Isoflavone-Rich Soy Protein Isolate Suppresses Androgen Receptor Expression without Altering Estrogen Receptor-β Expression or Serum Hormonal Profiles in Men at High Risk of Prostate Cancer

Abstract

The purpose of this study was to determine the effects of soy protein isolate consumption on circulating hormone profiles and hormone receptor expression patterns in men at high risk for developing advanced prostate cancer. Fifty-eight men were randomly assigned to consume 1 of 3 protein isolates containing 40 g/d protein: 1) soy protein isolate (SPI+) (107 mg/d isoflavones); 2) alcohol-washed soy protein isolate (SPI-) (<6 mg/d isoflavones); or 3) milk protein isolate (0 mg/d isoflavones). For 6 mo, the men consumed the protein isolates in divided doses twice daily as a partial meal replacement. Serum samples collected at 0, 3, and 6 mo were analyzed for circulating estradiol, estrone, sex hormone-binding globulin, androstenedione, androstanediol glucuronide, dehydroepiandrosterone sulfate, dihydrotestosterone, testosterone, and free testosterone concentrations by RIA. Prostate biopsy samples obtained pre- and postintervention were analyzed for androgen receptor (AR) and estrogen receptor-beta expression by immunohistochemistry. At 6 mo, consumption of SPI+ significantly suppressed AR expression but did not alter estrogen receptor-beta expression or circulating hormones. Consumption of SPI- significantly increased estradiol and androstenedione concentrations, and tended to suppress AR expression (P = 0.09). Although the effects of SPI- consumption on estradiol and androstenedione are difficult to interpret and the clinical relevance is uncertain, these data show that AR expression in the prostate is suppressed by soy protein isolate consumption, which may be beneficial in preventing prostate cancer.

Does equol production determine soy endocrine effects?

“…Anti-androgenic properties of genistein and equol were demonstrated both in vitro and in vivo. Both inhibit 5a-reductase enzyme (which converts testosterone to DHT) in human genital skin fibroblasts [7], and consumption of soy protein isolate by men at high risk of prostate cancer suppresses the expression of the AR [117]. In men, isoflavones concentrate in prostatic tissue and fluid [54,118].…”

Dietary interventions in prostate cancer

“…The 11 randomized diet-related clinical trials conducted to date are summarized in Table 1. The trials of single dietary constituents are featured fi rst [25], followed by those that tested multiple components [26][27][28][29][30], and fi nally trials involving functional foods [31][32][33][34] and multi-behavior interventions involving diet, exercise, and stress-management therapies [35•]. These 11 trials provide examples of the most rigorous dietary intervention trials conducted to date regarding prostate cancer, but there are still signifi cant limitations.…”

Severe &amp; Moderate BPH Symptoms in Mid-Aged Men Improve with Isoflavonoid-Equol Treatment: Pilot Intervention Study

“…Also, it is known that equol (particularly S-equol) has relatively high affinity for ER-β where it can act as a selective estrogen receptor modulator or SERM [19,25]. Previous laboratories, including ours, have shown that isoflavones binding to ER-β in the prostate can down regulate the AR and thus decrease negative androgen hormone actions [28]. Moreover, this may explain how isoflavonoid molecules accumulate in prostate tissue and prostatic fluid after oral supplementation [29,30].…”