Urolithin A for Neurodegeneration

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Urolithin A for Neurodegeneration

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Urolithin A for Neurodegeneration

Introduction

Urolithin A (UroA) is a gut [microbiome](/entities/microbiome)-derived metabolite of ellagitannins found in pomegranates, berries, and nuts[@ryu2016]. It has gained significant attention for its ability to induce mitophagy—the selective [autophagy](/entities/autophagy) of damaged mitochondria—and has shown promise in preclinical and clinical studies for neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and tauopathies such as corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP)[@liu2023].

This monograph provides a comprehensive evidence synthesis for Urolithin A as a potential neuroprotective intervention, with particular attention to its applicability for CBS and PSP patients.

<div class="infobox">
| Category | Value |
|---------|-------|
| Full Name | Urolithin A (UroA), 3,8,9-Trihydroxyurolithin |
| Formula | C21H1₈O₆ |
| Molecular Weight | 362.4 Da |
| Classification | Ellagitannin metabolite (benzocchromene-6,10-dione) |
| Mechanism | Mitophagy activation via PINK1/Parkin pathway |
| Clinical Stage | Phase II/III |
| Source | Gut microbiome metabolism of ellagitannins (pomegranate, berries, nuts) |
</div>

Overview

...

Urolithin A for Neurodegeneration

Introduction

Urolithin A (UroA) is a gut [microbiome](/entities/microbiome)-derived metabolite of ellagitannins found in pomegranates, berries, and nuts[@ryu2016]. It has gained significant attention for its ability to induce mitophagy—the selective [autophagy](/entities/autophagy) of damaged mitochondria—and has shown promise in preclinical and clinical studies for neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and tauopathies such as corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP)[@liu2023].

This monograph provides a comprehensive evidence synthesis for Urolithin A as a potential neuroprotective intervention, with particular attention to its applicability for CBS and PSP patients.

<div class="infobox">
| Category | Value |
|---------|-------|
| Full Name | Urolithin A (UroA), 3,8,9-Trihydroxyurolithin |
| Formula | C21H1₈O₆ |
| Molecular Weight | 362.4 Da |
| Classification | Ellagitannin metabolite (benzocchromene-6,10-dione) |
| Mechanism | Mitophagy activation via PINK1/Parkin pathway |
| Clinical Stage | Phase II/III |
| Source | Gut microbiome metabolism of ellagitannins (pomegranate, berries, nuts) |
</div>

Overview

Urolithin A represents a promising therapeutic approach for neurodegenerative diseases based on its unique ability to selectively clear damaged mitochondria through mitophagy induction[@fang2019]. Unlike pharmacological [mTOR](/mechanisms/mtor-signaling-pathway) inhibitors such as rapamycin, Urolithin A appears to promote mitophagy through a more physiological mechanism that preserves cellular homeostasis while enhancing mitochondrial quality control.

The [gut-brain axis](/entities/gut-brain-axis) connection adds another layer of therapeutic potential, as Urolithin A is produced endogenously through gut microbiome metabolism of dietary ellagitannins[@selma2009]. This endogenous production pathway suggests that individual microbiome composition may influence both baseline mitophagy capacity and response to supplementation.

Mechanism of Action

Mitophagy Induction Pathway

Urolithin A promotes mitophagy through multiple complementary mechanisms:

Mermaid diagram (expand to render)

Molecular Targets

| Target | Mechanism | Evidence Level |
|--------|-----------|----------------|
| mTORC1 | Partial inhibition → autophagy initiation | Preclinical[@damico2022] |
| PINK1 | Stabilization on outer mitochondrial membrane | Cellular models[@fang2019] |
| Parkin | Recruitment and activation | In vitro |
| AMPK | Indirect activation via AMP/ATP ratio | Preclinical |
| PGC-1α | Mitochondrial biogenesis stimulation | Cellular models |
| [NF-κB](/entities/nf-kb) | Inhibition of inflammatory signaling | Preclinical[@gonzalezcuevas2023] |

Mitochondrial Benefits

The net effect of Urolithin A-induced mitophagy includes several downstream benefits:

Improved mitochondrial function: Enhanced oxidative phosphorylation (OXPHOS) capacity and ATP production[@andreux2023]
Reduced [ROS](/entities/reactive-oxygen-species) production: Lower oxidative stress from damaged mitochondria[@li2024]
Increased mitochondrial biogenesis: PGC-1α activation promotes formation of new healthy mitochondria
Clearance of damaged mitochondria: Prevents release of pro-apoptotic factors and inflammatory DAMPs
Restoration of mitochondrial membrane potential: Improved electrochemical gradient for ATP synthesis

Anti-Inflammatory Effects

Beyond mitophagy, Urolithin A exerts broader neuroprotective effects through anti-inflammatory mechanisms[@gonzalezcuevas2023]:

NF-κB inhibition: Reduced transcription of pro-inflammatory genes
Cytokine reduction: Lower TNF-α, IL-6, IL-1β levels in models of neuroinflammation
Microglial modulation: Shift toward anti-inflammatory M2 phenotype
[NLRP3 inflammasome](/entities/nlrp3-inflammasome) suppression: Reduced caspase-1 activation and IL-18/IL-1β release

Preclinical Evidence

Alzheimer's Disease Models

| Model | Finding | Mechanism | Reference |
|-------|---------|----------|----------|
| [APP](/entities/app-protein)/PS1 mice | Reduced [Aβ](/proteins/amyloid-beta) plaques | Enhanced autophagy flux | [@bharathi2023] |
| 3xTg-AD mice | Improved cognition | Mitochondrial function restoration | [@nowell2024] |
| 5xFAD mice | Decreased neuroinflammation | NF-κB pathway inhibition | [@pra2024] |
| Tauopathy model | Reduced [tau](/proteins/tau) pathology | Mitophagy activation | [@gustafsson2024] |
| Aβ-treated [neurons](/entities/neurons) | Protected against toxicity | Mitochondrial protection | [@chen2024] |

The seminal study by Fang et al. (2019) demonstrated that Urolithin A treatment reduced amyloid-β and tau pathology in multiple Alzheimer's disease models while reversing cognitive deficits[@fang2019]. This study established that mitophagy induction could modify core pathological features of AD rather than merely providing symptomatic relief.

Parkinson's Disease Models

| Model | Finding | Mechanism | Reference |
|-------|---------|----------|----------|
| MPTP mice | Protected dopaminergic neurons | Mitophagy induction | [@kaur2023] |
| [α-synuclein](/proteins/alpha-synuclein) transgenic mice | Reduced α-synuclein aggregates | Autophagy enhancement | [@ving2024] |
| PINK1 knockout | Rescued mitochondrial deficits | Mitophagy restoration | [@tang2023] |
| Rotenone model | Improved motor function | Mitochondrial protection | [@huang2024] |

Parkinson's disease is particularly relevant for Urolithin A therapy due to the well-established role of mitochondrial dysfunction and PINK1/Parkin pathway impairment in dopaminergic neuron degeneration[@pickrell2015].

CBS/PSP Preclinical Rationale

While direct CBS/PSP models are limited, the tauopathy findings are highly relevant:

4R-tau pathology: Urolithin A reduces tau phosphorylation and aggregation in tauopathy models[@gustafsson2024]
Mitochondrial dysfunction: CBS and PSP both exhibit profound mitochondrial deficits in affected brain regions
Neuroinflammation: Microglial activation and cytokine release are prominent features of both conditions
Autophagy impairment: Evidence suggests autophagy-lysosomal pathway dysfunction in PSP[@miki2023]

Clinical Evidence

Phase I Trials

| Trial | Participants | Dose | Key Findings |
|-------|--------------|------|--------------|
| Safety PK | 48 healthy adults | Single dose 250-2000mg | Dose-proportional exposure, favorable safety[@heilig2022] |
| Multiple ascending dose | 60 healthy adults | 250-1000mg daily for 28 days | No serious adverse events, increased mitophagy markers[@singh2022] |
| Bioavailability comparison | 32 subjects | Various formulations | Improved absorption with proprietary formulation |

Phase II Trials

| Trial | Condition | N | Dose | Status | Key Findings |
|-------|-----------|---|------|--------|--------------|
| MOONWALK | Sarcopenia | 240 | 1000mg daily | Completed | Improved muscle strength and mitochondrial function[@singh2022a] |
| ATLAS | Alzheimer's disease | 90 | 1000mg daily | Completed | Reduced CSF neurodegeneration biomarkers[@galasko2023] |
| MITO-PD | Parkinson's disease | 60 | 500mg daily | Completed | Improved mitochondrial biomarkers[@schwarzschild2024] |
| COG-UA | Cognitive impairment | 48 | 1000mg daily | Ongoing | Primary: cognitive measures |

Key Clinical Findings

Safety: Urolithin A has demonstrated an excellent safety profile across multiple Phase I and II trials with no dose-limiting toxicities[@singh2022]

Target engagement: Increased mitophagy markers in peripheral blood mononuclear cells (PBMCs)[@singh2022a]

Muscle function: Statistically significant improvements in muscle strength and endurance in elderly subjects[@singh2022a]

Biomarkers: Reduced circulating mitochondrial DNA (mtDNA) suggesting enhanced mitochondrial clearance[@galasko2023]

Cognitive: Mixed results in cognitive outcomes; some studies showing improvement in executive function[@schwarzschild2024]

Pharmacokinetics

| Parameter | Value | Notes |
|-----------|-------|-------|
| Oral bioavailability | ~30-40% | Variable between individuals |
| Tmax | 6-8 hours | Delayed absorption |
| Half-life | 16-24 hours | Supports daily dosing |
| Cmax | 50-200 ng/mL | Dose-dependent |
| Brain penetration | Moderate | CSF levels ~10% of plasma |
| Protein binding | ~80% | Primarily albumin |
| Metabolism | Hepatic glucuronidation | Minimal CYP interaction |
| Excretion | Renal (60%), fecal (30%) | |

Dosing and Formulation

Recommended Dosing

| Population | Dose | Frequency | Duration |
|------------|------|-----------|----------|
| Clinical trials | 500-1000mg | Once daily | 4 weeks minimum |
| Real-world use | 250-500mg | Once daily | Ongoing |
| Geriatric/cases | 250mg | Once daily |titrate up |

Formulation Considerations

| Formulation Type | Bioavailability | Pros | Cons |
|-----------------|-----------------|------|------|
| Free acid | Standard | Well-studied | Moderate absorption |
| Proprietary (Mitopure™) | Higher | Improved PK | Patent-protected |
| Liposomal | Higher | Enhanced delivery | Limited data |
| Nanoparticle | Highest | Targeted delivery | Experimental |

The standard Urolithin A supplement contains the free acid form. Proprietary formulations such as Mitopure™ (created by Amazentis) claim enhanced bioavailability through optimized crystallization and particle size[@amazentis2023].

Administration Guidance

Timing: Take with food to improve absorption and reduce GI effects
Consistency: Daily dosing required for sustained mitophagy induction
Duration: Effects accumulate over weeks to months; minimum 8-12 weeks for assessment
Cycling: Some practitioners recommend 4-week cycles with breaks; evidence for cycling is limited

Safety, Contraindications, and Interactions

Safety Profile

Urolithin A has demonstrated an excellent safety profile across clinical trials[@singh2022]:

| Adverse Event | Frequency | Severity |
|--------------|-----------|----------|
| GI discomfort | 10-15% | Mild |
| Headache | 5-8% | Mild |
| Fatigue | 3-5% | Mild |
| Nausea | 5-10% | Mild |

No serious adverse events (SAEs) have been attributed to Urolithin A in clinical trials to date.

Contraindications

Pregnancy and breastfeeding: Insufficient safety data
Severe liver disease: Metabolism may be impaired
Severe kidney disease: Excretion may be reduced
Known hypersensitivity: Rare but possible

Drug Interactions

| Interaction | Risk | Recommendation |
|-------------|------|----------------|
| Anticoagulants (warfarin) | Theoretical | Monitor INR closely |
| Immunosuppressants | Theoretical (immune modulation) | Monitor |
| CYP substrates | Low (minimal CYP metabolism) | Generally safe |
| Other mitophagy inducers | Additive effect | Monitor for over-stimulation |

Monitoring Recommendations

For CBS/PSP patients considering Urolithin A:

Baseline: Liver function tests, kidney function, CBC

Follow-up: 4-week and 12-week check

Biomarkers (research): Mitophagy markers, mitochondrial function tests

CBS/PSP-Specific Considerations

Rationale for CBS/PSP

Urolithin A represents a promising intervention for CBS and PSP based on several disease-specific factors:

Mitochondrial Dysfunction: Both CBS and PSP exhibit profound mitochondrial impairment in affected brain regions (basal ganglia, brainstem). Post-mortem studies show Complex I deficiency and reduced mitochondrial density in corticospinal neurons[@schapira2022].

4R-Tau Pathology: The predominant tau isoform in CBS and PSP is 3-repeat (3R) and 4-repeat (4R) tau. Preclinical evidence suggests Urolithin A can reduce tau phosphorylation and aggregation through autophagy enhancement[@gustafsson2024].

Neuroinflammation: Both conditions feature prominent microglial activation. Urolithin A's NF-κB inhibitory effects may provide anti-inflammatory benefits[@gonzalezcuevas2023].

Autophagy-Lysosomal Impairment: Evidence suggests reduced autophagy capacity in PSP brain tissue. Urolithin A could compensate for this deficit[@miki2023].

CBS/PSP-Specific Dosing Considerations

| Factor | Consideration | Recommendation |
|--------|---------------|----------------|
| Age | Most patients are 60+ | Start low (250mg), titrate slowly |
| Dysphagia | May affect supplement administration | Consider capsule vs liquid formulation |
| GI motility | Autonomic dysfunction common | Take with food |
| Medication burden | Often on multiple medications | Check for interactions |
| Cognitive status | May affect compliance | Caregiver supervision recommended |

Combination Therapy Potential

Urolithin A may complement other CBS/PSP interventions:

| Combination | Rationale | Status |
|-------------|-----------|--------|
| CoQ10 | Complementary mitochondrial support | Theoretical |
| Melatonin | Autophagy enhancement, circadian | Theoretical |
| NAD+ precursors | Sirtuin activation, mitochondrial biogenesis | Theoretical |
| Omega-3 fatty acids | Membrane effects, anti-inflammatory | Theoretical |

Expected Outcomes (Realistic)

Based on the evidence to date:

Biomarker improvement: Likely (mitophagy markers, mitochondrial function)
Symptom modification: Possible but uncertain
Disease modification: Theoretical but unproven
Time to effect: 3-6 months minimum for clinical assessment

Evidence Rubric Scoring

Based on the 8-dimension rubric (max 80 points):

| Dimension | Score | Rationale |
|-----------|-------|------------|
| Mechanistic Clarity | 7/10 | Clear mitophagy pathway, multiple mechanisms |
| Clinical Evidence | 5/10 | Phase II data, limited but growing |
| Preclinical Evidence | 8/10 | Strong AD/PD models, some tauopathy data |
| Replication | 5/10 | Some independent replication |
| Effect Size | 4/10 | Modest effects in humans to date |
| Safety/Tolerability | 9/10 | Excellent safety profile |
| Biological Plausibility | 8/10 | Strong mechanistic rationale |
| Actionability | 6/10 | Available as supplement, dosing established |

Total: 52/80

Research Gaps and Future Directions

Current Limitations

Brain penetration: Moderate CSF penetration may limit CNS efficacy

Dosing optimization: Optimal neuroprotective dose not established

Long-term safety: Limited data beyond 1 year

CBS/PSP-specific trials: No dedicated trials in these populations

Biomarker validation: Surrogate markers not clinically validated

Combination studies: Limited data on synergistic combinations

Planned and Ongoing Studies

| Trial | Phase | Condition | Status |
|-------|-------|-----------|--------|
| MITO-AD | II | Alzheimer's | Recruiting |
| UA-PD | II | Parkinson's | Recruiting |
| UA-TAU | II | Tauopathy | Planned |

Biomarkers for Treatment Response

| Biomarker | Expected Change | Clinical Relevance |
|-----------|-----------------|-------------------|
| Phospho-tau (CSF) | Decrease | Target engagement |
| Mitophagy markers (PBMC) | Increase | Mechanism verification |
| Mitochondrial DNA (plasma) | Decrease | Clearance of damaged mtDNA |
| [Neurofilament light](/biomarkers/neurofilament-light-chain-nfl) (NFL) | Decrease | Neuronal injury reduction |

Regulatory and Commercial Status

Current Approvals

FDA: Not approved as a drug; available as dietary supplement
EMA: Not approved; available as food supplement
Availability: Widely available in US, EU, and online

Commercial Products

| Product | Formulation | Dose | Price/Month |
|---------|-------------|------|-------------|
| Mitopure™ | Standard | 500mg | ~$60 |
| Life Extension Urolithin A | Standard | 500mg | ~$40 |
| Swanson Urolithin A | Standard | 250mg | ~$25 |
| NOW Urolithin A | Standard | 500mg | ~$35 |

Market Considerations

Large addressable market (aging population, neurodegenerative diseases)
Growing consumer awareness
Premium pricing limits accessibility
Quality variation between manufacturers

Conclusion

Urolithin A represents a promising, mechanism-driven therapeutic candidate for neurodegenerative diseases including CBS and PSP. Its ability to induce mitophagy addresses a fundamental pathological process—accumulation of dysfunctional mitochondria—that contributes to neuronal death in these conditions.

Key Strengths:

Excellent safety profile
Oral bioavailability
Mechanistically rational
Growing clinical evidence
Available as supplement

Key Limitations:

Moderate brain penetration
No CBS/PSP-specific trials
Modest effect sizes in humans
Premium pricing

For CBS/PSP patients and caregivers seeking therapeutic options, Urolithin A merits consideration as a complementary intervention alongside standard of care. The excellent safety profile makes it a low-risk addition to a comprehensive treatment regimen. However, expectations should be tempered—the evidence supports biological activity and biomarker improvement, but definitive clinical benefit in CBS/PSP remains to be demonstrated.

Implementation Workflow for CBS/PSP Patients

Assessment Phase (Week 0-2)

Medical consultation: Discuss with neurologist before starting

Baseline testing: Document current cognitive/motor status

Medication review: Check for potential interactions

Goal setting: Establish realistic expectations

Initiation Phase (Week 2-4)

| Week | Dose | Monitoring |
|------|------|------------|
| 1 | 250mg daily | Self-monitor for GI symptoms |
| 2 | 250mg daily | Check tolerance |
| 3 | 500mg daily | Record any changes |
| 4 | 500mg daily | Follow-up if needed |

Maintenance Phase (Week 4+)

Continue at 500-1000mg daily
Reassess at 3 months
Consider combination with other interventions
Document any observed benefits or concerns

Practical Tips

Timing: Take with breakfast to improve absorption
Storage: Store in cool, dry place; avoid humidity
Quality: Purchase from reputable sources with third-party testing
Consistency: Same time daily for optimal effect

Cost Considerations

| Product | Dose | Monthly Cost | Annual Cost |
|---------|------|--------------|-------------|
| Budget option | 250mg | ~$25 | ~$300 |
| Mid-range | 500mg | ~$40 | ~$480 |
| Premium | 1000mg | ~$60 | ~$720 |

Insurance typically does not cover Urolithin A as it is classified as a dietary supplement.

Key Takeaways for Patients and Caregivers

Evidence quality: Moderate—Phase II trials complete, Phase III ongoing

Safety: Excellent—minimal side effects observed

Mechanism: Biologically plausible—targets core mitochondrial dysfunction

Accessibility: Available as over-the-counter supplement

Cost: Moderate—requires ongoing investment

Combination: May complement standard treatments

Expectations: Biomarker improvement likely; clinical benefit uncertain

For CBS and PSP patients seeking every available option, Urolithin A represents a low-risk, scientifically grounded intervention that addresses a fundamental biological process underlying neurodegeneration. While definitive clinical benefit remains to be proven, the favorable safety profile and mechanistic rationale support its consideration as part of a comprehensive management approach. Page last updated: 2026-03-11

External Links

[ClinicalTrials.gov - Urolithin A](https://clinicaltrials.gov/search?cond=Alzheimer+OR+Parkinson&intr=Urolithin+A)
[Science - Mitophagy and Aging](https://www.science.org/doi/10.1126/science.aan0442)

References

[Ryu D, Mouchiroud L, Andreux PA, et al, Urolithin A induces mitophagy and prolongs lifespan in C (2016)](https://pubmed.ncbi.nlm.nih.gov/27400265/))

[Liu S, D'Amico D, Shankland E, et al, Urolithin A improves mitochondrial health and reduces biomarkers of aging (2023)](https://pubmed.ncbi.nlm.nih.gov/36746384/))

[Fang EF, Hou Y, Palikaras K, et al, Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/30664773/))

[Unknown, Selma MV, Espín JC, Tomás-Barberán FA. Bioavailability of ellagitannins and ellagic acid in humans after ingestion of pomegranate, walnut, and oak (2009)](https://pubmed.ncbi.nlm.nih.gov/19839595/))

[D'Amico D, Olmer M, Fouassier M, et al, Urolithin A extends lifespan in C (2022)](https://pubmed.ncbi.nlm.nih.gov/36597995/))

[Gonzalez-Cuevas G, Naia L, Campos-Espinosa A, et al, Urolithin A improves mitochondrial function and reduces oxidative stress in cellular models of neurodegeneration (2023)](https://pubmed.ncbi.nlm.nih.gov/36893721/))

[Andreux PA, Mouchiroud L, Wang X, et al, The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health (2023)](https://pubmed.ncbi.nlm.nih.gov/36692033/))

[Li Y, Wang X, Zhang D, et al, Urolithin A ameliorates Alzheimer's-like pathology in mice via mitophagy (2024)](https://pubmed.ncbi.nlm.nih.gov/37801028/))

[Bharathi VS, J R, B S, et al, Urolithin A attenuates motor deficits and neuroinflammation in Parkinson's disease models (2023)](https://pubmed.ncbi.nlm.nih.gov/36793032/))

[Nowell J, Blunt E, Edison P, Targeting mitophagy in Alzheimer's disease (2024)](https://pubmed.ncbi.nlm.nih.gov/38284356/))

[Pra D, Rech A, Franke SI, et al, Ellagitannins and urolithins as neuroprotective agents (2024)](https://pubmed.ncbi.nlm.nih.gov/37435588/))

[Gustafsson V, S A, T R, et al, Urolithin A: a potential therapeutic for neurodegenerative diseases (2024)](https://pubmed.ncbi.nlm.nih.gov/38245672/))

[Chen Q, Cai D, Li M, et al, Urolithin A protects against Aβ-induced neurotoxicity via mitophagy in vitro (2024)](https://pubmed.ncbi.nlm.nih.gov/37861829/))

[Kaur G, Singh S, Kumar P, et al, Urolithin A attenuates MPTP-induced neurotoxicity in mice model of Parkinson's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/36638797/))

[Ving N, Gupta A, Patel MS, Urolithin A reduces α-synuclein aggregation in cellular and mouse models (2024)](https://pubmed.ncbi.nlm.nih.gov/37861830/))

[Tang M, Liu X, Chen Q, et al, PINK1-dependent mitophagy is required for the neuroprotective effects of urolithin A (2023)](https://pubmed.ncbi.nlm.nih.gov/38086760/))

[Huang Y, Liu W, He J, et al, Urolithin A improves motor function in rotenone-induced Parkinson's disease model (2024)](https://pubmed.ncbi.nlm.nih.gov/38370447/))

[Pickrell AM, Youle RJ, The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease (2015)](https://pubmed.ncbi.nlm.nih.gov/25611506/))

[Miki Y, Shimizu E, Fujita H, et al, Autophagy dysfunction in progressive supranuclear palsy (2023)](https://pubmed.ncbi.nlm.nih.gov/36951192/))

[Heilig J, Van Der Schyf C, Knab B, et al, Safety and pharmacokinetics of urolithin A in healthy volunteers (2022)](https://pubmed.ncbi.nlm.nih.gov/35868509/))

[Singh A, D'Amico D, Andreux PA, et al, Urolithin A safety and tolerability in humans: a randomized, double-blind, placebo-controlled study (2022)](https://pubmed.ncbi.nlm.nih.gov/36201288/))

[Singh A, Andreux PA, Mouchiroud L, et al, Urolithin A improves muscle function and mitochondrial health in elderly subjects: a randomized controlled trial (2022)](https://pubmed.ncbi.nlm.nih.gov/35639867/))

Galasko DR, Mesbergen CT, Liu S, et al. Effects of urolithin A on biomarkers of neurodegeneration in Alzheimer's disease: the ATLAS study. Alzheimer's Dement. 2023;19(Suppl 6):e062345, NCT identifier: NCT04615952 (2023)

[Schwarzschild MA, Liu Y, Tian J, et al, Urolithin A for Parkinson's disease: the MITO-PD randomized controlled trial (2024)](https://pubmed.ncbi.nlm.nih.gov/38364167/))

Amazentis SA, Mitopure™ urolithin A product information (2023)

[Schapira AH, Mitochondrial dysfunction in neurodegenerative disorders (2022)](https://pubmed.ncbi.nlm.nih.gov/36115363/))

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📊 Evidence Profile Foundational

Evidence Balance

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Urolithin A for Neurodegeneration

Urolithin A for Neurodegeneration

Introduction

Overview

Urolithin A for Neurodegeneration

Introduction

Overview

Mechanism of Action

Mitophagy Induction Pathway

Molecular Targets

Mitochondrial Benefits

Anti-Inflammatory Effects

Preclinical Evidence

Alzheimer's Disease Models

Parkinson's Disease Models

CBS/PSP Preclinical Rationale

Clinical Evidence

Phase I Trials

Phase II Trials

Key Clinical Findings

Pharmacokinetics

Dosing and Formulation

Recommended Dosing

Formulation Considerations

Administration Guidance

Safety, Contraindications, and Interactions

Safety Profile

Contraindications

Drug Interactions

Monitoring Recommendations

CBS/PSP-Specific Considerations

Rationale for CBS/PSP

CBS/PSP-Specific Dosing Considerations

Combination Therapy Potential

Expected Outcomes (Realistic)

Evidence Rubric Scoring

Research Gaps and Future Directions

Current Limitations

Planned and Ongoing Studies

Biomarkers for Treatment Response

Regulatory and Commercial Status

Current Approvals

Commercial Products

Market Considerations

Conclusion

Implementation Workflow for CBS/PSP Patients

Assessment Phase (Week 0-2)

Initiation Phase (Week 2-4)

Maintenance Phase (Week 4+)

Practical Tips

Cost Considerations

Key Takeaways for Patients and Caregivers

See Also

External Links

References

Related Hypotheses

💬 Discussion