Pentosan Polysulfate
Joint Health / Disease-Modifying CompoundapprovedAlso known as: PPS, Cartrophen, Elmiron, Pentosan Polysulfate Sodium, NaPPS
A semi-synthetic polysaccharide (heparin-like compound) used clinically for interstitial cystitis and osteoarthritis, with disease-modifying effects on cartilage, joints, and the glycosaminoglycan layer.
Overview
Pentosan polysulfate sodium (PPS) is a semi-synthetic, low-molecular-weight heparin-like polysaccharide derived from beechwood hemicellulose. While technically not a peptide, it is frequently included in peptide clinic protocols for joint health. PPS is FDA-approved as Elmiron for interstitial cystitis (IC) / painful bladder syndrome and is widely used in veterinary medicine (as Cartrophen Vet) for osteoarthritis in dogs and horses. It acts as a disease-modifying osteoarthritis drug (DMOAD) by stimulating cartilage matrix synthesis, inhibiting cartilage-degrading enzymes, and improving synovial fluid quality. PPS also has fibrinolytic, anti-inflammatory, and lipid-clearing properties. In recent years, concerns have emerged about a potential association between long-term oral PPS use and a unique pigmentary maculopathy of the retina, prompting FDA warnings and renewed scrutiny of its risk-benefit profile.
Mechanism of Action
PPS acts through multiple pathways: (1) Stimulates proteoglycan and hyaluronic acid synthesis by chondrocytes and synoviocytes; (2) Inhibits matrix metalloproteinases (MMPs) and aggrecanases that degrade cartilage; (3) Restores the glycosaminoglycan (GAG) layer on the bladder urothelium in IC; (4) Inhibits complement activation and inflammatory cascades; (5) Has mild fibrinolytic activity, improving microcirculation in joint tissues; (6) Reduces subchondral bone remodeling; (7) Improves synovial fluid viscosity and joint lubrication; (8) Inhibits histamine release from mast cells.
Molecular Formula
Complex polysaccharide — average MW ~4,000-6,000 Da
Molecular Weight
4000-6000 Da (average)
Sequence
N/A — semi-synthetic polysaccharide, not a peptide
Dosage Protocols
Dose Range
100mg – 100mg
Frequency
Three times daily
Route
oral
Cycle Length
3-6 months initial trial; ongoing if effective
FDA-approved dose. Take 1 hour before or 2 hours after meals on empty stomach. Response may take 3-6 months. Oral bioavailability is low (~3%).
Source: FDA-approved prescribing information (Elmiron)
Side Effects
| Effect | Severity |
|---|---|
| GI upset | mild |
| Headache | mild |
| Hair loss (alopecia) | moderate |
| Easy bruising | mild |
| Pigmentary maculopathy | severe |
Pros & Cons
FDA-approved with decades of clinical use and extensive safety data
Disease-modifying for osteoarthritis — not just symptomatic relief but actual cartilage protection
Injectable form provides much higher bioavailability and faster onset than oral
Multi-mechanism action on joints: stimulates repair, inhibits degradation, reduces inflammation
Risk of pigmentary maculopathy with long-term oral use — requires ophthalmologic monitoring
Very low oral bioavailability (~3%) limits effectiveness of approved oral route
Injectable form not FDA-approved for human use — requires off-label prescribing
Mild anticoagulant effects contraindicate use with blood thinners
Research Studies
Legal Status
FDA-approved as Elmiron (oral) for interstitial cystitis. Available by prescription. Injectable forms available in veterinary medicine (Cartrophen) and off-label human use from compounding pharmacies. Widely used in Australian and European medicine.
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