For detailed information on the studies summarised above, continue reading.
Please note this describes published clinical studies and therefore contains information of a scientific nature.
Isoflavones are naturally-occurring antioxidant molecules which are found almost exclusively in plants of the legume family. In recent studies, isoflavones were demonstrated to regulate genes important for the development of metastasis in animal models of prostate cancer, thereby significantly inhibiting metastatic bone tumour growth (Li, et al. 2004; Mentor-Marcel, et al. 2005), and advanced prostate cancer development (Wang, et al. 2007). Isoflavones have also been shown to switch off genes important for growth and proliferation in cultured prostate cells (Rabiau, et al. 2010), and also sensitise cultured prostate cancer cells to chemotherapy drugs (Li, et al. 2005) and radiation therapy (Singh-Gupta, et al. 2009), increasing the effectiveness of these treatments.
Selenium is an essential micronutrient for humans and is required for certain antioxidant enzymes to function. It is found in small amounts in nuts, cereals, meat, fish, and eggs. Recent studies (Hawkes, et al. 2009) into the use of selenium as a prostate cancer therapy have demonstrated that it can directly control the proliferation of cultured prostate epithelial cells, and this effect can be further enhanced by simultaneously treating these cells with isoflavones (Zhao, et al. 2009). Selenium has also been shown to increase the production of tumour suppressing proteins in cultured prostate cancer cells (Berggren, et al. 2009). Selenium has further been shown (Wang, et al. 2009) to increase apoptosis (preprogrammed cell death) and decrease the proliferation of tumour cells, and thereby decrease the rate of cancer progression in a mouse model of prostate cancer, which results in significantly increased survival in these animals.
Lycopene is an antioxidant carotenoid which is commonly found in tomatoes and other red fruits and vegetables. Although lycopene appears to have little to no effect on the proliferation of cultured cancer cells directly (Burgess, et al. 2008), it is thought to have beneficial effects by reversing the stimulatory effect of hormones such as testosterone (Liu, et al. 2008), which are known to promote cancer growth. In addition, lycopene has been shown in other studies (Wang, et al. 2007; Gunasekera, et al. 2007) to cause apoptosis (preprogrammed cell death) in cultured prostate cancer cells.
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Clinical Studies Relevant To This Nutraceutical
(A brief note on "PSA": Almost all clinical trials into treatments for prostate cancer use "serum PSA" as a marker of treatment benefit. PSA, or "prostate-specific antigen", is a protein produced by the prostate that is released into the blood, and high levels of PSA are usually a marker of prostate cancer or other prostate disorder. Rising levels of serum PSA over time in patients can be a marker of prostate cancer progression and metastasis. Stabilization or a decrease in PSA levels is frequently associated with an improved outcome for prostate cancer patients, and is therefore one of the markers of a successful treatment.)
Prostate Cancer Treatment
Several small clinical trials have investigated the effect of isoflavones, lycopene and/or selenium for the treatment of prostate cancer. In one study (Schröder, et al. 2005) into supplements for prostate cancer, 46 prostate cancer patients were given a supplement containing isoflavones, lycopene, silymarin, and antioxidants, which resulted in a significant increase in the time it took for PSA levels in these patients to double (from an average of 445 days to 1150 days) compared to patients taking a placebo. Another study (Grainger, et al. 2008) on prostate cancer survival, in which patients were given a special diet rich in both lycopene and isoflavones for 8 weeks, found that 34% of men experienced a decrease in serum PSA levels as a result. In a similar study (Vaishampayan, et al. 2007), 71 prostate cancer patients with rising PSA levels were given lycopene or lycopene plus isoflavones. Successful PSA stabilization was achieved in 95% of the patients taking the lycopene supplement, though in contrast to other studies, a smaller number patients (67%) taking the lycopene + isoflavone supplement experienced PSA stabilization. It was not immediately clear why this should be the case in this study, although it may be due to random effects associated with the small number of patients included in the trial.
A fourth study (Dalais, et al. 2004) also demonstrated that prostate cancer patients on a special diet rich in isoflavones showed a significant change in serum PSA levels (an average 12.7% decrease) compared to similar patients on control diet (who experienced an average 40% increase). A fifth study (Schwarz, et al. 2008) seeking to improve prostate cancer prognosis showed that giving lycopene to prostate cancer patients for 6 months significantly both decreased serum PSA levels and stopped further prostate enlargement compared to a group taking a placebo. Lycopene was also beneficial in sixth study (Ansari, et al. 2003) in which patients given lycopene after orchidectomy. After six months PSA levels were reduced more significantly than in the patients not given lycopene, and after two years almost twice the number of patients taking lycopene had a complete PSA response, and significantly less patients had died from their disease. In a similar trial (Kucuk, et al. 2002), 26 men newly diagnosed with prostate cancer were given either lycopene or a placebo for 3 weeks before radical prostatectomy. After treatment, those taking lycopene had smaller tumours, less spread of tumour cells through the prostate, and lower PSA levels than those taking the placebo.
In another study (Aronson, et al. 2010), 18 men with prostate cancer were put on a low fat/high fibre diet supplemented with isoflavones for 4 weeks. Their blood serum retarded the growth of cultured prostate cancer cells significantly more than men on a regular diet, although unlike in other studies, their PSA levels were not significantly changed. Similar generally positive results for the use of isoflavones for decreasing serum PSA levels in prostate cancer patients were also observed in several other studies (Hussain, et al. 2003; Kwan, et al. 2010).
Isoflavones have also been used as a prostate cancer supplements and shown to beneficially alter hormone levels in prostate cancer patients. In one study (van Veldhuizen, et al. 2006) of natural products for prostate cancer, isoflavone-containing supplements were given to 11 prostate cancer patients, and they observed that 9 of them experienced a decrease in serum testosterone levels, a hormone which promotes the growth of prostate cancer cells. In another study (Kranse, et al. 2005), prostate cancer patients with rising PSA levels were given supplements rich in both isoflavones and selenium, and found that although PSA doubling times were unaffected, both serum PSA and hormone levels significantly decreased.
Prevention of Prostate Cancer
A recent exhaustive review (Hwang, et al. 2009) of 13 studies into the effects of soy isoflavones on prostate cancer prevention which included 91,862 participants, of which 5,224 had prostate cancer, showed that soy isoflavones had a significant protective effect, with an average 31% lower incidence of prostate cancer in individuals that consumed high levels of soy isoflavones compared to those who did not. Likewise, one study (Reid, et al. 2008) showed that taking selenium supplements decreased total cancer incidence by 25% in a large group of individuals, and another, which combined data from 16 studies including over 168,000 individuals, showed that higher selenium intake helped in preventing prostate cancer and was associated with a 28% lower risk of the disease. In contrast to these studies however, two other large trials (Lippman, et al. 2009; Allen, et al. 2008) which followed 35,533 and 2,018 men over several years showed that taking selenium supplements did not have a significant effect on the risk of developing prostate cancer. In addition, one study (Kirsh, et al. 2006) that investigated lycopene intake in 29,361 men (including 1338 with prostate cancer) found that it was not significantly associated with preventing the occurrence of prostate cancer. It has been hypothesized that differences in the outcomes of trials using selenium may be at least partly due to the populations studied - in individuals with already high intakes of selenium, taking more will not have a significant effect, whereas those individuals who have a lower intake of selenium will benefit from the supplement.
Other Beneficial Effects
Isoflavones, selenium, and lycopene have a range of other important effects on the body. Isoflavones have been shown to lower cholesterol levels and decrease the risk of heart disease. There is also some weak evidence to suggest they may be beneficial for the treatment of osteoporosis.
Selenium is important for the normal functioning of the thyroid gland. Deficiencies in selenium can result in heart abnormalities and degeneration of cartilage tissue. There is some weak evidence to suggest that it may decrease the risk of diabetes.
Lycopene is a powerful antioxidant, particularly as a quencher of singlet oxygen, thought to be the primary cause of skin aging. Some scientific studies have also suggested that lycopene may be protective against diabetes, cardiovascular disease, and osteoporosis.
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We would highly recommend that anyone interested in researching these nutritional supplements or prostate cancer further look at the main database of scientific and clinical studies, PubMed. It is free to search and view abstracts from millions of scientific studies published in peer-reviewed scientific journals over the past several decades. Full tutorials and help using PubMed can be found here. While they are generally of a technical nature and intended for a scientific/medical professional audience, non-specialists should also find them extremely useful.
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Rabiau N, Kossaï M, Braud M, Chalabi N, Satih S, Bignon YJ, Bernard-Gallon DJ. Cancer Epidemiol. 2010 Jan 22. Genistein and daidzein act on a panel of genes implicated in cell cycle and angiogenesis by Polymerase Chain Reaction arrays in human prostate cancer cell lines.
Li Y, Che M, Bhagat S, Ellis KL, Kucuk O, Doerge DR, Abrams J, Cher ML, Sarkar FH. Neoplasia. 2004 Jul-Aug;6(4):354-63. Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein.
Mentor-Marcel R, Lamartiniere CA, Eltoum IA, Greenberg NM, Elgavish A. J Nutr. 2005 May;135(5):989-95. Dietary genistein improves survival and reduces expression of osteopontin in the prostate of transgenic mice with prostatic adenocarcinoma (TRAMP).
Wang J, Eltoum IE, Lamartiniere CA. J Carcinog. 2007 Mar 16;6:3. Genistein chemoprevention of prostate cancer in TRAMP mice.
Li Y, Ahmed F, Ali S, Philip PA, Kucuk O, Sarkar FH. Cancer Res. 2005 Aug 1;65(15):6934-42. Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells.
Singh-Gupta V, Zhang H, Banerjee S, Kong D, Raffoul JJ, Sarkar FH, Hillman GG. Int J Cancer. 2009 Apr 1;124(7):1675-84. Radiation-induced HIF-1alpha cell survival pathway is inhibited by soy isoflavones in prostate cancer cells.
Kwan W, Duncan G, Van Patten C, Liu M, Lim J. Nutr Cancer. 2010;62(2):198-207. A phase II trial of a soy beverage for subjects without clinical disease with rising prostate-specific antigen after radical radiation for prostate cancer.
Hwang YW, Kim SY, Jee SH, Kim YN, Nam CM. Nutr Cancer. 2009;61(5):598-606. Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies.
Aronson WJ, Barnard RJ, Freedland SJ, Henning S, Elashoff D, Jardack PM, Cohen P, Heber D, Kobayashi N. J Urol. 2010 Jan;183(1):345-50. Growth inhibitory effect of low fat diet on prostate cancer cells: results of a prospective, randomized dietary intervention trial in men with prostate cancer.
Grainger EM, Schwartz SJ, Wang S, Unlu NZ, Boileau TW, Ferketich AK, Monk JP, Gong MC, Bahnson RR, DeGroff VL, Clinton SK. Nutr Cancer. 2008;60(2):145-54. A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen.
Vaishampayan U, Hussain M, Banerjee M, Seren S, Sarkar FH, Fontana J, Forman JD, Cher ML, Powell I, Pontes JE, Kucuk O. Nutr Cancer. 2007;59(1):1-7. Lycopene and soy isoflavones in the treatment of prostate cancer.
van Veldhuizen PJ, Thrasher JB, Ray G, Cherian R, Ward J, Holzbeierlein J, Gutow S, Banerjee SK. Oncol Rep. 2006 Dec;16(6):1221-4. Dose effect of soy supplementation in prostate cancer: a pilot study.
Schröder FH, Roobol MJ, Boevé ER, de Mutsert R, Zuijdgeest-van Leeuwen SD, Kersten I, Wildhagen MF, van Helvoort A. Eur Urol. 2005 Dec;48(6):922-30; discussion 930-1. Epub 2005 Oct 17. Randomized, double-blind, placebo-controlled crossover study in men with prostate cancer and rising PSA: effectiveness of a dietary supplement.
Hussain M, Banerjee M, Sarkar FH, Djuric Z, Pollak MN, Doerge D, Fontana J, Chinni S, Davis J, Forman J, Wood DP, Kucuk O. Nutr Cancer. 2003;47(2):111-7. Soy isoflavones in the treatment of prostate cancer.
Wang L, Bonorden MJ, Li GX, Lee HJ, Hu H, Zhang Y, Liao JD, Cleary MP, Lü J. Cancer Prev Res (Phila Pa). 2009 May;2(5):484-95. Methyl-selenium compounds inhibit prostate carcinogenesis in the transgenic adenocarcinoma of mouse prostate model with survival benefit.
Hawkes WC, Wang TT, Alkan Z, Richter BD, Dawson K. Biol Trace Elem Res. 2009 Dec;131(3):229-44. Selenoprotein W modulates control of cell cycle entry.
Zhao R, Xiang N, Domann FE, Zhong W. Nutr Cancer. 2009;61(3):397-407. Effects of selenite and genistein on G2/M cell cycle arrest and apoptosis in human prostate cancer cells.
Berggren M, Sittadjody S, Song Z, Samira JL, Burd R, Meuillet EJ. Nutr Cancer. 2009;61(3):322-31. Sodium selenite increases the activity of the tumour suppressor protein, PTEN, in DU-145 prostate cancer cells.
Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, Parnes HL, Minasian LM, Gaziano JM, Hartline JA, Parsons JK, Bearden JD 3rd, Crawford ED, Goodman GE, Claudio J, Winquist E, Cook ED, Karp DD, Walther P, Lieber MM, Kristal AR, Darke AK, Arnold KB, Ganz PA, Santella RM, Albanes D, Taylor PR, Probstfield JL, Jagpal TJ, Crowley JJ, Meyskens FL Jr, Baker LH, Coltman CA Jr. JAMA. 2009 Jan 7;301(1):39-51. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
Allen NE, Appleby PN, Roddam AW, Tjønneland A, Johnsen NF, Overvad K, Boeing H, Weikert S, Kaaks R, Linseisen J, Trichopoulou A, Misirli G, Trichopoulos D, Sacerdote C, Grioni S, Palli D, Tumino R, Bueno-de-Mesquita HB, Kiemeney LA, Barricarte A, Larrañaga N, Sánchez MJ, Agudo A, Tormo MJ, Rodriguez L, Stattin P, Hallmans G, Bingham S, Khaw KT, Slimani N, Rinaldi S, Boffetta P, Riboli E, Key TJ; European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2008 Dec;88(6):1567-75. Plasma selenium concentration and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).
Reid ME, Duffield-Lillico AJ, Slate E, Natarajan N, Turnbull B, Jacobs E, Combs GF Jr, Alberts DS, Clark LC, Marshall JR. Nutr Cancer. 2008;60(2):155-63. The nutritional prevention of cancer: 400 mcg per day selenium treatment.
Kranse R, Dagnelie PC, van Kemenade MC, de Jong FH, Blom JH, Tijburg LB, Weststrate JA, Schröder FH. Int J Cancer. 2005 Feb 20;113(5):835-40. Dietary intervention in prostate cancer patients: PSA response in a randomized double-blind placebo-controlled study.
Dalais FS, Meliala A, Wattanapenpaiboon N, Frydenberg M, Suter DA, Thomson WK, Wahlqvist ML. Urology. 2004 Sep;64(3):510-5. Effects of a diet rich in phytoestrogens on prostate-specific antigen and sex hormones in men diagnosed with prostate cancer.
Burgess LC, Rice E, Fischer T, Seekins JR, Burgess TP, Sticka SJ, Klatt K. Toxicol In Vitro. 2008 Aug;22(5):1297-300. Epub 2008 Mar 14. Lycopene has limited effect on cell proliferation in only two of seven human cell lines (both cancerous and noncancerous) in an in vitro system with doses across the physiological range.
Liu X, Allen JD, Arnold JT, Blackman MR. Carcinogenesis. 2008 Apr;29(4):816-23. Lycopene inhibits IGF-I signal transduction and growth in normal prostate epithelial cells by decreasing DHT-modulated IGF-I production in co-cultured reactive stromal cells.
Schwarz S, Obermüller-Jevic UC, Hellmis E, Koch W, Jacobi G, Biesalski HK. J Nutr. 2008 Jan;138(1):49-53. Lycopene inhibits disease progression in patients with benign prostate hyperplasia.
Wang A, Zhang L. Wei Sheng Yan Jiu. 2007 Sep;36(5):575-8. [Effect of lycopene on proliferation and cell cycle of hormone refractory prostate cancer PC-3 cell line]
Gunasekera RS, Sewgobind K, Desai S, Dunn L, Black HS, McKeehan WL, Patil B. Nutr Cancer. 2007;58(2):171-7. Lycopene and lutein inhibit proliferation in rat prostate carcinoma cells.
Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, Dixon LB, Urban DA, Crawford ED, Hayes RB. Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):92-8. A prospective study of lycopene and tomato product intake and risk of prostate cancer.
Ansari MS, Gupta NP. BJU Int. 2003 Sep;92(4):375-8; discussion 378. A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer.
Kucuk O, Sarkar FH, Djuric Z, Sakr W, Pollak MN, Khachik F, Banerjee M, Bertram JS, Wood DP Jr. Exp Biol Med (Maywood). 2002 Nov;227(10):881-5. Effects of lycopene supplementation in patients with localized prostate cancer.