The Safety, Efficacy, and Stability of Saw Palmetto for the Treatment of Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms in Men

Robert I-San Lin, Ph.D., CNS, FICN Lucinda G. Miller, Pharm. D. BCPS*
*Reviewer and contributing author.

Abstract

Saw palmetto berry has been consumed as a folk medicine (or dietary supplement) for centuries as a safe treatment for benign prostatic hyperplasia (BPH) and/or lower urinary tract symptoms (LUTS). Recently, a preparation of an extract of the berries has been scientifically proven to be safe and moderately effective for these conditions without affecting serum prostate specific antigen (PSA) level. BPH and LUTS affect a large segment of the over-50 male population and are major public health problems. There is currently a lack of sufficiently effective treatment that are safe and cost-effective for the mild to moderate forms of BPH. Permitting saw palmetto berries and properly prepared saw palmetto berry extracts to make the health claim concerning its benefits in mitigating/reducing the symptoms of BPH/LUTS is of substantial public interest and economic importance. Available scientific data support the approval of a health claim that 320 mg/day of saw palmetto extracts can reduce the symptoms of mild to moderate BPH/LUTS. There is substantial scientific agreement among qualified experts on this matter.

Introduction

Benign prostatic hyperplasia (BPH) is a common adenomatous hyperplasia of the periurethral prostate gland estimated to affect at least 65 % of men over 55 years old.2 The enlarged tissues cause various degrees of obstruction of the urinary tract and lead to progressive urinary frequency, urgency, nocturia, hesitancy, intermittency, decreased urinary flow rate, sensation of incomplete emptying, dribbling at the end of urination, urine retention, and many other symptoms. Without proper treatment, incomplete emptying and/or prolonged obstruction can lead to infections and subsequent inflammatory changes in the bladder and the upper urinary tract, hypertrophy of the bladder detrusor, bladder diverticula, hydronephrosis, formation of calculus, and hematuria due to rupture of the surrounding veins. Severe BPH may eventually cause progressive renal failure and azotemia.

Like many other chronic diseases, the symptoms can vary substantially, and can have periods of worsening, improvement, or even remission. Anticholinergic and sympathomimetic drugs, and alcohol aggravate the conditions. Despite the common practice of watchful waiting, BPH must be treated properly and timely to prevent the development of irreversible damage.

It is common to include various symptoms of urination difficulties (LUTS) in BPH, but LUTS may or may not be related to the constriction of urinary tract in the prostate region or enlargement of the prostate. BPH and/or LUTS are a substantial public health problem. BPH and/or LUTS cause approximately 2 million office visits and $3 billion expenditures annually. With an increasing proportion of older people in the United States, the expenditures on BPH and/or LUTS are bound to increase rapidly, unless some preventive or alternative treatment measures are taken now.

Presently, definitive treatments for advanced BPH are transurethral resection of the prostate (TURP), open surgery, transurethral microwave therapy, and transurethral needle therapy. Those procedures are very costly. Furthermore, TURP is frequently associated with significant complications. For mild to moderate patients of BPH/LUTS, there is a great need for an effective inexpensive nonsurgical treatment. Saw palmetto is advised for mild to moderate BPH. In accordance with the United States Department of Health and Human Services "Guidelines for Benign Prostatic Hyperplasia: Diagnosis and Treatment," patients with BPH complications (e.g., recurrent infection, urinary retention, renal failure, gross hematuria, bladder stones and bladder diverticuli) should always seek surgical consults (McConnell JD, `Benign prostatic hyperplasia: treatment guidelines and patient classification," Br J Urol, 76 (Suppl): 29-46, 1995).

The 5,a-reductase inhibitor finasteride has been approved for use as a noninvasive treatment for BPH. As discussed below, finasteride is approximately as effective as a saw palmetto preparation and has substantially more adverse effects, including disturbances in sexual function. Alpha-blockers approved for BPH treatment are associated with adverse effects such as postural hypotension (3.9%) abd tachycardia (0.9%) although this has been minimized with the newer alpha-blocker, tamsulosin (See Physician's Desk Reference and package inserts for finasteride and alpha-blocker products). Saw palmetto berry or its preparations can provide very similar benefits and does not have the drawbacks of the adverse effects and of lowering serum PSA level (vide infra) and would cost a consumer approximately $300 less per year than fmasteride or alpha-blockers.

Saw palmetto, scientifically named Serenoa repens (also called Serenoa serrulata, Sabal serrulata, Sabalis serrulatae, pan palm, dwarf American palm, or dwarf palmetto) is the hardiest of the palms (the Arecaceae family) and grows widely over large areas in the Southern part of the United States and the West Indies. Its prostrate and creeping branches tend to grow into great masses of foliage. The plurality of its name is due to its broad use in different parts of the world for various conditions. The fruit (saw palmetto berry) had been used as a folk medicine by Native Americans for centuries as a tonic and a treatment for various diseases.' The 1939 book Back To Eden" specifically describes the use of the berry for treating prostate conditions. In addition to other information, the book states that the fresh or dried berries have the medicinal properties of "antiseptic, sedative, cardiac." It further states the saw palmetto berry to be "a very useful article in asthma and all kinds of throat troubles, especially when there is excessive mucous discharge from the head and nose, colds, bronchitis, la grippe, whooping cough, and where the throat is irritated and painful. Valuable in all diseases of the reproductive organs, ovaries, prostate, testes, etc. Very useful in Bright's disease and diabetes." (Underlines added). Another part of the book lists saw palmetto berries as a specific treatment of prostate gland conditions. Apparently, the saw palmetto berry had been used for treating prostate conditions for a substantial length of time before modern interest in this matter developed. Preparations of saw palmetto berry and/or its extracts are among the very commonly prescribed/sold drugs in Europe.

Dr. Robert I-San Lin has over 40 years of experience in scientific research and clinical use of phytotherapeutic agents and functional foods. Dr. Lucinda G. Miller is a board certified pharamacotherapy specialist with many years of research and investigational experience in the field of phytotherapies and herbal medicine. Drs. Lin and Miller have conducted a review of the scientific literature concluded that numerous studies, including clinical trials and meta-analyses, overwhelmingly support the safety, efficacy, and stability of saw palmetto berry and properly prepared saw palmetto extract for use in BPH/LUTS.

Safety of Saw Palmetto Berry and Its Extracts for the Treatment of Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms

The widespread use of saw palmetto berry and the above passages from Kloss' book indicate that saw palmetto berry is at least free of obvious short term and long term toxic or serious side effects when used for various medicinal purposes. In addition, saw palmetto has not been found to affect blood chemistries (Carraro 1996)(Newall CA, Anderson La, Phillipson JD eds. Herbal medicines: a guide for health care professionals. London: The Pharmaceutical Press 1996; 23738). Although impotence and ejaculation disorders have been reported in patients taking saw palmetto (0.32%), the incidence of said side effects is ten times more prevalent with finasteride (3.95 and 2.8%, respectively).

One of the most recent reviews6 on clinical trials on the use of saw palmetto berry extracts for treating prostate conditions contained the following statement on adverse effects: "Adverse effects due to S repens were generally mild and comparable with placebo. Withdrawal rates were S repens, 9.1%; placebo, 7.0%; and finasteride, 11.2% (P=.02 for S repens vs placebo and P=.87 vs finasteride). Erectile dysfunction was reported in 1.1 % of men taking S repens; placebo 0.7%; and finasteride 4.9% (P=.58 for S repens vs placebo and P<.001 vs finasteride). Minor gastrointestinal effects were reported in 1.3% of men taking S repens; placebo, 0.9%; and finasteride, 1.5% (P> .50 vs placebo and finasteride)." These data were derived from 18 randomized controlled trials involving 2939 men using a dose of 320 mg/day of saw palmetto extract. Most scientists would concur with the reviewer on the safety of the saw palmetto berry preparation. For a comparison, the safety data of the approved drug finasteride were derived primarily from human clinical trials having a total of approximately 2300 to 2500 patients. Thus the strength of the conclusions should be comparable in both cases.

However, it is important to note that finasteride does suppress serum PSA level. Since serum PSA is commonly used for early detection of prostate cancer, this lowering effect of finasteride is always a concern. One of the marketers of finasteride, Merck & Co., stated that: "In controlled clinical trials PROSCAR (a finasteride drug) did not appear to alter the rate of prostate cancer detection. "7 This statement does not relieve the concern because the physicians and the patients in controlled clinical trials are heightened to the detection of prostate cancer. It is very doubtful that this conclusion is applicable to the usual cases of BPH and LUTS. Finasteride's lowering of PSA does obscure its utility as a tumor marker for prostate cancer (Facts and Comparisons, Finasteride monograph, St. Louis, MO: Facts and Comparisons, Inc. 1999). In fact, a 5 mg dose of finasteride has been associated with a significant 50% decrease in PSA levels (Gormley GJ, Stoner E, Bruskewitz RC et. al., The effect of finasteride in men with benign prostatic hyperplasia. NEJM 1992;327:1185-91.)Therefore, saw palmetto berry and properly prepared extracts of saw palmetto berry offer definite advantages over finasteride in this safety aspect.

In a well-written and extensive review of the efficacy and pharmacology of saw palmetto berry for the treatment of BPH, Plosker and Brogden8 stated that "In general, Serenoa repens is well tolerated, with only 2% of the patients spontaneously reporting adverse events in a large noncomparative trial of 500 men with BPH receiving the drug for 3 months. Similar results were noted in smaller placebo-controlled trials, and discontinuation of Serenoa repens because of poor tolerability occurred only rarely. The most common adverse events in clinical trials have been minor gastrointestinal complaints, such as nausea and abdominal pain. In a large comparative trial with finasteride, Serenoa repens tended to be associated with a higher incidence of hypertension, headache, urinary retention and back pain, whereas gastrointestinal complaints, impotence, dysuria and decreased libido tended to be more frequently reported among men receiving finasteride. Clinically significant changes in laboratory parameters did not occur with Serenoa repens in clinical trials... All complaints... were resolved when Serenoa repens was taken with meals; none of the patients had to discontinue therapy because of adverse events."

Plosker and Brogden are correct except the passage related to hypertension, headache, urinary retention, back pain. The researchers were comparing a saw palmetto berry preparation with finasteride and concluded that "No statistically significant differences were noted between the two treatment groups for any intercurrent event." (Intercurrent events refer to hypertension, headache, urinary retention, back pain, impotence, and decreased libido.) It is not known for certain whether these intercurrent events would be statistically significant when compared to placebo, because there was a lack of a placebo group in the study. Such a comparison would be more meaningful, because it would reveal whether the preparation can cause such side effects and the degree of the side effects. Absent such a comparison, the very infrequent incidences (occurring in 3.1% or less of the patients) indicate that the observed hypertension, headache, urinary retention and back pain are extremely unlikely to be due to the treatments, because no other study with the preparation reported similar occurrences. The Serenoa preparation used in these reviewed studies was a "lipidosterolic" extract of S. repens. Whether such minor gastrointestinal problems belong specifically to this preparation or are intrinsic to saw palmetto berry and all saw palmetto berry preparations is not known for certain. As noted above, saw palmetto berry is not known to cause disturbances of the digestive tract and many other studies on saw palmetto berry extracts did not report any problem, gastrointestinal irritation or otherwise.

In a double-blind, placebo-controlled study on treatment of BPH with a saw palmetto preparation (Permixon), Reece Smith et al.9 reported in the first paragraph of the Results section that: "Eighty patients were included in the trial. Four patients, however, failed to attend for further follow-up and two withdrew after a few days because of 'intolerable' side effects. Of the 74 patients for whom records were available, three were withdrawn because of acute urinary retention requiring surgery...." Unfortunately, the authors did not specify which group these 6 patients belonged to and apparently did not contact the four patients who did not follow-up to ascertain the reasons for abandoning the trial. Further, the authors did not specify what were the intolerable side effects. The information would be of help in ascertaining the safety of the saw palmetto preparation. Later in the Side Effects section of the report, the authors state: "Two patients stopped Permixon treatment after two days and withdrew from the trial because of nausea and vomiting. One further patient stopped Permixon therapy for 2 or 3 days because nausea and one patient stopped Permixon for 1 day because of dizziness. No significant side effects were reported." Apparently, the two patients who experienced intolerable side effects were in the Permixon group and the intolerable side effects were nausea and vomiting. Reece Smith, et al. were not alone in finding some (up to a very small percentage) patients experienced mild gastrointestinal disturbances. In this case, these observations should be discounted due to a lack of quality in Reece Smith's study. Gastrointestinal disturbances, such as nausea reported by these researchers, are among the most commonly observed, subjective response of people taking anything orally, food, drug, or placebo. In any case, the great majority of the studies did not find any gastrointestinal disturbances. (See Table 1.) Thus, the evidence overwhelmingly proves that saw palmetto extract is free of any side effects, gastrointestinal disturbances or otherwise. Unfortunately, several careless reviewers/metaanalysts have mistakenly mentioned gastrointestinal disturbances as side effects. (See Table 1.) Some of these reviewers/meta-analysts were so confused that they even reported wrong number of patients on which statistical analyses were conducted.

TABLE 1. SAFETY OF SAW PALMETTO EXTRACT FOR THE TREATMENT OF BENIGN PROSTATIC HY'PERPLASIA AND/OR LOWER URINARY TRACT SYMPTOMS

Author, year	Key Features of the study	Author's Conclusions on the Safety of Saw Palmetto Extract	Remarks
Miller, 1998, Ref. 22	not applicable NA), a review article,	Adverse effects appear minimal and are characterized mostly by gastrointestinal upsets.	The author erred. Tasca et al. reported that 2 out of 13 patients in the placebo group and none 14 patients in the saw palmetto.
		This conclusion is based on the work of Tasca et al. Ref. 23.)	Group experienced gastrointestinal disturbances. Thus, a reverse conclusion would appear more valid, i.e., the saw palmetto preparation has a protective effect against gastrointestinal disturbances. On the other hand, one of the 14 patient receiving saw palmetto experienced tremor vertigo and cold sweating, whereas none in the placebo group. Whether these disturbances were related to the placebo or saw palmetto treatment is not known.
Gerber et al., 1998, ref. 18	prospective, open- label, 50 patients, 6 months, 320 mg/d	No significant side effects were reported by patients receiving saw palmetto and there were no significant changes in serum chemistry noted.
Wilt et al. 1998 ref. 6	meta-analysis	Adverse effects due to S repens were generally mild and comparable with placebo, saw palmetto extract treatment was associated with fewer adverse treatment events in comparison with finasteride.	See text for details.
Braeckman et al. 1997 ref. 24	double-blind, - placebo-controlled randomized, 229 patients, 3 months, 320 mg/d.	"In the placebo group they (side effects) were: gastrointestinal (2), allergic reactions (2). In the Serena group they were: gastro-intestinal (1), sexual (1), and important fatigue (1)…„	The placebo caused more gastrointestinal disturbances than the saw palmetto preparation. This is contrary to some reviewers' opinions.
Plosker and Brogden 1996 ref. 8	NA (a review article)	"In general, Serenoa repens is well tolerated, with only2% of patients spontaneously reporting adverse events... Clinically significant changes did not occur with Serenoa repens…”	See text on the detailed remarks on this work.
Carraro et al.	Double-blind,	"Permixon (a saw palmetto	See discussions on Carraro et
1996 ref. 13	randomized, 1098 patients, comparing a saw palmetto preparation with finasteride, 6 months, 320 mg/d.	extract preparation) fared, better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence.	al.'s in the text.
Fitzpatrick & Lynch 1995 ref. 12	NA. A review article.	"The safety of the agents (phytotherapies, including saw palmetto berry extracts) is well known..."	These conclusions are not valid. See discussions in on their study in the text.
Descotes et al. 1995 ref. 16	Double-blind, placebo controlled, randomized, 176 patients, 1 month, 320 mg/d.	"Permixon (a saw palmetto extract preparation) appears to be well tolerated..."	See discussions in on their study in the text.
Romics, Schmitz, & Frang 1993 ref. 26	open study, 32 patients, 12 months, 320 mg/d.	The drug was "well- tolerable, without any side effects."	This study clearly substantiates that long term use of the saw palmetto extract preparation is safe.
Carbin, Larsson, and Lindahl 1990 ref. 27	double-blind, placebo-controlled, randomized, 53 patients, 3 months, 480 mg!d saw palmetto extract and 480 mg/d pumpkin seed extract.	"No untoward side effects were noted."	This study indicates that short term use of a high dose of saw palmetto extract preparation is safe. Although the presence of pumpkin extract complicates the interpretation.
Reece Smith et al. 1986 ref. 9	double-blind, placebo-controlled, randomized, 70 patients, 12 weeks, 320 mold, with a follow up at the end of the 6th month after the treatment.	See text on detailed discussions on this study.	See text on detailed discussions on this study.
Tasca et. al. 1985 ref. 23	double-blind, placebo-controlled, randomized, 27 patients, 1-3? months, 320 mg/d.	"Systemic tolerance of the product (saw palmetto extract) (blood pressure, pulse rate, examination of different organs and systems, laboratory values) proved to be optimal: only one patient complained.	See Remarks on Miller's study.
		about gastric disturbances which led to the discontinuation of the treatment. "
Champult G, Patel JC, & Bonnard AM. 1984 ref. 28	double-blind, placebo-controlled, randomized, 94 patients, 1 month, 320 mg.	"(The saw palmetto berry extract preparation) was extremely well tolerated with less side-effects being reported... by patients receiving (the extract) than those receiving placebo. All side-effects reported were minor (e.g., headache). In addition standard blood chemistry measurements showed no alterations."	This study strongly support the safety of saw palmetto extract for use in BPH/LUTS.
Boccafoschi and Annoscia. 1983. ref. 29	double-blind, placebo-controlled, randomized, 22 patients, 60 days, 320 mg/d.	"As for tolerability, we recorded practically no secondary or side effects with the placebo or with Permixon (a saw palmetto extract reparation)."	This study strongly support the safety of saw palmetto extract for use in BPH/LUTS.
Emili, Cigno, & Petrone 1983 ref.30	double-blind, placebo-controlled, randomized, 30 patients, 30 days, 320 mg/d.	No side effects were observed.	This study strongly support the safety of saw palmetto extract for use in BPH/LUTS.
Mandressi et al. 1983 ref. 31	double-blind, placebo-controlled, randomized, 34 patients, 30 days, 320 mg/d.	"We certainly confirm the clinical reliability of the extract of Serenoa repens (sic) (Permixon) both in terms of effectiveness and tolerability."	This study support the safety of saw palmetto extract for use in BPH/LUTS.

In Reece Smith's study, blood chemistry scans were performed and showed no change during the course of the trial, except in one patient. The researchers reported that this particular patient "showed a marked rise in SGOT to a pathological level on completion of the trial. However, at this stage he was in hospital with an acute myocardial infarction." Here again, the report failed to specify which group, placebo or Permixon, that this patient belonged to and whether this occurrence is statistically significant. In any case, this in not a quality report as shown by other omissions, e.g., methods of measuring urine flow rate, which may affect the accuracy of the measurement. Furthermore, these measurements are not reported with the standard deviations, which would also reveal the quality of these measurements. This report does provide some assurance that the saw palmetto berry preparation is probably free of any serious side effects. Other researchers also found no change in blood chemistry (see Table 1).

In animals studies, 300 mg/day /mouse for 12 days1° and 1800 mg/day/rat for 7 days" did not cause observable adverse effects or toxicity. These dosage levels are equivalent to approximately 1300 and 1500 times, respectively, the regular and effective human dose of a typical saw palmetto berry preparation for approximately 6 to 10 months. These data overwhelmingly indicate that the regular and effective human dose of the preparation is well within the safe range. However, no human datum on the toxicity of saw palmetto berry or its extracts is available presently.

Even the strongest critics of using "phytotherapeutic agents" for managing BPH concur that "These agents have... achieved patient satisfaction, and so have achieved popularity with physicians and patients alike. This has been sustained by the ease with which they can be bought and also the absence of any side effects...The safety of the agents is well known...' 12 (the agents that they referred to include a saw palmetto berry preparation. Underlines added). (However, the passage "absence of any side effects" appears to be slightly exaggerated, because minor gastrointestinal irritations occurred in a very small percentage of the patients when the preparation was not taken with meals. This article does not have high scientific quality as will be discussed below. Thus, statements tl erein should be taken with a degree of reservation.)

Interactions with other drugs and /or nutrients have yet to be reported . Miller2' pointed out: "Adverse effects appear minimal and are characterized mostly by gastrointestinal upset. While no drug herb interactions have been documented to date, it would be prudent to avoid concomitant use with other hormonal therapies (eg, estrogen replacement therapy and oral contraceptives) which may provide an additive effect." These comments are of little value and should be discounted. (Asarosa C, Cosci o di Coscio M, Fratta M. Lack of effects of a liposterolic extract of Serenoa repens on plasma levels of testosterone, follicle-stimulating hormone, and lutenizing hormone, Clin Ther 1988;5:585-88)(Elghamry MI, Hansel R. Activity and isolate phytoestrogen of shrub palmetto fruits (Serenoa repens Small), a new estrogenic plant. Experentia 1969;25:828-9)(DiSilverio F, D'Eramo G, Lubrano C et. al., Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients. Fur Urol 1992;21:309-14). Comments based on Tasca's study21may conclude that gastrointestinal upset is the side effect. In Tasca's study gastrointestinal upset occurred in the placebo group but did not occur in the saw palmetto group (See Table 1).

Regarding the concern on additive effects with estrogen therapy, it is not conclusive at all that saw palmetto extracts have a significant estrogenic activity. Extracts of saw palmetto berry are also reported to be antiestrogenic", thus it is doubtful that the extract can have additive effect with estrogen therapy. Looking this issue from another point of view, phtytoestrogens exist very widely in plants including commonly consumed plant-derived foods, but few plants are known to contain sufficient estrogenic activity that would require modification of an estrogenic treatment regimen. Phytoestrogens refers to mainly bi-phenolic compounds that bind competitively to estrogenic receptors. How phytoestrogens affect the body and interact with drugs and nutrients is poorly understood.' Furthermore, any concerns about the interaction with estrogenic replacement therapy and contraceptive is not an issue here, because we are dealing with men instead women. The long history of use of saw palmetto berry for BPH/LUTS without report of side effects is consistent with a conclusion that saw palmetto berry, and probably its extracts, does not have a significant effect on sex hormone status in the body. Although the concern on antiandrogenic effects, antiestrogeniceffects, and additive or antagonistic effects of concomitant use of saw palmetto berry or its extract cannot be absolutely ruled out, from a practical point of view, this is not an issue.

Pizarro et al. expressed a concern that the tannin content of saw palmetto berry and its extract may impair iron absorption . Hence concomitant use should be avoided (Pizarro F, Olivares M. Hertrampf E, Walter T. Factors which modify the nutritional state of iron: tannin content of herbal teas. Arch Latinoan Nutr 1994;44:277-80). Saw palmetto berry is not particularly rich in tannin, a group of compounds that exist very widely among plant-derived foods. Grape seed extracts and grape pigments have much higher contents of tannin than saw palmetto extract and saw palmetto berry. (Grape seed extract and grape p 2ments are commonly sold as dietary supplements, but substantial part of these pigments are tannin (Lin RIS & Hilton BW. 1980. Purification of Commercial Grape Pigment. J. Food Sci. 45:297-306.) Although iron deficiency is a major nutritional problem worldwide, practically, iron deficiency is a result of insufficient dietary intake. Tannin content of food has not been shown to be a significant factor, despite many common foods are very rich in tannin, such as teas, persemont, and many other fruits. Saw palmetto berry has been consumed for a long period of time, but there is no report that it can cause iron deficiency. Regarding the possibility that saw palmetto berry extract can interfere with iron absorption, it is very doubtful that the hexane extract contain any significant amount of tannin. It is well known that tannin is not extractable with hexane.

A search of the Medline and FDA's dverse event monitoring system databases revealed no allergy citations concerning saw palmetto. The adverse event system did list three reports: 1) paroxysmal atrial fibrillation with rapid ventricular response with symptomatic lightheadedness and palpitations (mfg: Vitamin Shopp); 2) death-excessive fatigue on exertion. 3 wk later symptoms of MI; probably ventricular rupture (mfg: Nutrition Headquarters, Inc.); and 3)rectal bleeding (mfg: High Health Products). The value of those reports is negligible. It is not clear from how this database was constructed or if these reports came from consumers or health care providers. The level of causation, doses, and the temporal relationship are not addressed in the reports. Finally, a Medline search yielded no citations for vitamin interactions with saw palmetto.

In contrast to saw palmetto berry or its extracts, the approved drug for BPH/LTUS, finasteride, is a strong 5,a-reductase inhibitor and as such it may cause abnormalities of the external genitalia of a male fetus of a pregnant woman who is exposed to finasteride. Thus, when the patient's sexual partner is or may become pregnant, the patient should either avoid exposure of his partner to semen or he should discontinue finasteride. Furthermore, finasteride can cause disturbances in male sex function. For example, in a trial with 5 mg/day/patient for 12 months, the incidence of impotence was 3.7% , decreased libido 3.3%, and decreased volume of ejaculation 2.8%; in contrast, the incidence of these distrubances in the placebo group was 1.1 %, 1.6%, and 0.9%, respectively.' These findings by the manufacturer of the finasteride drug are consistent with the findings of others, e.g., Carraro et al.'s study'3. Although impotence and ejaculation disorders have been reported in patients taking saw palmetto (0.32%), the incidence of said side effects is ten times more prevalent with finasteride (3.95 and 2.8%, respectively). Finasteride side effects of breast tenderness and enlargement have not been reported with saw palmetto (Ibid, Facts and Comparisons).

As discussed by Dr. Lin in the book Functional Food 5: "A pure phytochemical and a plant containing the same amount of the phytochemical may differ substantially in safety, stability, and efficacy. Consumption of a certain quantity of pure phytochemical may not be safe, even if consumption of the whole plant that contains the same quantity of the phytochemical is safe (and vice versa). This is so because the whole plant contains many compounds, which may counteract each other and reduce the toxicity." Thus, one might argue that the safety of saw palmetto berry and that of saw palmetto berry extract are not the same. The long history of use of saw palmetto berries in folk medicine without any report of unsafe situations or contraindications does strongly indicate that the berry is safe for various medicinal purposes. Modem controlled studies on saw palmetto berry extracts show the extracts are also free of any significant side effects when taken with meals for treating BPH and/or LUTS. This consistency between the safety of the berry and the safety of its extracts reinforce each other and clearly underscores the safety of saw palmetto berry and properly prepared extracts of the berry for the treatment of BPH and LUTS.

Saw palmetto berry has been sold in the health food market in the United States for decades for use in treating BPH and/or LUTS. There are no known safety concern about the use of the berry. During past three decades, Dr. Lin has observed, and evaluated, administration of saw palmetto berry powder, alone or in conjunction with other herbs, to over a thousand people without any side effects. This long history safe use of saw palmetto berry and Dr. Lin's extentive expereience are consistent with the conclusion that saw palmetto berry and proper preparations of saw palmetto berry are safe for long term consumption as dietary supplements.

Efficacy of Saw Palmetto Berry and Its Extracts in the Treatment of Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms

Multiple randomized and controlled clinical trials demonstrate that saw palmetto has a beneficial effect on urinary flow rates (3.12 ml/s versys 0.58 with placebo), nocturnal frequency (1.61 days versus 0.53 with placebo and post void volume (27 ml versus 1,2 ml with placebo) which significantly exceed any placebo effect. See Tables 2, 3, and 4.

TABLE 2: DOUBLE-BLIND PLACEBO-CONTROLLED STUDIES

STUDY	DURATION SIZED (dose per day)	NOCTURNAL FREQUENCY (days)	CHANGE IN FLOW RATE (ml/sec)	CHANGE IN PVR (ml)
Boccafoschi 1983	2 months N=22 320mg	-2.2 A -1.0 P	4.1 A 1.9 P	-48 A -29.2 P
Braeckman 1997	3 months N=229 320mg	NA	NA	NA
Carraro 1996	6 months N=1098 320mg	NA	2.7 A 3.2 F	NA
Carbin 1990	3 months N =1098 320mg	-0.6 A -0.1 P	3.0 A 0.3 P	-42.5 A -7.6 P
Champault 1984	1 month N=110 320mg	-1.43 A -0.5 P	2.7 A 0.3 P	-42 A -9 P
Cukier 1985	2 months N=146	-1.1 A -0.5 P	NA	-16 A 55 P
Descotes 1995	1 month N=176 320mg	-0.7 A -0.3 P	14 A 1.1 P	NA
Emili 1983	1 month N=30 320mg	-1.65 A -0.35 P	3.4 A 0.2 P	-36 A -12 P
Gabric and Miskic 1987	6 weeks N=59 Combination	NA	4 .1 A -0.8 P	-5.7 A -4.8 P
Mandressi 1983	1 month N=59 320mg	2.6 A 0.96 P	1.42 A 1.11 P	-1.11 A -1.00 P
Tasca 1985	1-3 months N=30 320mg	-2.6 A -1.2 P	3.3 A 0.6 P	NA
AVERAGES:		-1.61 A -0.53 P	3.12 A 0.58 P 3.2 F	-27 A -1.2 P

A=active treatment, P=placebo, F=finasteride, NA=not assessed NS: did not achieve statistical significance

References for Petition for Health Claim Concerning Saw Palmetto and BPH

The American Medical Association Family Medical Guide, 3d Ed. (New York: Random House, 1994) pp. 615-616.
Bach D. Ebling L, "Long-term drug treatment of benign prostatic hyperplasia: results of a prospective 3-year multicenter study using sabal extract IDS 89," Phytomedicine, 3: 105-111, 1996.
Boccafoschi C and Annoscia S, "Confronto fra estratto di Serenoa repens, e placebo mediate prova clinica controllata in paziente con adenomatosi prostatica," Urologia, 50: 1257-1268, 1983. English translation included.
Boyle P, et al., "Prostate Volume Predicts Outcome of Treatment of Benign prostatic Hyperplasia with Finateride: Meta-Analysis of Randomized Clinical Trials," Urology, 48: 398-405 1996.
Braeckman J, et al., "A double-blind, placebo-controlled study of the plant extract Serenoa repens in the treatment of benign hyperplasia of the prostate," Fur J Clin Res, 9: 247-259, 1997.
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