >3,400 mg/kg in rats (enormous margin). Zero SAEs across 220+ subjects. Exceptionally clean.
Side Effect Profile (1.2/5.0) Mild myalgia, headache at rates equal to placebo. Essentially side-effect-free.
Financial Cost (3.5/5.0) $50-80/mo for quality Mitopure. One of the more expensive daily supplements. Generic alternatives are unreliable (6/10 failed lab testing).
Time/Effort Burden (1.2/5.0) Take a capsule. Minimal.
Opportunity Cost (2.0/5.0) Could eat pomegranate/walnuts, but only works for the 40% who are efficient converters.
Dependency/Withdrawal (1.0/5.0) No dependency.
Reversibility (1.0/5.0) Fully reversible.
Verdict
✅ Best for: Older adults, sedentary individuals, or anyone with compromised mitochondrial function seeking a well-tolerated mitophagy inducer. Especially compelling for the 60% of people who cannot efficiently produce urolithin A from dietary sources. Use Mitopure (Timeline) specifically, as generic quality is unreliable.
❌ Avoid if: Price-sensitive (this is expensive for uncertain individual benefit). Already fit and metabolically healthy (least likely to notice effects). Using generic brands without third-party testing.
Use Case Breakdown
The overall BioHarmony score reflects the intervention's primary evidence profile. These subratings are independent assessments per use case.
| Use Case | Score | Summary |
|---|---|---|
| 💪 Mitochondrial | 7.0 | Core mechanism: PINK1/Parkin mitophagy induction; acylcarnitine shifts reliably demonstrated across RCTs |
| ⚖️ Anti-Inflammatory | 5.5 | CRP, TNF-alpha, IFN-gamma reductions across trials; consistent signal |
| ⚖️ Geriatric / Aging Population | 5.5 | Older adults most likely to benefit from mitophagy induction; declining mitochondrial function with age |
| ⚖️ Muscle Growth / Hypertrophy | 5.0 | Hamstring strength improvement in one trial; muscle endurance data from Singh 2022 |
| ⚖️ Longevity / Lifespan | 5.0 | Lifespan extension in C. elegans (Ryu 2016); core mitophagy mechanism is a longevity pathway |
| ⚖️ Healthspan | 5.0 | Mitochondrial renewal is a healthspan mechanism; human functional data still insufficient |
| ⚖️ Autophagy | 5.0 | Selective mitophagy (not general autophagy) is the core mechanism; PINK1/Parkin pathway |
| ○ Immune Function | 4.5 | One 4-week trial showed naive CD8+ T-cell expansion; CRP/TNF-alpha reduction |
| ○ Strength / Power | 4.5 | +12% hamstring strength at 500mg in one trial; single study |
| ○ Endurance / Cardio | 4.5 | +10% VO2max trend (p=0.058); +33m 6MWT within-group only |
| ○ Recovery / Repair | 4.0 | Mitochondrial renewal supports recovery; indirect mechanism |
| ○ Cellular Senescence | 4.0 | Mitophagy clears dysfunctional mitochondria associated with senescence; indirect |
| ○ Energy / Fatigue | 4.0 | Mitochondrial renewal improves cellular energy production; subjective reports mixed |
| ○ Metabolic Health | 3.5 | Downstream of mitochondrial improvement; no direct metabolic endpoint data |
| ○ Cardiovascular | 3.0 | Indirect via mitochondrial function; no direct cardiovascular RCTs |
How This Score Could Change
BioHarmony scores are living assessments. New research, regulatory changes, or personal context can shift the score up or down. These are the most likely scenarios that would change this intervention's rating.
| Scenario | Dimension changes | New score |
|---|---|---|
| Independent lab replicates muscle/endurance outcomes | Evidence 2.5→3.5, Efficacy 2.5→3.0 | 7.4 / 10 💪 Strong recommend |
| 650-person brain health trial shows cognitive benefit | Breadth 2.8→3.5, Efficacy 2.5→3.0 | 7.3 / 10 💪 Strong recommend |
| Price drops to $20/mo via patent expiry | Cost 3.5→2.0 | 7.0 / 10 💪 Strong recommend |
| Long-term study shows no functional benefit despite biomarkers | Efficacy 2.5→1.8 | 6.4 / 10 👍 Worth trying |
Key Evidence Sources
- Andreux PA et al. First human RCT of urolithin A. Nature Metabolism 2019 — First-in-human RCT; biomarker changes at 4 weeks
- Singh A et al. Muscle endurance RCT. Cell Rep Med 2022 — +12% hamstring strength at 500mg; muscle endurance improvements
- Liu S et al. Immune remodeling with urolithin A. Nature Metabolism 2022 — Naive CD8+ T-cell expansion in 4-week trial
- D'Amico D et al. Mitophagy mechanism review. Nature Reviews 2021 — Comprehensive review of PINK1/Parkin mitophagy pathway
- Ryu D et al. Urolithin A extends lifespan in C. elegans. Nature Medicine 2016 — Lifespan extension via mitophagy in model organisms
- Denk D et al. Systematic review of urolithin A RCTs. 2025 — Concluded 'insufficient evidence' for functional outcomes despite biomarker shifts
- Toney AM et al. Urolithin A and inflammation. Nutrients 2019 — Anti-inflammatory mechanisms and CRP reduction
- Espín JC et al. Ellagitannin metabolism metabotypes. J Agric Food Chem 2013 — 40/30/30 metabotype distribution for UA production
- Keats EC et al. ATLAS trial 4-month data. 2023 — Extended trial data on functional outcomes
- FDA GRAS Notice GRN 000791. 2018 — NOAEL: 3,451-3,826 mg/kg in rats; GRAS determination
Other interventions for Anti-Inflammatory
See all ratings →📊 How BioHarmony scoring works
BioHarmony translates a weighted expected-value calculation into a reader-facing 0–10 score. 5.0 is neutral (benefits and risks balance). Above 5 = benefits outweigh risks; below 5 = risks outweigh benefits.
Harm-type downsides (safety risk, side effects, reversibility, dependency) carry a 1.4× precautionary multiplier. Harm weighs more than benefit. Opportunity-type downsides (financial cost, time/effort, opportunity cost) are subtracted at face value.
Use case subratings are independent assessments of how well the intervention addresses specific health goals. They are not components of the overall score. Each subrating reflects the scorer's judgment based on use-case-specific evidence, safety, and effect sizes.
Every dimension is evaluated on a 1–5 scale, and the baseline (1) is subtracted before weighting. A perfect intervention with zero downsides contributes zero penalty rather than a residual floor, so top-tier scores are actually reachable.
EV = Upside − Downside
EV = 1.445 − 0.311 = 1.134
EV ranges from −5 to +5. Adding 7 shifts to 2–12, dividing by 12 normalizes to 0–1, then ×10 gives the 0–10 score.
Score = ((1.134 + 7) / 12) × 10 = 6.8 / 10
