Gregor Reid, Chair, Human Microbiology and Probiotics, Lawson Health Research Institute, London, ON
Feature
Evidence-based probiotics
I
s there a case for using an evidence-
based approach when assessing the role
of probiotics in the various applications
which companies promote? In fact,
by definition probiotics need to have been
shown to confer a health benefit on the host
simply to be called probiotic (FAO/WHO,
2002). Thus, in some ways the question is
redundant. However, as with most things in
life, its not that simple.
In Canada, the use of the word probiotic
is not yet adequately legislated or controlled.
In theory, you could have a probiotic smart
car. Thankfully, we havent stooped that low,
but there are still too many companies adding
bacterial strains to different product formula-
tions (orange juice, chocolate, cereal, milk,
bread, frozen yogurt, etc.) and branding the
product probiotic. The simple inclusion of
bacterial strains, even Lactobacillus or Bifido-
bacterium, that are widely used in probiotic
products, does not make every product probi-
otic. As the Food and Agriculture Organiza-
tion/World Health Organization (FAO/WHO)
Guidelines and many subsequent publications
clearly state, the product becomes probi-
otic by proving that it confers health benefits
above and beyond placebo effects. The onus
is on the company to show this evidence for
the application being promoted.
The list of products available in Canada,
and with scientific and clinical evidence of
conferring benefits, is growing. The follow-
ing is not necessarily an exhaustive list of
proven products (based on a table in Reid et
al. 2008), but papers on these products can
be found on PubMed (http://www.ncbi.nlm.
nih.gov/pubmed/).
Health Canada is making some positive
steps in regulating the probiotic market. In
October, 2009 the agency stated When mak-
ing any probiotic claim, the manufacturer or
importer of the product should have docu-
mentation supporting the identification, safe-
ty, viability, concentration, and stability of
the probiotic strain(s) added to the food prod-
uct. The strain(s) must be written with a
registered strain number, for example Lac-
tobacillus acidophilus xyz. Unfortunately,
the agency then provided a very generic list
of bacterial species, such as Bifidobacterium
adoloscentis which is not a probiotic, as there
Volume 17/Issue 2 Summer 2010
is no strain number, nor any evidence from gut flora. What is a healthy gut flo-
clinical trials that this species is probiotic. ra? Nobody knows. How is it defined?
Furthermore, Health Canada has ap- (iv)Provides live microorganisms that
proved four general claims: contribute to healthy gut flora. Same
(i)Probiotic that naturally forms part of problem as in (iii).
the gut flora. The term flora should be Thus, companies are allowed to make
replaced by microbiota, and no probi- generic claims when there are no good sci-
otic remains in the gut or integrates with entific methods to prove the basis for the
the existing microbiota. claims. Instead, if a company reports that
(ii)Provides live microorganisms that Lactobacillus acidophilus, for example, is
naturally form part of the gut flora. found in the stool, it might argue that this
Same problem as in (i).
(iii)Probiotic that contributes to healthy Continued on page 23
Product Microbial content Basis of clinical evidence
Saccharomyces boulardii lyo
Florastor, Medical Futures Inc. Clinically shown to treat and
Proven Probiotic help prevent diarrhea in
adults and children.
DanActive (Actimel) Lactobacillus casei DN 114-001 Clinically shown to reduce
milk drink, Danone Proven Probiotic duration of colds and
diarrhea
Activia yogurt, Danone Bifidobacterium animalis Clinically shown to improve
DN 173-010 Proven Probiotic transit time (regularity)
VSL#3, Seaford Pharma 8 strains of lactobacilli, Clinically shown to help
bifidobacteria and streptococcus prevent pouchitis and retain
Proven Probiotic remission, and is an adjunct
treatment for mild to
moderate UC (ulcerative
colitis)
Fem-Dophilus, Jarrow Lactobacillus rhamnosus GR-1 Anti-inflammatory, anti-yeast
Formulas; RepHresh Pro-B and Lactobacillus reuteri RC-14 effects and helps resolve
Lil Drug Store* Proven Probiotic bacterial vaginosis
Bio K Plus Lactobacillus acidophilus Reduced incidence of
CL1285 and L. casei CL antibiotic associated
Proven Probiotic diarrhea
Align, P&G (purchase on line) Bifidobacterium infantis 35624 For relief from irritable
http://www.aligngi.com/index.shtml Proven Probiotic bowel disease
Tu Zen, Lactobacillus plantarum 299v Sold in capsules but clinical
Ferring Pharmaceuticals Potential Probiotic data comes from studies in
drinks and fermented
oatmeal gruel.
Jamieson Advanced Lactobacillus acidophilus LA-5, Sold in capsules but data on
4-Strain Probiotic Bifidobacterium lactis BB-12, capsule studies not easy to
Streptococcus thermophilus and find. Data for milk studies shows
Lactobacillus delbrueckii ssp. benefits against diarrhea
Bulgaricus and other gut ailments.
Potential probiotic
*Note: I helped develop this product and declare a conflict.
21
 Viewpoint
Continued from page 22
Designer Medicine. Dr. Christopher Frank
has written an article in this issue of Advo-
cate that discusses polypharmacy as it relates
to the elderly. Also in this issue is an article
by Dr. Lea Velsher, medical geneticist. She
discusses how our genome and epigenome
can help us to predict how we will respond to
several different medications. Some authors
see this as having a huge impact in the treat-
ment of some disorders.
In summary: The research, develop-
ment, and marketing of drugs have made
multi-national companies into multi-billion
dollars a year businesses. The never-ending
search for the next blockbuster drugs has
raised several questions. In some cases it
appears that what has been previously con-
sidered to be variations of otherwise normal
behaviour, requiring no medication, is now
having drugs promoted for their treat-
ment.
Another issue that has been raised is that
some new, expensive drugs have subsequently
been shown to be no better than the drugs they
were intended to replace - in some cases, place-
bos have been shown to be almost as effective
as the drug. Also, ethical issues have arisen in
how products are advertised and distributed.
Last but not least, there is concern that
a potential conflict of interest may exist
between some of the academics who assess
the efficiency of the new drugs and the pos-
Feature
Continued from page 21
proves that their product with a Lactobacil-
lus acidophilus is part of the gut flora. What
should occur is the company uses molecular
techniques to specifically identify the strain,
then at the very least show that this strain is
present several weeks after its ingestion has
ceased. This implies at least survival and
likely replication in the gut, although it still
does not prove colonization.
As noted from the table, each product has
benefits which for the most part are not shared
by any (or many) other products. Thus, the
evidence is specific and means that people
intending to purchase a probiotic product
should consider the intended benefit. A person
traveling to a place where there is a risk of
diarrhea would choose one product, while a
Contact Dr. Reid at: 268 Grosvenor Street, London, ON N6A 4V2, Canada Tel: 519-646-6100 x 65256 Email: gregor@uwo.ca
Volume 17/Issue 2 Summer 2010
sible financial interest that they may have
with the companies.
References
1
The race for the next great sex drug,
CTV Media Site, November 13, 2008;
www.ctvmedia.ca/releases/release.
asp?id=10920&num
2
Big Pharma: Its Enough to Make You
Sick, A review of Selling Sickness, Dr
Abby Lippman (see appendix1)
3
Congress of the European Society for
Sexual Medicine, 2009
4
Side Effects: A Prosecutor, a Whistle-
blower and a Bestselling Antidepressant
on Trial, Dr. Alison Bass (see appendix)
5
PLoS One, Dr. Kevin Weinfurt, 3(5),
e2128, 2008
6
Globe and Mail, Thursday, March 5,
2009 (Life Section)
A call for the regulation of prescription
7
mining, Dr. D. Zoutman, B. Douglas
Ford, Assil R. Bassili, Canadian Medical
Association Journal, 2000;163(9):1146-8
The confidentiality of patient and physi-
8
cian information in pharmacy prescrip-
person with gut regularity issues would
choose another. Someone who does not like
or cannot tolerate milk products would likely
select a capsule or powder formulation.
It is easy to search PubMed and find out
what probiotic strains have been studied.
Company websites can be helpful, but too
often they cite generic reviews, studies with
another product (which cant be translated to
the product they are selling), or unpublished
internal reports. The key question to ask your-
self, your pharmacist, or someone in a health
food store is What scientific data have been
published on THIS product? Do not read-
ily accept an answer such as Ive had a few
people say this really helps them, but there
are no published studies on it. The perceived
benefits might have been a placebo effect, so
whilst personal testimonials are comforting to
tion records, Dr. D. Zoutman, B. Douglas
Ford, Assil R. Bassili, Canadian Medical
Association Journal, 2004;170(S)
9
Dr. Grande, Archives of Internal Medi-
cine, May 2009
10
Ibid
11
PLoS, Dr. Susan Chimonas and Dr. Je-
rome Kassirer, May, 2009
Appendix
1
Selling Sickness: How the Worlds Biggest
Pharmaceutical Companies Are Turning
Us All into Patients; Ray Moynihan and
Alan Cassels, Greystone Press.
2
Side Effects: A Prosecutor, a Whistle-
blower, and a Bestselling Antidepressant
on Trial, Alison Bass, Algonquin Books
of Chapel Hill.
3
Our Daily Meds: How the Pharmaceu-
tical Companies Transformed Them-
selves into Slick Marketing Machines
and Hooked the Nation on Prescription
Drugs, Melody Petersen, see www.our
dailymedsthebook.com.
4
Shyness: How Normal Behavior Became
a Sickness, Christopher Lane, Yale Uni-
versity Press.
read, scientific rigor is the ultimate credential
for a products effectiveness.
Literature Cited
FAO/WHO 2002. Regulatory and clini-
cal aspects of dairy probiotics. Food and
Agriculture Organization of the United
Nations and World Health Organization
Expert Consultation Report. Food and
Agriculture Organization of the United
Nations and World Health Organization
Working Group Report. http://www.fao.
org/ag/agn/agns/micro_probiotics_en.asp
Reid G, Anukam K, Koyama T. Probi-
otic products in Canada with clinical
evidence: what can gastroenterologists
recommend? Can J Gastroenterol. 2008
Feb; 22(2):169-75
23