The Ethnobotany of Saw Palmetto (Serenoa repens (Bartr.) Small) in Florida

PAGE 1

THE ETHNOBOTANY OF SAW PALMETTO ( Serenoa repens (Bartr.) Small) IN FLORIDA BY BETHANY HIGHSMITH A Thesis Submitted to the Division of Natural Sciences New College of Florida In partial fulfillment of the requirements for the degree Bachelor of Arts in Environmental Studies Under the sponsorship of Dr. Amy Clore Sarasota, Florida May, 2009

PAGE 2

A cknowledgements Thanks to my sponsor, Dr. Clore for her continual support and long hours spent meticulously reading my rough drafts. I could not have asked for someone more thoughtful, intelligent, and caring to guide me through the writing process. Thanks to Dr. Andrews for teaching me ethnobotanical methods and encouraging me to pursue my interests. Thanks to Dr. McCord for shar ing his botanical knowledge and teaching me taxonomy. I am grateful to Dr. Portugal and Dr. Andrews for helping me with Spanish grammar. Thanks to Dr. Lowman for her ecological advice. Thanks to those at Aquatic Plants of Florida, Inc., without whom I never would have met people involved in saw palmetto be rry harvesting. A special thanks to Justin Sklaroff for his kindness and for taking me out into the scrub. Thanks to William VanGelder for sharing his vast knowledge of ecology and land management with me. Thanks to Arthur Kersey. I am especially i ndebted to Rosario Cordero for her patience, loyal friendship, emotional support, and help w ith my thesis. Thanks to Jose, Jesus and Nina. Thanks to my mother and sister for th eir careful readings and writing advice. Thanks to my friends Danielle Smith, La uren Caprio, David Anderson, Carli Cooper, Jenna Ervin, Eldridge Wisely, Ashley J ohnson, Chris Wilson, Corianne Etheredge, and Trevor Caughlin for their support and wise a dvice. I am especially grateful to Jesse Wheeler for her invaluable insight and lifelong friendship. Warm thanks to Rachel Renne, for showing me how to make saw palmetto crafts and drawing prostate illustrations. Thanks to Carol Mahler for the wealth of information she gave me about Seminole uses of saw palmetto. She was extremely thoughtful and an indefatigable source. Financial support was provided by the Environmental Studies Program. ii

PAGE 3

Table of Contents Page List of Figures......................................................................................................................v Abstract....................................................................................................................... ......vii Resumen........................................................................................................................ .....ix 1. Introduction to Saw Palmetto ( Serenoa repens Bartr. (Small))...................................... 1 1.1. Nomenclature.............................................................................................................. ..1 1.2. Life History.......................................................................................................1 1.3. Ecological Importance......................................................................................6 1.4. Fire and Reproduction.......................................................................................9 1.5. Fire Research Conducted by Abrahamson......................................................10 1.6. Resource Management....................................................................................12 1.7. Overview.........................................................................................................15 2. Historical Uses of Saw Palmetto....................................................................................16 2.1. Food................................................................................................................16 2.2. Fiber................................................................................................................18 2.3. Seminole and Miccosukee Crafts and Ceremonies.........................................20 2.4. Other Uses.......................................................................................................27 2.5. A Medical History...........................................................................................30 3. Benign Prostatic Hyperplasia a nd Lower Urinary Tract Symptoms.............................35 3.1. Hormonal Regulation of Prostatic Growth.....................................................39 3.1.1. Androgens........................................................................................39 3.1.2. Genetic Polymorphisms...................................................................40 3.1.3. Estrogens..........................................................................................43 3.2. Stromal-Epithelial Interactions.......................................................................43 3.3. Growth Factors................................................................................................43 3.4. Inflammation...................................................................................................45 3.5. Measures of Severity and Incidence...............................................................46 3.6. Treatment........................................................................................................46 4. Saw Palmetto as a Treatment for BPH and LUTS.........................................................49 4.1. Inhibition of COX Enzyme s and Lipid Peroxidation.....................................50 4.2. Cell Growth Inhibition....................................................................................51 4.3. Androgen Levels.............................................................................................52 4.4. Insulin-Like Growth Factors...........................................................................54 4.5. Other Clinical Trials.......................................................................................54 4.6. Meta-Analyses................................................................................................56 4.7. Placebo Effect.................................................................................................57 4.8. Adverse Effects...............................................................................................57 4.8.1. Cytochrome Inhibition.....................................................................59 iii

PAGE 4

Table of Contents (continued from iii) Page 5. Harvesting......................................................................................................................61 5.1. The Berry Boom.............................................................................................61 5.2 Collection Methods: Past and Present..............................................................62 5.3. Demographics.................................................................................................63 5.4. Brokerage........................................................................................................64 5.5. Trespassing.....................................................................................................65 5.6. The Market......................................................................................................66 5.7. Drying Methods..............................................................................................68 5.8. Sorting Berries................................................................................................69 5.9. Shipping..........................................................................................................69 5.10. Capitalism vs. Conservation.........................................................................70 6. Perspectives....................................................................................................................73 6.1. Improving Methodologies...............................................................................73 6.1.1. Quality Control................................................................................74 6.1.1.1. Batch Variation.................................................................75 6.1.1.2. European Regulations.......................................................75 6.1.1.3. Dosage Variation..............................................................76 6.1.2. Differentiating between BPH and Prostate Cancer..........................76 6.1.3. Designing Better Clinical Trials......................................................77 6.2. Other Ailments................................................................................................78 6.3. Managing the Crop.........................................................................................80 6.3.1. Punishing Poachers..........................................................................81 6.4. Does Saw Palmetto Extract Really Work?.....................................................82 References..........................................................................................................................83 Appendix..........................................................................................................................104 iv

PAGE 5

List of Figu res Page Figure 1.1. Stand of saw palmetto growing at average height (Plant Database website)....................................................................................2 Figure 1.2. Spiny petiole (Pla nt Database website).............................................................3 Figure 1.3. Inflorescences (Pla nt Database website)...........................................................4 Figure 1.4. Saw palmetto berries (www.eattheweeds.com).................................................5 Figure 1.5. Silver saw palmetto amongst green saw palmetto (Nursery at TyTy website).................................................................................5 Figure 1.6. Medicine used to treat BP H (Pierre Fabre Ibrica website)............................13 Figure 1.7. How to conduct a prescribed bur n (Division of Forestry website).................14 Figure 2.1. Seminole women with palm etto baskets (Downs, 1995: 202)........................20 Figure 2.2. Seminole sifting baskets made of palmetto, 1970s (Downs, 1995:197).........21 Figure 2.3. Harriet Bedell with Seminole women, ca. 1934 ( Miami News Collection 1920-1928)..............................................................22 Figure 2.4. Seminole man-on-horseback doll made of palmetto fiber (Downs, 1995:218)..........................................................................................25 Figure 2.5. Mikasuki dancing with palm etto fronds, 1938 (Sturtevant, 1954:60).............26 Figure 2.6. Illustration from The Yearling of a boy playing with a "flutter-mill" that he made (Rawlngs, 1966:1)................................................29 Figure 2.7. Whistle made of saw palmetto petiole and leaf. Made and photographed by Bethany Highsmith.............................................29 Figure 3.1. Lower urinary tract with nor mal sized prostate. Illustration by Rachel Renne..............................................................................................36 Figure 3.2. Lower urinary tract with enlarged prostate. Note pressure on bladder, urethra, and colon. Illu stration by Rachel Renne.............................................36 Figure 3.3. The human prostate. I llustration by Rachel Renne.........................................38 v

PAGE 6

List of Figu res (continued from v) Page Figure 5.1. Harvesters working for Saw Pa lmetto Berries Co-Op (Thorner, 2003)..........63 Figure 5.2. Harvesters fill a bag with 150 pounds of berries (HeraldTribune.com)..........67 Figure 5.3. The Saw Palmetto Harvesting Companys industrial drying station...............68 Figure 6.1. Mega Bust produc t (Mega Bust website)........................................................79 vi

PAGE 7

THE ETHNOBOTANY OF SAW PALMETTO ( Serenoa repens (Bartr.) Small) IN FLORIDA Bethany Highsmith New College of Florida, 2008 ABSTRACT Serenoa repens (Bartr.) Small, commonly known as saw palmetto, is a rhizomatic palm of the Arecaceae family that grows th roughout the southeastern United States. Palms, in general, are acknowledged for thei r utility as construction materials, food, clothing, medicine and more (B alick and Cox, 1997). This local shrub in particular has not only served as such to the Seminole Indi ans and pioneers, but has generated its own growing industry. Every summer freelance worker s scour the south Florida scrublands for ripe saw palmetto berries that sell by the pound in Immokalee (Thorner, 2003). Harvesting the fruit is an arduous and danger ous (albeit somewhat lucrative) process, which is now performed mostly by immigrant workers and often on trespassed land. The berries obtained are processe d into supplements purported to cure a wide range of ailments, from hair loss to testical atrophy; however, the main focus of medical research of saw palmetto berry extrac t is on the treatment of beni gn prostatic hyperplasia (Davis, 2002). vii

PAGE 8

Historical uses of S. repens are num erous, and this thesis seeks to synthesize the ethnobotany of saw palmetto in the past with the present. I endeavor to document the human interactions with S. repens from historical uses and harvesting practices through to modern medical uses and their potential efficacy, for a thorough ethnobotanical review of this little palm. _________________________________ Dr. Amy Clore Division of Natural Sciences viii

PAGE 9

ix RESUMEN Serenoa repens (Bartr.) Small, conocido comnmente como la palma enana americana (ingls: saw palmetto), de la familia Arecaceae, es una palma en que se forman rizomas, que crece en los matorrales del sure ste de los Estados Unidos. Las palmas en general son reconocidas por su utilidad como material de construccin, comida, ropa, medicina y ms (Balick y Cox, 1997). Ese arbusto ha sido utilizado por los indios prehispnicos y Seminoles y por los pioneros, y su cosecha es una i ndustria creciente en tiempos actuales. Cada vera no trabajadores autnomos re corren los campos y bosques del sur de Florida para obtener las bayas madur as de la palma, que se venden por la libra en Immokalee. La cosecha es un proceso ar duo y peligroso (aunque algo lucrativo), que ahora es realizado en su mayor parte por trabajadores inmigrantes, quienes frecuentemente invaden propiedades privadas ilegalmente en busca del bayal. El extracto obtenido de la s bayas se vende como medicamento que supuestamente cura una gama de dolencias, desde la prdida del cabello a la atrofia testical; no obstante, el enfoque principal de los estudios mdico s del extracto de palma enana americana es sobre su uso para el tratamiento de la hi perplasia benigna de pr stata (Davis, 2002). Hay numerosos usos histricos de S. repens y esta tesis presenta una sntesis de la etnobotnica pasada y presente de la palma. Incluye documentacin de usos histricos y procedimientos de cosecha actuales, junto con un asesoramiento de su eficacia medicinal. _________________________________ Dr. Amy Clore Division of Natural Sciences

PAGE 10

Chapter One: Introduction to Saw Palmetto ( Serenoa repens Bartr.(Small)) 1.1. Nomenclature Saw palmetto was given its first scientific names, Corypha repens (the prostrate variety) and Corypha oblique (the erect type), in 1791 by William Bartram (an American naturalist) while he was trav eling through St. Simons Island in Georgia (as reviewed in Hilmon, 1969). In 1803, the French botanist and explorer, Michaux, named the palm again, as Chamaerops serrulata (as reviewed in Hilmon, 1969). In 1830, it was called Sabal serrulata by the Austrian botanists, Josef August Schultes and Julius Hermann Schultes, and later described as Brahea serrulata by the German botanist Hermann Wendland in 1878 (as reviewed in Hilmon, 196 9). The current generic name was given by Sir Joseph Dalton Hooker in 1883 in honor of the Harvard botanist Sereno Watson (as reviewed in Austin, 2004). Then, Nichol son adjusted the name accordingly to Serenoa serrulata in 1887, and it was finally dubbed Serenoa repens by Small in 1926 (as reviewed in Hilmon, 1969). The common name, saw palmetto, was coined by William Bartram (Austin, 2004). It is likely that th e monicer "palmetto" comes from the Spanish word for little palm, "palmto"; and anyone who has been cut by the teeth along the petioles of the plant will unde rstand wherein lies the 'saw' (Kennedy, 1991; Davis, 2002). 1.2. Life History Serenoa repens grows in the West Indies and the southeastern United States. It is especially common in the wet and dry flat woods and hammocks of Florida (Wunderlin, 2003). Saw palmetto is a branching palm (the only one native to Fl orida), and its trunks 1

PAGE 11

are typ ically either subterrane an or reclining, but occasionally they grow at an upward angle reaching up to seven meters (Hilmon, 1969; Bennet and Hicklin, 1998). The average height (Fig. 1.1), however, is less than two meters (Stevenson, 1974). The trunks Fig. 1.1. Stand of saw palmetto growing at average height (from Plant Database website). are clothed with brown fibrous matting (S tevenson, 1974; Bennet and Hicklin, 1998). From the axillary buds emerge both the fr onds and the inflorescences, as well as the vegetative suckers (Fisher and Tomlins on, 1973). During early development of the axillary buds, it is impossible to discern which ones will become inflorescences and which will become suckers. In later developm ent, one can characterize the buds that will become suckers by their thicker and less crescent-shaped attachment (Fisher and Tomlinson, 1973). In a mature plant, approximately half of the axillary buds abort. Of the half that survive, about 80% develop into inflorescences, and only 20% turn into suckers (Fisher and Tomlinson, 1973). Infl orescences emerge from a cr own of healthy leaves, but the suckers do not develop until after the leaves have died (Fisher and Tomlinson, 1973). 2

PAGE 12

The production of inflorescences an d vegeta tive suckers from axillary buds along the adult axis of S. repens has no systematic order. This unpredictable production makes saw palmetto unique from other palms in its br anching habit (Fisher and Tomlinson, 1973). The palmate fronds are approximately one meter wide and one to two meters in length, measuring from the base of the petiole to the distal tips (Bennet and Hicklin 1998). The petioles are normally lined with sh arp, curved teeth (F ig 1.2.), hence the name "saw", but sometimes these spines are not present (Morton 1974). Fig 1.2. Spiny petiole (from Plants Database website). The growing tips produce up to five infloresce nces, between February and April (Bennet and Hicklin 1998). The inflorescences grow up to one meter long and take the form of solitary panicles (Morton 1974; Stevenson 1974; Davis 2002). Every inflorescence (Fig. 1.3.) has thousands of individual flowers that begin blossoming in March (Davis 2002). The fragrant flowers are almost sessile on th e spikelets and have th ree off-white petals (Morton 1974; Davis 2002). 3

PAGE 13

Fig 1.3. Inflorescences (from Plants Database website). The flowers mature into drupes about 2 cm long that turn orange and then dark blue or black when ripe. The majority of fr uits (Fig. 1.4) mature throughout the summer, and typically ripen in September and October (Fisher and Tomlinson, 1973). In comparison to the amount of flowers produced, re latively few fruit reach maturity (Davis 2002). Two types of S. repens are commonly acknowledgedgreen and silver (Fig. 1.5.). Silver saw palmetto naturally occurs on the Atlantic coast of Florida (Moldenke, 1967; Essig et al. 2000). It is generally less comm on than the green variety. Taylor (1995) wrote a masters thesis on the distribut ion patterns and leaf su rface anatomy of the 4

PAGE 14

Fig. 1.5. Saw palmetto berrie s (from www.eattheweeds.com). Fig. 1.5. Silver saw palmetto amongst green saw palmetto (from The Nursery at TyTy website). 5

PAGE 15

different saw palmetto varieties. She f ound that morphological differences in the epicuticular wax patterns on th e upper leaf surfaces exist be tween the silver and green types of S. repens and also suggested that an intermed iate (i.e., intermediate in color and amount of wax) type exists (Taylor, 1995; Essig et al. 2000). She hypothesized that the color differences were a result of varyi ng amounts of epicuticular wax; however, no statistical analysis was apparent in her research (Taylor, 1995; Essig et al. 2000). More recent research corroborates the connection between epicuticular wax topography and taxonomy in general (Shayanmehr et al. 2008). 1.3. Ecological Importance Saw palmetto is a vital member of seve ral ecosystems, including pine flatwoods, dry prairies, scrub, pinelands, temperate hardwood forests, south Florida rockland, freshwater marshes, dunes, sandhills, and ma ritime forests (Abrahamson, 1990; Kushlan, 1990; Myers, 1990; Platt, 1990; Snyder, 1990). Sa w palmetto can be found in the highest densities in poorly drained pi ne flatwoods, and in the lowe st densities in well-drained sandhills (Abrahamson, 1995). Generally, S. repens occurs most frequently in poorly and moderately drained soils (Abrahamson, 1995). Ho wever, it can tolerate a variety of soil conditions, including Entisol1, Inceptiol2, and Spodosol3 soils (Abrahamson, et al. 1984). Note: Unless otherwise cited, all footnotes are referenced from www.dictionary.com. 1 EntisolSoil order that lacks horizons. If a so il cannot be classified in any of the other six soil orders, then it is an Entisol (Brown et al. 1990). 2 InceptisolSoil order with some differen tiation of horizons, but less differentiation than all other orders except Entisols (Brown et al. 1990). 3 SpodosolSoil order that possesses a spodic horizon, which is a zone of organic matter mixed with aluminum and/or iron that has seeped downward. Soil is typically sandy, but may have a zone of clay-si zed particles (an argillic hor izon) under the spodic horizon (Brown et al. 1990). 6

PAGE 16

Saw palmetto is associated with a wide variety of plant and animal species, as will be discussed briefly below. For a more in-d epth description of the immensely complex habitats in which saw palmetto lives, the reader is encouraged to consult Ecosystems of Florida edited by Myers and Ewel (1990). Saw palmetto is an important source of food and shelter for several animal species. Both the endangered Florida grasshopper sparrow ( Ammodramus savannarum floridanus Mearns) and the wild turkey ( Meleagris gallopavo L. ) nest under the cover of saw palmetto (Tanner and Mullahey, 2009). Ground nesting rodents, including the Florida woodrat ( Neotoma floridana smalli) use the subterranean stems of saw palmetto for structural support (Tanner and Mullahe y, 2009). The Florida panther uses saw palmetto both for natal dens and day re sting cover, and white-tailed deer ( Odocoileus virginiana Zimm.) take cover under saw palmetto when being pursued, or for warmth during cold, windy days (Tanner a nd Mullahey, 2009). Black bears ( Ursus americanus Pall.), white-tailed deer, raccoons ( Procyon lotor L.), opossums ( Didelphis virginiana Kerr), rodents, gopher tortoises ( Gopherus polyphemus Daudin), feral hogs ( Sus scrofa L.), and gray foxes ( Urocyon cinereoargenteus Schreb.) all consume saw palmetto berries (as reviewed in Bennet and Hicklin, 199 8). The apical meristem (a.k.a., the heart) of the plant, is ripped out and eaten by bl ack bears and feral hogs (Tanner and Mullahey, 2009). Cattle graze on saw palmetto blades (Hilmon, 1969), but saw palmetto is not a natural food source for cows (VanGelder SWFWMD, pers. comm. 2009; Strickland, cattle broker, pers. comm., 2009; Tanner a nd Mullahey, 2009). However, in the dry season, ranchers feed their cattle urea-cont aining molasses; the ur ea irritates the cows' stomachs, inciting the cattle to eat large quant ities of saw palmetto as roughage to clean 7

PAGE 17

out the ir digestive tracts. This common practice is performed in order to keep cattle fat when resources are scarce (W. VanGelder, SWFWMD land manager, pers. comm. 2009; J. Strickland, cattle br oker, pers. Comm., 2009). S. repens naturally occurs as a dense shrub layer in pine flatwoods, sometimes accompanied by other shrub species in lower densities, with a sparse understory of herbaceous plants. The following herbaceous pl ants commonly grow near saw palmetto: wiregrass ( Aristida beyrichiana Trin. & Rupr.), creeping bluestem [ Schizachyrium scoparium (Michx.) Nash var. scoparium ], lopsided Indiangrass (Sorghastrum secundum Ell Nash), goldenaster [ Pityopsis graminifolia (Michx.) Nutt.], vanilla plant [ Carphephorus odoratissimus (J.F. Gmel.) Herbert], tarflower (Bejaria racemosa Vent.), and slender blazing star ( Liatris tenuifolia Nutt. Var. quadriflora Chapman) (Carrington and Mullahey, 2006; Tanner and Mullahey, 2009) These shrubs are as sociated with saw palmetto: wax myrtle ( Myrica cerifera L.,), gallberry [ Ilex glabra (L.) A. Gray], fetterbush [ Lyonia lucida (Lam.) K. Koch], staggerbush [ Lyonia fruticosa (Michx.) G.S. Torr.], rusty lyonia [ Lyonia ferruginea (Walter) Nutt.], Florida rosemary (Ceratiola ericoides Michx.), and runner oaks ( Quercus spp. L.) (Myers, 1990; Carrington and Mullahey, 2006; Tanner and Mullahey, 2009). Slash pine (Pinus elliottii Engelm.), longleaf pine (Pinus palustris Mill.), or pond pine ( Pinus serotina Michx.) trees occur as a sparse overstory in healthy pine flat woods (Bennet and Hicklin, 1998). In scrubby flatwoods, saw palmetto is frequently co -dominant with oak species (Tanner and Mullahey, 2009). S repens does not have much competitive in terference from other plant species (Abrahamson, 1995). Saw palmetto is sympatric with scrub palmetto ( Sabal etonia 8

PAGE 18

Swingle ex Nash) (Abraham son, 1995). S. repens and S. etonia have similar growth habits, reproduction, responses to fire, and habitats, but they are able to coexist noncompetitively because they have differe nt microhabitats (Abrahamson, 1995). Saw palmetto is integral to Florida's fi re ecology. It is one of the primary fuel sources for the frequent fires th at keep Florida's habitats heal thy and true to their natural state (Main and Tanner, 2003; W. VanGelder, pers. comm., 2009). Saw palmetto itself is pyric, and relies on fire for heal thy reproduction (Abrahamson, 1995). 1.4. Fire and Reproduction While external factors such as fire aff ect reproductive activitie s such as flowering and fruiting, internal factors must be considered as well (Abrahamson, 1999). Research has shown that many perennial species must r each a certain size before they are capable of flowering (Gross and Werner, 1983; Sa mson and Werk, 1986). This may help to explain why a fire that would normally induce flowering in a fire-stimulated species may not cause flowering in all the individual plants of that species (Glenn-Lewin, et al. 1990 as cited in Abrahamson, 1999). Interactions betw een plant size and fire with respect to flowering have not yet been sufficiently re searched (Abrahamson, 1999). Besides fire and plant size, other factors likely contribute to reproductive response, such as soil type and amount of available light (Abrahamson, 1999) Abrahamson (1999) posits that flowering of fire-stimulated species is hierarchical. He suggests that fire provides the right cocktail of conditions for flowering (such as increas ed light and soil fertility, and decreased tissue), but that plant size is the limiting factor th at governs whether or not an individual plant will respond by flowering when pres ented with a reproductively conducive environment (Abrahamson, 1999). Indeed, larger saw palmetto plants have been shown to 9

PAGE 19

flower m ore often, and to create a greater number of inflorescences during flowering events (Abrahamson, 1999). As previously mentioned, each inflores cence has thousands of individual flowers (Davis, 2002; Carrington et al. 2003). The three-petaled flow ers are each approximately 5 mm long, with three white petals, six stamen s, one pistil, and a th ree-ovulate superior ovary (Carrington et al. 2003). Usually only one ovule ma tures into a seed (Godfrey, 1988 as cited in Carrington et al. 2003). The flowers are pollin ated by insects, especially honeybees (Tanner and Mullahey, 2009). Large saw palmettos are often hundr eds of years old. The lifespan of S. repens is estimated at over 700 years (Abrahamson, 1995). S. repens is an exceptionally slow growing species, requiring decades or mo re to mature to a reproductive age (Abrahamson, 1995; Abrahamson, 1999). Although saw palmetto seems indestructible to farmers, it is quite vulnerable to anthropogenic effects since it is unable to make a quick recovery (Abrahamson, 1999). Larger palms produced more new leaves after fire or clipping events, and thus were more vigor ous, as measured by the number of leaves produced per unit time (Abrahamson, 1999). Vigor is an indicator of recent fire, since recently burned palmettos have increased rates of leaf production (Abrahamson, 1999). 1.4.1. Fire Research Conducted by Abrahamson Abrahamson (1999) investigated the ways in which fires affected the reproduction of S. repens in its native, fire-prone habitat. He carefully monitored the populations of saw palmettos between fire events, by taking annual censuses. He marked various populations of palmettos in 1980, 1985, and 1989 in the study, which lasted a total of 17 years (Abrahamson, 1999). Each census comp rised measurements of crown height, 10

PAGE 20

crown m aximum width, crown wi dth perpendicular to the maximum width, number of green leaves, number of leaves added since the last census, number of inflorescences produced during the last growing season, and th e number of stem sprouts (Abrahamson, 1999). In addition to tracking growth in between fi res, he also analyzed what aspect of a fire event resulted in a flow ering response by mimicking certain aspects of fire events through clipping and fertilizing experiments. Clipping the leaves was conducted in an effort to imitate the biomass removal cause d by a fire, and fertilizing was conducted to mimic the nutrients released into the soil by the ashes of a fire. Abrahamson randomly subjected each of 150 saw palmetto indivi duals to one of the following treatments: clipping all the leaves, except for the bud l eaf, fertilizing, or c lipping and fertilizing (Abrahamson, 1999). Since he did not have the opportunity to test the effect of reduced canopy level by actually removing the trees overhead, he simply assessed the canopy levels at different sites to dedu ce their effects (Abrahamson, 1999). He found that those palmettos that had been clipped, and those that had been clipped and fertilized both exhibited increased floweri ng (Abrahamson, 1999). On the other hand, those that had only been fertil ized did not have enhanced reproduction. Therefore, he concluded that while cr own loss may trigger episodic reproduction, increased soil fertility alone has l ittle to no effect (Abrahamson, 1999). Abrahamson (1999) concluded that fire is a crucial extern al cue for episodic reproductive events in S. repens In unburned scrubs with dense canopy layers, virtually no flowering occurred. The palmettos that did flower were present in the areas of the scrub with gaps in the canopy, indicating that a dense canopy greatly inhibits flowering. 11

PAGE 21

In this scrub site, after a fire occurred, th ere was a three year l ong episode of flowering am ong more than 50% of the individual palmettos (Abrahamson, 1999). Similar fireinduced episodic reproduction ha s been documented in other plant species of fire-prone habitats (Baird, 1977; Pyke, 1983; Herndon, 1988), but S. repens along with Sabal etonia Swingle ex Nash, are the only palms know n to not only flourish in fire-prone habitats, but virtually require fi re for reproduction (Abrahamson, 1999). 1.6. Resource Management In the past, saw palmetto was consider ed an irascible pest by many farmers and range managers (Lewis, 1970; as reviewed in Carrington et al. 1997). One range scientist even claimed that saw palmetto "suppresses yiel d and availability of better forage plants, interferes with tree planting, a nd contributes to fire hazards in tree stands" (Lewis, 1970: 276). Much early research on saw palmetto focused on its control or eradication (Hough, 1968). Its carbohydrate reserves were even eval uated, in order to assess the best way to burn it to death (Hough, 1968). Alth ough people tried to eradi cate palmetto on the land by burning, to their surprise the fire actually had the oppos ite effect (Hough, 1968). Thus, mechanical and chemical means were employed to kill unwanted stands of S. repens Clear-cutting, roller-chopping, diski ng, web-plowing (Lewis, 1970; Moore et al. 1982; Tanner et al. 1988), and herbicides (Kalmbacher a nd Martin, 1984) effectively removed saw palmetto, but the latter was more expensiv e than mechanical removal, and therefore, less commonly used (Lewis, 1970). Conversely, saw palmetto is now not only recognized as key habitat for threatened and endangered animal species (Tanner and Mullahey, 2009), but also as a profitable crop (Carrington et al. 1997; Tanner and Mullahey, 2009). Florida saw 12

PAGE 22

palm etto populations are valued by the pharmaceutic al industry as the main source of saw palmetto berry extract, which is used to ma ke both herbal supplements and prescription drugs, such as Permixon (Fig. 1.5), that treat benign prosta tic hyperplasia among other ailments (Maccagnano et al. 2006; Saw Palmetto Harv esting Company website). Although there are a few saw palmetto farms, th e majority of the berry crop is picked by freelancers at other locations (Carrington et al. 2003; Saw Palmetto Harvesting Company website). Currently, it is common practice for migrant workers to trespass on Fig.1.5. Medicine used to treat benign prostati c hyperplasia (from Pierre Fabre Ibrica website). private ranches or government-owned conservati on lands to pick saw palmetto berries in order to supplement their income (Balut, 2007 ; J. Perez, former berry harvester, pers. comm., 2009). While this distur bance does not typically hurt th e prolific palmetto plants, according to William VanGelder, a land ma nager for the Southwest Florida Water Management District, it does flush out an imals taking cover from the sun, posing a potential threat to some endangered speci es (W. VanGelder, pers. comm., 2009). Land managers carry out the important duty of performing pr escribed burns in preserved palmetto scrubs and flatwoods. These controlled burns are necessary for habitat maintenance now that Florida's ecosystems are fragmented and wildfires can no longer 13

PAGE 23

sweep acros s the state (W. VanG elder, certified prescribed burn manager, pers. comm., 2009). By carefully applying fire to vegetative fuels in the proper way (Fig. 1.6.), the risk Fig. 1.6. How to conduct a prescribed burn (from Division of Forestry website). of wildfire is decreased, grazing habitat is improved, forest regeneration is encouraged, nutrients are cycled through the ecosystem, and fire-dependent species such as saw palmetto remain healthy (Long, 2002). Cert ified prescribed burn managers (land managers often have this certification) mu st undergo thorough training and comply with extensive regulations to ensure wise resource management and the safety of wildlife and humans. In addition to conducting prescribed burns, recently, land managers and other 14

PAGE 24

conservation officials have also been attem p ting to eradicate the illegal and potentially harmful practice of saw palmetto berry poaching, as will be discussed later in this thesis. 1.7. Overview S. repens is an excellent plant for ethnobotan ical examination because it has been utilized by different groups of people in myri ad ways throughout hist ory. It is a focus of modern medical research, and is vied over by conflicting inte rests. Chapter Two of this thesis reviews the historical uses of saw pa lmetto, including medical uses. Chapter Three explains the pathology of benign prostatic hyperplasia, the condition which is probably the most commonly targeted for treatment with saw palmetto. Chapter Four discusses the medical literature regarding the efficacy of saw palmetto berry extract for benign prostatic hyperplasia and other illnesses and conditions. Chapter Five describes the methods of harvesting and the ethical concerns that palmetto poaching raises. Chapter Six offers fresh perspectives on saw palmetto medical research, land management, and harvesting, as well as the inters ections between these interests. 15

PAGE 25

Chapter Two: Historical Uses of Saw Palmetto 2.1. Food Saw palmetto has been a source of food in Florida since pre-Columbian times (Reitz and Scarry, 1985; Widmer, 1988). Saw palmetto berries are a marked fixture among food remains in archaeological sites a ll over the state of Florida (Scarry and Newsom, 1992; Austin, 2004). In pre-Columbia n non-agricultural societies, the berries were a seasonal fruit enjoyed in the fall. They could be dried and saved for other times of the year, whenever other, more preferable sources of food (such as meat) were scarce (Milanich and Fairbanks, 1980; Reitz a nd Scarry, 1985; Widmer, 1988; McGoun, 1993). Later, the Seminole and Miccosukee tribes ate the berries plain (Bennett and Hicklin, 1998). The Minorcan settlers of St. Augustine, who left the Balear ic Island of Minorca for Florida in 1768 under contracts as indent ured plantation worker s, considered the wine-soaked fruits to be a delicacy and named them "Minorcan plums" (Reynolds, 1886; Kennedy, 1991; Landers, 2000). In addition, Serenoa repens has been found in food remnants of Spanish settlements from the 16th century (Reitz and Scarry, 1985). "Shiope sofkee" was a sweet Seminole drink made fr om the fruits (Bennett and Hicklin, 1998; Austin, 2004). In more recent times, at the beginning of the 20th century, a soft drink called "metto" was sold on the streets of Mi ami; it was a mixture of saw palmetto berry juice and carbonated water (Morton, 1977; Mo rton, 1986). Additionally, saw palmetto berries soaked in brine have been substituted for pickled olives (Stokes, 1940). The petiole of the saw palmetto is also edible. The Seminoles used the petioles to make a type of flour, called fecula, which was part of "sofkee", a warm corn drink similar to watery grits (Downs, 1995; Bennett a nd Hicklin, 1998; Holt, 2007). This flour was 16

PAGE 26

considered to be substandard in com parison to coontie flour, but a su itable substitute in times of need (Smith, 1839). Fecula was ma de from the inner portion of the petiole, which was chipped up as log-wood (Sm ith, 1839:140). The chips were ground with a large mortar and pestle made from a near by hardwood log, and strained through a sieve made of palmetto fronds (Smith, 1839). Next a cotton cloth was staked to the ground above a large deerskin, which was also staked to the ground by its corners. The already strained substance was put in the cotton cloth and water was poured over it while someone mixed the substance with her hands. The wet flour settled on the deer skin, and then was dried for a final time on a clean cotton cloth (Smith, 1839). The final product was kept in bags of dressed deer skin. Beside s being used in sofkee, fecula was also fried to make battercakes (Smith, 1839). In addition, the terminal vegetative buds of the shrub are also edible and have been said to be comparable to "swamp cabbage" of Sabal palmetto (Walt.) Lodd., but smaller a nd more tender (Morton, 1977). Opinions regarding the taste of saw palme tto vary widely and have been deliberated in literature. Jonathan Dickinson, a European merchant who was shipwrecked on the coast of Florida and captured by the indi genous peoples, wrote about his unpleasant experience with saw palmetto consumption: In some time after we had been in the house, came in Indian women laden with baskets of berries, mostly of the palm, some seaside coco-plums and seaside grapes: of the two latter we could eat; but of the palm-berries we could not bear the taste in our mouths. We tasted them, but not one amongst us could suffer them to stay in our mouths; for we coul d compared the taste of them to nothing else, but rotten cheese steeped in tobacco (Dickinson 1985). In the historical novel set during the civil war entitled God Has a Long Face one of the characters describes an area near St. Augustine thus: "Ain't a soul living there but one old coot tryin' to make a tonic out of the palmetto berries. Took some of it once. Tastes like a 17

PAGE 27

mouthful of cockro aches" (W ilder, 1940, as cited in Morton, 1986:13). Finally, in his 1898 publication Saw Palmetto Edward Hale gives an analysis of the taste that is more generous: The berries are at first exceedingly sweet to the taste, but in a few seconds this is followed by an acrid, pungent sensation that spreads to the fauces4, nasal mucous membrane and larynx. This is in turn succeeded by a feeling of smoothness in all those parts, as if they had been coated with oil. The general impression is that of a sweet and decidedly strong, though not unpleasant, butyraceous5 taste, which increases with the age of the fruit (Hale, 1898). A product that is perhaps held in better regard by the general public, taste-wise, is saw palmetto honey. S. repens is a major source of honey in Florida, often producing surplus honey crops (Hilmon, 1969; Morton, 1986; Sanford, 2003). Saw palmetto honey is a light green to amber color, and has a high moisture content (Sanford, 2003). One gourmet honey vendor touts that saw palmetto honey has a flavor that can only be described by the taster. It ha s a distinct floral bouquet and an equally fine finish that would be used to describe a marvelous wine (Saw Palmetto Honey website). 2.2. Fiber Over the years, fibers from the fronds, petioles, and roots have been used for a variety of goods, with varying success. The Calusa used the fibers as twine, but contemporary tests determined that they are of insufficient quality for commercialization (Robinson, 1947; Bomhard, 1963). During the 19th century, the French made a product from it that was a horse-hair substitute (U.S. Department of Agriculture, 1879). In 1898, Hale noted that the dried fronds were sold in bales as paper (Hale, 1898). Cheap scrub brushes were made from saw palmetto root s (Dodge, 1897; Hale, 1898). The roots, which 4 faucesthe posterior part of the mouth that leads to the pharynx 5 butyraceousresembling butter 18

PAGE 28

are typically three to five in ches in diam eter, were cut in to disks about an inch thick. Then, the pulp was scraped away from two-thir ds of the length of the root by toothed scraping wheels, baring the stiff fibers to serve as bristles (Dodge, 1897). Fibers from the fronds and petioles were previously ut ilized in upholstery fill (Robinson, 1947). In 1901, the trunk fiber sold for $20 a ton in New Jersey as excelsior6 (Morton, 1986). To make mattress stuffing, the plant was shredded with a hackle, then boiled and sun-dried for a few days (Porcher, 1869; U.S. Depart ment of Agriculture, 1879). Selling twisted, hard palmetto fiber as mattress stuffing was a relatively sizeable industry in the late 19th century--special machines were even patent ed to manufacture it (U.S. Department of Agriculture, 1879). There was competiti on, though, between American fiber and imported African fiber. A late 19th century manufacturer from Volusia County, Florida complained: There is a very great hindrance to th e successful manufacture of this fiber here by the importation of the African fi ber, which is the product of convict labor in a French prison at or near Algiers, and the only means of encouragementwould be a heavier duty on the imported article (U.S. Department of Agriculture, 1879:554). In the mid-twentieth century, commercial use of the saw palmetto was further investigated, and seemed a promising endeavor ( Forest Farmer 1947). In 1947, the McCrary Engineering Co mpany had big plans: McCraryreached deep into the unsolved mysteries of scrub palmetto and came up with a new wallboard and numer ous other products. He declares that the wallboard can be dyed any colo r, never needs paint, is stormproof, decay proof, termite-proof, and fireproof. Already his company has planned to build several plants for processing palmetto and will build the first in Stuart, Florida this year. The new plants will not only produce wallboard, but also tannic acid in quantity, fine fibers and palmetto cork. Estimated yieldis 1200 pounds of fiber cork and 100 gallons of tannic 6 excelsiorcurved wood shavings used as packing material 19

PAGE 29

acid solution from one t on of palmetto roots (Forest Farmer 1947: 6). In addition to being added to prefabricated wallboard, saw palmetto fiber was mixed into plaster, as a substitute for cows hair (D odge, 1897). It was called Nassau plastering fiber, and reputed to be both inexpensive and long-lasting, because it was impervious to lime (Dodge, 1897). Saw palmetto trunk fiber was he lpful during WWII; it was processed into a cork substitute to form floats and gun cartridge plugs (Robinson, 1947; Bomhard, 1963). However, shortly thereafter, attempts to industrialize the fibers were generally abandoned (Hilman, 1969). 2.3. Seminole and Miccosukee Crafts and Ceremonies The Seminole and Miccosukee people of Florida do not weave fibers or cloth out of saw palmetto, but they do make baskets (Fig. 2.1.), for ceremonies and profit (Sturtevant, Fig. 2.1. Seminole women with baskets made from saw palmetto, ca. 1930 (Downs, 1995: 202). 1955; Blackard, 1990; Downs, 1995). The Seminole word for saw palmetto is 20

PAGE 30

siyaphintali (Sem inole: siyaph nt:l, Sturtevant, 1955). Colle cting the siyaphintali stems for the craft is an ordeal, a nd can take an entire day. The longest stems are chosen and harvested with a machete. Later a knife is us ed to split them into sections, and then a smaller knife is employed to scrape them in to smoother, thinner strips of equal width (Downs, 1995). The Seminole and Miccosukee made a vari ety of baskets, mostly during the late 19th and early 20th century (Garbarino, 1972; Bucuvalas, et al. 1994; Downs, 1995). One kind is the corn-sifting basket. These baskets ar e made in sets of three (Fig. 2.2.) for the Fig. 2.2. Seminole sifting baskets made of palmetto, 1970s (Downs, 1995:197). Green Corn Dance ceremony (Downs, 1995), a nd can only be made by married women 21

PAGE 31

(Belland and Dyen 1982 as cited in Downs, 1995). Currently, grain-sifting baskets are only m ade to be sold to tourists (Bucuvalas, et al. 1994). Another item is called the old little box, a key part of a medicine mans repe rtoire, consisting of tw o thin baskets that nestle together forming an envelope shaped container for healing herbs (Sturtevant 1970, as cited in Downs, 1995). Seminole medicine baskets have been documented as early as 1857. One of the most recent specimens, under th e care of the Florida Museum of Natural History, is loosely dated from the 1930s-1950s (Downs, 1995). Unfo rtunately, there are hardly any medicine baskets present in mu seum collections, and the crafting of these baskets is mostly a thing of the past (Downs, 1995). There was a resurgence in the 1930s when Deaconess Harriet Bedell, a missionary from the Episcopal church, founded the Glades Cross Mission to help the Seminole and Miccosukee women support themselves financ ially through their folkart (Fig. 2.3.). She Fig. 2.3. Harriet Bedell with Seminole women, ca. 1934 ( Miami News Collection 1920-1928). 22

PAGE 32

urged them to use the plentiful palmetto in their environment to fashion practical square baskets for the touris t industry (Bucuvalas, et al. 1994). The women also made special items for themselves, such as baby toys (Sturtevant, 1955). One documented article was a rattle woven from a single frond, with the stem as the handle and small piece of charcoal inside to make the noise (Downs, 1995). A lthough many baskets are woven entirely out of siyaphintali, such as the ones previously described, some are woven out of sweet grass with a base consisting of cardboard covere d in saw palmetto husk fiber (Buculavas, et al. 1994). Seminole and Miccosukee baskets are st ill produced today by some artists (Congdon, 2006). However, most of the curren t basketry focuses on sweet grass and chevron patterns of embroidery thread more than saw palmetto (Blackard, 1990; Downs, 1995). Furthermore, the art of basket making among the native Floridians is said to be slipping away as fewer and fewer young people learn the tradition (Buculavas, et al. 1994; Downs, 1995). Another craft that is becoming less popul ar among the Seminole youth, but that is quite lucrative, is the making of Seminol e palmetto dolls (G arbarino, 1972; Blackard, 1990; Bucuvalas, et al. 1994). The first documented Seminole dolls in the late 19th century were simple toys made of sticks and rags that showed little resemblance to actual people, due to a taboo. According to Howa rd Osceola, the Seminole and Miccosukee people avoid creating likenesses of things, b ecause they are concerned it will bring them misfortune (Downs, 1995). Later, though, as tourist demand for more complicated dolls became apparent in the early 20th century, financial concerns overcame the cultural taboo (Downs, 1995). By 1918, women had started ma king palmetto husk dolls dressed in 23

PAGE 33

trad itional Seminole clothing to sell to touris ts from their chickees. By 1922, they were appearing in Florida gi ft shops (Bucuvalas, et al. 1994; Downs, 1995). The production of palmetto dolls is a relatively involved pr ocess. Although the dolls are primarily made by women, it is of ten a man who collects the fiber. After a satisfactory saw palmetto is chosen, the leaves are cut off, and the trunk is felled with a machete or axe (Downs, 1995). Fiber is collec ted with a smaller knife and wrapped in a cloth (Bucuvalas, et al. 1994). Smooth fiber is the mo st sought-after (Bucuvalas, et al. 1994; Downs, 1995), since it is the least irritating to the skin (Downs, 1995). One palmetto plant makes an average of four to five dolls, obviously depending on the size of the dolls and the shrub (Bucuvalas, et al. 1994; Downs, 1995). After the fiber is collected, it dries for a couple days (if it is wet) and is then cut to an appropriate length for the desired doll size. Dolls are typi cally four, six, eight, or 10 inches in height (Bucuvalas, et al. 1994; Downs, 1995). The heads are made first: they are stuffed with scrap palmetto fiber, tied off at the neck, and the facial features are sewn on with white, black, and red embroidery thread (Bucuvalas, et al. 1994; Downs, 1995). Next a cylindrical body is stuffed with palmetto fiber or cotton, and capped with a circular cardboard base, which is covered with fiber. Then, the head is attached, and the doll is given hair and dressed in traditional costume, complete with beaded jewelry (Bucuvalas, et al ., 1994; Downs, 1995). Previously, a doll could easily be dated because its hair and dress matched the contemporary style of Seminole and Miccosukee women. Beginning in the 1960s, however, that method of dating ceased to work, since doll makers started choosing ol der styles of dress for their work (Downs, 1995). Although most palmetto dolls are female, the trend started in the 1940s to sell dolls 24

PAGE 34

in gender binary pairs (Downs, 1995). Male do lls have lim bs and wear big shirts with scarves and turbans. Some of the nicer ones come with underwear as well. However, only post-menopausal women are allowed to make male dolls according to cultural taboo (Downs, 1995). The man on horseback doll (Fig. 2.4) was popularized in the 1940s, around the same time that residents of the Bi g Cypress Reservation became involved in Fig. 2.4. Seminole man-on-horseback doll made of palmetto fiber (Downs, 1995:218). the Florida cattle industry (Downs, 1995). Besides usage for dolls and baskets, the Seminole also used saw palmetto fronds for other, nonsaleable items. For example, they used them in their ball games and for the Green Corn Dance Ceremony (Capron, 1953). Seminole boys and girls played a ball 25

PAGE 35

gam e similar to lacrosse every evening around sunset, using a deerskin ball and rackets. Usually the rackets were made of green laurel, but when laur el was not available, a green palmetto leaf stem served as a (more fr agile) substitute (Capron, 1953). The palmetto stem was bent in a loop for the frame a nd tied together with cord (Capron, 1953). Moreover, they used saw palmetto fronds in various ceremonial dances (Capron, 1953; Sturtevant, 1954; Sturte vant, 1955). The men, in particular, would hold the palmetto leaves in front of their faces dur ing the Green Corn Dance (Fig. 2.5.). If an onlooker at the dance happened to be holdi ng a palmetto frond, the dance boss could order the person to dance (Capron, 1953). Th e women sat in palmetto stands smoking Fig. 2.5. Mikasuki dancing with palmetto fronds, 1938 (Sturtevant, 1954:60). cigarettes and watching the dancing when they, themselves, were not busy dancing. Small children that could not be left alone in camp (which is apart from the dancing ground) during the all-night-long dance were cared for and let to sleep in the saw palmettos underneath muslin canopies (Capron, 1953). 26

PAGE 36

2.4. Other Uses Saw palm etto fronds are a suit able thatch material for temporary structures, and were employed by both the indigenous peoples and European colonists of Florida (Hale, 1898; Morton 1986; Bennett and Hicklin, 1998) Later on, the fronds were a favorite thatch material with the new homesteader, whose first house is a palmetto hut, and very comfortable and picturesque dwellings th ey make (Dodge, 1897:294). Additionally, the Seminole and Miccosukee were noted to have used saw palmetto to make fishing drag nets as well as fire starter (Sturtevant, 1955). Beds of saw palmetto fronds were also fashioned by the Florida pioneers. In a letter home, a U.S. Army officer who led soldiers in the construction of a road from Fort Brooke (now in Tampa) to Micanopy in 1828 wrote of a bed he made: Supper having been dispatched, we cut a few leaves of the saw-palmetto for our beds, threw more wood on th e fire, and lying down were soonat least I can speak for onewrapt in the arms of Morpheus (McCall, 1974:193). S. repens served not only as food and shelter for many, but for other practical purposes as well, such as a sort of clothe sline and an escape fr om muddy terrain. On Dania (now Hollywood) Reservation, circ a 1950, the Seminole people hung their laundry out on wax myrtle and saw palmettos to dry (Mahler, in press). In a pinch, Florida Crackers would place saw palmetto fronds in fr ont of their tires to get unstuck from mud or sand, in a practice called fanning th e ground (Nash, 1931; Mahler, pers. comm., 2009). Additionally, indigenous Floridians used sa w palmetto to make atlatls, or spear throwers, for hunting (Mahler, pers. comm 2009). Atlatls were developed during the Archaic tradition, from 8000-700 B.C., and prec eded the bow and arrow (Perdue, 2001). 27

PAGE 37

Am ong prehistoric Florida peoples, found atla tl specimens were made of wood (Griffin, 2002) or bone (Purdy, 1991). However, more recently, the Seminole sometimes used saw palmetto petioles for their atlatls (Reynolds in Mahler, 2009). For th e launcher, they cut a stiff, long saw palmetto stem and made it wedge-shaped at the end (Reynolds in Mahler, 2009). They used another saw palmetto st em for the spear, trimming the frond into a feather shape to make it aerodynami c (Reynolds in Mahler, 2009). As previously stated, the fronds are al so an artistic medium employed (not exclusively) by the Seminole and Miccosukee, and are used for weaving baskets, brooms, fans, and hats, among other things (Benne tt and Hicklin, 1998). Although cabbage palm fronds are more commonly used for these cr afts, some artisans prefer saw palmetto because the fronds are softer and mo re pliable (Cooke and Sampley, 1947). In the 1800s, hats were manufactured from saw palmetto by African Americans (Porcher, 1869; U.S. Department of Agriculture, 1879). Before being woven, the leaves were brushed with oxalic acid and exposed to burning sulfur fumes in order to bleach them (U.S. Department of Agriculture, 1879). Additionally, the so-called Florida Crack ers made (and some people still make) toys out of the palmetto, such as water wh eels and whistles for chil dren (Rawlings, 1966; Mahler, pers. comm., 2009). Marjorie Kinnan Rawlings gives a detailed description of a boy making a flutter-mill from saw palmetto (Fig. 2.6.) in The Yearling He used cherry twigs for the framework, but made the mill-wh eel using strips of palmetto leaves for paddles (Rawlings, 1966; see appendix for excerpt from the narrative). Whistles (Fig. 2.7.) were made by inserting a strip of palmetto leaf into a partiall y split portion of the petiole (Wilson in Mahler, 2009). 28

PAGE 38

An added benefit of saw palmetto is that it is a good source of tannic acid, and in the 19th century, palmetto tanneries were established that extracted tannin for leather and also produced paper stock (Dodge, 1897). Supposed ly, it was more cost effective to tan leather with saw palmetto than with oa k or hemlock bark (Dodge, 1897). One such tannery was founded by a C.B. Warrand in Savannah, Georgia. He produced tannin, bedding fiber, and plastering fiber (Dodge, 1897). Manufacture of a saw palmetto wax was also contemplated, but after expe rimentation, the product was determined substandard (Wilder and Kitzke, 1954). Fig. 2.6. Illustration from The Yearling of a boy playing with a "flutt er-mill" that he made (Rawlings, 1966:1). Fig. 2.7. Whistle made of saw palmetto petiole and leaf by Bethany Highsmith. Modeled by Eldridge Wisely. Photograph taken by Bethany Highsmith. 29

PAGE 39

Finally, one additional use for the fronds are in floral displays for Palm Sunday, Christmas, and Easter (Vines, 1960). However, the more typical frond used in religious ceremonies honoring Palm Sunday is that of the Sabal palmetto (Reasoner, 1902; Constantine, 2005). 2.5. A Medical History First recognized for its curative powers by the indigenous peoples of North America, and later embraced by descendant s of slaves (Dupon, 1892; Sherrard, 1894), S. repens had its debut in modern medicine in 1879 when Dr. J. B. Read of Savannah, Georgia published a laud atory article in the American Journal of Pharmacy (Read, 1879). In his piece, entitled The Saw Palmetto (Sabal serrulata ), Dr. Read expressed surprise that the plant had not been more commonly ac knowledged earlier. He decided that it was a worthwhile candidate for further research as a curative agent when he was on a hunting trip in Florida and noticed that when anim als fed on saw palmetto berries they gained weight quite quickly and seemed to impr ove in health (Rea d, 1879). He therefore recommended saw palmetto for the following: In all cases where a highly nutritive agent is needed, it seems to apply well and to fulfill the indications. By its peculiar soothing power on the mucous membrane it induces sleep, relieves the most troublesome coughs, promotes expectoration, impr oves digestion, and increases fat, flesh, and strength. Its sedative and diur etic properties are remarkable. It has been used with benefit in cardiac asthma, phthisis7 (especially laryngeal phthisis), chronic bronchitis and dilation of the bronchial tubes. Its action in catarrhal8 affections is rapid and permanent. A cold in the head may be abated by two or three doses. Mixed in boi ling water, and 7 phthisistuberculosis 8 catarrhinflammation of the mucous membranes 30

PAGE 40

used by inhalation, it has been found ve ry beneficial in chronic ozena9. (Read, 1879:170-1) After Dr. Read presented his claims, saw palmetto received much attention in medical literature in the late 19th century and early 20th century as a cure-all for the genito-urinary tract and respiratory sy stem (Dupon, 1892; Sherrard, 1894; Eldridge, 1896; Kenner, 1900; Wyeth, 1901). It was offi cially listed as a drug in the U.S. Pharmacopoeia from 1906 to 1917 (Buck, 2004). Saw palmetto extract was marketed in many forms, including flui d extract, globules, fluid saw palmetto compound, solid extract, pills, compressed tablets, soluble el astic compounds, and elixirs (Parke, Davis, & Co. Catalog, 1901). In fact, a plethora of r ecipes for various saw palmetto tonics and elixirs abound in old materia medica. Many of the compounds for prostate health and/or gonorrhea contained a mixture of saw palme tto extract and santal (sandalwood) oil (Marcus; 1898; Kenner, 1900; Parke, Davis, & Co., 1901). Doctors (and pharmacists) claims for the efficacy of these treatments were seemingly unlimited. Saw palmetto was said to increase appetite, di gestion, weight, flesh and strength, and to act as a sedative, diuretic, and expectorant (Shoemaker, 1893; Culbreth, 1917). It was also purported t o have a special tonic effect upon the reproductive system and to exert a beneficial influence upon [the] enlarged prostate (Shoemaker, 1893:872-3). It was prescribed for whooping cough, bronchitis, tonsillitis, pertussis10, laryngitis, tuberculosis, coryza11, catarrh, cardiac asthma, phthisis pulmonalis, prostatitis, testical atrophy, uterine atrophy, afflictions of the breasts and 9 ozenaa chronic nasal disease where the nose atrophies and is accompanied by a fetidsmelling crusty discharge 10 pertussiswhooping cough 11 coryzasymptoms of a head cold 31

PAGE 41

ovaries, inflammation, croup, im potency, spermatorrhoea12, headache, neuralgia, paralysis, dysmenorrhea, gonorrhea, sexual atony13, and general debility (Knapp, 1891 Dupon, 1892; Shoemaker, 1893; Wyeth, 1901; Za ndt, 1905; Culbreth, 1917). Examples of the acclaim that saw palmetto therapy has re ceived in the past may be enhanced by narrative by Robert Boocock, M.D. from Hale's Saw Palmetto ; this The special vitalizing action of Sa w Palmetto affects the reproductive organs generally. The mamm, under its continued use, increase in size; the atrophied uterus and its inactive appendages are awakened; and by it the cold female is aroused from her sexual lassitude. In the male, the action of Saw Palmetto is just as prom pt and efficient. The cold, atrophied testes and penile organ, even if in part due to masturba tion or varicocele, are given new life and a more generous supply of blood through the influence of Saw Palmetto. Waning se xual power is restored; impotence is dethroned, and man is made new. (Hale, 1898: 64-65) I had before commencing a scalding feeling on passing my water, and a burning smarting afterwards; all which were entirely removed so that it was a comfort to pass water; the stream was larger and stronger; no getting up of nights. I changed to 2 drops of tincture three times daily. This aroused up some amorous feelings; good, firm erections, but the feelings fully under control of moral will power. The embracing was very satisfactory, and my partner wanted to know what made me so fierce; the work was very good; flow not too th in, neither was it too soon, but gave full enjoyment to both sides, as it used to be with me thirty or forty years ago. (Hale, 1898: 24-25) In an effort to back these incredible clai ms, chemical analyses of the extracts were performed (Sherrard, 1894; Gildemeister a nd Hoffmann, 1900). Dr. J. B. Read was the first professional doctor to mention oils from the fruit of the saw palmetto, but seemingly, he did not actually extract them himself (Mann, 1915). In 1890, John Lloyd affirmed that distillation produces a volatile oil which is the active ingredient of the saw palmetto berry. He warned, however, against the potential folly of prizing one constituent without 12 sexual atonylack of muscle tone in the sexual organs 13 spermatorrhoeainvoluntary semi nal discharge, without orgasm 32

PAGE 42

taking into account the potent ial chem ical effects of other seemingly inert ingredients (Hale, 1898). In 1894, C. C. Sherrard, a pharmaceutical chemist, published a report of his analysis of the mature, dried berry, in which he analyzed the moisture, inorganic constituents of the ash, and organic constitu ents. He described two fixed oils and one volatile oil, as well as a ch loroformic extract (Sherrard, 1894). He maintained, however, that of the extracted component s, the oils, resins, and total acidulated extract were the most important (Sherrard, 1894). In 1895, Coblentz distilled a small amount of oil from saw palmetto fruit, and reported the constituen ts to be volatile oil, fixed oil, fat, an alkaloid, dextrin, glucose, a nd a resin (Hale, 1898; Gildemeister and Hoffmann, 1900). A chemical report from Parke, Davis & Co. de termined that the saw palmetto fruit was comprised of bland oil and resins (Hale, 1898). The company discounted the volatile oil as possibly an ester or ethereal salt (H ale, 1898). In 1915, Charles Mann performed an extensive (for his time) chemical study on saw palmetto berry extract (Mann, 1915). He concluded that the volatile oil is not a volatile oil in the true sense of the term, but rather a mixture of ethyl esters of fatty acids (Ma nn, 1915). Modern chemical analysis using gas chromatography and mass spectrometry has show n that the fatty acids present in the saw palmetto fruit include caprylic, capric, lauric, myristic, palmitic, palmitoleic, stearic, oleic, vaccenic, linoleic, linolenic, arachid ic, gondoic, behenic, and lignoceric acids (Schantz, et al. 2008). Saw palmetto was listed in the U.S. National Formulary from 1926 to 1950, when it was removed because scientists had been una ble to pin down an active ingredient in the plant (Buck, 2004). In 1940, a masters thesis was written by Robert Cleo Stokes at the University of Florida, entitled A Pharmacognostical Study of Serenoa serrulata (Stokes, 33

PAGE 43

1940). The author described the com mercial collection processes of the berries for pharmaceuticals and examined the histology of th e seed and fruit. He culminated with a proposed change to the descri ption of "Powdered Sabal" ( S. repens ) in the National Formulary VI (see appendix for description), bu t did not perform any research to test the medical efficacy of S. repens for his thesis (Stokes, 1940). Throughout the twentieth century, claims continued to be made about the curative properties of saw palmetto (Gould, et al. 1935; Gutman, 1949; Bernard, 1966; Grie ve, 1971), but no further research supporting those claims was made until th e 1980s. The following chapter discusses benign prostatic hyperplasia and lower urinary tract symptoms, since these disorders have been the main focus of saw palmetto treat ments and medical research. Chapter Four reviews the modern research of saw palmetto as a treatment for these urogenital diseases. 34

PAGE 44

Chapter Three: Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms Benign prostatic hyperplasia (BPH) affect s millions of men worldwide, including approximately 24% of men in their 50s, 30% of men in their 60s, and 50% of men over 70 (McVary, 2007; Fernndez et al ., 2008). This common disease is the nonmalignant enlargement of the prostate gland, leading to constriction of the urethra (see Figs. 3.1. and 3.2.) and ultimately resulting in lower urinar y tract symptoms (LUTS) such as urgency, frequency, nocturia14, weak stream, and incomplete bladder voiding (McVary, 2006, 2007; Fernndez et al ., 2008). The prostate produces pr ostate-specific antigen (PSA), which is an enzyme that keeps semen in the liquid state (PSA Rising website; WebMD). Besides producing about one third of the semi nal fluid, the prostate also helps to keep urine out of the semen, and also plays a role in pleasurable sexual sensations (PSA Rising website; WebMD). Untreated BPH can lead to acute urinary rete ntion, urinary tract infection, incontinence, obstructive uropathy, bladder stones, hematuria15, hypotonic bladder16, bladder calculi17, obstructive nephropathy18, and even renal insufficiency and failure (Beckman and Mynderse, 2005; McVary, 2006 and 2007). Both herbal supplements and prescription drugs containing saw palmetto ex tract are used to treat BPH (Maccagnano et al. 2006; Alvins et al. 2008). Although the mechanisms responsible for benign prostate hyperplasia (BPH) 14 Nocturiawaking up at night to urinate. 15 hematuriapresence of blood in urine. 16 hypotonic bladderweak bladder muscle. 17 bladder calculihard minera l buildup in the bladder. 18 obstructive nephropathypermanent kidney damage caused by obstruction. 35

PAGE 45

Fig. 3.1. Lower urinary tract with normal sized prostate. Illustration by Rachel Renne. Fig. 3.2. Lower urinary tract with enlarged prostate. Note pressure on bladder, urethra, and colon. Illustration by Rachel Renne. remain uncertain, it is acknowledged that an dropause (hormonal changes, including a decline in testosterone in the aging ma le) is a contributing factor (Arruzazaba et al ., 2005; Angwafor and Anderson, 2008). Growth of the prostate gland is dependent upon 36

PAGE 46

androgen stimulation, mainly via dihydrotesto sterone (DHT), which the prostate gland crea tes from testosterone using prostate 5reductase (Arruzazaba et al ., 2005; BonnarPizzorno et al ., 2006; Fernndez et al ., 2008). The increased amount of estrogen in the prostate gland also leads to BPH, because it augments the activity of pathways that stimulate cell growth (Arruzazaba et al ., 2005). Another cause of BPH is the enhanced tone of the bladder and prostate sm ooth muscle, due to the activation of 1-adrenoceptors (Arruzazaba et al ., 2005; Fernandez et al ., 2008). In order to better understand the mechanisms that orchestrate BPH, it is best to briefly review the anatomy (Fig. 3.3.) and physio logy of the prostate. This is especially useful because the anatomy of the prostate has been described using various (and sometimes incongruent) systems over the pa st century (as reviewed in Timms, 2008). Some models described the prostate in terms of lobes, but the most up to date anatomical model of the prostate, according to Timms (2008), is defined by zones as coined by McNeal (1983): namely, the central zone, pe ripheral zone, and tr ansition zone (Timms, 2008). The central zone is a section of tissu e that constitutes th e prostatic base and encases the ejaculatory ducts. The peripheral zone stretche s around most of the central zone, and extends down along the distal por tion of the urethra. The transition zone includes the urethral glands and urethral sphincter, and is the sole area where BPH manifests. Surrounding the three zones of th e prostatic epithelium is the anterior fibromuscular stroma, comprised of blood vessels, nerves, smooth muscle, collagen, lymphatics, and fibrous tissue. The stroma suppor ts the epithelial ducts, and is an integral player in the differentiation of the epit helium (Taylor and Risbridger, 2008). 37

PAGE 47

Figure 3.3. The human prostate. Illustration by Rachel Renne. References consulted: radiograpics.rsnajnls.org and www.ajronline.org. Stromal-epithelial interactions and specifically a "reawaken ing of embryonic inductive interactions," as first proposed by McNeal (1983 ), are believed to be one of the origins of BPH (McNeal, 1983; McConnell, 1991; Barclay et al. 2005; Timms, 2008). The prostatic epithelium consists of three cell types: secretory luminal, basal, and neuroendocrine cells (Bonkhoff and Rember ger, 1996; Kasper, 2008; Taylor and Risbridger, 2008). Secretory luminal cells se crete prostate-specifi c antigen (PSA) and prostatic acid phosphatase (PAP) (Bluer et al. 2008). Increases in PSA and PAP production occur when the prostate malfunc tions. Therefore, both PSA and PAP are serum markers that can diagnose pros tate cancer and its progression (Yang et al. 2007); however, PAP is no longer routinely used, b ecause PSA tests are more sensitive and specific (Drug Information Online). Secretor y luminal cells also express the androgen 38

PAGE 48

recep tor and the cytokeratins (CK) CK8 and CK18 (Bluer et al. 2008; Kasper 2008; Taylor and Risbridger, 2008). The type of cytokeratin that is expressed can be used to classify the type of epithelial cell (Bluer et al. 2008) as well as the stage of development or transformation of the cell (i.e., such as in carcinoma) (Trompetter et al. 2008). Neuroendocrine cells are sparsely scattere d throughout the lumi nal epithelial layer (Taylor and Risbridger, 2008). They express neuropeptides such as serotonin, bombesin, calcitonin, somatostatin, and ne urophysin, but they do not ex press the androgen receptor (AR) or secrete PSA (Kasper, 2008; Taylor a nd Risbridger, 2008). The third type of cells, basal cells, is of special interest because the basal cell compartment may be the home of prostatic stem cells (Taylor and Risbridger, 2008). Basal cells produce CK5 and CK14 (Bluer et al. 2008; Kasper, 2008). They do not requi re androgen for cellular upkeep, but can be stimulated to grow and differentiate by androgens (Taylor and Risbridger, 2008). 3.1. Hormonal Regulation of Prostatic Growth 3.1.1. Androgens For BPH to manifest, an aging male must possess testicular androgens. BPH does not occur in men who have any of a number of genetic diseases that hinder androgen production, or in men who have been castrat ed at a prepubescent age (McConnell, 1991). Additionally, levels of DHT and AR remain high throughout the aging process, even though a decrease occurs in the peripheral le vels of testosterone (McConnell, 1991). Furthermore, the removal of androgen by cas tration or prescription drugs causes the hyperplastic prostate to shrink slightly (McConnell, 1991). It is believed that the hormonal regulation of prostatic growth involve s the stimulation of cell proliferation, as well as the reduction of cell death, but the m echanisms responsible for the proliferative 39

PAGE 49

process are not well understood (Begley et a l. 2005). Nevertheless, there is evidence for the involvement of DHT, AR, estrogen recep tors, stromal-epithelial interactions, and growth factors in the deve lopment of BPH (Risbridger et al. 2007; Berry, et al. 2008). The prostate is unique among androgen-dependent organs in that it remains receptive to androgens until death. The penis virtually stops expressing androgen receptors after puberty (Roehrborn et al ., 1987; Takane et al. 1991 as cited in McConnell, 1991), but if it retained androgen receptors akin to th e manner of the prosta te, it would exhibit androgen dependent growth until death (Barrack et al ., 1983; Husmann et al., 1990; Rennie et al. 1988; Takane et al. 1991 as cited in McConnell, 1991: 358). This theoretical analogy aids in the visualiza tion of the ever-growing, aging prostate. 3.1.2. Genetic Polymorphisms Findings suggest that some men are genetically predisposed to develop BPH. In the cell, DHT binds with AR to form a DHT-AR complex which binds DNA sequences to alter transcription of the AR gene. The AR gene has a CAG repeat region within exon 1 that encodes a polyglutamine tr act of variable length (Konwar et al. 2008). Men with CAG repeat lengths over 40 have clinical androgen insensitivity as well as Kennedys disease19 (Igarashi et al. 1992; MacLean et al. 1996; Giovannucci et al. 1999). Even in men with "normal" CAG repeat lengths (less than 40), shorter repeat lengths have been associated with the risk of defective sperm production (Tut et al. 1997). Transfection20 research has exhibited inverse and linear co rrelations between CAG repeat length in the AR gene and transcriptional activation, implying that a longer polyglutamine chain 19 Kennedy's diseasea degenerative neuromus cular disease that only affects males; related to mutation of the AR (Barkhaus, 2008). 20transfectiona change in cell properties cause d by the artificial in troduction of foreign DNA into cultured eukaryotic cells (www.mercksource.com). 40

PAGE 50

im pairs AR expression (Chamberlain et al ., 1994; Kazemi-Esfarjani et al ., 1995; Tut et al. 1997; Giovannucci et al., 1999). Some researchers have extrapolated that since shorter CAG repeat lengths are linked to incr eased AR expression, this in turn incites BPH (Choong et al ., 1996; Giovannucci et al. 1999). However, some studies show that only specific lengths are of significance to AR expression (Beilin et al .,2000). In other words, CAG repeat length cannot be viewed as a continuum wherein the longer th e polyglutamine tract, the gr eater the risk for prostate diseases. Conversely, due to more recent finding s, many argue that only relatively modest effects of CAG repeat length on AR expression can be demonstrated, and therefore it should not be attributed such importance as a potential contributor to prostatic disease (Ding et al. 2004). Nevertheless, CAG repeat length is still being researched for its relation to BPH and prostate cancer, and ev idence suggesting that shorter CAG repeat length decreases the risk for BPH is still being published (Das et al. 2008). Klotsman et al. (2004) evaluated the steroid 5reductase type I ( SRD5A1 ) and type II (SRD5A2 ) genes for their association with severi ty of BPH. An association was found between polymorphisms in SRD5A1 and severity of BPH, but no association with polymorphisms in SRD5A2 was documented (Klotsman et al ., 2004). Salam et al (2005) examined three polymorphisms in the SRD5A2 gene for their associations with BPH and prostate cancer in a clinical trial of 606 men of various ethni cities in Los Angeles, CA. They found an association between the V 89L polymorphism and BPH and prostate cancer (Salam et al. 2005). Additionally, their research showed that the polymorphism V89L was associated with higher PSA serum levels in men with BPH. They proposed that V89L may be associated with BPH severity; however, further research is needed to 41

PAGE 51

clearly define this relationship. Polym orphisms in cytokine genes are also being researched for their role in causing BPH. Konwar et al. (2008) recently explored the relationships between BPH and the cytokines interleukin (IL)-4, IL-1 and IL-1 IL-4 belongs to the Th2 cytokine family, and it has powerful anti-inflammatory effects (Konwar et al ., 2008). It also causes proliferation of fibroblasts and inhibits clonal prostatic stromal smooth muscle cell growth (Konwar et al. 2008). IL-1 and IL-1 are in the IL-1 family and have inflammatory effects (Konwar et al. 2008). IL-1 and IL-1 compete with the IL-1 receptor antagonist (IL-1Ra) (Arend et al. 1998). Prostatic epithe lial cells generate IL1 which in turn triggers fi broblast growth factor (FGF)-7 expression in the stroma (Konwar et al ., 2008). FGF-7 then stimulates proliferation of the epithelial cells and more IL-1 expression, forming a cyclical proliferatio n of tissue in the transition zone (Konwar et al. 2008). Secreted IL-1 is thought by some to be a ma jor potential contributor to the development of BPH (Ricote et al ., 2004). As part of a rando mized clinical trial of 510 Caucasian men from Olmsted County, Minne sota, no significant relationship was found between BPH and the IL-1, IL-8, or IL10 genetic polymorphisms, however (Mullan et al. 2006). Much research on genetic polymorphisms and BPH regards BPH as just an early stage of prostate cancer, when in actuality, they stem from two distinct pathogeneses. BPH is a stromal disease that originates in the periurethral tissues while prostate cancer is an epithelial disease that typically forms in the peripheral regions (Ekman, 1989). Furthermore, the correlation between ethnic ity, genetics, and the pathogenesis of BPH needs to be further explored. 42

PAGE 52

3.1.3. Estrogens Estrogens, metabolites of androgens, play a key role in the development of BPH (Risbridger et al. 2007). Estrogen receptors (ERs) can both stimulate and inhibit prostatic cell proliferation. ER has a proliferative effect, while ER has an inhibitory effect (Risbridger et al 2007). Therefore, either overexpression of ER or inhibition of ER (or a combination), can result in BPH (Risbridger et al. 2007). Moreover, recent research by Zhang et al (2008) indicates that estrogen can activate the extracellular signal-regulated kinase (ERK) pathway and thereby induce prostatic stem cell proliferation (Zhang et al. 2008). In general, the comple x role of estrogens in the incidence of BPH is not that well defined a nd begs further researc h. Further defining the relationship between estrogens and BPH could potentially lead to better treatments for the prostatic disease. 3.2. Stromal-Epithelial Intera ctions and Proliferation Studies show that stromal-epithelial para crine signaling is part of the complex process that mediates epit helial cell differentiation (McConnell, 1991). It has been hypothesized that BPH results from a disrup tion of this mediation and consequent unchecked cell proliferat ion (McConnell, 1991). Barclay et al. (2005) developed a system for studying epithelial-stromal interactions in BPH. They grafted BPH stro mal cells (BPH-S) under the renal capsules of nude mice. They discovered that BPH-S can cause induction in prostatic tissue recombinants (Barclay et al. 2005). 3.3. Growth Factors A few studies have examined the role of growth factors in the development of BPH. Insulin-like growth factors (IGFs) are involved in prostate growth and 43

PAGE 53

developm ent, and altered IGF activity has been observed in BPH tissue (Eaton, 2003; Cohen et al., 2000; Lee and Peehl, 2004). When IGF-1 binds to the IGF-1 receptor, the ERK arm of the mitogen activated protein kinase (MAPK) cascade21 and the phosphoinositol-3 kinase/protein kinase B cascade (PI3K/Akt) 22 are activated (Wadsworth et al. 2004). Transforming growth factorhas been established as a regulator of Insulin-like Gr owth Factor Binding Protein (IGFBP) production, and more specifically as a stimulator of IGFBP-3 and a cell-growth inhi bitor (as reviewed in Cohen et al. 2000). It is thought that inhibition of IGF-signaling co uld be a potential treatment for BPH (Wadsworth et al. 2004). Several in vitro experiments have shown that the IGF axis plays an important role in human prostatic cellular grow th (as reviewed in Neuhouser et al. 2008). Many clinical trials have been performed in an attempt to clarify the role that IGFs play in BPH. Unfortunately, there are conflicting results among some recent studies. Chokkalingam et al. (2002) investigated the ri sk of BPH associated with IGFs. Their research demonstrated a positive correlation between pl asma levels of IGF-1 and IGF-3 and the risk of BPH in Chinese men. Howe ver, a clinical trial by Mullan et al (2006) failed to show any significant association between BPH and IGF-1, epidermal growth factor (EGF), or IGFBP-3, which binds to IGF-1. IGF-3 was not tested (Mullan et al. 2006). Nonetheless, Neuhouser et al. (2008) carried out a nested -case-control study in the placebo set of the prostate cancer prevention trial. They found that men with severe 21 MAPK/ERK pathwayis a complex signa l transduction pathway that relates intracellular responses such as proliferation to the binding of growth factors to cell surface receptors (Karp, 2005). 22 PI3 kinases are associated with cell grow th, proliferation, diffe rentiation, and signaling (Karp, 2005). 44

PAGE 54

sym ptoms had lower levels of IGFBP-3. They also found a positive correlation between the IGF-1:IGFBP-3 ratio and risk of BPH (Neuhouser et al. 2008). By examining surgically removed human prostatic tissue, Soulitzis et al (2006) found that characteristic grow th factors, transforming growth factor(TGFB1), vascular endothelial growth factor (VEG F), and IGF-1 were underexpressed in the hyperplastic prostate, and suggested these as potential candidates for disease detection (Soulitzis et al. 2006). Trojan et al. (2006) provided evidence th at serum levels of IGF-2 should be used in conjunction with levels of PSA to discrimi nate between BPH and prostate cancer (Trojan et al. 2006). Ideally, advances in this field will lead to earlier disease detection. 3.4. Inflammation Current research purports that BPH is not so much induced by an embryonic reawakening of differential tissues in the prostate, but rather is an immune-mediated inflammatory disease (Kramer et al ., 2002; Kramer et al. 2007; Nuez et al ., 2008). Approximately 40% of BPH patients who have had histologic examinations exhibited inflammatory symptoms (Sciarra et al. 2007). A study by Kramer et al. (2007) found inflammatory infiltrates (of CD4+T lymphocytes and proinfla mmatory cytokines) in nearly all of the BPH specimens teste d. They also found cytokine production in association with the inflammatory infiltrates. Their data, as well as other recent findings which indicated BPH stromal cells as inducers of inflammation (Penna et al. 2009), strongly support that BPH is an immune -mediated inflammatory disease (Kramer et al. 2007; Sciarra et al. 2007). 45

PAGE 55

3.5. Measures of Severity and Incidence Lower Urinary Tract Symptom s (LUTS) resulting from BPH can be grouped into two categories, those with obstructive sympto ms and those with irritative symptoms. Obstructive symptoms include hesitancy, weak stream, straining, incomplete voiding, and dribbling (Rong et al. 2008). Irritative symptoms ar e supposedly caused by detrusor23 overactivity, and cons ist of urgency, frequency, and nocturia (Rong et al. 2008). Of men diagnosed with BPH, 50% have moderate to severe LUTS (Wasserman, 2006). Severity of LUTS and BPH is measured with the In ternational Prostate Symptom Score (IPSS) (Nickel et al. 2008). The IPSS is determined from a seven question questionnaire from the American Urological Association sympto m index (AUA-SI) with one added question concerning how urinary symptoms affect quality of life (Nickel et al., 2008; Rong et al ., 2008). 3.6. Treatment Treatment options for BPH and LUTS vary, from surgery to synthetic drugs to herbal supplements such as saw palmetto. In the past, surgical treatment was the normal procedure, but according to US Medicare data there has been a marked decrease since the late 1980s in prostatectomies received for BPH related conditions, presumably due to the increase in medical altern atives (McVary, 2007). Even ca stration has been used as a drastic, but effective treatment for BPH (Ekman, 1989). Currently, the most common treatments are prostate 5 -reductase inhibitors and 1-adrenoreceptor antagonists. There are three subtypes of 1-adrenoreceptors: 1A, 1B, and 1D, each with different functions (as reviewed in McVary, 2007). The 1A subtype mediates smooth muscle tone in the prostate and bladder neck. The 1B subtype controls blood pre ssure by contraction of the 23 detrusorthe muscle that pushes urine out of the bladder. 46

PAGE 56

sm ooth muscle in blood vessels. The 1D subtype is related to sacral spinal cord innervation and bladder muscle contr action (as reviewed in McVary, 2007). 1adrenoreceptor antagonists effectively relax th e smooth muscle of the prostate, thereby relieving urethral constric tion and other LUTS (McVary, 2006; McVary, 2007). Prostate 5 -reductase inhibitors have been shown to prevent further prostate growth and complications (McVary, 2006; McVary, 2007; Fernndez et al ., 2008). Clinical studies show that, for the most part, 1-adrenoreceptor antagonists and prostate 5 -reductase inhibitors are effective; however, they are not without adverse effects (McVary, 2007; Fernndez et al ., 2008). Common side effects of 1 adrenoreceptor antagonists include dizziness, headache, edema24, weakness, nasal congestion, orthostatic hypotension25, abnormal ejaculation, erectile dysfunction, palpitations, and fatigue (Beckman and M ynderse, 2005; McVary, 2007). Adverse effects of prostate 5 -reductase inhibitors include urog enital effects, decreased libido, ejaculatory dysfunction, erectile dysfunction, ort hostatic hypotension, and gynecomastia26 (Beckman and Mynderse, 2005; McVary, 2007). Although relegated to the realm of unregulated herbal supplements in the United States, medications containing saw palmetto berry extract and other compounds are widely used to treat BPH in Europe, particul arly in Germany, Aust ria, France, and Spain (Rong et al. 2008). While many phytotherapy treatments for BPH are currently on the market, including products made fr om South African star grass ( Hypoxis rooperi ), stinging nettle ( Urtica diocia ), African plum ( Pygeum africanum ) and rye pollen (Secale 24 edemaan abnormal accumulation of flui d beneath the skin or in a body cavity 24 orthostatic hypotensionform of low blood pressure that causes dizziness when one stands after sitting or lying down (from www.mayoclinic.com). 25 gynecomastiaabnormal breast enlargement in males 47

PAGE 57

48 cereale ), saw palmetto is by far the most commonly used (Madersbacher et al. 2007). The next chapter will examine the efficacy of saw palmetto berry extract as a treatment for BPH and LUTS.

PAGE 58

Chapter Four: Saw Palmetto as a Treatment for BPH and LUTS Over the past twenty years, saw palmetto has been a major focus of prostatic research. The mechanism by which saw palmetto acts is still uncertain, but four different mechanisms have been proposed, linked to various ingredients in the berry extract (Dedhia and McVary, 2008). It was previously thought that perhaps saw palmetto extract relaxed the smooth muscle of the prostate through 1-adrenergic receptors. In earlier in vitro research, it seemed like there was great potential for this to be a mechanism (Goepel et al. 1999 as cited in Dedhia and McVary, 2008). In spite of this, a later experiment involving healthy young medical students seem ed to demonstrate that saw palmetto extract does not block 1-adrenoreceptors in vivo (Goepel et al. 2001); on the other hand, the methodology of this study was questionable since it only involved 12 participants (Goepel et al. 2001). Nonetheless, one study using rat prostate glands showed that saw palmetto induces 1-adrenoreceptor-mediated contractions instead of inhibiting them (Cao et al. 2006). A second, more in vogue proposed mechanism of saw palmetto extract is the antiinflammatory effect (Goldman et al. 2001; Raman et al. 2008). The basis for this mechanism was the discovery of inhibitory effects of acidic lipophilic agents in saw palmetto extract on the synthesis of cyclooxygenase and 5-lipoxygenase in vitro (Buck, 2004). The latter are implicated in the inflammatory process (Covey et al. 2007; Leone et al. 2007). A third proposed mechanism is an antiandrogenic effect (Buck, 2004). Research of the popular brand of saw palmetto extract called Permixon indicates that saw palmetto functions as a 5 -reductase inhibitor, and as such inhib its the conversion of testosterone to DHT (Dedhia and McVary, 2008). In vitro experiments have 49

PAGE 59

dem onstrated that the saw palmetto extrac t called IDS 89 dose-dependently inhibits 5 reductase activity in benignly hyperplastic human epithelial and st romal cells (Weisser et al. 1996). On the other hand, other evidence main tains that Permixon does not have a 5 -reductase inhibitory effect at physiological doses (Rhodes et al. 1993). A final potential mechanism is that saw palmetto ex tract possesses an apoptotic effect (i.e., promotes programmed cell death) and inhi bits cellular proliferation (Vacherot et al ., 2000 as cited in Dedhia and McVary, 2008). There is supporting evidence for this mechanism based upon the Bax-to-Bcl-2 expression ratio and caspase-3 activity (molecular markers of the apoptotic process), which indicated that Permixon increased apoptosis in the prostatic tissue of patients with BPH (Vela-Navarrete et al. 2005). 4.1. Inhibition of COX Enzy mes and Lipid Peroxidation Cyclooxygenase (COX) enzymes are inte gral players in inflammation, and therefore, in the developmen t of BPH. The COX enzyme has two isoforms, COX-1 and COX-2. COX-1, the constitutive form, regulates basic cellular function and takes part in prostaglandin production (Cryer and Dubois, 1998). COX-2, the inducible form, is generated as a reaction to inflammation, and is also found in high levels in many types of cancers (Hsi et al ., 1999; Lipsky, 1999). Inhibitors of both COX-1 and COX-2 are thought to be useful in the prevention and treatment of cancer (Leone et al. 2007). COX2 enzyme inhibitors are also potentia lly useful anti-inflammatories (Raman et al. 2008), but, they are known to cause serious cardiovas cular problems (as revi ewed in Zarraga and Schwarz, 2007). Additionally, COX-1 inhibitors have the adverse effect of gastric ulcerations, since COX-1 is needed for prostaglandin production and prostaglandins are 50

PAGE 60

necessary for the m aintenance of the mucosa l lining of the stomach (as reviewed in Zarraga and Schwarz, 2007). Raman et al. (2008) tested a variety of botanical supplements for their ability to inhibit COX-1, COX-2, and lipid peroxidation using bioassays. The latter was studied because lipid peroxidation has been linked to several diseases, and because inhibiting lipid peroxidation in the body can thwart free radical generation and resultant oxidative tissue damage (Raman et al. 2008). They tested COX-1 prepared from ram seminal vesicles. COX-2 activity was assessed us ing a form of COX-2 known as human prostaglandin H synthase isoenzyme 2 (hPGHS-2) cloned in insect cells. The lipid peroxidation assay was performed by oxi dizing a model liposome using fluorescence spectroscopy (Raman et al. 2008). Their results demonstrat ed selective COX-1 enzyme inhibitory activity (~10%) at 100 g/mL saw palmetto extract, and also a modest inhibition of lipid peroxidation at 25 g/mL of the extract (Raman et al. 2008). Additionally, Goldmann et al. (2001) reported a rela tionship between saw palmetto and COX-2 in a prostatic cell culture system and determined that saw palmetto berry extract inhibited COX-2 enzyme expression at the translational level (Goldmann et al. 2001). 4.2. Cell Growth Inhibition Goldmann et al. (2001) also investigated the inhib ition of cell growth in prostatic cancer cells by comparing the gr owth of normal prostate and prostate cancer cell lines in the presence and absence of saw palmetto berry extract. Their data showed growth inhibition of 20-25% of a normal prostatic derived cell line and 50% inhibition of two 51

PAGE 61

prostatic carcinom a cell lines in the presence of saw palmetto berry extract (Goldmann et al. 2001). Other research on a saw palmetto herbal blend containing 106 mg of saw palmetto berry lipoidal extract along with nettle root pumpkin seed oil, and lemon bioflavonoid extracts plus beta-carotene, evaluated the effects of this treatment on prostatic tissue contraction and PSA level (Marks et al. 2000). Men treated with the saw palmetto blend experienced a significant increase in their prostatic atrophy indexes (Marks et al ., 2000). Atrophy index was defined as the percen tage of atrophic prostatic tissue upon 4x magnification examination of the whole core (Marks et al. 2000). The percent of epithelial tissue in the transition zone d ecreased significantly af ter six months of treatment with the herbal bl end. Nevertheless, there were no significant changes in the PSA levels of the participants (Marks et al. 2000). It was hypothesi zed, therefore, that the atrophy of prostatic epith elial tissue occurred via some nonhormonal mechanism (Marks et al. 2000). 4.3. Androgen Levels Marks et al. (2001) quantified androgen levels in prostatic biopsy cores to observe the effects of a saw palmetto herbal blend (the same blend described above as used by Marks et al. (2000)) versus finasterid e in men with BPH. Finasteride is a prescription drug that treats BPH and prostate cancer by inhibiting type II 5-al pha reductase. Forty men participated in a randomized six month trial, receiving either the herbal blend or a placebo (Marks et al. 2001). Fifteen men who were undergoing chronic finasteride therapy were also examined. In the clinical trial, it was dete rmined that the saw palmetto herbal blend caused DHT levels in the prosta te tissue to decrease 32% after six months. 52

PAGE 62

In com parison to the finasteride effect on DHT levels (80% lower than prostatic levels in untreated patients), the effect of saw palme tto was modest, but statistically significant (Marks et al. 2001). Moreover, although finasteride substantially increased prostatic tissue testosterone levels, no increase was seen in those men treated with the saw palmetto herbal blend. The researchers state that their findings are consistent with the hypothesis that saw palmetto acts as an in vivo 5reductase inhibitor (Marks et al. 2001). In a mouse experiment, high doses (300 mg/kg of body weight daily) of saw palmetto extract reduced levels of DH T in the prostate by 31% (Wadsworth et al. 2007). Low doses of saw palmetto extract (50 mg/ kg of body weight daily), on the other hand, did not significantly alter prostatic DHT levels. Both circulating androgen levels and prostatic testosterone levels were not significantly altered by either low or high doses of saw palmetto extract (Wadsworth et al. 2007). An earlier clinical trial compared fina steride and Permixon (a French brand composed of a lipidosterolic extract of S. repens ) to evaluate their inhibitory effects on 5reductase in healthy male volunteers (Strauch et al. 1994). Their randomized, placebocontrolled trial was only a week long, and involved just 32 participants. The measurement of 5reductase inhibition was determined by serum DHT levels, and serum testosterone levels we re also measured (Strauch et al. 1994). Permixon had no significant effect on the serum DHT levels. Th erefore, the data in this study do not support that S. repens extract works through a 5reductase inhibitory mechanism (Strauch et al. 1994). 53

PAGE 63

4.4. Insulin-Like Grow th Factors As discussed previously, the IGF axis pl ays an important role in human prostatic cellular growth, and therefore, has been targeted in research as a lead to new possible treatments for BPH (as reviewed in Neuhouser et al. 2008). Wadsworth et al. (2004) studied insulin-like growth f actor (IGF) signaling in human prostatic epithelial cells, and discovered that saw palmetto berry extract ha d an inhibitory effect on this type of signaling. Their ground-breaking re sults revealed that saw palm etto berry extract inhibits the phosphoinositide 3-kinase/protein kinase B (P13K/Akt) signaling pathway and activates the proapoptotic en zyme known as stress activated protein kinase/cjun -NH2kinase (SAPK/JNK) (Wadsworth et al. 2004). To my knowledge, no further research investigating the effect of S. repens on IGFs has been conducted (PubMed and Web of Science database searches26). 4.5. Other Clinical Trials Older clinical trials have shown, bot h subjectively and objectively, that saw palmetto extract is helpful in the treatment of LUTS (C rimi and Russo, 1983; Champault et al. 1984; Descotes et al. 1995; Carraro et al. 1996; Gerber et al. 2001). Unfortunately, the majority of these studies have glaring methodological flaws, such as inadequately long study periods, insufficient evaluation of obj ective measures of bladder obstruction, and failure to use standardized questionnaires to assess efficacy (Gerber et al. 1998). Gerber et al ., (1998) performed a well designed study of 50 patients in which they measured several objective urodynamic parame ters, including measurement of urinary 26Search was performed on 1/15/09 using keywor ds insulin like growth factor, and saw palmetto 54

PAGE 64

flow rate, postvoid residual volum e of the bl adder, measurement of PSA level and other serum levels, in addition to an IPSS questionn aire and other analys es. After receiving 160 mg of saw palmetto supplement twice a day fo r six months, the partic ipants in this study had a significant average improvement in their IPSS, but no other significant improvements in urodynamic parameters occurred (Gerber et al. 1998). Also noteworthy, no adverse effects to the saw palme tto extract were perceived by or noted in participants of this study. In addition, it s hould be mentioned that this trial was not placebo controlled (Gerber et al. 1998). As discussed below, more recently, however, even better designed trials failed to show improvement in patients with BPH after treatment with saw palmetto extract (Willetts et al. 2003; Bent et al. 2006). In a 12-week double-blind, placebo-controlled, randomized trial, 100 men with BPH symptoms were randomly given a daily do se of either 320 mg of saw palmetto extract or a placebo (Willetts et al. 2003). To test efficacy, IPSS, peak urinary flow rate, and the Rosen International Index of Erectile Function (IIEF) were measured. There was a significant improvement in both IPSS and peak urinary flow rate among all the men after treatment, but with no si gnificant difference between th ose receiving saw palmetto and those receiving the placebo (Willetts et al. 2003). There was no significant change in the IIEF scores after treatment, nor between the placebo and S. repens groups. Age was the only factor that contributed significantly to the IIEF scores, which measured sexual function (Willetts et al. 2003). Bent et al. performed a one year long, double-blind, randomized, placebocontrolled trial with 225 men ove r 49 years old who had moderate to severe symptoms of BPH (Bent et al. 2006). The health indicators measured were American Urological 55

PAGE 65

Association Sy mptom Index (AUASI) scores, maximal urinary flow rate, prostate size, residual urinary volume after voi ding, quality of life, seru m prostate-specific antigen levels, and adverse events (Bent et al. 2006). This larger clinic al trial also showed no significant difference in measured outcomes between saw palmetto extract and the placebo and thus conflicts with some of the prior evidence regarding the efficacy of saw palmetto (Bent et al. 2006). 4.6. Meta-Analyses Several meta-analyses have attempted to draw conclusions from the variety of idiosyncratic methodologically flawed studies evaluating the efficacy of saw palmetto against BPH and LUTs. Wilt et al (1998) carried out a meta -analysis of 18 studies regarding the efficacy of saw palmetto as a treatment for BPH. The compilation of research included a total of 2, 939 men analyzed (Wilt et al. 1998). Of the 18 studies, 13 were placebo controlled, 16 were double-blind, and only 10 involved saw palmetto extract alone without any othe r herbal ingredients. The data from 10 studies exhibited improved urinary symptom scores and nocturi a in men treated with saw palmetto as compared to those receiving a placebo (Wilt et al. 1998). Eight studies demonstrated an improvement in maximum urinary flow am ong men being treated with saw palmetto. None of the findings presented in the meta-analysis demonstrated that saw palmetto extract had any effect on either prostate volume or PSA (Wilt et al., 1998). Boyle et al. performed a meta-analysis of all cl inical trials published that used Permixon as a treatment for men with BPH. This analysis included a total of 17 studies and 4280 patients, but only eight of them were placebo-controlled. The random-effects meta-analysis demonstrated a mean reduction in IPSS (however, only six studies used the 56

PAGE 66

IPSS) and nu mber of nocturnal voids and an increase in urinary flow rate (Boyle et al. 2004). There was also a placebo effect toward urinary flow rate and number of nocturnal voids, but the effect of Permixon was greater (Boyle et al ., 2004). 4.7. Placebo Effect A major concern in clinical trials inves tigating the efficacy of treatment with saw palmetto extract is the placebo effect. One of the main flaws in many randomized studies of men with LUTS and BPH is the failure to take the placebo effect into account. Gerber et al. (2001) performed a randomized, double-blind, placebo-controlled trial of saw palmetto in men with LUTS. They assessed the symptoms of their participants using the IPSS, a sexual function questionnair e, and urinary flow rate (Gerber et al. 2001). All participants were given a placebo for the first month of the study, and those that significantly responde d to the placebo were eliminated. The remaining participants were randomly admini stered either saw palmetto extract or placebo for six months. Men in both groups expe rienced a decrease in their IPSSs, but the decrease of the group taking saw palmetto was significantly greater stat istically than that of the placebo group (Gerber et al. 2001). Neither group experienced an improvement in sexual function. Both groups had a slight increas e in their urinary flow rates, but there was no significant difference in the degree of improvement between them. 4.8. Adverse Effects With all medical treatments, it is critical to assess not only th eir efficacy, but also their safety. Most clinical trials evaluating the efficacy of saw palmetto extract against BPH reported no significant difference in the occurrence of adverse events between men 57

PAGE 67

taking saw palm etto and men taking the placebo (Bent et al. 2006; Avins et al. 2008). A few studies have been specifi cally designed to evaluate the safety of saw palmetto. In a year-long, randomized clinical tr ial among 225 men with BPH, comparing a standardized saw palmetto berry extrac t with a placebo, called the STEP, or (S aw P almetto for T reatment of E nlarged P rostates) study, it was found that twice daily doses of 160 mg of saw palmetto extract were not associated with a ny significant adverse effects (Avins et al. 2008). On the other hand, the STEP study also showed no indication that saw palmetto extract had any effect on alleviating BPH or LUTS symptoms (Avins et al. 2008). Finally, it is important to note that a year-long study is not sufficient to ascertain potentially rare but serious side effects that may become evident over a longer period of time (Avins et al. 2008). Perhaps even more import antly, it was noted that very few clinical trials in BPH patients even mention a methodology for systematically assessing adverse effects of saw palmetto (Avins et al. 2008). In a small study to determine the effect of certain herbal medicines (including saw palmetto) on platelet function, in whic h 10 people were given the manufacturers recommended dose of saw palmetto for two weeks and then their platelet function assessed, no adverse effects of saw palmetto were found (Beckert et al. 2007). This study was intended to discover the risk of peri operative bleeding among patients taking herbal supplements (Beckert et al. 2007). Although the researchers cl aim that their data prove that saw palmetto extract does not affect plat elet function, the value of their findings is questionable due to their miniscule subject pool and the relatively short duration of the study. 58

PAGE 68

There is one case report that discusse d a possible link betw een intraoperative hemorrhage and the use of saw palmetto extract (Cheema et al. 2001). Although quite serious, no other incidents have been repor ted connecting hemorrhaging to use of saw palmetto. Another case report implicated sa w palmetto in the induction of both acute hepatitis and pancreatitis (Jibrin et al. 2006). Furthermore, two different incidents of men taking saw palmetto who underwent cataract surgery led Yeu and Grostern (2007) to suggest that saw palmetto extract could cause loss of iris tone and intraoperative floppyiris syndrome (Yeu and Groste rn, 2007). It is r ecommended that cataract surgeons ask patients about any supplements they might be using and take into account complications that could be caused by saw palmetto supplements (Yeu and Grostern, 2007). Several less severe side effects, such as night sweats, diarrhea, nausea, and abdominal pain have been reported in associ ation with saw palmetto ; however, these side effects are not significant compared to the placebo in placebo-c ontrolled studies (as reviewed in Maccagnano et al. 2006; Shi et al. 2008). Non-placebo-controlled studies have also recorded similar effects (Gurley et al. 2004; Angwafor and Anderson, 2008). 4.8.1. Cytochrome Inhibition Although much research suggests that, wh en taken by itself, saw palmetto has no serious adverse side effects (Bent et al. 2006; Avins et al., 2008), it could possibly produce adverse effects when taken in combina tion with other medications. Of particular concern is the cytochrome inhibitory action of saw palmetto extract, since cytochromes are necessary for the metabolism of the bulk of current medications (Foti and Wahlstrom, 2008:67). The cytochrome P450 s uperfamily is also associat ed with the synthesis and metabolism of steroids, fatty acids, bile acid s, vitamins, and prosta glandins (Schuster and 59

PAGE 69

Bernhardt, 2007). Individual form s of cytochro me P450 have a wide variety of functions, ranging from gene regulation to signal tran sduction and other activities; therefore, cytochromes are targeted as potential therapeu tic agents (Schuster and Bernhardt, 2007). Saw palmetto has exhibited inhibitory activity of CYP2C9, CYP2D6, and CYP3A4 in vitro (Yale and Glurich, 2005) On the other hand, in vivo studies in humans taking saw palmetto documented absolutely no effect on the marker activities of CYP1A2, CYP2D6, CYP2E1, and CYP3A4 (Markowitz et al ., 2003; Gurley et al ., 2004). Furthermore, in a two-week study performed on healthy huma n volunteers, no evidence was found of interactions between typical doses (320 mg daily) of saw palmetto extract and medications that are dependent on the CY P2D6 or CYP3A4 pathways (Markowitz et al. 2003). A slightly longer (28 da y) study on healthy human volunteers implied that it is unlikely that saw palmetto would cause CYP1A2-, CYP2D6-, CYP2E1-, or CYP3A4mediated drug interactions (Gurley, et al. 2004). Incidentally, it s hould be noted that the number of participants in these two tria ls was surprisingly smalleach had only 12 participants (Markowitz et al. 2003; Gurley et al. 2004). Further research is needed to impr ove treatment for BPH and LUTS, and to definitively determine whether or not saw palm etto is a valuable addition to treatment regimens. In the final chapte r of this thesis, improvement s to methodologies of future clinical studies will be s uggested, and other potential me dical uses for saw palmetto extract will be discussed. The next chapter explores the arduous palmetto berry harvesting in Florida that supplies pharmaceu tical companies with the raw materials for their medicines. 60

PAGE 70

Chapter Five: Harvesting This chapter is a small glimpse at the saw palmetto berry harvesting industry in Florida through the eyes of a few people from diverse backgrounds. I chose to interview a berry harvester in Vero Beach, a land ma nager from the Southwest Florida Water Management District, and a man from Wauchula whom I wo uld describe as a berry broker. Protocol approval was obtained from New College of Florida's Institutional Review Board for these interviews (IRB# 08041). The real names of the berry harvester and berry broker are not used in this thesis for their protection. The former will be referred to as Julian Perez, and the latter as Randy Delaney. This chapter provides case reports of human interactions with saw palm etto in modern times. Generally, it is no longer being used for thatch, scrub brushes, and soft drinks. Instead saw palmetto berries are a lucrative medicinal export product, a nd their harvest provides work for many each year, while still others, such as land manage rs and conservation officials, struggle to protect the palmetto from disturbance. 5.1. The Berry Boom The berry market boomed in the late 1990s (R. Delaney, berry broker, pers. comm., 2009). In 1996, researcher s at the Institute of Food and Agricultural Sciences (IFAS) at the University of Florida thought that saw palme tto berries could soon become one of the Florida's biggest cash crops (UF/IFAS News, 1996). Suddenly, ranchers started to see the saw palmetto that they had always cursed as a potential source of extra income. In 1997, the Florida legislature de clared the berry as a legitimate crop (Fooksman, 2006). It has been estimated that saw palmetto yields an average of 1,000 pounds per acre (UF/IFAS News, 1996). Thus, even when the market price is low, at 25 61

PAGE 71

cents per pound, a rancher could m ake a pr ofit of up to $100 per acre. Compared to selling cattle, selling saw palmetto berries is a lucrative affair (UF/IFAS News, 1996). 5.2. Collection Methods: Past and Present Harvesting berries to sell to pharmac eutical companies has presumably been occurring since businesses such as Parke, Davis, & Co. sold elixirs made with saw palmetto in the early 1900s (Parke, Davis & Co. Catalog, 1908). Th e earliest in-depth description of berry collection methods that I was able to find is in Richard Cleo Stokes masters thesis, A Pharmacognostical Study of Serenoa serrulata (Michx.) Hook. (Saw Palmetto) from 1940. Stokes interviewed experienced collectors of his day and reported their opinions and experiences (Stokes, 1940). He observed that fruit production was of ten more abundant every other year, but he did not know why (Stokes, 1940). His obser vation might, in part, be explained by the fact that fruit production quite frequently increases the year after a fire (Carrington and Mullahey, 2006; W. VanGelder, land manager, pers. comm., 2009). Of course, this leaves the fruit production dependent on the frequency of fires; but, in natu ral Florida habitats, fires occurred quite frequently (Carrington and Mullahey, 2006; W. VanGelder, pers. comm., 2009). The collection methods that Stokes witnessed were simple and are basically the same today. The fruiting stalks were cut w ith pruning shears and then shaken over an ordinary bean hamper to drop the berries (Stokes, 1940). Men that I have recently interviewed who harvest palmetto berries told me that they employed similar methods. If the berries are less ripe, then they cut the stalks as Stokes said, and run their hands over the berries to drop them from the stalk, either into a bucket or a sack (J. Sklaroff, pers. comm., 2008; J. Perez, pers. comm., 2009; R. Delaney, pers. comm., 2009). If the berries 62

PAGE 72

are da rker and more ripe, then they simply put the collecting container under the fruiting stalk and a gentle agitation is enough to cause the berries to fall (see Fig. 5.1.; J. Sklaroff, pers. comm., 2008; J. Perez, pers. comm., 2009). Since S. repens is so sharp, men often wear socks on their arms in addition to glove s for protection, as well as long pants, long sleeve shirts, and boots for the rattlesn akes (R. Delaney, pers. comm., 2009). Fig. 5.1. Harvesters workin g for Saw Palmetto Berries Co-Op (from Thorner, 2003). 5.3. Demographics In 1940, Stokes stated that experienced, white collectors were responsible for the harvesting (Stokes, 1940). I find that a p eculiar statement, and wonder if it was more reflective of his personal beliefs or bias than on the true demographics of the collectors at the time. William VanGelder, a land manager from Southwest Florida Water Management District (SWFWMD) said that in his personal experience, he has only discovered hispanic pickers trespassi ng on SWFWMD land for saw palmetto (W. VanGelder, pers. comm., 2009). When asked about the racial demographics of the collectors, Julian Perez, a former harvester fr om Vero Beach, said that they are mostly hispanic, but that recently he has seen a lot more Caucasion people in the field (J. Perez, pers. comm., 2009). Berry broker Randy Delane y hires laborers in Immokalee to pick 63

PAGE 73

berries for him He estimates that approximate ly one third of his labor force is Haitian, and the rest of the men are Hispanic (R. Delaney, pers. comm., 2009). Today, the typical collector is a migrant agricultural worker, either supplementing his/her income on the weekends or collecting full-time during the saw palmetto season if otherwise unemployed (W. VanGelder, pers. comm., 2009; J. Perez, pers. comm., 2009). Many collectors freelance harvest and sell thei r berries to berry brokers, or directly to harvesting companies (J. Perez, pers. co mm., 2009, Saw Palmetto Harvesting Company website). 5.4. Brokerage Harvesting companies often hire brokers, such as Delaney, to organize pickers for them. Delaney makes deals with landowners all over Hardee County, and brings in laborers from Immokalee to harvest the palmetto berries. During season, Delaney typically brings about 60 to 80 men with him to harvest. Working from 7:00 in the morning to 4:00 in the afternoon, they can cover from 150 to 300 acres per day, harvesting about 30,000 to 50,000 pounds (R. Dela ney, pers. comm., 2009). The average worker harvests from 400 to 600 pounds per day. However, according to Delaney, Some exceptional guys can pick 1,000 pounds a dayguys that can really pick. Delaney pays the pickers market price for the berries, a nd takes them to Plantation Medicinals, where they pay him slightly more than market pr ice for his brokerage services (R. Delaney, pers. comm., 2009). In addition to buying berries from broke rs, harvesting companies have contracts with palmetto plantation owners to grow saw palmetto berries (Saw Palmetto Harvesting Company website). There is even a farm that grows certified organic saw palmetto 64

PAGE 74

berries, called Venrick F arms, in Winter Ha ven, FL (Saw Palmetto Harvesting Company website). 5.5. Trespassing Few plantation owners who specifically gr ow palmetto berries as a cash crop to sell to either the harvesting companies or di rectly to pharmaceutical companies seem to exist (Carrington et al., 2003; pers. obs.). Since saw palmetto supplements are so ubiquitous these days, and Florida is the main geographical source for the berries, trespassing is common. There is much documenta tion of freelance harvesters trespassing on government-owned conservation lands and ra nchers private proper ty (Kridel, 2005; Fooksman, 2006; Lewan, 2006; Balut, 2007). I spoke to a former berry picker to investigate the normal harvesting locations. Julian Perez is from Mexico, but now lives in Vero Beach. Last year, he was stopped by police for palmetto poaching on government property. He had to pay a fine of approximately $100 for trespassing, and has not gone picking again since (J. Perez, pers. comm., 2009). Although the berrie s bring a pretty penny, he does not want to go to jail. Palmetto poaching is a dangerous endeavoron e has to face rattle snakes, alligators, swarms of bees, the blazing summer sun, a nd ranchers with guns, not to mention the police. While some trespassers are just strippe d of their berries and warned not to come back (Kridel, 2005; W. VanGelder, pers. comm ., 2009), others go to court or jail, and an unlucky few may get deported if they are wa nted for other crimes (Balut, 2007; W. VanGelder, pers. comm., 2009; J. Perez, pers. comm., 2009). I told Perez that I was confused as to how anyone picks the berries without trespassing. He explained th at, although many people do trespass on government or 65

PAGE 75

private land, others sim ply ask ranchers for pe rmission to pick their berries. Most of the time, he indicated that they say yes. For ex ample, there is one couple in which the wife (who is American) goes up to the house and nego tiates with the ranchers before going to pick the berries with her Mexican husband (J. Perez, pers. comm ., 2009). Sometimes the ranchers want a percentage of the profits, but they are frequently willing to just give the berries away (J. Perez, pers. comm., 2009). Additionally, although there are not many palmetto farms, per se, hundreds of ranchers happen to have large tracts of saw palmetto on their land. These individuals do business either with groups of pickers, be rry brokers, or directly with harvesting companies, and thus constitute a substantial source of berries (Thorner, 2003; R. Delaney, pers. comm., 2009; Saw Palmetto Harvesting Company website). 5.6. The Market Immokalee was relatively recently reported by The New York Times to be the heart of the saw palmetto berry market (B urney, 2003). During season (late July-early October), pickers and buyers gather on New Ma rket Road to make business transactions (Clary, 1997; Burney, 2003; R. Delaney, pers. comm., 2009). Randy Delaney, who hires harvesters to pick (with permission) on othe r peoples ranches and sells the berries to Plantation Medicinals, says that migrant workers line New Market Road with trucks full of palmetto berries to sell (see small-scal e loading in Fig. 5.2.), and the buyers set up stations from which to purchase. So they can bring them to me, Ill weigh them right there and buy them, and then I ll load them up on a semi. We load everything in (those) regular white vegetable bins explained Delaney. The price of berries is highly variable. A harvester interviewed in the 1930s, who 66

PAGE 76

had been picking for 43 years, claim ed to have received as much as $2.75 per pound of berries, and $2 per pound from a pharmaceutical company for berries produced in Fig. 5.2. Harvesters fill a bag with 150 pounds of berries (from HeraldTribune.com). 100,000 pound lots (Stokes, 1940). In the 1930s, when Stokes wrote A Pharmacognostical Study of Serenoa berry prices typically ranged from 32 cents per pound, in 1935, to two cents per pound in 1938 (Stokes, 1940). By the 1990s, the price had risen to $3 per pound, according to Clary (1997). However, Perez, who picked and sold his berries in Vero Beach, stated that ove r the past six years, he has seen the price range from 20 to 90 cents per pound, and last season, he sold his berries for 50 cents per pound (J. Perez, pers. comm., 2009). Organic be rries are worth about seven to twelve 67

PAGE 77

cents per pound m ore than conventional berries (R. De laney, pers. comm., 2009). Delaney has seen the price range from as low as 12 cents up to $1.10 per pound. He says, "It's just a farmer's market. Every day changes, depends on who's buying, who's not". 5.7. Drying Methods Stokes described the berry processing pro cedure that he observed as typical in the 1930s. After the harvest, the be rries were spread out in la th-slatted trays on benches inclined at approximately 30 degrees, and left to dry in the sun for six to eight weeks (Stokes, 1940). Although one or two rains were considered beneficial as a means to wash off the syrupy exudate, any more than that w ould cause the berries to rot, so protective tarps were used in times of frequent precipitation (Stokes, 1940). Modern harvesting companies have i ndustrial dryers (Fig. 5.3.). The Saw Palmetto Harvesting Company uses a stainl ess steel dryer that can dry 750,000 pounds (about 15 semi-truck loads) of berries per day (Saw Palmetto Harvesting Company website). This dryer reduces the moisture co ntent of the berries from approximately 66% Fig. 5.3. The Saw Palmetto Harvesting Company's industrial drying station. down to 7-8%, using temperatures not exceeding 140F (Saw Palmetto Harvesting Company website). 68

PAGE 78

5.8. Sorting Berries Stokes described a careful hand-sorting of the berries (Stokes, 1940). When I asked Perez about different conditions of berries, however, he replied that his buyer accepted all conditions of berries for the same price (J. Perez, pers. comm., 2009). His buyer, though, was an owner of a Mexican f ood store, and Perez did not know to whom that man sold the berries or if he perfor med any sorting later (J. Perez, pers. comm., 2009). Delaney works as a broker for Plantation Medicinals, Inc.. Some of the berries he works with are certified organi csimply picked on ranch land that is not close to farms (R. Delaney, pers. comm., 2009). According to De laney, it is not hard to ensure that saw palmetto berries are organic. Since fertilizer s do not seem to improve them, saw palmetto requires no maintenance except for controll ed burns (R. Delaney, pers. comm., 2009). Other than keeping the organic and conven tional berries separate, though, Delaney said there is no sorting. Since picker s wait until the berries are mostly ripe (yellow to black), everything that is picked is accep ted (R. Delaney, pers. comm., 2009). 5.9. Shipping After the berries were sorted, by Stokes account, they were packed without any additives to be shipped. He re ported that they were either shipped fresh and ripe, semimoist, or after they had been dried (St okes, 1940). Stokes cla ssified his described methods of harvesting and drying as those followed by conscientious collectors. He mentions that there were unscrupulous co llectors who were less discriminating and therefore responsible for slashing berry prices driving honest collect ors out of business, and selling berries that were not medically effective (Stokes, 1940:18). There are a few harvesting companies in Florida that process saw palmetto berries 69

PAGE 79

and ship them to Europe to be m anufactur ed into prescription drugs (Saw Palmetto Harvesting Company website; Bennet and Hicklin, 1998). Prominent companies include Plantation Medicinals, The Saw Palmetto Harvesting Company, and Saw Palmetto Berries Co-op of Florida; see the appendix for more information (Bennet and Hicklin, 1998; Saw Palmetto Harvesting Company website). The Saw Palmetto Harvesting Company has a very informative, user-friendly website. 5.10. Capitalism vs. Conservation Those trespassing on conservation lands however, are not likely to negotiate harvesting permission. William VanGelder regard s palmetto poaching as an annual battle. It is not that he is stingy with the fruitharvesting the fr uit does not really hurt the plantalthough some animals, such as black bears, gray foxes, white-tailed deer, raccoons, bobwhite quail, and gopher tortoi ses consume the fru it (Carrington and Mullahey, 2006). The greater problem is the massive disturbance that the harvesters cause (W. VanGelder, pers. comm., 2009). When a group of pickers moves in (they almost always work in groups (J. Perez, pers. comm., 2009; W. Va nGelder, pers. comm., 2009)), they flush all the ground nesting birds from the saw palmetto, and upset other animals that use the palmetto for midday c over from the sun. Furthermore, pickers often destroy fences, leave trash behind them, a nd cut up the area with machetes (Fooksman, 2006; Balut, 2007). In light of these problems, it is important to note that Big Cypress National Preserve, listed as one of the nati on's ten most endangered national parks by the National Parks Conservation Asso ciation, is a major palmetto poacher attraction (Deneen, 2002). VanGelder summarized the conflict well: "t here are very few areas that still have 70

PAGE 80

palm etto in a large enough stand that it is economically feasib le for a group of individuals to go out, harvest, and be profitable. So wher e it does exist, it's a constant battle. He said, pointing to a nearby fence, People doing agriculture right here on this side of the fence line, they know its here. In between s easons of agriculture, in between when the tomatoes aren't ripe, and they've already plan ted and there's nothing for them to be doing, and they look across the fence and they see palmetto. This is a lucr ative source of work for a lot of these individuals. ... but on st ate conservation lands, it's not always about making money on the land, it's about providing ha bitat and land for species to exist, and to promote those species" (W. VanGelder, pers. comm., 2009). The main way of dealing with poachi ng is through law enforcement. Some counties, however, put more energy into stop ping palmetto poaching than others. In Palm Beach County, policemen dressed in camouflage, army boots, and black helmets, actually hold stakeouts in remote swamps waiting to catch palmetto poachers (Lewan, 2006). They have an army of off-road vehicles, in cluding six all terrain vehicles, six 4x4s, two Ford F250s, and a military jeep that can drive partially submerged (Lewan, 2006). Policemen are armed with Glock pistols, tasers, semiautomatic rifles, 12-gauge shotguns, batons, and pepper spray (Lewan, 2006). They are also equipped with night-vision goggles and infared binoculars, not to men tion the helicopter patrol (Lewan, 2006). Describing "Operation Berry Picker", Deputy Robinson stated, "We take this seriously. The message we want to send is that Palm Beach County won't tolerate this berry picking" (Lewan, 2006). Conversely, in most of Florida, punishing palmetto poachers is less of a priority. Often, poachers are charged with fines or a couple months in jail (Balut, 2007; J. Perez, 71

PAGE 81

pers. comm ., 2009; W. VanGelder, pers comm., 2009). Southwest Florida Water Management District also hires Timberland s ecurity to guard thei r land, but their budget does not allow for constant patrolling of all properties (W. VanGelder, pers. comm., 2009). Many policemen simply make poachers leave (Kridel, 2005; W. VanGelder, pers. comm., 2009). Poachers know what they are doing is illegal, but so many poachers leave uncaught or unpunished, that the risk of conf lict is acceptable to them (Kridel, 2005; R. Delaney pers. comm., 2009; W. VanGelder, pers. comm., 2009). While some poachers fear policemen, they still consider themse lves lucky when only caught by officers about once a week (Kridel, 2005). Besides, many poachers are desperately poor and may feel that berry picking is one of their few op tions. As Lucas Benitez, co-founder of the Coalition of Immokalee Workers, put it: "The tomato fields are picked clean. There are no more oranges on the trees. Fam ilies are eating crackers for di nner. It is all they can do to hang on for the start of the palmetto season" (Lewan, 2006). 72

PAGE 82

Chapter Six: Perspectives This chapter summarizes my findings and offers my perspectives on how to improve the research and management of S. repens Although much research has evaluated the efficacy of saw palmetto extr act as a treatment for BPH and prostate cancer, further studies should be conducted with improved methodologies. Additionally, research of saw palmetto extract is expa nding to explore its use for other ailments. Moreover, as the pharmaceutical demand for saw palmetto extract increases, the responsibilities of land managers, conservation officials, and law enforcement officers are increasing. We face challenges, such as how to produce a sustainable harvest, how to determine who has the rights to collect and sell the fruit, and how to balance environmental preservation and dire economic need. 6.1. Improving Methodologies Despite the fact that the quantity of research assessing saw palmetto extract's medicinal properties is quite large, the pub lished studies are riddled with methodological flaws. Many clinical trials ha ve been performed with a small sample pool and insufficient duration (e.g., Strauch et al. 1994; Gerber et al. 1998; Marks et al. 2000; Beckert et al. 2007) Other clinical trials have failed to document proof of a properly disguised placebo (e.g., Strauch et al. 1994; Gerber et al. 1998; Gurley et al. 2004; Angwafor and Anderson, 2008). A great number of studies did not analyze the chemical content of the saw palmetto extract or supplement that they used, and simply assumed that the manufacturer's label on the bot tle was sufficient (e.g., Gerber et al. 1998; Willets et al. 2003; Shi et al. 2008). 73

PAGE 83

6.1.1. Quality Control When analyzing research studies that have been conducted on the efficacy of saw palmetto berry extract supplements, it is importa nt to keep in mind the lack of regulation of botanical supplements in the United States. Ever since the Dietary Supplement Health and Education Act of 1994 was passed, botanical supplements have been considered to be food products by the FDA, and hence, are regulated as such (Grippo et al. 2007). Some additional regulations were added under the Current Good Manufacturing Practices Final Rule in 2007, but many consider these rules to be weak, and companies with fewer than 20 employees do not have to comply with the regulations until June 2010 (USFDA website). Furthermore, the Final Rule is undermined by the Interim Final Rule, which allows manufacturers to petition for an exemp tion from identity testing of the ingredients in their dietary supplements (USFDA website). Before the Final Rule became effective (in June 2008 for large companies), ther e was no mandatory testing of herbal supplements to evaluate content, purity, or safety, and worse yet, the manufacturer was not even required to guarantee that the activ e ingredient was present in the supplement (Grippo et al ., 2007). One example of inadequate supplement regulation can be found in a study that analyzed the c ontent of some dietary supplements. One brand of saw palmetto extract was found to contain a sm all amount of the phyt oestrogen daidzein, although the package was not labeled accordingly (Grippo et al. 2007). In 2005, an analysis was performed to check herbal supplement content in published randomized controlled trials (Wolsko, 2005). Of the trials examined, a me re 15% reported tests to quantify the contents of the supplements used in the trials (Wolsko, 2005). It is essential 74

PAGE 84

that future researchers take into account th e quality contro l issues when designing herbal supplement clinical trials. 6.1.1.1. Batch Variation Different batches of the same produc t by the same manufacturer can have drastically different bioactivities, and thus, effects (Ong, 2004; Scaglione et al. 2008). In a study of acidic aqueous extracts of dietary supplements by Raman et al. (2008), bioassay results fluctuated among products from different batches by the same manufacturer. Furthermore, sign ificant discrepancies in bioa ctivitiy between supplements made from the same plant but produced by diffe rent manufacturers have also been shown (Raman et al. 2008; Scaglione et al. 2008). Possible reasons fo r these inconsistencies include variations in extraction proce dures and product manufacturing (Scaglione et al. 2008). Additionally, the geographical source of the plant, as well as climactic growing conditions, can have a great impact on the final product, since environmental conditions play a considerable role in the creation of bioactive metabolites (Savikin-Fodulovic, 1998; Jorge et al. 2008). Furthermore, some products only state the generic name of the plant, leaving room for specu lation about the species and cu ltivar that is being sold (Raman et al. 2008). 6.1.1.2. European Regulations In order to obtain a more standardiz ed product, it is often better to use medications produced, and thus regulated, in Eu rope. For example, there is little mystery in the contents of Permixon, the most popul ar brand of medicati on derived from saw palmetto. Produced by Pierre Fabre Mdicament, Permixon is a lipidosterolic hexane extract of S. repens and contains 80% free fatty acids, 7% esterified fatty acids, sterols, 75

PAGE 85

polyprenic com pounds, arabinose, glucose, galactose, uronic acid, and flavonoids (Maccagnano et al. 2006). A more comprehensive delineation of the contents is provided in their article, entitled A Critical Analysis of Permixon in the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Enlargement (Maccagnano et al. 2006). Several other European saw palmetto products have been tested for their ingredients, which are published in an analysis by Scaglione et al. (2008). 6.1.1.3. Dosage Variation Besides lack of standardi zation of supplement content, another obstruction to drawing conclusions from saw palmetto suppleme nt research is the variety of doses used in experiments with rats and human clinical tr ials. Most clinical tria ls used two doses of 160 mg of saw palmetto extract per day, but a few deviated from the norm (Dedhia and McVary, 2008). Inconsistencies among different studies make sound comparison difficult. 6.1.2. Differentiating between BPH and Prostate Cancer As I previously mentioned in Chapter Four, some researchers simply regarded BPH as an early stage of prostate cancer (a s reviewed in Ekman, 1989). Current research shows that this is an incorrect classifica tion, as BPH and prostate cancer actually stem from two distinct pathogeneses (Arenas et al. 2000). Although it is important to acknowledge that BPH and prostate cancer are different disorders, saw palmetto extract shows promise for treating both prostatic diseases (McLaughlin et al. 2006; Shi et al. 2008). Recent studies have shown saw palmetto extract to have antiproliferative e ffects on the human prosta te cancer cell lines, PC-3, DU-145 (McLaughlin et al. 2006; Yang et al ., 2007), and LNCaP, (Yang et al. 76

PAGE 86

2007). Saw palm etto extract has also been show n to inhibit LNCaP cell growth in tumors xenografted onto mice (Yang et al. 2007). Furthermore, there is evidence that S. repens extract and its components -sitosterol and stigmasterol inhibit the growth of DU-145 cells by increasing p53 protein expression a nd decreasing p21 and p27 protein expression (Scholtysek et al. 2009). These proteins are import ant cell cycle regulators. The p53 protein protects an organism from developi ng cancer by directing genetically damaged cells to apoptosis, and the cytokinase inhibitors, p21 and p27, are active in cell differentiation (Karp, 2005). 6.1.3. Designing Better Clinical Trials In order to progress medical knowledge of saw palmetto extract, I suggest that future researchers design clinical trials as follows. Ideally, a clinical trial evaluating the efficacy of saw palmetto should be double-blind, randomized, and placebo-controlled. The majority of trials that have been conduc ted so far have had a duration of six months or less (Strauch et al., 1994; Gerber et al. 1998; Marks et al. 2000; Beckert et al. 2007), thus future trials should conti nue for at least 13 months, prefer ably five years or longer. I suggest 13 months in order to allow for a one month placebo period to eliminate participants that respond si gnificantly to the placebo, and still leave a year for the duration of the study. One year is a reasona ble amount of time to assess short term effects, and five years or more are needed to assess the long term effects (which could be rare and take years to devel op) of a drug. Moreover, a well-d esigned clinical trial should involve at least 200 participants with moderate to severe symptoms of BPH, as well as a control group, in order to get an adequate subset of the population. A prerequisite to a well-designed clinical trial tes ting a supplement is an accurate chemical analysis of that 77

PAGE 87

supplem ent, in order to define with certainty the herbal product gi ven to patients (Ong, 2004; Scaglione et al. 2008). One recommended method of analysis is High Performance Liquid Chromatography (HPLC), because of th e method's high reproducibility, complete linear range, ease of automation, and its capability to delineate the number of ingredients in a botanical preparation (Ong, 2004). In orde r to properly test for the placebo effect, the saw palmetto extract pi ll and the placebo should be identical in appearance, smell, and taste. To keep clinical data consis tent, men should receive a 160 mg dose of the saw palmetto extract twice a da y, as this seems to be the most commonly recommended manufacturer's dose (Dedhia a nd McVary, 2008). To accurately determine the health effects of saw palmetto extract, participants should be physically examined before, after, and periodica lly during the trial. The following health indicators are suggested for periodic as sessment: International Pros tate Symptom Score (IPSS), American Urological Association Symptom I ndex (AUASI) score, maximal urinary flow rate, average number of noctu rnal voids, prostate size, residual urinary volume after voiding, serum prostate-specific an tigen levels, "quality of lif e" (as self-reported through a questionnaire). Adverse effect s should be also be systematically assessed, to monitor the safety of the extract. 6.2. Other Ailments Since saw palmetto extract is believed by some to act as a 5 -reductase inhibitor (Scaglione et al. 2008), it has been suggested as a po ssible treatment for other androgen dependent diseases, such as hirsutism27 symptomatic of polycystic ovary syndrome28 27 hirsutismabnormally excessive growth of bod y hair, especially in females, caused by increased androgen production 78

PAGE 88

(Bratoeff et al. 2005) as well as androgenic alopecia29 (Prager et al. 2002; Bratoeff et al. 2005), seborrhea30, and precocious puberty31. However these areas of research are still new and more has been speculated than actually proven (as reviewed in Bratoeff et al. 2005). Saw palmetto extract is also marketed as a key ingredient in natural breast enlargement supplements (Ameri-Breast we bsite; Mega Bust website) and sexual performance enhancing drugs (Fig. 6.1.; Mega Bust website; Probido website; Red Rooster Pills website). It supposedly en larges the mammary gland and maximizes lactation (Bennet and Hick lin, 1998). Furthermore, S. repens extract when part of general Fig. 6.1. Mega Bust Product manufactured by the Saw Palmetto Harvesting Company (from Mega Bust website) sexual tonics, is advertised as having soothing effects on the ovaries and uterus, stimulating urinary flow (Bennet and Hickli n, 1998), and increasing blood flow to the sexual organs (Bennet and Hicklin, 1998; Red Rooster Pills website). 28 polycistic ovary syndromethe growth of multiple ovarian cysts, accompanied by the absence of ovulation, and increased androgen production 29 androgenic alopeciabaldness 30 seborrheaoverproduction of sebum which resu lts in skin conditions such as oiliness or dry, crusty scales 31 precocious pubertyonset of puberty before the age of eight in girls, or before ten in boys 79

PAGE 89

However, no clinical trials have been co mpleted to evaluate the efficacy of the saw palmetto-containing Ameri-Breast, Mega Bust, or the Red Rooster sexual enhancement cocktail (Ameri-Breast website; Mega Bust website; Web of Science database search32). In fact, it appears that no clinical trials on the efficacy of any bust or sexual performance enhancing herbal s upplemements have been published (FughBerman, 2003; Web of Science database search33), although these products are widely advertised through amusing testimonials (Ameri-Breast website; Mega Bust website; Probido website; Red Rooster website). 6.3. Managing the Crop Saw palmetto is a hearty crop. Amazingly, virtually no maintenance is required to ensure fruit production (R. Delaney, pers. comm., 2009). The only care that improves yields is burning during the gr owing season every five to eight years (Carrington and Mullahey, 2006). Battling saw pa lmetto's pathogens, the fungus Colletotrichum gloeosporioides (Penz.) Penz. and Sacc., and the cabbage palm caterpillar ( Litoprosopus futilis G. and R.), could also be helpful. C. gloeosporioides causes premature fruit drop, and the cabbage palm caterpillar eats saw palmetto inflorescences (Carrington and Mullahey, 2006; Davis, 2002). However, it appe ars that the development of practices to combat these pathogens is not an active ar ea of research (Carri ngton and Mullahey, 2006; Web of Science database search34). 32 Search was performed on 4/1/09 using ke ywords Ameri-Breast, Mega Bust, or Red Rooster 33 Search was performed on 4/1/09 using keyw ords breast enlargement or enhancement and saw palmetto or Serenoa or phytotherapy 34 Search was performed on 4/1/09 using ke ywords saw palmetto and management, control, fruit drop, Colletotrichum or caterpillar 80

PAGE 90

6.3.1. Punishing Poachers How can different interest groups coope rate and achieve their goals without exploiting each other or the environment? W ho decides which practices are detrimental to the environment and which practices are for the greater good? For example, in Chapter Five, I reported the virtual army that Palm Beach County policemen bring into the swamp for "Operation Berry Picker." It is hard for me to imagine justifying an operation of such magnitude, with such large and expensive equipment, when there are so many other crimes to be dealt with. Driving ATVs, F 250s, and a submersible military jeep through the swamp seems much more disruptive to en dangered wildlife and the ecosystem, than palmetto poaching. If Palm Beach County wa nts to send the message that they "won't tolerate this berry picking" (Lewan, 2006), then perhaps they should convey that message in a less expensive, destructive, and hypocri tical way. However, I am not justifying the illegal practice of poaching, and I believe that poachers that have littered or have been destructive to fences or ot her property should receive ha rsher punishment. On the other hand, if berry pickers simply ask private land owners for permission to harvest the land, I feel that much conflict could be avoided. Indeed, many harvesters do ask permission and pay the ranchers a fee for their crop; in this way, exploitation is minimized (J. Perez, pers. comm., 2009). Another practical, profitable, at times legal me thod is for harvesters to find work through a harvesting company or broker (R. Delaney, pers. comm., 2009). This may be a better option for harv esters who do not speak Engl ish well enough to negotiate with ranchers themselves. While this simple practice works well for privately owned property, it does not solve the problem of poaching on conservati on lands. Unfortunately, neither do security 81

PAGE 91

82 stakeouts with night vision goggles. Palmetto poaching is a symptom of a much larger socio-economic problem, and is unlikely to go away until the poverty among migrant workers in Florida is ameliorated. Not surprisingly, many, including myself, do not consider poaching a particularly heinous crim e. Palmetto harvester, Bernabe Morales, succinctly summarizes a common sentiment among poachers, "There's a lot of laws here in America that I probably don't know about," he stated, "but I do know there's no law anywhere that says a man has to starve" (Lewan, 2006). 6.4. Does Saw Palmetto Extract Really Work? Research regarding the medical efficacy of saw palmetto extract is extensive and conflicting. It has been suggest ed that saw palmetto extract works against BPH through a variety of mechanisms, including, but not limited to: inhibition of COX enzymes, lipid peroxidation, cell growth, and type II 5reductase; decrease in DHT levels and alteration of IGF signaling in the prostate. Nevertheless, published medical studies thus far completed have not provided sufficien t evidence to determine which specific mechanism may make saw palmetto extract an effective treatment (Suzuki et al. 2007; Fernndez et al. 2008). Inconsistencies between studi es, such as dosage, duration, and sample size and composition, might explain why re sults have been cont radictory at times. Though I am no expert, I believe that certain high quality saw palmetto extracts could have a place in the treatment of BPH as well as prostate cancer. However, it will be difficult to ensure that any American brands of saw palmetto extract are dependable until stricter regulation of herbal s upplements is put into practice.

PAGE 92

References Abrahamson, W. G. 1984. Post-fire recovery of Florida Lake Wale s Ridge vegetation. American Journal of Botany. 71(1):35-43. Abrahamson, W. G. 1995. Habitat distribu tion and competitive neighborhoods of two Florida palmettos. Bulletin of the Torrey Botanical Club. 116: 215-228. Abrahamson, W. G. 1999. Episodic repr oduction in two fire-prone palms, Serenoa repens and Sabal etonia (Palmae). Ecology. 80(1): 100-115. Abrahamson, W. G., Hartnett, D. C. 1990. Pine flatwoods and dry prairies. In: Myers, R. L., Ewel, J. J., eds. Ecosystems of Florida University of Central Florida Press: Orlando, FL: 103-149. Ameri-Breast website. 2007. . Accessed: 3/24/09. Angwafor, F. and M. L. Anderson. 2008. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. Journal of the International Society of Sports Nutrition 5(12): 1-7. Arashvand, K., Bacon, J., and R. Pearson. Epithelia l iris cyst with a progressive precipitate. Journal of Cataract & Refractive Surgery 33: 927-928. Arenas, M. I., Romo, E., Royuela, M., Frai le, B. and R. Paniagua. 2000. E-, Nand Pcadherin, and -, and -catenin protein expression in normal, hyperplastic and carcinomatous human prostate. The Histochemical Journal. 2 (11): 659-667. Arend, W. P., Malyak, M., Guthridge, C. J., and C. Gabay. 1998. Interleukin-1 receptor antagonist: role in biology. Annual Review of Immunology 16: 27-55. Arruzazabala, M. L., Ms, R., Carbajal, D., and V. Molina. 2005. Effect of D-004, a lipid extract from the Cuban Royal Palm fruit, on in vitro and in vivo effects mediated by a-Adrenoceptors in rats. Drugs in R & D. 6(5): 281-289. Avins, A. L., Bent, S., Staccone, S., Badua, E., Padula, A., Goldberg, H., Neuhaus, J., Hudes, E., Shinohara, K., and C. Kane. 2008. A detailed safety assessment of a saw palmetto extract. Complementary Therapies in Medicine 16: 147-154. Austin, D. F. 2004. Florida Ethnobotany. CRC Press, Boca Raton, FL. Balut, D. 2007. 4 men arrested for picking saw palmetto berries. Tampa Bay's 10 News Riverview, FL. < http://www.wtsp.com /news/local/story.aspx?storyid=62393>. Accessed: 3/29/09. 83

PAGE 93

Barclay, W W., Woodruff, R. D., Hall, M. C., and S. D. Cramer. 2005. A system for studying epithelial-stromal interactions reveal s distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer. Endocrinology, 146(1):13-18. Barkhaus, P. E. 2008. Kennedy Disease. Emedicine from WebMD website. . Accesed: 4/3/09. Barrack, E. R., Bujnovszky, P., and P. C. Walsh. 1983. Subcellular Distribution of Androgen Receptors in Human Normal, Benign Hyperplastic, and Malignant Prostatic Tissues: Characterization of Nuclear Salt-resistant Receptors. Cancer Research. 43: 1107-1116. Beckert, B. W., Concannon, M. J., Henry, S. L ., Smith, Daniel S. M.D.; Puckett, Charles L. The Effect of Herbal Medicines on Platelet Function: An In Vivo Experiment and Review of the Literature. Beckman, T. J., and L. A. Mynderse. 2005. Ev aluation and medical management of benign prostatic hyperplasia. Mayo Clinic Proceedings (80)10: 1356-1362. Begley, L., Monteleon, C., Shah, R. B., MacDonald, J. W., and J. A. Macoska. 2005. CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro. Aging Cell 4:291-298. Beilin, J., Ball, E. M. A., Favaloro, J. M., and J. D. Zajac. 2000. Effect of the androgen receptor CAG repeat polymorphism on tran scriptional activity: specificity in prostate and non-prostate cell lines. Journal of Molecular Endocrinology. 25(1):85-96. Bennett, B. C. and J. R. Hicklin. 1998. Uses of saw palmetto ( Serenoa repens Arecaceae) in Florida. Economic Botany 52(4): 381-393. Bent, S., Kane, C., Shinohara, K., Neuhaus, J ., Hudes, E. S., Goldberg, H., and A. L. Avins. 2006. The New England Journal of Medicine. 354(6):557-566. Bernard, R. 1966. Herbal Elixirs of Life Published by Health Re search in Mokelumne Hill, CA. Berry, P. A., Maitland, N. J. and A. T. Collins. 2008. Androgen receptor signaling in prostate: effects of stromal fact ors on normal and cancer stem cells. Molecular and Cellular Endocrinology. 288 (1-2): 30-37. Blackard, D. M. 1990. Patchwork and Palmettos: Seminole/Miccosukee Folk Art Since 1820. Fort Lauderdale Historical Society, Fort Lauderdale, FL. Bluer, M., Tammela, T. L., and T. Ylikomi. 2008. A novel tissue-slice culture model for non-malignant human prostate. Cell Tissue Research. 332(3):489-498. 84

PAGE 94

Bom hard, M. L. 1963. Palm trees in the United States. Agriculture Information Bulletin No. 22. U.S. Department of Agriculture, Forest Service. Bonkhoff, H., and Klaus Remberger. 1996. Differentiation pathways and histogenetic aspects of normal and abnormal prostatic growth: a stem cell model. The Prostate 28: 98-106. Bonnar-Pizzorno, R. M., Littman, A. J., Kestin, M., and E. White. 2006. Saw palmetto supplement use and prostate cancer risk. Nutrition and Cancer. 55(1): 21-27. Boom in natural medicine pushes saw palmetto into agricultural big time. 1996.UF/IFAS News website. Accessed: 3/20/09. < http ://news.ifas.ufl.edu/story.aspx?id=23>. Boyle, P., Robertson, C., Lowe, F., and C. Roehrborn. 2004. Updated meta-analysis of clinical trials of Serenoa repens extract in the treatment of symptomatic benign prostatic hyperplasia. BJU International. 93(6): 751-756. Bratoeff, E., Cabeza, M., Ramrez, E., Heuze, I., and E. Flores. 2005. Recent advances in the chemistry and pharmacological activity of new steroidal antiandrogens and 5 alpha-reductase inhibitors. Current Medical Chemistry. 12: 927. Brown, R. B., Stone, E. L., and V. W. Carlisle. Soils In: Myers, R. L., Ewel, J. J., eds. Ecosystems of Florida University of Central Flor ida Press: Orlando, FL: 35-69. Buck, A. C. 2004. Is there a scientific basis fo r the therapeutic effects of Serenoa repens in benign prostatic hyperplasia? Mechanisms of action. The Journal of Urology 172:1792-1799. Bucuvalas, T., Bulger, P. A., and S. Kennedy. 1994. South Florida Folklife University Press of Mississippi, Jackson, MS. Burney, T. 2003. A Hope for the Prostate Among the Rattlesnakes. The New York Times. . Accessed: 10/4/08. Callahan, J. L., Barnett, C., and J. W. Cates. 1990. Palmetto prairie creation on phosphate-mined lands in central Florida. Restoration & Management Notes 8(2): 94-95. Cao, N., Haynes, J. M., and S. Ventura. 2006. Saw palmetto is an indirectly acting sympathomimetic in the rat-isolated prostate gland. The Prostate 66:115-123. Capron, L. 1953. The medicine bundles of the Florida Seminoles and the Green Corn Dance. Bureau of American Ethnology 151:155-210. Reprinted in 1987 in A Seminole Sourcebook Ed. by W. C. Sturtevant. Garland Publishing, Inc., New York, NY. 85

PAGE 95

Carraro, J. C ., Raynaud J. P., Koch G., Chisholm, G. D., Di Silverio, F., Teillac, P., Da Silva, F. C., Cauquil, J., Chopin, D. K., Hamdy, F. C., Hanus, M., Hauri, D., Kalinteris, A., Marencak, J., Perier, A., Perrin, P. 1996. Comparison of phytotherapy (Permixon) with finasterid e in the treatment of benign prostate hyperplasia: A randomized inte rnational study of 1,098 patients. The Prostate. 29(4): 231-240. Carrington, M.E., Mullahey, J.J., and F. R oka. 1997. Saw palmetto: a fountain of youth. Proceedings of the American Forage and Grassland Council. 6: 233-237. Carrington, M. E., Gotfried, T. D., and J. J. Mullahey. 2003. Pollination biology of saw palmetto (Serenoa repens ) in southwest Florida. Palms. 47(2): 95-103. Carrington, M. E. and J. J. Mullahey. 2006. E ffects of burning season and frequency on saw palmetto ( Serenoa repens ) flowering and fruiting. Forest Ecology and Management 230:69-78. Chamberlain, N. L., Driver, E. D., and R. L. Miesfeld. 1994. The length and location of CAG trinucleotide repeats in the androgen N-terminal domain affect transactivation function. Nucleic Acids Res 22: 3181-3186. Champault, G., Patel, J. C., and A. M. Bonnard. 1984. A double-blind trial of an extract of the plant Serenoa repens in benign prostatic hyperplasia. British Journal of Clinical Pharmacology. 18 (3): 461-462. Cheema, P., El-Mefty, O., and A. R. Jazieh. 2001. Intraoperative haemorrhage associated with the use of extract of Saw Palme tto herb: a case re port and review of literature. Journal of Internal Medicine 250:167-169. Chokkolingam, A. P., Gao, Y., Deng, J., Stanczyk, F. Z., Sesterhenn, I. A., Mostofi, F. K., Fraumeni, J. F., and A. W. Hsing. 2002. Insulin-like growth factors and risk of benign prostatic hyperplasia. 52(2): 98-105. Choong, C. S., Kemppainen, J. A., Zhou, Z. X., and E. M. Wilson. 1996. Reduced androgen receptor gene expression with first exon CAG repeat expansion. Molecular Endocrinology 10(12):1527-1535. Clary, M. 1997. Berry rich in hype becomes a cash crop. Los Angeles Times . Accessed: 3/28/09. Cohen, P., Nunn, S. E., and D. M. Peehl. 2000. Transforming growth factor-beta induces growth inhibition and IGFbinding protein-3 production in prostatic stromal cells: abnormalities in cells cultured from benign prostatic hyperplasia tissues. Journal of Endocrinology. 164(2): 215-223. 86

PAGE 96

Congdon, K. G. 2006. Just Above th e Water. The University Press of Mississippi, Jackson, MS. Constantine, A. J. 2005. Know Your Woods: A Complete Guide to Trees, Woods, and Veneers. Lyons Press, Guilford, CT. Cooke, V. J. and J. M. Sampley. 1947. Palmetto Braiding and Weaving The Manual Arts Press, Peoria, IL. Covey, T. M., Edes, K., and F. A. Fitzpatrick. Akt activati on by arachidonic acid metabolism occurs via oxidation and in activation of PTEN tumor suppressor. 2007. Oncogene. 26(39): 5784-5792. Crimi, A. and A. Russo. 1983. Extract of Serenoa repens for the treatment of the functional disturbances of prostate hypertrophy. Med Praxis. 4:47-51. Cryer, B. and A. Dubois. 1998. The advent of highly selective inhibitors of cyclooxygenasea review. Prostaglandins & Other Lipid Mediators 56:341361. Culbreth, D. M. 1917. Sabal Sabal. 94-98. A Manual of Materia Medica and Pharmacology 6th Ed. Published in Philadel phia, PA by Lea & Febiger. Das, K., Cheah, P. Y., Lim, P. L., Zain, Y. B., Stephanie, F. C., Zhao, Y., Cheng, C., and W. Lau. 2008. Shorter CAG repeats in androgen receptor and non-GG genotypes in prostate-specific antigen loci are a ssociated with decreased risk of benign prostatic hyperplasia and prostate cancer. Cancer Letters. 268(2): 340-347. Davis, M. S. 2002. The Effects of Fire and Fire Influenced Canopy on the Inflorescence Production of Saw Palmetto ( Serenoa repens (Bartr.) Small) and on the Distribution of the Cabba ge Palm Caterpillar ( Litoprosopus futilis (Grt. & Rob.)). Undergraduate Thesis. New Colle ge of Florida, Sarasota, FL. Deane. 2008. Eat the Weeds. < http://www.eattheweeds.com/>. Accessed: 4/1/09. Dedhia, R. C. and K. T. McVary. 2008. Phytotherapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia. The Journal of Urology. 179:21192125. DeGraaf, Richard M., Scott, Vi rgil E., and R. H. Hamre. 1991. Forest and rangeland birds of the United States: Natural history and habitat use. Agric. Handb. 688. Washington, DC: U.S. Department of Agriculture, Forest Service. 625 p. Delaney, R. 2009. Interview in Ona, FL. 3/25/09. 87

PAGE 97

Deneen, S. 2002. The orchid thieves: Am eri ca's parks are the scene of the crime for plant theft. E: The Environmental Magazine. . Accessed 4/10/09. Descotes, J. L., Rambeaud, J. J., Desc haseaux, P., and G. Faure. 1995. PlaceboControlled Evaluation of the Efficacy a nd Tolerability of Permixon in Benign Prostatic Hyperplasia after Exclusion of Placebo Responders. Clinical Drug Investigation. 9(5): 291-297. Dickinson, J. D. 1985. Jonathan Dickinson's Journal or, God's Protecting Providence Florida Classics Library, Port Salerno, FL. Ding, D., Xu, L., Menon, M., Reddy, G. R.V., and E. R. Barrack. 2004. Effect of a Short CAG (Glutamine) Repeat on Human Androgen Receptor Function. The Prostate 58: 23-32. Dodge, C. R. 1897. A Descriptive Catalogue of Usef ul Fiber Plants of the World, Including: The Structural and Ec onomic Classifications of Fibers U.S. Department of Agriculture, Report No. 9. Washington, D.C. Downs, D. 1995. Art of the Florida Seminol e and Miccosukee Indians. University Press of Florida, Tampa, FL. Drug Information Online. < http://www.druginformationonline.org/>. Accessed: 4/1/09. Dupon, S. F. 1892. Sabal serrulatasaw palmetto. 51-52. The American Therapist. No.1. Vol.1. Published in New York, NY. Eaton, C. L. 2003. Aetiology and pathogenesis of benign prostatic hyperplasia. Current Opinion in Urology. 13(1): 7-10. Eldridge. 1896. Saw palmetto in bronchitis. 538. The Medical Age Vol. XIV. Ed. by G. A. Stockwell. Published in De troit, MI by George S. Davis. Ekman, P. 1989. BPH epidemiology and risk factors. The Prostate Supplement (2): 2331. Essig, F. B., Taylor, Y. R., and D. TeStrake 2000. Floridas wax palm: the silver form of Serenoa repens (Arecaceae). Florida Scientist. 63(1):13-16. Fernndez, L. C., Mas, R., Fernndez, J., Mend oza, S., Gmez, R., and B. Pardo. 2008. Effects of D-004, a lipid extract of the fr uit of the Cuban royal palm (Roystonea regia) or the lipidosterolic extract of sa w palmetto (Serenoa repens) on the sexual activity in male rats: a co ntrolled, experimental study. Current Therapeutic Research 69 (1): 65-74. 88

PAGE 98

Fisher, J. B. and P. B. Tom linson. 1973. Br anch and inflorescence production in saw palmetto (Serenoa repens ). Principes 17(1):10-19. Fooksman, L. 2006. Deputies put the squeeze on illegal berry pickers. Florida Farmers Inc. website. . Accessed 3/29/09. Forest Farmer. 1947. New uses for scrub palmetto. 6:6. Foti, R. S., and J. L. Wahlstrom. 2008. The role of dietary supplements in cytochrome P450-mediated drug interactions. Boletn Latinoamericano y del Caribe de Plantas Medicinales y Aromticas 7(2):66-84. Fugh-Berman, A. 2003. Bust enhancing herbal products. Obstetrics & Gynecology 101(6): 1345-1349. Garbarino, M. S. 1972. Big Cypress: A Changing Seminole Community Holt, Rinehart, and Winston, Inc., Atlanta, GA. Gerber, G. S., Zagaja, G. P., Bales, G. T., Chodak, G. W., and B. A. Contreras. 1998. Saw palmetto ( Serenoa repens ) in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms. Urology 51(6): 1003-1007. Gerber, G. S., Kuznetsov, D., Johnson, B. C.,and Burstein, J. D. 2001. Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms. Urology 58(6):960-965. Gildemeister, E. and F. Hoffmann. 1900. Oil of saw palmetto. 300-301. The Volatile Oils. Pharmaceutical Review Publ. Co., Milwaukee, WI. Giovannucci, E., Platz, E., Stampfer, M., Ch an, A., Krithivas, K., Kawachi, I., Willett, W., and P. Kantoff. 1999. The CAG Rep eat Within the Androgen Receptor Gene and Benign Prostatic Hyperplasia. The Journal of Urology 162(1): 269-270. Goepel, M., Dinh, L., Mitchell, A., Schfers, R. F., Rbben, H., and M. C. Michel. 2001. Do saw palmetto extracts block human 1-adrenoceptor subtypes in vivo? The Prostate 46:226-232. Goldmann, W. H., Sharma, A. L., Currier, S. J., Johnston, P. D., Ra na, A., and C. P. Sharma. 2001. Saw palmetto berry extract inhibits cell growth and COX-2 expression in prostatic cancer cells. Cell Biology International 25(11):11171124. Gould, G. M., Scott, R. J., and C. V. Brownlow. 1935. Goulds Medical Dictionary: The Words and Phrases Generally Used in Medicine and the Allied Sciences, with 89

PAGE 99

their Pronunciation and Derivation. P. Blakistons Son & Co., Inc., University of California. Grieve, M. 1971. A Modern Herbal. Published by Dover in New York, NY. Griffin, J. W. 2002. Archaeology of the Everglades University Press of Florida, Tampa, FL. Grippo, A. A., Capps, K., Rougeau, B., and B. J. Gurley. 2007. Analysis of flavonoid phytoestrogens in botanical and ep hedra-containing dietary supplements. The Annals of Pharmacotherapy. 41:1375-1382. Gross, R. S., and P. A. Werner. 1983. Probabili ties of survival and reproduction relative to rosette size in the common burdock ( Arctium minus : Compositae). American Midland Naturalist.109(1): 184-193. Gurley, B. J., Gardner, S. F., Hubbard, M. A., Williams, D. K., Gentry, W. B., Carrier, J., Khan, I. A., Edwards, D. J., and A. Shah. 2004. In vivo assessment of botanical supplementation on human cy tochrome P450 phenotypes: Citrus aurantium Echinacea purpurea milk thistle, and saw palmetto. Clinical Pharmacology & Therapeutics. 76(5):428-440. Gutierrez, M., Garcia de Boto, M. J., Cantabra na, B., and A. Hidalgo. 1996. Mechanisms involved in the spasmolytic effect of extrac ts from Sabal serrulata fruit on smooth muscle. General Pharmacology 27(1): 171-176. Gutman, J. 1949. Modern Drug Encyclopedia and Therapeutic Index: A Compendium. Published by Yorke Medical Group. Hale, E. M. 1898. Saw Palmetto. (Sabal Serrulata. Serenoa Serrulata ) Its History, Botany, Chemistry, Pharmacology, Provings, Clinical Experience and Therapeutic Applications Boericke & Tafel, Philadelphia, PA. Herald Tribune. . Accessed: 3/30/09. Herndon, A. 1988. Ecology and systematic of Hypoxis sessilis and H. wrightii (Hypoxidaceae) in southern Florida. American Journal of Botany. 75(12): 18031812. Hill, B. and Kyprianou, N. 2004. Effect of Permixon on human prostate cell growth: lack of apoptotic action. The Prostate. 61:73-80. Hilman, J. B. 1969. Autoecology of saw palmetto, Serenoa repens (Bartr.) Small. Ph.D. dissertation, Duke University, Durham, NC. Holt, K. 2007. Blue Heron tells elementary students of state's Indian roots. T he Destin 90

PAGE 100

Log Destin, FL. Hough, W A. 1968. Carbohydrate reserves of saw-palmetto: seasonal variation and effects of burning. Journal of Forest Science. 14 (4): 399-405. Hsi, L.C., Angerman-Stewart, J., and T. E. Eling. 1999. Introduction of full-length APC modulates cyclooxygenase-2 expression in HT-29 human colorectal carcinoma cells at the translational level. Carcinogenesis 20 (11):2045-2049. Husmann, D. A., Wilson, C. M., McPhaul, M. J., Tilley, W. D., and J. D. Wilson. 1990. Antipeptide antibodies to two distinct regions of the androgen receptor localize the receptor protein to the nuclei of targ et cells in the rat and human prostate. Journal of Molecular Endocrinology. 27: 321. Igarashi, S. Tanno, Y., Onodera, O., Yamazaki, M., Sato, S., Ishikawa,A., Miyatani, N., Nagashima, M., Ishikawa, Y., Sahashi, K ., Ibi, T., Miyatake, T., and S. Tsuji. 1992. Strong correlation between the nu mber of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy. Neurology 42: 2300-2302. Jibrin, I., Erinle, A., Saidi, A. and Z. Y. Aliyu. 2006. Saw palmetto-induced pancreatitis Southern Medical Journal 99(6): 611-612. Jorge, R., Furtado, N.A., Sousa, J. P., da Silva, A. A., Gregorio, L. E., Martins, C. H., Soares, A. E., Bastos, J. K., Cunha, W. R., and M. L. Silva. 2008. Brazilian Propolis: Seasonal variation of the prenylated p-Coumaric acids and antimicrobial activity. Pharmaceutical Biology. 46(12): 889893. Kalmbacher, R. S. and F. G. Martin. 1984. Chopping and tebuthiuron effects on saw palmetto. Soil and Crop Science Society of Florida Proceedings 43: 86-89. Karp, G. 2005. Cell and Molecular Biology: Concepts and Experiments 4th ed. John Wiley & Sons, Inc. Kasper, S. 2008. Exploring the origins of the normal prostate and pr ostate cancer stem cell. Stem Cell Review 4:193-201. Kazemi-Esfarjani, P., Triforo, M. A., and L. Pinsky. 1995. Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenetic relevance for the (CAG)n-expanded neuronopathies. Hum Mol Genet. 4: 523-527. Kenner, R. C. 1900. Globules of saw palmetto and santal in the treatment of gonorrhea: with clinical reports. 10. Therapeutic Notes No.1. Published in Detroit, MI by Parke, Davis, & Co. Kennedy, S. 1991. Palmetto Country Florida Atlantic University Press, Gainesville, FL. 91

PAGE 101

Knapp, H. 1891. Saw palm etto.Obstetrical forceps. 27-28. The Medical World. Vol. IX. Ed. by C. F. Taylor and J. J. Taylor. Published in Philadelphia, PA. Klotsman, M., Weinberg, C. R., Davis, K., Binnie, C. G., and K. E. Hartmann. 2004. A case-based evaluation of SRD5A1 SRD5A2, AR, and ADRA1A as candidate genes for severity of BPH. The Pharmacogenetics Journal 4: 251-259. Kohut, M. L., Thompson, J. R., Campbell, J., Brown, G. A., Vukovich, M. D., Jackson, D. A., King, D. S. 2003. Ingestion of a dietary supplement containing dehydroepiandrosterone (DHEA) and a ndrostenedione has minimal effect on immune function in middle-aged men. Journal of the American College of Nutrition 22 (5):363-371. Konwar, R., Chattopadhyay, N., and H. K. Bid. 2008. Genetic polymorphism and pathogenesis of benign prostatic hyperplasia. BJU International 102: 536-543. Kramer, G., Steiner, G. E., Handisurya, A., Stix, U., Haitel, A., Knerer, B., Gessl, A., Lee, C., Marberger, M. 2002. Increase d expression of lymphocyte-derived cytokines in benign hyperpla stic prostate tissue, iden tification of the producing cell types, and effect of differentia lly expressed cytokines on stromal cell proliferation. The Prostate 52(1):43-58 Kramer, G., Mitteregger, D ., Marberger, M. 2007. Is Benign Prostatic Hyperplasia (BPH) an Immune Inflammatory Disease? European Urology 1202-1216. Kridel, K. 2005. Migrants cashi ng in on wild berry harvest. Herald Tribune website. . Accessed: 3/28/09. Kuchler, A. W. 1964. Manual to accompany the map of potential vegetation of the conterminous United States. Special Publication No. 36. New York: American Geographical Society. 77 p. Kushlan, J. A. 1990. Freshwater Marshes. In: Myers, R. L., Ewel, J. J., eds. Ecosystems of Florida. University of Central Florida Press: Orlando, FL: 324-363. Landers, J.G. 2000. Colonial Plantations and Economy in Florida. University Press of Florida, Tampa, FL. Lee, K. L., and D. M. Peehl. 2004. Molecular and cellular pathogenesis of benign prostatic hyperplasia. The Journal of Urology. 172: 1784-1791. Leone, S., Ottani, A., and A. Bertolini. 2007. Dual acting anti-inflammatory drugs. Current Topics in Medicinal Chemistry. 7(3): 265-275. Lewan, T. 2006. Fla. police and poachers pl ay cat-and-mouse over prized palmetto 92

PAGE 102

berries. PoliceOne website. Loxahatchee Slough Natural Area, FL. . Accessed: 3/29/09. Lewis, C. E. 1970. Responses to chopping and rock phosphate on south Florida ranges. Journal of Range Management. 23(4): 276-282. Lipsky, P. E. 1999. The clinical potential of cyclooxygenase-2-specific inhibitors. The American Journal of Medicine. 106: 51S-57S. Long, A. J. 2002. Prescribed Burning Regulations in Florida. FOR 67, one of a series of the School of Forest Resources and Conservation, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences. . Accessed: 4/2/09. Maccagnano, C., Salonia, A., Briganti, A., Teillac, P., Schulman, C., Francesco, M. and P. Rigatti. 2006. A critical analysis of Permixon in the treatment of lower urinary tract symptoms due to benign prostatic enlargement. European Urology Supplements 5:430-440. MacLaughlin, B.W., Gutsmuths, B., Pretner, E., Jonas, W. B., Ives, J., Kulawardane, D.V., and H. Amri. 2006. Effects of home opathic preparations on human prostate cancer growth in cellular and animal models. Integrative Cancer Therapies 5(4): 362-372. MacLean, C. D. 1996. Principles of cancer screening. Medical Clinics of North America. 80(1): 1-14. Madersbacher, S., Ponholzer, A., Berger, I., and M. Marszalek. 2007. Medical management of BPH: role of plant extracts. European Association of Urology and European Board of Urology, 197-205. Mahler, C. 2009. Personal Communication. 1/27/09, 2/3/09. Mahler, C. 2009. How to Make an Atlatl with a Saw Palmetto, as told to her by J. A. Reynolds, 2/12/09 in Arcadia, FL. Transcription of interview in possession of C. Mahler. Mahler, C. 2009. How to Make a Saw Pa lmetto Whistle, as told to her by Wilson, 1/27/09 in Arcadia, FL. Transcri ption of interview in possession of C. Mahler. Mahler, C. Guy LaBree: Barefoot Artist of the Florida Seminoles. Illustrated by Guy LaBree. University Press of Florida, Gainesville, FL. In press. Main, M. B. and G. W. Tanne r. 2003. Effects of fire on Fl oridas wildlife and wildlife habitat. WEC 137, from a series of the Wildlife Ecology and Conservation 93

PAGE 103

Department, Florida Cooperative Extension Service, Inst itute of Food and Agricultural Sciences, University of Florida. < http://edi s.ifas.ufl.edu/UW132>. Accessed:4/9/09. Mann, C. A. 1915. Saw Palmetto: A Phytochemical Study of the Fruit of Sabal Serrulata. Bulletin of the University of Wisconsin No. 767. Science Series 4(8):277-336. Marcus, H. D. 1898. Gonorrhea. 77-78. The International Journal of Surgery Vol. XI. No.1. Markowitz, J.S., Donovan, J. L., DeVane, C. L., Taylor, R. M., Raun, Y., Wang, J., and K. D. Chavin. 2003. Multiple doses of saw palmetto (Serenoa repens ) did not alter cytochrome P450 2D6 and 3A 4 activity in normal volunteers. Clinical Pharmacology & Therapeutics 74:536-542. Marks, L. S., Partin, A. W., Epstein, J. I., Ty ler, V. E., Simon, I., Macairan, M. L., Chan, T. L., Dorey, F. J., Garris, J. B., Velt ri, R. W., Santos, P. B., Stonebrook, K. A., and J. B. DeKernion. 2000. Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. The Journal of Urology. 163:14511456. Marks, L. S., Hess, D. L., Dorey, F. J., Macaira n, M. L., Santos, P. B. C. and V. E. Tyler. 2001. Tissue effects of saw palmetto and finasteride: use of biopsy cores for in situ quantification of prostatic androgens. Urology 57(5):999-1005. McCall, G. A. 1974. Letters from the Frontiers Facsimile reproduction of the 1868 edition with introduction by J. K. Mahon. Bicentennial Floridiana Facsimile Series. University Presses of Florida, Gainesville, FL, p. 193. McConnell, J. D. 1991. The pathophysiol ogy of benign prostatic hyperplasia. Journal of Andrology. 12 (6): 356-363. McGoun, W. E. 1993. Prehistoric Peoples of South Florida The University of Alabama Press, Tuscaloosa, AL. McPherson, H. 2008. Birds? Bees? We're talking flavor, honey. The Orlando Sentinel Orlando, FL. McNeal, J. E. 1983. Relationship of the or igin of benign prostatic hypertrophy to prostatic structure of ma n and other mammals. pp. 152-166. Benign Prostatic Hypertrophy F. Hinman, ed. Springer-Verlag: New York, NY. McVary, K. T. 2006. BPH: Epidemiology and Comorbidities. The American Journal of Managed Care 12(5): 122-127. McVary, K. T. 2007. A review of combination therapy in patients with benign prostatic hyperplasia. Clinical Therapeutics. 29 (3): 387-398. 94

PAGE 104

Mega Bust website. 200 7. . Accessed: 3/24/09. Miami News Collection 1899-1934. Tamiami Trail Photo Series, Reclaiming the Everglades. Digitized from photographs at the Historical Museum of Southern Florida, Miami, Florida. . Access Date: 3/4/09. Milanich, J. T. and C. H. Fairbanks. 1980. Florida Archaeology Academic Press, New York, NY. Moore, W. H., Swindel, B. F., and W. S. Terry. 1982. Vegetative response to clearcutting and chopping in a north Florida flatwoods forest. Journal of Range Management. 35(2): 214-218. Morton, J. F. 1977. Wild Plants for Survival in South Florida Fairchild Tropical Gardens, Miami, FL. Morton, J. F. 1986. Plants of long ago: being mostly quotations from historical literature. Morton Collectanea Communication #4. Mullan, R. J., Bergstralh, E. J., Farmer, S. A., Jacobsen, D. J., Hebbring, S. J., Cunningham, J. M., Thibodeau, S. N., Lieb er, M. M., Jacobsen, S. J., and R. O. Roberts. 2006. Growth factor, cytoki ne, and Vitamin D receptor polymorphisms and risk of benign prostatic hyperplasi a in a community-based cohort of men. Adult Urology 67: 300-305. Myers, F. L.. 1990. Scrub and High Pine. In: Myers, R. L., Ewel, J. J., eds. Ecosystems of Florida University of Central Fl orida Press: Orlando, FL: 150-193. Myers, R. L. and J. J. Ewel, eds. 1990. Ecosystems of Florida. University of Central Florida Press: Orlando, FL. Nash, R. 1931. Survey of the Seminole Indians of Florida. 71st Congress, 3rd Session, Senate Doc. No. 314 [Serial 9347]. Reprinted in 1987 in A Seminole Sourcebook Ed. by W. C. Sturtevant. Garla nd Publishing, Inc., New York, NY. Neuhouser, M. L., Schenk, J., Song, Y. J., Ta ngen, C. M., Goodman, P. J., Pollak, M., Penson, D. F., Thompson, I. M., and A. R. Kristal. 2008. Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and risk of benign prostate hyperplasia in the prostate cancer prevention trial. The Prostate. 68: 1477 1486. Nickel, J. C., Sander, S., and T. D. Moon. 2008. A meta-analysis of the vascular-related safety profile and efficacy of alpha-adren ergic blockers for symptoms related to benign prostatic hyperplasia. Int J Clin Pract 62 (10): 1547-1559. Nuez, C., Cansino, J. R., Bethencourt, F ., Prez-Utrilla, M., Fraile, B., Martnez95

PAGE 105

Onsurbe, P., Olmedilla, G., Paniagua, R., and M. Royuela. 2008. TNF/IL1/NIK/NFB transduction pathway: a comparative study in normal and pathological human prostate (b enign hyperplasia and carcinoma). Histopathology 53: 166-176. Ong, E. S. 2004. Extraction methods and chemical standardization of botanicals and herbal preparations. Journal of Chromatography B. 812 (1-2): 23-33. Ortner, E. R., Hayes, R. B., Weissfeld, J., and E. P. Gelmann. 2006. Effect of homeodomain protein NKX3.1 R52C pol ymorphism on prostate gland size. Adult Urology 67(2): 311-315. Parda, D. S., Thraves, P. J., Kuettel, M. R ., Lee, M., Arnstein, P., Kaighn, M. E., Rhim, J. S., Dritschilo, A. 1993. Neoplastic transformation of a human pr ostate epithelial cell line by the v-Kiras oncogene. The Prostate 23(2):91-98. Parke, Davis & Co. 1901. Saw palmetto. 451. Physicians Manual of Therapeutics Referring Especially to the Products of the Pharmaceutical and Biological Laboratories of Parke, Davis & Company Detroit, MI. Penna, G., Fibbi, B., Amuchastegui, S., Co ssetti, C., Aquilano, F., Laverny, G., Gacci, M., Crescioli, C., Maggi, M., and L. Adorini. 2009. Human benign prostatic hyperplasia stromal cells as inducers a nd targets of chronic immuno-mediated inflammation. The Journal of Immunology. 182: 4056-4064. Perez, J. 2009. Interview in Vero Beach, FL. 3/15/09. Perdue, T., and M. D. Green. 2001. The Columbia Guide to American Indians of the Southeast Columbia University Press, New York, NY. Pitman, W. D. 1993. Evaluation of sa w palmetto for biomass potential. Bioresource Technology. 43: 103-106. Plants Database website. USDA Natu ral Resources Conservation Service. . Accessed: 4/6/09. Platt, W. J. and M. W. Schwartz. 1990. Te mperate Hardwood Forests. In: Myers, R. L., Ewel, J. J., eds. Ecosystems of Florida University of Central Florida Press: Orlando, FL: 194-229. Porcher, F. P. 1869. Resources of the Southern Fields and Forests, Medical, Economical, and Agricultural; Being also a Medical Botany of the Southern States; with Practical Information of the Useful Pr operties of the Trees, Plants, and Shrubs. Walker, Evans, & Cogswell, Printers, Charleston, SC. pp. 604. Prager, N., Bickett, K., French, N., Ma rcovici, G. 2002. A randomized, double-blind, 96

PAGE 106

placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-reductase in the treatment of androgenetic alopecia. The Journal of Alternative and Complementary Medicine. April 2002, 8(2): 143-152. Probido website. 2007. . Accessed: 3/24/09. PSA Rising website. 2008. The Prostate. < http://www.psarising.com/prostatecancer/prostate.htm>. Accessed: 4/10/09. Purdy, B. A. 1991. The Art and Archaeology of Floridas Wetlands CRC Press, Boca Raton, FL. Pyke, G. H. 1983. Relationship between time since the last fire and flowering in Telopea speciosissima R. Br. and Lambertia formosa Sm. Australian Journal of Botany. 31(3) 293 296. Raman, P., DeWitt, D. L., and M. G. Nair 2008. Lipid peroxidation and cyclooxygenase enzyme inhibitory activities of acid ic aqueous extracts of some dietary supplements. Phytotherapy Research. 22:204-212. Rawlings, M. K. 1966. The Yearling. Charles Scribners Sons, New York, NY. Read, J. B. 1879. Saw palmetto ( Sabal serrulata ).169-171. The American Journal of Pharmacy. Volume LI. Fourth Series, Volume IX. Edited by J. M. Maisch. Published in Philadelphia, PA, by Philadelphia College of Pharmacy. Reasoner, E.N. 1902. Ser ena serrulata. pp. 1661. Cyclopedia of American Horticulture Ed. by L.H. Bailey. The Macm illan Company, New York, NY. Red Rooster website. . Accessed: 3/24/09. Reitz, E. J. and C. M. Scarry. 1985. Reconstructing Historic Subs istence, with an Example from Sixteenth-Century Spanish Florida The Society for Historical Archaeology, Glassboro, NJ. Rennie, P. S., Bruchovsky, N., Goldenberg, S., and S. Larry. 1988. Relationship of androgen receptors to the growth and regression of the prostate. American Journal of Clinical Oncology. 11:S13-7. Reynolds, C. B. 1886. Old St. Augustine: a Story of Three Centuries E.H. Reynolds, St. Augustine, FL. Rhodes, L., Primka, R. L., Berman, C., Vergult G., Gabriel, M., Pierre-Malice, M., B. Gibelin 1995. Comparison of finasteride (Proscar), a 5 reductase inhibitor, and various commercial plant extract s in in vitro and in vivo 5 reductase inhibition. The Prostate. 22 (1): 43-51. 97

PAGE 107

Ricote, M., Garca-Tun, I., Bethencourt, F. R., Fraile, B., Paniagua, R., and M. Royuela. 2004. Interleukin-1 (IL-1 and IL-1 ) and its receptors (IL-1RI, IL1RII, and IL-1Ra) in prostate carcinoma. Cancer 100: 1388-1396. Risbridger, G. P., Ellem, S. J., and S. J. McPherson. 2007. Estrogen action on the prostate gland: a critical mix of e ndocrine and paracrine signaling. Journal of Molecular Endocrinology 39:183-188. Robinson, B. B. 1947. Minor fiber industries. Economic Botany. 1(1): 47-56. Roehrborn, C. G., Lange, J. L., George, F. W., and J. D. Wilson. 1987. Changes in amount and intracellular distribution of a ndrogen receptor in human foreskin as a function of age. The Journal of Clin ical Investigation. 79 (1): 44-47. Rong, S., Xie, Q., Gang, X., Lun, J., Cheng, L., Pantuck, A., and J. Rao. 2008. Effect of saw palmetto soft gel capsule on lower urinar y tract symptoms associated with benign prostatic hyperplasia: a rando mized trial in Shanghai, China. The Journal of Urology 179: 610-615. Salam, M. T., Ursen, G., Skinner, E. C ., Dessissa, T., and J. K. Reichardt. 2005. Associations between polymorphisms in the steroid 5reductase type II (SRD5A2) gene and benign prostatic hyperplasia and prostate cancer. Urologic Oncology: Seminars and Original Investigations 23:246-253. Samson, D. A., and K. S. Werk. 1986. Size-de pendent effects in the analysis of reproductive effort in plants. American Naturalist. 127(5): 667-680. Sanford, M. T. 2003. Beekeeping: Florida be e botany. Circular 686 from the Entomology and Nematology Department, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences, University of Florida. Savikin-Fodulovic, K., Grubisi c, D., Culafic, L., and Menkovic, N. 1998. Diosgenin and phytosterols content in leaves and rhizomes of Dioscorea balcanica Kos. (Dioscoreaceae). Pharmaceutical and Phar macological Letters. 8(2): 87-89. Saw Palmetto Harvesting Company webs ite. . Accessed: 3/24/09. Saw Palmetto Honey. 2006. . Accessed: 2/23/09. Scaglione, F. Lucini, V. Pannacci, M., Ca ronno, A. and C. Leone. 2008. Comparison of the potency of different brands of Serenoa repens extract on 5 -reductase types I and II in prostatic co-cultured epithelial and fibroblast cells. International Journal of Experimental and Clinical Pharmacology. 82 (4): 270-275. Scarry, C. M. and L. A. Newsom. 1992. Archaeobotanical research in the Calusa 98

PAGE 108

heartland. C ulture and Environment in the Domain of the Calusa Ed. W. H. Marquardt. University of Fl orida, Gainesville, FL. p. 375-401. Schantz, M. M., Bedner, M., Long, S. E., Mo lloy, J. L., Murphy, K. E., Porter, B. J., Putzbach, K., Rimmer, C. A., Sander, L. C., Sharpless, K. E., Thomas, J. B., Wise, S. A., Wood, L. J., Yen, J. H., Yarita, T., NguyenPho, A., Sorenson, W. R., and J. M. Betz. 2008. Development of saw palmetto ( Serenoa repens) fruit and extract standard reference materials. Analytical and Bioanalytical Chemistry. 392:427-438. Scholtysek, C., Krukiewicz, A. A., Alonso, J., Sharma, K. P., Sharma, P. C., and W. H. Goldmann. 2009. Characterizing components of the saw palmetto berry extract (SPBE) on prostate cance r cell growth and traction. Biochemical and Biophysical Research Communications 379:795-798. Schuster, I. and R. Bernhardt. 2007. Inhibi tion of cytochromes P450: existing and new promising therapeutic targets. Drug Metabolism Reviews. 39 (2-3): 481-499. Sciarra, A., Di Silverio, F., Salciccia, S., Gomez, A. M., Gentilucci, A., and V. Gentile. 2007. Inflammation and chronic prostatic diseases: evidence for a link? European Urology 52:964-972. Shayanmehr, F., Jalali, S. G., Ghanati, F ., and D. Kartoolinejad. 2008. Discrimination of Pinus eldarica MEDW. and its two new species by epicuticular wax, lignin content, electrophoretic isozym e and activity of peroxidase. Feddes Repertorium 119(7-8) : 644. Sherrard, C. C. 1894. Saw palmetto ( Sabal serrulata ). 309-315. Proceedings of the American Pharmaceutical Association at the Forty-Second Annual Meeting Published in Baltimore, MD by the American Pharmaceutical Association. Shi, R., Xie, Q., Gang, X., Lun, J., Cheng, L., Pantuck, A., Rao, J. 2008. Effect of saw palmetto soft gel capsule on lower urinar y tract symptoms associated with benign prostatic hyperplasia: a randomi zed trial in Shanghai, China. Journal of Urology. 179(2): 610-615. Shoemaker, J. V. 1893. Sabal serrulata saw palmetto. A Practical Treatise on Materia Medica and Therapeutics with Especial Reference to the Clinic al Application of Drugs 2nd Ed. Volume II. Published in Philadelphia, PA by The F. A. Davis Co., Publishers. Sklaroff, J. 2008. Personal Communication. 10/7/08. Smith, P.F. 1839. Fecula of the saw-palmetto, used by the Indians as food. The American Medical Intelligencer Ed. R. Dunglison. A. Waldie, Philadelphia, PA. p.139-140. 99

PAGE 109

Snyder, J. R., Herndon, A., and W B. Robertson. 1990. South Florida Rockland. In: Myers, R. L., Ewel, J. J., eds. Ecosystems of Florida University of Central Florida Press: Orlando, FL: 230-277. Soulitzis, N., Karyotis, I., Delakas, D., a nd D. A. Spandidos. 2006. Expression analysis of peptide growth factors VEGF, FGF 2, TGFB1, EGF, and IGF1 in prostate cancer and benign prostatic hyperplasia. International Journal of Oncology 29(2): 305-314. Stevenson, G. 1974. Palms of South Florida. Banyan Books, Miami, FL. Stokes, R. C. 1940. A Pharmacognostical Study of Serenoa serrulata (Michx.) Hook. (Saw Palmetto). A masters thesis, University of Florida, Gainesville, FL. Strauch, G., Perles, P., Vergulyt, G., Gabrie l, M., Gibelin, B., Cummings, S., Malbecq, W., and M. Malice. 1994. Comparison of finasteride (Proscar) and Serenoa repens (Permixon) in the inhibition of 5-alpha reductase in healthy male volunteers. European Urology 26:247-252. Strickland, J. 2009. Personal Communication. 3/6/09. Sturtevant, W. C. 1954. The medicine bundles and busks of the Florida Seminole. Florida Anthropologist. Reprinted in 1987 in A Seminole Sourcebook. Ed. by W. C. Sturtevant. Garland Publishing, Inc., New York, NY. Sturtevant, W. C. 1955. The Mikasuki Seminole: Medical Beliefs and Practices A Dissertation Presented to th e Faculty of the Graduate School of Yale University in Candidacy for the Degree of Doctor of Philosophy. Suzuki, M., Oki, T., Sugiyama, T., Umegaki, K., Uchida, S., and S. Yamada. 2007. Muscarinic and Alpha 1-Adrenergic r eceptor binding characteristics of saw palmetto extract in rat lower urinary tract. Urology 69(6): 1216-1220. Tanner, G. W. and J. J. Mullahey. 2009. Saw-palmetto: an Ecologically and Economically Important Native Palm. Circular WEC-109 from the Wildlife Ecology and Conservation Department, Fl orida Cooperative Extension Service, Institute of Food and Agricultural Sciences, University of Florida. Tanner, G. W., Wood, J. M., Kalmbacher, R. S., and F. G. Martin. 1988. Mechanical shrub control on flatwoods range in south Florida. Journal of Range Management. 41(3): 245-248. Taylor, R. A., and G. P. Risbridger. 2008. Th e path toward identifying prostatic stem cells. Differentiation 76: 671-681. The Nursery at TyTy. < http:// www.tytyga.com/>. Accessed: 4/3/09. 100

PAGE 110

Thorner, J. 2003. The lure of wild berries. St. Petersburg Times website. . Accessed: 3/29/09. Timms, B. G. 2008. Prostate developm ent: a historical perspective. Differentiation. 76 (6): 565-577. Trojan, L., Bode, C., Weiss, C., Mayer, D ., Grobholz, R., Alken, P., and M. Michel. IGF-II serum levels increase discrimination between benign prostatic hyperplasia and prostate cancer and improve the pred ictive value of PSA in clinical staging. European Urology 49(2): 286-292. Trompetter, M., Smedts, F., Van Der Wijk, J., Schoots, C., De Jong, H. J., Hopman, A., and J. De La Rosette. 2008. Keratin prof iling in the developing human prostate. A different approach to understanding epithelial lineage. Anticancer Research. 28(1A): 237-243. Tut, T. G., Ghadessy, F. J., Triforo, M.A., Pinsky, L., and E. L. Yong. 1997. Long polyglutamine tracts in the androgen recep tor are associated with reduced transactivation, impaired sperm production, and male infertility. Journal of Clinical Endocrinology and Metabolism 82(11): 3777-3782. United States Department of Agriculture. 1879. Report of the Secret ary of Agriculture. United States Food and Drug Administrati on, Center for Food Safety and Appli Nutrition. 2007. Fact Sheet: Dietary Supplement Current Good Manufacturing Practices (CGMPs) and Interim Final Rule (IFR) Facts. . VanGelder, W. 2009. Interview in Gilley Creek Tract, Manatee County, FL. 3/06/09. Van Zandt, I. L. 1905. Saw palmetto in tonsillitis and enlarged tonsils. Medical Record: A Weekly Journal of Medicine and Surgery. 67(1): 937. New York, NY. Vela-Navarrete, R., Escribano-Burgos, M., Farr, A. L., Garca-Cardoso, J., Manzarbeitia, F., and C. Carrasco. 2005. Serenoa repens treatment modifies Bax/Bcl-2 index expression and caspase-3 activity in prostatic tissue from patients with benign prostatic hyperplasia. The Journal of Urology. 173:507-510. Vines, R. A. 1960. Trees, Shrubs, and Woody Vines of the Southwest. University of Texas Press, Austin, TX. Wadsworth, T. L., Carroll, J. M., Mallinson, R. A., Roberts, C. T. and C. E. Roselli. 2004. Saw palmetto extract suppresses insulin-like growth factor-1 signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells. Endocrinology. 145(7):3205-3214. 101

PAGE 111

Wadsworth, T. L., W orstell, T. R., Greenberg, N. M., and C. E. Roselli. 2007. Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mouse prostate model (TRAMP). The Prostate. 67:661-673. Wasserman, N.F. 2006. Benign prostatic hyperplasia: a review and ultrasound classification. Radiologic Clinics of North America. 44(5): 689-710. WebMD. 2008. Human Anatomy: The Pr ostate. . Accessed: 4/10/09. Weisser, H., Tunn, S., Behnke, B., and M. Kr ieg. 1996. Effects of the Sabal serrulata extract IDS 89 and its subfractions on 5 -reductase activity in human benign prostatic hyperplasia. The Prostate. 28:300-306. Widmer, R. J. 1988. The Evolution of the Calusa: a Nonagricultural Chiefdom on the Southwest Florida Coast University of Alabama Press, Tuscaloosa, AL. Wilder, E. A., and E. D. Kitzke. 1954. Waxy constituents of the saw palmetto, Serenoa repens (Bartr.) Small. Science 120: 108-109. Wilder, R. 1940. God has a long face G. P. Putnam's Sons, New York, NY. Willetts, K. E., Clements, M. S., Champion, S., Ehsman, S., and J. A. Eden. 2003. Serenoa repens extract for benign prostate hyperplasia: a randomized controlled trial. BJU International 92:267-270. Wilt, T. J., Ishani, A., Stark, G., MacDonald, R., Lau, J., and C. Mulrow. 1998. Saw palmetto extracts for treatment of be nign prostatic hyperplasia: a systematic review. The Journal of the Americ an Medical Association 280 (11): 1604-1609. Wolsko, P. M., Solondz, D. K., Phillips, R. S ., Schachter, S. C., Eisenberg, D. M. 2005. Lack of herbal supplement characteriza tion in published rand omized controlled trials. The American Journal of Medicine. 118:1087-1093. Wunderlin, R. P. and B. F. Hansen. 2003. Guide to the Vascular Plants of Florida. University Press of Florida, Gainesville, FL. Wyeth, J. 1901. An Epitome of Therapeutics with Sp ecial Reference to the Laboratory Products of John Wyeth & Brother, Inc. Philadelphia, PA. Yale, S. H., and I. Glurich. 2005. Analysis of the inhibitory potent ial of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of Cytochrome P450 3A4, 2D6, and 2C9. The Journal of Alternative and Complementary Medicine. 11 (3): 433-439. Yam, J., Schaab, A., Kreuter, M., and J. Drewe. 2008. Piper cubeba demonstrates anti102

PAGE 112

estrogenic and anti-inflammatory properties. Planta Med 74:142-146. Yang, Y., Ikezoe, T., Zheng, Z., Taguchi, H., Koeffler, H. P., and W. Zhu. 2007. Saw palmetto induces growth arrest and ap optosis of androgen-dependent prostate cancer LNCaP cells via inactivation of STAT 3 and androgen receptor signaling. International Journal of Oncology 31: 593-600. Yeu, E., and R. Grostern. 2007. Saw palmetto and intraoperative floppy-iris syndrome. Journal of Cataract & Refractive Surgery 33:927-928. Zarraga, I. G., and E. R. Schwarz. 2007. Coxibs and heart disease: what we have learned and what else we need to know. Journal of the American College of Cardiology 49(1):1-14. Zhang, Z., Duan, L., Du, X., Ma, H., Park, I., Lee, C., Zhang, J., and J. Shi. 2008. The proliferative effect of estradiol on human prostate stem cells is mediated through activation of ERK. The Prostate 68:508-516. 103

PAGE 113

Appendix 1 : Excerpt from The Yearling describing a boy making a flutter-mill A low palmetto brushed him. It remi nded him that his knife was snug in his pocket; that he had planned as long ago as Christmas, to make himself a flutter-mill. He had never built one alone. Grandma Huttos son Oliver had always made one for him whenever he was home from sea. He went to work intently, frowning as he tried to recall the exact angle necessary to make the mill-wheel turn smoothly. He cut two forked twigs and trimmed them into two Ys of the same size. Oliver had been very particular to have the crossbar round and smooth, he rememb ered. A wild cherry grew half-way up the bank. He climbed it and cut a twig as even as a polished pencil. He selected a palm frond and cut two strips of the tough fiber, an inch wide and four inches long. He cut a slit lengthwise in the center of each of them, wide enough to insert the cherry twig. The strips of palm frond must be at angles, like the arms of a windmill. He adjusted them carefully. He separated the Y-shaped twigs by nearly the length of the cherry cross-bar and pushed them deep into the sand of the branch bed a few yards below the spring. The water was only a few inches deep but it ran strongl y, with a firm current. The palm-frond mill-wheel must just brush the waters surface. He experimented with depth until he was satisfied, then laid the cherry bar between the twigs. It hung motionless. He twisted it a moment, anxiously, helping it to fit itself into its forked grooves. The bar began to rotate. The current caught the flexible tip of one bit of palm frond. By the time it lifted clear, the rotation of the bar brought the angled tip of the second into contact with the stream. The small leafy paddles swung over and over, up and down. The little wheel was turni ng. The flutter-mill was at work. It turned with the easy rhythm of the great water-mill at Lynne that ground corn into meal. (Rawlings, 1966: 5-6) 104

PAGE 114

Appendix 2 : Stokes Suggested Change for the description of S. repens (a.k.a. Sabal) in the National Formulary Powdered Sabal: Yellowish brown, fr agments of inner epicarp, the cells containing a reddish to reddish brow n amorphous material and yellowish colored oil globules; yello wish fragments of meso carp, the cells having somewhat thickened colorless walls a nd containing a pale yellow to straw colored amorphous material and one to several oil globules; whitish fragments of endosperm numerous, th e cell walls of which may or may not be uniformly thickened and usually showing large, characteristic pore canals; numerous stone cells, colorless to straw colored, varying in shape from tabular, to oval, to polygonal to elongated, from 0.020 mm. to 0.189 mm. in length, with walls from 0.005 mm. to 0.036 mm. in thickness, many of these cells showing numer ous simple or branching pores and polarizing light with a distinct cros s; occasional frag ment of elongated sclerenchyma fibers, having thickened walls and narrow lumina; fragment of spiral vessels only rarely present; straw to pale ye llowish oil globules scattered throughout the powder, many of which are free and not located in cells; fragments of testa numerous the cells usually containing a reddish to reddish brown amorphous s ubstance; occasional fragment of tegmen, the cells having thin, non-pitte d walls and containing a yellowish to yellowish brown amorphous ma terial. (Stokes, 1940: 45-46) 105

PAGE 115

106 Appendix 3 : Contact Information for Harvesting Companies Plantation Medicinals, Inc. 1401 County Rd Ste 830 Felda, FL 33930 Phone: (863) 675-2984 Saw Palmetto Berries Co-op of Florida, Inc 1206 Kings Way Naples, FL 34104 Phone: (239)775-1243 Fax: (239)775-9818 E-mail: prostaterxx@earthlink.net The Saw Palmetto Harvesting Company http://www.sawpalmetto.com/ Corporate Office 1969 310th Ave. Lengby, MN 56651 Phone: (218)935-2697 Fax: (218)935-2697 E-mail: sawpalm@gmail.com Processing Plant Phone: (863) 635-4857 4000 Hwy 27 Frostproof, FL 33843