A randomised double blind placebo controlled trial of a polyphenol rich dietary food supplement in men with prostate cancer
The Pomi-T Study
This randomised controlled trial has now completed. The results were announced as a full oral presentation at the world's largest and most prestigious cancer conference ASCO in June 2013. The full paper was published in a Nature Journal in 2014.
Further studies involving this supplement are ongoing. In the mean time the manufacturers who supplied this supplement for this trial have now made it available to the public - link to Pomi-T website
The supplement used in this trial had the highest practicable quality assurance, including specific test for authenticity, purify and lack of heavy metal or bacterial contamination of the ingredients. In addition, an independent academic body performed mass spectrometry to ensure no unexpected additives were present. The original manufacturers agreed with the clinical trials committee to continue this high quality assurance programme but unfortunately unregulated copies have since appeared on some UK and international websites. If you are interested in taking Pomi-T we recommend you refer to the original regulated website and avoid discount stores which may not adhere to the same quality assurance.
Background to the study
An increasing numbers 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, arthritis, skin aging, macular degeneration and more recently cancer [Rezai-Zadeh], [Maclarty]. Women with early breast cancer taking higher than the recommended “5 a day” amount of fruits and vegetable have been found to lower their risk of recurrence risk by one third especially if combined with physically activity [Pierce 2009]. Breast cancer recurrence has been demonstrated to be lower amoung women regularly drinking green tea [Ogunleye 2010] or eating foods rich in dietary lignans [Buck 2011], isoflavones and flavanones [Boyapati 2005]. A full scientific review of the evidence for polyphenols and cancer has been conducted by the trials team and can be downloaded free.
Although the benefits of boosting the diet with polyphenol rich whole food supplements for individuals with cancer have been investigated in small phase II studies, they have rarely been evaluated within an adequately powered Randomised Controlled Trials. For this reason, the UK’s government’s clinical trials design committee decided to set up a national trial to investigate whether there are any anticancer benefits. These committee green tea, broccoli, turmeric and pomegranate of chose these foods as they originate from separate categories (spice, herb, fruit, vegetable), hypothesising that their diverse polyphenol profile would have synergistic action whilst avoid 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 [Mclarty, Ogunleye Porrini, Liao].
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 [Retitig, Lansky, Malik, Barber, Rocha, Wang, Pantuck, Carducci, Paller].
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 [Kakarla, Handler, Shah, Zhang, Dorai]
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, up regulate cancer suppressor genes [Gasper, Joseph, Heinen].
Two hundred and three men, aged 53-89 yrs (average 74 yrs), 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 characteristics except the placebo group were slightly older which, if anything would be more advantageous to the placebo group. The power calculation and independent statistical analysis took place at Cranfield University and men were recruited from across the UK. Enthusiasm to enter the study was overwhelming. The trials team completed the quota 10 months ahead of schedule (see graph).
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 independently audited to ensure it adherence to European Good Clinical Practice Guidelines. The manufacturers performed in house analysis to ensure authenticity and purity and a further independent mass spectrometry was performed to confirm purity. Statistical evaluation was independent to the trials unit.
Results: Two men from each group men withdraw before the first 3 month evaluation. of the remaining 199 men, the median rise in PSA in the Pomi-T was 14.7% (95% CI 3.4-36.7%) v 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 (nr 9-29) FSH 9.2 iu/l (nr 2-12), LH 7.4 iu/l (nr 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, no man remaining on Pomi-T had MRI defined progression.
In this cohort of men with prostate cancer managed with AS or WW this study demonstrated 6 months of Pomi-T demonstrated highly statistically significant short term favourable effect on the percentage rise in PSA compared to placebo. It was well tolerated without any significant adverse effects or concomitant drug interactions and resulted in significantly more men remaining on AS or WW avoiding the toxicities and expense of medical interventions. No change in testosterone levels occurred in men taking Pomi-T and disease seen on MRI correlated with PSA dynamics.
Professor Robert Thomas MRCP MD FRCR
Consultant Oncologist, Cranfield University, Bedford & Addenbrooke’s, NHS Hospital Trusts. .
This study was developed with the help of the National Cancer Research Institute Complementary Therapies Clinical studies Design Group.
National Research Ethics (NREC) approval was granted in October 2011. National trials number 11/EE/0314.
This trial was adopted and supported by the UK National Cancer Research Network NCRN
The trial was funded from an unrestricted educational grant awarded by the charity - Prostate Action
Pat Bellamy - Statistician, Cranfield University.
Mr Michael Vogel - Patient representative
Mike Hollingworth - Patient Representative and Chairman, PCaSO Prostate Cancer Network
Alasdair MacSween - Principal Lecturer in Research Governance, Chair of School of Health & Social Care Research Ethics Committee
Sharon Love - Senior Statistician and Head of CR-UK Statistical Support, Centre for Statistics in Medicine, Oxford
Harbinda Sharma - Consultant Urologist Bedford Hospital
Cathryn Woodward - Consultant Oncologist Addenbrooke’s and Bury St Edmonds
Anne Willis - Trials Nurse Bedford Hospital
Primrose Oncology Research Unit
Dr Jeremy Sizer
Head of R&D, Bedford Hospital
Bedford MK42 9DJ, Tel: 01234 792274
Post trial production:
Pomi-T® was manufactured in the UK and now Switzerland, from natural ingredients, to the highest quality assurance standards and EU compliance regulations. Pomi-T is owned by natureMedical and Helsinn Integrative Health.It was supplied to the trial centres in blank bottles together with an identical placebo pills.
The trial centres are unable to supply the supplement to participants outside the trial. Furthermore, during or even after the trial has finished Pomi-T® will not be able to be prescribed by a doctor because it is classed as a food not a drug. The trial centres has no legal or official connection to suppliers of Pomi-T® outside the parameters of this study .The committee of this trial as advised that we signpost where individuals can find more information on Pomi-T® .
To contact the company please see Website: www.pomi-t.co.uk | Email: firstname.lastname@example.org.
What's next for our trials unit
A second evaluation has taken place involving men who have continued to take pomi-t post trial. It specifically addressed the issue of of whether PSA correlated with underlying changes in Cancer size seen on MRI. It involved men followed for up to 2 years on active surveillance.
The results, as shown in the adjacent picture, should a 100% correlation between PSA and underlying disease indicating that the PSA effect on the main Pomi-t trial was unlikely to be just a chemical effect but related to actual prostate cancer itself - read full paper
The next national evaluation of this supplement which is now know as Pomi-t will be part of the PROVENT STUDY. This is lead by Professor Jack Cuzik and Mr Paul Cathcart from the Institute of Preventative Medicine. The first pilot will be vitamin D plus aspirin versus Placebo. Then it will expand to include Pomi-t.
The trials team has now designed a RCT evaluating a polyphenol rich nail balm with the aim of reducing chemotherapy induced nail damage this trial is underway - read more.
The team has also performed two evidence reviews summarising the evidence for polyphenols and exercise. A further evidence review examining the Biology of exercise has been write wth Coventry University and Stacey Kenfield from the University f South California and been submitted to the British Journal of Sports medicine.
They are moving on to evaluate the evidence for a polyphenol rich supplement to improve arthritis and exercise levels.
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