June 20, 2013
Journal of Clinical Oncology
TAKE-HOME MESSAGE
- Do polyphenol-rich foods have anti-neoplastic effects in men with prostate cancer?
- A clinical trial of 200 men with localized prostate cancer were randomized to a supplement containing pomegranate seed, green tea, broccoli, and turmeric vs placebo for 6 months.
- Results are promising in terms of prostate-specific antigen level, at least for the short-term. Trials studying longer-term effects are warranted.
Primary Care
Written by David Rakel MD, FAAFP
Often we extract what we believe to be the active ingredient from a plant, isolate it, put it in a pill, and give it in high doses. This can be effective but also potentially harmful, as is the case with high-dose vitamin E increasing all-cause mortality.1
This study looked at how a combination of food nutrients may work better when used together to create a therapeutic synergy. The “super foods” used were pomegranate seed (fruit), green tea (herb), broccoli (vegetable), and turmeric (spice).
Take green tea, for example; it is important that the whole leaf be used to ensure inclusion of all four types of catechins, and you get all of them when you drink a cup of green tea. In a study of 60 patients with prostatic intraepithelial neoplasia treated with 200 mg of mixed green tea catechins three times daily, only 3% progressed to prostate cancer in the green tea group vs 30% in the placebo group.2 Cruciferous vegetables like broccoli, kale, cabbage and Brussels sprouts have four leaves that cross (cruc = cross). These vegetables contain sulforaphane and indole-3-carbinol, which are thought to have “cancer fighting” properties. A study showed a 59% reduction in prostate cancer progression in men who ate these vegetables regularly.3 Turmeric, the yellow spice found in curry (curcumin) is known to have COX inhibitory effects. COX inhibition reduces inflammation and has been found to regulate the expression of p53 tumor-suppressor protein in prostate cancer.4 I often use a COX inhibitor (1000 mg two times a day) for people who have arthritis pain but cannot tolerate NSAIDS. Throw some pomegranate seed into the mix—it contains lycopene, a nutrient found in any red fruit or vegetable—and you have a combination that reduced the level of prostate-specific antigen in men with prostate cancer by almost 68% compared with placebo. Even more importantly, more men randomized to the food nutrients group were retained in the “watchful waiting” group—fewer needed to transition to more aggressive therapy.
After this study was presented, the supplement (POMI-T) sold out. There is no magic to this product, which contained about 100 mg of each food. You get more than this by drinking a cup of green tea or eating 2 to 3 flowers of broccoli. And the benefit of eating these foods is the potential synergy of combining them with other healthy foods, with people you enjoy and a glass of red wine with a chunk of dark chocolate for dessert. More polyphenols. More synergy. More fun!
1. Miller ER, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Int Med. 2005;142(1):37–46.
2. Bettuzzi S, Brausi M, Rizzi F, et al. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 2006;66(2):1234–1240.
3. Richman EL, Carroll PR, Chan JM. Vegetable and fruit intake after diagnosis and risk of prostate cancer progression. Internat J Cancer. 2012;131(1):201-210.
4. Creţu E, Trifan A, Vasincu A, et al. Plant-derived anticancer agents – curcumin in cancer prevention and treatment. Rev Med Chir Soc Med Nat Iasi. 2012;116(4):1223-1229.
Summary
Background: Polyphenol-rich foods such as pomegranate, green tea, broccoli and turmeric have demonstrated anti-neoplastic effects in cell lines and animal models. Although some have been investigated in small phase II studies, this combination had never been evaluated within an adequately powered nationally certified RCT.
Methods: 203 men, average age 74 yrs, had localised prostate cancer, 59% managed with active surveillance and 41% with watchful waiting (progressive PSA relapse following previous radical interventions). They were randomised to receive a b.d. oral capsule containing a blend of pomegranate seed, green tea, broccoli and turmeric or an identical placebo for 6 months. The groups were statistically balanced in terms of gleason grade, body mass index (BMI), treatment category and fasting cholesterol although there was a difference in average age at baseline; 71.8 yrs in the food supplement group (FSG) versus 76.4 years in the placebo group (PG). Four men withdrew after randomisation.
Results: The median rise in PSA in the FSG was 14.7% (95% CI 3.4-36.7%) versus 78.5% in the PG (95% CI 48.1-115.5%) (63.8% difference, ANCOVA analysis of covariance, p=0.0008). 46% of men had stable or lower PSA at trial completion in the FSG versus 14% in the PG (32% difference, chi2, p=0.00001). There were no significant differences in PSA% change within the predetermined subgroups (age, gleason grade, treatment category, BMI). There were no differences in cholesterol, blood pressure, blood sugar or c-reactive protein. 24% men recorded events in the FSG and 34% in the PG (non significant). Mild gastro-intestinal effects were (17%) in the FSG but 8% of these reported an improvement in stool quality.
Conclusions: This study found a statistically significant short-term favourable effect on the percentage rise in PSA in these men managed with observation following intake of this specific food supplement. Although many men would see this as useful addition to their self help strategies, future trials should look at the longer-term clinical benefits particularly in terms of preventing medical intervention.