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Comparison of immunological effects of commercially available β-glucans


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Biological and most of all immunological effects of natural immunomodulator glucan are already well established. However, since hundreds of individual glucans, isolated from various sources, used at different concentrations and having different physicochemical characteristics are being used, the current scientific knowledge is not complete. In addition, direct comparisons of individual glucans are quite rare. In the present paper, we tested fifteen varieties of glucans differing in source and solubility. Whereas no direct connection between source and immunological effects was found, we can conclude that the best glucans have pleiotropic effects stimulating all facets of immunological reactions, whereas other glucans have low effects or none at all.
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Applied Scientic Reports
ISSN 2054-9903 | Volume 1 | Article 2
Special Section | Biological Sciences | Research Open Access
Comparison of immunological effects of commercially
available β-glucans
Vaclav Vetvicka* and Jana Vetvickova
Biological and most of all immunological effects of natural immunomodulator glucan are already well
established. However, since hundreds of individual glucans, isolated from various sources, used at different
concentrations and having different physicochemical characteristics are being used, the current scientific
knowledge is not complete. In addition, direct comparisons of individual glucans are quite rare. In the
present paper, we tested fifteen varieties of glucans differing in source and solubility. Whereas no direct
connection between source and immunological effects was found, we can conclude that the best glucans
have pleiotropic effects stimulating all facets of immunological reactions, whereas other glucans have low
effects or none at all.
Keywords: Glucan, phagocytosis, IL-2, antibodies, breast cancer, superoxide anion
© 2014 Vetvicka et al; licensee Herbert Publications Ltd. is is an Open Access article distributed under the terms of Creative Commons Attribution License
( is permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
β1, 3-D-glucans (hereafter referred to as glucans) form part of
a group of natural biologically active compounds generally
called biological response modifiers. These molecules are highly
conserved carbohydrates forming structural components of
cell walls of yeast, fungi, seaweed, and cereals. Generally, the
term glucan is some times used as a chemical name of glucose
polymer and represents a group of chemically heterogeneous
carbohydrates consisting of various numbers of glucose mol-
ecules bound together in several types of linkages.
The history of glucan began over 50 years ago with two diff-
erent starting points—one originated in Europe and the United
States and the second in Japan. Research on glucans in the
Euro-American milieu was based on the immunomodulatory
effects of zymosan (mixture of polysaccharides isolated from
the cell walls of Saccharomyces cerevisiae). On the other hand,
the Japanese research was based on Asian medicine, where
consuming medicinal mushrooms (such as shiitake or reishi)
has been a long tradition.
The biological effects of glucans are already well established
and reach from stimulation of anti-infectious immunity to
potentiation of cancer defense, from stress reduction to red-
uction of cholesterol (for review see [
]). In addition to various
animal studies, where glucans were found to be active in wide
range of species, basically from shrimp to horses, the effects
of glucans have also been also examined in human models.
Soluble glucan was found to decrease the infection incidence
and need for antibiotics [3]. Recently, glucan was successfully
used as part of a vaccine for high risk neuroblastoma [
]. In
addition, a series of clinical studies showed strong effects on
the treatment of children with chronic respiratory problems
[5,6]. In Japan, glucan has been widely used, since 1983, in the
treatment of gastrointestinal cancer [7].
Over 7,000 publications describing various biological eff-
ects of glucans can be found in scientific literature. One of the
problems resulting in low acceptance of glucans in current
medicine is the fact that, despite the overwhelming number
of scientific reports, far too many individual glucans have
been used that differ widely in source, solubility, molecular
weight, branching and other physicochemical characteristics.
Diverse data on the comparison of structure, molecular size,
and biological effects can be found in the literature [2]. Some
studies suggest that the effects are dependent on the helical
conformation [
]. However, the triple helix structure most likely
is not a solely effective form of glucan, because alkaline treat-
ment, used in most isolation procedures, destroys this structure
In addition, various concentrations and routes of admini-
stration (oral, intraperitoneal, intravenous, subcutaneous) have
been tested. All this leads to severe confusion, with numerous
Department of Pathology, University of Louisville, Louisville, KY, USA.
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Vetvicka et al.
Applied Scientic Reports
doi: 10.7243/2054-9903-1-2
manufacturers claiming that their glucan possesses the highest
biological activities. The problem of diverse data can be solved
only by comparative studies. However, scientific reports directly
comparing individual glucans are limited [
], with only
one really comprehensive study being published during last
5 years [16]. This led us to the current comparative review of
15 different commercially available glucans.
Female, 8 week old BALB/c mice were purchased from the
Jackson Laboratory (Bar Harbor, ME). All animal work was done
according to the University of Louisville IACUC protocol. Ani-
mals were sacrificed by CO
asphyxiation followed by cervical
All glucans were either donated or purchased from the manu-
facturers or distributors as shown in Table 1.
Cell lines
Human myeloblastic cell line HL-60 was obtained from the ATCC
(Manassas, VA). The BALB/c mouse-derived mammary tumor
cell line Ptas 64 was generously provided by Dr. Wei-Zen Wei
of the Michigan Cancer Foundation, Wayne State University,
Detroit, MI. The cells were maintained in RPMI 1640 (Sigma
Chemical Co., St. Louis, MO) medium containing HEPES (Sigma)
buffer supplemented with 10% heat-inactivated FCS (Hyclone
Lab., Logan, UT), without antibiotics, in plastic disposable
tissue culture flasks at 37°C in a 5% CO2/95% air incubator.
Tumor inhibition in vivo
Mice were injected directly into their mammary fat pads with
/mouse of Ptas64 cells in PBS. The experimental treat-
ment was begun after palpable tumors were found (app. 14
days after injection of cells) and after mice were assigned to
experimental groups. Experimental treatment was achieved
by intraperitoneal injections of tested samples diluted in PBS
(once/day for 14 days). After treatment, the mice were sacrificed,
tumors removed and weighed [17]. These experiments were
repeated three times with 3 mice per each group.
Phagocytosis of synthetic polymeric microspheres was de-
scribed earlier [
]. Briefly: 0.1 ml of peripheral blood from mice
injected with various doses of glucan or PBS was incubated
in vitro with 0.05 ml of 2-hydroxyethyl methacrylate particles
(HEMA; 5x108/ml). The tubes were incubated at 37oC for 60 min.,
with intermittent shaking. Smears were stained with Wright
stain (Sigma). The cells with three or more HEMA particles were
considered positive. Mice were injected with either glucan or
PBS (control). All experiments were performed in triplicate. At
least 300 cells were examined in each experiment.
IL-2 secretion
Purfed spleen cells (2x10
/ml n RPMI 1640 medum wth 5%
FCS) obtaned from mce njected wth 100 mg glucan or PBS
were added nto wells of a 24-well tssue culture plate. Cells
were ncubated for 48 hrs n a humdfed ncubator (37
C, 5%
CO2/95% ar). Addton of 1 mg of Concanavaln A (Sgma)
was used as a postve control. At the endpont of ncubaton,
supernatants were collected, fltered through 0.45 mm flters
and tested for the presence of IL-2 usng a Quantkne mouse
IL-2 kt (R&D Systems, Mnneapols, MN).
Antibody formation
The technique was described earlier [
]. Briefly: formation
of antibodies was evaluated using ovalbumin (Sigma) as an
Glucan Source Solubility Manufacturer
Beat Max Ye a s t Insoluble Chisolm Biological Laboratories, Aiken, SC
Oat Beta Glucan Oat Insoluble Health Breakthroughs, Lake Oswego, OR
Bio-Glucan Ye a st Insoluble Pharma Nord, Vojens, Denmark
Qore defense Mushroom Insoluble Quivana, Provo, UT
Immunox 3-6 Ye a s t Insoluble Xymogen, Orlando, FL
Betacan 500 Ye a s t Insoluble Arrowhead Healthworks, Cedarpine Park, CA
Glucan Real Mushroom Soluble QueGen Biotech, South Korea
MC-Glucan Mushro om Soluble Macrocare Tech, South Korea
Beta Glucan (Germany) Ye a s t Insoluble Biotikon, Germany
Barley Glucan Barley Insoluble Sigma, St. Louis, MO
Beta Glucan Mushroom/yeast Partly soluble Vitabase, Monroe, GA
Reishi Mushroom Soluble Hostdefence, Olympia, WA
Beta Glucan Yea s t Insoluble Greenpath, Wrightsville Beach, NC
Hliva ustricna Mushroom Insoluble Walmark, Trinec, Czech Republic
Glucan #300 Ye a s t Insoluble Transfer Point, Columbia, SC
Table 1. Types of glucan used.
Vetvicka et al.
Applied Scientic Reports
doi: 10.7243/2054-9903-1-2
antigen. Mice were injected twice (two weeks apart) with 100
µg of albumin and the serum was collected 7 days after last
injection. Experimental groups were getting daily ip. injections
of glucan. Level of specific antibodies against ovalbumin was
detected by ELISA. As positive control, combination of oval-
bumin and Freunds adjuvant (Sigma) was used.
Superoxide production
Mouse neutrophils were isolated using Ficoll-Hypaque
separation as described [
]. Cells (either peripheral blood
neutrophils or HL-60 cell line) were incubated in a final volume
of 200 µl of medium containing 0.1% gelatin and 100 µM
cytochrome C (Sigma). Mice were challenged with 100 µg of
individual glucans 24 hrs earlier. Cells were incubated with
1 µg/ml of glucans for 24 hrs. For the superoxide production,
the reaction was initiated by the addition of 5 ng/ml PMA
(Sigma). Incubation was terminated by rapid cooling the cells.
Superoxide production was quantitated by measuring the
reduction of cytochrome c (Type VI, Sigma, 100 nmol/tube).
After gentle mixing, the absorbance was measured 30 minutes
after incubation at 37
C using multiwell spectrophotometer at
550 nm. Results are expressed as nanomoles of cytochrome
C reduced/2.5x105 cells/30 minutes, after subtraction of the
superoxide dismutases and spontaneous release controls [
IFNγ production
Twenty four hours after ip. injection with 100 µg of glucan,
the mice were sacrificed, blood collected, serum prepared
and filtered through 0.45 µm filter. The level of IFNγ was deter-
mined using Quantikine mouse IFNγ kit (R&D Systems, Min-
neapolis, MN, USA) as described earlier [14].
Glucans are manufactured, tested and used in almost every
country of the world. For our study, we decided to use several
samples differing in the source (yeast, mushroom, oat and
barley), solubility (both soluble and insoluble), and origin
(United States, Germany, Denmark, South Korea and Czech
Republic). All of these glucans are commercially available,
often in several countries. Basic information about individual
types of glucan and their manufacturers or distributors are
given in Table 1. Almost none of the manufacturers provide
any information about solubility. We tested the solubility by
solubilization of three different concentrations of glucan in
water at 22oC under constant shaking for 30 minutes. Based
on the amount of sugar measurable in the solution after filtra-
tion (data not shown), we called the sample soluble (over 90%
of glucan), semisoluble (20-89%) or insoluble (below 20%).
The effects of glucans on cellular immunity are well estab-
lished. Usually, the test of choice are the effects on phagocytosis,
as if the glucan does not stimulate phagocytosis, it might have
little effects on additional facets of the defense reactions. As
in our previous comparative study, we employed synthetic
hydroxyethyl methacrylate particles [16] known for minimal
nonspecific adhesion to the membrane of phagocytosing
cells [
]. We injected the mice with different doses of glucan
and 24 hrs later tested the effects of glucans on phagocytic
ability of peripheral blood neutrophils. Data shown in Table 2
Dose (mg) 25 50 100 200 400 800
BetaMax 33.1±2.9 30.9±3.1 35.1±4.2 37.7±3.2*38.8±3.5*37.9±2.9*
Oat Beta Glucan 30.7±1.9 32.5±2.7 34.1±2.8 33.6±2.6 35.5±3.7 36.2±2.8
Bio-Glucan 32.5±2.6 34.1±2.5 38.8±3.1*40.2±3.0*42.8±3.3*44.1±3.1*
Qore defense 30.9±2.2 33.7±2.9 34.9±3.2 35.9±3.1 36.6±1.8 36.8±4.2
Immunox 3-6 38.5±2.2*39.9±3.3*43.4±4.1*45.3±3.1*46.2±4.1*46.9±3.2*
Betacan 500 32.1±1.8 33.2±2.8 34.8±3.3 36.6±2.8 35.8±2.9 37.7±3.2
Glucan Real 31.8±1.8 34.2±3.3 37.1±1.2*40.2±1.7*42.2±1.9*44.4±2.9*
MC-Glucan 31.8±1.6 34.1±0.9 34.1±2.7 38.1±1.9 38.9±2.2 40.7±2.2
Beta Glucan (Germany) 32.6±2.2 35.1±2.1 37.1±1.8*37.9±2.2*38.1±1.9*41.1±2.1*
Barley Glucan 31.8±1.1 32.1±0.8 33.1±0.9 34.1±2.1 35.8±3.2 34.8±2.2
Beta Glucan (Vitabase) 32.6±2.2 32.6±0.8 33.1±1.9 32.9±2.3 34.7±2.8 35.1±4.3
Reishi 31.7±0.7 33.1±0.9 35.6±1.9 37.6±1.0*38.9±2.4*40.6±2.7*
Beta Glucan (Greenpath) 30.9±0.9 31.8±1.1 33.1±1.5 34.0±1.1 34.6±2.3 35.1±3.3
Hliva ustricna 31.5±1.1 32.8±2.1 34.1±2.4 35.2±3.0 34.7±2.4 35.1±2.8
Glucan #300 44.1±2.5*48.8±2.1*55.7±3.2*56.1±2.9*55.9±3.2*60.9±4.0*
Control values (PBS) were 31.3±2.7. e dose means a single ip. injection in PBS/mouse.
*Signicant dierences between glucan and PBS at <0.05 level. Results shown as percentage of
phagocytosing blood neutrophils represent mean±SD, n was always more than 10.
Table 2. Eects of various glucans on phagocytosis.
Vetvicka et al.
Applied Scientic Reports
doi: 10.7243/2054-9903-1-2
demonstrate the effects of various doses of tested glucan
on phagocytosis of peripheral blood neutrophils. Several
trends can be observed–clear dose-dependency, several
glucans showed no activity even at the highest doses, and
the most active glucan (Glucan #300) reached the plateau at
a dose of 100 µg, with the level of stimulation not achieved
by other glucans even at a dose of 800 µg. The glucans with
consistent significant effects were Immunox 3-6 and Glucan
#300. Several others were active from the higher doses (Bio-
Glucan, Glucan-Real, Reishi and Beta Glucan from Germany).
Phagocytosis results in internalization of the prey, but rep-
resents only one of the several subsequent steps, leading to
burst of metabolic activity and final killing and/or destruction
of the ingested material. Therefore, we evaluated the effects of
our glucans on production of superoxide anion. To make sure
the test produced accurate data, we used two experimental
in vitro models–human cell line HL-60 and mouse neutro-
phils. Data shown in
Table 3
confirmed that almost all tested
glucans significantly increased the formation of superoxide
anion, with only Oat Beta Glucan and Barley Glucan having
no activity at all. The most active glucan was Glucan #300
followed by Bio-Glucan and MC-Glucan. For comparison, the
levels obtained using resveratrol-vitamin C-glucan mixture
reached 1.99 nmol/2.5x105 cells.
Glucans also have significant effects on various cytokines.
To compare the effects of our group of glucans, we measured
the production of IFN-γ in the blood (in vivo experiment) and
Glucan Mouse neutrophils
(nmol/2.5x105 cells)
BetaMax 1.12±0.11*1.23±0.25*
Oat Beta Glucan 0.35±0.05 0.44±0.11
Bio-Glucan 1.44±0.23*1.48±0.37*
Qore Defense 0.65±0.24*0.64±0.15*
Immunox 3-6 1.07±0.25*1.22±0.21*
Betacan 500 0.87±0.30*0.79±0.29*
Glucan Real 1.31±0.25*1.43±0.36*
MC-Glucan 1.44±0.41*1.55±0.26*
Beta Glucan (Germany) 0.78±0.22*0.99±0.32*
Barley Glucan 0.38±0.09 0.43±0.12
Beta Glucan (Vitabase) 0.78±0.13*0.88±0.23*
Reishi 0.99±0.23*1.12±0.34*
Beta Glucan (Greenpath) 0.76±0.22*0.89±0.24*
Hliva ustricna 0.56±0.12*0.75±0.21*
Glucan #300 1.69±0.34*1.55±0.27*
PBS 0.25±0.08 0.35±0.07
*Signicant dierences between glucan sample and PBS
control at P<0.05 level. Results represent mean±SD,
n was always more than 10.
Table 3. Eect of individual glucans on superoxide anion
IL-2 by splenocytes (in vitro). The secretion of IL-2 by untreated
murine splenocytes is zero, therefore all glucans significantly
increased the IL-2 production (
Table 4
). It is clear, that the
Concanavalin A elicited the highest response, with Glucan
#300 being close. Several other glucans showed high activ-
ity–Bio-Glucan, Immunox 3-6, Glucan Real and MC-Glucan.
Similar effects were seen in stimulation of IFN-γ secretion.
Again, due to absolutely minimal level of IFN-γ in control
mice, all glucan caused statistically significant stimulation.
The glucans with highest activity were Glucan #300, Immunox
3-6, Beta Glucan (Germany) and Reishi. As positive control, we
used in vivo stimulation with LPS which increased the IFN-γ
level in the blood up to 400-500 pg/ml.
Table 4. Eect of individual glucans on IL-2 and IFN-γ secretion.
All glucans showed signicant stimulation of IL-2 secretion
at P<0.01 level. e PBS control showed no IL-2 production.
All glucans showed signicant stimulation of IFNγ secretion
when compared to PBS (P<0.01 level). Results represent
mean±SD, n was always more than 10.
In the next step, we focused on the role of tested substances
in cancer development. As an experimental model, we used
mice challenged with Ptas64 mammary tumors. Two weeks
of glucan injections caused significant reduction of cancer
growth (measured as tumor weight) in five cases–Glucan
#300, Immunox 3-6, Glucan Real, Beta Glucan (Germany) and
Reishi. In all other cases, the reduction was either statistically
insignificant or the glucans had no effects at all (Table 5).
In the last part of our study, we evaluated the less known
area of glucan effects-antibody response. We used an immuni-
zation of mice with ovalbumin, where glucans were applied
Glucan IL-2 (pg/ml) IFNγ (pg/ml)
BetaMax 78.3±8.9 25.3±1.9
Oat Beta Glucan 62.2±5.5 41.2±2.5
Bio-Glucan 363.3±14.4 65.2±4.0
Qore Defense 30.1±2.1 30.3±2.4
Immunox 3-6 611.1±83.9 116.1±7.8
Betacan 500 87.9±6.6 27.9±2.1
Glucan Real 442.2±87.5 82.3±2.5
MC-Glucan 459.9±64.4 59.9±2.4
Beta Glucan (Germany) 223.6±11.8 103.6±5.8
Barley Glucan 12.9±1.1 22.3±1.0
Beta Glucan (Vitabase) 230.8±11.3 39.8±1.1
Reishi 288.8±24.4 128.5±4.9
Beta Glucan (Greenpath) 174.4±36.6 84.0±6.2
Hliva ustricna 39.9±3.2 9.9±0.8
Glucan #300 983.9±122.8 201.2±11.5
Con A 1 103.3±291.2 ND
PBS 0 2.1±0.2
Vetvicka et al.
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doi: 10.7243/2054-9903-1-2
together with two separate intraperitoneal injections of anti-
gen. As positive control, ovalbumin was used with Freund’s
adjuvant. The results summarized in Table 6 showed that six
different glucans significantly increased the specific antibody
response–Qore Defense, Immunox 3-6, Glucan Real, Beta
Glucan (Germany), Reishi and Glucan #300/.
Glucan Tumor weight (mg)
BetaMax 512.7±49.9
Oat Beta Glucan 501.7±45.5
Bio-Glucan 499.1±46.2
Qore Defense 501.3±33.7
Immunox 3-6 348.9±40.2*
Betacan 500 522.3±47.8
Glucan Real 467.7±34.7*
MC-Glucan 511.8±40.1
Beta Glucan (Germany) 476.2±38.8*
Barley Glucan 611.6±53.6
Beta Glucan (Vitabase) 512.8±42.4
Reishi 411.1±32.7*
Beta Glucan (Greenpath) 601.0±52,3
Hliva ustricna 603.5±55.6
Glucan #300 286.1±23.5*
PBS 622.6±52.5
Table 5. Eect of individual glucans on suppression of breast
*Signicant reduction of tumor weight at P<0.05
level (individual glucans vs. PBS control). Each
group consisted of at least 9 mice evaluated in three
independent experiments. Results represent mean±SD.
Glucan % of control
BetaMax 102.4±10.8
Oat Beta Glucan 111.6±21.2
Bio-Glucan 125.4±14.8
Qore Defense 133.1±12.5*
Immunox 3-6 296.1±17.2*
Betacan 500 128.3±20.3
Glucan Real 201.3±18.5*
MC-Glucan 129.9±9.9
Beta Glucan (Germany) 207.6±16.8*
Barley Glucan 111.9±11.0
Beta Glucan 130.6±14.8
Reishi 189.8±14.7*
Beta Glucan 126.1±17.2
Hliva ustricna 109.2±9.8
Glucan #300 343.9±43.1*
Ovalbumin+adjuvant 509.9±45.5*
Table 6. Eect of individual glucans on antibody formation.
*Signicant stimulation at P<0.05 level. Results represent
mean±SD, total number of mice was 9/group.
Glucans are carbohydrates consisting of linked glucose mole-
cules, which are major structural components of the cell walls
of yeast, fungi and some bacteria. In addition, cereals such as
barley and oat contain glucans as a part of their endosperm.
Glucans are the most studied natural immunomodulators
which, due to the numerous ongoing human clinical trials,
have the strongest chance to become an approved drug even
in Western medicine. However, it is often difficult to compare
the effects of glucan differing in source, isolation techniques,
solubility and other physicochemical characteristics such
as branching or molecular weight. These comparisons are
possible only when individual glucans are compared in one
study using identical experimental design. Despite thousands
of scientific papers, often describing new and new types of
glucan, comprehensive reviews comparing individual biological
or immunological activities are rare. Most of them are focused
more on the relation between biological activities and chemical
properties [
], which does not fully help to answer the
question which glucan is better. Other comparative studies
focused on comparison of glucans extracted from oat, wheat
or barley, but the studied effects were focused on effects on
liver and glucose regulation [15]. However, there are no similar
comparative studies on glucan and immune reactions.
In our previous work, we directly compared 16 different
glucans [16]. From the time of publishing of the original study,
the number of commercially available glucans multiplied in
numerous countries. This inspired us to compare the new
batch of available glucans. In the present paper, we used some
of the same reactions (phagocytosis, superoxide formation,
antibody reaction and IL-2 secretion) that have already been
published. However, the original study showed that some
glucans stimulate some types of immune reactions, and are
without any activity in other areas of immunity. Therefore,
for better evaluation of individual glucans, we added two
more activities - IFN-γ secretion in blood and suppression of
breast cancer growth.
Phagocytosis usually represents the first studied effects of
glucan, as this molecule was originally described as nonspecific
modulator of macrophages. In our study, we employed the
synthetic microbeads based on 2-hydroxyethyl methacrylate
polymer, since they represent good experimental material
for these types of the study. These microbeads are known
for their minimal nonspecific adhesion to the cell membrane,
thus limiting the false positivity [20]. Our data showed that
50% of the tested glucans had no stimulative activity even
after the highest dose (800 µg). On the other hand, the best
glucans demonstrated significant activity even at the lowest
dose. The differences in dose required to elicit significant stim-
ulation might be up to 8x. In addition, most glucans did not
reached the activities of the most active glucan even at 32x
higher dose.
Another part of the internalization process is the subse-
quent burst of metabolic activity. Part of it is the production
Vetvicka et al.
Applied Scientic Reports
doi: 10.7243/2054-9903-1-2
of active oxidative species, necessary for killing and destruc-
tion of bacteria (for review see [23]). Glucans were repeatedly
shown to stimulate oxidative burst [24,25]. All mushroom-and
yeast-derived glucans stimulated production of superoxide
anion, where as oat-derived glucans did not. One can only
speculate why the oat glucan had no such activity, even when
they can be as active in cancer inhibition as glucan from other
sources. The most probable explanation might be the low
purity of the oat glucans used in this study or by higher vis-
cosity of these glucans.
Glucans are well known to stimulate production and se-
cretion of various cytokines, with a wide range from IL-1, IL-2,
and IL-6 to TNFα, and IFNγ [26,27]. In fact, there is only one
known glucan without any significant stimulation of cytokine
production [28]. For our purposes, we measured the effects
of glucans on production of IL-2 by splenocytes and level of
IFNγ in peripheral blood. Under normal circumstations, spleno-
cytes do not produce IL-2, so the basal levels are almost zero.
As a result, all glucans showed significant stimulation of Il-2
production, with Glucan #300, Bio-Glucan, Glucan Real, Im-
munox 3-6 and MC-Glucan showing highest effects. However,
only Glucan #300 reached levels comparable with positive
control (Concanavalin A). A similar situation has been found
in case of IFNγ, where the strongest activity was associated
with Glucan #300, Immunox 3-6, Beta Glucan (Germany) and
Reishi. It is clear, therefore, that individual glucans significantly
differ in their abilities to stimulate production and/or secre-
tion of individual cytokines.
Recently, glucans have been shown to stimulate not only
the cellular branch of immune reactions, but also the antibody
formation [29,30], leading to suggestions that glucan can be
part of vaccination. In farmed animals such as fish or chicken,
glucan inclusion in vaccine is already being intensively studied
]. Six of our group of glucans significantly stimulated
secretion of specific anti-ovalbumin antibodies, with Glucan
#300 being the most active one.
The last part of our study was devoted to the effects of
glucans on breast cancer growth. We used previously estab-
lished technique using murine cell line [
]. Five of our glucans
significantly decreased the growth of breast cancer cells.
Our study clearly demonstrated that there are severe differ-
ences in immunological activities among our selected group of
glucans. Similarly to our previous study [
], we tested fifteen
varieties of glucans differing in source and solubility. Based on
previous studies, we included Glucan #300 as the benchmark.
We confirmed that some glucans can have significant effect
on some defense reactions, whereas have little or no activity
on others (e.g., Qore Defence had no activity on tumor sup-
pression, but stimulated antibody secretion). Several glucans
consistently showed higher biological activities, most of all
Immunox 3-6, Glucan Real, Beta-Glucan (Germany) or Reishi,
but in every tested reaction, the Glucan #300 was the most
active sample. The differences between individual glucans
found in this report might explain the sometimes confusing
results published in the literature. It is clear that the immu-
nological and biological effects of individual glucan are not
connected to their source or solubility.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
Publication history
Editor: Joseph L. Evans, P & N Development Ventures, USA.
Received: 05-May-2014 Final Revised: 01-Aug-2014
Accepted: 13-Aug-2014 Published: 23-Aug-2014
Authors’ contributions VV JV
Research concept and design ✓ ✓
Collection and/or assembly of data ✓ ✓
Data analysis and interpretation ✓ ✓
Writing the article ✓ ✓
Critical revision of the article ✓ ✓
Final approval of article ✓ ✓
Statistical analysis ✓ ✓
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... They are recognized by the organism which triggers a Review of the Literature series of events in the immune response. It is common knowledge in the scientific community that β-glucan is a powerful molecule and can be used to treat several diseases (Akramienè et al., 2007;Vetvicka & Vetvickova, 2014). ...
... AST is often used as an indicator of muscle damage [40]. However, 286 creatine kinase, another enzyme used to judge muscle [6], was unaffected by treatment. ...
... The style and the punctuation of the references must be in conformity with the following examples: Philadelphia, 1991, 162-194. In the text, the references are called by their sequence number between square brackets: [ 5 ], [5][6][7][8]11 ], [ 6,45,78 ]. ...
The peri-partum period is a critical time for small ruminants because nutritional requirements are very high and feed intake is often limited. Nutritional diseases, such as pregnancy toxemia, can develop. Farmers try to limit these problems. β-glucan and saponin-based plant extracts have been shown to have favourable effects on animal production: immune-modulation for the former and reduced methane production and modification of rumen fermentation patterns for the latter. However, little is known about their effects on metabolism. Therefore, the general objective was to better understand the effects of 1) β-glucan injections and 2) dietary saponin, on metabolism and rumen fermentation in small ruminants during the transition period. The influence of β1,3-glucan (i.m. injections, 1ml/animal/week for 60 days) on the metabolic profile of 14 Santa Inês ewes in the last weeks of gestation was studied. Two groups of ewes were formed in late gestation: a glucan group (G, n=7) and a control group (C, n=7). Nutritional requirements during the experiment were covered. Blood samples were collected throughout the study. Blood samples were analysed for metabolites, ions and enzymes. All ewes were clinically healthy. Glucose, L-lactate, non-esterified fatty acids and β-hydroxybutyrate peaked at parturition (p<0.05). Aspartate aminotransferase (AST) was higher in C vs. G (p<0.05) and there was a similar trend for fructosamine and albumin (p<0.10). Urea tended to be higher in G vs. C (p<0.10). In conclusion, the changes with time were consistent with a change in physiological status (gestation/lactation). β1,3-glucan appeared to protect muscle and liver because AST levels were lower than in controls and it did not negatively affect metabolism. The influence of a dietary saponin-based additive (25g saponin/animal/day) on the metabolic and rumen fermentation profile of Saanen and Alpine dairy goats during two different metabolic situations: metabolic neutrality (mid-lactation) and metabolic imbalance (pregnancy/lactation) was studied in two experiments. Experiment 1, used mid-lactating goats (Saponin group (S), n=10; Control group (C), n=10). The 6 week experiment was divided into: 1 week of C diet, 4 weeks either S or C and 1 week C. Experiment 2, used peri-parturient goats (Saponin group (S), n=12; Control group (C), n=12). The 7 week experiment was divided into: 1 week C diet, 4 weeks either S or C (stopping at parturition) and 2 weeks C. Nutritional requirements during the experiments were covered. Blood samples and rumen fluid were collected throughout both experiments. Blood samples were analysed for metabolites, ions and enzymes. All the goats were clinically healthy. There was no effect of saponin in experiment 1 on animal husbandry measures, plasma metabolites and ruminal fermentation (p>0.05). The ruminal acetate to propionate ratio tended to be affected by treatment (S < C; p=0.057). There was no effect of saponin in experiment 2 on blood metabolites (p>0.05), except for plasma urea (S > C; p=0.054). Total protozoa numbers tended to be affected by treatment (S > C; p<0.10). Most of the animal husbandry, plasma and ruminal variables showed a time effect around parturition (p<0.05). In conclusion, dietary saponin during mid-lactation or the peri-partum period had little effect on metabolism and ruminal fermentation. The trends observed in blood urea, total protozoa count and acetate/propionate ratio could be potentially beneficial. Lastly, the potential for saponin to influence ruminal fermentation may depend on the level, the period of administration and the type of diet. β-glucan and saponin did not have a negative effect on metabolism and it would be interesting to conduct further work in animals suffering from pregnancy toxemia. Studies could also be conducted on the possible immune actions of β-glucan and saponin.
... Algae β-glucans have demonstrated improved immunity in dogs [141]. In mice, the bioactives had significant effects as a prophylactic treatment to reduce anthrax infection and inhibition of cancer cells through stimulation of cytokines [142,143]. Sheep oral supplementation to ewes had positive effects on reproductive performance, growth rate and body composition [144]. Lambs, when administered β-glucans, had a significant increase in phagocytic and respiratory burst activities [145,146]. ...
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β-glucans are complex polysaccharides that are found in several plants and foods, including mushrooms. β-glucans display an array of potentially therapeutic properties.
... Fungal and yeast β-glucans comprise of (1,6)-β-linked side chains on a (1,3)-β-linked backbone and hold immense immunemodulating effects (Stier et al., 2014). Vetvickova (2014 and2016) have described the role of β-glucan in increasing phagocytosis, and production of IL-2, IFNγ, and antibodies. Murphy et al. (2020) demonstrated the utility of β-glucans in alleviating lung infections in ARDS. ...
... To better understand the biological effects of glucans and to further increase the chance that glucans are used in Western medicine, it is important to directly compare glucans using identical methods. Our previous studies compared over 60 individual glucans (12,31,32), but the ever increasing multiplication of new commercial glucans led us to compare some of the new glucans with glucan #300, which has been previously shown to be superior. ...
Background/aim: The aim of this study was to directly compare the anti-infectious and anti-cancer effects of five commercially available glucans. Materials and methods: We used five different glucans isolated from algae, yeast, bacteria, oat, and mushroom. We compared their effects on the stimulation of phagocytosis of blood cells, on the secretion of IL-2, and on the inhibition of melanoma and breast and lung cancers. In addition, we evaluated the effects of glucan supplementation on two experimental models of infection. Results: Most of the tested glucans stimulated phagocytosis and IL-2 secretion, reduced cancer growth, and ameliorated some effects of experimental infections. Conclusion: Glucans can produce significant pleiotropic effects, but the activity varies among individual samples.
... In addition to affording energy, carbohydrates also play important roles in physiology, nutrition and immunology (Lopez et al. 2003). For example, glucans have been found to have pleiotropic effects stimulating all facets of immunological reactions (Vetvicka & Vetvickova 2014). Different carbohydrate sources influenced the growth, body composition, ammonia tolerance and hepatopancreas histology of L. vannamei ). ...
Because of the increasing market potential of Pacific white shrimp (Litopenaeus vannamei) and limited availability of coastal areas for production, culture of L. vannamei at low salinity is a growing trend throughout the world. Dietary manipulation could improve the growth performance of L. vannamei at low salinity. This study reared L. vannamei with glucose, sucrose and corn starch as dietary carbohydrate sources, respectively, at a low salinity. The results indicated that the sucrose and glucose feeding groups showed better growth performance. An Illumina-based sequencing method was used to examine the intestinal bacterial composition and the results indicated that Proteobacteria were the most prevalent members, but abundance of Actinobacteria decreased while Firmicutes increased in the corn starch-fed group. Furthermore, bacteria related to complex carbohydrate degradation were in lower abundance, whereas the abundance of opportunistic pathogenic bacteria increased in corn starch-fed group than the other two groups, suggesting that the diet imposes selective pressure on the intestinal microbiota. Complex carbohydrates were not the ideal energy sources for L. vannamei at low salinity because the host has higher energy demand in the stressful conditions while the complex carbohydrate degradation efficiency of the gut microbiota in L. vannamei is limited.
... Despite numerous interesting reviews summarizing the current knowledge of glucan activities (24)(25)(26)(27), the best compare individual glucans against each other using identical experimental designs. In our previous studies, we directly compared over 50 individual glucans (12)(13)(14)(15)(16)18). However, the number of commercially available glucans has multiplied in many countries since, prompting us to compare the new batch of available glucans with glucan #300, which consistently showed the highest activities in the previous studies. ...
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Background/aim: β-Glucans are well-established immunomodulators with strong effects across all immune reactions. Due to the extensive amount of studies, glucans are steadily progressing from a non-specific immunomodulator to a licensed drug. However, direct comparisons of higher numbers of different glucans are rare. Materials and methods: In this study, we used 16 different glucans isolated from yeasts, mushroom, algae, and oat and compared their effects on phagocytosis, IL-2 production, antibody secretion, and inhibition of three experimental cancer models. Results: Our results showed significant differences among tested glucans, showing that despite the fact that glucans in general have strong stimulating effects on most aspects of the immune system, it is necessary to choose the right glucan. Conclusion: Based on our studies, we can conclude that highly purified and active glucans have significant pleiotropic effects.
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With the COVID-19 pandemic causing huge threat to public health and definite treatment modalities and preventive vaccines yet to be arrived at, some of the key indicators of relevance to its prognosis have started emerging. One such independent predictor of outcome has been fasting plasma glucose (FPG) at the time of admission. Earlier, co-morbidities such as diabetes also have been reported to have a risk of relatively increased mortality due to COVID-19. In this background, we herein report on the beneficial effects of Biological response modifier glucan (BRMG) secreted by the black yeast Aureobasidium pullulans AFO-202 which has been proven to bring under control blood sugar levels in human subjects and also has potential in enhancing & regulating the immune parameters in relevance to COVID-19. We further recommend that this BRMG be tried in clinical studies of COVID-19 to provide a prophylactic effect for validation.
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Nonalcoholic steatohepatitis (NASH) is becoming a huge global health problem. Studies showed that β‐glucan displayed potent anti‐inflammatory and other multi‐beneficial pharmacological properties. Thus, the objective of this study was to investigate the effects of β‐glucan on NASH mice induced by the MCD diet. After 8 weeks of β‐glucan treatments, results showed that β‐glucan effectively decreased the serum ALT and AST levels compared with the MCD model. Besides, histopathological results demonstrated that β‐glucan significantly attenuated the fat accumulation, steatosis, and inflammation in the liver compared with that of the MCD group. Furthermore, the ER stress‐responsive proteins, including GRP78, p‐eiF‐2α, and p‐JNK, were markedly restrained by β‐glucan, while ERp57, p‐MAPK, and p‐Akt were significantly increased after β‐glucan treatment. Collectively, our results suggested that β‐glucan beneficially resisted NASH induced by the MCD diet. The ER stress response may be involved in the mechanisms of action of β‐glucan. Practical applications This study is the first to report the hepatoprotective activity of β‐glucan against MCD diet‐induced NASH in mice, mainly reflecting its ability to ameliorate hepatic lipid accumulation and inflammation, with the mechanism possibly involving mediating the ER stress signaling pathway. Our results suggest that the β‐glucan has good application prospects to be used as a raw material in functional foods for the clinical treatment of NASH.
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Background: The COVID-19 pandemic has been causing varying severities of illness. Some are asymptomatic and some develop severe disease leading to mortality across ages. This contrast triggered us explore the causes, with the background that a vaccine for effective immunization or a drug to tackle COVID-19 is not too close to reality. We have discussed strategies to combat COVID-19 through immune enhancement, using simple measures including nutritional supplements. Discussion: A literature search on mortality-related comorbid conditions was performed. For those conditions, we analyzed the pro-inflammatory cytokines, which could cause the draining of the immune reservoir. We also analyzed the immune markers necessary for the defense mechanism/immune surveillance against COVID-19, especially through simple means including immune enhancing nutritional supplement consumption, and we suggest strategies to combat COVID-19. Major comorbid conditions associated with increased mortality include cardiovascular disease (CVD), diabetes, being immunocompromised by cancer, and severe kidney disease with a senile immune system. Consumption of Aureobasidium pullulans strain (AFO-202) beta 1,3-1,6 glucan supported enhanced IL-8, sFAS macrophage activity, and NK cells' cytotoxicity, which are major defense mechanisms against viral infection. Conclusion: People with co-morbid conditions who are more prone to COVID-19-related deaths due to immune dysregulation are likely to benefit from consuming nutritional supplements that enhance the immune system. We recommend clinical studies to validate AFO-202 beta glucan in COVID-19 patients to prove its efficacy in overcoming a hyper-inflammation status, thus reducing the mortality, until a definite vaccine is made available.
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The role of glucan in stimulation of immune reactions has been well-established. In this report, we focused on the antibody production in glucan-supplemented children with chronic respiratory problems. We measured the levels of salivary IgA, IgM and IgG in 40 children aged 8-12 years and evaluated the effects of 100 mg d −1 oral dose of glucan. We found a significant increase in production of all tested antibodies in the glucan-stimulated group, but a decrease of antibody production in the control group. A thirty-day oral application of yeast-based natural immunomodulator β-glucan strongly stimulated the mucosal immunity of children with chronic respiratory problems.
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Background: The role of glucan in the stimulation of immune reactions is well established. In our report, we focused on the effects of orally administered glucan on nonspecific immunity of children with chronic respiratory problems. Materials and methods: We measured the levels of albumin, lysozyme. C-reactive protein (CRP) and calprotectin in the saliva of 60 children ages 8-12 years and evaluated the effects of 30-day treatment with 100 mg/d oral dose of glucan. Results: We found a significant increase in the production of lysozyme, CRP and calprotectin in glucan-treated children. Conclusions: Short-term oral application of natural immunomodulator β-glucan significantly stimulated mucosal immunity of children with chronic respiratory problems.
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Background: The role of glucan in stimulation of immune reactions has been studied for several decades. In this report, we focused on the effects of orally administered glucan Maitake and Shiitake on immune reactions. Materials and methods: We measured phagocytosis, NK cell activity, and secretion of IL-6, IL-12, IFN-γ as well as C-reactive protein (CRP) after 14 days of oral application of tested glucans. For comparison, active hexose correlated compound (AHCC) was used in all reactions. Results: We found significant stimulation of defense reaction. In all cases, the most active was the Maitake-Shiitake combination, with Maitake alone being the second strongest, followed by Shiitake on its own and AHCC. Conclusions: Short-term oral application of natural immunomodulating glucans from Maitake and Shiitake mushrooms strongly stimulated both the cellular and humoral branch of immune reactions. These activities were significantly higher than those of AHCC.
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Purpose: To report on a phase I trial designed to find the maximally tolerated dose in children of the immunologic adjuvant OPT-821 in a vaccine containing neuroblastoma-associated antigens (GD2 and GD3; NCT00911560). Secondary objectives were to obtain preliminary data on immune response and activity against minimal residual disease (MRD). Treatment also included the immunostimulant β-glucan. Experimental design: Patients with neuroblastoma in ≥2nd complete/very good partial remission received vaccine subcutaneously (weeks 1-2-3-8-20-32-52). Vaccine contained 30 μg each of GD2 and GD3 stabilized as lactones and conjugated to the immunologic carrier protein keyhole limpet hemocyanin; and OPT-821, which was dose escalated as 50, 75, 100, and 150 μg/m(2) per injection. Oral β-glucan (40 mg/kg/day, 14 days on/14 days off) started week 6. Results: The study was completed with 15 patients because there was no dose-limiting toxicity at 150 μg/m(2) of OPT-821 (the dosing used in adults). Thirteen of fifteen patients received the entire protocol treatment, including 12 who remain relapse-free at 24+ to 39+ (median 32+) months and 1 who relapsed (single node) at 21 months. Relapse-free survival was 80% ± 10% at 24 months. Vaccine and β-glucan were well tolerated. Twelve of fifteen patients had antibody responses against GD2 and/or GD3. Disappearance of MRD was documented in 6 of 10 patients assessable for response. Conclusions: This immunotherapy program lacks major toxicity and is transportable to any outpatient clinic. Patient outcome is encouraging but the efficacy is uncertain because of the complexity and heterogeneity of prior therapies. A larger phase II trial is underway.
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Glucans, or polymers of D-glucose linked by (1→3)-β and (1→6)-β glycosidic linkages are the common polysaccharides of the fungal cell wall. They are usually located in the inner part of the wall and play the role of skeletal polysaccharide contributing to the shape and rigidity of the cell wall. The β-glucan molecules are interlinked by the hydrogen bonds and sometimes occur in a complex with other polysaccharides, such as chitin.β-Glucans isolated from the various yeast and fungal species may have different molecular weight or other structural parameters such as degree of branching or the length of the side-chains which may affect their solubility in water. Many fungal β-glucans possess remarkable ability to enhance the immune system, i.e. act as immunomodulators. Numerous studies have demonstrated the activity of β-glucans as biological response modifiers that are able to exert beneficial effect in host by demonstrating antitumor, antibacterial, antiviral and antiparasitic activities. Some studies have attempted to correlate biological activity of individual β-glucans to their spatial structure or helical conformation. However neither such correlation nor the precise mechanism of the activation of the immune system by β-glucans have been unambiguously proven.The present article reviews the existing knowledge on the immunological activity of the fungal β-glucans and provides some recent results on the radioprotective and antimutagenic activity of the β-glucan isolated from the baker's yeast.
Immunologists as well investigators in other disciplines may often use protocols involving the isolation, cultures and characterization of different types of leukocytes. Advanced Methods in Cellular Immunology is a collection of techniques in an easy-to-use format. Each chapter provides readers with related program information, a step-by-step description of the methodology, alternative techniques, pertinent references, and information about commercial sources for materials and regents. In addition to leukocytes, the authors guide readers through the processes of cell culture as well as inflammation and autoimmunity in a variety of animal models. Covering topics such as PCR and Apoptosis, this book will serve a guide to commonly used procedures in cellular immunology while utilizing both human and murine models.
Objective: To examine the safety and efficacy of multiple doses of PGG-glucan (poly- [ 1-6]-B-Dglucopyranosyl-[ 1-3]-B-D-glucopyranose) in high-risk patients undergoing major thoracic or abdominal surgery. Design: An interventional, multicenter, double-blind, randomized, placebo-controlled study. Setting: Four university-affiliated medical centers. Patients: Sixty-seven high-risk patients undergoing major thoracic or abdominal surgery. Intervention: Patients were randomized in a 1:1:1:1 ratio to receive saline placebo or PGG-glucan at a dose of 0.1 mg/kg, 0.5 mg/kg, and 1.0 mg/kg or 2.0 mg/kg. One dose was administered before surgery and three doses were administered after surgery. Main Outcome Measures: To examine the safety and efficacy of PGG-glucan infusion and to identify potentially important factors for a planned phase III study. Results: A dose-response trend with regard to infection incidence among patients who received PGG-glucan was observed. Serious infections occurred in four patients who received placebo and in three patients who received PGG-glucan at a dose of 0.1 mg/kg. However, only one patient who received PGG-glucan at a high dose had a serious infection. The incidence and severity of adverse events was comparable in all groups. Conclusions: PGG-glucan was generally safe and well tolerated, may decrease postoperative infection rates, and warrants further investigation in a planned phase III trial.(Arch Surg. 1994;129:1204-1210)
Physicochemical properties of different β-glucan purified from oat, barley and wheat, were investigated by measuring the composition, molecular weight, intrinsic viscosity ([η]), and rheological properties. The main objective was to investigate the relationship between effects of regulation of cholesterol metabolism and antioxidant property on db/db diabetic mice of β-glucans and their molecular weights and viscosities. Metformin was used as the positive control. The levels of blood glucose, serum lipid, liver lipid, superoxide dismutase (SOD) and malondialdehyde (MDA) in liver were determined. Results showed that average values of molecular weight (MW) of β-glucan from oat, wheat and barley were 172 kDa, 635 kDa and 743 kDa; the viscosities of β-glucans were positively correlated with their corresponded molecular weights, and wheat and barley β-glucan showed significant shear thinning ability compared to oat β-glucan; Barley β-glucans had higher G′ compared to wheat and oat, and the latter had higher G″. Blood glucose differences were not significant due to high variability, however serum TC, TG, liver TC, TG and LDL-C were lower in β-glucan fed groups compared to control. Moreover, the HDL-C was higher in β-glucan fed groups compared to control group. The addition of β-glucan fed to the db/db diabetic mice significantly (P < 0.05) increased their liver SOD activities and reduced their MDA levels (P > 0.05). A correlation between the measured biological parameters and the molecular weight or viscosity of β-glucan was observed. Lack of β-glucanase degeneration was the main cause of the low MW β-glucan and its diminished physiological effect.