Pulse and Rotation
Letter for Doctors & Patients October 2001
Probiotics: Viable single or mixed culture of microorganisms
which when applied to animal or man, beneficially affects their
host by improving the properties of the indigenous microflora.1
Over the last decade, other definitions have been applied
to the term, but they all basically agree, at least in general
terms. The increased interest in defining exactly what probiotics
are has arisen, in large part, from the increasing demand for
probiotics. Probiotics have found application in a wide variety
of products including, yogurt, dietary supplement capsules,
tablets, milk, butter, cheese, salami, soy sauce, sour dough.2
They are even being used as antimicrobials for the poultry
industry due to their ability to inhibit salmonella growth
Probiotics are clearly here to stay and the market, despite
its incredible growth over the last few years, is still in
its infancy. Presently, there are identifiable trends in the
use of probiotics. These trends can be generalized as a heightened
awareness of differing quality in the organisms. From the manufacturing
side, that includes such things as production of well-document,
clinically-backed strains, ability to survive gastric acid
and bile salts, adherence, long-term stability. Also issues
such as milk/casein-free are important for products addressing
From the end-user or medical perspective all the above are
important, but there are additional considerations. The additional
considerations all boil down to; what is the best way to use
the probiotics in the most clinically efficacious manner?
Ten years ago, most probiotic
products contained either Lactobacillus acidophilus or Bifidobacterium
lactis (bifidum). If one was
really lucky, they could find a combination of the two and
possible a couple of yogurt strains (i.e., Lactobacillus bulgariucus)
thrown in. Many of these contain only a few hundred million
viable cells at the time of manufacture. While that may sound
like a lot of organisms, especially when we are conditioned
to think of bacteria as being "bad", current data
tells us that those numbers were probably far too low to be
doing very much good. At least in the short-term, therapeutic
application of the probiotics.
As more and more data comes in, it is becoming apparent that
at least a billion organism are need per dose to achieve any
real clinical significance. In a recent study, ten billion
Bifidobacterium in milk per day were given and immune markers
measured.5 A significant increase in phagocytic activity of
granulocytes was observed.
In a randomized, double-blind placebo controlled study, the
prophylactic effect of probiotics on infections in neutropenic
patients undergoing cytoreductive chemotherapy for acute leukemia
was studied. Thirty patients (35 episodes) were included in
the study. The lactobacilli were given as two capsules thrice
daily for 30 days, starting at the initiation of chemotherapy.
The occurrence of fever was significantly (P = 0.033, Mann-Whitney
rank sum test) postponed from a median time of 8 days to 12
days. Capsules contained 50/50 Bifidobacterium lactis/lactobacillus
acidophilus containing 4billion / capsule.6
In addition to immune parameters, the reduction of circulating
ammonia has also been observed by Deguchi et al, using 5 billion
organisms of either B. lactis or B. breve in caecal contents.7
They also observed a corresponding drop in the pH of the caecal
contents. This lends support for the use of probiotics in detoxification
protocols, which has been reported elsewhere.8
Probiotic supplementation has
been demonstrated to be very safe and effective for a wide
variety of disturbances including
antibiotic side effects, diarrhea/constipation, lactose malabsorption,
and cholesterol reduction. Dosages ranging from one to almost
500 billion organism have been used without complications.9,10
Current trends seem to indicate a range of 10-100 billion live
organisms as being efficacious for the variety of conditions
mentioned above. At least two different companies have "high-dose" products
on the market with 20 and 30 billion organisms per capsule.11,12
These products should serve as a portent for the market as
they were both originally designed for different markets, the
environmentally challenged and autism (and down syndrome),
respectively. These are excellent demonstrations of two principles
that are developing. First, is a need for high-dose probiotics
to treat selective conditions. Second, is the need for a variety
What we are learning is while a low-dose run-of-the-mill L.
acidophilus (providing it is well produced) can be great for
a general maintenance program, often times a much higher dose
is required to achieved clinical significance. Additionally,
it is becoming increasingly apparent that the inclusion of
other strains, such as Lactobacillus rhamnosus or Lactobacillus
plantarum (an exciting up-and-coming star) can have a dramatic
effect.13-15 The inclusion of multiple strains is not only
beneficial for the specific conditions, but also may play another
important role in the application of probiotics.
Increasingly, with the use of mono- or bi-strain products,
there are reports of a reduction of clinical effects seen over
time. For instance, in the case of autism, a child that pre-treatment
had either diarrhea, or some other gastrointestinal distress,
improves dramatically when first supplemented with those products.
The child starts producing well-formed stools on a regular
basis. However, in some cases, the child can undergo a reversion
to the previous distressed state. Two approaches seem to have
found a resolution for this consternating phenomenon.
First, is the "pulse" method. Here, when the clinical
effect begins to change, the physician can cease the probiotic
supplementation for a period of time, followed by a repeat
application. The body appears to be "resetting" itself
after cessation of the therapy. During this period, changes
are occurring in the gastrointestinal tract that may be making
the local environment more hospitable to the probiotics. Additionally,
there are certainly changes in the immune functioning of the
It is well established that the intestines are a major source
of immune competence.16 It is also well established that there
are genetic elements that respond to heavy metals, and in particular
to mercury.17 What may be happening is that upon initial exposure
to the probiotics, the gut associated immune system is mobilized
and may be attacking the probiotics. After withdrawal of the
probiotics, the immune reaction tapers off until any subsequent
exposure. This is not a bad thing and can be used efficaciously
by pulsing the probiotics. Also, a variation on that theme
can be employed. That is to say, instead of withdrawing all
probiotics for any period of time, a substitution of another
product, which contains different organisms would seem the
logical next step.
For instance, if a product
that just L rhamnosus is being used and the above condition
presents, a product of just Bifidobacterium
could be employed. If a single strain of Bifidobacterium is
used, and again the same situation occurs, then a third product
with several strains could be administered. It most certainly
is going to have to go on a case-by-case basis, according to
the physician's observations. In the foreseeable future, there
will be products designed specifically to address the issue
in this way. This "probiotic rotation" will be applicable
in a variety of situations.
As can be seen, the area of probiotics is still in its infancy.
This neonate is soon to grow-up, however, as major pharmaceutical
companies enter this exciting and efficacious area of healthcare.
As clinical data from the application of probiotics to conditions
such as autism, down syndrome, cancer, lactose intolerance,
etc, comes to light, consumer/patient demand awareness of the
importance of these organisms will concomitantly increase.
With that, we can expect better products, tailored to specific
conditions to also be developed.
1. Havenaar & Huis in 't
2. Mitsuoka, T. 1978Intestinal Bacteria and Health.Iwanami
Shoten. Tokyo. Japan.
3. Brudnak, MA 2001 Probiotics
and Autism. Townsend
Letter for Doctors & Patients.April.
4 Wieder Nutrition International. Personal Communication.
5. Schiffrin et al, 1995. Journal of Dairy Science, 78: 491-497.
7. Deguchi, Y. et al 1994.Microbial Ecology In Health and
Disease Vol. 6:85-94.
8. Brudnak, MA. High-dose Probiotics
for Detoxification Townsend
Letter for Doctors & Patients.
6. Presented at The Seventh International Symposium on Infections
in the Immunocompromised host. June 21-24, 1992, Boulder, Colorado,
9. Hove H, Nordgaard-Andersen I, Mortensen PB. Effect of lactic
acid bacteria on the intestinal production of lactate and short-chain
fatty acids, and the absorption of lactose. Am J Clin Nutr.
10. Gaon, D., et al. Lactose digestion by milk fermented with
human strains of Lactobacillus acidophilus and Lactobacillus
casei. 1995. Medicina (Buenos Aires), 55:237-242.
10. Kirkman Laboratories, Wilsonville OR. USA. Personal Communication.
12. Klaire Laboratories, Solana Beach CA. USA. Personal Communicatoin.
13. Mangiante G, Colucci G, Canepari P, Bassi C, Nicoli N,
Casaril A, Marinello P, Signoretto C, Bengmark S. Lactobacillus
plantarum Reduces Infection of Pancreatic Necrosis in Experimental
Acute Pancreatitis. Dig Surg. 2001;18(1):47-50.
14. Philippe R Marteau, Michael
de Vrese, Christophe J Cellier, and Jürgen Schrezenmeir
Protection from gastrointestinal diseases with the use of
probiotics . Am J Clin Nutr 2001 73:
430S-436S. [Abstract] [Full Text]
15. Gregor Reid Probiotic agents to protect the urogenital
tract against infection Am J Clin Nutr 2001 73: 437S-443S.
16. Brudnak MA, Application of Genomeceuticals to the Molecular
and Immunological Aspects of Autism. Med Hypotheses. In Press.
17. Badou A, Savignac M, Moreau M, Leclerc C, Pasquier R Druet
P, Pelletier L. HgCl2-induced interleukin-4 gene expression
in T cells involves a protein kinase C-dependent calcium influx
throughL-type calcium channels. J Biol Chem. 1997 Dec 19;272(51):32411-8.
Please feel free to contact
Mark A. Brudnak PhD, ND
957 Lake Shore Road
Grafton, WI 53024