Table 1.
Summarised epidemiological and human studies for the dietary bioactives discussed. ADT: androgen deprivation treatment; PCa: prostate cancer; PSA: prostate-specific antigen; SFN: sulforaphane; ITC: isothiocyanate; FFQ: food frequency questionnaire
| Author, Year | Study Type | Patient Cohort/Intervention | Analysis |
|---|---|---|---|
| Glucoraphanin and Sulforaphane from Cruciferous Vegetables | |||
| Liu et al. 2012 [39] | Meta-analysis 6 case-control 7 cohort studies |
10 studies USA/Canada, 1 Asia, 2 Europe. | RR = 0.90; 95% CI 0.85–0.96 for overall cruciferous vegetable intake RR = 0.79; 95% CI 0.69–0.89 for case control studies |
| Richman et al. 2012 [40] | Prospective study n = 1560 |
USA PCa registry. Biopsy-verified localised PCa. Clinical survey and FFQ at baseline and every 6 months | 59% reduced risk of PCa progression for highest vs. lowest intake of cruciferous vegetables. HR: 0.41, 95% CI 0.22–0.76 (p = 0.003) |
| Zhang et al. 2019 [44] | 2-arm parallel randomised double-blinded intervention trial n = 98 |
USA cohort. Intervention for 4-6 weeks prior to prostate biopsy procedure | Accumulation of urine and plasma SFN ITCs and individual SFN metabolites. 40 differentially expressed genes correlated with treatment Downregulation of AMACR and ARLNC1 genes No significant difference in HDAC activity or prostate tissue biomarkers |
| Traka et al. 2019 [45] | 3-arm parallel randomised double-blinded 12-month intervention trial n = 49 |
UK cohort. Prostate biopsies at the start and end of 12-month intervention | Dose-dependent attenuation of gene expression and associated oncogenic pathways |
| SACSO from Alliaceous Vegetables | |||
| Hsing et al. 2002 [53] | Population based study 238 case subjects 471 control subjects |
Shanghai, China. Cases: histologically confirmed PCa. In-person interviews and FFQ. |
Highest allium intake (>10.0 g/day) OR = 0.51, 95% CI 0.34–0.76 p < 0.001 Garlic (OR = 0.47, 95% CI 0.31–0.71; p < 0.001) |
| Zhou et al. 2013 [54] | Systematic literature review 6 case-control 3 prospective cohort studies |
3 studies Europe, 3 studies USA, 2 studies Asia, 1 Australia. Interview or self-administered FFQ | OR = 0.82 95% CI 0.70–0.97 for allium intake OR = 0.77 95% CI 0.64–0.91 for garlic intake |
| Lycopene from Tomatoes | |||
| Rowles et al. 2017 [77] | Systematic literature review 43 case control studies |
32 studies N. America, 6 Europe, 2 Australia, 2 Asia (China and Singapore), 1 S. America. FFQs and 1 x interview |
RR = 0.88, 95% CI 0.78−0.98, p = 0.017 (for localised PCa risk) RR = 0.88, 95% CI 0.79−0.98, p = 0.019 for circulating lycopene concentrations (and localised PCa risk) Dose-response seen. No effect for risk of advanced PCa. |
| Wang et al. 2015 [78] | Systematic review and dose-response meta-analysis 10 cohort 11 nested case-control 13 case-control studies |
22 studies N. America, 7 studies Europe, 2 Australia, 2 Asia, 1 S. America | RR = 0.86, 95% CI 0.75–0.98 (localised PCa risk) RR 0.81, 95% CI 0.69–0.96 for blood lycopene levels. Dose-response seen No effect for risk of advanced PCa |
| Van Hoang et al. 2018 [79] | Case-control study n = 652 |
Vietnamese cohort. Cases (244) with localised PCa, and PSA 4 ng/mL. Face-to-face interviews using a structured semi-quantitative validated FFQ |
OR = 0.46 95% CI 0.27–0.77 for highest lycopene intake |
| Key et al. 2015 [80] | Pooled Analysis of 15 studies 15 case-control studies n = 29780 |
6 studies Europe, 6 studies US, 1 study Afro-Caribbean, 1 Australia, 1 Mixed-cohort (Australia and Europe) | No association between intake and overall risk of PCa. OR 0.65 95% CI: 0.46, 0.91; p = 0.032 for risk of advanced stage PCa and aggressive disease |
| Giovannucci et al. 2002 [82] | Prospective Study n = 47365 |
US male health professional cohort – ‘Health Professionals Follow-Up Study’ (HPFS) | RR = 0.84 CI 0.73–0.96 p = 0.03 for total intake RR 0.77 95% CI 0.66–0.90 p < 0.001 for high tomato sauce intake RR = 0.65 95% CI 0.42–0.99 for high tomato sauce intake and extra-prostatic cancers |
| Kim et al. 2003 [83] | Double-blinded 2-arm randomised control trial n = 32 |
US cohort. Tomato sauce intervention vs. no intervention for 3 weeks prior to prostatectomy | Increased abundance of apoptotic cells (from 0.84 +/- 0.13% to 2.76 +/- 0.58% p = 0.0003) and degree of apoptotic cell death (from 0.84 +/- 0.13% to 1.17 +/- 0.19% p = 0.028) in resected tumour areas |
| Resveratrol from Wine | |||
| Vartolomei et al. 2018 [99] | Meta-analysis 17 studies n = 611169 Meta-analysis of moderate wine intake: 14 studies n = 455413 6 cohort 8 case control studies |
4 studies Canada, 4 studies Europe, 4 studies USA, 2 studies Australia | No increased risk of PCa 0.98 95% CI 0.92–1.05, p = 0.57 (for all wine) Increased risk of PCa with moderate intake of white wine (RR 1.26 95% CI 1.10–1.43 p = 0.001) Decreased risk of PCa with moderate intake of red wine RR 0.88 95% CI 0.78–0.999 p = 0.047 (risk reduction of 12%) |
| Catechins from Green Tea | |||
| Guo et al. 2017 [109] | Systematic review and meta-analysis: 7 observational: 4 cohort 3 case control 3 randomised controlled trials |
6 studies Asia (incl. 1 Singapore, 4 Japan, 1 China), 2 Europe, 1 N. America, 1 Africa | RR 0.75 95% CI 0.53–1.07 for highest versus lowest category of green tea intake Dose response with each 1 cup/day increase of green tea 0.954 (95% CI 0.903–1.009) p = 0.08 after removal of heterogeneity and undertaking sensitivity analysis RR of 0.38 (95% CI 0.16–0.86, p = 0.02) - Patients with high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP) |
| Curcumin from Turmeric | |||
| Choi et al. 2019 [126] | Randomised double-blind, placebo-controlled trial n = 82 |
S. Korean cohort. Curcumin capsule intervention or placebo from the beginning of ADT withdrawal. |
PSA progression: 10.3% (treatment) vs 30.2% (control) p = 0.0259 |
| Hejazi et al. 2016 [127] | Randomised double-blind, placebo-controlled trial n = 40 |
Iranian cohort. Curcumin capsule intervention or placebo during external-beam radiotherapy. |
Increase in plasma total antioxidant capacity (TAC) significantly higher in the treatment arm (p < 0.001) Reduction in activity of superoxide of superoxide dismutase (SOD) in the treatment arm (p = 0.026) |
| Ellagitannins from Pomegranate | |||
| Pantuck et al. 2006 [144] | Phase II two-stage clinical trial n = 46 |
US cohort. PSA 0.2–5ng/mL documented as rising. 8 ounces of pomegranate juice daily (570 mg total polyphenol gallic acid) until disease progression | Increase in mean PSA doubling time significantly increased with treatment: 15 months at baseline to 54 months post-treatment (p < 0.001) |
| Paller et al. 2013 [145] | Randomised phase II study n = 104 (n = 92 for analysis) |
US cohort (multi-centre). Rising PSA without evidence of metastasis. 1g vs. 3g pomegranate extract capsules daily for up to 18 months. | Increase in PSA doubling time with treatment: 11.9 months at baseline to 18.5 months post-treatment (p < 0.001) |
| Stenner-Liewen et al. 2013 [146] | Randomised placebo-controlled trial n = 109 (advanced PCa) |
Swiss cohort. PCa with PSA 5ng/mL. 500mL pomegranate juice vs. placebo beverage daily for 4 weeks, then all 250mL POM juice for 4 weeks. PSA measured at defined timepoints. | No significant difference in PSA levels at 28 days (p = 0.11) |
| Freedland et al. 2013 [147] | Randomised double-blind placebo-controlled trial. n = 69 |
US cohort. Pomegranate extract capsules or placebo for up to 4 weeks prior to prostatectomy | Urolithin A accumulation (p = 0.031) No effect on oxidative stress / proliferation / progression / PSA levels |