#serenoa repens

Saw palmetto (Serenoa repens)

Am Fam Physician. 2003 Mar 15;67(06):1281-1283.

Saw palmetto is an herbal product used in the treatment of symptoms related to benign prostatic hyperplasia. The active component is found in the fruit of the American dwarf palm tree. Studies have demonstrated the effectiveness of saw palmetto in reducing symptoms associated with benign prostatic hyperplasia. Saw palmetto appears to have efficacy similar to that of medications like finasteride, but it is better tolerated and less expensive. There are no known drug interactions with saw palmetto, and reported side effects are minor and rare. No data on its long-term usage are available. The herbal product also has been used to treat chronic prostatitis, but currently there is no evidence of its efficacy.

Saw palmetto, also known as Serenoa repens or Sabal serrulatum, is an herb that is most commonly used to treat problems related to benign prostatic hyperplasia (BPH). The medicinal element of saw palmetto is taken from the partially dried ripe fruit of the American dwarf palm tree, which is indigenous to the coastal regions of the southern United States, from the Carolinas and Florida to California.

BPH is a nearly universal result of the aging process in men. As the prostate gland enlarges, it can cause both obstructive and irritative symptoms; however, the size of the prostate gland is not predictive of the symptoms that patients experience.

Saw palmetto is widely used in other countries; for example, it is used in 50 percent of treatments for BPH in Italy and in 90 percent of such treatments in Germany.1 The active part of the plant is the sterols and free fatty acids found in the berry. The particular solvent used in the extraction process affects the resulting formulation of the product. The most widely studied form of saw palmetto is Permixon, which uses the solvent hexane; other formulations have used ethanol, methanol, and liquid carbon dioxide as solvents. Historically, saw palmetto was administered with nettle root and pumpkin seeds, and some modern formulations include these elements.

It is unclear which components are the most active, and the mechanism of action is not fully understood. Some of the mechanisms proposed include anti-inflammatory activity,2 blocked conversion of testosterone to dihydrotestosterone (DHT),3,4 and prostate epithelial involution similar to effects noted with the use of finasteride (Proscar).5

Relief of Symptoms

Treatments for BPH can be evaluated by their effect on symptoms such as diminished urine stream, post-void dribbling, overflow incontinence, and urinary retention, or by less useful measures such as urine flow rate, changes in prostate size, and residual volume. In a Cochrane Review, investigators conducted a meta-analysis of randomized controlled studies comparing saw palmetto with placebo or other drugs.6 [Evidence level A: systematic e r view of randomized controlled trials RCTs] The review combined the results of 21 trials with durations of four to 48 weeks. The 21 studies included a total of 3,139 men with a mean age of 65 years (range: 40 to 88 years). According to the International Prostate Symptom Scale, these men had moderate symptoms, with an average urologic score of 14.4 points out of a possible 35 (moderate BPH symptoms range from eight to 19).6 In the 13 studies that reported symptom scores, saw palmetto improved symptom scores, individual symptoms, and flow measures more than placebo. Patients and physicians were more likely to report improvement in symptoms with saw palmetto treatment than with placebo. In the12 studies that reported nocturia results, saw palmetto reduced nocturia by 25 percent compared with placebo.

In two studies, saw palmetto and finasteride had similar positive effects on urinary symptom scores and peak urine flow. Adverse effects caused by saw palmetto were mild and infrequent and comparable to side effects from placebo. Withdrawal rates among patients receiving placebo, saw palmetto, and finasteride were 7.1, 8.9, and 9.0 percent, respectively.

Results similar to those in the Cochrane Review were produced by a more recent r e view.7[Evidence level A: RCTs] Saw palmetto has not been compared with surgical approaches in the treatment of BPH. Saw palmetto is also widely used for treatment of chronic prostatitis, although scientific evidence of benefit is lacking.

Contraindications, Adverse Effects, and Interactions

The primary side effect occurring in humans is gastrointestinal distress, which is mild and can be minimized by taking saw palmetto with food. Saw palmetto is believed to be quite safe, although formal toxicology studies have not been completed. One study8 found no mutagenic or teratogenic effects in rats and dogs that were fed saw palmetto in a dosage of 2 g per kg daily for six months, and this dosage was well tolerated. No clinically relevant changes in laboratory parameters have been found in human clinical trials.9

There has been some concern that saw palmetto could mask prostate cancer by lowering prostate-specific antigen (PSA) levels. However, a randomized study10 of more than 1,000 patients did not demonstrate this effect on PSA levels. The same study showed that finasteride decreased PSA levels by 41 percent.

Dosage

Clinical studies have used a dosage of 160 mg twice daily or 320 mg once daily of a lipophilic extract containing 80 to 90 percent of the volatile oil. A daily dosage of 480 mg was not found to be any more effective in a six-month study of dosages.8 Teas are not considered to be effective because they do not contain the volatile oils. The whole berries can be used at the recommended dosage of 1 to 2 g daily.11 As with most herbal medications, the recommended dosage for saw palmetto may vary because of the lack of standardization of such products in the United States.

Herbal medication products that are commonly available for purchase may not be the same as those used in clinical studies and, therefore, may not produce the same results. There are no known drug interactions with saw palmetto. The cost for typical saw palmetto products ranges from $6 to $20 per month at a dosage of 160 mg twice daily.

Final Comment

Saw palmetto is an effective treatment for the symptoms of BPH. It appears to be as effective as finasteride and is better tolerated, less expensive, and less likely to decrease PSA levels. No research has evaluated the effect of saw palmetto on long-term outcomes in patients with BPH. Table 1 reviews the efficacy, safety, tolerability, and cost of saw palmetto.

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Key Points About Saw Palmetto

Efficacy

Reducing symptoms of BPH: effective

Treatment of chronic prostatitis: evidence lacking

Adverse effects: Mild gastrointestinal distress: infrequent. Not known to interfere with the diagnosis of prostate cancer

Interactions: No known drug interactions

Dosage: Varies; most studies have used 160 mg twice daily or 320 mg once daily

Cost: $6 to $20 per month, depending on brand, for a dosage of 160 mg twice daily

Bottom line: Safe herbal medicine; effective for treatment of symptoms of BPH

BPH = benign prostatic hyperplasia.

The Author: ANDREA E. GORDON, M.D., is on the faculty of the Harrisburg Family Practice Residency, Harrisburg, Pa. She received her medical degree from Jefferson Medical College in Philadelphia. Dr. Gordon completed a family practice residency program at the University of Connecticut, Hartford, and a fellowship in family practice faculty development at St. Margaret Memorial Hospital, Pittsburgh, Pa. She is currently enrolled in an integrative medicine fellowship at the University of Arizona, Tucson....

REFERENCES

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1. Di Silverio F, D'Eramo G, Lubrano C, Flammia GP, Sciarra A, Palma E, et al. Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients. Eur Urol. 1992;21:309–14.

2. Lowe FC, Ku JC. Phytotherapy in treatment of benign prostatic hyperplasia: a critical review. Urology. 1996;48:12–20.

3. Briley M, Carilla E, Roger A. Inhibitory effect of Permixon on testosterone 5a-reductase activity of the rat ventral prostate. Br J Pharmacol. 1984;83(suppl):401P.

4. Marks LS, Hess DL, Dorey FJ, Macairan ML, Cruz Santos PB, Tyler VE. Tissue effects of saw palmetto and finasteride: use of biopsy cores for in situ quantification of prostatic androgens. Urology. 2001;57:999–1005.

5. Marks LS, Partin AW, Epstein JI, Tyler VE, Simon I, Macairan ML, et al. Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J Urol. 2000;163:1451–6.

6. Wilt T, Ishani A, MacDonald R. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002;3:CD001423.

7. 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;58:960–4.

8. Small JK, Bombardelli E, Morazzoni P. Serenoa repens (Bartram). Fitoterapia. 1997;68:99–113.

9. Plosker GL, Brogden RN. Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia. Drugs Aging. 1996;9:379–95.

10. Carraro JC, Raynaud JP, Koch G, Chisholm GD, Di Silverio F, Teillac P, 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.

When we think about long lived plants, our minds tend to fixate on bristlecone pines (Pinus longaeva), coastal redwoods (Sequoia sempervirens), or that clonal patch of quaking aspen (Populus tremuloides) in Utah. What would you say if I told you that we can add a palm tree to that list? Indeed, recent evidence suggests that the saw palmetto (Serenoa repens) can reach a ripe old age measured in thousands (yes, thousands) of years.

Now, at this point some of you are probably thinking "how can you measure the age of a palm when there are no annual growth rings?!" This is a legitimate hurdle that had to be overcome before such a claim was made. Using a lot of attention to detail and some crafty mathematics, a team of researchers was able to age saw palmettos in Florida's most ancient habitats.

This work was performed on a peculiar geological formation. Aptly named the "Mid-Florida Ridge," this 150 mile sand ridge bisects the middle of the state. Throughout much of the Pliocene and early Pleistocene, sea levels were as much as 50 meters higher than they were today. Nearly all of Florida was underwater during this time. All that stuck out above the water were a series of small islands. These islands served as refugia for flora and fauna pushed south by repeated glaciations. Once sea level receded to its current level, these islands were left high and dry, thus forming the ridge in question. Because of its history as a refugium, the Mid-Florida Ridge is home to a staggering array of plant species, some of which are endemic to this relatively small area of Florida.

Because of its relative stability through time, the Mid-Florida Ridge is a haven for long lived plant species. Thus, it was a prime location for trying to understand the longevity of the charismatic and ecologically important saw palmetto. By tagging individual palms and observing them year after year, researchers were able to get an idea of exactly how fast this species can grow. Depending on the soil conditions of the immediate area, saw palmettos grow at a rate of somewhere between 0.88 and 2.2 cm per year. They certainly aren't winning any speed races at that rate. Regardless, you can begin to see that an estimate of yearly growth rate can shine a light on how long these palms have been around. Measurements of tagged palmettos growing on the sand ridge show that individuals aged at a staggering 500 years are not uncommon!

This estimate gets a bit complicated when we consider another aspect of saw palmetto biology - they are clonal. For a variety of reasons, as saw palmettos grow, their sprawling stem will often branch out, creating clones of themselves. Over time, the trunk portions that connect these clones rot away, giving the impression that they are unique individuals. Genetic analyses showed that many of the palmettos in the study area were actually clones. Using some pretty sophisticated models coupled with their DNA evidence, the research team was able to reconstruct the growth history of many of these clones, thus allowing them to more accurately age these clonal colonies.

Their results are staggering to say the least. Based on the rate of growth and spread, the estimated age of these clonal patches of saw palmetto range anywhere between 1227–5215 years! At this point you should be asking yourself "how accurate are these data?" The truth is that the researchers were actually being quite conservative in their estimates. For instance, there were likely many clones well outside their study area. If so, they were likely underestimating the growth time of these clonal colonies. Additionally, they were only using the growth rates of adult saw palmettos in calculating average growth rates.

Seedling saw palmettos have been shown to have a reduced growth rate compared to adults, only 0.3 cm per year. Thus, they did not take into account the time it takes for seedlings to reach maturity. The team feel that accounting for such variables could increase the age estimates for such clonal patches to well over 8,000 years! I don't think we should be looking into buying that many birthday candles just yet, however, even their reported estimates are shocking to say the least.

What we can say is that for as long as Florida has been above water, saw palmettos have played an integral role in the ecology of the region. Long before humans began developing the state, the saw palmetto was functioning as a major player, shaping these sand ridge communities into the ecosystems they are today. It is without a doubt, a species worthy of our admiration and respect.

Scientific Names: Serenoa repens (synonyms: S. serrulata, Sabul serrata) Other Common Names: American dwarf or cabbage palm, palmier Nain, sabal fructus Overall Safety: 😊  

Therapeutic Efficacy and Considerations:

BPH: 😊 Saw palmetto has been frequently compared to placebo and to finasteride for the treatment of BPH. Several meta-analyses of these studies have been performed and conclusions have all been similar: saw palmetto decreases symptoms and improves urine flowmetry to a mild-to-moderate extent with fewer side effects than finasteride. Prostate volume and PSA levels are not affected. Two trials against α-blockers found that the α-blockers had more effects on obstructive symptoms, with saw palmetto having similar or more effects on irritative symptoms. A recent high-quality trial found no difference between saw palmetto and placebo. Overall, current evidence does support a recommendation for treatment of mild-moderate BPH, especially irritative symptoms. Patients with primarily obstructive symptoms or greatly enlarged prostates will probably not benefit as much from therapy. Dose: 320 mg/day of extract standardized to 80-95% fatty acids and sterols given in one or two doses. Note: because of the possibility of masking the symptoms of prostate cancer and delaying diagnosis and treatment, patients must be screened and diagnosed by a physician prior to treating BPH with saw palmetto or any other dietary supplement. Saw palmetto is first line therapy for BPH in several European countries.

Chronic Prostatitis: 🙁 One trial has compared finasteride and saw palmetto for the treatment of chronic prostatitis. Symptoms in the saw palmetto group were improved to a similar extent as finasteride at 3 months but worsened over the rest of the treatment year. The current evidence does not support a recommendation for use for this indication.

Hair Growth Stimulant: 🙁 Only one small trial has examined efficacy for stimulation of hair growth. Although some improvement was seen, the change was not statistically significant. More research is warranted but saw palmetto cannot currently be recommended for this indication.

Prostate Cancer Prevention: 🙁 One large epidemiological study found no relationship between use and the risk of prostate cancer. Saw palmetto is not recommended for this indication.

Chemistry/Pharmacology: Saw palmetto has benefit for BPH through several mechanisms. It is a non-competitive inhibitor of both subtypes of 5-α-reductase (finasteride only inhibits type 2), the enzyme that converts testosterone into the more active dihydrotestosterone (DHT). Effects seem to be more localized; systemic levels of DHT are not generally lowered with saw palmetto therapy. Competitive inhibition of DHT receptor binding seems to occur. Apparent anti-inflammatory effects are via inhibition of cyclooxygenase and lipoxygenase, as well as mast cell inhibition. Epithelial proliferation induced by growth factor is inhibited and involution of prostate epithelium occurs. In vitro studies have demonstrated some α1 blocker activity, but this does not seem to occur in vivo. Prostate size and PSA levels are not affected with saw palmetto therapy.

Drug Interactions: Hormonal or anti-hormonal therapies (due to possible opposing or additive effects); anticoagulants (due to possible increased bleeding risk, monitor closely). Although in vitro studies noted inhibition of α1 blocker binding, clinical significance is unknown. A pharmacokinetic study determined that saw palmetto has no effect on CYP450 2D6, 1A2, 2E1, or 3A4.

Contraindications/Precautions: Pregnancy/lactation (absolute contraindication due to hormonal effects); therapeutic androgens (due to antiandrogenic activity). This medication should be used with caution in patients already receiving an alpha-blocking agent for the treatment of BPH.

Abstract

OBJECTIVE:

Men affected with Benign Prostate Hyperplasia (BPH) and Lower Urinary Tract Symptoms (LUTS) are demonstrating to require an increasing amount of attention from Urologists and Primary-care Physicians. Over the years, common urological medications were based on either alpha-blockers and/or 5alpha-reductase inhibitors. During the last decade the phytotherapeutic drugs are gaining a more often central role in the BPH and LUTS managements. In particular, clinical usage of the extract of the dried ripe fruit of serenoa repens with a dosage of 320 mg per day, has shown its clinical efficacy and its superiority. Purpose of this multicentric observational retrospective study was to evaluate all the urological aspects (clinical, biochemical, instrumental and pathological) of patients affected by BPH and LUTS, with a PSA < 10 ng/ml, a previous negative prostatic biopsy and in therapy with a daily dose of 320/640 mg of serenoa repens.

PATIENTS AND METHODS:

The study was conducted in 8 different centers throughout Italy from September 2010 to November 2011. Data and information of 298 men with an average of 63 years (mean PSA of 5.4 ng/ml and mean prostate gland volume of 57 cc), affected by non-acute urinary symptoms caused by BPH, a dosed PSA level inferior to 10 ng/ml, a previous negative prostate biopsy and in therapy with serenoa repens alone or associated to an alpha-blocker, were retrospectively inserted in an extensive on-line SIUrO Database. Comprehensive questionnaires were filled in for each patient at 3 and 6 months of follow-up. Each questionnaire contained various sections, each of them composed by several items: dosed PSA levels, uroflowmetry, International Prostate Symptoms Score (IPSS), International Index of Erectile Function (IIEF-5), trans-rectal ultrasound (TRUS) patterns, digital rectal examinations (DRE) aspects, previous prostate bioptical results (histology) and side effects.

RESULTS:

PSA levels weren't subjected to an increase, revealing a stabilizing or downward trend. Percentage of patients with PSA below the level of 4 ng/mL was lower at the end of the study. The overall changes in the uroflowmetry were similar and parallel both in the group with only serenoa repens intake and in the group with serenoa repens plus alpha-blocker. The mean medium flow and the mean maximum flow had a slightly increase along the observation time. There was a substantial decreasing in the amount of patients presenting severe prostatic symptoms. Patients reported through the IIEF-5 score a sexual activity substantially unchanged after 6 months of follow-up. The serenoa repens intake resulted in an improvement of the "inflammatory-like reports", in terms of ultrasound patterns, DRE and bioptical features.

CONCLUSIONS:

SERENOA REPENS

O que é?

É uma palmeira-anã encontrada nos EUA, desde os estados davCarolina do Norte e Carolina do Sul até o Texas.

Extratos não purificados de Serenoa repens alivia as manifestações clínicas da hiperplasia prostáticas benigna.

Esta planta conserva a saúde da próstata por meio da redução do metabolismo e da ação dos esteróides masculinos. Serenoa repens reduz a atividade da 5-alfa- redultase, que estimula a conversão de testosterona em diidrotestosterona (DHT), sua forma mais ativa. A DHT é necessário para o crescimento excessivo (hiperplasia) da próstata e seus níveis estão aumentado na hiperplasia prostática benigna, a inibição da 5-alfa- redutase e, portanto, da produção de DHT, aliviaria a HPB e a compressão associada da uretra (a estrutura tubular que atravessa a glândula prostática ao levar a urina da bexiga para o meio exterior).

Estudos já mostraram que a Serenoa repens ajuda a inibir a produção de vários fatores inflamatórios, provavelmente por causa de um efeito dos ácidos graxos, reduzindo assim a inflamação prostática total.

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