Researchers have shown that a compound derived from broccoli linked to reducing the risk and progression of prostate cancer accumulates in prostate tissue, providing evidence for how the protection may work.
Scientists and clinicians from the Quadram institute and Norfolk and Norwich University Hospital (NNUH) made the finding after carrying out a clinical trial involving patients from Norfolk with known or suspected prostate cancer who volunteered to take supplements ahead of their routine prostate biopsies.
The results, published in the journal Nutrients, answer a key question about how dietary compounds may exert their influence on normal and cancerous tissue in the prostate, by demonstrating that they accumulate to significant levels in the prostate gland itself. This provides more supportive evidence that dietary interventions that provide these compounds could benefit patients with prostate cancer.
Diets rich in cruciferous vegetables such as broccoli, and alliaceous vegetables such as garlic, have been correlated with a reduction in the risk of developing aggressive prostate cancer, and its progression. The protective activity of these foods is thought to be due to the activity of the foods’ breakdown compounds. These compounds are broken down by plant enzymes or our gut bacteria into other biologically active compounds that protect against prostate cancer in studies on cells or in animals.
But how do these experiments translate to what happens in the body after we eat them?
Measurements show that the levels of the compounds circulating in the blood are lower than that typically used in experimental systems, and barely detectable after 24 hours. So, to exert an effect, could these compounds be accumulating in the prostate?
Robert Mills, Consultant Urological Surgeon NNUH and NHS co-investigator, Dr Antonietta Melchini, Human Study Lead at Quadram Institute Bioscience and Tracey Livingstone Urology Research Fellow and Principal Investigator of the ‘Norfolk ADaPt’ study
To answer this question, the “Norfolk ADaPT” trial was established, led by Urology Registrar Tracey Livingstone, as part of her MD research at the Quadram Institute, working with NNUH Urology Consultant Mr Robert Mills, and Prof. Richard Mithen, now based in the Liggins Institute at the University of Auckland. The study was funded by the UKRI Biotechnology and Biological Sciences Research Council and the Prostate Cancer Foundation.
The trial recruited 40 men who were due to undergo prostate biopsies for suspected prostate cancer, or those with known prostate cancer who were under a programme of active surveillance. This means that they have been diagnosed with early, localised, slow growing prostate cancer, and are being regularly monitored to ensure the cancer hasn’t become more aggressive or advanced.
For the ADaPT Trial, the men were asked to take supplements for four weeks before their routine prostate biopsy. The supplements contained either glucoraphanin from broccoli, or alliin from garlic – two compounds associated with protecting against prostate cancer – or a placebo. Neither the patients nor the researchers knew which supplement combination they received.
Transperineal prostate biopsies, where samples of prostate tissue are taken via the skin of the perineum, were taken at the end of the study and then sent to identify and characterise cancerous cells. In addition to the diagnostic samples taken as part of their routine clinical care, eight additional samples were taken from tissue not believed to be cancerous, for researchers to analyse the levels of bioactive breakdown products of the supplements.
The analysis found that consuming the glucoraphanin supplement significantly increased the concentration of its active compound, sulforaphane, in all zones of the prostate sampled. This supports the theory that it can exert a local effect on cancer cells in the prostate in the same way seen in lab experiments. Alliin from garlic was also detected in prostate tissue but not to significantly higher concentrations compared to those who hadn’t taken the garlic supplements, with the exception of one zone, suggesting that the metabolism of compounds derived from garlic are different to that of those derived from broccoli.
Tracey Livingstone, Urology registrar and Principal Investigator of the ADaPt trial, said:
“There is a wealth of evidence suggesting that dietary compounds found in cruciferous and alliaceous vegetables reduce the risk, or progression of prostate cancer. However, the way in which the prostate gland becomes exposed to these active compounds, was until now largely unknown.”
“These exciting results demonstrate for the first time that the bioactive compounds attributed to this link, derived from broccoli in particular, are indeed capable of accumulating within the prostate tissue to significantly higher levels than those consuming a placebo after only a short 4-week intervention.”
“This contributes to our understanding of a potential mechanistic explanation for this link, suggesting that the accumulation of these compounds may result in local protective effects on prostate cells, which may explain the reduced risk of prostate cancer following the consumption of these vegetables.”
“A large cohort of men in the UK are on a programme of active surveillance for low-risk slow-growing prostate cancer, which at present requires no treatment, but may do in the future. Whilst further research assessing the clinical outcome of dietary supplementation on such patients is required, targeted dietary intervention may prove beneficial in such patient groups in the future, or indeed for any men looking to reduce their risk of developing prostate cancer.”
“We wish to thank all the men who volunteered to be involved in this study.”
More work is now ongoing in the Quadram Institute to understand how these broccoli-derived compounds influence prostate cells where they’re now known to accumulate.
Trying to crack this part of the puzzle is PhD student Gemma Beasy. Gemma is funded by The Big C, Norfolk’s Cancer Charity, and with her PhD supervisors and Dr Maria Traka Gemma is studying how the sulfur compounds from broccoli that accumulate in prostate tissue influence the metabolism and genes of the cells.
Reference: Accumulation of Sulforaphane and Alliin in Human Prostate Tissue, Tracey L. Livingstone, Shikha Saha, Federico Bernuzzi, George M. Savva, Perla Troncoso-Rey, Maria H. Traka, Robert D. Mills, Richard Y. Ball and Richard F. Mithen. Nutrients 2022, 14(16), 3263; DOI: 10.3390/nu14163263