Techniques in Urology: Treatment of Interstitial Cystitis with a Quercetin Supplement
* •Floyd Katske, M.D., * •Daniel A. Shoskes, M.D., •Mark Sender, M.D., •Ray Poliak, M.D., *Kim Gagliano, L.V.N., and * •Jacob Rajfer, M.D.
• Division of Urology, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance, and * Institute of Male Urology, Encino, California, U.S.A.
Purpose: Interstitial cystitis (IC) is a disorder of unknown etiology with few effective therapies. Oral bioflavonoid therapy utilizing quercetin recently proved to be clinically effective in men with chronic pelvic pain syndrome, a disorder with similarities to IC. We therefore tested in an open-label trial a quercetin-based supplement in patients with clinically proven IC.
Materials and Methods: Twenty-two patients (5 men and 17 women; average age 53.1 years) with classically documented IC received one capsule of Cysta-Q complex (equivalent to 500 mg of quercetin) twice a day for 4 weeks. Symptoms were assessed before and after therapy by the IC problem and symptom indices as well as by global assessment of pain (range 0-10).
Results: Two patients did not complete the study. In the remaining 20 patients, Improvement was seen in all three parameters tested. After 4 weeks of treatment, the mean (:I: SEM) problem index improved from 11.3.:o!: 0.6 to 5.1:1: 0.7 (p = .000001), the mean symptom index improved from 11.9 :I: 0.9 to 4.5 :1:0.5 (p= .000001), and the mean global assessment score improved from 8.2:1: 0.4 to 3.5:1: 0.4 (p = .000001). None of the patients experienced any negative side effects, and all but one patient had at least some improvement in every outcome measure.
Conclusion: Oral therapy with the quercetin supplement Cysta-Q was well tolerated and provided significant symptomatic improvement in patients with IC. Larger, randomized, placebo-controlled trials appear warranted based on these preliminary open-label results.
Key Words: Interstitial cystitis-Quercetin-Bioflavonoid.
Techniques in Urology Vol. 7, No. 1, pp. 44-46
@ 2001 Lippincott Williams & Wilkins, Inc., Philadelphia
Participants: Floyd Katske, M.D., *Daniel A. Shoskes, M.D., Mark Sender, M.D., RayPoliakin, M. *Kim Gagliano, L.V.N., and *Jacob Rajfer, M.D.
Material and Methods
Twenty-two patients who carried the clinical diagnosis of IC and were complaining of “painful bladder syndrome” elected to take this supplement. The diagnosis of IC was based on symptoms and cystoscopic findings; 10 patients also had bladder biopsies. All patients were considered clinical failures from their multiple previous therapies for IC, which included hydrodistention, pentosan polysulfate dimethylsulfoxide (DMSO) instillations, parasympopatholytics, and tricyclic antidepressants. Symptoms were assessed using the IC symptom and problem indices (7). In addition, patients rated their symptoms subjectively on a global scale ranging from 0 (no symptoms) to 10 (worse symptoms imaginable) before and after completion of their 4 weeks of therapy.
Patients then received a 1-month supply of an herbal supplement containing 500 mg of quercetin as well as bromelain and papain (Cysta-Q, Farr Laboratories, California, USA); the latter two compounds were to increase intestinal quercetin absorption. Patients took one capsule orally with food twice a day. Because the patients were clinical failures, they were asked not to discontinue whatever therapy they were receiving for IC. After 30 days, patients returned the bottle for a capsule count and for readministration of the symptom indices.
Statistical comparison between groups was performed using a paired t-test. Significance was set at p <0.5.
The average age of the patients was 52 ± 3 years (range 38-87 years), and median duration of symptoms was 5 years (range 1-15 years). Two patients did not complete the protocol because of development of appendicitis in one and noncompliance in the other. Of the remaining 20 patients, there were no side effects or adverse reactions. All 20 patients who completed the study reported improvement in each of the three symptom indices, except for one patient whose symptom index was unchanged, although improvement was reported in that patient’s two other indices (Table 1).
Using the validated IC symptom index, after 4 weeks of treatment with Cysta-Q, the mean problem index improved from 11.3 ± 0.6 (range 5-15) to 5.1 ± 0.7 (range 0-10) (p = .000001), and the mean symptom index improved from 11.9 ± 0.9 (range 4-19) to 4.5 ± 0.5 (range 0-8) (p = .000001). The global assessment score improved from 8.2 ± 0.4 (range 4-10) to 3.5 ± 0.4 (range 0-7) (p = .000001) after 4 weeks of treatment. The total symptom score improvement ranged from 23% to 100% (average 57%). Using an intent-to-treat analysis, 20 (91%) of the original 22 patients derived significant clinical improvement. At the conclusion of the study, all 20 patients requested the opportunity to continue on Cysta-Q therapy and have continued to do so.
Interstitial cystitis is a potentially debilitating disorder that to date has eluded characterization of its pathophysiology and development of effective, durable therapies. Standard therapeutic approaches have included pain relief with hydrodistention (8), anti-inflammatory intravesical therapy with DMSO (9), steroids and heparin (10), oral therapy with pentosan polysulfate (11) and neuroleptic therapy with tricyclic antidepressants (12) and gabapentin. Newer therapies that have been attempted include intravesical BCG (13), oral L-arginine (14), and immunosuppression with cyclosporine (15). Although these therapies may seem to have little in common pathophysiologically, most of these maneuvers could have an effect on nitric oxide production within the bladder (9,14).
Bioflavonoids are potent anti-inflammatory agents found in fruits, vegetables, and some spices (4). When treated with a supplement primarily containing quercetin, men with chronic pelvic pain syndrome (CPPS, chronic prostatitis category III) demonstrated significant symptom improvement (3, 16). It is our theory that increased oxidant stress is the final common pathway of several forms of prostatic injury that can lead to CPPS and that all effective therapies reduce the levels of oxidant stress markers such as isoprostanes (17). When assayed, the levels of oxidant stress in the prostatic fluid of these men with CPPS treated with quercetin were reduced (3). This led to the hypothesis that patients with IC may have similar biochemical mechanisms for their pain and, therefore, also might benefit from oral bioflavonoid therapy.
In the present study, all 20 patients who finished 1 month of therapy with the quercetin-based supplement Cysta-Q had a significant reduction in symptoms as assessed by the IC symptom index, which measures pain, urinary frequency, and the quality-of-life impact of these conditions (&). Event including the two patients of the original 22 who did not complete the study, the intent-to-treate response rate was 91%. This compares favorably with published response rates of 25% to 60% for pentosan polysulfate (18), L-arginine (14), and BCG therapy (13). Our study is limited because it was open label and relatively short term. Nevertheless, the placebo response rate in this group of patients seldom exceeded 25%, which, coupled with the very low standard deviations in symptom indices seen in our 20 patients, suggests that we probably are observing a true response rate. Further confirmation will require a formal randomized, double-blind, placebo-controlled study that is currently under way.
1. Curhan, G.C., Speizer, F.E., Hunter, D.J., et a.: Epidemiology of interstitial cystitis: A population based study. J. Urol., 161: 549-52, 1999.
2. Miller, J.L., Rothman, I., Bavendam, T.G., et al: Prostatodynia and interstitial cystitis: One and the same? Urology, 45: 587-90, 1995.
3. Shoskes, D.A., Zeitlin, S.I., Shahed, A., et al: Quercetin in men with category III prostatitis: A preliminary prospective, double-blind, placebo-controlled trial. Urology, 54: 960-3, 1999.
4. de Groot, H. and Rauen, U.: Tissue injury by reactive oxygen species and the proatective effects of flavonoids. Fundam. Clin. Pharmacol., 12: 249-55, 1998.
5. Peet, G.W., and Li, J.: IkappaB kinases alpha and beta show a random sequential kinetic mechanism and are inhibited by staurosporine and quercetin. J. Biol. Chem., 274: 32655-61, 1999.
6. Lowe, F.C., and Ku, J.C.: Phytotherapy in treatment of benign prostatic hyperplasia: A critical review. Urology, 48: 12-20, 1996.
7. O’Leary, M.P., Sant, G.R., Fowler, F.J., Jr., et al: The interstitial cystitis symptom index and problem index. Urology, 49: 58-63, 1997.
8. Nigro, D.A., Wein, A.J., Foy, M., et al: Associations among cystoscopic and urodynamic findings for women enrolled in the Insterstitial Cystitis Data Base (ICDB) Study. Urology, 49: 86-92, 1997.
9. Birder, L. A., Kanai, A.J., and de Groat, W.C.:DMSO: Effect on bladder afferent neurons and nitric oxide release. J. Urol., 158: 1989-95, 1997.
10. Ghoniem, G.M., McBride, D., Sood, O.P., et al: Clinical experience with multiagent intravesical therapy in interstitial cystitis patients unresponsive to single-agent therapy. World J. Urol., 11: 178-82, 1993.
11. Hwang, P., Auclair, B., Beechinor, D., et. Al: Efficacy of pentosan polysulfate in the treatment of interstitial cystitis: A meta-analysis. Urology, 50: 39-43, 1997.
12. Pranikoff, K., and Constantino, G.: The use of amitriptyline in patients with urinary frequency and pain. Urology, 51: 179-81, 1998.
13. Peters, K.M., Diokno, A.C., Steinert, B.W., et al: The efficacy of intravesical bacillus Clamette-Guerin in the treatment of interstitial cystitis: Long-term followup. J. Urol., 159:1483-6; discussion 1486-7, 1998.
14. Korting, G.E., Smith, S.D., Wheeler, M.A., et al: A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J. Urol., 161: 558-65, 1999.
15. Forsell, T., Ruutu, M., Isoniemi, H., et al.: Cyclosporine in severe interstitial cystitis. J. Urol., 155: 1591-3, 1996.
16. Shoskes, D.A.: Use of bioflavonoid quercetin in patients with longstanding chronic prostatitis: J. Am. Neutraceut. Assoc., 2: 18-21, 1999.
17. Basu, S.: Radioimmunoassay of 8-iso-prostaglandin in F2alpha: An index for oxidative injury via free radical catalysed lipid peroxidation. Prostaglandins Leukot Essent Fatty Acids, 58: 319-25, 1998.
18. Mulholland, S.G., Hanno, P., Parsons, C.L., et al.: Pentosan polysulfate sodium for therapy of interstitial cystitis. A double-blind placebo-controlled clinical study. Urology, 35: 552-8, 1990.