Jillian L. Capodice, LAc introduces a variety of botanicals and supplements commonly known as “prostate-specific” and provides an overview on some of the available research.

by Jillian L. Capodice, LAc

Abstract: Various prostate conditions may affect many men over their lifetime. These common disorders include acute or chronic inflammation of the prostate gland, benign prostatic hyperplasia and prostate cancer. Complementary, alternative and integrative medicine strategies such as those that investigate and utilize botanicals and dietary supplements as potential preventive and therapeutic agents are important. While many promising agents are available, evidence-based research on both preclinical mechanism(s) of action and potential utility in the clinic must be determined before definitive recommendations can be made. This article briefly introduces a variety of botanicals and supplements commonly known as “prostate-specific” and provides a quick overview on some of the available research.


Disorders of the prostate may affect many men over their lifetime. These conditions range from mild inflammation of the prostate gland, to benign enlargement and prostate cancer.  The aforementioned conditions all have significant prevalence and are vastly different pathological conditions; however one shared feature is that advances in preclinical and clinical research will enable us to learn more about the prevention and treatment of these diseases. Integrative medicine, which is the application of evidence-based complementary and alternative medicine (CAM) strategies into the clinic, includes biologic-based CAM therapies including botanicals and supplements and practitioner-based therapies such as acupuncture and massage. Many CAM therapies are popular and are in broad public use and investigation of them in an evidence-based manner is necessary for the sustainability of integrative medicine. This article introduces some of the botanicals and supplements associated with prostate health and begins to highlight research on each agent under investigation for the potential prevention and treatment of prostate cancer and other prostate disorders.       

Background on Prostate Cancer and Prostate Terms

Prostate cancer (CaP) has been estimated to affect one in six men at some point during their lifetime and an estimated 218,890 new cases are predicted in 20071,2.  Prostate cancer risk is associated with a number of factors including advanced age (increases with each decade >50), family history (father or siblings), race (greater prevalence in African American men) and lifestyle (e.g.: smoking). However an extremely important fact about prostate cancer is that it may be close to one hundred percent survivable if it is detected in its early stages3. This information coupled with epidemiologic data on the role of nutritional, dietary and lifestyle behaviors and cancer also illustrates prostate cancer as an excellent model for chemoprevention4. Chemoprevention is a term that was coined to define natural, synthetic or biologic agents used to reverse, suppress or prevent the development of the process of carcinogenesis6. Currently the only proven agent for CaP chemopreventive is the 5-α-reductase inhibitor finasteride5.

The study of finasteride as a chemopreventive agent was based on epidemiological evidence and observation on its clinical utility in reliving the symptoms of benign prostatic hyperplasia (BPH). The mechanism of action of finasteride is based on inhibition of the 5-α reductase enzyme which catalyzes the conversion of testosterone to dihydrotestosterone (DHT), thus sequestering DHT availability which fuels the growth of androgen dependant CaP5,7,8. While finasteride is the only proven cheompreventive agent for CaP, the mechanism of inhibition of the 5- α reductase enzyme has been hypothesized as a potential mechanism of action of various botanicals and supplements. I will discuss some of the pre-clinical and clinical data on these agents and stress that evidence-based research of these agents are necessary before definitive recommendations can be made. While this article is not designed to substitute as a visit to your health care professional, a few basic terms including the definition of the prostate, prostate specific antigen (PSA), biopsy and Gleason score are outlined in Table 1 in order to familiarize the reader with frequently mentioned terms. Table 2 further defines other conditions related to the prostate often referred to throughout this article including chronic prostatitis and benign prostatic hyperplasia (BPH).

A Primer on Herbal Products for Prostate Health: From A-Z

Anecdotal information and the impact of product marketing have suggested that botanicals and supplements may be efficacious in the prevention and treatment of various cancers, but to date, no agents have been validated as curative treatment or as prevention for any cancer. Promising preclinical and/or early phase clinical experimentation testing the anti-cancer potential and prostate health benefit(s) of many supplements and botanicals are both compelling and promising. Below we will outline some of the most common supplements and botanicals being studies for prostate cancer and prostate health. Table 3 provides a quick reference of all the botanicals and supplements mentioned in the article.

A: Arginine

L-arginine is an essential amino acid that is present in the proteins of all life forms. It is synthesized in the kidneys and can also be found in some meats, vegetables, miso and yogurt.  L-arginine is a precursor to the amino acids L-ornthine and L-proline, fundamental building blocks of collagen. Initial research on L-arginine was based on clinical observation of decreased arginine levels in patients with certain traumatic conditions including burns, sepsis and surgical trauma9,10. These observations spurred investigation on the potential anti-oxidant and cardio-protective activity of L-arginine as well as its potential chemopreventive ability11,12.

While L-arginine has found it way onto the list of many male-specific supplements, evidence-based research is sparse. Currently, no studies were found evaluating L-arginine for prostate health and only a handful of studies were found examining the potential activities of L-arginine. These include one study demonstrating growth inhibitory activity in a breast cancer cell line13 and research on the potential role of arginine and its role during immunosupression14. While these data are compelling, there is no substantial evidence at this time to support the benefits of L-arginine supplementation for the prevention or treatment of CaP and/or other prostate disorders.

B: Beta-sitosterol

Beta-sitosterol is one of the most abundant phytosterols in the diet and is commonly found in many plants, legumes and botanicals such as saw palmetto (Serona repens) and pygeum (Pygeum africanum). It is thought to be one of the key active ingredients in many of the prostate-specific herbs and is present in many combination products for male and prostate health. Preclinical research has demonstrated that beta-sitosterol inhibits the growth of prostate cancer cell lines15,16 and reduces xenograph tumor volumes (Awad et al 2001). Additionally, two clinical trials have reported preliminary efficacy of beta-sitosterol in the treatment of voiding symptoms related to BPH and demonstrate improvement in symptoms such as flow rate and decreased post void residual urine volume17,18,19. Further trials need to confirm these promising results and additional studies on botanicals containing beta-sitosterol (saw palmetto and pygeum) are mentioned below.   

C:  Curcumin (see: turmeric)

D: Vitamin D

Vitamin D is created by a reaction between UV light and the skin. Since it is not readily available in many sources, foods such as dairy products, breads and cereals are now fortified with vitamin D. Vitamin D is also available as a single supplement, an ingredient in some calcium supplements and in multi-vitamins made by numerous manufactures. The chemical structure is 1-α, 25-dihydroxyvitamin D or 1, 25(OH2)D9.        

Previous epidemiological data had loosely correlated vitamin D deficiency with increased CaP risk though more recent studies have not found any association9. Current research and development of synthetic vitamin D analogs and vitamin D ligand receptors such as calcipotriol and calcitrol are underway. These agents may have inhibitory activity against prostate cancer cell lines and/ or synergistic activity with conventional chemotherapeutic agents21-24. Many of these preclinical and clinical investigations are underway and will further determine the utility of these agents.

E: Vitamin E, Essential Fatty Acids (see: fish oils, see omega-3)

Vitamin E is an antioxidant with potential cardio-protective and chemopreventive activity. Vitamin E describes 4 tocopherols and 4 tocotrienols but the most commonly supplemented form of vitamin E is a-tocopherol9.  

While recent clinical data suggests that long-term (>4 years) and high-dose (>400IU) vitamin E supplementation may increase the risk of cardiovascular events in patients with diabetes mellitus and vascular disease, a large phase III trial entitled the Selenium and Vitamin E Cancer Prevention Trial (SELECT) is underway testing vitamin E supplementation (400 IU/day, all rac alpha-tochopheryl acetate) alone or in combination with the trace mineral, selenium (200 ug/day, L-selenomethionine) for prostate cancer chemoprevention25,26. The primary endpoint of the SELECT study is the clinical incidence of CaP as determined by a routine clinical work-up, including yearly digital rectal examination (DRE) and serum prostate specific antigen (PSA) levels. The final results of SELECT are anticipated in 201326.

F: Fish oils

Fish oils are tremendous sources of essential long-chain polyunsaturated fatty acids (LCPFA). These LCPFA’s are found in other plants including flax, evening primrose and algae; however fish oils are one of the richest sources of these lipids. Two of the most commonly studied fish oils are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Both EPA and DHA are being examined for their potential anti-inflammatory activity and possible utility in chronic inflammatory conditions including cardiovascular disease and cancer27-29. Regarding prostate health, epidemiological studies have found conflicting evidence regarding fish oil supplementation and CaP incidence30,31. However preclinical investigations have also demonstrated that EPA and DHA are able to inhibit the growth of the prostate cancer cell line LNCaP and decrease mRNA levels of five up-regulated genes32. Recent in vivo data also suggest that rats fed a diet high in omega-3 stearidonic acid demonstrated decreased tumor growth, increased apoptosis and decreased proliferation in tumor cells33. While further research including placebo-controlled clinical trials will hopefully address these discordant results, no clear evidence is yet available suggesting the benefit of fish oil for prostate health.

G: Garlic, Ginger, Green Tea


Garlic (Allium sativum) is a commonly used herb in many cuisines and its posited health benefits are mainly derived from anecdotal evidence and a few epidemiological studies34,35. Recently, investigators have proposed hypotheses testing the anti-cancer potential of garlic but only a few preclinical studies were found testing garlic and diallyl trisulfide (an active component of garlic) for their potential inhibitory activity in the PC-3 and DU-145 prostate cancer cell lines36-38.


Ginger (Zingiber officinalis) is another well-known culinary herb that is also recognized to stimulate the digestive system and decrease subjective symptoms such nausea and motion sickness39,40. It has only been recently proposed as a powerful anti-inflammatory and potential anti-cancer agent in various preclinical cancer cell model systems including a colon cancer cell line and the epidermal mouse cell line JB6 often used to study tumor progression41. However no studies were found solely testing ginger or ginger products in a prostate cancer cell model system and only one study was found testing a combination formulation containing ginger called Zyflamend®, which exhibited inhibitory activities in the LNCaP cancer cell line42.

Green Tea

Green tea is a beverage that is traditionally drank in many Asian countries. There are many varieties of green tea and the most common plant is Camellia sinensis. Compositional analysis of green tea has revealed potent polyphenolic compounds termed catechins, which are further subdivided into flavan-3-ols. Green tea contains four major flavanols; (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epicatechin (EC) (Medical Economics 1998). EGCG is the most widely in studied both in vitro and in vivo chemoprevention studies.

In vitro studies have begun to elucidate the complex molecular mechanisms of action of ECGC and green tea polyphenols against prostate cancer cell lines and different investigators have demonstrated that inhibitory effects are due to induction of apoptosis43 inhibition of cell cycle progression44, and inhibition of key cell signaling pathways45. Many of these preclinical data have yielded translational phase I studies assessing the pharmacokinetics, safety and tolerability of green tea46 which have led to larger phase II and III clinical trials (currently underway) of green tea as a potential chemopreventive agent in breast, colon and prostate cancers47,48.

I: Isoflavones (soy isoflavones)

Soy isoflavones are considered phytoestrogens, plant-derived non-steroidal compounds with estrogen-like biological activity. Soy isoflavones consist of three main glycosylated aglycones, genistein, daidzein and glycitein, and each has been found to have both weak estrogenic and anti-estrogenic effects in vitro49. Pre clinical data have also demonstrated the anti-cancer activity of soy isoflavones in prostate, colon and breast cancer cell models50,51.

Initial clinical trials investigating the pharmacokinetic evaluation of genistein and daidzein demonstrated no clinically significant behavioral or physical changes regarding toxicity and rapid plasma and urine clearance of free and total genistein and daidzein ((1, 2, 4, 8, or 16 mg/kg body wt) in 30 healthy men) (t1/2 (elimination half-life) values of 3.2 h (free genistein) and 4.2 h (free daidzein))52. Other clinical trials tested the effect of various soy compounds on biomarkers. One pilot study confirmed a decreased percent change of free and total PSA ratios in prostate cancer patients consuming soy containing bread versus controls ((27.4% versus 15.6% respectively (p = 0.01))52. These and other promising investigations suggest that isoflavones may be potential prostate cancer chemopreventive agents and further clinical trials are necessary.

L: Lycopene

Lycopene is a member of the carotenoid family. It serves as an accessory light-gathering pigment and antioxidant in plants and algae and is responsible for giving vegetables and fruits their color.  Lycopene is available in watermelons, papaya, pink guava, grapefruit, tomatoes and tomato-based products including tomato sauce, tomato juice and ketchup. Processed tomato products generally have more available dietary lycopene than fresh tomatoes9.

Regarding its role as a potential prostate cancer chemopreventive agent, a thorough meta-analysis of 11 case-control studies and 10 cohort studies assessed the use of tomato, tomato products, and/or lycopene and the relative risk of CaP53.  The main findings were that the relative risk (RR) of prostate cancer among consumers of high amounts of raw tomato (5th quintile of intake) was 0.89, (95% CI 0.80–1.00) and less than nonfrequent users of tomato products (1st quartile of intake)52. In addition, lycopene intake from tomato products and particularly cooked tomato products seemed more bioavailable52-54. Based on these epidemiologic studies, current clinical trials are attempting to determine dose and response rates of supplemented lycopene.  A recent phase I-II trial of lycopene supplementation in 36 men with biochemically relapsed prostate cancer (as determined by PSA) received daily lycopene supplementation of 15, 30, 45, 60, 90, and 120 mg/day for 1 year and demonstrated that lycopene was well tolerated in this patient population but supplementation at the doses used in the study did not result in any serum PSA response55. In conclusion, lycopene has potential as a potential chemopreventive agent although larger clinical trials are warranted.

O:  Omega-3 Fatty Acids (Alpha-linoleic Acid)

Aloha-linoleic acid is an omega 3 fatty acid that contains 18 carbon atoms and 3 double bonds. It is also known as ALA9. ALA is metabolized to eicosapaentenoic acid (EPA) and docosahexaenoic acid (DHA) and EPA is a precursor to multiple eicosaniods which have both anti-inflammatory and anthi-arterogenic porpoerties.  Numerous studies on prostate cancer risk have demonstrated conflicting results. Alpha-linolenic acid (ALA) is the most common omega-3 fatty acid in the Western diet however the relationship between dietary intake of ALA to prostate cancer risk remains unresolved. In 2004, Leitzman et al prospectivley evaluated the association between dietary intakes of alpha-linoleic  and other fatty acids including, EPA (eicosanpentaenoic), DHA (docosahexaenoic), LA (linoleic), and AA (arachidonic acids and prostate cancer risk in 47,866 men56.  Theses results demonstrate that of total cases, ALA intake was unrelated to risk, however, multivariate analyses demonstrated that in general, men with high intakes of ALA from meat and dairy were less likely to undergo CaP screening  than those with greater ALA intakes from non-animal sources. However overall analysis determined that there was a weaker association for ALA intake (multivariate RR: 1.70; 95%CI:1.08,2.68;P for trend =0.04) than the authors previous report in 198657. Certain limitations regarding ALA studies and dietary intake vary depending on the oil type used in processed food versus sources from fish, meats, fruits, vegetables and grains. Moreover, studies of blood ALA levels are controversial due to low concentrations in most tissues including plasma and erythrocytes58. Based on the literature, at this time, it is difficult to make recommendations based on ALA intake, however it seems source of ALA intake and other risk factors including family history, genetic factors other dietary and lifestyle habits are all factors.

P: Pomegranate, pygeum

Pomegranate fruit (Punica granatum) is widely consumed as a fruit and juice and both anecdotal and epidemiological evidence suggest that the consumption of pomegranate juice may be a valuable cardioprotective agent and antioxidant59,60. Constitutional analysis of pomegranate seeds and husks reveals sugars, sterols, proteins, pectins and potent polyphenolic compounds including punicalagin and ellagic acid (of which punicalagin seems to be the most widely active and abundant)61.

Initial biochemical and cell based analysis has revealed preliminary effectiveness of pomegranate juice as a cardioprotective and anti-artherosclerotic agent and suggested it may have potential chemopreventive activity against human breast, colon, and prostate cancer cell62-64.

While there are only a few studies of pomegranate extract as a chemopreventive agent for prostate cancer, initial studies suggest that various elements of pomegranate juice (ellagic acid, lutieloin and caffeic acid from the juice and pericarp and steroidal chemicals 17-α estradiol, campesterol, gamma tocopherol, punicic acid) may act synergistically to enhance its antiproliferative activities in prostate cancer cell lines65. These same investigators also noted that pomegranate fractions may also inhibit the action of PC-3 prostate cancer cells across Matrigel ™ protein matrix membranes66.

While no human clinical trial data is available testing pomegranate juice as a potential chemopreventive, bioavailability data analysis suggests that ellagic acid and tannins found in pomegranate extracts are detectable in human plasma after oral consumption of pomegranate juice (180ml)67.  In addition, pomegranate juice has been tested in a phase II trial of men with rising PSA following primary therapy for prostate cancer. This phase II study evaluated daily supplementation of 8 oz of pomegranate juice in men with a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7, until disease progression. The results demonstrated a significant increase in mean PSA doubling time with treatment from a mean of 15 months at baseline to 54 months post treatment (p < 0.001) and corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis68. Together these promising in vitro and in vivo analyses of pomegranate juice demonstrate its promise as a chemopreventive agent for prostate cancer and its potential protective activity following prostate cancer treatment. 


Pygeum (Pygeum africanum) is a tree commonly found in the mountains of central and southern Africa. Its bark is anecdotally known to offer relief from lower urinary tract disorders thus spurring its popularity as an herb for prostate health. Compositional analysis of pyguem has revealed antioxidants, ferrulic esters and beta-sitosterol (see: beta-sitosterol)9. Despite this compelling anecdotal evidence and a few positive case-reports, evidence-based research has yet to determine its efficacy for BPH or as a potential chemopreventive for CaP.

R: Resveratrol

Resveratrol is a polyphenolic chemical known as 3,4′,5 trihydroxystilbene and exists in cis- and trans-stereoisomeric forms of which the trans-form is more active. It is most commonly known as a component found in grapes, grape skins and grapevines (resulting in higher resveratrol concentrations in red wines) but is also an active constituent in plants such as mulberries, peanuts and Polygnim cuspidatum (hu zhang in the traditional Chinese materia medica)69.

Initial biochemical analysis of resveratrol has suggested that both resveratrol and its synthetic analogues are able to inhibit growth of prostate and other cancer cell lines70,71. Molecular-based studies have similarly focused on the mechanistic effects of resveratrol and its ability to induce apoptosis and affect critical cell cycle signaling events in prostate cancer cell lines.

Despite the abundance of molecular data, only one in vivo study was found testing the effects of resveratrol and red wine consumption for its potential cardio-protective effects on platelet aggregation72. In addition, there were no Medline listed trials testing resveratrol in in vivo rodent or xenograph models of CaP or in human prostate cancer toxicity-based or chemoprevention clinical trials73,74. Finally, the question of whether resveratrol activity can be achieved at physiological doses has yet to be determined.  Taken together, further analysis of the potential chemopreventive or therapeutic capability of resveratrol is warranted.

S: Saw palmetto

Saw palmetto (Serenoa repens) has received a great deal of attention in urology due to anecdotal evidence regarding its prostate specific properties.  Compositional analysis has determined that beta-sitosterol, fatty acids and antioxidants may all contribute to its potential therapeutic activity9. Initial studies implied that the potential mechanism of action of saw palmetto might mimic the pharmaceutical 5-α reductase inhibitors though these data are weak75-76. Nevertheless ongoing studies on the mechanism, utility, and efficacy of saw palmetto as a potential chemopreventive agent may make clear the controversy surrounding this popular prostate herb. It is also important to note that a recent double-blind trial of saw palmetto for lower urinary tract symptoms demonstrated no significant effect of saw palmetto supplementation on American Urological Association Symptom Index scores (AUASI) (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01) and maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38)77.

T: Tomato products (see: lycopene), Turmeric

Turmeric (Curcuma longa) is a popular herb used in Indian and Asian cuisine and is widely know for giving curry its golden color. Composition of the herb includes antioxidants, essential oils and the well known potent polyphenolic compounds called curcuminoids. The major curcuminoids are curcumin, bisdemethoxycurcumin and demethoxycurcumin of which 75% of the total curcuminoids are curcumin9. There are many turmeric supplements available on the market with a wide variety of levels of standardization of curcumin and related curcuminoids. While the majority of in vitro analysis has been done on curcumin alone, it has been suggested that synergistic actions of the whole turmeric spice may exert additional potent antioxidant and chemopreventive activities.

Curcumin is a widely studied herb and initial analysis has focused on its antioxidant and anti-inflammatory activities78,79. Molecular analysis of curcumin has demonstrated its ability to induce apoptosis in LNCaP and PC-3 cell lines as well as the bone metastatic CaP cell lines C4-2B80-82. While there seems to be less in vivo data, some experimentation on curcumin has established that it was able to significantly inhibit LNCaP tumor size in nude mice, decrease cellular proliferation via BrdU analysis and inhibit angiogenesis as measured by CD31 antigen staining83. On the contrary, curcumin was not found to be effective against 3, 2’-dimethyl-4-aminobiphenol (DMAB) – and 2-amino-1-methylimidazo [4, 5-b] pyridine (PhIP)-induced rat ventral prostate cancer tumors84

Despite the provocative in vitro and in vivo analysis, more confirmatory data regarding the mechanism of action of curcumin, its synergistic potential and its effect in human chemoprevention trials are necessary.

W: Wine (see: resveratrol)

Z: Zinc

Zinc is an essential element of human nutrition with multiple functions including presence in all organs, tissues, fluids and secretions and maintenance of biological membranes. Zinc is involved in sperm formation and testosterone metabolism, which may contribute to its reputation as an important mineral for men’s health. In addition, the potential immunomodulatory activity of zinc has been suggested.  It is available in a wide variety of supplemental forms including zinc gluconate and zinc aspartae. It is also a common ingredient in many multivitamins. The controversy surrounding zinc supplementation as a risk factor for prostate cancer, a potential chemopreventive agent with inhibitory activity in the prostate and as a potential prognostic marker in combination with PSA is evident85-88.  A recent analysis of trace mineral supplemtnation also reported mixed results from case–control and cohort studies. Kolonel et al  studied the association between dietary Zn intake and risk and reported a statistically significant positive association between total Zn (including foods and supplement Zn) and prostate cancer risk among Hawaiian men over the age of 70 years but not among men under 70 years of age89,90. Conversely, a borderline inverse association between prostate cancer risk and Zinc supplementation found a statistically non-significant 37% decreased risk of prostate cancer in association with toenail Zn levels91. Currently there are no convincing answers regarding zinc supplementation as a chemopreventive agent for prostate cancer. Additional concern regarding zinc supplementation and its potential to decrease the absorption of concomitant intake of bisphosphonates and quinilone antibiotics commonly used in the treatment of  CaP and chronic prostatitis respectively, is notable9,92. Until important preclinical and clinical studies are able to determine the effects of zinc, no ultimate recommendations can be made.


A variety of botanicals and supplements exist for the potential treatment of prostate health. While many of the abovementioned agents have strong anecdotal history and/or long use in traditional medical healing systems, evidence-based medicine and the necessity for rigorous research determining potential risk(s) and benefit(s) is necessary. However, one of the difficulties, surrounding the study of botanicals and supplements are the determination of active component(s), synergistic activity and concomitant use with pharmaceutical agents. The long term goals of the clinician, researcher and patient are to focus on education, awareness and research in order to facilitate integrative medicine. In the case of prostate cancer and prostate health, good diet, nutrition and botanical and dietary supplementation seems important and until all the research is done, it can’t hurt to add an extra cup of green tea and a nice tomato salad to one’s daily diet.


1.  American Cancer Society. Cancer Facts & Figures 2007. Atlanta, GA: American Cancer Society, 2007.

2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ.  Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96.

3. Kamangar F, Dores GM, Anderson WF.  Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006 May 10;24(14):2137-50.

4. Canby-Hagino ED, Thompson IM. 2005. Mechanisms of disease: Prostate cancer–a model for cancer chemoprevention in clinical practice. Nat Clin Pract Oncol, 2(5):255-61.

5. Thompson IM, Goodman PJ, Tangen CM, et al. 2003. The influence of finasteride on the development of prostate cancer.  New Engl J Med, 349:215-224.

6. Sporn MB. 1976. Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res, 36:2699–702.

7. Habib GK, Bissas A, Neill WA et al. 1989. Flow cytometric analysis of cellular DNA in human prostate cancer: relationship to 5-alpha-reductase activity of the tissue. Urol. Res, 17:239–243.

8. Goodman PJ, Tangen CM, Crowley JJ, et al. 2004.  Implementation of the Prostate Cancer Prevention Trial (PCPT). Control Clin Trials, 25(2):203-22.

9. Medical Economics (ed) Physician’s Desk Reference (PDR) for Herbal Medicines, Montvale, NJ: Thomson Healthcare, 1998.

10. Chiarla C, Giovannini I, Siegel JH. 2006. Plasma arginine correlations in trauma and sepsis. Amino Acids, 30(1):81-6.

11. Augustyniak RA, Thomas GD, Victor RG, et al 2005. Nitric oxide pathway as new drug targets for refractory hypertension. Curr Pharm Des, 11(25):3307-15.

12. Basu HN, Liepa GU. 2002. Arginine: a clinical perspective. Nutr Clin Pract, 17(4):218-25.

13. Caso G, McNurlan MA, McMillan ND, et al 2004. Tumor cell growth in culture: dependence on arginine. Clin Sci (Lond), 07(4):371-9.

14.  Grimble RF. Immunonutrition. Curr Opin Gastroenterol. 2005 Mar;21(2):216-22.

15.  Awad AB, Gan Y, Fink CS. 2000. Effect of beta-sitosterol, a plant sterol, on growth, protein phosphatase 2A, and phospholipase D in LNCaP cells. Nutr Cancer, 36(1):74-8.

16.  Jourdain C, Tenca G, Deguercy A, et al.  2006. In-vitro effects of polyphenols from cocoa and beta-sitosterol on the growth of human prostate cancer and normal cells. Eur J Cancer Prev, 15(4):353-61.

17. Berges RR, Windeler J, Trampisch HJ, et al. 1995.  Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group. Lancet, 345(8964):1529-32.

18. Klippel KF, Hiltl DM, Schipp B. 1997. A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto Study group. Br J Urol, 80(3):427-32.

19. Berges RR, Kassen A, Senge T. 2000. Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: an 18-month follow-up. BJU Int, 85(7):842-6.

20. Baron JA, Beach M, Wallace K, et al. 2005. Risk of prostate cancer in a randomized clinical trial of calcium supplementation.  Cancer Epidemiol Biomarkers Prev, 14(3):586-9.

21. Yee YK, Chintalacharuvu SR, Lu J, Nagpal S. 2005. Vitamin D receptor modulators for inflammation and cancer. Mini Rev Med Chem, 5(8):761-78.

22. Brown AJ. 2001. Therapeutic uses of vitamin D analogues. Am J Kidney Dis, 38(Suppl 5):S3-S19.

23. Pinette KV, Yee YK, Amegadzie BY, et al. 2003. Vitamin D receptor as a drug discovery target. . Mini Rev Med Chem, 3(3):193-204.

24.  Beer, T. M., Hough, K. M., Garzotto, M., et al. 2001. Weekly high-dose calcitriol and docetaxel in advanced prostate cancer. Semin Oncol, 28: 49.

25. Yan L, Spitznagel EL. 2005. Meta-analysis of soy food and risk of prostate cancer in men. Int J Cancer, 117(4):667-9.

26. Lippman SM, Goodman PJ, Klein EA, et al. 2005. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Natl Cancer Inst, 97(2):94-102.

27. Hardman WE. 2004. (n-3) fatty acids and cancer therapy. J Nutr,134(12 Suppl):3427S-3430S.

28. Mori TA, Beilin LJ. 2004. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep, 6(6):461-7.

29. Moyad MA. 2005. An introduction to dietary/supplemental omega-3 fatty acids for general health and prevention: part I. Urol Oncol, 23(1):28-35.

30. Astorg P. 2004. Dietary N-6 and N-3 polyunsaturated fatty acids and prostate cancer risk: a review of epidemiological and experimental evidence. Cancer Causes Control, 15(4):367-86.

31. Leitzmann MF, Stampfer MJ, Wu K, et al 2003. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst, 95(13):1004-7.

32.  Chung BH, Mitchell SH, Zhang JS, et al. 2001.  Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells. Carcinogenesis, 22(8):1201-6.

33. Kelavkar UP,  Hutzley J, Dhir R et al. 2006. Prostate tumor growth and recurrence can be modulated by the omega-6:omega-3 ratio in diet: athymic mouse xenograft model simulating radical prostatectomy. Neoplasia, 8(2):112-24.

34.  Kris-Etherton PM, Hecker KD, Bonanome A, et al. 2002. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med, 113 Suppl 9B:71S-88S.

35.  Hsing AW, Chokkalingam AP, Gao YT, et al. 2002.. Allium vegetables and risk of prostate cancer: a population-based study. J Natl Cancer Inst, 94(21):1648-51.

36. Arunkumar A, Vijayababu MR, Srinivasan N, et al. 2006. Garlic compound, diallyl disulfide induces cell cycle arrest in prostate cancer cell line PC-3. Mol Cell Biochem, 288(1-2):107-13.

37.  Xiao D, Singh SV. 2006. Diallyl trisulfide, a constituent of processed garlic, inactivates Akt to trigger mitochondrial translocation of BAD and caspase-mediated apoptosis in human prostate cancer cells. Carcinogenesis, 27(3):533-40.

38. Borrelli F, Capasso R, Aviello G, et al .2005. .Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol. 105(4):849-56.

39. Grzanna R, Lindmark L, Frondoza CG. 2005. Ginger–an herbal medicinal product with broad anti-inflammatory actions. J Med Food, 8(2):125-32.

40.  Manju V, Nalini N. 2005. Chemopreventive efficacy of ginger, a naturally occurring anticarcinogen during the initiation, post-initiation stages of 1,2 dimethylhydrazine-induced colon cancer. Clin Chim Acta, 358(1-2):60-71.

41.  Bode AM, Ma WY, Surh YJ, et al. 2001. Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol. Cancer Res, 61(3):850-3.

42.  Bemis DL, Capodice JL, Anastasiadis AG, et al. 2005.  Zyflamend, a unique herbal preparation with nonselective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression. Nutr Cancer, 52(2):202-12.

43.   Hastak K, Gupta S, Ahmad N, et al. 2003. Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells. Oncogene,22(31):4851-9.

44.  Gupta S, Ahmad N, Nieminen AL, et al. 2000. Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (-)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. Toxicol Appl Pharmacol,164(1):82-90.

45.   Ren F, Zhang S, Mitchell SH, et al. 2000. Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells. Oncogene, 19(15):1924-32.

46.    Chow HH, Cai Y, Hakim IA, et al. 2003. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res,9(9):3312-9.

47.  Greenwald P.  2004. Clinical trials in cancer prevention: current results and perspectives for the future. J Nutr, 134(12 Suppl):3507S-3512S.

48.  Jatoi A, Ellison N, Burch PA, et al. 2003. A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer, 97(6):1442-6.

49.  Yan L, Spitznagel EL. 2005. Meta-analysis of soy food and risk of prostate cancer in men. Int J Cancer, 117(4):667-9.

50.  Knight DC, Eden JA. 1996.A review of the clinical effects of phytoestrogens. Obstet Gynecol, 87(5 Pt 2):897-904.

51.  Busby MG, Jeffcoat AR, Bloedon LT, et al. 2002. Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men. Am J Clin Nutr, 75(1):126-36.

52. Etminan M, Takkouche B., Caamano-Isorna, F. 2004 The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies. Cancer Epidemiol. Biomark. Prev. 13:340-345.

53.  Giovannucci E. 2005. Tomato products, lycopene, and prostate cancer: a review of the epidemiological literature. J Nutr, 135(8):2030S-1S.

54. Giovannucci, E. 1999. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J. Natl. Cancer Inst. 91:317-331.

55. Clark PE, Hall MC, Borden LS Jr, et al. 2006. Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse of prostate cancer after definitive local therapy. Urology, 67(6):1257-61.

56.  Leitzmann MF, Stampfer MJ, Michaud DS, et al. 2004. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr, 80(1):204-16.

57.  Giovannucci E, Rimm EB, Colditz GA, Stampfer MJ, Ascherio A, Chute CC, Willett WC. 1993. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst. Oct 6;85(19):1571-9. 

58.  Attar-Bashi NM, Frauman AG, Sinclair AJ.2004. Alpha-linolenic acid and the risk of prostate cancer. What is the evidence? : J Urol. Apr;171(4):1402-7. 

59.  Wang RF, Xie WD, Zhang Z, et al. 2004. Bioactive compounds from the seeds of Punica granatum (pomegranate). J Nat Prod, 67(12):2096-8.

60. Seeram NP, Adams LS, Henning SM, et al. 2005. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem, 16(6):360-7.

61. Sumner MD, Elliott-Eller M, Weidner G, et al. 2005. Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease. Am J Cardiol, 96(6):810-4.

62.  Kawaii S, Lansky EP. 2004. Differentiation-promoting activity of pomegranate (Punica granatum) fruit extracts in HL-60 human promyelocytic leukemia cells. J Med Food, 7(1):13-8.

63.  Kohno H, Suzuki R, Yasui Y, et al. 2004. Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats. Cancer Sci, 95(6):481-6.

64.  Mehta R, Lansky EP. 2004. Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture. Eur J Cancer Prev,13(4):345-8.

65. Lansky EP, Harrison G, Froom P, et al. 2005. Pomegranate (Punica granatum) pure chemicals show possible synergistic inhibition of human PC-3 prostate cancer cell invasion across Matrigel. Invest New Drugs, 23(2):121-2.

66. Lansky EP, Jiang W, Mo H, et al. 2005. Possible synergistic prostate cancer suppression by anatomically discrete pomegranate fractions. Invest New Drugs, 23(1):11-20.

67. Seeram NP, Lee R, Heber D. 2004. Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clin Chim Acta, 348(1-2):63-8.

68. Pantuck AJ, Leppert JT, Zomorodian N, et al. 2006. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res, 12(13):4018-26.

69.  Ratan HL, Steward WP, Gescher AJ, et al. 2002.  Resveratrol–a prostate cancer chemopreventive agent? Urol Oncol, 7(6):223-7.

70.  Hsieh TC, Wu JM. 1999. Differential effects on growth, cell cycle arrest, and induction of apoptosis by resveratrol in human prostate cancer cell lines. Exp Cell Res, 249(1):109-15.

71. Stewart JR, Artime MC, O’Brian CA. 2003. Resveratrol: a candidate nutritional substance for prostate cancer prevention. J Nutr, 133(7 Suppl):2440S-2443S.

72.  Wang Z, Huang Y, Zou J, et al 2002. Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med, 9(1):77-9.

73.  Aziz MH, Kumar R, Ahmad N. 2003. Cancer chemoprevention by resveratrol: in vitro and in vivo studies and the underlying mechanisms (review). Int J Oncol, 23(1):17-28.

74.  Bertelli AA, Giovannini L, Stradi R, et al. Kinetics of trans- and cis-resveratrol (3,4′,5-trihydroxystilbene) after red wine oral administration in rats. Int J Clin Pharmacol Res, 16(4-5):77-81.

75.  Anderson ML. 2005. A preliminary investigation of the enzymatic inhibition of 5alpha-reduction and growth of prostatic carcinoma cell line LNCap-FGC by natural astaxanthin and Saw Palmetto lipid extract in vitro. J Herb Pharmacother, 5(1):17-26.

76.  Vela-Navarrete R, Escribano-Burgos M, Farre AL, et al. 2005. Serenoa repens treatment modifies bax/bcl-2 index expression and caspase-3 activity in prostatic tissue from patients with benign prostatic hyperplasia. J Urol, 173(2):507-10.

77. Bent S, Kane C, Shinohara K, et al. 2006. Saw palmetto for benign prostatic hyperplasia. N Engl J Med, 354(6):557-66.

78.  Satoskar RR, Shah SJ, Shenoy SG. 1986. Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol, 24(12):651-4.

79.  Sharma OP. 1976. Antioxidant activity of curcumin and related compounds. Biochem Pharmacol, 25(15):1811-2

80. Dorai T, Gehani N, Katz A. 2000. Therapeutic potential of curcumin in human prostate cancer-I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. Prostate Cancer Prostatic Dis, 3(2):84-93.

81. Dorai T, Dutcher JP, Dempster DW, et al. 2004. Therapeutic potential of curcumin in prostate cancer–V: Interference with the osteomimetic properties of hormone refractory C4-2B prostate cancer cells. Prostate, 60(1):1-17.

82. Nakamura K, Yasunaga Y, Segawa T, et al. 2002. Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int J Oncol, 21(4):825-30.

83.  Dorai T, Cao YC, Dorai B, et al 2001. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate, 47(4):293-303.

84.  Imaida K, Tamano S, Kato K, et al. 2001. Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carcinogenesis. Carcinogenesis, 22(3):467-72.

85.  Feng P, Li TL, Guan ZX, et al. 2003. Effect of zinc on prostatic tumorigenicity in nude mice. Ann N Y Acad Sci, 1010:316-20.

86.  Costello LC, Franklin RB, Feng P, et al 2005. Zinc and prostate cancer: a critical scientific, medical, and public interest issue (United States). Cancer Causes Control, 16(8):901-15.

87.  Li XM, Zhang L, Li J, et al. 2005. Measurement of serum zinc improves prostate cancer detection efficiency in patients with PSA levels between 4 ng/mL and 10 ng/mL. Asian J Androl, 7(3):323-8.

88.  Vartsky D, Shilstein S, Bercovich A, et al. 2003. Prostatic zinc and prostate specific antigen: an experimental evaluation of their combined diagnostic value. J Urol, 170(6 Pt 1):2258-62.

89. Kolonel LN, Yoshizawa CN, Hankin JH.  1988 Diet and prostatic cancer: a case–control study in Hawaii. Am J Epidemiol 127:999–1012.

90. Navarro Silvera SA, Rohan TE. 2007.  Trace elements and cancer risk: a review of the epidemiologic evidence. Cancer Causes Control. Feb;18(1):7-27.      

91. Platz EA, Helzlsouer KJ, Hoffman SC, et al 2002. Prediagnostic toenail cadmium and zinc and subsequent prostate cancer risk. Prostate 52:288–296.

92.  Moyad MA. 2004. Zinc for prostate disease and other conditions: a little evidence, a lot of hype, and a significant potential problem. Urol Nurs, 24(1):49-52.

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