TABLE 1.

Clinical studies evaluating the potential of soy isoflavones in reducing PSA levels.

Clinical study protocol	Outcome	PMIDs	References
Healthy men (N = 112 aged 50–80 years) were randomly allocated to groups drinking either a soy protein drink with 83 mg of isoflavones (+ISO) or a comparable drink with isoflavones removed in a double-blind, parallel-arm, randomized experiment for 12 months	In the isoflavone therapy group, there was no significant change in blood PSA level, velocity, or PCa incidence	15066931	Adams et al.  (2004)
For 3 months, 24 males were put on a high or low soy diet in a randomized, double-blind, crossover clinical trial	14% decrease in circulating blood PSA levels was observed but with no change in testosterone levels	16775579	Maskarinec et al. (2006)
In a randomized study, 58 men at high risk of PCa were allocated to groups taking one of three protein isolates containing 40 g/d protein at random (107 mg/d isoflavones, <6 mg/d isoflavones, or 0 mg/d isoflavones) for 6 months	Soy protein isolate intake reduces AR expression in the prostate but did not affect ER β expression	17585029	Hamilton-Reeves et al. (2007)
Twenty patients with increasing PSA following previous local treatment were treated with soy milk with 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months in an open-labeled phase II study	In six patients, the slope of PSA after study enrollment was substantially lower than that before entering the study, while in two individuals, the slope of PSA after study admission was significantly greater	18471323	Pendleton   et al.    (2008)
In a randomized, double-blind experiment, 25 PCa patients were given placebo or soy isoflavone supplements for 2 weeks before prostatectomy	In PCa patients, soy isoflavones decreased prostate COX-2 mRNA while increasing p21 mRNA	19127598	Swami et al. (2009)
In the phase II trial, 29 patients with increasing PSA levels following intense radiotherapy for prostate cancer were told to drink 500 ml of soy beverage every day for 6 months	In 41% of PCa patients, soy caused a substantial delay in PSA doubling time	20099194	Kwan et al. (2010)
53 men with PCa took a daily supplement comprising 450 mg genistein, 300 mg daidzein, and other isoflavones for 6 months in a double-blind, placebo-controlled, randomized study	In men with low-volume PCa, there was no significant reduction in PSA levels	21058191	deVere White et al. (2010)
33 males undergoing androgen deprivation therapy for PC were given either 20 g of soy protein with 160 mg of total isoflavones or a taste-matched placebo (20 g whole milk protein) for a 12-weeks	In androgen-deficient males, high-dose isoflavones do not enhance metabolic or inflammatory markers	20798386	Napora et al. (2011)
Phase II, randomized, double-blind, placebo-controlled trial, or oral isoflavone (60 mg/day) for 12 months, N = 158	PSA levels did not significantly change, following treatment with isoflavones. The isoflavone group had a substantially reduced PCa incidence in 53 individuals aged 65 years	21988617	Miyanaga et al. (2012)
47 Norwegian patients were given 30 mg genistein or placebo capsules daily for 3–6 weeks before prostatectomy in a phase 2 placebo-controlled, randomized, double-blind clinical study	mRNA level of KLK4 in tumor cells was considerably decreased, while androgen and cell cycle-related biomarkers were not significantly lowered	22397815	Lazarevic et al. (2012)
A double-blinded, randomized, placebo-controlled trial included 86 men given soy isoflavone capsules (80 mg/d of total isoflavones and 51 mg/d aglucon units) for 6 weeks	After consuming soy isoflavones for a short time, no significant changes in blood hormone levels, total cholesterol, or PSA were observed	`23874588	Hamilton-Reeves et al. (2013)
In 177 men at high risk of recurrence following radical prostatectomy for PCa, a randomized, double-blind trial comparing daily use of beverage powder containing 20 g of protein in the form of either soy protein isolate (n = 87) or as placebo calcium caseinate (n = 90). Within 4 months of surgery, supplementation was started and was followed up for 2 years	Following radical prostatectomy, daily intake of a beverage powder supplement containing soy protein isolate for 2 years did not prevent biochemical recurrence of PCa in men at high risk of PSA failure	23839751	Bosland et al. (2013)