Life Extension Spring Clearance Sale

Life Extension Magazine

LE Magazine February 2007

image

An Overlooked Strategy to Prevent Prostate Cancer

By William Faloon

by William Faloon

If the prostate gland was not located in such a sensitive and difficult-to-reach area of the body, one could argue that most men should consider having it removed around the age of 50.

I made this seemingly bizarre statement 12 years ago, because the vast majority of aging men will contract benign or malignant prostate disease, either of which can lessen the quality and duration of life.1

While benign prostate disease is not usually thought of as life threatening, the sleep disturbance it causes due to nighttime urinary urgency could very well increase mortality. That is because people who do not get enough sleep overproduce inflammatory cytokines that inflict damage to arteries, joints, bones, and neurons.2-4 So while benign prostate enlargement itself seldom kills, the chronic sleep deprivation it induces may very well hasten death.

After the reproductive years, the prostate gland not only becomes a nuisance, but also hinders the ability of men to take advantage of validated anti-aging therapies. Elderly men frequently join Life Extension seeking a solution for the multiple degenerative diseases they have contracted. These ailing men are almost always severely deficient in testosterone and other critical hormones. Regrettably, many also have evidence of prostate cancer, which precludes them from gaining access to the benefits made possible by restoring all hormones to youthful levels.

Deficiencies of testosterone and DHEA are closely related to a host of common age-related diseases.5-31 In fact, low levels of these hormones can further spike dangerous inflammatory cytokine levels.32-37

Illustration of the male pelvis showing bladder wall (top center) and urine retention due to an enlarged prostate gland (benign prostatic hyperplasia). The enlarged prostate is visible in the center of the image, surrounding the urethra. The rectum is the pink area to the far right.

The dilemma we face today is that certain age-related disorders can be partially reversed by restoring hormones to youthful ranges. For elderly men afflicted with prostate disease, this knowledge is of little practical value because they are unable to restore their full complement of hormones.

I cannot tell you how many cases I have encountered where elderly males suffer systemic disorders directly related to hormone imbalances. If it were not for their defective prostate glands, these men could enjoy the rejuvenating effects that have been shown when their hormones are returned to optimal ranges.

Take Control of the Statistics

More than 230,000 men are diagnosed each year with prostate cancer in the United States, and nearly 30,000 will die directly from it.38 Not counted in these epidemic statistics are the disabilities and deaths that occur in response to prostate cancer treatment.

Prostate cells are especially prone to mutation and malignant transformation.39-55 This process accelerates as men age past 50. Interestingly, cells of other tissues in the anatomical region of the prostate almost never become cancerous.

Are there ways to avoid becoming a victim of these grim statistics? We think so. First of all, the human body obviously has control mechanisms that keep isolated groups of malignant prostate cells in check. This is demonstrated by the high detection rate during autopsies of prostate cancer cells in males between the ages of 30 and 40.56 Men this young are almost never diagnosed with prostate cancer, but many have cancer cells lurking in their prostate glands. By harnessing the growth-control mechanisms of cancer cells, it would be possible to prevent (or delay) isolated cancer cells in the prostate gland from developing into full-blown disease.

Incidences of prostate cancer vary dramatically across the world. It is least common in South and East Asia, more common in Europe (especially northern Europe), and most common in the United States.57-61 Comparing prostate cancer rates in different regions of the world provides guidance as to what may be done to reduce risk. For instance, men in Sweden are eight times more likely to die of prostate cancer than men in Hong Kong.57,62

Scientists have identified a number of dietary factors that explain why certain population groups have such low prostate cancer rates.63-91 The encouraging news is that most Life Extension members are following at least some of the dietary and supplement guidelines that have been associated with reduced prostate cancer risks.

Are Men Doing Enough to Prevent Prostate Cancer?

A large percentage of men over the age of 70 already have cancer cells present in their prostate glands.59 The majority of these men, however, will never know they have prostate cancer. The reason is that most of them die of some other cause before prostate cancer manifests as clinical disease.

Life Extension members, on the other hand, are taking extraordinary steps to achieve a very long and healthy life. Instead of needlessly dying from a preventable disease, many male Life Extension members are likely to live long enough to encounter prostate problems.

So while health-conscious males take vitamin E,92-97 selenium,95,98-103 vitamin D,104-108 lycopene,109-115 gamma tocopherol,92,93,95 pomegranate,116-119 boron,120-123 fish oil,124-131 and other nutrients76,78,85,132-142 to prevent (or delay) prostate cancer, there is still a critical need to identify how relatively dormant cancer cells in the prostate gland eventually break through the body’s protective barrier to become clinically diagnosed prostate cancer.

Novel Mechanism to Impede Progression of Existing Prostate Cancer Cells

Since people are now living longer than ever, delaying the manifestation of prostate cancer is desirable, but may not result in the disease being altogether prevented. The lead article in this month’s issue of Life Extension magazine is titled “Eating Your Way to Prostate Cancer.” This article describes a little-known pathological mechanism that explains why ingesting the wrong foods increases prostate cancer risk.

Telling knowledgeable members about foods they know cause cancer does not do much good—unless a solution to impede the progression of existing prostate cancer growth is provided. The reason I state this is that many men reading this article have cells in their prostate glands that have mutated and/or have already become cancerous. While improving one’s diet at any age is of tremendous value, more has to be done to interfere with the progression of existing cancer cells that remain confined to the prostate gland.

In the breakthrough report you are about to read, we describe a patented plant extract that may provide aging men with additional protection against prostate cancer via a novel mechanism.

Members of the Life Extension Foundation do not have to concern themselves as to whether or not they need to include this patented plant extract in their daily program. It was added several months ago, at no additional cost, to the most popular prostate support formula Foundation members already use.

In the hormone-deficient aging male, the prostate gland too often becomes his Achilles heel. By taking aggressive steps to combat prostate disease, elderly men may enjoy their full complement of youth hormones . . . and still sleep through the night.

How Life Extension Protects Its Members’ Lives

Today’s apathetic physicians exhibit little in the way of curiosity when it comes to incorporating novel medical findings in their clinical practices. Life Extension researchers, on the other hand, are both personally motivated and have the dedicated time to meticulously review the scientific literature in order to identify novel strategies to prevent and treat age-related disorders.

If it were not for our fervent desire to eradicate needless suffering and death, these findings would remain buried in the thousands of pages of scientific text published every day.

In our daily battle against age-related disorders, Life Extension researchers uncover methods to enable elderly adults to achieve a more youthful biochemistry. Over the past two months, we have utilized these discoveries to upgrade virtually every popular supplement that members use every day.

Every time you purchase a product from us, you nourish your body with the world’s most advanced nutrients, and also directly contribute to aggressive life extension research that could save enormous numbers of human lives.

This time of year, members take advantage of the annual Super Sale to stock up on a large supply of avant-garde natural products at reduced prices. During this annual winter event, every Life Extension product is discounted to enable members to enjoy huge savings on our top-of-the-line supplements.

This year’s Super Sale ends on January 31, 2007. I encourage members to check their personal supplies and to stock up on the Life Extension products they need during this one-time-a-year price reduction.

Prostate Cancer and Aging

As men age, their risk of contracting prostate cancer skyrockets. The following chart published by the Centers for Disease Control and Prevention143 shows how vulnerable aging men become to prostate cancer as they age.

RISK OF BEING DIAGNOSED WITH PROSTATE CANCER BY AGE

AGE

RISK

45

1 in 2,500

50

1 in 476

55

1 in 120

60

1 in 43

65

1 in 21

70

1 in 13

75

1 in 9

Ever

1 in 6

These startling statistics should be a wake-up call for men over the age of 50 to take aggressive action to prevent prostate cancer from manifesting in their bodies.

 

For longer life,
image
William Faloon

References

1. Glynn RJ, Campion EW, Bouchard GR, Silbert JE. The development of benign prostatic hyperplasia among volunteers in the Normative Aging Study. Am J Epidemiol. 1985 Jan;121(1):78-90.

2. Vgontzas AN, Bixler EO, Lin HM, et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J Clin Endocrinol Metab. 2001 Aug;86(8):3787-94.

3. Vgontzas AN, Mastorakos G, Bixler EO, et al. Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes: potential clinical implications. Clin Endocrinol (Oxf). 1999 Aug;51(2):205-15.

4. Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab. 1999 Aug;84(8):2603-7.

5. Genazzani AR, Inglese S, Lombardi I, et al. Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. Aging Male. 2004 Jun;7(2):133-43.

6. Okun MS, McDonald WM, DeLong MR. Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity. Arch Neurol. 2002 May;59(5):807-11.

7. Okun MS, DeLong MR, Hanfelt J, Gearing M, Levey A. Plasma testosterone levels in Alzheimer and Parkinson diseases. Neurology. 2004 Feb 10;62(3):411-3.

8. Hak AE, Witteman JC, de Jong FH, et al. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab. 2002 Aug;87(8):3632-9.

9. Ponholzer A, Plas E, Schatzl G, Jungwirth A, Madersbacher S. Association of DHEA-S and estradiol serum levels to symptoms of aging men. Aging Male. 2002 Dec;5(4):233-8.

10. Khalil A, Fortin JP, LeHoux JG, Fulop T. Age-related decrease of dehydroepiandrosterone concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation. J Lipid Res. 2000 Oct;41(10):1552-61.

11. Labrie F, Belanger A, Cusan L, Gomez JL, Candas B. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab. 1997 Aug;82(8):2396-402.

12. Flynn MA, Weaver-Osterholtz D, Sharpe-Timms KL, Allen S, Krause G. Dehydroepiandrosterone replacement in aging humans. J Clin Endocrinol Metab. 1999 May;84(5):1527-33.

13. Kupelian V, Page ST, Araujo AB, et al. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab. 2006 Mar;91(3):843-50.

14. Dhindsa S, Prabhakar S, Sethi M, et al. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab. 2004 Nov;89(11):5462-8.

15. Svartberg J, Jenssen T, Sundsfjord J, Jorde R. The associations of endogenous testosterone and sex hormone-binding globulin with glycosylated hemoglobin levels, in community dwelling men. The Tromso Study. Diabetes Metab. 2004 Feb;30(1):29-34.

16. Haffner SM, Karhapaa P, Mykkanen L, Laakso M. Insulin resistance, body fat distribution, and sex hormones in men. Diabetes. 1994 Feb;43(2):212-9.

17. Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care. 2000 Apr;23(4):490-4.

18. Barrett-Connor E, Khaw KT, Yen SS. Endogenous sex hormone levels in older adult men with diabetes mellitus. Am J Epidemiol. 1990 Nov;132(5):895-901.

19. Marin P, Krotkiewski M, Bjorntorp P. Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues. Eur J Med. 1992 Oct;1(6):329-36.

20. Corrales JJ, Almeida M, Burgo R, et al. Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency. J Endocrinol. 2006 Jun;189(3):595-604.

21. Malkin CJ, Pugh PJ, Jones RD, Jones TH, Channer KS. Testosterone as a protective factor against atherosclerosis—immunomodulation and influence upon plaque development and stability. J Endocrinol. 2003 Sep;178(3):373-80.

22. Hanke H, Lenz C, Hess B, Spindler KD, Weidemann W. Effect of testosterone on plaque development and androgen receptor expression in the arterial vessel wall. Circulation. 2001 Mar 13;103(10):1382-5.

23. Feldman HA, Johannes CB, Araujo AB, et al. Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study. Am J Epidemiol. 2001 Jan 1;153(1):79-89.

24. English KM, Mandour O, Steeds RP, et al. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J. 2000 Jun;21(11):890-4.

25. Allolio B, Dambacher M, Dreher R, et al. Osteoporosis in the male. Med Klin (Munich). 2000 Jun 15;95(6):327-38.

26. Szulc P, Delmas PD. Osteoporosis in the aged male. Presse Med. 2002 Nov 23;31(37 Pt 1):1760-9.

27. Pope HG, Jr., Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry. 2003 Jan;160(1):105-11.

28. Moffat SD, Zonderman AB, Metter EJ, et al. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab. 2002 Nov;87(11):5001-7.

29. Barrett-Connor E, Von Muhlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study. J Clin Endocrinol Metab. 1999 Feb;84(2):573-7.

30. Anon. Testosterone and depression in men. TreatmentUpdate. 2000 May;12(3):7-8.

31. Perry PJ, Yates WR, Williams RD, et al. Testosterone therapy in late-life major depression in males. J Clin Psychiatry. 2002 Dec;63(12):1096-101.

32. Young DG, Skibinski G, Mason JI, James K. The influence of age and gender on serum dehydroepiandrosterone sulphate (DHEA-S), IL-6, IL-6 soluble receptor (IL-6 sR) and transforming growth factor beta 1 (TGF-beta1) levels in normal healthy blood donors. Clin Exp Immunol. 1999 Sep;117(3):476-81.

33. Straub RH, Konecna L, Hrach S, et al. Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab. 1998 Jun;83(6):2012-7.

34. Kipper-Galperin M, Galilly R, Danenberg HD, Brenner T. Dehydroepiandrosterone selectively inhibits production of tumor necrosis factor alpha and interleukin-6 [correction of interlukin-6] in astrocytes. Int J Dev Neurosci. 1999 Dec;17(8):765-75.

35. Schifitto G, McDermott MP, Evans T, et al. Autonomic performance and dehydroepiandrosterone sulfate levels in HIV-1-infected individuals: relationship to TH1 and TH2 cytokine profile. Arch Neurol. 2000 Jul;57(7):1027-32.

36. Verthelyi D, Klinman DM. Sex hormone levels correlate with the activity of cytokine-secreting cells in vivo. Immunology. 2000 Jul;100(3):384-90.

37. Straub RH, Scholmerich J, Zietz B. Replacement therapy with DHEA plus corticosteroids in patients with chronic inflammatory diseases--substitutes of adrenal and sex hormones. Z Rheumatol. 2000;59 Suppl 2II/108-II/118.

38. Available at: http://www.cancer.org/downloads/STT/CAFF2006PWSecured.pdf. Accessed September 21, 2006.

39. Pang ST, Weng WH, Flores-Morales A, et al. Cytogenetic and expression profiles associated with transformation to androgen-resistant prostate cancer. Prostate. 2006 Feb 1;66(2):157-72.

40. Gallucci M, Merola R, Farsetti A, et al. Cytogenetic profiles as additional markers to pathological features in clinically localized prostate carcinoma. Cancer Lett. 2006 Jun 8;237(1):76-82.

41. Yildiz-Sezer S, Verdorfer I, Schafer G, et al. Assessment of aberrations on chromosome 8 in prostatic atrophy. BJU Int. 2006 Jul;98(1):184-8.

42. Saramaki OR, Porkka KP, Vessella RL, Visakorpi T. Genetic aberrations in prostate cancer by microarray analysis. Int J Cancer. 2006 Sep 15;119(6):1322-9.

43. Hughes S, Yoshimoto M, Beheshti B, et al. The use of whole genome amplification to study chromosomal changes in prostate cancer: insights into genome-wide signature of preneoplasia associated with cancer progression. BMC Genomics. 2006;765.

44. Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005 Oct 28;310(5748):644-8.

45. Finnis M, Dayan S, Hobson L, et al. Common chromosomal fragile site FRA16D mutation in cancer cells. Hum Mol Genet. 2005 May 15;14(10):1341-9.

46. Celep F, Karaguzel A, Ozgur GK, Yildiz K. Detection of chromosomal aberrations in prostate cancer by fluorescence in situ hybridization (FISH). Eur Urol. 2003 Dec;44(6):666-71.

47. Matsuyama H, Pan Y, Yoshihiro S, et al. Clinical significance of chromosome 8p, 10q, and 16q deletions in prostate cancer. Prostate. 2003 Feb 1;54(2):103-11.

48. Liu L, Yoon JH, Dammann R, Pfeifer GP. Frequent hypermethylation of the RASSF1A gene in prostate cancer. Oncogene. 2002 Oct 3;21(44):6835-40.

49. Laitinen S, Karhu R, Sawyers CL, Vessella RL, Visakorpi T. Chromosomal aberrations in prostate cancer xenografts detected by comparative genomic hybridization. Genes Chromosomes Cancer. 2002 Sep;35(1):66-73.

50. Schulz WA, Elo JP, Florl AR, et al. Genomewide DNA hypomethylation is associated with alterations on chromosome 8 in prostate carcinoma. Genes Chromosomes Cancer. 2002 Sep;35(1):58-65.

51. Nelson WG, DeWeese TL, DeMarzo AM. The diet, prostate inflammation, and the development of prostate cancer. Cancer Metastasis Rev. 2002;21(1):3-16.

52. Verhagen PC, Hermans KG, Brok MO, et al. Deletion of chromosomal region 6q14-16 in prostate cancer. Int J Cancer. 2002 Nov 10;102(2):142-7.

53. Haapala K, Rokman A, Palmberg C, et al. Chromosomal changes in locally recurrent, hormone-refractory prostate carcinomas by karyotyping and comparative genomic hybridization. Cancer Genet Cytogenet. 2001 Nov;131(1):74-8.

54. Phillips JL, Hayward SW, Wang Y, et al. The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis. Cancer Res. 2001 Nov 15;61(22):8143-9.

55. Sinha R, Caporaso N. Diet, genetic susceptibility and human cancer etiology. J Nutr. 1999 Feb;129(2S Suppl):556S-9S.

56. Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD. The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol. 1993 Aug;150(2 Pt 1):379-85.

57. Available at: www.jncicancerspectrum.oxfordjournals.org/cgi/statContent/cspectfstat%3b99. Accessed November 16, 2006.

58. Available at: http://seer.cancer.gov/publications/prostate/. Accessed September 26, 2006.

59. Breslow N, Chan CW, Dhom G, et al. Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France. Int J Cancer. 1977 Nov 15;20(5):680-8.

60. Hsing AW, Tsao L, Devesa SS. International trends and patterns of prostate cancer incidence and mortality. Int J Cancer. 2000 Jan 1;85(1):60-7.

61. Sim HG, Cheng CW. Changing demography of prostate cancer in Asia. Eur J Cancer. 2005 Apr;41(6):834-45.

62. Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer—analysis of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000 Jul 13;343(2):78-85.

63. Available at: Available at: http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/943. Accessed September 21, 2006.

64. Kesse E, Bertrais S, Astorg P, et al. Dairy products, calcium and phosphorus intake, and the risk of prostate cancer: results of the French prospective SU.VI.MAX (Supplementation en Vitamines et Mineraux Antioxydants) study. Br J Nutr. 2006 Mar;95(3):539-45.

65. Hedelin M, Klint A, Chang ET, et al. Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the cancer prostate Sweden study (Sweden). Cancer Causes Control. 2006 Mar;17(2):169-80.

66. Chan JM, Holick CN, Leitzmann MF, et al. Diet after diagnosis and the risk of prostate cancer progression, recurrence, and death (United States). Cancer Causes Control. 2006 Mar;17(2):199-208.

67. Ornish D, Weidner G, Fair WR, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005 Sep;174(3):1065-9.

68. Leitzmann MF. Is there a link between macronutrient intake and prostate cancer? Nat Clin Pract Oncol. 2005 Apr;2(4):184-5.

69. Shukla S, Gupta S. Dietary agents in the chemoprevention of prostate cancer. Nutr Cancer. 2005;53(1):18-32.

70. Colli JL, Colli A. Comparisons of prostate cancer mortality rates with dietary practices in the United States. Urol Oncol. 2005 Nov;23(6):390-8.

71. Chan JM, Gann PH, Giovannucci EL. Role of diet in prostate cancer development and progression. J Clin Oncol. 2005 Nov 10;23(32):8152-60.

72. Tseng M, Breslow RA, Graubard BI, Ziegler RG. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am J Clin Nutr. 2005 May;81(5):1147-54.

73. Walker M, Aronson KJ, King W, et al. Dietary patterns and risk of prostate cancer in Ontario, Canada. Int J Cancer. 2005 Sep 10;116(4):592-8.

74. Bidoli E, Talamini R, Bosetti C, et al. Macronutrients, fatty acids, cholesterol and prostate cancer risk. Ann Oncol. 2005 Jan;16(1):152-7.

75. Augustin LS, Galeone C, Dal ML, et al. Glycemic index, glycemic load and risk of prostate cancer. Int J Cancer. 2004 Nov 10;112(3):446-50.

76. Sonoda T, Nagata Y, Mori M, et al. A case-control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet. Cancer Sci. 2004 Mar;95(3):238-42.

77. Tseng M, Breslow RA, DeVellis RF, Ziegler RG. Dietary patterns and prostate cancer risk in the National Health and Nutrition Examination Survey Epidemiological Follow-up Study cohort. Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):71-7.

78. Vij U, Kumar A. Phyto-oestrogens and prostatic growth. Natl Med J India. 2004 Jan;17(1):22-6.

79. Dewailly E, Mulvad G, Sloth PH, et al. Inuit are protected against prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003 Sep;12(9):926-7.

80. Hsing AW, Chokkalingam AP, Gao YT, et al. Allium vegetables and risk of prostate cancer: a population-based study. J Natl Cancer Inst. 2002 Nov 6;94(21):1648-51.

81. Chan JM, Giovannucci EL. Vegetables, fruits, associated micronutrients, and risk of prostate cancer. Epidemiol Rev. 2001;23(1):82-6.

82. Chan JM, Giovannucci EL. Dairy products, calcium, and vitamin D and risk of prostate cancer. Epidemiol Rev. 2001;23(1):87-92.

83. Kolonel LN. Fat, meat, and prostate cancer. Epidemiol Rev. 2001;23(1):72-81.

84. Mucci LA, Tamimi R, Lagiou P, et al. Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system? BJU Int. 2001 Jun;87(9):814-20.

85. Strom SS, Yamamura Y, Duphorne CM, et al. Phytoestrogen intake and prostate cancer: a case-control study using a new database. Nutr Cancer. 1999;33(1):20-5.

86. Hebert JR, Hurley TG, Olendzki BC, et al. Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study. J Natl Cancer Inst. 1998 Nov 4;90(21):1637-47.

87. Wynder EL, Cohen LA. Correlating nutrition to recent cancer mortality statistics. J Nat Cancer Inst. 1997 Feb 19;89(4):324.

88. Whittemore AS, Kolonel LN, Wu AH et al. Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. J Natl Cancer Inst. 1995 May 3;87(9):652-61.

89. Shimizu H, Ross RK, Bernstein L, et al. Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer. 1991 Jun;63(6):963-6.

90. Mettlin C, Selenskas S, Natarajan N, Huben R. Beta-carotene and animal fats and their relationship to prostate cancer risk. A case-control study. Cancer. 1989 Aug 1;64(3):605-12.

91. Severson RK, Nomura AM, Grove JS, Stemmermann GN. A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res. 1989 Apr 1;49(7):1857-60.

92. Weinstein SJ, Wright ME, Pietinen P, et al. Serum alpha-tocopherol and gamma-tocopherol in relation to prostate cancer risk in a prospective study. J Natl Cancer Inst. 2005 Mar 2;97(5):396-9.

93. Galli F, Stabile AM, Betti M, et al. The effect of alpha- and gamma-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation. Arch Biochem Biophys. 2004 Mar 1;423(1):97-102.

94. Virtamo J, Pietinen P, Huttunen JK, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA. 2003 Jul 23;290(4):476-85.

95. Helzlsouer KJ, Huang HY, Alberg AJ, et al. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst. 2000 Dec 20;92(24):2018-23.

96. Smigel K. Vitamin E reduces prostate cancer rates in Finnish trial: U.S. considers follow-up. J Natl Cancer Inst. 1998 Mar 18;90(6):416-7.

97. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998 Mar 18;90(6):440-6.

98. Waters DJ, Shen S, Glickman LT, et al. Prostate cancer risk and DNA damage: translational significance of selenium supplementation in a canine model. Carcinogenesis. 2005 Jul;26(7):1256-62.

99. Corcoran NM, Najdovska M, Costello AJ. Inorganic selenium retards progression of experimental hormone refractory prostate cancer. J Urol. 2004 Feb;171(2 Pt 1):907-10.

100. Vogt TM, Ziegler RG, Graubard BI, et al. Serum selenium and risk of prostate cancer in U.S. blacks and whites. Int J Cancer. 2003 Feb 20;103(5):664-70.

101. Duffield-Lillico AJ, Reid ME, Turnbull BW, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):630-9.

102. Platz EA, Helzlsouer KJ. Selenium, zinc, and prostate cancer. Epidemiol Rev. 2001;23(1):93-101.

103. Yoshizawa K, Willett WC, Morris SJ, et al. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst. 1998 Aug 19;90(16):1219-24.

104. Vijayakumar S, Mehta RR, Boerner PS, Packianathan S, Mehta RG. Clinical trials involving vitamin D analogs in prostate cancer. Cancer J. 2005 Sep;11(5):362-73.

105. John EM, Schwartz GG, Koo J, Van Den BD, Ingles SA. Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer. Cancer Res. 2005 Jun 15;65(12):5470-9.

106. Li H, Stampfer M, Giovannucci E, et al. Prediagnostic plasma vitamin D levels, vitamin D receptor gene polymorphisms, and susceptibility to prostate cancer. Presented at the 2005 Multidisciplinary Prostate Cancer Symposium; February 16-19, 2005; Orlando, FL. Abstract 2.

107. Crescioli C, Maggi M, Luconi M, et al. Vitamin D3 analogue inhibits keratinocyte growth factor signaling and induces apoptosis in human prostate cancer cells. Prostate. 2002 Jan 1;50(1):15-26.

108. Lou YR, Qiao S, Talonpoika R, Syvala H, Tuohimaa P. The role of Vitamin D3 metabolism in prostate cancer. J Steroid Biochem Mol Biol. 2004 Nov;92(4):317-25.

109. Ansari MS, Gupta NP. Lycopene: a novel drug therapy in hormone refractory metastatic prostate cancer. Urol Oncol. 2004 Sep;22(5):415-20.

110. Binns CW, LJ LJ, Lee AH. The relationship between dietary carotenoids and prostate cancer risk in Southeast Chinese men. Asia Pac J Clin Nutr. 2004;13(Suppl):S117.

111. Bowen P, Chen L, Stacewicz-Sapuntzakis M, et al. Tomato sauce supplementation and prostate cancer: lycopene accumulation and modulation of biomarkers of carcinogenesis. Exp Biol Med (Maywood). 2002 Nov;227(10):886-93.

112. Giovannucci E. A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med (Maywood). 2002 Nov;227(10):852-9.

113. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst. 2002 Mar 6;94(5):391-8.

114. Gann PH, Ma J, Giovannucci E, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res. 1999 Mar 15;59(6):1225-30.

115. Giovannucci E, Ascherio A, Rimm EB, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst. 1995 Dec 6;87(23):1767-76.

116. Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res. 2006 Jul 1;12(13):4018-26.

117. Malik A, Mukhtar H. Prostate cancer prevention through pomegranate fruit. Cell Cycle. 2006 Feb;5(4):371-3.

118. Malik A, Afaq F, Sarfaraz S, et al. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci USA. 2005 Oct 11;102(41):14813-8.

119. Albrecht M, Jiang W, Kumi-Diaka J, et al. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food. 2004;7(3):274-83.

120. Available at: http://www.annieappleseedproject.org/efofborsuppr.html. Accessed September 25, 2006.

121. Gallardo-Williams MT, Chapin RE, King PE, et al. Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicol Pathol. 2004 Jan;32(1):73-8.

122. Cui Y, Winton MI, Zhang ZF, et al. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004 Apr;11(4):887-92.

123. Zhang ZF, Winton MI, Rainey C, et al. Boron is associated with decreased risk of human prostate cancer. Presented at Experimental Biology. March 31-April 4, 2001; Orlando, FL.

124. Brown MD, Hart CA, Gazi E, Bagley S, Clarke NW. Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs. Br J Cancer. 2006 Mar 27;94(6):842-53.

125. Kelavkar UP, Hutzley J, Dhir R, et al. 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. 2006 Feb;8(2):112-24.

126. Rose DP. Effects of dietary fatty acids on breast and prostate cancers: evidence from in vitro experiments and animal studies. Am J Clin Nutr. 1997 Dec;66(6 Suppl):1513S-22S.

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

128. Hardman WE. (n-3) fatty acids and cancer therapy. J Nutr. 2004 Dec;134(12 Suppl):3427S-30S.

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

130. Terry P, Lichtenstein P, Feychting M, Ahlbom A, Wolk A. Fatty fish consumption and risk of prostate cancer. Lancet. 2001 Jun 2;357(9270):1764-6.

131. Rose DP. Dietary fatty acids and prevention of hormone-responsive cancer. Proc Soc Exp Biol Med. 1997 Nov;216(2):224-33.

132. Lee MM, Gomez SL, Chang JS, et al. Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol Biomarkers Prev. 2003 Jul;12(7):665-68.

133. Hedelin M, Balter KA, Chang ET, et al. Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer. Prostate. 2006 Oct 1;66(14):1512-20.

134. Lee AH, Fraser ML, Meng X, Binns CW. Protective effects of green tea against prostate cancer. Expert Rev Anticancer Ther. 2006 Apr;6(4):507-13.

135. Holzbeierlein JM, McIntosh J, Thrasher JB. The role of soy phytoestrogens in prostate cancer. Curr Opin Urol. 2005 Jan;15(1):17-22.

136. Pelucchi C, Galeone C, Talamini R, et al. Dietary folate and risk of prostate cancer in Italy. Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):944-8.

137. Davis-Searles PR, Nakanishi Y, Kim NC, et al. Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. Cancer Res. 2005 May 15;65(10):4448-57.

138. Singh RP, Agarwal R. Prostate cancer and inositol hexaphosphate: efficacy and mechanisms. Anticancer Res. 2005 Jul;25(4):2891-903.

139. Agarwal C, Dhanalakshmi S, Singh RP, Agarwal R. Inositol hexaphosphate inhibits growth and induces G1 arrest and apoptotic death of androgen-dependent human prostate carcinoma LNCaP cells. Neoplasia. 2004 Sep;6(5):646-59.

140. Kumar NB, Cantor A, Allen K, et al. The specific role of isoflavones in reducing prostate cancer risk. Prostate. 2004 May 1;59(2):141-7.

141. Jian L, Xie LP, Lee AH, Binns CW. Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer. 2004 Jan 1;108(1):130-5.

142. Barnes S. Role of phytochemicals in prevention and treatment of prostate cancer. Epidemiol Rev. 2001;23(1):102-5.

143. Available at: http://www.cdc.gov/cancer/prostate/publications/decisionguide/. Accessed November 20, 2006.