What You Never Knew About Pentosan!

At a recent SSRP (Seeds Scientific Research and Performance) conference, a lecture entitled “What You Never Knew about Pentosan” was presented.  Most of you have never heard of pentosan even though this medication has been used successfully since the 1940s in both humans and veterinary medicine.

This blog is a summary of the lecture and a review of this medication which could benefit many with chronic disease explaining why pentosan may become one of the most popular medications ever and may convince you pentosan may benefit you!

Pentosan

Pentosan polysulfate sodium (PPS) is a semi-synthetic medication manufactured from wood chips of European beech trees.  It is a sulfated pentosyl polysaccharide with heparin-like properties.  It has anti-inflammatory properties, tissue regenerative properties, as well as mild anti-thrombotic activity.

PPS has been used since the 1940s for interstitial cystitis and in the EU for preventing blood clots.  In 1996, the FDA approved pentosan for use as an oral medication for symptoms of interstitial cystitis to relieve bladder pain and discomfort.  Pentosan works by preventing irritation to the bladder and treating chronic pelvic pain which was a game changer for treatment of interstitial cystitis and pelvic pain.

However, pentosan has an incredible number of multiple applications for chronic diseases without many side effects.  The literature for pentosan and its multi-faceted uses has exploded in the past year.

Pentosan, A Potent Anti-Inflammatory for Osteoarthritis:  

Many people resort to NSAIDs such as ibuprofen and naproxen for various pains, most notably joint pain and arthritis, however these medications come with risks and even long-term worsening of joints.

Pentosan used off label in humans has been shown to be better than NSAIDS, PRP (platelet rich plasma), glucosamine, chondroitin, or Euflexxa for osteoarthritis.  This has been the main focus for pentosan’s application.

Pentosan is a potent “anti-inflammatory and inhibitor of cartilage enzymatic breakdown.  It decreases inflammation by at least 10 different mechanisms.”  It works on sensory nerve cells, immune cells, tissue cartilage cells, and capillary endothelial cells.

• A 20-patient study done in 2010 showed clinical improvement and improvement in cartilage in knee osteoarthritis after one injection for 6 weeks.

What Are Pentosan’s Mechanisms of Actions in Osteoarthritis?

Some of PPS mechanisms of action include:

1. Improves blood flow to sub-chondral bone under worn cartilage.
2. Stimulates cartilage matrix synthesis building cartilage
3. Prevents cartilage breakdown by enzymes
4. Maintains proteoglycan (collagen) content in the articular cartilage (cartilage in the joint)
5. It reduced 5 synovial fluid inflammatory markers and increased one inhibitor of cartilage degradation as well as decreased bone lesions seen on MRI.

Essentially, pentosan:

• Reduces the degradation of cartilage by influencing inflammatory chemicals,
• Increases proteins available for keeping cartilage healthy,
• Mitigates inflammation,
• Increases joint fluid viscosity to better lubricate joints.
• Has mild blood-thinning properties, improving blood flow.

PPS is not approved for osteoarthritis in humans, but is used off label for osteoarthritis in humans showing great results!  After a long history of use for osteoarthritis in horses, in 2022, the FDA approved Zycosan, an injectable PPS for horses to control clinical signs of osteoarthritis.

How Does It Work on a Cellular Level?  

When substances called glucuronoxylans are sulfated, they produce a product mimicking glycosaminoglycans (GAGs).  GAGs are involved with decreasing inflammation, regulation of cell growth proliferation, promotion of cell adhesion, anticoagulation and wound repair.  There are 4 groups of GAGs synthesized by cell organelles.  The availability of a sulfated PPS significantly affects the biosynthetic rate of production of sulfated GAGs.  In this group are:

• Heparin sulfate PSS
• Chondroitin sulfate/dermatan sulfate
• Keratan sulfate
• Hyaluronic acid

One plausible explanation PPS is being used successfully in the treatment of interstitial cystitis is because an underlying cause implicated in interstitial cystitis is a disruption of the GAG layer of the bladder.  The GAG layer is a key defense layer of the bladder to prevent the adherence of bacteria and urinary substances through the cells.

How Long Does It Take to Work?

PPS decreased pain and resulted in functional improvement in >90% of cases over 8 weeks.  In another study, “Following 6 weeks of Pentosan injection therapy, 80% of patients reported feeling either moderately better with a slight but noticeable change, better with a definite improvement that has made a real and worthwhile difference, or a great deal better with a considerable improvement that has made all the difference in…pain with knee flexion…pain with walking…pain with stair climbing for one year following treatment.”

How Safe Is It?

PPS has been studied extensively in several species of animals and in humans for more than 50 years.  It has been used orally, infused in the bladder, IV, IM, subcutaneously and intranasally.  There have been over 22,000 clinical exposures and is in phase 3 study to determine the best tolerated and most effective method of use.

Adverse events were shown to be less than placebo. Side effects include hair loss, diarrhea, upset stomach, headache, heartburn, rash, difficulty falling, or staying asleep, dizziness, moodiness.

Long term, used consistently at a dose of 250 mg per week orally over more than 15 years has been shown to cause pigmentary maculopathy in 0.0005%.  This includes loss of central vision, blurry or distorted vision, loss of color vision, or impaired depth perception.  Low-dose injectable pentosan does not carry this risk.

What Other Conditions May Pentosan Treat?

Pentosan may be especially beneficial for patients with arthritis and those at high-risk for developing arthritis such as athletes.  It has a high degree of success for those with interstitial cystitis and chronic pelvic pain.

However, the many other exciting  potential uses of pentosan include:

• Improving cardiac function and inhibiting atherosclerosis
• Treating Benign prostate hyperplasia (BPH) by decreasing muscle proliferation and protecting tissue in non-bacterial prostatitis
• Gut healing and minimizing development of colon cancers
• The human gut has bacteria that can transform pentosan into xylo-oligosaccharides, an emerging prebiotic!
• Anti-tumor agent in various cancer types
• Stopping metastasis in all cancers
• Anti-viral treatment: It has been shown in vitro to kill every virus exposed to it including COVID
• Osteoporosis by regulating osteoclast activity, the cells responsible for degrading bone
• Promoting post-surgical recovery of cartilage and tendon damage from trauma
• Protecting the brain from neuroinflammation
• Inhibiting the progression of severe diabetic nephropathy
• Restoring kidney function in chronic renal disease, renal failure, polycystic kidney disease
• Reversing prostate cancer cells in vitro

Conclusion

Pentosan has been in use for over 60 years with an incredible number of applications and minimal side effects.  Most notably, it has been used for the treatment of osteoarthritis and interstitial cystitis, but the research is promising for a range of conditions.  In 60 years it has been FDA approved for only one application, interstitial cystitis.

Key features of the activity of PPS are its anti-inflammatory, tissue regenerative properties, and its mild anti-thrombotic activity.

It is amazing to be at the forefront of healing therapeutic options such as PPS; ongoing and future research of PPS may reveal even more diversity of its use and full potential for the future of medicine.

Have an Awesome Day!  Dr D and Drew Chernisky, PA-C