Study: Chocolate Eclairs to Treat Prostate Cancer?

reference

Cipolla BG, Havouis R, Moulinoux JP. Nutritional therapy with a polyamine-reduced diet (PRD) in patients with hormone-refractory prostate cancer.Biomed Pharmacother. 2010;64(5):363-368.

design

The study enrolled 42 volunteer patients with hormone-refractory prostate cancer (HRPC). The intervention group (n=26) adhered to a polyamine-reduced diet. They also underwent partial intestinal decontamination in which they were administered either neomycin or nifuroxazide every two weeks. The remaining 16 participants did not eat a special diet or take antimicrobial medications. Parameters measured include World Health Organization (WHO) performance status, European Organization for Research and Treatment of Cancer (EORTC) pain scale, body weight, blood count and serum proteins.

Key findings

The diet was well tolerated and average adherence was 25 (±24) months. Performance status and pain significantly improved at both 3 months (P = 0.03) and 6 months (P = 0.02) compared to baseline. Of note, the intervention in this study was significantly better when delivered within 9 months of the diagnosis of hormone refractory status. The median cancer-specific survival time for patients who start the diet before the 9-month cutoff is 44 months versus 34 months for those who start later (P = 0.014). The mean cancer-specific survival times for the intervention groups overall compared to the control groups were 36 months versus 17 months, respectively (P = 0.004).

Effects on practice

HRPC is defined by the ineffectiveness of testosterone lowering by castration or antiandrogen medications in controlling prostate cancer growth. The prognosis for these patients is poor because HRPC does not respond well to chemotherapy drugs. The most recent reports of survival data can be obtained from clinical trials for the newly approved antineoplastic agent Sipuleucel-T (Provenge®). This immunomodulatory therapy received FDA approval in April 2010 based on increasing the median overall survival of HRPC patients from approximately 21 months to 25 months.¹

Polyamines (e.g. putrecin, spermidine, spermine) increase cell proliferation and are found in higher concentrations in cancer cells, including prostate cancer.²There are three sources of polyamines: 1) naturally occurring in foods and beverages, 2) production by gut microbes, and 3) intracellular synthesis of polyamines. In the early 1990s, studies in rodents showed that triple treatment with a diet lacking polyamines, intestinal decontamination with antimicrobials, and administration of a drug that blocks the first enzyme in its synthesis (e.g., ornithine decarboxylase) resulted in significantly reduced tumor growth.³The authors of the current abstract published much of the early work in rodent cancer models that repeatedly demonstrated effective tumor inhibition by polyamine deficiency by targeting all three sources of the compounds.^4,5,6,7,8

In this study, the dietary intervention consisted of dividing foods and drinks into three groups. Group 1 was foods with less than 100 nmol/g/ml that could be consumed freely. Group 2 was foods containing 101-200 nmol/g/ml that could be taken 3-4 times per week. Group 3 had a polyamine concentration greater than 201 nmol/g/mL and was prohibited except twice every 7 days.

This nutritional protocol is very different from what we think of as good nutrition. First of all, we assume that the intestinal flora is beneficial; We would rarely encourage taking antibiotics specifically to eradicate them. Secondly, we avoid foods that we would otherwise classify as very nutritious. Group 3 includes, for example, garlic, cabbage, broccoli, tomatoes, almonds, bananas, mushrooms and sauerkraut. Conversely, group 1, the category that could be freely consumed, included pork products, canned vegetable soup, dairy products (except aged cheese), beer, coffee and pound cake. The French authors include chocolate eclairs in the group of foods that can be consumed freely. This diet is significantly different from anything we have routinely recommended to our patients.

There are many more foods on the list and there is no apparent way to memorize the foods. Therefore, a food list must be used to follow the diet.

While one would assume that it might be difficult for patients to stick to restrictive food groups without an obvious connection, diet adherence was extremely high in this study.

While one would assume that it might be difficult for patients to stick to restrictive food groups without an obvious connection, diet adherence was extremely high in this study. Of course, allowing unlimited intake of foods that are considered indulgent by most nutritional standards could explain participants' good compliance.

The intervention in this study targeted the polyamine pool produced by gut microbes and involved partial “gut decontamination” with neomycin or nifuroxazide, consisting of a daily oral dose of the antimicrobial taken every two weeks. The intestinal flora that have been shown to produce polyamines include:Klebsiella pneumonia,Enterobacterspp. AndSerratiaspp.⁹The fact that antimicrobials were an essential part of these patients' therapy reminds us that the foundations of general health, in this case healthy microflora, should not be discarded as too weak or too fundamental to have a profound impact on cancer treatment. Based on our understanding of probiotic growth suppression, it is expected that probiotics would reduce polyamine synthesis in the gut by controlling bacterial growth. In fact, studies with certain probiotics have shown a reduction in polyamines.¹⁰

Ultimately, gut microbiota testing may be warranted in our patients with HRPC, as many of the above organisms would be detected in a thorough stool microbial test. Natural antimicrobials may also be used and the patient retested to assess the success of the treatment. Judicious use of antimicrobial agents is not an option in patients with HRPC given the serious prognosis and relative risk-benefit ratio of the drugs.

This study is small and only includes 42 participants. Nevertheless, the results reached statistical significance, which can only be achieved if the benefit is quite large in small studies. The dietary intervention does not pose any risk of disadvantage because reducing polyamine consumption does not lead to nutrient deficiencies. Therefore, the risk-benefit ratio of dietary intervention is certainly favorable, especially considering the poor prognosis of patients with HRPC. Of note, this particular study was conducted in France, where ethnic differences in food choices make it difficult to directly infer the different food groups given to these patients. Additionally, there was no objective measurement of polyamine status, such as: B. Urine or stool values, which could help estimate the level at which a benefit arises.

In addition to the early rodent studies that confirmed the effectiveness of polyamine reduction, Cipolla and colleagues published a pilot study in 2003 involving 13 volunteers with HRPC.¹¹In this previous study, pain and performance status improved during dietary intervention but returned after diet discontinuation. Prostate-specific antigen (PSA) was also determined. One patient had a reduction of >50%, three patients had a reduction of <50%, and all others had progressive worsening of their PSA. The dietary intervention was significantly shorter, with average dietary adherence occurring at 8 (±7) months. The cancer-specific survival time was 14 (±7) months, which is also much shorter than the current study but may be due to participants discontinuing the diet. Additionally, patients in this previous study began dietary intervention at a later time point after their initial HRPC diagnosis (12 (±8) months) than in the current study (10 (±8) months). The current study suggests that starting a dietary intervention at a later date provides significantly less benefit. Clinically, the use of a low polyamine diet can be considered to “do no harm” and may actually provide significant benefit to patients with HRPC. Probiotics also have a highly favorable side effect profile and should be considered as part of any treatment protocol for HRPC patients. Further examination of intestinal flora and treatment of dysbiotic bacteria should also be considered. The use of drugs that block polyamine synthesis is gaining increasing interest, and future studies could guide their use and dosage in select cancers. As drug development continues to focus on inhibiting polyamine synthesis, it appears that today we can help our patients with nutrition and gut health, particularly our patients with HRPC.

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