Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Serum prostate-specific antigen but not testosterone levels decrease in a randomized soy intervention among men

European Journal of Clinical Nutrition volume 60, pages 1423–1429 (2006)Cite this article

Abstract

Background:

Low prostate cancer incidence and high soy intake in Asian countries suggest a possible protective effect of soy foods against prostate cancer. The goal of this pilot study was to evaluate the feasibility of a randomized, crossover soy trial among men and to investigate the effects of daily soy intake on serum prostate-specific antigen (PSA) and testosterone levels.

Methods:

We randomized 24 men to a high or a low soy diet for 3 months. After a 1-month washout period, the men crossed over to the other treatment. During the high soy diet, the men consumed two daily soy servings; during the low soy diet, they maintained their usual diet. During the entire study each man donated four blood samples and five overnight urine samples. Dietary compliance was assessed by soy calendars, 24-h dietary recalls, and urinary isoflavone excretion measured by high-pressure liquid chromatography with photodiode array detection. Blood samples were analyzed for serum testosterone and PSA by radioimmunoassay. When necessary, variables were log transformed. Two sample t-tests compared the two groups before each study period. Mixed models incorporating the repeated measurements were used to evaluate the effect of the soy diet on urinary isoflavone excretion and serum analytes.

Results:

Twenty-three men aged 58.7±7.2 years completed the study. The compliance with the study regimen was high according to self-reported soy food intake and urinary isoflavone excretion. No significant between-group and within-group differences were detected. During the high soy diet, dietary isoflavone intake and urinary isoflavone excretion increased significantly as compared to the low soy diet. A 14% decline in serum PSA levels (P=0.10), but no change in testosterone (P=0.70), was observed during the high soy diet in contrast to the low soy diet.

Conclusion:

The high adherence as shown by three measures of compliance in this pilot trial demonstrated the feasibility of an intervention based on soy foods among free-living men.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  • Adlercreutz H, Honjo H, Higashi A (1991). Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet. Am J Clin Nutr 54, 1093–1100.

    Article  CAS  Google Scholar 

  • Atkinson C, Skor HE, Fitzgibbons ED, Scholes D, Chen C, Wahala K et al. (2002). Overnight urinary isoflavone excretion in a population of women living in the United States, and its relationship to isoflavone intake. Cancer Epidemiol Biomarkers Prev 11, 253–260.

    CAS  PubMed  Google Scholar 

  • Blair RM, Appt SE, Franke AA, Clarkson TB (2003). Treatment with antibiotics reduces plasma equol concentration in cynomolgus monkeys (Macaca fascicularis). J Nutr 133, 2262–2267.

    Article  CAS  Google Scholar 

  • Center for Nutrition Policy and Promotion (1996). The Food Guide Pyramid. United States Department of Agriculture, Washington, DC.

  • Chen Z, Zheng W, Custer LJ, Dai Q, Shu XO, Jin F et al. (1999). Usual dietary consumption of soy foods and its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai. Nutr Cancer 33, 82–87.

    Article  CAS  Google Scholar 

  • Dai Q, Franke AA, Jin F, Shu XO, Hebert JR, Custer LJ et al. (2002). Urinary excretion of phytoestrogens and risk of breast cancer among Chinese women in Shanghai. Cancer Epidemiol Biomarkers Prev 11, 815–821.

    CAS  PubMed  Google Scholar 

  • Dillingham BL, McVeigh BL, Lampe JW, Duncan AM (2005). Soy protein isolates of varying isoflavone content exert minor effects on serum reproductive hormones in healthy young men. J Nutr 135, 584–591.

    Article  CAS  Google Scholar 

  • Ferlay J, Bray F, Pisani P, Parkin DM (2001). GLOBOCAN 2000: Cancer Incidence Mortality Prevalence Worldwide (1.0 IARC CancerBase No. 5). IARC Press: Lyon.

    Google Scholar 

  • Franke AA, Custer LJ, Cerna CM, Narala K (1995). Rapid HPLC analysis of dietary phytoestrogens from legumes and from human urine. Proc Soc Exp Biol Med 208, 18–26.

    Article  CAS  Google Scholar 

  • Franke AA, Custer LJ, Wang W, Shi SJ (1998). HPLC analysis of isoflavonoids and other phenolic agents from foods and from human fluids. Proc Soc Exp Biol Med 217, 263–273.

    Article  CAS  Google Scholar 

  • Franke AA, Hankin JH, Yu MC, Maskarinec G, Low SH, Custer LJ (1999). Isoflavone levels in soy foods consumed by multiethnic populations in Singapore and Hawaii. J Agric Food Chem 47, 977–986.

    Article  CAS  Google Scholar 

  • Gardner-Thorpe D, O'Hagen C, Young I, Lewis SJ (2003). Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men. Eur J Clin Nutr 57, 100–106.

    Article  CAS  Google Scholar 

  • Goebelsmann U, Bernstein GS, Gale JA, Kletzky OA, Nakamura RM, Coulson AH et al. (1979). Serum gonadotropin, testosterone, estradiol, and estrone levels prior to and following bilateral vasectomy. In: Lepow JH (ed). Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man pp. 165–175. Academic Press: New York.

    Google Scholar 

  • Habito RC, Montalto J, Leslie E, Ball MJ (2000). Effects of replacing meat with soyabean in the diet on sex hormone concentrations in healthy adult males. Br J Nutr 84, 557–563.

    Article  CAS  Google Scholar 

  • Hawaii Health Information Corporation (2004). Health trends in Hawaii: A Profile of the Health Care System. http://www.healthtrends.org/(6th). pp. 1–14.

  • Hedlund TE, Maroni PD, Ferucci PG, Dayton R, Barnes S, Jones K et al. (2005). Long-term dietary habits affect soy isoflavone metabolism and accumulation in prostatic fluid in caucasian men. J Nutr 135, 1400–1406.

    Article  CAS  Google Scholar 

  • Kampmann J, Siersbaek-Nielsen K, Kristensen M, Hansen JM (1974). Rapid evaluation of creatinine clearance. Acta Med Scand 196, 517–520.

    Article  CAS  Google Scholar 

  • Karr SC, Lampe JW, Hutchins AM, Slavin JL (1997). Urinary isoflavonoid excretion in humans is dose dependent at low to moderate levels of soy-protein consumption. Am J Clin Nutr 66, 46–51.

    Article  CAS  Google Scholar 

  • Kelly GE, Nelson C, Warin WA, Joannou GE, Reeder AY (1993). Metabolites of dietary (soya) isoflavones in human urine. Clin Chim Acta 223, 9–22.

    Article  CAS  Google Scholar 

  • Knudsen N, Christiansen E, Brandt-Christensen M, Nygaard B, Perrild H (2000). Age- and sex-adjusted iodine/creatinine ratio. A new standard in epidemiological surveys? Evaluation of three different estimates of iodine excretion based on casual urine samples and comparison to 24 h values. Eur J Clin Nutr 54, 361–363.

    Article  CAS  Google Scholar 

  • Kolonel LN, Hankin JH, Whittemore AS, Wu AH, Gallagher RP, Wilkens LR et al. (2000). Vegetables, fruits, legumes and prostate cancer: a multiethnic case–control study. Cancer Epidemiol Biomarkers Prev 9, 795–804.

    CAS  Google Scholar 

  • Kranse R, Dagnelie PC, van Kemenade MC, de Jong FH, Blom JH, Tijburg LB et al. (2005). Dietary intervention in prostate cancer patients: PSA response in a randomized double-blind placebo-controlled study. Int J Cancer 113, 835–840.

    Article  CAS  Google Scholar 

  • Kumar NB, Cantor A, Allen K, Riccardi D, Besterman-Dahan K, Seigne J et al. (2004). The specific role of isoflavones in reducing prostate cancer risk. Prostate 59, 141–147.

    Article  CAS  Google Scholar 

  • Lamartiniere CA, Cotroneo MS, Fritz WA, Wang J, Mentor-Marcel R, Elgavish A (2002). Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate. J Nutr 132, 552S–558S.

    Article  Google Scholar 

  • Lieberman R (2004). Evidence-based medical perspectives: the evolving role of PSA for early detection, monitoring of treatment response, and as a surrogate end point of efficacy for interventions in men with different clinical risk states for the prevention and progression of prostate cancer. Am J Ther 11, 501–506.

    Article  Google Scholar 

  • Littell RC, Milliken GA, Stroup WW, Wolfinger RD (1996). SAS System for Mixed Models. SAS Institute Inc., Cary, NC.

    Google Scholar 

  • Makela S, Pylkkanen L, Santti R, Adlercreutz H (1991). Role of plant estrogens in normal and estrogen-related altered growth of the mouse prostate. In: Proceedings of the Interdisciplinary Conference on Effects of Food on the Immune and Hormonal Systems: Euro Food Tox III, Schwerzenbach, Switzerland: Institute of Toxicology, Swiss Federal Institute of Technology & University of Zurich. 135–139.

  • Maskarinec G, Robbins C, Riola B, Kane-Sample L, Franke A, Murphy S (2003). Three measures show high compliance in soy intervention among premenopausal women. J Am Diet Assoc 103, 861–866.

    Article  Google Scholar 

  • Maskarinec G, Singh S, Meng L, Franke AA (1998). Dietary soy intake and urinary isoflavone excretion among women from a multiethnic population. Cancer Epidemiol Biomarkers Prev 7, 613–619.

    CAS  PubMed  Google Scholar 

  • Murphy SP (2002). Unique nutrition support for research at the Cancer Research Center of Hawaii. Hawaii Med J 61, 15–17.

    PubMed  Google Scholar 

  • Nagata C, Inaba S, Kawakami N, Kakizoe T, Shimizu H (2000). Inverse association of soy product intake with serum androgen and estrogen concentrations in Japanese men. Nutr Cancer 36, 14–18.

    Article  CAS  Google Scholar 

  • Ritchie MR, Morton MS, Deighton N, Blake A, Cummings JH (2004). Plasma and urinary phyto-oestrogens as biomarkers of intake: validation by duplicate diet analysis. Br J Nutr 91, 447–457.

    Article  CAS  Google Scholar 

  • Ryokkynen A, Nieminen P, Mustonen AM, Pyykonen T, Asikainen J, Hanninen S et al. (2005). Phytoestrogens alter the reproductive organ development in the mink (Mustela vison). Toxicol Appl Pharmacol 202, 132–139.

    Article  Google Scholar 

  • Sharma S, Murphy SP, Wilkens LR, Au D, Shen L, Kolonel LN (2003). Extending a multiethnic food composition table to include standardized food group servings. J Food Compos Anal 16, 485–495.

    Article  Google Scholar 

  • Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, Mack TM (1991). Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 63, 963–966.

    Article  CAS  Google Scholar 

  • Strom SS, Yamamura Y, Duphorne CM, Spitz MR, Babaian RJ, Pillow PC et al. (1999). Phytoestrogen intake and prostate cancer: a case–control study using a new database. Nutr Cancer 33, 20–25.

    Article  CAS  Google Scholar 

  • Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL et al. (2004). Prevalence of prostate cancer among men with a prostate-specific antigen level <or=4.0 ng per milliliter. N Engl J Med 350, 2239–2246.

    Article  CAS  Google Scholar 

  • Troyer DA, Mubiru J, Leach RJ, Naylor SL (2004). Promise and challenge: Markers of prostate cancer detection, diagnosis and prognosis. Dis Markers 20, 117–128.

    Article  CAS  Google Scholar 

  • United States Department of Agriculture (2002). USDA-Iowa State University Database on the Isoflavone Content of Foods. http://www.nal.usda.gov/fnic/foodcomp/Data/isoflav/isoflav.html(Release 1.3). 6–23–2005.

  • US Department of Agriculture, Agricultural Research Service (2003). USDA National Nutrient Database for Standard Reference, Release 14. http://www.nal.usda.gov/fnic/foodcomp/index.html4–30–2003.

  • Wakai K, Egami I, Kato K, Kawamura T, Tamakoshi A, Lin Y et al. (1999). Dietary intake and sources of isoflavones among Japanese. Nutr Cancer 33, 139–145.

    Article  CAS  Google Scholar 

  • Wang S, DeGroff VL, Clinton SK (2003). Tomato and soy polyphenols reduce insulin-like growth factor-I-stimulated rat prostate cancer cell proliferation and apoptotic resistance in vitro via inhibition of intracellular signaling pathways involving tyrosine kinase. J Nutr 133, 2367–2376.

    Article  CAS  Google Scholar 

  • Williams AE, Maskarinec G, Hebshi S, Oshiro C, Murphy S, Franke AA (2003). Validation of a soy questionnaire with repeated dietary recalls and urinary isoflavone assessments over one year. Nutr Cancer 47, 118–125.

    Article  Google Scholar 

  • Yamamoto S, Sobue T, Sasaki S, Kobayashi M, Arai Y, Uehara M et al. (2001). Validity and reproducibility of a self-administered food-frequency questionnaire to assess isoflavone intake in a Japanese population in comparison with dietary records and blood and urine isoflavones. J Nutr 131, 2741–2747.

    Article  CAS  Google Scholar 

  • Zheng W, Dia Q, Custer LJ, Shu XO, Wen WQ, Jin F et al. (1999). Urinary excretion of isoflavonoids and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 8, 35–40.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are very grateful to the dedicated study participants. This research was supported by a grant from the Friends of the Cancer Research Center. We also appreciate the support through food donations from Aloha Tofu Factory, Dr Soy Nutrition, and The Solae Company. We would like to acknowledge our staff members, including Laurie Custer, BS and Samantha Chen, BS. We also thank Kaiser Permanente Center for Health Research and in particular Dr Thomas Vogt for assistance with recruitment and Dr Ian Pagano for valuable advice on the statistical analysis.

Author information

Authors and Affiliations

  1. Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI, USA

    G Maskarinec, Y Morimoto, S Hebshi, S Sharma & A A Franke

  2. Department of Obstetrics and Gynecology, School of Medicine, University of Southern California, Los Angeles, CA, USA

    F Z Stanczyk

Authors
  1. G Maskarinec
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Morimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Hebshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A A Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F Z Stanczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G Maskarinec.

Additional information

Guarantor: G Maskarinec.

Contributors: GM conceived the idea for the study and directed the project, the data analysis, and the manuscript preparation; YM developed the nutritional education strategy, prepared the first draft, and contributed to the statistical analysis; SH coordinated the project and wrote part of the methods; SS provided nutritional consultation; AAF participated in the planning and was in charge of the isoflavone analyses; FZS was responsible for the PSA and testosterone analyses and their interpretation; all authors reviewed the final manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maskarinec, G., Morimoto, Y., Hebshi, S. et al. Serum prostate-specific antigen but not testosterone levels decrease in a randomized soy intervention among men. Eur J Clin Nutr 60, 1423–1429 (2006). https://doi.org/10.1038/sj.ejcn.1602473

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1602473

Keywords

This article is cited by

Search

Advanced search

Quick links