Table I.
Summary of human studies examining the effects of soy isoflavones on PC.
| Author, year | Study design | Dose and duration | Participants | Author conclusions | Country | (Refs.) |
|---|---|---|---|---|---|---|
| Hussain et al, 2003 | Pilot study | Supplement containing 100 mg of soy isoflavone (Novasoy); 6 months | Newly diagnosed and untreated patients with PC (n=41) with rising PSA (group I); or increased serum PSA following local therapy (group II); or receiving hormone therapy (group III) | Stabilization of PSA in 83% of patients in hormone-sensitive (group II) and 35% of hormone-refractory (group III) patients. Decrease in the rate of the rise of serum PSA in the whole group (P=0.01) with rates of rise decreasing from 14 to 6% in group II (P=0.21) and from 31 to 9% in group III (P=0.05) | USA | (101) |
| Kumar et al, 2004 | Prospective, randomized, placebo-controlled clinical trial | Dietary supplement of soy isoflavones (60 mg/day); 12 weeks | Patients with PC (n=76) with Gleason score of ≤6 and of all races and ethnicities | Serum free testosterone reduced or no change in 61% of subjects in the isoflavone group compared to 33% in the placebo group. Serum total PSA decreased or unchanged in 69% of subjects in the isoflavone-treated group compared to 55% in the placebo group; 19% of subjects receiving soy isoflavones reduced total PSA by ≥2 points during the intervention period | USA | (102) |
| Dalais et al, 2004 | Randomized, double-blind, placebo-controlled study | HT soy grits (50 g) or HT soy grits (50 g) + linseed (20 g); daily isoflavone levels: 117 mg (genistein, daidzein, and glycitein in aglycone form by weight); 22–27 days | Patients with PC (n=29) before radical prostatectomy randomized to one of three groups: Soy (high phytoestrogen); soy + linseed (high phytoestrogen); or wheat (low phytoestrogen) | Significant changes between the HT soy grits group and the control wheat group for: 1) % change in total PSA (−12.7 vs. 40%, P=0.02); 2) % change in free/total PSA ratio (27.4 vs. −15.6%, P=0.01). Significant changes between the HT soy grits group and the HT soy grits + linseed group for: 1) % change in free androgen index (16.4 vs. −15.5%, P=0.04); 2) % change in free/total PSA ratio (27.4 vs. −10%, P=0.007). | Australia | (103) |
| Schröder et al, 2005 | Randomized, double-blind, placebo-controlled crossover study | Soy isoflavone aglycones (62.5 mg Novasoy), plus lycopene, silymarin and a balanced mixture of antioxidants; 2 periods of 10 weeks separated by a wash-out period of 4 weeks | Patients with PC (n=49) with rising PSA levels after radical prostatectomy (n=34) or radiotherapy (n=15). | Reduced slope of total PSA during periods of utilization of the supplement with respect to the placebo periods. Significant decrease in PSA slope (P=0.030) and 2log PSA slope (P=0.041) | The Netherlands | (104) |
| Kranse et al, 2005 | Randomized, double-blind, placebo-controlled study | Beverage (3 servings of 200 ml/day) containing 100 mg isoflavones (60 mg genistein and 40 mg daidzein); 8 weeks | Hormonally untreated patients with PC (n=35) with PSA levels >0.1 ng/ml and no clinical evidence of (recurrent) PC after radical prostatectomy, radiotherapy or under watchful waiting | Unaffected total PSA doubling time. Free PSA, which increased during the placebo phase (average doubling time of 68 weeks), decreased during the verum period (average half-life of 13 weeks; P=0.02). In men in whom the free androgen index decreased (21 out of 32), there was a significant decrease in the slopes of both total and free PSA (P=0.04). No significant increase in overall total PSA doubling times during verum period | The Netherlands | (105) |
| Vaishampayan et al, 2007 | Phase II clinical trial | Tomato extract capsule containing 15 mg of lycopene alone (n=38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n=33) twice daily orally; 6 months | Patients with PC (n=71) with rising PSA levels or a minimum PSA of 10 ng/ml | No decline in serum PSA in either group. Stabilization of serum PSA level in 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group | USA | (106) |
| Grainger et al, 2008 | Randomized trial | 40 g of soy protein/day for 4 weeks. Combined tomato-rich diet (lycopene intake 43 mg +/- 15 mg) and soy supplements (39 g +/- 1 g) during weeks 4–8; 2 months | Patients with PC (n=41) | Serum PSA decreased between weeks 0 and 8 for 14/41 men (34%). PC patients consuming diets rich in tomato products and soy exhibited excellent compliance and bioavailability of phytochemicals | USA | (107) |
| Hamilton-Reeves et al, 2008 | Randomized, placebo-controlled trial | Protein isolates containing 40 g protein: 1) soy protein (SPI+, 107 mg isoflavones/day); 2) alcohol-washed soy protein (SPI-, <6 mg isoflavones/day); 3) milk protein isolate; 6 months | Men at high risk of PC or with low-grade PC (n=58). Serum collected at 0, 3 and 6 months | Consumption of SPI+ did not alter total and free PSA; 6 months SPI+ consumption did not alter prostate tissue biomarkers. SPI-consumption exerted mixed effects; lower incidence of PC was detected after 6 months of soy consumption regardless of isoflavone content | USA | (108) |
| Pendleton et al, 2008 | Open-labeled, phase II, nonrandomized trial | Soy milk containing 47 mg of isoflavonoid per 8 oz; 12 months | Patients with PC with rising PSA after local therapy (n=20). | The slope of PSA after study entry was significantly lower compared with before study entry in 6 patients and the slope of PSA after study entry was significantly higher compared with before study entry in 2 patients; there was no significant change in the slope of PSA in 12 patients | USA | (109) |
| Kumar et al, 2010 | Phase I dose-finding randomized controlled trial | Purified isoflavones (40, 60 and 80 mg); 30 (±3) days | Clinically localized patients with PC (n=40) randomized to arms 1 to 3 and instructed to consume one (arm 1, 40 mg), two (arm 2, 60 mg) or three (arm 3, 80 mg) capsules daily | Significant increase in serum free testosterone in the 60 mg isoflavone-treated arm; no significant changes in serum sex hormone-binding globulin, PSA or percentage of tissue Ki-67 with treatment for the sample size and duration of intervention | USA | (110) |
| deVere White et al, 2010 | Double-blind, placebo controlled, randomized trial | Supplement containing 450 mg genistein and 300 mg daidzein and other isoflavones; 6 months | Patients with PC (n=53) not previously treated with radiation, surgery or hormones | No association with changes in PSA concentrations after either 6 or 12 months, both in terms of absolute changes and PSA doubling times | USA | (111) |
| Kwan et al, 2010 | Phase II nonrandomized study | Soy beverage daily (500 ml; 50–100 mg isoflavones); 6 months | Patients with PC after radical radiation (n=34) | Declining trend or >2 times prolongation of PSA doubling time in 41% of subjects after 6 months of daily soy beverage consumption | Canada | (112) |
| Lazarevic et al, 2011 | Block-randomized double-blind, placebo-controlled trial | Synthetic genistein (30 mg); 3–6 weeks | Patients with PC before prostatectomy (n=54) | Serum PSA decreased by 7.8% in the genistein arm and increased by 4.4% in the placebo arm (P=0.051). PSA level reduced in tumor tissue compared to normal tissue in the placebo arm. In the genistein arm, the PSA level in tumor and normal tissue was comparable | Norway | (113) |
| Hamilton-Reeves et al, 2013 | Randomized, double-blinded, placebo-controlled trial | Soy isoflavone capsules (80 mg/day of total isoflavones, 51 mg/day aglucon units); 6 weeks | Patients with localized PC (n=86) | No significant changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA and total cholesterol in the isoflavone-treated group compared to patients receiving placebo | USA | (114) |
PC, prostate cancer; PSA, prostate-specific antigen; HT, heat-treated.