Title: The conundrum surrounding the use of natural health products in prostate
cancer patient care
Authors: Jennifer A. Locke1,2 and Emma S. Tomlinson Guns2
1Faculty
of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON
of Urologic Sciences, University of British Columbia, The Prostate Centre
at Vancouver General Hospital, 2660 Oak Street, Vancouver, BC
2Department
Corresponding author: jennifer.locke@utoronto.ca
Introduction
Several questions arise when debating the use of natural health products (NHPs) in
prostate cancer treatment regimes:
What are NHPs?
How do physicians and patients
perceive them? What therapeutic role do they play in the care of prostate cancer patients?
What are some of the issues surrounding NHPs? Most importantly for those prostate cancer
patients who want to take NHPs, how can physicians and regulatory bodies assist in their
decisions as well as the implementation of NHPs into treatment regimes in a safe and
efficacious manner? This article addresses many of these pressing questions.
Natural Health Products defined
Health Canada’s Natural Health Products Directorate defines a natural health product
(NHP) as any of the following: vitamins and minerals, herbal remedies, homeopathic
medicines, traditional medicines such as traditional Chinese medicines, probiotics and other
products such as amino acids and essential fatty acids1.
Perceptions of NHPs
As one would expect with the term “natural health products” many patients view them
as both “natural” and “healthy” and often assume they are safe. Fifty to fifty-two percent of
healthy adults in the United States take NHPs on a regular basis and the distribution of use
1
among this population is dependent on several factors including gender, age, dietary habits,
education level and physical activity2,3. Prostate cancer patients have been studied as a
population regarding their NHP intake and have a greater than average history of supplement
use4. In the prostate cancer prevention trial which was widely reported on in 2008, 85% of
patients poled regularly consumed at least one NHP5 while in Canada and the US 58% and
74% of all cancer patients, respectively, reported use of NHPs2,6.
On the other hand, the endorsement of NHP use among prostate cancer patients from
the physicians’ perspective remains controversial. Eighty-two and eighty percent of clinical
oncologists surveyed in Japan and Brazil, respectively, stated that NHPs were ineffective as
treatments for patients with cancer7,8. Views in North America differ in that many physicians
poled would not boldly state that NHPs are ineffective for their patients; however, these same
physicians were unlikely to recommend NHP use to their patients9. Many physicians attribute
the lack of NHP endorsement to the lack of clinical data to support their safety and efficacy10.
There is an obvious discrepancy between physician and patient perceptions of NHPs.
Evidence for the therapeutic role of NHPs use in prostate cancer patients
Historically, many of our drug therapies stem from naturally sourced tinctures and
concoctions and date back to some of mankind’s earliest records. Basic science and preclinical evaluation of NHPs including lycopene, soy, isoflavins, pomegranate, ginsenosides,
green tea, flax, various vitamins (ie. D and E) and minerals (ie. selenium) and others have
been pursued in context of prostate cancer for several years. Unique to the prostate cancer
field several of these efforts have resulted in the evaluation of NHPs in extensive in vitro, in
vivo studies as well as randomized clinical trials.
2
Data from pre-clinical in vitro and in vivo studies have suggested that lycopene11,12,
pomegranate13,14, green tea15,16, flax17, soy18, vitamin E19, selenium20 and other NHPs have
the potential to display efficacy in treating both locally developed prostate cancer as well as
progressing disease. Unfortunately, data from the randomized clinical trials to date (Table
1)21-27 do not clearly support the early studies or provide definitive evidence for the use of
NHPs in patient’s treatment regimes. All of the prostate cancer trials with positive outcomes
(as determined by prostate specific antigen measurements) outlined in Table 1 result from
small sample sizes except for the SELECT trial, in which efficacy was not demonstrated for
either selenium or vitamin E. Instead, these trials present data sets that are encouraging for
further evaluation of NHPs in more rigorous large-scale randomized control trials. With
Canada’s NHP Research Society’s mission “to facilitate and support meaningful, scientifically
rigorous research”, these large-scale randomized control trials building on those summarized
in Table 1 may be more optimally designed and conducted through collaboration of leading
experts in the field28.
3
Table 1: Clinical trials evaluating NHPs in prostate cancer patients
Pharmacological concerns regarding NHP use by prostate cancer patients
The classic story of grapefruit juice interaction with CYP3A4 metabolizing drugs
leading to death in some instances has highlighted the dangers of patients taking NHPs in
conjunction with other treatments29. Several studies have investigated the interactions of
common drugs for treating prostate cancer patients30-33; however, few have investigated the
interactions between common NHPs and drugs in the same population.
For example,
cytochrome P450’s have been shown to be altered in expression by NHPs such as
polyphenols34, pomegranate35, soy36 and ginsenosides37 and these interactions may interfere
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with the efficacy and safety of drugs targeting these enzymes such as finasteride, dutasteride,
ketoconazole and abiraterone acetate, all of which are currently used to treat patients with
prostate cancer38.
Other studies have also highlighted the possibility of NHP-drug
interactions. A pilot study by Faubert et al. found evidence to suggest that pediatric oncology
patients were on up to 55 potential NHP-drug interacting therapy regimes at any given time39.
Furthermore, in a systematic review of NHP-drug interactions Mills et al. found that potentially
significant drug interactions were observed with garlic, ginseng and St. John wort in cancer
patients40. The authors further concluded that research in this field is limited in number and
scope. These works highlight the potential danger of pharmacological NHP-drug interactions
to prostate cancer patients as well as the need for more rigorous evaluation of these
interactions in pre-clinical and clinical studies.
Regulatory concerns of NHP use in prostate cancer patients
In 2004 Health Canada instigated a new regulatory body, the Natural Health Products
Directorate, with a mandate to provide recommendations regarding product licensing, site
licensing and good manufacturing practices for NHPs.
There have been conflicting
perspectives as to the success of this regulatory body so far.
Health Canada itself has
shown a steady increase in the rate of product licensing due to their new “S.T.E.P.S.” strategy
with already over 10,000 products added to its electronic licensed natural health products
database41. Furthermore, in a study conducted by Laeeque et al. 17 out of 20 Canadian
industrial companies who were interviewed supported the existence of the NHP regulatory
body and were compliant with its recommendations42. Despite these efforts there are several
NHPs that remain unregulated by Health Canada and some health care workers are very
critical of the Directorate’s action to call.
Dr. Yoni Freedhoff recently criticized Health
5
Canada’s NHP Directorate for providing over 119 warnings regarding NHPs in weight loss
remedies but not following up to ban any of these from being sold to Canadians43.
Furthermore, an article published in the National Post this month highlighted the pressure that
the National Association of Pharmacy Regulatory Authorities has initiated on pharmacies to
stop selling unlicensed NHPs despite Health Canada’s Natural Health Products Directorate’s
“S.T.E.P.S.” strategy to have all of the NHPs on its waitlist evaluated for licensing by March
201044.
These criticisms attest to the challenges of not only ensuring that all NHPs become
regulated but also for regulations to be enforced and understood by the public in order to
procure safe and efficacious use of NHPs by patients.
Conclusions
There are several studies that need to be undertaken prior to our implementing
treatment regimens including use of NHPs by prostate cancer patients.
Until these are
conducted the current overall physicians’ hesitant perspective of NHP use among the patient
population remains justified.
Statistically 50-85% of prostate cancer patients already
subscribe to NHPs5 and they are becoming even more popular among this patient population
through support group attendance and disease characteristics (ie. Prostate cancer is a
relatively slow progressing disease and thus patients have more time to contemplate NHP
use)45. With this incongruent perspective between patients and their attending physicians
regarding NHP use the danger of potential drug-NHP interactions without physician
surveillance may become a common reality. To avoid this preventable issue we suggest
efforts at several levels: 1) at the regulatory level Health Canada’s Natural Health Products
Directorate should continue to strive for efficiency in evaluating the numerous NHPs on its
waitlist, provide the public with easily accessible electronic information regarding all NHPs
6
and aim to enforce the restriction of the sales of products that fail to meet these guidelines, 2)
at the research level, with the aid of the NHP Research Society, the design of randomized
control trials of NHPs for prostate cancer should include the evaluation of conventional
therapies concurrently used by the patient population in order to establish caution regarding
potential drug interactions with them as follow-up to trials evaluating the NHPs themselves for
efficacy and safety and 3) at the primary care level physicians and patients should keep an
open mind with a “safety first” approach to NHPs in their individual care and stay current
regarding the NHP research literature and Health Canada’s electronic information database.
Only with these issues in mind can discussions among patients and their attending physicians
regarding NHP use in their treatment regimes actually yield better and safer care.
7
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