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. Author manuscript; available in PMC: 2019 May 28.
Published in final edited form as: Cancer Lett. 2018 Feb 20;422:9–18. doi: 10.1016/j.canlet.2018.02.025

Table 1.

Selected published human clinical trials using natural chemopreventive agents against PCa.

Chemopreventive Agent Study design           Study Outcome Ref
Dose and Duration Subjects/Sample size/Phase
Tea polyphenols
Green tea, black tea or water 6 cups/day for 3 to 8 weeks PCa intervention, N=113; Phase II NF-κB staining in radical prostatectomy tissue, urinary 8-OHdG and serum PSA levels were significantly decreased in green tea, but not in black tea group. [18]
Green tea or water 6 cups/day for 3 to 8 weeks Clinically localized PCa, N=17 Methylated and nonmethylated forms of EGCG were detectable in prostatectomy tissue. [19]
Green tea, black tea or a caffeine-matched soda control 1.42 L daily for 5 day Prostatectomy scheduled Patients, N=20 Tea polyphenols and theaflavins were found bioavailable in the prostate, and therefore may be effective in the management of PCa. [17]
Green tea catechins (GTC) 3 × 200 mg capsules; total 600 mg) or placebo control daily for 1 year HGPIN volunteers, N=60 Decrease in the tumor incidence and PSA level, improved quality of life, and reduced lower urinary tract symptoms in GTC-supplemented men. In a follow-up study, further reduction in PCa were noticed suggesting long-lasting effect of GTC. [20, 21]
Polyphenon E 400 mg EGCG/day or placebo for 1 year HGPIN and/or ASAP N=97 No significant difference in the number of PCa cases, however, a decrease in PSA was reported in EGCG group. [22]
Polyphenon E 1.3 g of tea polyphenols including 800 mg EGCG or placebo daily for around 6 weeks Prostatectomy scheduled Patients, N=26; Phase II Significant decrease in serum levels of PSA, HGF, IGF-I, IGFBP-3, and VEGF in men with PCa. [23]
Polyphenon E 800 mg EGCG or placebo daily for 3–6 weeks Prostatectomy scheduled Patients, N=50; Phase II Favorable but statistically insignificant changes in systemic and tissue biomarkers including PSA. [24]
Vitamins and Minerals
Vitamin D Calcitriol 0.5 μg/kg) or placebo weekly for 4 weeks Histologically confirmed PCa, N=39 Calcitriol was found to downregulate vitamin D receptor expression in human PCa. [82]
Vitamin D analog 1α-hydroxyvitamin D2; 10 μg orally or placebo daily for 28 days Clinically localized PCa and HGPIN, N=60, Phase II Biologic activity of 1α-hydroxyvitamin D2 was minimal in both serum and tissue, and TGF-ß2 was the only biomarker found significantly reduced. [28]
Vitamin E 400 IU/day of all rac-α-tocopheryl acetate or placebo over 5 years (planned for 7–12 years). Healthy with negative digital rectal exam, N=35,533, Phase III There were non-significant increased risks of PCa in the vitamin E group. In subsequent follow-up study, vitamin E supplementation was found to be associated with significant increase in the risk of PCa. [35, 36]
Vitamin E 2,2,5,7,8-pentamethyl-6-chromanol APC-100, 900–2400 mg orally daily for 28 days Castrate-resistant PCa (CRPC), N=20, Phase I/IIa APC-100, which act as both antioxidant as well as antiandrogen, was found to have a slightly better response, as 5 out of 20 patients had stable disease. However, APC-100 was not detectable in plasma. [39]
Calcium carbonate 3 g; 1,200 mg of calcium or placebo, daily for 4 years Colorectal adenoma chemoprevention trial, N=673 There were 33 PCa cases in the calcium-treated group vs 37 in the placebo group after a mean follow-up of 10.3 years, suggesting protective effects of calcium. [83]
Selenium
Selenium As selenized yeast; 200 μg/day) or placebo for a mean of 4.5 years Men with history of non-melanoma skin cancer, N=974 Selenium was found to be associated with a significant reduction in the PCa incidence (secondary endpoint), in patients with lower baseline PSA and plasma selenium levels. [52, 8486]
Selenium As L-selenomethionin e; 200 μg/day) over 5 years (planned for 7-years) 12 Healthy men with negative digital rectal exam, N=35,533, Phase III No preventive effects against PCa were found. However, supplementation in men with high Se status increased the risk of high-grade PCa. [35, 87]
Selenium As selenized yeast; years 200 or 400 μg/day up to 5 Men with ≥1 negative sextant prostate biopsy, N=699, Phase III No effect on incidence of PCa or PSA velocity in men at high risk was found. [55, 88]
Selenium As selenized yeast; years 200 or 800 μg/day up to 5 Localized nonmetastatic PCa patients, N=140, Phase II No significant effect of selenium on PSA velocity was seen. Men in the highest quartile supplemented with the highest dose showed an increase in PSA velocity. [57, 89]
Selenium As selenomethionin e; 200 μg/day) over a 3-year period. Men diagnosed with HGPIN, N=423, Phase III Selenium had no effect on PCa risk, although a subset analysis found a trend of reduced PCa in Se vs placebo patients in the lowest quartile of baseline plasma Se levels. [56, 90]
Soy and isoflavones
Dietary soy High (2 servings of soy foods/day) and low (no added soy) via diet for 3 months Healthy men aged 58.7+/−7.2 years, N=24 The study found 14% decline in serum PSA levels, though statistically not significant, in the high soy diet in contrast to the low soy diet. [63]
Soy beverage 500 mL daily for 6 month Men with rising PSA after radical radiation, N=29 A declining trend in PSA levels and a trend towards >2 times prolongation of PSA doubling time in 41% of subjects. [64]
Isoflavone+ As soy protein drink; 83 mg/day, or isoflavone drink for 12 months Healthy men aged 50–80 years, N=112 No significant change in serum PSA level, velocity, or PCa incidence in isoflavone treatment group, or in other prostate conditions that affect serum PSA levels. [65]
Isoflavone 60 mg/day or placebo for 12 months Men with rising PSA, N= 158, Phase II No significant change in PSA levels after isoflavone treatment. However, 53 patients aged ≥65 years, showed significantly lower PCa incidence in the isoflavone group. [67]
Soy protein isolate 107 or <6 or 0 mg/day isoflavones for 6 months. High risk PCa patients, N=58 Isoflavone-rich soy protein significantly reduced AR expression, but no change in estrogen receptor-β or circulating hormones in men at high risk of PCa. [68]
Isoflavones 5g/day including 450 mg genistein, 300 mg daidzein, or placebo for 6 months Low-volume PCa patients, N=53 No significant reduction in PSA levels were found in men with low-volume PCa. [69]
Isoflavones 80 mg/day for up to 6 week Patients with localized PCa, N=86, Phase II No significant change in serum hormone levels, total cholesterol, or PSA after short-term intake of soy isoflavones. [66]
Genistein 30 mg/day or placebo for 3–6 weeks Patients with localized PCa, N=47, Phase II Significant reduction in the androgen-related biomarker KLK4, but no significant changes in proliferation-, cell cycle-, apoptosis-related biomarkers. [70]
Resveratrol and Grapes
Resveratrol 150 or 1,000 mg or placebo daily for 4 months Men suffering from the metabolic syndrome, N=66 High dose of resveratrol was associated with lower serum levels of androstenedione, dehydroepiandrosterone-sulphate, and dehydroepiandrosterone. However, there was no effect on prostate volume. [72]
Muscadine grape skin extract (500–4,000 mg) for 28 days Recurrent PCa N=14; phase I/II No patients exhibited a maintained fall in serum PSA from baseline. [75]