Prostate cancer is the most common cancer among U.S. men and the second most common cause of cancer death among American males.1 Globally, however, the incidence of and death from prostate cancer varies greatly.2 When men from low-risk countries move to high-risk countries, prostate cancer rates increase among the succeeding generations. This observation indicates that differences in prostate cancer risk are due to environmental factors such as lifestyle habits rather than genetic differences among populations. To this point, evidence suggests that diet may play a role in both the risk for prostate cancer and its prognosis in men who have the disease.3,4,5
In 1990, participants at a workshop sponsored by the U.S. National Cancer Institute identified isoflavones as chemopreventive (anti-cancer) agents.6 Isoflavones are diphenolic compounds with limited distribution in nature (the soybean is the only commonly consumed food to contain nutritionally-relevant amounts) that exhibit both hormone-dependent and hormone-independent effects under various experimental conditions.7,8,9
In 2009, a meta-analysis of 24 epidemiologic studies found that prostate cancer risk was significantly reduced by 24% in high-soy consumers compared to low-soy consumers.10 In addition, subanalysis of the data revealed that risk was reduced by 48% among Asian men whereas there were no differences in groups among the Western populations. It’s not surprising that soy consumption had no discernible effect among Westerners because few Western men in these studies would have typically consumed enough soy to exert physiological effects.11 The protective effects noted in the meta-analysis were supported by a more recent analysis of the epidemiologic literature by Korean researchers.12
Numerous investigators have examined the impact of isoflavones on blood levels of prostate specific antigen (PSA). PSA levels are commonly and routinely screened as a means of detecting prostate cancer and can also be used to assess treatment efficacy although the predictive ability of PSA has recently been challenged.13,14 Based on a review of studies published in 2006, there is no evidence that soy or isoflavones affect PSA levels in healthy men with normal PSA levels.15 However, this does not rule out benefits of isoflavones since clinical studies indicate that, in healthy men with low PSA levels, it is possible to reduce prostate cancer risk without affecting PSA.16
In contrast to the results found in healthy men, four of the eight trials involving men with prostate cancer, all of which were included in the previously cited review, showed that isoflavones slowed the rise in PSA levels, although no study reported an absolute decrease.15 Five other studies, published more recently, support the findings of this review. One of these studies was conducted for one year, two were six months in duration, one was three to six weeks and the other was conducted for two years.17,18,19,20,21 The results of the two-year trial are especially notable because all of the subjects had failed conventional treatment—that is, their PSA levels continued to rise—having undergone surgery and radiation with or without therapy to decrease testosterone levels.21 In half the subjects, PSA levels favorably responded to the consumption of three servings of soyfoods (primarily soymilk) per day.
Finally, a one-year clinical trial found that an isoflavone supplement reduced risk for progressing to prostate cancer among older Japanese men at high risk of developing the disease. In this study, men with precancerous conditions were given either a placebo or 60 mg of isoflavones daily. At study termination, 34 and 21 percent of the men in the placebo and isoflavone groups developed cancer, respectively. Even greater differences were observed among the older men in this study; among those =65 years of age, 57 and 28 percent of the men in the placebo and isoflavone groups developed cancer, respectively.22
In addition to helping prevent the development of prostate cancer and inhibit tumor growth, there is speculative but intriguing evidence from both animal and human studies suggesting that isoflavones may also be useful for stopping metastasis. For example, a study published in 2009 reported that levels of an enzyme that allows cells to invade tissues—matrix metalloproteinase-2–was markedly reduced in prostate cancer patients given genistein.23
Conclusions
Although no definitive conclusions can be made at this time, research findings suggest that soybean isoflavones and isoflavone-rich soyfoods may prevent the development of prostate cancer and aid in the treatment of this disease by inhibiting the spread of prostate tumors and slowing tumor growth. These findings also suggest that the consumption of two to three servings of traditional soyfoods (e.g., 1 cup soymilk, 3-4 ounces of tofu) is sufficient to derive the proposed benefits.
1. American Cancer Society. Cancer Facts and Figures 2011. Atlanta, GA, 2011.
2. Haas GP, Delongchamps N, Brawley OW, Wang CY, de la Roza G. The worldwide epidemiology of prostate cancer: perspectives from autopsy studies. The Canadian journal of urology. 2008; 15: 3866-71.
3. Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr. 2004; 134: 3479S-3485S.
4. Messina M, Lampe JW, Birt DF, Appel LJ, Pivonka E, Berry B, Jacobs DR, Jr. Reductionism and the narrowing nutrition perspective: time for reevaluation and emphasis on food synergy. J Am Diet Assoc. 2001; 101: 1416-9.
5. Dagnelie PC, Schuurman AG, Goldbohm RA, Van den Brandt PA. Diet, anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies. BJU Int. 2004; 93: 1139-50.
6. Messina M, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst. 1991; 83: 541-6.
7. Franke AA, Custer LJ, Wang W, Shi CY. HPLC analysis of isoflavonoids and other phenolic agents from foods and from human fluids. Proc Soc Exp Biol Med. 1998; 217: 263-73.
8. Oseni T, Patel R, Pyle J, Jordan VC. Selective estrogen receptor modulators and phytoestrogens. Planta Med. 2008; 74: 1656-65.
9. Li Y, Kong D, Bao B, Ahmad A, Sarkar FH. Induction of cancer cell death by isoflavone: The role of multiple signaling pathways. Nutrients. 2011; 3: 877-896.
10. Yan L, Spitznagel EL. Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. Am J Clin Nutr. 2009; 89: 1155-63.
11. Messina M. Western soy intake is too low to produce health effects. Am J Clin Nutr. 2004; 80: 528-9.
12. Hwang YW, Kim SY, Jee SH, Kim YN, Nam CM. Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies. Nutr Cancer. 2009; 61: 598-606.
13. McNaughton-Collins MF, Barry MJ. One man at a time–resolving the PSA controversy. N Engl J Med. 2011; 365: 1951-3.
14. Hernandez BY, McDuffie K, Franke AA, Killeen J, Goodman MT. Reports: plasma and dietary phytoestrogens and risk of premalignant lesions of the cervix. Nutr Cancer. 2004; 49: 109-24.
15. Messina M, Kucuk O, Lampe JW. An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels. J AOAC Int. 2006; 89: 1121-34.
16. Meyer F, Galan P, Douville P, Bairati I, Kegle P, Bertrais S, Estaquio C, Hercberg S. Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. Int J Cancer. 2005; 116: 182-6.
17. Pendleton JM, Tan WW, Anai S, Chang M, Hou W, Shiverick KT, Rosser CJ. Phase II Trial of Isoflavone in prostate specific antigen recurrent prostate cancer after previous local therapy. BMC Cancer. 2008; 8: 132.
18. Kwan W, Duncan G, Van Patten C, Liu M, Lim J. A phase II trial of a soy beverage for subjects without clinical disease with rising prostate-specific antigen after radical radiation for prostate cancer. Nutr Cancer. 2010; 62: 198-207.
19. Ide H, Tokiwa S, Sakamaki K, Nishio K, Isotani S, Muto S, Hama T, Masuda H, Horie S. Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate. 2010; 70: 1127-33.
20. Lazarevic B, Boezelijn G, Diep LM, Kvernrod K, Ogren O, Ramberg H, Moen A, Wessel N, Berg RE, et al. Efficacy and Safety of Short-Term Genistein Intervention in Patients with Localized Prostate Cancer Prior to Radical Prostatectomy: A Randomized, Placebo-Controlled, Double-Blind Phase 2 Clinical Trial. Nutr Cancer. 2011.
21. Joshi M, Agostino NM, Gingrich R, Drabick JJ. Effects of commercially available soy products on PSA in androgen-deprivation-naive and castration-resistant prostate cancer. South Med J. 2011; 104: 736-40.
22. Miyanaga N, Akaza H, Hinotsu S, Fujioka T, Naito S, Namiki M, Takahashi S, Hirao Y, Horie S, et al. A prostate cancer chemoprevention study: An investigative randomized control study using purified isoflavones in men with rising PSA. Cancer Sci. 2011.
23. Xu L, Ding Y, Catalona WJ, Yang XJ, Anderson WF, Jovanovic B, Wellman K, Killmer J, Huang X, et al. MEK4 function, genistein treatment, and invasion of human prostate cancer cells. J Natl Cancer Inst. 2009; 101: 1141-55.
MEN'S HEALTH
Soy and Prostate Cancer
Prostate cancer is the most common cancer among U.S. men and the second most common cause of cancer death among American males.1 Globally, however, the incidence of and death from prostate cancer varies greatly.2 When men from low-risk countries move to high-risk countries, prostate cancer rates increase among the succeeding generations. This observation indicates that differences in prostate cancer risk are due to environmental factors such as lifestyle habits rather than genetic differences among populations. To this point, evidence suggests that diet may play a role in both the risk for prostate cancer and its prognosis in men who have the disease.3,4,5
In 1990, participants at a workshop sponsored by the U.S. National Cancer Institute identified isoflavones as chemopreventive (anti-cancer) agents.6 Isoflavones are diphenolic compounds with limited distribution in nature (the soybean is the only commonly consumed food to contain nutritionally-relevant amounts) that exhibit both hormone-dependent and hormone-independent effects under various experimental conditions.7,8,9
In 2009, a meta-analysis of 24 epidemiologic studies found that prostate cancer risk was significantly reduced by 24% in high-soy consumers compared to low-soy consumers.10 In addition, subanalysis of the data revealed that risk was reduced by 48% among Asian men whereas there were no differences in groups among the Western populations. It’s not surprising that soy consumption had no discernible effect among Westerners because few Western men in these studies would have typically consumed enough soy to exert physiological effects.11 The protective effects noted in the meta-analysis were supported by a more recent analysis of the epidemiologic literature by Korean researchers.12
Numerous investigators have examined the impact of isoflavones on blood levels of prostate specific antigen (PSA). PSA levels are commonly and routinely screened as a means of detecting prostate cancer and can also be used to assess treatment efficacy although the predictive ability of PSA has recently been challenged.13,14 Based on a review of studies published in 2006, there is no evidence that soy or isoflavones affect PSA levels in healthy men with normal PSA levels.15 However, this does not rule out benefits of isoflavones since clinical studies indicate that, in healthy men with low PSA levels, it is possible to reduce prostate cancer risk without affecting PSA.16
In contrast to the results found in healthy men, four of the eight trials involving men with prostate cancer, all of which were included in the previously cited review, showed that isoflavones slowed the rise in PSA levels, although no study reported an absolute decrease.15 Five other studies, published more recently, support the findings of this review. One of these studies was conducted for one year, two were six months in duration, one was three to six weeks and the other was conducted for two years.17,18,19,20,21 The results of the two-year trial are especially notable because all of the subjects had failed conventional treatment—that is, their PSA levels continued to rise—having undergone surgery and radiation with or without therapy to decrease testosterone levels.21 In half the subjects, PSA levels favorably responded to the consumption of three servings of soyfoods (primarily soymilk) per day.
Finally, a one-year clinical trial found that an isoflavone supplement reduced risk for progressing to prostate cancer among older Japanese men at high risk of developing the disease. In this study, men with precancerous conditions were given either a placebo or 60 mg of isoflavones daily. At study termination, 34 and 21 percent of the men in the placebo and isoflavone groups developed cancer, respectively. Even greater differences were observed among the older men in this study; among those =65 years of age, 57 and 28 percent of the men in the placebo and isoflavone groups developed cancer, respectively.22
In addition to helping prevent the development of prostate cancer and inhibit tumor growth, there is speculative but intriguing evidence from both animal and human studies suggesting that isoflavones may also be useful for stopping metastasis. For example, a study published in 2009 reported that levels of an enzyme that allows cells to invade tissues—matrix metalloproteinase-2–was markedly reduced in prostate cancer patients given genistein.23
Conclusions
Although no definitive conclusions can be made at this time, research findings suggest that soybean isoflavones and isoflavone-rich soyfoods may prevent the development of prostate cancer and aid in the treatment of this disease by inhibiting the spread of prostate tumors and slowing tumor growth. These findings also suggest that the consumption of two to three servings of traditional soyfoods (e.g., 1 cup soymilk, 3-4 ounces of tofu) is sufficient to derive the proposed benefits.
1. American Cancer Society. Cancer Facts and Figures 2011. Atlanta, GA, 2011.
2. Haas GP, Delongchamps N, Brawley OW, Wang CY, de la Roza G. The worldwide epidemiology of prostate cancer: perspectives from autopsy studies. The Canadian journal of urology. 2008; 15: 3866-71.
3. Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr. 2004; 134: 3479S-3485S.
4. Messina M, Lampe JW, Birt DF, Appel LJ, Pivonka E, Berry B, Jacobs DR, Jr. Reductionism and the narrowing nutrition perspective: time for reevaluation and emphasis on food synergy. J Am Diet Assoc. 2001; 101: 1416-9.
5. Dagnelie PC, Schuurman AG, Goldbohm RA, Van den Brandt PA. Diet, anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies. BJU Int. 2004; 93: 1139-50.
6. Messina M, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst. 1991; 83: 541-6.
7. Franke AA, Custer LJ, Wang W, Shi CY. HPLC analysis of isoflavonoids and other phenolic agents from foods and from human fluids. Proc Soc Exp Biol Med. 1998; 217: 263-73.
8. Oseni T, Patel R, Pyle J, Jordan VC. Selective estrogen receptor modulators and phytoestrogens. Planta Med. 2008; 74: 1656-65.
9. Li Y, Kong D, Bao B, Ahmad A, Sarkar FH. Induction of cancer cell death by isoflavone: The role of multiple signaling pathways. Nutrients. 2011; 3: 877-896.
10. Yan L, Spitznagel EL. Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. Am J Clin Nutr. 2009; 89: 1155-63.
11. Messina M. Western soy intake is too low to produce health effects. Am J Clin Nutr. 2004; 80: 528-9.
12. Hwang YW, Kim SY, Jee SH, Kim YN, Nam CM. Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies. Nutr Cancer. 2009; 61: 598-606.
13. McNaughton-Collins MF, Barry MJ. One man at a time–resolving the PSA controversy. N Engl J Med. 2011; 365: 1951-3.
14. Hernandez BY, McDuffie K, Franke AA, Killeen J, Goodman MT. Reports: plasma and dietary phytoestrogens and risk of premalignant lesions of the cervix. Nutr Cancer. 2004; 49: 109-24.
15. Messina M, Kucuk O, Lampe JW. An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels. J AOAC Int. 2006; 89: 1121-34.
16. Meyer F, Galan P, Douville P, Bairati I, Kegle P, Bertrais S, Estaquio C, Hercberg S. Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. Int J Cancer. 2005; 116: 182-6.
17. Pendleton JM, Tan WW, Anai S, Chang M, Hou W, Shiverick KT, Rosser CJ. Phase II Trial of Isoflavone in prostate specific antigen recurrent prostate cancer after previous local therapy. BMC Cancer. 2008; 8: 132.
18. Kwan W, Duncan G, Van Patten C, Liu M, Lim J. A phase II trial of a soy beverage for subjects without clinical disease with rising prostate-specific antigen after radical radiation for prostate cancer. Nutr Cancer. 2010; 62: 198-207.
19. Ide H, Tokiwa S, Sakamaki K, Nishio K, Isotani S, Muto S, Hama T, Masuda H, Horie S. Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate. 2010; 70: 1127-33.
20. Lazarevic B, Boezelijn G, Diep LM, Kvernrod K, Ogren O, Ramberg H, Moen A, Wessel N, Berg RE, et al. Efficacy and Safety of Short-Term Genistein Intervention in Patients with Localized Prostate Cancer Prior to Radical Prostatectomy: A Randomized, Placebo-Controlled, Double-Blind Phase 2 Clinical Trial. Nutr Cancer. 2011.
21. Joshi M, Agostino NM, Gingrich R, Drabick JJ. Effects of commercially available soy products on PSA in androgen-deprivation-naive and castration-resistant prostate cancer. South Med J. 2011; 104: 736-40.
22. Miyanaga N, Akaza H, Hinotsu S, Fujioka T, Naito S, Namiki M, Takahashi S, Hirao Y, Horie S, et al. A prostate cancer chemoprevention study: An investigative randomized control study using purified isoflavones in men with rising PSA. Cancer Sci. 2011.
23. Xu L, Ding Y, Catalona WJ, Yang XJ, Anderson WF, Jovanovic B, Wellman K, Killmer J, Huang X, et al. MEK4 function, genistein treatment, and invasion of human prostate cancer cells. J Natl Cancer Inst. 2009; 101: 1141-55.