Replace Your Pain Drug
Guaranteed Pain Relief
Free Shipping on Month's Supply
www.appliedhealth.com
Sleep Well Wake Up Rested
We Sleep Great! So Should You.
Sleepease Rx - safe & guaranteed.
www.appliedhealth.com
Build Strong Immunity
Proven Safe, Guaranteed Results
Free Shipping on Month's Supply
www.appliedhealth.com

Saw Palmetto

Description

Introduction

Phytosterols are readily available over the counter as dietary supplements in the United States, and are promoted as a safe and natural way for men to maintain a healthy prostate. In 1999 consumers in this country spent over $140 million on saw palmetto (Serenoa repens) alone. Serenoa repens is a dwarf palm tree that grows in the southwest United States. Extracts of the plant contain a mixture of phytosterols such as -sitosterol, campesterol, and stigmasterol, as well as flavonoids and other compounds. Phytosterols used to treat benign prostatic hyperplasia (BPH) are also extracted from Hypoxis rooperi (South African star grass). This extract contains -sitosterol, with lesser amounts of other sterols, and is marketed in Europe under brand names Harzol and Azuprostat. Although both plant-derived extracts contain many phytosterols, -sitosterol often is considered the major active component. The mechanism of action of phytosterols in BPH, although not well described, reportedly includes alterations in cholesterol metabolism; antiestrogenic, antiandrogenic, and antiinflammatory effects; and decreases in sex hormone-binding globulin.

Phytosterols improved lower urinary tract symptoms (LUTS) and urinary flow measures in numerous clinical trials. According to a systematic review of 18 randomized, controlled studies of S. repens (alone or in combination with other phytotherapeutic agents) of 4-48 weeks' duration, compared with placebo, men treated with S. repens had decreases in LUTS scores and nocturia and greater improvement in peak urine flow.[1] Compared with finasteride, men treated with S. repens had similar improvements in LUTS scores and peak urine flow rates.

-Sitosterols also are efficacious in the treatment of BPH, improving urinary symptoms and flow measures in four placebo-controlled clinical trials. To date, the efficacy of phytosterols has not been compared with that of -blocking agents in the treatment of BPH.

The primary goals of treating BPH are to reduce LUTS and improve quality of life (QOL). Quality of life includes physical, psychologic, and social domains and is a subjective perception of how a disease or treatment affects health status. Despite frequent reports of use of herbal products to promote general health and well-being and to increase QOL, studies mainly focused on clinical outcomes, with QOL evaluated only occasionally as a secondary end point.

The American College of Clinical Pharmacy published a white paper that called for additional research on herbal products, listing QOL evaluations as an area in which further investigation is necessary. Quality of life was evaluated as a secondary end point in a number of clinical trials of -blockers and finasteride, the most efficacious medical treatments for BPH. Since they applied several QOL instruments, comparisons among drugs are difficult. Evidence shows, however, that -blockers excel over finasteride, with earlier onset of response, greater improvements in QOL, and fewer sexual side effects.[9] The combination of finasteride with an -blocker (terazosin, doxazosin) appears to improve QOL to a similar extent as the -blocker alone, but to a greater extent than finasteride alone or placebo. Finasteride's effect on QOL was most promising in patients with large prostate.

 

Nutritional Supplements/Phytosterols/Method of Action

It appears that phytosterols improve QOL in men with BPH. However, confirmatory studies that are more methodologically sound and have larger study populations are required to support these findings. Since few studies evaluated the effect of phytosterols beyond 6 months, there is little evidence of the compounds' long-term efficacy in reducing symptomatology or improving QOL Phytosterols have not been adequately compared with -blocking agents. Larger studies comparing them with other treatments of BPH must be conducted. In addition, consensus as to which questionnaires should be used to evaluate potential changes in QOL after treatment of BPH symptoms remains to be reached.

Method of Action

Information Not Available

Abstracts

The Effect of Phytosterols on Quality of Life in the Treatment of Benign Prostatic Hyperplasia

 

Craig I. Coleman, Pharm.D., John H. Hebert, Pharm.D., Prabashni Reddy, Pharm.D.

Pharmacotherapy 22(11):1426-1432, 2002.

Abstract

In the United States, phytosterols are available as over-the-counter dietary supplements and are promoted as a safe and natural way to maintain a healthy prostate. In men with benign prostatic hyperplasia (BPH), evidence suggests that the agents improve urologic symptoms and flow measures to a greater extent than placebo and to a similar extent as finasteride. The primary goal for treating men with BPH is to reduce lower urinary tract symptoms and increase quality of life (QOL). Therefore, QOL has become an increasingly important end point in clinical trials.

We reviewed all seven studies that determined the effect of phytosterols on QOL in patients with BPH. All trials assessed QOL with international prostate symptom score questions. Six studies found phytosterols to have beneficial effects on QOL; however, poor study design limits what can be learned from these evaluations. Most studies included a limited number of patients, and many were not placebo controlled. Since few of them evaluated the effect of phytosterols beyond 6 months, little evidence exists of the agents' long-term efficacy in reducing symptomatology or increasing QOL.

Finally, phytosterols have not been adequately compared with -blocking agents, one of the most widely administered and effective pharmacologic treatments of BPH. Larger studies comparing phytosterols with other treatments of BPH such as -blockers should be conducted. In addition, a consensus should be reached as to which questionnaires are best to evaluate potential changes in QOL after treatment of BPH.

Clinical Trials

The effects of phytosterols on QOL in patients with BPH were studied in seven clinical trials, four with S. repens and three with -sitosterols

Dosages of S. repens were 160-320 mg/day for up to 6 months. Two trials were dose-ranging studies, one study compared S. repens with finasteride and only one was placebo controlled.

Trials of -sitosterols used two standard preparations, Harzol and Azuprostat, containing 20 and 130 mg/day of -sitosterols, respectively. Two studies were placebo controlled, and the third was an open-labeled extension of one of the earlier studies.

Serenoa repens

In one study 305 men with untreated BPH took S. repens 160 mg twice/day for 3 months. The IPSS QOL score was evaluated at baseline and at days 45 and 90. Although actual scores were not provided, improvements were seen at both days (p<0.0001). The QOL score after 45 days remained unchanged in 33% of patients, improved in 65%, and worsened in 2%. At 90 days, scores were unchanged in 19%, improved in 78%, and worse in 3% of patients.

The article is limited in the amount and quality of data reported. Whereas 65% and 78% of patients showed improvement at 45 and 90 days, respectively, what constituted improvement was not defined. Lack of a placebo-control group limits what can be learned from any clinical trial, but it is especially difficult to draw conclusions from a BPH clinical trial, since up to 45% of patients will respond to placebo. As with previous studies, this one had a limited number of patients.

A 3-month, double-blind, randomized, parallel-group study compared the efficacy and tolerability of two regimens of the lipidosterolic extract of S. repens (Permixon). Ninety-two men aged 50 years or older with symptomatic BPH for at least 6 months were randomly allocated to S. repens 160 mg twice/day or 320 mg once/day. Changes from baseline in IPSS QOL score were measured after 3 months. Scores improved from baseline in men receiving both dosages at 3 months (4.0 ± 0.7 to 2.9 ± 1.2, p<0.0001, 4.0 ± 1.0 to 2.9 ± 1.3, p<0.001, respectively). The percentage of patients with at least a one-point decrease in the score was 66.7% with the twice-daily regimen and 72.4% with the daily regimen at 3 months (probability not reported).

In the largest study (> 1000 patients), S. repens 320 mg (Permixon) and finasteride 5 mg were compared in a 6-month, randomized equivalence trial in men with moderate BPH.[27] The primary QOL end point was the IPSS question at 26 weeks. The QOL improved from baseline in patients receiving S. repens for 26 weeks (3.63 ± 1.28 to 2.25 ± 1.29, p< 0.001), with similar changes in the finasteride group (3.66 ± 1.17 to 2.15 ± 1.26, p< 0.001). This improvement was similar in both groups (p=0.14). Over 50% of patients felt their QOL was improved (> 1-point decrease in the 7-point scale) regardless of which treatment they received.

After a 1-month run-in period, 85 men aged 45 years or older with LUTS and IPSS of 8 or greater, were randomized to receive S. repens 160 mg twice/day or placebo for 6 months. The IPSS QOL was measured at baseline and 6 months after randomization. No improvement in scores was noted between groups (S. repens -0.7, placebo -0.3, p = 0.20) at 6 months.

Potential study limitations included small sample and imperfectly matched treatment and placebo groups. Men receiving S. repens had a higher (although not statistically significant) IPSS at baseline compared with placebo recipients, which may have resulted in the former being more likely to show variability regarding improvement (regression to the mean).

Beta-Sitosterols

Two randomized, placebo-controlled, double-blind trials evaluated -sitosterols (Harzol). The first one randomized 187 patients with symptomatic BPH to -sitosterol 20 mg 3 times/day or placebo for 6 months. The IPSS QOL was administered at baseline and 6 months. At 6 months, IPSS QOL scores showed improvement, with a mean change from baseline of 1.4 ± 0.8 and 0.2 ± 1.0 (p<0.01) for -sitosterol and placebo, respectively.

An 18-month follow-up study was an open extension of the 6-month trial and is the only one to examine the long-term effects of phytosterols on QOL in patients with BPH.

Men in this phase were free to choose their treatment, with 117 of the initial 305 patients opting to participate. They were reevaluated with the IPSS QOL 18 months after randomization for the first study. Those previously treated with -sitosterol who continued the drug continued to have favorable QOL outcomes but did not receive any additional benefit from longer treatment. Men who previously received placebo and who began therapy with -sitosterol had improvement to the same extent as the original double-blind trial treatment group.

Patients who chose -sitosterol for further therapy had significant improvements in QOL at 18 months compared with those who did not receive -sitosterol in the open extension trial (p<0.01). Patients who received -sitosterols in the double-blind trial but decided not to take any phytotherapy in the follow-up arm still had improvement over those who had never received phytotherapy (p<0.01). The authors concluded that the effects on QOL of -sitosterol are maintained over at least 18 months in men with symptomatic BPH.

Another double-blind, placebo-controlled trial examined a -sitosterol (Azuprostat) in patients with symptomatic BPH.[31] A total of 177 patients received -sitosterol 130 mg/day or placebo once/day. After a 4-week washout period, patients were evaluated at baseline and 6 months for changes in QOL using the IPSS question. The IPSS scores improved to a greater extent in the -sitosterol group than in the placebo group (-1.8 ± 1.02 vs -0.9 ± 0.91, p<0.01).

Discussion

Based on the studies reviewed, phytosterols are generally well tolerated and potentially effective in treating symptoms of BPH and in improving QOL. Of the seven studies, six showed beneficial effects.

Use of herbal supplements is clearly on the rise in the United States. Millions of Americans frequently include the products as part of their routine health regimens to prevent or treat disease and improve QOL.Herbal supplements have been studied in both Europe and the United States to determine whether claims to improve health are justified. In many cases, such as with phytosterols for BPH, data supports their efficacy.

However, other herbals lack the support of well-conducted clinical trials. Because most herbal supplements aim to improve QOL, we initially planned to review the literature that investigated the effects of the 12 most commonly used herbals in the United States. This search revealed 23 studies investigating QOL as either a primary or secondary end point. Phytosterols have evidence supporting their clinical efficacy, but many herbals lacked a suitable number of studies to draw a solid conclusion. For this reason, we limited our review to the effects of phytosterols on QOL in patients with BPH.

A number of issues must be considered before drawing conclusions. First, poor design limits what can be learned from these studies. Most studies had a limited number of patients and were not powered to detect differences in QOL. Small studies often are not able to show statistical significance even when it exists.

Lack of a control group is also a confounding factor due to the large placebo effect (~45% improvement) realized in BPH clinical trials. There is little evidence of phytosterol's long-term efficacy (> 6 mo) in reducing symptomatology and increasing QOL.[1,4, 25-29, 31] In addition, the agents have not been adequately compared with finasteride and lack comparison with -blocking agents, the most widely used and effective drugs to treat BPH.

Next, it is difficult in the case of the IPSS QOL question to determine what constitutes a clinically significant change compared with a statistically significant one. A number of studies considered an increase in QOL score of more than 1 point (on a scale of 0-6) to be clinically significant. When applied to the reviewed studies, all those with statistically significant improvements would have clinically significant improvements in QOL. Potential downfalls were proposed with the use of the minimal clinically important difference (MCID) for QOL measures due to inherent problems related to their calculation that may result in oversimplification of results. Several issues should be considered when interpreting MCIDs, including cost of therapy and baseline QOL. A therapy that results in a statistically significant change always should be assessed in context of what it costs in terms of dollars and adverse effects. In addition, the clinical significance of a QOL change will depend on the patient's baseline assessment. When applying MCIDs to study results, these issues must be kept in mind.

We briefly reviewed a variety of BPH-specific QOL questionnaires that were applied in clinical trials. All the studies identified in this review used the IPSS QOL question. It may be that alternative questionnaires may be more accurate.

Finally, our ability to identify studies was limited by a number of factors. The National Library of Medicine does not consistently index articles on herbal supplements, so MEDLINE searches are not all-inclusive. Thus, we conducted searches for studies according to the Cochrane Database for Systematic Reviews' recommendations.

Additional searches of other databases were conducted, as well as reviews of references of identified studies and review articles. A second limitation to our review of the literature was exclusion of studies published in foreign languages. Herbal supplements such as phytosterols have greater acceptance in Europe than in the United States and it is possible that we missed many studies due to our inability to translate them.

References

  1. Witt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. Saw palmetto extracts for treatment of benign prostatic hyperplasia. JAMA 1998;280:1604-9.
  2. Blumenthal M, ed. The complete German Commission E monographs. Boston: American Botanical Council, 1998.
  3. Lowe FC, Fagelman E. Phytotherapy in the treatment of benign prostatic hyperplasia. Curr Opin Urol 2002;12:15-18.
  4. Wilt TJ, MacDonald R, Stark G, Mulrow C, Lau J. Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database Syst Rev 2;2002.
  5. Barry MJ. Evaluation of symptoms and quality of life in men with benign prostatic hyperplasia. Urol 2001;58(suppl 6A):25-32.
  6. Leidy NK, Revicki DA, Geneste G. Recommendations for evaluating the validity of quality of life claims for labeling and promotion. Value Health 1999;2:113-27.
  7. Harnack LJ, Rydell SA, Stang J. Prevalence of use of herbal products by adults in the Minneapolis/St. Paul, Minn., metropolitan area. Mayo Clin Proc 2001;76:688-94.
  8. Miller LG, Hume A, Harris M, et al. White paper on herbal products. Pharmacotherapy 2000;20:877-91.
  9. Rhodes PR, Kroogh RH, Bruskewitz RC. Impact of drug therapy on benign prostatic hyperplasia-specific quality of life. Urol 1999;53:1090-8.
  10. De la Rosette J, Alivizatos G, Madersbacher S, et al. EAU guidelines on benign prostatic hyperplasia. Eur Urol 2001;40:256-63.
  11. Lepor H, Williford WO, Barry MJ, Haakenson C, Jones K. The impact of medical therapy on bother due to symptoms, quality of life and global outcome, and factors predicting response. J Urol 1998;160:1358-67.
  12. Boyle P, Altwein JE, Bartsch G. Patients' perception of the effect of medical therapy for benign prostatic hypertrophy in the PREDICT trial [abstr]. J Urol 1999;161(suppl 266):A1029.
  13. Batista-Miranda JE, De la Cruz Diez M, Arano Bertran P, Villavicencio H. Quality-of-life assessment in patients with benign prostatic hyperplasia. Effects of various interventions. Pharmacoeconomics 2001;19:1079-90.
  14. Dickerson K, Scherer R, Lefebvre C. Systematic reviews: identifying relevant studies for systematic reviews. BMJ 1994;309:1286-91.
  15. Cockett ATK, Khoury S, Aso Y, eds. Proceedings of the 2nd international consultation on benign prostatic hyperplasia (BPH). Jersey, UK: SCI Ltd., 1993.
  16. Barry MJ, Fowler FJ, O'Leary MP, et al. The American Urological Association symptom index for benign prostatic hyperplasia. J Urol 1992;148:1549-57.
  17. Spilker B, ed. Quality of life and pharmacoeconomics in clinical trials, 2nd ed. New York: Lippincott Williams & Wilkins, 1996:41-8.
  18. Brazier JE, Harper R, Jones NM, et al. Validating the SF-36 health survey questionnaire -- new outcome measure for primary care. BMJ 1992;305:160-4.
  19. Hunskaar S, Vinsnes A. The quality of life in women with urinary incontinence as measured by the sickness impact profile. J Am Geriatr Soc 1991;39:378-82.
  20. The EuroQol Group. EurQol -- a new facility for the measurement of health related quality of life. Health Policy 1990;16:199-208.
  21. Donovan JL, Kay HE, Peters TJ, et al. Using the ICSQoL to measure the impact of lower urinary tract symptoms on quality of life: evidence from the ICS-BPH study. Br J Urol 1997;80:712-21.
  22. Lukacs B, Comet D, Grange JC, Thibault P. Construction and validation of a short from benign prostatic hypertrophy health related quality of life questionnaire. Br J Urol 1997;80:722-30.
  23. Barry MJ, Fowler FJ, O'Leary MP, et al. Measuring disease specific health status in men with benign prostatic hyperplasia. Med Care 1995;33(suppl A):S145-55.
  24. Epstein RS, Deverka PA, Chute CG, et al. Validation of a new quality of life questionnaire for benign prostatic hyperplasia. J Clin Epidemiol 1992;45:1431-5.
  25. Braeckman J. The extract of Serenoa repens in the treatment of benign prostatic hyperplasia: a multicenter open study. Curr Ther Res 1994;55:776-85.
  26. Stepanov VN, Siniakova LA, Sarrazin B, Raynaud JP. Efficacy and tolerability of the lipidosterolic extract of Serenoa repens (Permixon) in benign prostatic hyperplasia: a double-blind comparison of two dosage regimens. Adv Ther 1999;15:231-9.
  27. Carro JC, Raynaud JP, Koch G, et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Prostate 1996;29:231-40.
  28. Gerber GS, Kuznetsov D, Johnson BC, Burstein JD. Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms. Urology 2001;58:960-5.
  29. Berges RR, Windler J, Trampisch HJ, Senge TH. Randomized, placebo-controlled, double-blind clinical trial of b-sitosterol in patients with benign prostatic hyperplasia. Lancet 1995;345:1529-32.
  30. Berges RR, Kassen A, Senge T. Treatment of symptomatic benign prostatic hyperplasia with b-sitosterol: an 18-month follow-up. Br J Urol Int 2000;85:842-6.
  31. Klippel KF, Hiltl DM, Schipp B. A multicentric, placebo-controlled, double-blind clinical trial of b-sitosterol (phytosterol) for treatment of benign prostatic hyperplasia. Br J Urol 1997;80:427-32.
  32. Blendon RJ, DesRoches CM, Benson JM, Brodies M, Altman DE. Americans' views on the use and regulation of dietary supplements. Arch Intern Med 2001;161:805-10.
  33. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997. Results of a follow-up national survey. JAMA 1998;280:1569-75.
  34. O'Hara M, Kiefer D, Farrel K, Kemper K. A review of 12 commonly used medicinal herbs. Arch Fam Med 1998;7:523-36.
  35. Hays RD, Woolley JM. The concepts of clinically meaningful differences in health-related quality-of-life research. How meaningful is it? Pharmacoeconomics 2000;18:419-23.
Signup Free
Applied Health Journal
FREE Sample Issue
Your email address is all we need to start you on a better path to health.
  
We respect your privacy.
Recent Issues
 
 
Back Issues
archives
Only a click away
Give your energy a lift with Foundation blue-green algae.