The Safety, Efficacy, and Stability of Saw Palmetto for the Treatment of

Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms

Robert I-San Lin, Ph.D., CNS, FICN

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 for these conditions other than costly surgery and some other procedures.  However, these procedures may have many side effects, can achieve only partial correction of symptoms, and are performed primarily on patients with severe BPH/LUTS.1  Permitting saw palmetto berries and properly prepared saw palmetto berry extracts to make a health claim of being useful for mitigating/reducing the risk of BPH/LUTS is of substantial public interest and economic importance.  Available scientific data support the approval of a health claim that properly prepared dietary supplements that contain saw palmetto berry or extracts of saw palmetto berry can help maintain the health of urinary tract and may reduce of the risk of 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 treatment for BPH are transurethral resection of the prostate, open surgery, which is used in the cases of large benign prostate, and some other procedures.  These procedures are not only costly but also are frequently associated with complications, and are performed primarily on severe BPH/LUTS.  With an increasing proportion of older people in the United States, there are simply not enough surgeons and surgical facilities available to cope with this situation.  For mild to moderate patients of BPH/LUTS, there is a lack of sufficiently effective drug treatment.  The 5,a-reductase inhibitor finasteride has been approved for use as an 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.  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).

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 Unawed 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.3  The 1939 book Back To Eden4 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, who has over 40 years of experience in scientific research and clinical use of phytotherapeutic agents and functional foods, has 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.  (Dr. Lin was the first to provide the concept of phytochemicals in health and disease in the 1980's.  Later in 1994, he provided the definition for the term "phytochemical" in the authoritative book Function Foods.5  His curriculum vita is attached herewith.)

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.  Otherwise its toxicity would be worth the mention of these authors and noted in other folk medicine books or professional books.

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).  Gastrointestinal adverse 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 randomiwd controlled trials involving 2939 men.  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.  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."  The reviewers 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 p metto 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 one of the very few research teams that observed some (up to a very small percentage) of patients who experienced 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 I.)   Thus, the evidence overwhelmingly proves that saw palmetto extract is free of any side effects, gastrointestinal disturbances or otherwise.  Unfortunately, several careless reviewers/meta-analysts have mistakenly mentioned gastrointestinal disturbances as side effects.  (See Table I.)  Some of these reviewers/meta-analysts were so confused that they even reported wrong number of patients on which statistical analyses were conducted.

Table I.  Safety of Saw Palmetto Extract for the Treatment of

Benign Prostatic Hyperplasia 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."  (This conclusion is based on the work of Tasca et al.  Ref. 23.)	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 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 Serenoa 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 only 2% 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. 1996 ref. 13	Double-blind, randomized, 1098 patients, comparing a saw palmetto preparation with finasteride, 6 months, 320 mg/d.	"Permixon (a saw palmetto extract preparation) fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence.	See discussions on Carraro et 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 mg/d, 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 about gastric disturbances which led to the discontinuation of the treatment."	See Remarks on Miller's study.
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 preparation)."	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 I).  Thus, saw plametto treatment has no effect on blood chemistry.

In animals studies, 300 mg/day /mouse for 12 days10 and 1800 mg/day/rat for 7 days11 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 therein should be taken with a degree of reservation.)

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.7   These findings by the manufacturer of the finasteride drug are consistent with the findings of others, e.g., Carraro et al.'s study13.

As discussed by Dr. Lin in the book Functional Foods5: "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 thewerry is safe for various medicinal purposes.  Modern controlled studies on saw palmetto berry extracts show the extracts are also free of any 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.  That experience in combination with the aforementioned safety information compel 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

A well-designed and conducted multicenter study13 on the treatment of BPH was published in 1996.  The 1098-patient study was conducted in nine European countries with the participation of an American biostastistician.  In the study the subjects were given 320 mg Permixon (a preparation of saw palmetto berry extracts)/day or 5 mg finasteride/day for 6 months, under double-blind randomly assigned conditions.  Both Permixon and finasteride caused substantial decrease in the International Prostate Symptom Score (-37% and -39%, respectively), improved quality of life (38% and 41%, respectively), and increased peak urinary flow rate (25% and 30%, respectively).  The researchers stated that "Permixon fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence" than finasteride.  However, finasteride differ from Permixon in that Permixon did not decrease prostate volume and serum prostate-specific antigen.  Those conclusions are correct.  These difference are important in that there is no possibility for saw palmetto berry or its extract to interfere with prostate cancer detection by lowering serum PSA level.  The lack of effect on prostate volume does not necessarily indicate that saw palmetto berry or its extract is ineffective on treating LUTS.

Two meta-analyses on the treatment of BPH with a preparation of saw palmetto berry extract were published in 1998.  Wilt et al.6 reviewed 18 randomized controlled trials involving 2939 men, including the study mentioned above.  The mean study duration was 9 weeks (range: 4 to 48 weeks).  As compared with men receiving placebo, treatment with the saw palmetto berry extract caused a decrease in urinary tract symptom scores of 1.41 points (scale range: 0 to 19) and nocturia of 0.76 times, an increase in peak urine flow of 1.93 mL/second, and improvements in subjective self-rating of urinary tract symptoms.  In many important aspects, Permixon yielded benefits that are practically not different from the benefits of finasteride, e.g., in International Prostate Symptom Score (the different being 0.37 out of 0 to 35 scale range).  These meta-analysts concluded that "the evidence suggests that S repens improves urological symptoms and flow measures.  Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events."  This conclusion should be accepted with a reservations.  Bach, Schmitt and Ebeling14 reported recently that in a 3-year, 309 patient trial, a saw palmetto preparation was shown to improve objective urinary flow rate and subjective symptoms substantially, and a 50% in postvoid volume, whereas finasteride improved the flow rate only slightly and did not improved the post void volume.  Thus, to state that the saw palmetto berry/its preparation is comparably as effective as finasteride in treating BPH/LUTS may be an understatement.  However, the authors also stated that "further research is needed...to determine its long-term effectiveness and ability to prevent BPH complications."  That statement is in error because one of the reviewed studies, Carraro et al.'s13, was 6 months long, involving 87 urological centers in 9 European countries with 1098 patients.  The patient base is greater than one-third of the total number of patients reviewed by the authors.  In all senses, a study that lasted 6 months is a long term study.  If a drug or nutrient does not show its effects in 6 months, it must be considered ineffective.  On the other hand if efficacy is properly demonstrated within this period, as is the case of Carraro et al.'s study, the efficacy must be accepted.  In clinical trials with therapeutic agents, the requirement of a trial duration greater than 6 months has hardly been required.  Fitzpactrick and Lynch14 believe that in clinical trials it took 3 to 6 months to develop placebo effects.  This study demonstrated that a preparation of saw palmetto berry extracts (Permixon) is practically as effective as a "proven" and "approved" drug finasteride in treating BPH.  If finasteride is acceptable as safe and effective, then this saw palmetto berry extract preparation must be accepted as safe and effective, even though a placebo group was not used in the study.

Published in the same year is the report of the Committee on Other Medical Therapies of the Fourth International Consultation.15  The 7 studies reviewed by this committee were also a part of the database that was reviewed by Wilt et al.  The Committee stated that "the placebo-controlled studies are the ones being examined in this paper...Seven placebo-controlled studies with Permixon have been published, with the longest duration being 3 months...Only four of these included more than 50 patients in each study; in three of these trials, Permixon was statistically significant better than placebo in terms of effects on urinary frequency (nocturia and daytime) as well as peak flow rate.  Peak flow rate improved by 26-50% in the Permixon patients, but only 2-35% in the placebo-treated patients.  The over-all symptom improvement demonstrated in the placebo-controlled trials was a reduction of baseline nocturia by 33-74% with Permixon compared to 13-39% with placebo."

The Committee draw heavily on Descotes' study16 and stated: "In the study of Descotes...there was statistically significant improvement in frequency, nocturia, and flow rate.  However, the same study showed that 'despite this evidence of symptomatic improvement, there was little difference between either the patients' or the physicians' global assessments of the efficacy of Permixon and placebo.'  Patients satisfaction was 71% for Permixon and 68% for placebo (P>0.05, NS), while the physicians' assessments were 57% for Permixon and 47% for placebo (P>0.05, NS).  Thus, the symptomatic improvement seen with Permixon after 1 month of treatment, although statistically significant, was felt to be of limited overall clinical significance by the patients with BPH in this study.  Clearly, no definitive conclusions can be drawn from these aforementioned studies concerning Permixon since they were all short-term with a maximum duration of 3 months...."  Those conclusions are not justified and the Committee have apparently overlooked some unique experimental procedures that might have contributed to the large improvements in the subjective scores of the placebo group.  The extremely large placebo effects (68% and 47%) observed in the Descotes' study require careful examination of the study procedures to ascertain whether these data are acceptable.  In most clinical trials, placebo effects range between 0% to 35%.  The Descotes et al.'s study is unique in that the researchers wanted to minimize placebo effect by having the patients to go through a base-line, placebo run-in period of 30 days.  Only patients showing <30% improvement from base-line in peak urinary flow rate ("the nonresponding patient") were selected for the placebo-controlled study.  Dr. Lin's experience as research scientist indicates that this type placebo run-in base-line period can cause exaggerated placebo effects in the subsequent actual study.  This is probably due to the fact that patients in both treated and placebo groups somehow realized that they were entering a more important or more serious study period, and their mind subconsciously worked on the matter.  Thus, the large placebo effect of the subjective assessment of the placebo group and treated group should be both discounted.  The more objective measurements of daytime and nocturnal urinary frequency and peak flow rate should be depended upon to make conclusions.  In these cases, both objective parameters improved significantly with the saw palmetto berry preparation in comparison with the placebo group.  (Although one can counter argue that frequency of urination and the urine flow rate are subject to the control of the mind to certain degrees and are thus not objective parameters, this argument cannot prevail because these functions, like most other bodily functions, are primarily physiologically controlled and not psychologically controlled.  If one stretches psychosomatic interactions to the extreme, then all objective physiological measurements could be called subjective measurements.  But such extremism is not the standard practice in biomedical sciences.)  Thus, a definitive conclusion should have been made that the saw palmetto berry preparation was at least effective for short term (30 days) treatment of BPH.

Critics of phytotherapy of BPH have relied heavily on the placebo effect to argue that the efficacy observed in open-label studies, which are often short term, should be discounted.  Meta-analysts, including Fitzpactrick and Lynch12, and Schulze et al.17 are of the opinion that placebo effects of drug trials on BPH could occur as early as 3 to 6 months and last for at least 2 years.  Such an argument has tow problems.  Firstly, before the 4th month, placebo effects would be assumed to be nonexistence or small.  The Descotes' data clearly do not support this contention.  Secondly, had placebo effect be so long lasting and so powerful, then many placebos would be potent and long lasting drugs for BPH and patients of BPH would benefit from various placebos.  This is certainly not the experience of patients of BPH and urologists.  In reality, the placebo effect has sometimes been unscientifically used as a weapon to attack the results that are not consistent with the critics opinions. 

Many other studies on the mitigating effects of saw palmetto berries or its preparations were not blinded and placebo-controlled and were not reviewed by these authors.  Nevertheless, these studies can provide highly valuable information on the efficacy and safety of these substances and are discussed below.

Gerber et al.'s open-label without placebo control study18 was published after these reviews and meta-analyses.  The authors studied the efficacy of a commercial saw palmetto berry extract, 320 mg daily, on 46 BPH/LUTS patients for 6 months.  They concluded that: " The mean IPSS (International Prostate Symptom Score, ± standard deviation) improved from 19.5 ± 5.5 to 12.5 ± 7.0 (P<0.001).  Significant improvements in the symptom score were noted after treatment for 2 months.  An improvement in IPSS of 50% or greater after treatment for 2, 4, 6 months was noted in 21%, 30%, and 46% of the patients, respectively."  They observed no significant change in peak urinary flow rate, postvoid residual urine volume, detrusor pressure at peak flow, and serum prostate specific antigen (PSA) level.  The researchers used an 8F transurethral catheter to measure urodynamic parameters, and a 14F transrectal catheter to measure abdominal pressure.  The testing procedures were described as the "bladder was filled with room temperature water at a rate of 50 mL/min.  Bladder pressure, volume infused, and rectal pressure were recorded.  Patients were then asked to void in a standing position.  Urinary flow rate, bladder pressure, rectal pressure, volume voided, and subtracted detrusor pressure were simultaneously recorded."  These testing conditions were very unnatural/unphysiological.  For example, the infusion water should be of body temperature instead of room temperature.  Otherwise, the temperature change can cause contractions of the bladder and/or the urethra.  The lack of improvement in flow rate and residual volume could be artifacts of the highly unnatural measurement procedures.  Furthermore, even minor changes in the flow rate and residual volume can cause substantial changes in the subjective symptoms.  In other words, the changes in flow rate and residual volume are not sensitive indexes for estimating the symptom changes.  Thus, Gerber et al.'s results do not necessarily mean that there was a lack of improvements in flow rate and residual volume that were sufficient to cause some degree of symptom improvements.  PSA is not a factor directly related to the symptom of LUTS.  The absence of an effect on PSA is an advantage of using saw palmetto berry or its extracts for treating BPH and LUTS.

Common to the situations in many other medical fields, some "meta-analysts" and reviewers are articulate but not properly qualified.  Sometimes these less qualified meta-analysts and reviewers made mistakes or misleading statements that caused controversies, perhaps due to their lack of knowledge on the clinical details.  For example, Plosker and Brogden8 stated: "Serenoa repens (Permixon) has been available for several years for the treatment of men with benign prostatic hyperplasia (BPH).  The drug is the n-hexane lipdosterolic extract of the dwarf American palm...."  Similarly, Lowe et al.15 stated that: "Serenoa repens (saw palmetto berry) is the most widely used phytotherapeutic preparation for the treatment of BPH/LUTS."  Fitzpatrick and Lynch12 reviewed some studies on the use of phytotherapeutic agents for BPH, including saw palmetto berry.  They stated: "Serenoa repens, which is an extract of the dwarf palm tree, has been used in the treatment of BPH and has a purported androgenic effect...the rationale for an extract of a dwarf palm tree to be used in BPH was not demonstrated."  (underline added).  Serenoa repens is the scientific name of the species or the entire plant, not saw palmetto berry.  The whole plant is not used as an herbal medicine.  Rather the berry is used as a medicine for BPH/LUTS.  These statements reveal that these authors were perhaps ignorant about the difference between the berry (or the drug made from the berry) and the plant.  Or they were simply careless.  Such sloppiness and/or a lack of expertise does not lend credence to their arguments.  These were the authors who were more inclined to argue against the use of saw palmetto berry for treating BPH and LUTS.  In the case of Plosker and Brogden's paper, many other mistakes and/or omissions, have indeed rendered their point of view less valuable.

Negative results on the Trials with Saw Palmetto

In the 12-week, double-blind, placebo-controlled study on 70 BPH patients, Reece Smith et al.9 concluded that: "whilst the regime of Permixon (a saw palmetto preparation) used in this trial was...associated with considerable symptomatic improvement, we have no evidence that this improvement was due to anything more than the psychosocial value of being involved in the trial and meeting a number of sufferers from a similar condition.  In particular, a significant proportion of patients came to a greater understanding of their disease and no longer required surgical treatment.  Thus it may be that if more time were spent counselling patients with symptoms of benign prostatic hypertrophy, the operative workload would be reduced."  The parameters that they measured included subjective assessments by the investigators (difficulty in micturition, impairment of stream, urinary urgency, hesitancy, intermittency, terminal dribbling, incomplete voiding, average daytime micturitions, and average nocturnal micturitions), by the patients (difficulty in passing urine, difficulty in starting urination, intermittency, terminal dribbling, sensation of incomplete voiding, poor stream, urgency, average daytime micturitions, average nocturnal micturitions), and objective measurements (urinary flow rate and bladder residual volume).  However, as mentioned above, this is a poor quality report.  The report fails to provide any statistical analysis on bladder residual volume measurement and the standard deviations of the flow rate measurements, two of the most important objective measurements.  Measuring urinary flow rate usually has large standard deviations.  For example, in a similar study with more than twice as many patients (n=205), the standard deviation for flow rate measurements are ca. 35% of the means, and that for the residual volume (using the same echogram method) are ca. 68% of the means.  As for the subjective evaluations, the data become even more unreliable, particularly the measurements used in this study is hard to quantify and not related to a scale of symptoms, which would be more quantifiable even though they are still subjective.  Of special concern, the patients apparently socialize among themselves.  A well conducted double-blind, placebo-controlled study would discourage participants from socializing among themselves, which may cause them to compare the treatment and to break the blind code.  For these reasons, the conclusions are questionable.

The strongest negative comments came from Fitzpatrick and Lynch12, who in 1995 concluded that "It is unthinkable, therefore, that plant extracts should be considered as legitimate therapy for symptomatic BPH without undergoing the same strict control...it is preferable that they should be respected scientifically because of proven efficacy in multicenter placebo-controlled trials."  However, these comments should now be ignored.  After the publication of this article, high quality scientific multicenter, double-blind and placebo-controlled studies have proven that an extract of saw palmetto berry is effective in treating BPH, as discussed above.  They also stated that: "It has never been proved, although it has been suggested, that plant extracts will decrease outflow resistance and also reduce the size of the prostate."  The first part of this 1995 comment is no more valid because it has been conclusively demonstrated that treatment with a saw palmetto berry preparation can indeed improve urinary flow, as discussed above.  Regarding reduction of the size of prostate, there is still a lack of evidence presently.  But as discussed above, prostate size may or may not be a factor in determining the symptoms and severity of LUTS.  They further stated: "To date, no absolute rationale for the use of plant extracts in symptomatic BPH has been demonstrated.  It is absolutely necessary, given the widespread use of these agents (saw palmetto berry extracts and other plant materials), that other studies be performed in this regard."  It should be noted that a "rationale" or mechanistic explanation is desirable but not absolutely required for many special nutritionals and drugs.  Many nutrients and drugs that are now in use do not have a "rationale" or mechanistic explanations on how they work or have explanations that appear to be wrong.  The scientific interpretations of the relation between pellagra and niacin are typical examples.  Most herbs have many active principles.  At the current state of knowledge, it would be very difficult or impossible to explain their modes of action, because the interactions among the multiple active principles and between these active principles and the body is often beyond the comprehension of scientists.  In any case, one should not give Fitzpatrick and Lynch's opinion much weight because the mistakes and/or carelessness , as stated above.  Please review Table II, which contains more data on the efficacy.

Table II.  Efficacy of Saw Palmetto Extract for the Treatment of

Benign Prostatic Hyperplasia and/or Lower Urinary Tract Symptoms

Author(s), year	Key Features of the Study	Author(s)' Observations/Conclusions	Remarks
Miller, 1998.  Ref. 22.	Not applicable (NA); (a review article).	"the most common use for saw palmetto is for benign prostatic hypertrophy...both objective (eg, frequency of nocturia and urine flow rate) and subjective (dysuria intensity and patient's self-rating) data indicated significant (P<0.01) improvement when saw palmetto (320 mg/d) was compared with placebo.)	The conclusion is valid and supports the efficacy of saw palmetto for treating BPH/LUTS..
Gerber et al., 1998, ref. 18	prospective, open-label, 50 patients, 6 months, 320 mg/d.	The International Prostate Symptom Score improved 19.5±5.5 to 12.5±7.0 (P<0.001).	See text for comments.
Lowe et al. 1988 ref. 15	NA. (A review article).	"No definitive conclusion can be drawn."	See text for comments.
Wilt et al. 1998 ref. 6	meta-analysis.	"evidence suggests that S repens improves urologic symptoms and flow measures...Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow ..."	See text for comments.
Braeckman et al. 1997 ref. 24	double-blind, randomized, placebo-controlled, 205  patients, 3 months, 320 mg/d.	Saw palmetto treatment caused reductions in pollakiuria (P<0.05), nocturia (P<0.05), dysuria (P<0.01), urgency (P<0.01), and hesitancy.	This study strongly support the efficacy of saw palmetto extract for use in BPH/LUTS.
Plosker and Brogden 1996 ref. 8	NA. (A review article).	"oral administration of Serenoa repens...was generally superior to placebo."	See text on the detailed remarks on this work.
Lowe & Ku 1996, ref. 25	meta-analysis.	"the studies evaluating the efficacy of SPB (saw palmetto berry) extract are inconclusive...For example, the 3-month trial by Reece Smith et al. demonstrated a significant increase in flow rate and decrease in symptoms with both placebo and SPB; therefore, it was concluded that SPB was no better than placebo."	These conclusions are not justified.  See text for discussions on Reece Smith's study.
Carraro et al. 1996 ref. 13	Double-blind, randomized, 1098 patients, comparing a saw palmetto preparation with finasteride, 6 months, 320 mg/d.	"Both (saw palmetto extract and finasteride) treatments relieve the symptoms of BPH in about two-thirds of patients..."	See discussions on Carraro et al.'s in the text.
Fitzpatrick & Lynch 1995 ref. 12	NA.  (A review article.)	"It would seem that plant extracts (including extracts of saw palmetto and other plant materials) rely to a major degree on the so-called placebo effect..."	These conclusions are not valid.  See discussions 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 significantly more effective than placebo..."	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 following improvements in symptoms were observed: number of daily urinations 29%, number of night urinations 39%, hesitancy 73%, interrupted stream 75%, residue feeling 77%, terminal dribbling 67%, weak stream 76%.  Significant to substantial improvements were also observed in: duration of urination, duration until maximum flow, maximum flow, average flow, uroflow index, residue, bladder capacity, AP diameter of prostate volume, and transverse diameter of prostate.	Although these long term observations are consistent with the observations of many other researchers and lend support to the efficacy of saw palmetto, the study was not blinded.  Thus, how much placebo effect contributing the observed improvements is not known.
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.	"Urinary flow, micturition time, residual urine, frequency of micturition and a subjective assessment of the effect of treatment were all significantly improved in the treatment group."	Although these observations are consistent with the observations of many other researchers and lend support to the efficacy of saw palmetto, the study was not blinded.  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 mg/d, with a follow up at the end of the 6th month after the treatment.	"There was no significant difference between the results of treatment in either group (saw palmetto and placebo)."	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.	"Clearly positive results were obtained in 42.9% of the patients treated with the active substance (saw palmetto extract) and in 15.4% of those treated with the placebo."	The conclusion is valid and supports the efficacy of saw palmetto for treating BPH/LUTS.
Champult G, Patel JC, & Bonnard AM. 1984 ref. 28	double-blind, placebo-controlled, randomized, 94 patients, 1 month 320 mg/d.	Significant to substantial improvements (P<0.001) were observed in nocturia, flow rate, postvoid residue, dysuria and other subjective indexes.	These results strongly support the efficacy of the saw palmetto extract.
Boccafoschi & Annoscia 1983 ref. 29	double-blind, placebo-controlled, randomized, 22 patients, 60 days 320 mg/d.	Significant to substantial improvements (P<0.05 or smaller) were observed in volume of urination, maximum and average flow rate, clinical scores of dysuria and nocturia.	This is a well conducted and written study.  These results strongly support the efficacy of the saw palmetto extract.
Emili, Cigno, & Petrone 1983 ref. 30	double-blind, placebo-controlled, randomized, 30 patients, 30 days 320 mg/d.	"The hexane extract of Serenoa repens B was shown in our study to be useful improving the clinical and instrumental parameters...."	These results is consistent with other studies and support the efficacy of the saw palmetto extract.
Mandressi et al. 1983 ref. 31	double-blind, placebo-controlled, randomized, 34 patients, 30 days 320 mg/d.	"there was a clearly greater reduction in the points (symptoms) for the subjects treated with Serenoa Repens (sic) (Permixon) compared to those treated with a placebo.  Especially relative to nocturia...the group treated with a placebo actually showed a slight increase in symptoms, almost to the point of indicating a progression of the disease, while the subject treated with Serenoa Repens (sic) (Permixon) showed a considerable reduction of the phenomenon."	These results is consistent with other studies and support the efficacy of the saw palmetto extract.

Importantly, no reviewer or meta-analysts has denied that saw palmetto berry preparations can provide certain benefits to BPH/LUTS patients.  Critics often attribute these benefits to placebo effects.  If saw palmetto berry provided only placebo benefit in the treatment of BPH/LUTS, then why numerous other plants that were more available to Native Americans for centuries were not used?  There must be something unique that links these berries to BPH and/or related LUTS.  The unique factor most likely is the efficacy of saw palmetto berries in the treatment of BPH and/or related LUTS.  The most recent discovery19 that a saw palmetto berry extract, not extracts of some other plants, potently and non-competitively inhibited human a-adrenoceptors is consistent with the uniqueness of saw palmetto berry in the treatment of BPH and/or LUTS.

With regard to the lack of effects on prostate volume and serum PSA level, these two indexes may or may not have material effects on the symptoms of BPH/LUTS, which include difficulty in passing urine and in starting urination, intermittency, terminal dribbling, sensation of incomplete voiding, poor stream, urgency, frequent daytime and nocturnal micturition with a smaller quantity of urine for each urination.  The lack of effect of saw palmetto berry on prostate volume and PSA does not necessarily compel us to conclude that the observed benefits are placebo benefits.  The lack of effect on serum PSA level is actually an advantage, as discussed above.

The Stability of Saw Palmetto Berries and Preparations of Saw palmetto berry

Little scientific information is available about the stability of saw palmetto berries, except that the dried berries and powder that have been stored for years are still effective for many of the intended medicinal purposes.  Thus, the dried berries of saw palmetto and their active principles, like many other herbs and their active principles, are stable for at least several years.  The stability of preparations of saw palmetto berry extracts are not known to me.  Since the active principles are reported to be acylglycerides20 and phytosterols, we can expect a stability of at least several months to a few years, this range of stability is adequate for dietary supplement, whose requirement for stability ranges from a few weeks (as for acidophilus products) to a few years (as for vitamins).  For comparison, most over the counter drugs have shelf-life of 1 to 3 years.

Active Principles and Physiological and/or Pharmacological Modes of Action

Our knowledge in this area is limited, and many conclusions of pharmacological studies are often misleading.  Nevertheless, many researchers believe that the active principles are fatty acids/fat extractable substances, and phytosterols.  Most likely, these substances contribute to the efficacy of saw palmetto berries.

The proposed mechanisms of saw palmetto include: antiandrogenic effects (inhibition by competition with dihydrotestosterone for binding to the androgenic receptors, inhibition of 3, H-methyl-trielenone binding to the receptor, inhibition of 5,a-reductase, which converts testosterone into dihydrotestosterone, and inhibition of 3,a-oxireductase), antiestrogenic effects21, modulation of the function of eicosanoids, and inhibition of prostate dell proliferation.  Most recently, Goepel et al.19 reported that a saw palmetto berry extract potently and non-competitively inhibited human a-adrenoceptors in vitro.  Such an inhibition is unique to saw palmetto berry extract; extract of other commonly used phytotherapies for BPH, pumpkin seed, a beta-sitosterol preparation, and stringing nettles were not effective.

At best the above information provides only a partial picture.

Legal and Regulatory Point of View

Three main issues, safety, efficacy, and stability, must be addressed when considering a health claim that saw palmetto berry or its extracts are beneficial for reducing the risk of or to be capable of mitigating BPH and/or LUTS.  Regarding safety, statements about the use of phytochemicals in food fortification, such as "A phytochemical must be tested for safety more rigorously than a drug would be, before the pure compound can be used for food fortification.  A reason for a more stringent test is that the consumers' exposure to phytochemicals is expected to be greater than their  exposure to drugs.  Another reason is that the benefit of a phytochemical is expected to be lower than that of a drug, at least in the short term.  Therefore, the use of a phytochemical must have a very low safety risk in order to achieve an acceptable benefit/risk ratio."5 applies.

"A more difficult and serious problem related to functional foods is that a plant/phytochemical may reduce the risk of certain diseases in some individuals, but may increase the risk of other diseases in some other individuals, or even in the same individuals... many foods (phytochemicals) have an effect of counterbalancing certain imbalanced physiological states, so that the risk of certain diseases associated with the imbalance may be mitigated.  A phytochemical may enhance the balance in some, but may cause excess in others.  Typical examples: anti-occlusive phytochemicals can reduce the risk of occlusive cardiovascular diseases in the majority of people, but they may also increase the risk of hemorrhages in a certain segment of the population...In my opinion, the substantiation of the safety of phytochemicals must be more stringent than that of drugs, and the substantiation of the efficacy of phytochemicals must be more relaxed than that of drugs."5  Since saw palmetto berries have been consumed for a long time for medicinal purposes, including benign prostate hyperplasia and/or lower urinary tract symptoms, without known adverse or toxic effects and since a preparation of its extracts has been studied extensively in clinical trials without any statistically significant adverse effects when taken with meals, the safety of saw palmetto berry and proper extracts of the berry for use in benign prostate hyperplasia and/or lower urinary tract symptoms has been confirmed and is sufficient for approving them as a dietary supplement for such purposes.

Regarding the efficacy issue, as stated in Functional Foods: "Proving efficacy is perhaps the most difficult aspect of the phytochemical matter.  In many cases, the required degree of proof for drugs is not obtainable with phytochemicals, simply because the risk/reward ratio is too great to justify subjecting seemingly healthy humans to the testing conditions of a drug test.  In drug clinical trials, the expected relief from the suffering and/or the expected reduction of the risk of death from a disease may justify the risk of trying an unproven drug; but in the case of phytochemicals and/or functional foods there is a lack of strong justifications for risk taking."  Thus, when consider a health claim for saw palmetto berry and/or its extracts the government must lower the standard that is required for drug approval.  The above discussions clearly demonstrate that a preparation of saw palmetto berry extract is effective in mitigating benign prostate hyperplasia and/or lower urinary tract symptoms, though not as potent as many dwgs used in treating other diseases.  (However, the commonly used drug for BPH/LUTS, finasteride is only as effective as saw palmetto berry.)  Considering that saw palmetto berries have been used for similar purposes for a long period of time, it is appropriate to generalize the efficacy to other properly prepared saw palmetto berry preparations.  The combined evidence of efficacy of saw palmetto berry and proper extracts of the berry for use in benign prostate hyperplasia and/or lower urinary tract symptoms is adequate for approving them as a dietary supplement for such purposes.

Looking at it from another angle, BPH and LUTS are not life threatening diseases.  As a matter of fact, even the so-called "watchful waiting" is considered an acceptable alternative for the patients to take!  The treatment of these conditions does not require drugs of high potency and of very precisely quantified efficacy.  This is in contrast with the treatment of many other diseases, e.g., treating Type I diabetes with insulin, for which precisely metered doses must be dispensed timely.  The primary concern here is safety, including that the treatment does not affect the detection of much more serious and may be deadly prostate cancer (e.g., not affecting serum PSA level).  Saw palmetto berry and its extracts are very safe and do not affect PSA level.  Thus, saw palmetto berry and its extracts can be valuable dietary supplement for use in the mitigation and/or risk reduction of benign prostatic hyperplasia and lower urinary tract Symptoms.  Even though the efficacy of the berry and its extracts is not as precisely substantiated.

Summary

The available information supports the safety, efficacy, and stability of saw palmetto berry and properly prepared saw palmetto berry extracts for use in mitigating and/or reducing the risk of benign prostatic hyperplasia and/or lower urinary tract symptoms.  There is substantial scientific agreement among experts on thiswatter.  Approval of a health claim that such a product may mitigate and/or reduce the risk of benign prostatic hyperplasia and lower urinary track symptoms is of substantial public interest and is of great economic importance.

References

1.         Kawachi I, Barry MJ, Giovannucci E, Rimm EB, Colditz GA, Stampfer MJ, and Willett WC.  1996.  The impact of different therapies on symptoms of benign prostatic hyperplasia: a prospective study.  Clin. Therap. 18:1118-27.

2.         Berry SJ, Coffey, Walsh PC et al. 1984.  The development of human benign prostatic hyperplasia with age.  J Urology 132:474-9.

3.         Murray M and Pizzorno J.  1994.  Encyclopedia of Natural Medicine.  John Bastyr University Publishing.  Seattle.

4.         J. Kloss, author, Back To Eden Books, publisher.  Loma Linda, California.

5.         Lin RIS.  1994.  "Phytochemicals and Antioxidants" in Functional Foods (Goldberg I. ed., Chapman & Hall publ., New York).

6.         Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, and Mulrow C.  1998.  Saw palmetto extracts for treatment of benign prostatic hyperplasia.  J. Am. Med. Assoc. 280: 1604-9.

7.         See the FDA appoved brochure accompanying the drug PROSCAR.

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

9.         Reece Smith H, Amemon, CJ Smart, and K Dewbury.  1986.  The value of Permixon in benign prostatic hypertrophy. Br. J. Urology. 58:36-40.

10.       Stenger A, Tarayre J-P, Carilla E et al.  1982.  Pharmacologic and biochemical study of the hexane extract of Serenoa repens B(PA109).  La Gazette Medicale de France 89:2041-8.

11.       Rhodes L, Primka RL, Berman C et al.  1993.  Comparison of finasteride (Proscar), a 5-a reductase inhibitor, and various commercial plant extracts in in vitro and in vivo 5-a reductase inhibition.  Prostate 22:43-51.

12.       Fitzpatrick JM and Lynch TH.  1995.  Phytotherapeutic agents in the management of symptomatic benign prostatic hyperplasia.  Adv. Benign Prostatic Hyperplasia 22:407-12.

13.       Carraro JC, JP Raynaud, G Koch, GD Chishom, F Di Silverio, P Teillac, FC Da Salva, J Cauquil, DK Chopin, FC Hamdy, M Hanus, D Hauri, A Kalinteris, J Marencak, A Perier, and P Perrin.  1996.  Comparison of phytotherapy (Permixon) with Finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients.  Prostate 29:231-40.

14.       Bach D, Schmitt M, Ebeling L. 1997.  Phytopharmaceutical and synthetic agents in the treatment of benign prostatic hyperplasia (BPH).  Phytomed. 3-4:209-13.

15.       Lowe FC, Dreikorn K, Borkowski A, Braeckman J., Denis L, Ferrari P, Gerber G, Levine R, Perrin P, and Senge T.  1998.  Review of recent Placebo-controlled trials utilizing phytotherapeutic agents for treatment of BPH.  Prostate 37:187-93.

16.       Descotes JL, Rambeaud JJ, Deschaseaux P, and Faure G.  1995.  Placebo-controlled evaluation of the efficacy and tolerability of Permixon in benign prostatic hperplasia after exclusion of placebo responders.  Clin. Drug Invest. 9:291-7.

17.       Schulze H, Berges H, Paschold K, et al.  1982.  Neue konservative Therapieausaetze bei der benignen Prostahyperplasiie.  Urologe A 31:8-13.

18.       Gerber GS, Zagaja GP, Bales GT, Chodak GW, and Contreras BA.  1998.  Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms.  Urology 51:1003-7.

19.       Goepel M, Hecker U, Krege S, Rubben H, Michel MS.  1999.  Prostate 38:208-15.

20.       Shimada H, Tyler VE, and Mclaughlin JL.  1997. Biologically active acylglycerides from the berries of saw-palmetto.  J.Nat. Prod. 60:417-8.

21.       Elghamry MI, Hansel R.  1969.  Activity and isolated pgytoestrogen of shrub palmetto fruits (Serenoa repens Small): an estrogenic plant.  Experientia 24:828-9.

22.       Miller L.  1998.  Herbal Medicinals:  Selected clinical sonsiderations focusing on known or unknown drug-herb interactions.  Arch. Intern. Med. 158:2200-2211.

23.       Tasca A.  1985.  Treatment of Obstruction in prostatic adenoma using an extract of Serenoa repens: double-blind clinical test vs placebo.  Minerva Urol. Nefrol. 37:887-91.

24.       Braeckman J, Denis L, de Leval J, Keuppens F, Cornet A, De Bruyne R, De Smedt E, Pacco J, Timmermans L, Van Vliet P, Bruhwyler J, Kaufman L, Derde MP.  1997.  A double-blind, placebo-controlled study of the plant extract Serenoa repens in the treatment of benign hyperplasia of the prostate.  Europ. J. Clinical Res. 9:247-59.

25.       Lowe FC and Ku JC.  1996.  Phytotherapy in treatment of benign prostatic hyperplasia: a critical review.  Urology 48:12-20.

26.       Romics I, Schmitz H, Frang D.  1993.  Experience in treating benign prostatic hypertrophy with Serenoa serrulata for one year.  Intern. Urol. Nephrol. 25:565-9.

27.       Carbin BE, Larsson B, and Lindahl O.  1990.  Treatment of benign prostatic hyperplasia with phytosterols.  Brit. J Urolo. 66:639-41.

28.       Champult G, Patel JC, & Bonnard AM.  1984.  Adouble-blind trial of an extract of the plant Serenoa repens in benign prostatic hyperplasia.  Br. J Clin. Pharmac. 18:461-2.

29.       Boccafoschi C and Annoscia.  1983.  CONFRANTO FRA ESTRATTO DI SERENOA REPENS E PLACEBO MEDIANTE PROVA CLINICA CONTROLLATA IN PAZEINT CON ADENOMATOSI PROSTATICA.  Urology 50:1257-68.

30.       Emili E, Cigno ML, & Petrone U.  1983.  RISULTATI CLINICI SU UN NOUVO FARMACO NELLA TERAPIA DELL'IPERTROFIA DELLA PROSTATA (PERMIXON).  (Terapia Medica)  Urologia 50:1042-8.

31.       Mandressi A, Tarallo U, Maggioni A, Tombolini P, Rocco F, Quadraccia S.  1983.  TERAPIA MEDICA DELL'ADENOMA PROSTATICO: CONFRONTO DELLA EFFICACIA DELL'ESTRATTO DI SERENOA REPENS (PERMIXON) VERSUS L'ESTRATTO DI PIGEUM AFRICANUM E PLACEBO.  (Terapia Medica) Urologia 50:752-7.

Dr. Robert I-San Lin, Ph.D., CNS, FICN

Box 50632, Irvine, CA 92619-0632, USA

Fax 714-8546170, tel 714-8544855, e-mail: drlin@juno.com

Education:                    Ph.D.   UCLA. 1968. Biophysic & Nuclear Medicine.  Studied under Nobel Laureate, Willard Libby.  Conducted research on mechanisms, treatment, and prevention of injuries caused by nuclear radiations; physiological mechanisms of steroid hormones; synthesis of subcellular organells; and regulation of gene expression.

M.S.    UCLA. 1968. Plant biochemistry.

B.Sc.    National Taiwan University. Premedical Science.

Postdoctoral training:                California Institute of Tchnology.  1968-70.  Conducted research on mmoleuclar biology and biotechnology in Norman Davidson's team, which includes Philip Sharp (postdoctoral trainee then and later Nobel Laureate) and Louis Chow (a graduate student then and later one the hihest honor awardee, American Chemical Society)

UCLA Medical Center.  1970-71. nutrition and metabolic diseases.

Massachusettes Institute of Technology. 1971-72.  Nutrition.

Executive training:                                 Harvard University. 1973.

Leadership training:                               University of Maryland/Center for Creative Leadership.  1982.

Employment Histroy:                 Nutrition International Co.  1990-present.  Executive Vice President in charge of matters related science and technology in the biomedical field, including: research in biomedical field (vitamins, minerals, herbs, phytochemicals, hormones, intermediate metabolites), regulatory affairs, and product development.

Weider Health & Fitness Co.  1988-90.  Senior Vice President in charge of matters related science and technology related to sport physiology, sport medicine, and sport nutrition.

Makers of Kal Co.  1986-88.  Senior Vice President in charge of matters related science and technology related to vitamins, minerals, herbs, phytochemicals, hormones, and intermediate metabolites.

Moxie Industry, Inc.  1984-86.  Vice President in charge of matters related science and technology, and product development in vitamins, minerals, herbs, phytochemicals, hormones, intermediate metabolites, and regulatory affairs.

Richardson-Vicks, Inc.--Natural Product Division.  1982-84.  Vice President and Director of Nutrition in charge of matters related to the sciences and technology of vitamins, minerals, herbs, phytochemicals, hormones, intermediate metabolites), and development of drugs and dietary supplements.

PepsiCo, Inc./Frito-Lay.  1975-82.  Chief Scientist in charge research in biomedical, nutritional, and food science; and development of new nutritional and food products.

Worthington Biochemical Division of Millipore, Inc.  1973-75.  Director of Research in charge of research in application of enzyme in biomedical field and development of products for enzyme treatment and diagnosis of diseases.

GTE Laboratories.  1972-73.  Manager of Life Sciences in charge of biomedical research, including biomedical effects of nonionizing radiations, development of medical equipments.

Professional Activities:              Founding member and a current Director of the Certification Board for Nutrition Specialist.  Hve written many questions for the certification examinations to be taken by candidate nutritionists with advanced degrees and 3 years of experience.

Advisor, Chinese Society of Food Science and Technology.

Organized and Chaired the session on biological oxidation in health and disease of the 6th World Congress on Clinical Nutrition.  1997.  Canada.

A member of the Nutrition Federation of California.

Organized the First World Congress on the Health Significance of Garlic and Garlic Constituents.  1990.  Washington, D.C.

Organized the session on nutrition of the 7th World Congress of Food Science and Technology.  1987.  Singapore.

Organized and Chair a conference on the nutritional and medicinal properties of Chinese medicinal herbs.  1977.  San Francisco.

Professional Membership:         American College of Nutrition.

International College of Nutrition (Fellow).

American College of Sports Medicine.

Sigma Xi/Research Society of America (life member).

New York Academy of Sciences (life member).

The Nutrition Society (Republic of China).

The Obesity Society (China).

Publications (Partial List)

1.         Steiner M, Khan AH, Holbert D, Lin RIS.  1996.  Abouble-blind crossover study in moderately hypocholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids.  Am J Clin Nutr 64:866-70.

2.         Lin RIL.  Comments on standardization of garlic products.  A chapter in the Proceedings of The First World Congress on the Health Significance of Garlic and Garlic Constituents. 1990.

3.         Lin, R.I.S. 1987. Lipid Nutrition and Cardiovascular Diseases. in Trends in Nutrition and Food Policy, A.H. Ghee ed.-in-Chief, K.W. Lu and K.A. Kim eds. Singapore National University Press.

4.         Lin RIS.  1986.  Garlic: New Perspectives.  A book available form Nutrition International Co.  P.O. Box 50632, CA 92619-0632, U.S.A.

5.         Qureshi AA, Lin RIS, Abuirmeileh N, and Qureshi N.  Inhibition of cholesterol synthesis by Kyolic (aged garlic extract) and S-allyl cysteine in a hypercholesterolemic model.  A chapter in the Proceedings of The First World Congress on the Health Significance of Garlic and Garlic Constituents. 1990.

6.         Qureshi N, Lin RIS, Abuirmeileh N, and Qureshi AA.  Dietary Kyolic (aged garlic extract) and S-allyl cysteine reduces the level of plasma triglycerides, thromboxane B2 and platelet aggregation in a hypercholesterolemic model.  A chapter in the Proceedings of The First World Congress on the Health Significance of Garlic and Garlic Constituents. 1990.

7.         Lee ES, Steiner M, and Lin RIS.  Thioallyl compounds: Potent inhibitors of cell proliferation.  Biochim Biophys 1994; 1221:73-77.

8.         Freeman F, Huang GB, Lin RIS.  Garlic Chemistry.  Nitric oxide oxidation of S-(2-propenyl)cysteine and (+)-S-(2-propenyl)-L-cysteine sulfoxide.  J Org Chem 1994; 59:3227-9.

9.         Liu J, Lin RI, Milner JA.  Inhibition of 7,12-dimethylbenz(a)anthracene-induced mammary tumors and DNA adducts by garlic powder.  Carcinogenesis 1992; 13:1847-51.

10.       Li G, Qiao CH, Lin RI, Pinto J, Osborne MP, Tiwari RK.  Anti-proliferative effects of garlic constituents in cultured human breast cancer cells.  Oncology Rep 1995; 2:787-91.

11.       Hoon DSB, Sze L, Lin RI, Irie RF. Modulation of cancer antigens and growth of human melanoma by aged garlic extract.  A chapter in the Proceedings of The First World Congress on the Health Significance of Garlic and Garlic Constituents. 1990.

12.       Lin RIL, Phytochemicals and Antioxidants.  A chapter in Functional Foods, I. Goldberg, ed., Chapman & Hall, New York. 1994

13.       Shjeide A & Lin RIL. Synthesis of Cytomembranes.  A chapter in Cell Differentiation.  Shjeide A & De Vries, ed. Mosby, New York. 1969.

14.       Lin RIS.  1994.  Pharmacological Properties and Medicinal use of Pepper (Piper nigrum L.).  (A chapter in Spices, Herbs, and Edible Fungi.  G. Charalambous, ed., Elsevier, publ., New York.)