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Food and Nutrition Sciences, 2012, 3, 738-746
doi:10.4236/fns.2012.36100 Published Online June 2012 (http://www.SciRP.org/journal/fns)
A Double-Blind, Randomized, Placebo-Controlled
Nutritional Study Using an Insoluble Yeast Beta-Glucan
to Improve the Immune Defense System
Hans-Joachim Graubaum, Regina Busch, Heike Stier, Joerg Gruenwald
Analyze & Realize AG, Berlin, Germany.
Email: hstier@analyze-realize.com
Received February 21st, 2012; revised April 5th, 2012; accepted April 13th, 2012
ABSTRACT
Purpose: In a placebo-controlled, double-blind, randomized clinical trial, the effect of an insoluble yeast beta-glucan
preparation on the incidences of common colds and its effect on common cold symptoms were compared to placebo.
Methods: 100 healthy participants with recurring infections were randomly assigned to receive either placebo or yeast
beta-glucan (Yestimun®; n = 50 each group) over a period of 26 weeks. The subjects had to document each common
cold episode in a diary, and rate 6 predefined infections symptoms on a 3-point rating scale during an infection period,
resulting in an infection score. The common cold episodes were confirmed by the investigators. Results: A total of 171
common cold episodes were documented. Of these, 76 were experienced by 38 subjects in the beta-glucan group and 96
were experienced by 48 subjects in the placebo group (p = 0.406). The beta-glucan group had significantly more sub-
jects without incidences of common cold than the placebo group (15.6% vs 2.0%; p = 0.019). During the most intense
infection season (first 13 weeks of the study), the beta-glucan group had significantly less infections compared to pla-
cebo (p = 0.02). Beta-glucan significantly reduced the typical cold symptoms (“sore throat and/or difficulty swallow-
ing”, “hoarseness and/or cough” and “runny nose”) as opposed to placebo. Conclusion: The present study demonstrates
a prophylactic effect of yeast beta-glucan on the occurrence of common colds as opposed to placebo. In addition, when
these episodes occurred, they were from the beginning less pronounced and subsided faster.
Keywords: Randomized Placebo-Controlled Study; Insoluble Yeast Beta-Glucan; Common Cold; Immune System
1. Introduction
Beta-glucans are natural polysaccharides containing D-
glucose subunits, linked by beta-glycosidic bindings.
They are found in cell walls of bacteria, yeast, fungi,
algae, but also in the walls of grain and other plants.
Initial studies investigating the inmunomodulatory ac-
tivity of beta-glucan were performed in 1956. In that
study, a chitin/beta-glucan preparation led to an unspe-
cific stimulation of the immune system, leading to an
increased anti-bacterial and anti-viral activity after ap-
plication of the substance to rabbits and guinea pigs [1].
Since these early studies, numerous publications and
patents on the effects and mode of actions of beta-glu-
cans have been published.
Beta-glucan is neither synthesized by the human or-
ganism nor is it a component of the human body, there-
fore it is identified by the immune system as foreign,
leading to activation of both the innate as well as the
adaptive immune response [2]. Even though the mode of
action is not fully understood, several effects of beta-
glucan on various parts of the immune system have been
demonstrated. It has been found that Dectin-1 and toll-
like receptors (TLR), expressed on macrophages, neu-
trophils and dendritic cells are responsible at least par-
tially for the innate immune response, leading to acti-
vated immune cells and the release of various cytokines.
Via binding to the activated complement receptor 3
(CR3), cell lysis or monoclonal antibody reaction might
be potentiated by beta-glucans [2,3].
Many of these effects found in in vitro investigations
have been confirmed in vivo. Studies on breeding cattle
demonstrated a positive effect of beta-glucans on their
ability to activate their immune system. Fleischer et al.
(2001) investigated the effect of (1,3)-(1,6)-
-D-glucan
on the immune system of chicks and breeding sows [4].
During this study, the regular animal feed was mixed
with yeast beta-glucan. Several immune parameters (such
as number of monocytes, activation status of macro-
phages and monocytes by the indicator neopterin, im-
Copyright © 2012 SciRes. FNS
A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble
Yeast Beta-Glucan to Improve the Immune Defense System
739
munoglobulin A etc.) were measured to determine the
immune status under various conditions (under physical
exertion, growth phases, pregnancy, birth and lactation).
As a result, they found that yeast beta-glucan, when
mixed with the regular feed, led to increased resistance
against Escherichia coli in the growing chick, the breed-
ing sows as well as in their offspring.
In another study, (1,3)-(1,6)-
-D-glucan was given to
piglets and the immunological effects were investigated
in vivo as well as in vitro. In vivo (1,3)-(1,6)-
-D-glucan
led to a reduced production of IL-6 and TNF
, and a
simultaneous increase of IL-10. The reduction of IL-6
und TNF
had also been observed in vitro [5].
All these studies demonstrate that beta-glucan streng-
thens the immune function in general. It has been shown
that beta-glucan is able to improve the resistance against
various invading pathogens. Animal studies showed pos-
itive effects on the defense against infection by Staphy-
lococcus aureus, Escherichia coli, Candida albicans,
Pneumocystis carinii, Listeria monocytogenes, Leishma-
nia donovani, and influenza virus but also against an-
thrax challenge (for review see [6]).
Beta-glucans are not a unique class, but occur in dif-
ferent molecular weight and structures. Depending on the
origin and structure of the molecule, they differ in their
biological specificity as well as in their efficacy. For the
biological activity, the molecular weight as well as the
branching structure seems to be important [6]. It seems
that the more complex the structure, the more potent are
the immunmodulatory effects [7]. Highly polymer beta-
glucans with a molecular weight of 100,000 Da - 200,000
Da expressed the highest immune stimulating activity,
whereas fractions of very short beta-glucans between
5000 Da - 10,000 Da, extracted from the same organism,
exhibited no activity [8]. Further investigations showed
that particles with
-(1,6) branching together with
-(1,3)
branching are more effective than
-(1,3) branching
alone [9]. It seems that at least for common cold preven-
tion, soluble (1,3)-(1,4)-
-glucan prepared from oat is
not effective [10]. Therefore it is very important to
clearly differentiate between results obtained from vari-
ous molecules.
In this study, the insoluble (1,3)-(1,6)-
-glucan made
from brewers’ yeast (Saccharomyces cerevisiae: Yes-
timun®, previously called Biolex Beta-HP), was used.
The positive effects of this specific preparation on the
immune system have been confirmed in various in vitro
studies [11-13]. Herein the common cold was used as a
model system to show that the insoluble beta-glucan
preparation activates the human defense system against
various pathogens. The common cold is a well-known
and, in most cases, harmless infection, typically affecting
adults 2 - 5 times per year [14]. The aim of this study
was to show that intake of a functional food composed of
beta-glucan led to less infections of reduced intensity in
the general population. The results of this human trial
with this product are presented here.
2. Methods
2.1. Study Design
This nutrition study was conducted as a prospective,
multi-centric, randomized, double-blind, placebo-controlled
study in healthy outpatient subjects, with recurring com-
mon colds, in Berlin (Germany) between November
2006 and September 2007. It was conducted in the prac-
tices of five physicians. The effect of an insoluble yeast
beta-glucan preparation on the incidences of common
colds was compared to placebo. The study was per-
formed according to the declaration of Helsinki/Hong
Kong 1989/Somerset 1996 as well as the ICH-GCP
guidelines (CPMP/ICH/135/95).
2.2. Study Population
One hundred healthy subjects with recurring common
colds were included in this nutritional study. They had to
meet the inclusion criteria: age ≥ 18, written consent to
participate, and at least three infections within the last six
months. The exclusion criteria were as follows: allergic
rhinitis or asthma, known sensibility to one of the ingre-
dients of the study product, fever (≥39˚C), severe organ
or systemic disorders, stomach or intestinal diseases,
intake of preparations that can influence the study out-
come, such as immunosuppressives or common cold
therapeutics, bacterial tonsillitis, incidence of alcohol,
medication or drug abuse, cancer or being HIV positive,
pregnancy or nursing, participation in a clinical study
within the previous 30 days, or problems with compli-
ance or following the protocol due to language difficul-
ties.
All of the screened subjects met the inclusion criteria
and did not violate the exclusion criteria and were ran-
domized into this nutritional trial. They represent the
intention to treat (ITT) population (see Figure 1). In total,
six subjects withdrew from the study. One case was due
to insufficient efficacy (placebo group = PG), two were
without giving a reason (active group = AG), one was
due to a move (AG), one stated aversion to capsules
(AG), and one (AG) was due to loss of motivation.
Therefore, in total 94 subjects completed the entire study.
Of these 94 subjects who completed the entire study,
nine were excluded from the per protocol (PP) analysis
due to poor compliance (4 PG, 5 AG) resulting in n = 85
subjects (41 AG, 44 PG).
Of the 100 subjects taken into the study, 58 were
Copyright © 2012 SciRes. FNS
A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble
Yeast Beta-Glucan to Improve the Immune Defense System
Copyright © 2012 SciRes. FNS
740
Figure 1. Schematic representation of the study population. ITT: intention to treat; PP: per protocol.
Table 1. Characteristics of the participants at baseline.
women and 42 were men. All subjects reported that they
had experienced at least three cold episodes in the six
months prior to beginning the study. The mean height,
weight and body mass index (BMI) for the subjects are
provided in Table 1. All the study participants were clas-
sified as Caucasian. With respect to these baseline char-
acteristics, there were no statistically significant differ-
ences between the beta-glucan group and placebo group
(Table 1).
Study population
Beta-glucan (n = 50) Placebo (n = 50) p-value
Age (years) 45.6 ± 16.9 47.1 ± 16.4 0.629
Sex (m/f) 22/28 20/30 0.685
Height (cm) 173.5 ± 9.1 171.5 ± 9.1 0.394
Body weight (kg) 74.4 ± 13.8 74.6 ± 17.1 0.929
BMI kg/m2 24.7 ± 3.8 25.3 ± 5.2 0.672
2.3. Interventions
The study participants were instructed to take two times
daily one capsule of the active treatment (one capsule
contains 450 mg insoluble yeast beta-glucan; Yestimun®,
formerly called Biolex Beta-HP; Leiber, Germany) or
placebo (microcrystalline cellulose) over a period of 26
weeks (prophylactic treatment). The beta-glucan prepara-
tion is an insoluble (1,3)-(1,6)-
-glucan made from
brewers’ yeast (Saccharomyces cerevisiae), with a purity
of min. 85% on dry matter. (branching factor approxi-
mately: 1,3 (backbone):1,6 (side chain):1,3/1,6 (branch-
ing) = 10:1:0.6). During the study period, three regular
visits (V1 at baseline, V2 after 12 - 14 weeks, and V3
after 25 - 27 weeks) were performed in the practices of
one of the five investigators. In case of a beginning
common cold episode, the participant took for a period of
five days two times daily two capsules of the assigned
product (active treatment or placebo) and had to visit the
investigator for the first episode visit. After these five
days (day six), the participant had to consult once more
the investigator for the second episode visit. For each
occurring infection, the same procedure was performed.
Thus, the total number of visits per participant varies
depending on the number of infection episodes.
Participants with a common cold episode at the begin-
ning of the nutritional study (for no longer than 24 h),
started with the two capsules two times daily for five
days treatment, followed by the prophylactic phase
(regular intake two times daily one capsule).
All the subjects were encouraged to continue their
normal background diet during the duration of the study.
2.4. Outcome Measures
2.4.1. Primary Outcome
The primary objective of this double-blind, randomized,
placebo controlled nutritional study was to prove a sig-
nificant reduction of common cold episodes by the in-
soluble yeast beta-glucan preparation, as compared to
placebo, in subjects with an increased risk of common
cold infections, over a period of 26 weeks. All the com-
mon cold episodes had to be documented in a diary and
confirmed by an investigator.
2.4.2. Secondary Outcome
The secondary objective was to prove a significant re-
duction of common cold symptoms by the yeast insolu-
A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble
Yeast Beta-Glucan to Improve the Immune Defense System
741
ble beta-glucan as compared to placebo within the first
five days of each common cold episode. During the in-
fection episode, the participants had to rate six prede-
fined common cold symptoms (general malaise, head-
ache and/or pain in the limbs, “sore throat and/or diffi-
culty swallowing”, “hoarseness and/or cough”, “runny
nose”, insomnia due to common cold) on a rating scale (0
points = complaint free, 1 point = weak symptoms, 2
points = strong symptoms) and had to document them in
his/her dairy. By summation of the scores of the individ-
ual symptoms, a sum of scores (=total score) was calcu-
lated.
2.4.3. Concurrent Variable
As a concurrent variable, the efficacy of the investiga-
tional product was evaluated by the subjects and the in-
vestigator at the end of each common cold episode as
“very good” “good”, “moderate”, or “poor”.
2.4.4. Safety Assessment
The safety and tolerability of the product was evaluated
by the documentation of adverse events as well as by the
global evaluation of the tolerability by the investigator
and the subject at the end of the study.
2.5. Randomization/Blinding
The human study was conducted double-blind; neither
the participants nor the investigators knew which study
participants had the active or placebo treatment.
Group assignment to the two study groups was per-
formed during the first examination (baseline) randomly
and double-blind, if the inclusion and exclusion criteria
were met. The randomization was performed by block
randomization (block size 4) using the randomization
scheme EDGAR (Experimental Design Generator and
Randomizer). The issued containers comprising the ac-
tive treatment or the placebo product were pre-numbered
(externally) according to the randomization. The random
code remained blinded until the final closing of the data-
base.
2.6. Statistical Methods/Sample Size Calculation
All the variables contained in the data collection were
presented descriptively using their statistical key data or
their frequency distribution and statistically analyzed in
view of the group specific differences ( 2
p
-value). Or-
dinal and metric data were evaluated using the U-test as
well as the Mann-Whitney U-test for independent sample
testing (pu-values), and the Wilcoxon-test for dependent
sample testing. The t-test was additionally used for met-
ric data (pt-values), whereby testing for equality of vari-
ances in comparison to independent or paired data was
performed by means of an F-test. All statistical analyses
were carried out on an intention-to-treat (ITT) and per
protocol (PP) basis with SPSS. Values of p < 0.05 were
considered significant. Means are given with standard
deviation (SD).
A sample size calculation was not performed, due to
missing preliminary data. The number of subjects was
adjusted to 50 subjects each group.
3. Results
3.1. Total Number of Infections
For the primary objective (total number of infections),
the ITT population consisted of only 94 subjects, due to
six drop-outs, which had a shorter study period and
therefore unavoidably less total infections (see Figure 1).
Within the ITT population, a total of 171 cold episodes
occurred in the prophylactic period of 26 weeks (Table
2). Of these, 76 affected 38 subjects of the active group
(AG; 44.4%) and 95 affected 48 subjects in the placebo
group (PG; 55.6%). Even though the AG showed 25%
less infection episodes than the PG, and a total of seven
subjects (15, 6%) of the AG compared to only one of the
PG (2%) had no common cold episode during the entire
study period ( 2
p
= 0.019), the difference in the fre-
quency distribution showed only a tendency towards sig-
nificance between the two treatment groups (ITT: 2
p
= 0.094; PP: 2
p
= 0.060), and no significant difference
in the total number of episodes (ITT: pu = 0.406; PP: pu =
0.614, respectively).
However, if the same data analysis was made for the
first half (13 weeks) of the prophylactic period, from
Table 2. Number of common cold episodes during the entire
study (26 weeks) in the intention to treat (ITT) and per
protocol (PP) population.
AG (ITT n = 45/PP n = 41) PG (ITT n = 49/PP n = 44)
Number of
episodes Number % Number %
0 7/7 15.6/17.1 1/1 2.0/2.3
1 11/10 24.4/24.4 18/18 36.7/40.9
2 19/17 42.2/41.5 18/16 36.7/36.4
3 5/4 11.1/9.8 10/8 20.4/18.2
4 3/3 6.7/7.3 1/0 2.0/0
7 0/0 0/0 1/1 2.0/2.3
Total 76/68 100/100.1 95/81 99.8/100.1
pu 0.406/0.614
2
p
0.094/0.060
pu: p-value for total number of episodes; 2
p
: p-value for distribution; AG:
active group; PG: placebo group.
Copyright © 2012 SciRes. FNS
A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble
Yeast Beta-Glucan to Improve the Immune Defense System
742
November to March, when most of the common cold
episodes occurred, the AG had significantly less infec-
tions as compared to PG (pu = 0.020; see Tables 3 and
4).
3.2. Reduction of the Common Cold Symptoms
(Secondary Objective)
To evaluate the effect of beta-glucan on the common
cold episodes, each subject rated the six predefined
symptoms during each episode for five days. The symp-
tom “general malaise” was excluded from summation,
because it has been shown that this parameter was un-
specific and was without group difference in 95% of all
the episodes ( 2
p
= 0.818).
Table 5 summarizes the total score during the course
of the episodes. It is obvious that the total scores were
significantly lower in the AG than in the PG at all stages
of the episodes.
For the three typical cold symptoms “sore throat
Table 3. Number of common cold episodes during common
cold episode season (13 weeks) in the intention to treat (ITT)
and per protocol (PP) population.
AG (ITT n = 45/PP n= 41) PG (ITT n = 49/PP n=44)
Number of
episodes Number % Number %
0 13/13 28.9/31.7 6/6 12.2/13.6
1 20/18 44.4/43.9 20/20 40.8/45.5
2 9/7 20.0/17.1 18/15 36.7/34.1
3 3/3 6.7/7.3 4/2 8.2/4.5
4 0/0 0/0 1/1 2.0/2.3
total 47/41 100/100 72/60 99.9/100
pu 0.020/0.045
pu: p-value for total number of episodes; AG: active group; PG: placebo
group.
Table 4. Mean common cold episodes after 13 and 26 weeks
(intention to treat population).
Common cold episodes
Time point Number of
Episodes AG PG pu-value
Total 47 72 0.020
13 weeks
Average ± SD 1.04 ± 0.88 1.47 ± 0.89 0.022
Total 76 95 0.406
26 weeks
Average ± SD 1.69 ± 1.08 1.94 ± 1.13 0.277
pu: p-value obtained by U-test; AG: active group; PG: placebo group; SD:
standard deviation.
and/or difficulty swallowing”, “hoarseness and/or cough”,
and “runny nose”, a significantly higher success (defined
as being complaint-free during the first five days of an
episode) was shown in the AG (p = 0.034, respectively <
0.0001, respectively 0.001). These three typical cold
symptoms and the total cold sum score were significantly
less pronounced at the beginning of the episodes in the
AG than in the PG ( 2
p
= 0.011 to 0.046, respectively
pu = 0.029).
The results of the secondary objectives clearly demon-
strate that the prophylactic intake of beta-glucan led to
milder common cold symptoms in case of an infection
episode.
3.3. Global Evaluation of the Efficacy during
Episodes (ITT)
Global evaluation of the efficacy after each episode was
judged as “very good” or “good” for 74.1% of partici-
pants of the active treatment and for 48.3% of partici-
pants of the placebo treatment, as assessed by physicians,
and for 76.6% (49.4%) of participants, as assessed by
participants. Both participants and physicians rated the
efficacy of the beta-glucan preparation significantly better
than the placebo ( 2
p
= 0.001, 2
p
= 0.002, respec-
tively; Table 6).
3.4. Safety Evaluation
All measured clinical parameters, body weight, tempera-
ture, heart rate and blood pressure remained almost con-
stant during the study, with no significant differences
between the two study populations.
The global assessment of tolerability for both treat-
ments was rated at the end of the study as “very good” by
approximately 2/3 of participants and physicians, or as
“good” by approximately 1/3 of participants and physi-
cians with no group differences ( 2
p
= 0.568, 2
p
=
0.395, respectively).
Adverse Events
A total of six adverse events occurred during this nutri-
tional study. Four of them occurred in the AG (gastro-
intestinal infection, hypertonic blood pressure, pain in
lumbar spine region during physical activity, pain/
swelling of the upper ankle joint after playing soccer)
and two in the PG (cut into finger, pain in the knee joint).
All of them were “not severe”, did not lead to termina-
tion of the study, and were judged as being “unlikely”
connected to the intake of the investigational product.
The two study groups did not differ in the proportion of
subjects with adverse events (AG: 8.0% vs PG: 4.0%;
2
p
= 0.4). None of the adverse events led to a preterm
rop-out. d
Copyright © 2012 SciRes. FNS
A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble
Yeast Beta-Glucan to Improve the Immune Defense System
Copyright © 2012 SciRes. FNS
743
Table 5. Total score values in the course of the common cold episodes.
Common cold score
Day 1 mean ± SD Day 2 mean ± SD Day 3 mean ± SD Day 4 mean ± SD Day 5 mean ± SD
Total 5.1 ± 2.3 5.3 ± 2.4 4.2 ± 2.4 2.9 ± 2.4 1.7 ± 2.0
AG 4.6 ± 2.1 4.8 ± 2.3 3.5 ± 2.1 2.4 ± 1.9 1.4 ± 1.6
PG 5.5 ± 2.6 5.7 ± 2.4 4.8 ± 2.5 3.4 ± 2.6 2.0 ± 2.3
pU-value 0.029 0.014 0.001 0.015 0.059
pt-value 0.018 0.009 0.001 0.005 0.034
pu or pt: p-value obtained by U-test or t-test; AG: active group; PG: placebo group; SD: standard deviation.
Table 6. Global evaluation of the efficacy by the investiga-
tors and participants.
Evaluation [%]
Group
Very good Good Moderate Poor p-value
By investigators
AG 24.7 49.4 22.1 3.9
PG 20.2 28.1 31.5 20.2
0.002
By patients
AG 23.4 53.2 19.5 3.9
PG 20.2 29.2 31.5 19.1
0.001
2
p
: p-value for distribution; AG: active group; PG: placebo group.
4. Discussion
During this placebo-controlled, randomized, nutritional
study, the effect of an insoluble yeast beta-glucan on the
body’s resistance against invading pathogens was inves-
tigated. The common cold was used as a model system.
Over a period of 26 weeks, the number of common cold
infections was evaluated in subjects with recurring
common colds. The beta-glucan group had significantly
fewer subjects without infections (AG 15.6% vs PG
2.0%; p = 0.019), and 20% fewer infections compared to
placebo (AG n = 76 versus PG n = 95 infection), but both
groups did not differ statistically regarding the total
number of infections (p = 0.406).
However, if the data of the first half of the study (first
13 weeks—which was during the most intense infection
time) are analyzed, then the beta-glucan group has sig-
nificantly fewer infections than the PG group. During
this time of intense infection, 69.5% of the infections
occurred (119 of 171) from which only 47 occurred in
the beta-glucan group and 72 in the PG group (p = 0.02).
The low incidence of common colds during the second
half of the study, March till June, cannot be explained by
the efficacy of beta glucans on the subjects in the active
group, since the number of infections occurring in the
placebo group was equal to the number of infections in
the active group. This reduction of common cold epi-
sodes might be caused by higher temperatures and gen-
erally increased well-being of humans during spring and
summer time. Thus, the greatest effect of Yestimun® on
the primary outcome variable, which was the number of
common cold infections, was observed during the winter
season.
One limitation of the study was the number of partici-
pants included into this nutritional being determined to
be 50 per group, due to missing previous product-specific
studies. Furthermore, the included subjects had to be
susceptible to common cold (at least three within the last
six months). However, the subjects of the PG had fewer
episodes than expected (mean number of infections in
PG: 1.94 within 26 weeks). The small number of partici-
pants, together with the lower rate of actual infection,
and the realization of the second study half during spring
and summer time were probably responsible for the fail-
ure to show statistical significance regarding the total
number of infections during the whole study duration.
Therefore, the effects observed in this study have to be
confirmed in a larger scale study exclusively during the
winter period with increased risk of common cold.
Several investigations using other beta-glucan prepa-
rations to prevent the risk of common cold infections
have already been published.
In one study, the effect of beta-glucan preparations has
been investigated on the respiratory tract of athletes [15].
Enhanced exercises seem to weaken the immune system
and may cause increased risk of upper respiratory tract
infections [16,17]. In the study by Talbott, marathon run-
ners were treated with either 250 or 500 mg of a β-1,3/
1,6-glucan preparation from Saccharomyces cerevisiae
(Wellmune WPG®) for four weeks post-marathon. Both
beta-glucan groups reported significantly fewer infec-
tions symptoms and better overall health, compared to
placebo. While only 8% of the subjects of both beta-
glucan groups reported infections at week four, 24% of
A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble
Yeast Beta-Glucan to Improve the Immune Defense System
744
the placebo group subjects reported infection symptoms.
Furthermore, the subjects reported better overall health
and a more positive mood state compared to placebo four
weeks after completing the marathon [15]. In another
study, the effect of a beta-glucan preparation made from
Pleurotus ostreatus together with vitamin C on the cellu-
lar immune response and upper respiratory tract infec-
tions (URTI) was investigated on athletes of different
sports disciplines [18]. Fifty athletes took either two cap-
sules containing 100 mg beta-glucan and 100 mg vitamin
C or 100 mg vitamin C alone for three months. In that
trial, the beta-glucan-treated athletes reported signifi-
cantly less URTI than the vitamin C group (65 versus
117 episodes) [18]. In one clinical trial lasting 12 weeks
[19], the effect of beta-glucan (500 mg/day) from Sac-
charomyces cerevisiae (Wellmune WPG®) was com-
pared to placebo in healthy subjects. In that study, the
investigators found no difference in the incidence of
common cold infections. Even though the number of
infections was not different, the symptoms strength was
reduced in the beta-glucan group since none of the sub-
jects missed school or work due to colds, while the pla-
cebo group did so on average for 1.38 days.
The results of these above cited studies cannot be di-
rectly compared to our study, since time courses, applied
dosages, subject populations or measured outcomes are
not comparable. However, subjects treated with the
above-described beta-glucan preparation had fewer in-
fections or reduced symptoms, like in the study presented
here. All these studies were made with insoluble be-
ta-glucan preparations.
It is known that various beta-glucan preparations have
different effects on the immune system, where not only
the size and the degree of branching are responsible but
also the solubility [7,9,20]. One explanation could be the
fact that for activation of the Dectin-1 receptor, whole
beta-glucans are necessary, as shown very recently.
Smaller size particles or soluble beta-glucans are inactive,
despite efficient binding to the receptor [21]. Based on
this result, Goodridge et al. [21] hypothesized “that a
larger molecule may be required to provide a greater de-
gree of receptor crosslinking to permit activation”.
Beta-glucan is thought to strengthen the immune sys-
tem by activation of innate and adaptive immune re-
sponse mechanisms [2]. Various other nutritional and
herbal agents have been investigated for their immune
system strengthening abilities. One of them is Echinacea,
commonly used for prevention of common cold infection
and known for its immune system stimulating abilities.
Its efficacy, however, is discussed controversially [22-
24]. Due to the fact that all of the intervention trials dif-
fer in study collectives, time courses and primary and
secondary outcomes it is not possible to directly compare
the effect of Echinaceae preparations to the preventive
effect of beta-glucan. In one trial, the effect of an Echi-
naceae preparation was also investigated on subjects
with recurring infections [25]. However, the treatment
duration was only 8 weeks. Within that period, 25.9% of
the placebo-treated subjects were free from infections
compared to 35.2% of the active group. Based on this
data, the effect size was calculated to be 9.3% (difference
Echinacea treatment versus placebo). Similar results
were also observed by Grimm and Müller [26]. During
their two months study, they observed 35% of Echina-
ceae treated subjects without infections and 26% of the
placebo treated subjects in a group of subjects with re-
curring infection (effect size 9%). This data can be com-
pared to our data of the first 15 weeks of the study, where
28.9% of the AG and 12.2% of the PG were free from
infection, which represents an effect size of 16.7%.
Based on these results, we conclude that beta-glucan
might be at least as effective as Echinaceae in the pre-
vention of common colds. This, however, has to be
shown in a comparative two-armed study where both
preparations are compared directly.
As another treatment to prevent common cold, high
dosages of vitamin C are frequently used. However, in
the Cochrane review [27], the author came to the conclu-
sion that high intakes of Vitamin C do not reduce the
incidence of episodes in the normal population. Only
people with high physical stress (athletes or soldiers)
might benefit.
Zinc is also important for the normal function of the
immune system. When taken within 24 hours of onset of
a cold episode, the severity of symptoms and the duration
of the common cold is reduced. Further, when zinc is
supplemented for at least 5 months, the rate of incidences
as well the prescription of antibiotics in children is re-
duced [28]. However, it will not prevent common cold
episodes in the normal, non-deficient population.
Both substances, vitamin C and zinc, are undeniably
important for the function of our immune system. How-
ever, it seems that only subpopulations with a deficiency
of these substances may profit from supplementation,
which then reduces the incidences of cold episodes.
The insoluble beta-glucan preparation made of brew-
ers’ yeast used in this study was well tolerated when
taken for 26 weeks. Neither placebo nor beta-glucan
showed any difference in the number of observed ad-
verse events (p = 0.4), from which none was judged to be
treatment related. All the measured clinical parameters
(body weight, temperature, heart rate and blood pressure)
remained almost constant in both groups during the study.
Approximately 2/3 of the subjects evaluated the safety in
agreement with the investigators, without a group differ-
ence, as “very good” and about 1/3 as “good”. Consider-
Copyright © 2012 SciRes. FNS
A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble
Yeast Beta-Glucan to Improve the Immune Defense System
745
ing the six terminations and nine study plan violations,
compliance (intake of the capsules, adherence to the
study period) of the subjects was assessed as good for
this six months nutritional study. The overall good com-
pliance demonstrates the consumers’ acceptance of the
study product.
In conclusion, the present study demonstrates a pro-
phylactic effect of an insoluble yeast beta-glucan prepa-
ration on the occurrence of common colds as opposed to
placebo during seasons with increased common cold in-
cidences. When episodes occurred, they were from the
beginning less pronounced and subsided faster. This re-
sult, however, has to be confirmed by further investiga-
tions with an appropriate sample size.
5. Acknowledgements
The study was funded by Leiber GmbH (Bramsche,
Germany). The authors declare no conflict of interest.
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