AIDS TREATMENT NEWS #224, JUNE 2, 1995
Saccharomyces boulardii is a live yeast widely used in Europe
and elsewhere to treat diarrhea; millions of doses are sold
each year. Recently, with increasing interest in using it for
HIV-related diarrhea, this potential treatment has become one
of the top sellers at some AIDS buyers' clubs, including
Healing Alternatives in San Francisco, and the PWA Health
Group in New York.
A number of published clinical trials (almost all in HIV-
negative persons) have reported apparent usefulness in
preventing or treating diarrhea resulting from various
causes. No one knows how S. boulardii may work, however. It
does NOT seem to kill diarrhea-causing organisms directly;
instead, it may reduce inflammation in the gut, or increase
certain immune responses in the blood. (The latter theory
might explain how one study found S. boulardii may have been
modestly useful for treating acne, even though the yeast did
not leave the intestinal tract.)
Little research has been done with S. boulardii in persons
with HIV. In 1990, French researchers reported on 30 patients
who had four to eight liters of watery stools per day for at
least three months. When they were given three grams per day
of S. boulardii, "fecal output decreased to less than one
liter per day after 48 hours of treatment, and eight days
after the onset of the drug, stools were fully formed."(1)
The following year, the same research team reported on
improvement in 17 patients with HIV and diarrhea; in 12 of
them, the cause of the diarrhea could not be diagnosed. The
average number of stools decreased from 9 to 2.1 per day in
15 days, and there was an average weight gain of 8 kg (17.7
lbs).(2) Neither of these reports were from controlled
In 1992 French researchers reported the results of a placebo-
controlled trial of S. boulardii, in 36 patients with AIDS-
related diarrhea which -- importantly -- was not responsive
to any attempt to treat any known cause of the diarrhea.(3)
On entry into the trial, their average age was 34.8 years,
and their average weight was 58.7 kg (130 lbs). Thirty five
of the 36 patients completed the study. At the end of the
trial, 10 of 18 patients who received S. boulardii were
diarrhea free, vs. only 1 of 17 who received the placebo -- a
difference which is highly statistically significant. Also,
the treatment group gained 2.0 kg (4.2 lbs), while the
placebo group lost 3.1 kg (6.85 lbs); this difference is also
statistically significant. The length of the trial was not
stated in the abstract. As far as we know, this is the only
completed controlled trial of S. boulardii in persons with
The latest medical article anywhere on S. boulardii in HIV-
related diarrhea was published in 1993; it is a case report
of a successful treatment.(4) (Unfortunately, one major
computer database mis-translated the German title into
English as "Saccharomyces boulardii Therapy of HIV Associated
Failures," instead of "Saccharomyces boulardii Therapy of HIV
Associated Diarrhea," giving a completely wrong impression of
the article. But the MEDLINE database generally used in the
U.S. does have the correct translation of the title.)
Until recently, 26 persons with HIV were being studied in
controlled clinical trials in Seattle. During the first two
weeks, some were randomly assigned to receive a placebo. Then
everyone received the drug in decreasing doses, to help
define the safest and most effective maintenance dose.
Unfortunately, this trial was recently stopped -- for
business reasons, not because of any problem with the
treatment. (The sponsor decided to focus on another trial,
testing S. boulardii with antibiotics to prevent recurring
Clostridium difficile diarrhea; all the persons in that trial
must be HIV negative. That study may be finished by the end
of 1995; with luck, S. boulardii could be approved for
preventing C. difficile recurrences in about two years.)
S. boulardii appears to be quite safe; no serious adverse
effects have been found in any clinical trial. But one
theoretical danger is that this yeast could take advantage of
an immune deficiency and cause a systemic infection. Only two
cases of this have been reported, out of perhaps more than a
million people who have used the treatment since it was first
used for diarrhea in the 1950s. Both were probably HIV-
negative (neither had been tested, but neither was being
treated for anything HIV related); both previously had
serious intestinal problems which may have allowed the yeast
to leave the intestine and enter the bloodstream. Both cases
were successfully treated with amphotericin B, a powerful
Clinical Trials for Other Diseases
McFarland and Bernasconi(5) reviewed controlled trials
studying S. boulardii for treatment or prevention of diarrhea
due to various causes not related to HIV. All the results
reported below -- from studies they reviewed, and also from
more recent reports -- are from controlled trials, and are
Three large trials studied S. boulardii for prevention of
antibiotic-associated diarrhea.(6,7,8) This condition can
occur as a side effect of certain antibiotics, which can kill
beneficial organisms in the gut and thus allow an overgrowth
of disease-causing organisms which are normally kept under
control. In all three of the trials, S. boulardii reduced the
incidence of diarrhea by at least 50 percent.
Two other controlled studies showed that S. boulardii
treatment caused about a two-fold or three-fold reduction in
diarrhea caused by feeding with a nasogastric tube.(9,10)
S. boulardii, used with certain antibiotics, has also been
studied for treating C. difficile, a serious intestinal
infection. After several positive case reports and
uncontrolled studies, a major placebo-controlled trial found
that S. boulardii plus antibiotics prevented recurrences of
C. difficile better than the antibiotics alone,(11) but this
could only be established for patients with a history of
recurrences; for those with their initial C. difficile
infection, the difference between the treatment and placebo
groups was not statistically significant. (This failure to
reach statistical significance does not mean that S.
boulardii failed to help in these cases, however; "because of
the small numbers of patients with initial CDD who failed,
there was only a 10% power of detecting a significant
difference; therefore, the result could be a type II
A study in a few patients with Crohn's disease also found
statistically significant benefit of S. boulardii in reducing
Researchers in Austria tested S. boulardii in 3,000 healthy
volunteers for prevention of travelers diarrhea. They gave a
small dose (250 mg per day), a moderate dose (1 gram per day)
or a placebo to persons about to travel to distant regions.
Those who received the treatment, especially the higher dose,
were significantly less likely to get diarrhea.(13)
Studies of S. boulardii for treating ordinary diarrhea in
children(14,15) have shown significant benefit. And in a
trial in adults,(16) the treated group did not have a
significant reduction in the number of stools, but it did
have a lower proportion of watery stools.
S. boulardii does not remain in the intestine after use is
stopped, but is eliminated from the body within several
Research findings differ on whether the yeast needs to be
alive when taken. Even dead yeast may cause some of the
effects which have been observed.
Note: A number of laboratory studies, animal studies, and
uncontrolled human trials, NOT involving HIV in any way, have
suggested that S. boulardii might be helpful in treating
specific kinds of diarrhea or other illnesses. In this
article, we have not reviewed or referenced those studies.
Instead, we have focused on all HIV studies, and on placebo-
controlled human trials for any condition.
At least two different S. boulardii products are available in
AIDS buyers' clubs today.
Laboratoires Biocodex, the French company now running
clinical trials of S. boulardii, markets a lyophilized
(freeze-dried) form of the yeast in Europe, South America,
and Africa, but not in the U.S. It is sold under different
brand names (Ultra-Levure(tm), Thiemann(tm), Perenterol(tm),
Floratil(tm)) in different countries. This product is
available from the PWA Health Group, the largest AIDS buyers'
club in New York (212/255-0520). The three-gram per day dose
used in trials for AIDS-related diarrhea is moderately
expensive; at the PWA Health Group, a four-day supply costs
$36. Biocodex has been selling S. boulardii since 1962.
A competing product sold by Jarrow Formulas is less
expensive; but whether the two products are equivalent is
controversial. The PWA Health Group only carries the Biocodex
version; while Healing Alternatives, the major AIDS buyers'
club in San Francisco, carries only the Jarrow brand; both
can ship the product anywhere within the U.S. Some health-
food stores also sell the Jarrow brand.
With the Biocodex product, each 250-mg capsule is formulated
to contain one billion live yeasts, when tested six months or
more after manufacture. According to Biocodex, their in-house
testing, which has not previously been published, has shown
that there can be as much as a two log (99 percent) drop in
the number of live yeasts in the month after manufacture.
According to Jarrow Rogovin, president of Jarrow Formulas,
this does not happen if the capsules are refrigerated.
With the Jarrow product, each 310-mg capsule is formulated to
contain at least 500 million live yeasts when manufactured;
it may contain more.
We believe that what is most important is to find out whether
or not S. boulardii may be helpful for you -- and that the
best way to do this is to try a test with the more
established Biocodex product, starting with three grams a day
(twelve 250-mg capsules) for at least a week, and preferably
for two weeks. (You might want to order additional supply, to
avoid running out if it does seem to work.) After this test,
if you decide to continue with S. boulardii, you might be
able to reduce the cost by reducing the dose, and/or
switching to the Jarrow product, to see if a less expensive
regimen works as well for you.
How S. boulardii Is Used
Because of the lack of scientific studies of S. boulardii for
persons with HIV, information on how to use this treatment is
highly anecdotal and imprecise, and sometimes contradictory.
According to at least one of the buyers' clubs, most people
using S. boulardii for HIV-related diarrhea start with 3
grams a day, and then work down to 1 gram a day if that is
sufficient to keep the diarrhea controlled. Most people
divide the dose into two or three portions, and take the
capsules with a glass of water after eating. (One
recommendation we have seen says two hours after meals;
another just says after eating.) Some people take a gram a
day or less "for gut regulation or stomach aches," even
without diarrhea. According to the PWA Health Group, there
are no known drug incompatibilities, although it has been
suggested that if fluconazole maintenance is being used, the
two treatments should not be taken at the same time, so that
the fluconazole will be less likely to kill the yeast.
How many people have used S. boulardii for HIV-related
diarrhea? No one knows; the PWA Health Group estimates that
maybe a few hundred people have tried it; and they have
received only one report of a suspected side effect, a rash.
Healing Alternatives was selling about 90 bottles a month
before a recent article in a gay newspaper in San Francisco
increased demand. It has only heard one anecdotal report that
the treatment did not work; all the other reports have been
positive, even with severe diarrhea. (Readers should keep in
mind, however, that negative results are usually the least
likely to be reported; the treatment is probably not working
as well as the existence of so few negative reports might
Perhaps the most serious safety concern with S. boulardii is
that appropriate medical care could be delayed, if people
treat themselves for diarrhea without first getting medical
attention so that the underlying cause of the problem can be
diagnosed and treated, when possible. People should remember
that the HIV-related medical studies cited above were done
with patients whose diarrhea either could not be diagnosed,
or could not be treated by standard means. In many cases,
standard medical care cannot help; this is why new treatments
are needed. But failure to use available therapy for a
treatable condition, such as CMV infection, could lead to
So far there has been very little study of use of S.
boulardii for treating AIDS-related diarrheas. We have heard
that a trial is being conducted in Germany; as far as we
know, this is the only study anywhere of S. boulardii in
persons with HIV. Biocodex may study it again for HIV
diarrhea sometime in the future, but probably not until the
development for C. difficile is complete. It would be very
difficult for anyone to conduct a legal, U.S. study of S.
boulardii independently of Biocodex, either using its
product, or any other; collaboration might be possible,
Sally Cooper, executive director of the PWA Health Group in
New York, informally outlined some research directions she
would like to see, in a private communication to AIDS
TREATMENT NEWS on May 30, 1995:
"Things I'd like to see followed up: use in kids with HIV --
what a great thing to have a safe intervention for kids, who
have wicked diarrhea all the time, and there have been at
least two studies in non-HIV kids; amoebas (also a small
number of promising abstracts, much gentler than Flagyl and
even tinidazole, again safe for kids); various stomach
ailments; thrush and preventing the spread of thrush (as per
animal studies). 80% of the lymph is in the gut, so things
that work specifically in the gut, like S. boulardii and
ketotifen, seem especially interesting. Both are theorized
(and shown in people with ketotifen, but only in animals with
S. boulardii) to improve and maintain mucosal membrane health
in the gut. And people gain weight -- seems like more than
just stopping up the system. I suspect it might be an
excellent maintenance therapy for PWAs with low CD4 counts,
or anyone starting a major course of antibiotics, especially
clindamycin." [Note: tinidazole and ketotifen are drugs which
are approved in some countries but not in the U.S., and are
used by people with AIDS.]
The bad news is that none of this research is likely to start
for years; who would pay for it? But the good news is that a
great many people have used S. boulardii, and some people
have used it for AIDS-related diarrhea over the last several
years; from all we know at this time, the treatment appears
to be exceptionally safe.
The other good news is that if S. boulardii is going to work,
it works quickly, usually greatly reducing diarrhea within a
week or two. A short test should be enough to see if it is
going to work for you. If not, little has been lost. And if
the treatment does work, then the financial cost, and the
small, largely theoretical risk of serious side effects, may
be worth accepting.
1. Saint-Marc T, Sellem C, Rosello L, and Touraine JL.
Treatment of chronic diarrhea with Saccharomyces boulardii.
Sixth International Conference on AIDS, San Francisco, June
20-24, 1990 [abstract #Th.B.363].
2. Saint-Marc T, Rossello-Prats L, and Touraine JL.
Efficacite de Saccharomyces boulardii dans le traitement des
diarrhees du SIDA. ANNALES DE MEDECINE INTERNE. 1991; volume
142, number 1, pages 64-65.
3. Blehaut H, Saint-Marc T, and Touraine JL. Double
blind trial of Saccharomyces boulardii in AIDS related
diarrhea. Submitted to the Eighth International Conference on
AIDS, Amsterdam, 1992, but not published in the conference
4. Born P, Lersch C, Zimmerhackl B, and Classen M.
Saccharomyces-boulardii therapie HIV-assoziierter durchfalle.
DTSCH. MED. WOCHENSCHR. 1993; volume 118, number 20, page
5. McFarland LV and Bernasconi P. Saccharomyces
boulardii: A Review of an Innovative Biotherapeutic Agent.
MICROBIAL ECOLOGY IN HEALTH AND DISEASE. 1993; volume 6,
6. Adam J, Barret A, Barret-Bellet C, and others.
Essais cliniques controles en double insu de l'ultra-levure
lyophilisee. Etude multicentrique par 25 medecins de 388 cas.
GAZETTE MEDICALE DE FRANCE. 1977; volume 84, pages 2072-2078.
7. Surawicz CM, Elmer GW, Speelman P, McFarland LV,
Chinn J, and Van Belle G. Prevention of antibiotic-associated
diarrhea by Saccharomyces boulardii: a prospective study.
GASTROENTEROLOGY. 1989; volume 96, pages 981-988.
8. McFarland LV, Surawicz CM, Greenberg RN, and
others. Prevention of beta-lactam-associated diarrhea by
Saccharomyces boulardii compared with placebo. THE AMERICAN
JOURNAL OF GASTROENTEROLOGY. 1995; volume 90, number 3, pages
9. Tempe JD, Steidel AL, Blehaut H, Hasselmann M,
Lutun PH, and Maurier F. Prevention par Saccharomyces
boulardii des diarrhees de l'alimentation enterale a debit
continu. LA SEMAINE DES HOPITAUX DE PARIS. 1983; volume 59,
pages 1409- 1412.
10. Schlotterer M, Bernasconi P, Lebreton F, and
Wassermann D. Interet de Saccharomyces boulardii dans la
tolerance digestive de la nutrition enteral a debit continu
chez le brule. NUTRITION CLINIQUE ET METABOLISME. 1987;
volume 1, pages 31-34.
11. McFarland LV, Surawicz CM, Greenberg RN, and
others. A randomized placebo-controlled trial of
Saccharomyces boulardii in combination with standard
antibiotics for Clostridium difficile disease. JAMA. 1994;
volume 271, number 24, pages 1913-1918.
12. Plein K, and Holtz J. Therapeutic effects of
Saccharomyces boulardii on mild residual symptoms in a stable
phase of Crohn's disease with special respect to chronic
diarrhea -- a pilot study. Z. GASTROENTEROL. (Germany). 1993;
volume 31, number 2, pages 129-134.
13. Kollaritsch H, Holst H, Grobara P, and Wiedermann
G. Prevention of traveler's diarrhea with Saccharomyces
boulardii. Results of a placebo controlled double-blind
study. [English translation of the title.] FORTSCHR MED.
1993; volume 111, number 9, pages 152-156.
14. Chapoy P. Traitement des diarrhees aigues
infantiles: essai controle de Saccharomyces boulardii.
ANNALES DE PEDIATRIE 1985; volume 32, pages 561-563.
15. Cetina-Sauri G and Basto GS. Evaluacion
terapeutica de Saccharomyces boulardii en ninos con diarrea
aguda. TRIBUNA MEDICA. 1989; volume 56, pages 111-115.
16. Hochter W, Chase D, and Hagenhoff G. Saccharomyces
boulardii bei akuter erwachsenendiarrhoe. MUNCHENER
MEDIZINISCHE WOCHENSCHRIFT. 1990; volume 132, pages 188-192.