BERKELEY, CA (UroToday.com) - An increasing number of published studies have linked polyphenols, the natural plant-based phytochemicals found in healthy foods, with a lower risk of chronic illnesses such as dementia, high cholesterol, arthritis, skin aging, macular degeneration, and more recently, cancer. Although, the benefits of boosting the diet with polyphenol-rich whole food supplements such as green tea, broccoli, turmeric, and pomegranate have been investigated in small phase II studies, this combination has never been evaluated within an adequately powered RCT. The NCRI trials committee chose these foods as they originate from separate categories (spice, herb, fruit, vegetable), with a study hypothesis that their diverse polyphenol profile would have synergistic action whilst avoiding the accumulation of one particular phytochemical. Each ingredient has also demonstrated anti-oxidant activity, protecting cells from carcinogenic exposure, as well as direct anti-neoplastic activity within previous laboratory or phase II trials:
Green Tea, rich in epigallocatechin gallate, blocks ornithine decarboxylase resulting in reduced proliferation, angiogenesis, and de-differentiation in cancer cell lines. A meta-analysis of 5000 women showed that regular consumption had reduced breast cancer recurrence. Phase 2 studies have demonstrated reduced PSA in prostate cancer.
Pomegranate, rich in ellagic acid which in cancer cell lines reduced proliferation, apoptosis and adhesion. In 3 phase II studies it prolonged PSAdt and reduced oxidative stress.
Turmeric, rich in capsaicin reduced growth, invasion, migration, and TK activation of EGFR. In cancer stem cells it prevented progression to prostate, bowel and breast cancer but had no affect on normal stem cells. In humans has demonstrated Cox-I anti- inflammation effects.
Broccoli, rich in iothiocyanate in cell lines slows growth and promotes apoptosis. In humans, after regular consumption it alters genetic signature, down regulates promoting genes, and up regulates cancer suppressor genes.
Methods: 203 men, aged 53-89 years (average 74 years), with prostate cancer (95% Gleason 6/7, 5% >7), 59% managed with primary active surveillance or 41% with watchful waiting (WW) with a progressive PSA relapse following previous radical interventions were randomised to receive a Pomi-T or an identical placebo for 6 months. The randomised process produced no statistical difference in baseline characteristic except the placebo group were slightly older.
Quality assurance: This non-commercial academic trial received peer-reviewed sponsorship from Prostate Action, was designed by NCRI Complementary Therapies Research Committee, adopted by the UK’s NCRN, and was independently audited to ensure its adherence to European Good Clinical Practice Guidelines. The manufacturers performed in-house analyses to ensure authenticity and purity, and a further independent mass spectrometry was performed to confirm purity and well. Statistical evaluation was independent to the trials unit.
Results: Two men from each group of men withdraw before the first 3-month evaluation. Of the remaining 199 men, the primary end point, median rise in PSA in the Pomi-T was 14.7% (95% CI 3.4-36.7%) vs 78.5% in the PG (95% CI 48.1-115.5%). This difference of 63.8% was significant (ANCOVA p=0.0008). 18.6% more men stayed off interventions at the end of the trial in the Pomi-T group. There was no significant difference between any of the pre-determined subgroups.
Secondary end points: There was no effect on average serum sex hormone analysis: Testosterone 13.4 nmol/l (normal range: 9-29), FSH 9.2 iu/l (normal range: 2-12), LH 7.4 iu/l (normal range: 2-9). There was no effect on cholesterol, INR, or BP amoung men taking warfarin or ramipril. MRI scans, taken routinely as part of their AS protocol, were retrospectively evaluated. 35% had no visual disease, 15% had progressive disease with significant rises in PSA (removed from trial), 50% had visual disease with no progression, and no man remaining on Pomi-T had MRI defined progression. Conclusions in this cohort of men with prostate cancer, managed with AS or WW, after 6 months of Pomi-T:
- demonstrated statistically significant short term favourable effect on the percentage rise in PSA compared to placebo
- was well tolerated without any significant adverse effects or concomitant drug interactions
- resulted in significantly more men remaining on AS or WW, avoiding the toxicities and expense of medical interventions
- disease on MRI was linked with PSA dynamics
What is next for Pomi-T? In order to aid in the evaluation of the effects of Pomi-T or other lifestyle interventions, an iphone app (PSAcalc) has been developed which calculates and plots PSA-doubling time changes as well as absolute PSA (see cancernet.co.uk). The authors are working with the Institute of preventative Medicine and PROVENT team to include this supplement in further national study involving men with prostate cancer. Two further RCTs involving individuals with other cancers are also in design in South Africa and New York, and in the UK a study will evaluate its benefit for relief of joint pains pending negotiations with the main manufacturers (www.pomi-t.com).
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Written by:
Robert Thomas,1, 2, 3 Madeleine Williams,1 Harbinda Sharma,1 Assim Chaudry,2 and Pat Bellamy3 as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
1The Primrose Research Unit, Bedford Hospital, Bedford, MK42 9DJ UK
2Oncology Department, Addenbrooke’s Cambridge University NHS Trust, Cambridge, CB2 2QQ UK
3Department of postgraduate Medicine, Cranfield University. Cranfield MK42, UK
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