Download Safety Summary of LGG Perspective of a Gastrointestinal Health

Safety Summary of LGG
Perspective of a Gastrointestinal Health Care Professional
The safety concerns of the probiotic bacteria Lactobacillus GG (LGG) are addressed herein. As a
way of introduction it is important to understand that at birth the gastrointestinal tract is sterile.
During childbirth an infant swallows bacteria present in the birth canal, these bacteria rapidly
colonize the small and large intestine, and the intestinal immune system learns to recognize these
bacteria as a desired resident of the gastrointestinal tract. The organisms are well tolerated throughout
life and necessary for the normal functioning of the intestinal as well as systemic immune system.
Additionally, bacteriologists and infectious disease specialists have long noted that certain organisms,
primarily species of lactobacillus or bifidobacterium, appear to have health-promoting benefits when
provided in conditions which have altered the normal human gastrointestinal flora. The science of
probiotics is now focused on attempting to identify the most beneficial species and provide them in
food or dietary supplements to produce health promoting effects.
LGG serves as a prototypic strain of probiotic lactobacilli and has been used in food products in both
Europe and the United States for over 15 years. LGG has been evaluated in numerous clinical studies
involving preterm and term infants at dose levels ranging from 108 to 1010 CFU per day. Infants in
these studies received LGG for up to several months at a time and showed no evidence of adverse
reactions or intolerance to treatment. In contrast, most subjects experienced a health benefit such as a
reduced risk of experiencing diarrhea, shortening of the duration of acute diarrhea, or enhanced
immune response following viral diarrhea. Recent meta-analyses have demonstrated the positive
benefits of probiotics in the treatment of mild to moderate acute viral diarrhea in children [1-3]. A
similar study conducted in Brazil demonstrated no benefit in severe diarrhea requiring hospitalization
[4] however; in all of these studies no complications were reported.
The safety of LGG has been more extensively studied than the safety of any other probiotic
bacterium. L. rhamnosus GG, isolated from a healthy adult person, has a safe history of use in foods
since 1990 and reached annual per capita consumption of 6 L in Finland at the end of 1990’s. Large
epidemiological studies showed that rapidly increasing consumption of the strain in Finland did not
increase the incidence of Lactobacillus or L. rhamnosus isolates in blood culture samples [5] and no
risk groups of immunocompromized patients could be identified[6]. A guideline document by
European pediatric associations recommends the use of LGG in diarrheal diseases in children [7] and
a medical expert group additionally concluded in its report that probiotics are safe, and that based on
current knowledge, there is no need to restrict the use of them in any consumer groups [8].
LGG has been safely used for pre-term infants with very low birth weight (<1500 g) at the level III
neonatal intensive care unit of Turku University Hospital, Turku, Finland [9]. Over the twelve years
period, from 1997 to 2008, all enterally fed infants (n=644) were supplemented with LGG once a day
during their hospital stay. No incidence of septicemia connected to LGG was found out in the
retrospective study, confirming the safe use of the strain even to the most vulnerable population.
Whelan and Myers [10] collected safety data from all case reports, randomized trials, and nonrandomized trials receiving nutritional support supplemented with probiotics by July 2009.
Altogether, 72 articles fulfilled the inclusion criteria, and 32 cases of identified probiotics were found
out. These all were caused by the most commonly used probiotics, Saccharomyces
boulardii/Florastor (27 cases) or LGG (5 cases). The risk factors included central venous catheters
and disorders associated with increased bacterial translocation
The safety of LGG is supported by surveillance studies that evaluated potential increases in clinical
infections with increased probiotic consumption. Such studies showed that during a nine year period,
despite a notable increase in LGG consumption (~10-fold) in Finland, the number of infections
involving Lactobacillus species reported to Helsinki health authorities remained at a constant
background level of 10-20 cases per year [6].
Annual number of reported and confirmed lactobacilli in blood cultures
25
Reported as Lactobacillus
20
Available for identification
Identified as Lactobacillus
Whole Finland
15
10
Southern Finland
5
0
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
Salminen M et al 2002, CID
All known cases of clinical infections where probiotic lactobacilli involvement was suspected
occurred in subjects with some type of serious underlying disease or health condition (e.g., liver
abscess, diabetes, heart damage, short gut syndrome, cerebral palsy). There are numerous strains of
lactobacilli which can be identified and it is important to note that the relationship between the
clinical isolate and the strain of lactobacilli consumed by the subject was confirmed by appropriate
molecular methods in only a limited number of the cases. The infections which have been reported in
the infant population all involved hospitalized patients who received LGG supplementation in an
attempt to treat complications resulting from the underlying hospitalization [11,12]. These patients
also received the probiotic for several weeks prior to getting an infection so it is unlikely the bacteria
itself caused the infection but rather something changed in their healthy status making them more
prone to infection. LGG is susceptible to most antibiotics in clinical use and therefore easy to treat if
a sepsis occurs. All lactobacilli strains are resistant to vancomycin but the resistance genes are
distinct from the transferable genes and LGG does not carry the plasmids that can spread transferable
genes [13, 14]. Therefore, LGG has little potential for infectivity, with the possible exception of its
use in severely immune compromised patients.
Over 100 clinical studies have demonstrated no adverse impact on nutritional, metabolic, or immune
parameters. Of special note is the fact that an infant formula containing LGG has also been on the
market for several years in Europe with no reported safety concerns. Lactobacillus rhamnosus
species has achieved Qualified Presumption of safety (QPS) –status from the Scientific Committee of
European Food Safety Authority and according to U.S. Food and Drug Administration (FDA) the use
of L. rhamnosus GG in infant formulas contains no risk.
(http://www.accessdata.fda.gov/scripts/fcn/fcnNavigation.cfm?rpt=grasListing&displayAll=true ).
Any health risks of L. rhamnosus GG are not known even if consumed to excess.
In conclusion, extensive research involving the use of LGG in healthy subjects and those with less
severe medical conditions have established the safety of LGG.
References
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