Prostate cancer and gut health – The influence of boosting phytochemical rich foods plus or minus lactobacillus probiotics on symptoms and progression – a randomised, double-blind placebo-controlled trial.
ISRCTN: 81939514 | REC: 23/EM/0190 | IRAS: 321309 | Thomas R et al ASCO GU 2025
Authors: Prof Robert Thomas*+#@, Dr Madeleine Williams*, Dr Jeffrey Aldous+, Prof Stacey A. Kenfield%, Prof Robert U. Newton!, Dr Anita Mitra@, Dr Simon Russel# and Mr Zahoor Fazili*.
# Addenbrooke’s, Cambridge University, Hospitals, UK
* Bedfordshire Hospitals, UK
+ Department of Nutrition and Sports Science University of Bedfordshire, UK
% Depart of Urology & Biostatistics, University of California, San Francisco (UCSF), USA
! Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia
@University College London Hospital (UCLH), London, UK
Background:
Boosting phytochemical rich food intake and enhancing gut health are increasingly being recognised as influencing prostate cancer (PCa) incidence and progression via their effect on inflammation, oxidative stress and immune surveillance. Murine models have shown that improving the gut microbiome slows cancer progression. In clinical studies, enhancing phytochemical intake has previously been shown to slow Prostatic Specific Antigen (PSA) progression in men with indolent PCa. Since then, evidence of a potential benefit for further ingredients such as cranberry as well as methods to safely enhance and standardise phytochemical levels have evolved, hence the rationale for using this blend in this evaluation. In addition to their direct anti-cancer properties phytochemicals are also potent prebiotics which work in synergy with lactobacillus probiotics and prebiotics including inulin and vitamin D. Until now, no study has evaluated the combination of phytochemical rich foods and probiotics in men with PCa, hence the rationale for this study.
Methods:
212 men with PSA progressing PCa (average age 74.5 years) managed with surveillance were given a Phytochemical Rich Supplement (PRS) containing whole cranberry, green tea, pomegranate, turmeric, broccoli and ginger fortified with extracts from the same plants. Men were then randomised (1:1) to receive either a placebo (P) or a Probiotic blend (PB) of 5 lactobacillus probiotics with prebiotic inulin and vitamin D for 16 weeks.
No men were taking any therapeutic hormones or androgen deprivation therapy (ADT). They all stopped any other over the counter (OTC) supplements except Vitamin D, which was allowed. Baseline demographics including age, Gleason grade, tamsulosin intake, Body Mass Index (BMI) and ethnicity were similar in both randomised groups.
Results:
The average PSA rose from 6.0 at 4 months pre-trial to 7.3 at baseline (an average 21.6% rise), then after they all received the PRS, the average PSA dropped to 6.7 (an average 8.9% fall). This 30.5% difference in PSA dynamics was highly statistically significant (SS) (paired t-test p<0.0001) indicating a good response to the Phytochemical intervention.
The change in PSA dynamics amoung men on PRS + probiotic versus men on PRS + placebo was a highly SS 41.7% v 13.4% = 28.3%, (Independent samples t-test p<0.00001). This indicates a further specific benefit from the probiotics on top of the PRS.
Urinary symptoms: The average International Prostate Symptom Score (IPSS) for the entire cohort SS improved from baseline to 4 months 14.1 to 10.5 (difference 3.6, p=0.01).
Erectile Function: The average International Index of Erectile Function (IIEF) for the entire cohort statistically significantly improved from 23.7 at baseline to 26.6 at 4 months (difference 2.9 p=0.01).
Adverse events: Both arms had good tolerance, 9 men (4.2%) had grade 1-2 bloating but conversely 29 men (13.7%) reported improved gut symptoms. 1 man reported a short lasting Grade 1 skin rash in the PFS + P group.
Blood parameters: There was no significant changes in blood sugar, FBC, LFT’s, U&E. There was no difference in testosterone levels at 4 months between the two randomised groups (13.4 v 14.1).
Pre and post MRI were available in 180 men to date. In 9 men the disease was reported to have shrunk, 164 stabilised and 6 worsen. PSA had progressed at a higher than average all these 6, suggesting no PSA masking effect.
Conclusions:
Boosting phytochemical rich food intake, significantly slowed PSA progression, improved urinary symptoms and erectile function in men with indolent PCa. In addition, this is the World’s first double blind RCT to demonstrate that a lactobacillus intervention aiming to improve gut health further reduced PSA progression. Hopefully, these findings will encourage more microbiome related research in men with PCa. Evidence based information, such as this, helps men make informed dietary choices and will be welcomed by men on surveillance, with whom this trial was designed.
Appendix:
Appendix: Thanks to the Cambridge and Bedfordshire Prostate cancer support groups who provided vital support to the design of this study
Trial regulation and authorisation: The phytochemical rich supplements now known as YourPhyto have been specifically made by the UK manufacture’s (Redrose manufacturing Ltd) and supplied to the trial unit at zero cost. The probiotic complex, now known as YourGutPlus was made by Oxford Health Ltd and again supplied at zero cost to the trials unit. No member of the trial committee has any connection to the manufacturers, who will ensured the supplements comply with international food standards including heavy metal, pesticide and microbial analysis. The study has been peer reviewed and approved by the national ethics (IRAS) committee, approved by The Health Research authority and Bedfordshire Hospitals R&D department. There are no intellectual patent issues as these are common ingredients which are all already commonly available over the counter.
Lay Summary:
