Table 9.
RCTs examining the effect of combined antioxidant supplementation on PSA concentrations among men with PCa or increased PCa risk.
| First Author | Origin | Masking | Duration | Patients | Interventions | Results |
|---|---|---|---|---|---|---|
| Paur [177] | NO | Single-blind | 3 wks | n = 86 men with PCa | 1. Tomato products (30 mg lycopene/d) (n = 28) 2. Tomato products + Se, n-3 fatty acids, soy isoflavones, grape/pomegranate juice, green/black tea (n = 28) 3. Control diet (n = 30) |
No differences in the PSA concentrations between the intervention and control groups were noted. |
| Grainger [178] | US | NR | 8 wks | n = 41 men with PCa | 1. Wks 0–4: Tomato products (no soy) (>25 mg of lycopene/d). Wks 4–8: a combined tomato-rich diet and soy ONS (n = 20) 2. Wks 0–4: Soy (no tomatoes) (40 g of soy protein/d) Wks 4–8: a combined tomato-rich diet and soy ONS (n = 21) |
A reduction in % PSA concentrations was noted in the tomato (25%) and soy (43%) groups without any statistics being presented between groups. |
| Hoenjet [179] | NL | Double-blind | 21 wks | n = 70 patients with hormonally untreated PCa and rising PSA | 1. vitamin E (350 mg), Se (200 μg), vitamin C (750 mg), CoQ10 (200 mg) (n = 36) 2. placebo (n = 34) |
ONS with a combination of vitamin E, Se, vitamin C and CoQ10 did not affect serum PSA concentrations. |
| Oh †,‡ [182] | US | NR | NR | n = 85 men with histologic evidence of progressive androgen-independent PCa | 1. 3x3 PC-SPES caps with contained 320 mg of herbal combination (Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Isatis indigotica, Dendranthema morifolium, Seronoa repens, Panax pseudoginseng, and Glycyrrhiza uralensis) (n = 43) 2. DES (n = 42) |
Among those treated with PC-SPES, 6/16 patients had decreases in PSA. Among those treated with DES, 2/8 patients had a decrease in PSA, though neither achieved a 50% PSA response. |
| Kranse ‡ [183] | NL | Double-blind | 6 wk each arm with washout | n = 66 men with hormonally untreated PCa and increasing PSA concentrations | 1. Margarine [with plant estrogens (1.5 g), Vitamin E (50 mg), Se (0.2 mg)], carotenoids (10 mg lutein, 10 mg lycopene, 10 mg palm carotenoids), green tea (6 cups), isoflavones (100 mg phytoestrogens, 60 mg genistein, 40 mg daidzein) (n = 15) 2. placebo (n = 16) |
Total PSADT was unaffected. Free PSA increased during the placebo phase and decreased during the supplement period. |
| DeVere White [181] | US | Double-blind | 6 mo | n = 53 men with PCa on AS | 1. Genistein (450 mg), daidzein (300 mg), other isoflavones (n = 36) 2. Placebo (n = 30) |
PSA concentrations did not change in either group after intervention. |
| Thomas [180] | GB | Double-blind | 6 mo | n = 199 men with localized PCa | 1. Broccoli powder (100 mg) + turmeric (100 mg) + pomegranate (100 mg) + green tea 5:1 extract (10 mg) (n = 134) 2. Placebo (n = 65) |
A lower rise in PSA was observed in the supplement group, as opposed to the placebo. |
| Yoshimura [185] | JP | Open-label | 6 mo | n = 47 men with biochemical failure after radical treatment for non-metastasized PCa | 1. Senseiro (Agaricus blazei Murill mushroom) (n = 32) 2. Rokkaku Reishi (Ganoderma lucidum mushroom) (n = 15) |
No partial response in terms of PSA was observed. At 12 mo after entry, the PSADT of the Senseiro group was not prolonged and that of the Rokkaku Reishi arm was marginally prolonged compared with baseline values. |
| Vidlal [186] | CZ | Double-blind | 6 mo | n = 37 men, 2–3 mo post-radical prostatectomy | 1. Silymarin (570 mg) + Se (240 μg) (n = 19) 2. Placebo (n = 18) |
No difference in the PSA was noted between groups. |
| Van Die [187] | AU | Double-blind | 12 wks | n = 20 men with biochemically recurrent PCa and a moderate rise rate PSA | 1. 2 × 2 caps/daily containing curcumin (100 mg), resveratrol (120 mg), GTC (100 mg) + 2 × 2 caps broccoli (equivalent to 2 g fresh sprouts) (n = 9) 2. Placebo (n = 11) |
The active treatment arm experienced a non-significant increase in the log-slope of PSA, and the placebo arm experienced no change in the log-slope of PSA. |
| Schröder ‡ [188] | NL | Double-blind | 10 wks each, 4-wk washout | n = 49 men with PCa history and rising PSA post-radical prostatectomy or radiotherapy | 1. Soy, isoflavones, lycopene, silymarin, antioxidants (n = 49) 2. Placebo (n = 49) |
A 2.6-fold increase in PSADT from 445 to 1150 d was recorded for the supplement and placebo periods, respectively. |
| Gontero † [166] | IT | Double-blind | 6 mo | n = 60 men with primary mHGPIN and/or ASAP | 1. Lycopene (35 mg), Se (55 µg), and GTCs (600 mg) (n = 30) 2. placebo (n = 30) |
No significant variations in PSA concentrations were observed. |
| Vostalova [172] | CZ | Double-blind | 6 mo | n = 55 men with LUTS, BPH and PSA ≤ 2.5ng/mL | 1. Se (240 μg) + silymarin (570 mg) (n = 26) 2. Placebo (n = 29) |
A significant reduction in PSA in the intervention group was observed. |
| Fleshner [165] | US | Double-blind | 3 yrs | n = 303 men with HGPIN | 1. 2× soy protein (20 g), vitamin E (400 IU), Se (100 μg) 2. Whey-based placebo |
No differences were recorded in the PSA concentrations of participants between the two arms. |
| Vaishampayan [163] | US | NR | 6 mo | n = 71 patients with 3 successive rising PSA concentrations or >PSA of 10 ng/mL at 2 alternate evaluations | 1. 2 × 1 tomato extract caps (15 mg of lycopene) (n = 38) 2. 2 × 1 tomato extract caps (15 mg of lycopene) plus 2 × 1 caps (40 mg soy isoflavone mixture) (n = 33) |
No decline in serum PSA was noted in either group. |
| Lane † [167] | GB | Double-blind (caps), single-blind (foods) | 6 mo | n = 266 men with PSA concentrations of 2.0–2.95 ng/mL or 3.0–19.95 ng/mL and negative prostate biopsies | 1. Green tea drink (3 cups, unblinded) (n = 45) 2. Green tea caps (blinded, 600 mg flavan-3-ol EGCG) (n = 45) 3. Placebo (n = 43) 4. Lycopene-rich foods (unblinded) (n = 44) 5. Lycopene (15 mg/d) caps (blinded) (n = 44) 6. Placebo (n = 45) |
PSA concentrations did not differ between lycopene, green tea, or placebo groups at 6 months. |
| Morgia Š [164] | IT | Double-blind | 1 yr | n = 225 patients who underwent prostate biopsy when PSA ≥ 4 ng/mL, and/or suspicion of PCa | 1. Saw palmetto (320 mg), Se and lycopene (n = 75) 2. Tamsulosin (0.4 mg) (n = 75) 3. Saw palmetto (320 mg), Se, lycopene, and tamsulosin (0.4 mg) (n = 75) |
No differences in terms of mean changes in PSA between the groups were noted. |
| Suardi [169] | IT | Double-blind | 3 mo before surgery | n = 36 patients with BPH and obstructive symptoms, scheduled for surgery | 1. Saw palmetto, quercetin and β-sitosterol (n = 18) 2. No intervention (n = 18) |
No differences were noted in the PSA of the two groups. |
| Morgia [168] | IT | NR | 6 mo | n = 168 men with histological PCI diagnosis associated with BPH, HGPIN, and/or ASAP, and suspected PCa | 1a. Saw palmetto, Se and lycopene (n = 54) 1b. No intervention (n = 54) 2a. Saw palmetto, Se, and lycopene + a-blockers (n = 30) 2b. No ONS or a-blockers (n = 30) |
Mean PSA was reduced in group 1a as compared with the controls (1b). |
| Ide [170] | JP | Double-blind | 6 mo | n = 100 men undergoing systematic prostate biopsy for elevated PSA, without PCa or PIN diagnosis | 1. Curcumin (100 mg/d) + isoflavones (40 mg) (n = 50) 2. Placebo (n = 50) |
PSA concentrations decreased in patients with baseline PSA ≥ 10 treated with isoflavones and curcumin. |
| Meyer [175] | CA | Double-blind | 8 yrs | n = 5034 men (45–60 yrs) | 1. Vitamin C (120 mg), α-tocopherol (30 mg), β-carotene (6 mg), Se (100 μg), and Zn (20 mg) (n = 2522) 2. placebo (n = 2512) |
Supplementation did not affect PSA concentrations. Among men with normal PSA on ONS, a reduction in the rate of PCa was noted. In those with elevated PSA at baseline, ONS was associated with an increased PCa incidence of borderline significance. |
| Klein [61] | US | Double-blind | 7–12 yrs | n = 34,887 men with PSA ≤ 4.0 ng/mL, a DRE not suspicious for PCa, and age ≥ 50 yrs (black men) and ≥ 55 yrs (all others) | 1. Se (200 μg/d) (n = 8752) 2. Vitamin E (400 IU/d) (n = 8737) 3. Se (200 μg) + Vitamin E (400 IU) (n = 8702) 4. Placebo (n = 8696) |
2/3 of the men in each of the 4 groups had elevated PSA (NS). No difference was observed in the PSA velocity each consecutive year between groups. Vitamin E ONS increased the risk of PCa. |
| Marks [126] | US | Double-blind | 6 mo | n = 44 men (45–80 yrs) with symptomatic BPH | 1. Saw palmetto (106 mg) + herbs (nettle root, pumpkin) (n = 21) 2. Placebo (n = 23) |
A lack of a change in serum PSA was noted. |
| Preuss [171] | US | Double-blind | 3 mo | n = 127 men with BPH | 1. Cernitin, saw palmetto, B-sitosterol, vitamin E (n = 70) 2. Placebo (n = 57) |
The PSA scores showed no differences when comparing the intervention and placebo groups. |
AS, active surveillance; ASAP, atypical small acinar proliferation; BPH, benign prostate hyperplasia; CI, confidence intervals; CoQ10, coenzyme Q10; DES, Diethylstilbestrol; DRE, digital rectal examination; EGCG, (-)-epigallocatechin-3-gallate; GTCs, green-tea catechins; HGPIN, high grade prostatic intraepithelial neoplasia; HR, hazard ratio; IU, international units; LUTS, lower urinary tract symptoms; MC, multi-county; mHGPIN, multifocal high grade prostatic intraepithelial neoplasia; NS, not significant; PCa, prostate cancer; PCI, prostatic chronic inflammation; PIN, prostatic intraepithelial neoplasia; PSA, prostate-specific antigen; PSADT, prostate-specific antigen doubling time; RCT, randomized controlled trials; Se, selenium; Zn, zinc. † phase II trial; Š post-hoc analysis; ‡ cross-over trial.