May 25, 1999
PETITIONERS: Julian M. Whitaker, MD; Durk Pearson and Sandy Shaw;American Preventive Medical Association; and Pure Encapsulations, Inc.

ADDRESS: c/o Emord & Associates, P.C.
1050 Seventeenth Street, NW, Suite 600
Washington, DC 20036
SUBJECT: Petition for Health Claim: Saw Palmetto and Benign Prostatic Hyperplasia
Food and Drug Administration
Office of Food Labeling (HFS-150)
200 C Street, SW
Washington, DC 20204

I. Introduction and Statement of Purpose

The undersigned, Julian M. Whitaker, M.D.; Durk Pearson and Sandy Shaw; the
American Preventive Medical Association; and Pure Encapsulations, Inc. (Petitioners),
pursuant to Section 403 (r)(5)(D) of the Food, Drug & Cosmetic Act (FDCA) (21 USC §
343(r)(5)(D)), submit this petition for a health claim concerning the relationship between
the consumption of saw palmetto dietary supplements and Benign Prostatic Hyperplasia
(BPH). Attached hereto, and constituting a part of this petition, are all of the items
specified in 21 CFR 101.70 (f). The text of the proposed model claim is set forth in section III of this petition.
Petitioners believe that this petition represents a logical and valid evaluation of the
scientific studies and clinical trials involving saw palmetto and BPH symptom reduction.
Saw palmetto has been shown to be efficacious in reducing nocturia (frequent nighttime
urination) and voiding urgency and frequency, commonly associated with mild to moderate
BPH. The aging of the American population and the high likelihood of men developing BPH as they age make it imperative that safe, efficacious and cost-effective treatments for
BPH be identified and made widely known and available if health care costs are to be
contained and if a significant segment of the US male population is to enjoy a quality of life
in later years. Permitting a health claim that links consumption of saw palmetto dietary
supplements with reduction of symptoms of BPH is consistent with the US Department of
Health and Human Services (HHS) policy to meet the health needs of the aging US
population and reduce the health care burden on older Americans. In testimony before the
Senate Committee on Health, Education, Labor and Pensions, Subcommittee on Aging,
March 3, 1999, Jeanette C. Takamaura, Assistant Secretary for Aging, HHS, expressed that
policy, stating "older Americans should enjoy a `good quality of life and optimal health."
The federal government has also set as policy objectives improvement in "access,
quality, effectiveness, and outcomes of health care." Agency for Health Care Policy and
Research (AHCPR) "Benign Prostatic Hyperplasia: Diagnosis and Treatment," AHCR
Publication Number 94-0580. Permitting the proposed health claim on saw palmetto
dietary supplement labels and labeling will advance accomplishment of those objectives by
providing the public accurate information concerning a safe, inexpensive and effective
modality to reduce the symptoms of a condition that affects millions of male Americans.
Permitting the proposed health claim would enhance older male American independence,
decrease treatment costs, and improve health outcomes. It would also provide older male
Americans a greater choice of health improvement modalities.
A low cost, safe and effective treatment for BPH is in the interest of public health.
Urinary problems caused by BPH are common in older men, most frequently occurring
after age 60 (Ref. 1). Untreated BPH is associated with risk of urinary retention and infections (Refs. 1, 15, 19). In addition, normal life routines are disrupted by incontinence and other manifestations of bladder outlet obstruction (Refs. 1, 15, 19). BPH is not a condition that resolves with "watchful waiting" (Ref. 16). Using saw palmetto dietary supplements improves urologic symptoms and, thus, may decrease the risk of undesirable consequences. Adult male consumption of 320 mg/day of saw palmetto is, therefore, preferable to failure to treat mild to moderate symptomatic BPH.
For mild to moderate BPH symptom relief, saw palmetto is also preferable to reliance on synthetic pharmaceutical agents: finasteride and alpha blockers. Saw palmetto extract is a safer and more cost-effective mode of BPH treatment than use of those drugs. Impotence, ejaculation problems and decreased libido are adverse effects associated with finasteride treatment (Agency for Health Care Policy and Research (AHCPR), "Treating Your Enlarged Prostate, "AHCPR Publication No. 940584, 1994). Fatigue, vertigo, syncope, and hypotension are adverse effects associated with alpha-blockers. (Physician's Desk Reference, 48'h Ed. pp. 427-28, 1782-83, (Montvale, NJ: Medical Economics Data Production Company, 1994)). Wilt, et al., systematically analyzed eighteen clinical trials
and concluded that "compared to finasteride, S repens [saw palmetto] produces similar improvement in urinary tract symptoms and flow measures, has fewer adverse treatment effects, and costs less" by approximately $300 per person annually (Ref. 26; Attachment 2, "The Safety, Efficacy, and Stability of Saw Palmetto for the Treatment of Benign Prostatic 1-Iyperplasia and Lower Urinary Tract Symptoms in Men," by Drs. Robert I-San Lin and Lucinda G. Miller (Dr. Lin Report)). In addition, finasteride therapy may not be suitable for men with mild to moderate BPH. Boyle, et al., conducted a meta-analysis of six randomized trials of at least one year of finasteride compared to placebo in the treatment of BPH. That analysis revealed that finasteride was less effective in men with proportionately smaller prostates (Ref. 4). Moreover, Saw palmetto use does not produce the side effects associated with alpha blockers, such as postural hypotension (3.9%) and tachycardia (0.9%) (although side effects have been minimized with the newer alpha blocker, tamsulosin). (Refs. 17, 23, 20, 26; Dr. Lin Report at 2). Furthermore, saw palmetto does not affect serum prostate-specific antigen (PSA) levels whereas finasteride reduces PSA levels obscuring its utility as a tumor marker for prostate cancer (Facts and Comparisons, Finasteride monograph, St. Louis, MO: Facts and Comparisons, Inc. 1999). 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," NEJ.LI, 327:1185-91, 1992.) (Refs.7, 14; Dr. Lin Report at 2).2
A consumer's annual cost of 320 mg/ day of saw palmetto extract supplementation
is approximately $228.00 - $357.00. That cost is significantly less than a consumer's annual cost for 5mg/day of finasteride ($657.00) and 5mg/day of alpha blockers (Hytrin) ($566-665) (RS, McCaleb RS, "Medicinal Plants for Healing the Planet: Biodiversity and Environmental Health Care," Biodiversity and Human Health, Grifo and Rosenthal (Eds.), (Island Press: Washington, DC, 1997) pp. 221-242, 359; Murray MT, "Understanding the benefits of standardized botanical extracts," Ani J Vat Med 3: 6-12, 1996; and Published "Average Wholesale Price;" Dr. Lin Report at 2). Considering efficacy, cost effectiveness, and the low risk of side effects compared to the use of pharmacologic BPI-I agents, saw palmetto use in response to the proposed claim would clearly serve national policy(Dr.Lin
Report at 1,3,and 4).
Scientific data strongly support the claim that daily consumption of 320 mg of saw
palmetto reduces symptoms of BPH (nocturia and voiding frequency) with little or no side
effects or interactions with other drugs (Attachment 4, Commission E Monograph on Saw
Palmetto, January, 1991). Mild and transient gastrointestinal side effects, such as diarrhea,
constipation, nausea and vomiting, predominate affecting 25 patients in one study with an
overall incidence of <5% (Ref. 5) Other less frequently reported effects include dizziness,
insomnia, fatigue, muscular pain, breathlessness, and dry mouth (Ref. 5). More than 19
human studies between 1983 and 1998, taken as a whole, indicate that the petitioned claims
should be authorized (See Tables 1 and 2; Dr. Lin Report at 34). Standardized formulations
of saw palmetto are widely available and have been used safely in the US and Europe for
decades (Dr. Lin Report at 5, 12, 16, and 21; Attachment 3). As demonstrated in this
petition, a large body of scientific evidence documents the beneficial effects of saw
palmetto extract dietary supplements for persons exhibiting symptoms of mild to moderate
BPH.
Petitioners believe that truthful, succinct, and specific information of the type
proposed in this Petition will enable consumers to make prudent and effective choices about
their health care and lifestyles. Labeling and advertising for the saw palmetto dietary
supplement health claim would augment previously published statements by DHHS aimed
at increasing the older male population's knowledge of available treatments for reducing the
effects of BPH (AHCPR Publication No. 940584, 1994).

Consistent with the decision in Pearson v. Shalala, 164 F.3d 650, (D.C. Cir. 1999),
reh'g denied en banc, No. 98-5043, 1999 U.S. App. LEXIS 5954 (Apr. 2, 1999), Petitioners respectfully request that in its action on this petition agency define "significant scientific agreement" in 21 CFR § 101.14 by articulating clearly the principles that guide the agency
in reaching its decisions such that the Petitioners can perceive the degree, quality, and
nature of evidence FDA expects to satisfy its standard. In addition, and consistent with Pearson, if the agency finds the proposed claim not to satisfy "significant scientific agreement," the Petitioners request that the agency authorize the claim nevertheless, with such disclaimer or disclaimers as the agency reasonably deems necessary to avoid a potentially misleading connotation.
II. Preliminary Requirements
A. Saw palmetto extract meets the definitions of 21 CFR 101.14(a) and (b).
This petition seeks approval of the proposed claim for use on dietary supplements of Saw Palmetto extract manufactured in accordance with accepted industry standards and in compliance with USP specifications in the revised United States Pharmacopoeia (USP) saw palmetto monograph (1997) (Attachment 3). Saw Palmetto extract meets the definition of
"substance" provided by 21 CFR 101.14(a). Substance is defined as a specific food or a component of food, regardless of whether the food is in conventional food or dietary supplement form. The subject of this petition is the n-hexane lipidosterolic extract of the pulp and seed (fruit) of the dwarf American palm, Seronoa repens. It is a mixture of free fatty acids and their esters, small quantities of phytosterols, and various other polyprenic compounds, ( Ref. 17; Dr. Lin Report at 24; Attachments 3 and 4). The FDCA defines the term "dietary supplement as:

a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients:
(A) a vitamin;
(B) a mineral;
(C) an herb or other botanical;
(D) an amino acid;
(E) a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or
(F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), (D), or (E).
21 U.S.C.A. § 321(ft).
The extract of the saw palmetto is a botanical intended to be orally ingested. It therefore
meets the statutory definition of a dietary supplement.
B. Saw palmetto extract is associated with reducing symptoms of
benign prostatic hyperplasia, a major health-related condition.

The petitioned claim states that saw palmetto extract may reduce the symptoms of
mild to moderate BPI-I. BPH is a health-related condition and a disease for which the
general male population over age 50 is at risk. BPH is a benign adenomatous hyperplasia of
the periurethral prostate gland that occurs as men age. In BPH, the prostate develops
multiple fibroadematous nodules that displace other prostate tissue causing pressure against the urethra. As that pressure increases, the diameter of the urethra lumen is compromised and progressively obstructs urine outflow. Incomplete bladder emptying can cause stasis of urine in the lower urinary tract and "predisposes [it] to infection with secondary inflammation changes in the bladder and upper urinary tract" (Ref. 19).

BPH is "an almost universal phenomenon in aging men" (Ref. 15). Symptomatic

prostatic hyperplasia is very common, affecting more than one-half of men over age 60
(Agency for Health Care Policy and Research (AHCPR), "Treating Your Enlarged Prostate, "AHCPR Publication No. 940584, 1994) and 40-50% of all American men over
the age of 50 (Berry SJ, Coffey DS and Walsh PC, "The Development of Human Benign
Prostatic Hyperplasia with Age," J Urol, 132: 474 (1984). In fact, by the year 2000, in as
many as 9 million men will likely suffer from urologic symptoms associated with BPH
(US Bureau of the Census, "Resident Population of the United States, by Age and Sex,"
December 28, 1998; (Jacobson et. al. "New diagnostic and Treatment Guidelines for
Benign Prostatic Hyperplasia, Potential Impact in the United States, Arch Intern Med, 155:
477-481, 1995)). In ten years, the population of males over age 50 is estimated to grow to
42.1 million, an increase of more than thirty percent (Bureau of Vital Statistics (1998)
www.census.gov/population/estimates/nation). That increase in the older adult male
population means that in the near future more than 20 million men may be affected by
symptomatic BPH. Without question, BPH is a major health-related condition.
C. Saw palmetto is safe and conforms with 21 CFR § 101.14 (b)(3)(ii).

Saw palmetto extract has been safely used as a dietary supplement for decades
(Refs. 17, 20, 21, 27; Dr. Lin Report at 1). In Germany and Austria, phytotherapy is a first
line treatment for mild to moderate lower urinary tract symptoms and represents more than
90% of all therapies prescribed for BPH (Lowe 1996). The Commission E Monograph
(1991) states that there are no known interactions with other drugs and there are no known
contraindications for the use of saw palmetto extract (Refs. 17, 20, 21; Attachment 4). The
Commission E Monographs also indicates that the only known side effect associated with
the use of 320 mg /day of saw palmetto is "stomach problems" but such problems are said
to occur rarely. Saw palmetto has not been found to affect blood chemistries (Ref. 7; See
also, Newall CA, Anderson La, Phillipson JD eds. Herbal Medicines: A guide for health
care professionals. London: The Pharmaceutical Press 1996; 237-38). A search via
Medline revealed no reports of allergicinity associated with saw palmetto use. A search
of the database "Special Nutritionals Adverse Event Monitoring System" established by
the FDA for reporting by both health care providers and consumers disclosed no
allergicinity citations (Dr. Lin Report at 10).
In a meta-analysis of eighteen clinical trials that involved 2939 men, Wilt et al.
(1998) found that adverse effects due to saw palmetto were generally mild and comparable
with placebo (Ref. 26). The results of the 1986 study by Reece-Smith, et al. (1986)
confirmed the safety of 320mg/day of saw palmetto extract even though the efficacy data
are contrary to the findings of the other studies that support the association between saw
palmetto and BPH symptoms (Ref. 23). Based on the totality of the evidence, saw palmetto
qualifies as a safe dietary supplement (See also Ref. 21; Dr. Lin Report at 5-11).
Saw palmetto was shown to be safe in doses exceeding the 320 mg/ day identified in
the health claim (Ref. 21; Dr. Lin Report at 6-8). Saw palmetto has consistently been shown
to be safer and cause less adverse effects than the leading pharmaceutical agent, finasteride,
for treatment of mild to moderate BPH. Although impotence and ejaculation disorders have
been reported in patients taking saw palmetto (0.32%), the incidence of those side effects is
ten times more prevalent with finasteride (3.95 and 2.8%, respectively) (Refs. 4,7,21,26).
Finasteride side effects of breast tenderness and enlargement have not been reported with
saw palmetto (Ibid. "Facts and Comparisons").
The amount of saw palmetto extract necessary to justify a health claim (i.e., 320
mg/day) is expected to be consumed from dietary supplements clearly labeled with
recommended doses and serving sizes. The extract does not normally occur in conventional foods and, therefore, amounts that would reasonably be expected to be consumed in a day
are not likely to exceed known safe levels. Approval of the proposed health claim would
not result in potential consumption in excess of safe levels for saw palmetto extract dietary
supplements (Dr. Lin Report at 11).

III. Scientific Data Supporting the Proposed Claim

A. Significant scientific agreement exists to support the proposed claim.

There exists significant agreement among medical researchers and experts who
study the field of phytotherapeutic agents that an association between saw palmetto and
BPI-I exists. The n-hexane lipidosterolic extract of saw palmetto reduces the symptoms of
BPH, specifically urinary flow rate and post-void residual volume. Saw palmetto's
mechanism of action has not been conclusively determined. There is agreement among
scientists, however, that saw palmetto produces a relief of symptoms without affecting the
size of the prostate, presumably by antiandrogenic activity, inhibition of
dihydrotestosterone binding, and inhibition of 5-a-reductase activity on testosterone
(Ref.17, 20, 21, 22, 26; Dr. Lin report at 25). (See also, Elghamry MI, Hansel R, `Activity
and isolate phytoestrogen of shrub palmetto fruits (Serenoa repens Small), a new estrogenic plant," Experentia, 25:828-9, 1969; 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" Eur Urol, 21:309-14, 1992; and Sultan C, "Inhibition of
androgen metabolism and binding by a liposterolic extract ofSerenoa repens B in human
foreskin fibroblasts," JSterol Biochem Mol Biol,20:515-19, 1984.)

Because saw palmetto is a complex mixture of several compounds, pharmacokinetic data is difficult to obtain. Plasma concentrations of one of the components (unspecified; referred to as "component two")

were measured in 12 fasting healthy young men volunteers (mean age: 24 years) after administration of 320mg/ day of saw palmetto. Peak plasma concentrations of 2.6 mg/dl were obtained with 1.5 hours with results as measured by the "area under the curve" (AUC) of 8.2mg/l/h and elimination half-life of 1.9 hours (DeBemardi di Valserra M, et. al., "Serenoa repens capsules: a bioequivalence study," Ada Toxicol Ther, 15:21-39, 1994.) Oral administration to rats of 14C-labelled oleic or lauric acid or beta-sitosterol with saw palmetto demonstrates preferential uptake with higher concentrations found in the prostate gland than the liver, seminal vesicles or other genitourinary tissues ( Ref. 21).
The results of a meta-analysis of 18 randomized placebo controlled studies involving 2939 men, indicate that saw palmetto significantly improves the urologic symptoms associated with BPH (Ref. 26). As compared to placebo, patients taking saw palmetto had decreased nocturia (weighted mean difference (WMD) -1.41 points (scale 0.76 times per evening) and increased peak urine flow (WMD, 1.93 ml/s). When
compared to finasteride, men treated with saw palmetto had similar improvements in peak urine flow (W1'vlD, 0.74 ml/s) and improvements in urinary tract symptom scores (WMD 0.37 International Prostate Symptom Score points (scale range, 0-25)). Very few, and minor, side effects were associated with saw palmetto. Specifically, gastrointestinal side
effects occurred at a rate (1.3%) approximating that of finasteride (1.5%) (Ibid, Wilt 1998). In this report, consistent with other studies, erectile dysfunction occurred more frequently in patients taking finasteride (4.9%) than saw palmetto (1.1%) (Ref. 26). In a meta-analysis of 7 double blind placebo studies of saw palmetto, the treatment groups experienced a 33-74% decrease in nocturia compared to only a 2-35% decrease in those symptoms in the placebo groups (Ref. 17).

In clinical trials, saw palmetto significantly reduced the subjects' nocturia, reduced
voiding urgency, and improved urinary flow (Tables 1 and 2; Dr. Lin Report at
12,16,19,26).

TABLE 1: DOUBLE -BLIND PLACEBO CONTROLLED STUDIES

	DURATION/	NOCTURNAL	CHANGE IN	CHANGE IN PVR
STUDY	SIZE	FREQUENCY	FLOW RATE	(ml)
	Dose per day	(days)	(ml/sec)
Boccafoschi	2 months	-2.2 A	4.1 A	-48 A
1983	N=22	-1.0 P	1.9 P	-29.2 P
	320mg
Braeckman	3 months	NA	NA	NA
1997	N=238
	320mg
Carraro	6 months	NA	2.7 A	NA
1996	N=1098		3.2F
	320mg
Carbin	3 months	-0.6 A	3.0 A	-42.5 A
1990	N=1098	-0.1 P	0.3 P	-7.6 P
	320mg
Champault	1 month	-1.43 A	2.7 A	-42 A
1984	N=110	-0.5 P	0.3 P	-9 P
	320mg
Cukier	2 months	-1.1 A	NA	-16 A
1985	N=146	-0.5 P		55 P
Descotes	1 month	-0.7 A	3.4 A	NA
1995	N=176	-0.3P	1.1 P
	320mg
Emili	1 month -	-1.65 A	14 A	-36 A
1983	N=30	-0.35 P	0.2 P	-12 P
	320mg
Gabric and Miskic 1987	6 weeks	NA	4 .1 A	-5.7 A
	N=59		-0.8 P	-4.8 P
	Combination
Mandressi 1983	1 month	2.6 A	1.42 A	-1.11 A
	N=59	0.96 P	1.11 P	-1.00 P
	320mg
Tasca	1-3 months	-2.6 A	3.3 A	NA
1985	N=30	-1.2 P	0.6 P
	320mg
AVERAGES:		-1.61 A	3.12 A	-27 A
		-0.53 P	0.58 P	-1.2 P
			3.2 F

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

TABLE 2. ADDITIONAL STUDIES

Study	Type of	Duration	Saw	Nocturnal	Change in	Change
	Study	of Study	Palmetto	frequency	flow rate	in PVR
	Patient		Dose	(days)	(ml/sec)	(ml)
	Number
Bach 1996	multicenter,	3 years	320	73.3%	6.1	32
	prospective,		mg/day	response;
	open-label;			specific
	n=315			amounts
				unspecified
Braeckman	prospective,	3 months	320	NA	2.4	7.2
1994	open-label;		mg/day
	n=305
Gerber	controlled	6 months	320	NA	-0.7	-9.3
1998	clinical trial;		mg/day
	n=50
Redecker	prospective,	3 months	320	2.15	3.4	11
1998	open-label;		mg/day	baseline
	n=60			micturition
				frequency;
				1.16 A
Romics	prospective,	12 months	320	37.8%	2.5	50.5
1993	open-label;		mg/day	response;
	n=42			specific
				amounts
				unspecified
Ziegler	prospective,	3 months	320mg/d	NA	2.44	36.9
1998	open-label,	-	ay
	multicenter;
	n=110

B. Scientific evidence demonstrates the BPH symptom reduction effects of Saw Palmetto extract.

Multiple clinical trials demonstrate the association between saw palmetto fiber and BPH
symptom reduction. See Tables 1 and 2. (Refs. 2,3, 5-11, 13, 18, 22-25, 28; Dr. Lin Report
at 12, 16, 19, 26). The studies have consistently shown that 320mg/day is a therapeutically
effective dose and improves urologic symptoms and flow measures with little or no side
effects.
• In a recent double blind placebo study the treatment group's International Prostate
Symptom Score (IPSS) was significantly lower than the scores of the placebo group
(Ref. 14). The mean International Prostate Symptom Score (IPSS) improved from 19.5
+ 5.5 to 12.5 + 7.0 (p<0.001). Those results confirm earlier findings of double blind
placebo studies demonstrating significant decreases in symptoms associated with BPH
(Refs. 3, 6, 8, 9, 11, 25).
• In a six month double blind randomized equivalence study that compared th_, effects of
saw palmetto with those of finasteride in 1,098 men with moderate BPH, both groups
experienced improved IPSS scores (-37% and -39%, respectively), improved quality of
life (by 38 and 41%, respectively), and increased urinary peak flow (+25% and +30%,
p=0.035 respectively). Saw palmetto extract gave rise to fewer complaints of sexual
dysfunction, decreased libido, and impotence than did finasteride (Ref. 7).
• Patients in a twelve month open study showed that saw palmetto significantly improves
obstructive symptoms, residual volume (from 62.8 ml to 12.3 ml; p<0.001), and flow
rates (from 5.2 ml/s to 7.7 ml/s; p<0.001) within six months of treatment initiation
(Refs. 24).
• 309 patients enrolled in a 3 year multicenter study experienced increased urinary flow
rate to 6.1 mI/s with a 50% decrease in residual urine volume (from 64 +2.3 ml to 32 + 2.0 ml; mean + SEM) while taking saw palmetto versus only a slight improvement in urine flow and no change in residual volume while taking finasteride. Furthermore, this study demonstrates a sustained effect of saw palmetto (Ref. 2).
By contrast, a 1986 double-blind trial of 70 subjects compared the effect of saw
palmetto extract to placebo and concluded "the results obtained offer no support to the
suggestion that [saw palmetto] is of benefit in prostatic hypertrophy" (Ref. 23). That
conclusion was based on subjects' self-assessments after 12 weeks of treatment. The
method of measuring flow rates and omission of standard deviation evaluation for the
treatment and placebo groups make unreliable any conclusions based on those results (Dr.
Lin Report at 5-8). In addition, the subjects interacted amongst themselves and between the
two groups and may have thereby broken the blinding (Dr. Lin report at 5-8). The
investigators found, however, that the "regime of [saw palmetto] used in th[e] trial was
safe, well tolerated and associated with considerable symptomatic improvement" (Ref. 23).
Insufficient data exist to determine whether saw palmetto prevents long-term
complications of BPH such as acute urinary retention or the need for surgery (Ref. 26).
Finasteride has proven effective in reducing the development of acute urinary retention and
the need for surgical resection in men with large prostates (i.e., >40 cc) (Boyle P, Gould
AL, Roehrbom CG. Prostate volume predicts outcome of treatment of benign prostatic
hyperplasia with finasteride. Urology 1996;48:398-405). (Mcconnell JD, Bruskewitz R,
Walsh P, et. al., The effect of finasteride on the risk of acute urinary retention and the need
for surgical treatment among men with benign prostatic hyperplasia. NEJM 1998;338:557-
63). Saw palmetto, however, is posited for initial treatment of BPH with milder symptoms.
The currently available scientific literature supports the proposed claim. FDA
should approve the proposed health claim based on the information provided above and
based upon the following factors:
• The preponderance of scientific evidence from randomized controlled trials indicate that
saw palmetto exerts a beneficial effect on urinary flow rate (3.12 ml/s versus 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 exceeds that seen with
placebo and is as effective as finasteride.
• Scientific evidence demonstrates that this beneficial effect is maintained for prolonged
periods up to at least three years.
• Side effects secondary to saw palmetto use appear to be limited and minimal. They
include primarily gastrointestinal side effects such as nausea, vomiting, constipation and
diarrhea. Other reported effects include dizziness, insomnia, fatigue, muscular pain,
breathlessness, and dry mouth. Although impotence and ejaculation disorders have
been reported in patients taking saw palmetto (0.32%), the incidence of those side
effects is ten times more prevalent with finasteride (3.95 and 2.8%, respectively). The
overall incidence of saw palmetto side effects is low (<5%).
• Interference with the utility of the prostatic antigen assay (PSA) as a marker for
prostatic cancer constitutes a public health issue. Finasteride significantly interferes
with the assay producing a 50% decrease in PSA levels following a 5 mg dose. Saw
palmetto does not affect PSA levels, an obvious public health advantage.
In sum, the data overwhelmingly substantiates the efficacy and safety of saw
palmetto to reduce symptoms of BPH.

IV. Proposed Model Claim

Petitioners propose the following Model Claim for saw palmetto extract dietary
supplement:
Consumption of 320 mg daily of Saw Palmetto extract may improve urine flow,
reduce nocturia and reduce voiding urgency associated with mild benign prostatic
hyperplasia (BPI-ij.

V. Attachments

Attached are copies of the scientific studies and other information referenced in, and
constituting the basis for, this Petition. To the best of the Petitioners' knowledge, all non‑
clinical studies relied upon were conducted in compliance with the good laboratory
practices regulations set forth at 21 CFR Part 58. To the best of the Petitioners' knowledge,
all clinical or other human investigations relied upon were either conducted in accordance
with the requirements for institutional review set forth at 21 CFR Part 56 or were not
subject to such requirements in accordance with 21 CFR §§ 56.104 or 56.105. To the best
of the Petitioners' knowledge, all clinical or other human investigations relied upon were
conducted in conformance with the requirements for informed consent set forth in 21 CFR
§ 50 et seq. See generally 21 CFR § 101.70 (c)-(d).

VI. Environmental Impact

The requested health claim approval contained in this petition is categorically
excluded under 21 C.F.R. § 25.24.

VII. Conclusion and Certification

For the foregoing reasons, the Petitioners request that the FDA approve the
proposed health claim. The Petitioners look forward to working with the FDA in
promulgating a regulation authorizing the use of a dietary supplement health claim
concerning the association between saw palmetto extract and benign prostatic hyperplasia
(BPH).
Any questions concerning this Petition may be directed to Jonathan W. Emord, Esq.,
Emord & Associates, P.C., 1050 Seventeenth Street, NW, Suite 600, Washington DC
20036, (202) 466-6937.
The undersigned certify on behalf of the Petitioners that to the best of their
knowledge and belief, the Petition includes all information and views on which the
Petitioners rely and is a representative and balanced submission that includes unfavorable
information as well as favorable information, known by the Petitioners to be pertinent to
evaluation of the proposed health claim.
Respectfully submitted,

JULIAN M. WHITAKER, M.D.; DURK PEARSON AND SANDY SHAW; AMERICAN PREVENTIVE MEDICAL ASSOCIATION; and PURE' ENCAPSULATIONS, INC.

By
Jonathan W. Emord
Eleanor A. Kolton
Their Counsel

Jonathan W. Emord
Eleanor A. Kolton
Emord & Associates, P.C.
1050 Seventeenth Street, N.W.
Suite 600
Washington, D.C. 20036
P: (202) 466-6937
F: (202) 466-6938
e-mail: Emordall@aerols.com
Date:

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