Efficacy of daily intake of Lactobacillus casei Shirota on respiratory
symptoms and influenza vaccination immune response: a randomized,
double-blind, placebo-controlled trial in healthy elderly nursing
Karolien Van Puyenbroeck, Niel Hens, Samuel Coenen, Barbara Michiels, Caroline Beunckens, Geert Molenberghs,
Paul Van Royen, and Veronique Verhoeven
Background: Age is associated with immune dysregulation, which
results in an increased infection rate and reduced effectiveness of
Objective: We assessed whether an intervention with Lactobacillus
casei Shirota (LcS) in elderly nursing home residents reduced their
susceptibility to respiratory symptoms and improved their immune
response to influenza vaccination.
Design: Between October 2007 and April 2008, a randomized, dou-
ble-blind, placebo-controlled trial was conducted in 737 healthy
people aged ?65 y in 53 nursing homes in Antwerp, Belgium.
Volunteers were randomly assigned to receive a probiotic (n =
375; 2 bottles of fermented milk that contained ?6.5 · 109live
LcS/bottle) or a placebo (n = 362; similar drink with no bacteria)
for 176 d. After 21 d, all subjects received an influenza vaccination.
Primary outcome parameters were the number of days with respi-
ratory symptoms, the probability of respiratory symptoms, and anti-
influenza antibody titer by hemagglutination inhibition after
Results: Univariate and multivariate modeling showed no effect of
the probiotic on clinical outcome parameters. Generalized linear
mixed modeling showed no effect of the probiotic itself on the
probability of respiratory symptoms [OR of probiotic: 0.8715;
95% CI: 0.6168, 1.2887). No significant difference regarding the
influenza-vaccination immune response was shown.
Conclusion: The results of this study show that daily consumption
of a fermented milk drink that contains LcS has no statistically or
clinically significant effect on the protection against respiratory
symptoms. This trial was registered at clinicaltrials.gov as
NCT00849277. Am J Clin Nutr 2012;95:1165–71.
The numbers of elderly people in Western countries continue to
rise. Aging weakens the immune system and increases suscepti-
bility to infections (1). Furthermore, the clinical presentation of
a respiratory tract infection (RTI)4in elderly individuals is rather
unspecific, whereby an RTI with limited symptoms can have
serious consequences and often lead to hospitalization and death
(2–4). Immunosenescence is also characterized by decreased
antibody production and a shortened duration of protective im-
munity after vaccination and, in particular, by suboptimal func-
tioning of the cell-mediated immune response (5).
To decrease the morbidity and mortality associated with an-
nual seasonal influenza, the WHO recommends vaccination for
certain at-risk population groups. One important risk group is
people ?65 y of age, particularly if they are living in nursing
homes and other residential institutions. However, the ability of
these people to respond to the trivalent influenza vaccine is low;
studies have shown a decreased response to influenza vaccina-
tion in healthy elderly compared with that in young adults,
which makes the vaccination much less effective (6).
Lactobacillus casei Shirota (LcS) is a probiotic strain con-
sumed in a fermented milk product that has been produced for
.70 y and is now commercially available in many countries
worldwide (eg, Japan, Taiwan, Philippines, Indonesia, Brazil,
Mexico, and several European countries). Probiotics are be-
lieved to positively influence immune function, and several
studies reported immunomodulatory activity associated with
LcS (7–12). Most of the studies have been in vitro studies or
studies that focused on immunoregulatory pathways. The clin-
ical effect is still unclear. The few studies conducted on the
probiotic effect on RTIs have investigated healthy adults or
children, except for 2 studies in free-living elderly (13, 14). All
of these studies have given conflicting results (13–21), whereby
some studies showed no effect (13, 16, 17), whereas other
studies showed a lower incidence of RTIs in the probiotic group,
but this was not always significant (14, 15, 18–21). To our
1From the Department of Primary and Interdisciplinary Care (KVP, SC,
BM, PVR, and VV), the Vaccine & Infectious Disease Institute–WHO Col-
laborating Centre (NH and SC), and the Centre for Health Economics Re-
search and Modeling Infectious Diseases (NH), University of Antwerp,
Antwerp, Belgium, and I-BioStat, Hasselt University and Katholieke Uni-
versiteit Leuven, Diepenbeek, Belgium (NH, CB, and GM).
2Supported by Yakult Honsha Co Ltd.
3Address correspondence to K Van Puyenbroeck, Department of Primary
and Interdisciplinary Care, University of Antwerp, Universiteitsplein 1, 2610
Antwerp, Belgium. E-mail: firstname.lastname@example.org.
4Abbreviations used: GMT, geometric mean titer; LcS, Lactobacillus
casei Shirota; RCT, randomized controlled trial; RTI, respiratory tract in-
Received September 13, 2011. Accepted for publication February 2, 2012.
First published online March 21, 2012; doi: 10.3945/ajcn.111.026831.
Am J Clin Nutr 2012;95:1165–71. Printed in USA. ? 2012 American Society for Nutrition
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PROBIOTIC ADJUVANT AND EFFECT ON RTI IN ELDERLY