ArticlePDF Available

Evidence-Based Review of BioBran/MGN-3 Arabinoxylan Compound as a Complementary Therapy for Conventional Cancer Treatment


Abstract and Figures

Introduction: Conventional cancer treatment, including surgery, chemotherapy, and radiotherapy, may not be sufficient to eradicate all malignant cells and prevent recurrence. Intensive treatment often leads to a depressed immune system, drug resistance, and toxicity, hampering the treatment outcomes. BioBran/MGN-3 Arabinoxylan is a standardized arabinoxylan concentrate which has been proposed as a plant-based immunomodulator that can restore the tumor-induced disturbance of the natural immune system, including natural killer cell activity to fight cancer, complementing conventional therapies. Objectives: To comprehensively review the available evidence on the effects and efficacies of MGN-3 as a complementary therapy for conventional cancer treatment. Methods: Systematic search of journal databases and gray literature for primary studies reporting the effects of MGN-3 on cancer and cancer treatment. Results: Thirty full-text articles and 2 conference abstracts were included in this review. MGN-3 has been shown to possess immunomodulating anticancer effects and can work synergistically with chemotherapeutic agents, in vitro. In murine models, MGN-3 has been shown to act against carcinogenic agents, and inhibit tumor growth, either by itself or in combination with other anticancer compounds. Fourteen successful MGN-3 treated clinical cases were found. Eleven clinical studies, including 5 nonrandomized, pre-post intervention studies and 6 randomized controlled trials (RCTs) were located. Reported effects include enhanced immunoprofile, reduced side effects, improved treatment outcomes; one RCT established significantly increased survival rates. There are no reports on adverse events on MGN-3. Most of the clinical trials are small studies with short duration. Conclusion: There is sufficient evidence suggesting MGN-3 to be an effective immunomodulator that can complement conventional cancer treatment. However, more well-designed RCTs on MGN-3 are needed to strengthen the evidence base.
Content may be subject to copyright.
Integrative Cancer Therapies
1 –14
© The Author(s) 2017
Reprints and permissions:
DOI: 10.1177/1534735417735379
Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-
NonCommercial 4.0 License ( which permits non-commercial use,
reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open
Access pages (
Review Article
Cancer is a leading cause of death worldwide with an esti-
mated 14.1 million new cases and 8.2 million cancer
deaths occurring worldwide in 2012.1 Conventional can-
cer treatment, including surgery, chemotherapy, and
radiotherapy, which focuses on eliminating cancer cells,
can be effective in the short term.2 However, such
approaches are insufficient to eradicate all malignant
cells, especially in advanced cancer, resulting in recur-
rence. Repeated cycles of such intensive treatment can
suppress the immune system, promote chemotherapy-
and radiotherapy-resistant tumors, as well as local and
systemic toxicity.3 Immunotherapy, which uses nonchem-
ical, biological substances called biological response
modifiers (BRMs) or immunomodulators to induce,
boost, or restore the body’s natural defense capability to
fight cancer,4 is now being acknowledged as an important
735379ICTXXX10.1177/1534735417735379Integrative Cancer TherapiesOoi et al
1Centre of Complementary & Alternative Medicine, Singapore
2Charles Sturt University, Bathurst, New South Wales, Australia
3St George Hospital, Sydney, New South Wales, Australia
Corresponding Author:
Sok Cheon Pak, School of Biomedical Sciences, Charles Sturt University,
Panorama Avenue, Bathurst, New South Wales 2795, Australia.
Evidence-Based Review of BioBran/
MGN-3 Arabinoxylan Compound as a
Complementary Therapy for
Conventional Cancer Treatment
Soo Liang Ooi, MMath, BHSc (Comp Med)1, Debbie McMullen, BHSc (Comp Med)2,
Terry Golombick, PhD, Dipl Nut3, and Sok Cheon Pak, PhD2
Introduction: Conventional cancer treatment, including surgery, chemotherapy, and radiotherapy, may not be sufficient to
eradicate all malignant cells and prevent recurrence. Intensive treatment often leads to a depressed immune system, drug
resistance, and toxicity, hampering the treatment outcomes. BioBran/MGN-3 Arabinoxylan is a standardized arabinoxylan
concentrate which has been proposed as a plant-based immunomodulator that can restore the tumor-induced disturbance
of the natural immune system, including natural killer cell activity to fight cancer, complementing conventional therapies.
Objectives: To comprehensively review the available evidence on the effects and efficacies of MGN-3 as a complementary
therapy for conventional cancer treatment. Methods: Systematic search of journal databases and gray literature for primary
studies reporting the effects of MGN-3 on cancer and cancer treatment. Results: Thirty full-text articles and 2 conference
abstracts were included in this review. MGN-3 has been shown to possess immunomodulating anticancer effects and can work
synergistically with chemotherapeutic agents, in vitro. In murine models, MGN-3 has been shown to act against carcinogenic
agents, and inhibit tumor growth, either by itself or in combination with other anticancer compounds. Fourteen successful
MGN-3 treated clinical cases were found. Eleven clinical studies, including 5 nonrandomized, pre-post intervention studies and
6 randomized controlled trials (RCTs) were located. Reported effects include enhanced immunoprofile, reduced side effects,
improved treatment outcomes; one RCT established significantly increased survival rates. There are no reports on adverse
events on MGN-3. Most of the clinical trials are small studies with short duration. Conclusion: There is sufficient evidence
suggesting MGN-3 to be an effective immunomodulator that can complement conventional cancer treatment. However,
more well-designed RCTs on MGN-3 are needed to strengthen the evidence base.
MGN-3, BioBran, Arabinoxylan, Ribraxx, systematic review, cancer, complementary medicine, chemotherapy,
chemoprotective, immunomodulation, immunotherapy, adjunct therapy, rice bran, adenocarcinoma, carcinogenesis
Submitted June 11, 2017; revised August 6, 2017; accepted September 12, 2017
2 Integrative Cancer Therapies
cancer treatment strategy that can work in combination
with conventional therapies.5,6
BioBran/MGN-3 Arabinoxylan (MGN-3) is a natural
blend of hemicelluloses derived from partially hydrolyzed
rice bran with shiitake mushroom enzymes (Lentinus edodes
mycelia extract). It is developed and manufactured in Japan
by Daiwa Pharmaceutical Co, Ltd, and marketed worldwide
as a nontoxic food supplement under different brand names
such as BioBran (Globally), Lentin Plus (Japan/Asia),
Ribraxx (Australia/New Zealand), BRM4 (United States),
and others.7 The main chemical structure of MGN-3 is an
arabinoxylan with a xylose in its main chain and an arabi-
nose polymer in its side chain. The result of a methylation
analysis suggests that a complex structure of heteropolysac-
charide (arabinogalactan, arabinoxylan, arabinan, β-1,3:1,4-
glucan) is behind the immunomodulatory mechanisms and
antitumor activity of MGN-3.8 MGN-3 has been promoted
as a plant-based BRM for enhancing the depleted immune
system during and after conventional cancer treatment,
claiming support from research findings and good clinical
To perform a comprehensive literature review of the available
evidence on the effects and efficacies of MGN-3 as a comple-
mentary therapy to support conventional cancer treatment.
Systematic searches were conducted using research databases
including PubMed, ProQuest, MEDLINE, EBSCOhost (All),
Cochrane CENTRAL, Embase, and EBM Review (All) with-
out any restriction in year of publications. Keywords used
include “MGN-3,” “BioBran,” “arabinoxylan,” “rice bran,”
and “plant immunomodulators” in combination with “cancer”
or “chemotherapy.” Additionally, the collected papers on
MGN-3 published by BioBran Research Foundation,10 the
official website of MGN-3 (, the English
language website of Daiwa Pharmaceutical (http://www., and the references of included
articles were searched manually. The criteria for inclusion
were (1) primary research reports published in English inclu-
sive of in vitro, in vivo, clinical study, and case reports and (2)
research studies focused on the effects of MGN-3 on any form
of cancer alone or as a combination therapy, or the combined
effects of MGN-3 with one or more chemotherapeutic agents,
or the effects of MGN-3 on cancer patients.
Search Results
Systematic searches were conducted by 2 authors (DM and
SLO) independently between March to May 2017. The
searches yielded 166 unique records after duplications were
removed. After initial screening, 48 articles were assessed
for eligibility. Sixteen articles were excluded with reasons
as follows: duplication (5),11-15 not cancer focused (7),16-22
not primary study (3),23-25 and 1 case report article pub-
lished in Japanese was also excluded.26 Thirty full-text arti-
cles and 2 conference abstracts were included in this review,
consisting of 7 in vitro studies;27-33 1 article reporting results
from both in vitro and in vivo studies;34 7 in vivo stud-
ies;35-41 6 clinical case reports;42-47 and 11 clinical stud-
ies,48-58 with one of them also including case reports of
selected follow-up patients.48 The literature search flow is
summarized in Figure 1.
In Vitro Studies
The characteristics of the in vitro studies are listed in Table
1. In these studies, both the immunomodulating and syner-
gistic anticancer effects of MGN-3 were demonstrated.
Immunomodulating Anticancer Effect. The growth of squa-
mous cell carcinoma (SCC13) was arrested after incubating
in MGN-3 for up to 72 hours.27 Tumor cell growth was
arrested with the increase in apoptosis through the CD95
death receptor pathway. An increase of more than 200% in
the rate of apoptosis of MGN-3 pretreated tumor cells
(human T cell leukemic HUT 78) to the agonistic anti-CD95
antibody was observed. The effect was shown to be dose
dependent.28 Compared with resting NK cells, MGN-3
stimulated NK cells induced a higher expression of the acti-
vation associated receptors CD25 and CD69. Statistically
significant increases in cytotoxicity of MGN-3 stimulated
NK cells against several cancer cells were consistently
observed, but cytotoxicity was absent against normal cells.34
Synergistic Anticancer Effect. MGN-3 works synergistically
with natural anticancer substances such as Saccharomyces
cerevisiae (Baker’s yeast) and curcumin, as well as chemo-
therapy drugs (daunorubicin and paclitaxel) in a dose-
dependent manner.
Ghoneum and Gollapudi29,30 confirmed the ability of
MGN-3 to accelerate the phagocytosis of S cerevisiae in
breast cancer and enhance the yeast-induced apoptosis of
breast cancer cells (BCCs).29,30 After incubating different
BCCs (MCF-7, ZR-75, HCC70) with heat-killed S cerevi-
siae and MGN-3, a 2-fold increase was observed in the
attachment and uptake of yeast by the treated MCF-7 cells,
compared with untreated cells, in a time-dependent man-
ner.30 Treatment with MGN-3 also resulted in a 1.8- to 2.5-
fold increase in the percentage of apoptosis in different
BCC cell lines.29 The yeast-phagocytosis and apoptosis
effect was not present in nontumorgenic breast cells.30
Culturing human multiple myeloma (MM) cell line
U266 with MGN-3 (50 or 100 μg/mL) and curcumin
Ooi et al 3
(2.5-10 μM) for 3 days, Ghoneum and Gollapudi32 also
showed that the proliferation of U266 cells was inhibited by
MGN-3 alone or curcumin alone.32 However, an optimal
synergistic effect was observed with a combination of 100
μg/mL MGN-3 plus 10 μM curcumin, characterized by an
87% decrease in U266 cell numbers and a 2.6-fold increase
in the percentage of apoptotic U266 cells.32
The survival rates of BCCs (MCF-7 and HCC70 cells)
cultured for 3 days with different concentrations of dauno-
rubicin (1 × 10−9 to 1 × 10−6 M) with or without MGN-3
(100-1000 μg/mL) were measured.31 MGN-3 increased the
accumulation of daunorubicin in the cancer cells and sig-
nificantly decreased the cell survival of MCF-7 (by 5.5-
fold) and HCC70 cells (by 2.5-fold) as compared to BCCs
treated with daunorubicin alone.31 Through a similar exper-
imental design in a later study, MGN-3 was demonstrated to
sensitize non-metastatic human BCC MCF-7 and metastatic
murine BCC 4TI to paclitaxel and to increase their suscep-
tibility to the chemotherapeutic agent by over 100-fold. The
synergistic effects include causing DNA damage, enhanc-
ing apoptosis, and inhibiting cell proliferation of BCCs.33
In Vivo Studies
The characteristics of the in vivo studies are listed in Table
2. Through various murine models, these studies showed
that MGN-3 could potentially prevent cancer, inhibit its
growth, and work synergistically with other chemothera-
peutic agents.
Preventive Effect Against Carcinogenic Agents. Significantly
lower incidences of dysplasia and gastric cancer were
observed in male Wistar rats fed with carcinogen methylni-
tronitrosoguanidine (MNNG) plus MGN-3, compared with
those administered MNNG alone.39 The preventive effects
of MGN-3 observed include suppression of Ki-67 tumor
marker, upregulation of apoptotic gastric cancer cells via
the mitochondrial-dependent pathway, and protection
against decrease in lymphocyte levels.39
Male albino rats pretreated with MGN-3 before receiv-
ing carcinogenic N-nitrosodiethylamine (NDEA) and car-
bon tetrachloride (CCl4) showed a significant reduction in
liver tumor incidence, marked decrease in the percentage of
Figure 1. Literature search flow diagram (based on PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]
4 Integrative Cancer Therapies
preneoplastic foci in hepatic parenchyma, and inhibition in
the development of hepatocellular carcinoma, compared
with controls. MGN-3 treated rats were also able to main-
tain close to normal levels of hepatic diagnostic markers.41
Inhibition of Cancer Growth. Female Swiss albino mice
bearing solid Ehrlich carcinoma (SEC) tumors were
treated with intraperitoneal injections of MGN-3.37,38
Compared with controls, MGN-3-treated mice exhibited
a significant delay in tumor growth measured by tumor
volume (63.27%) and tumor weight (45.2%), without any
observed adverse side effects due to the treatment.37 The
anticancer mechanisms of MGN-3 were shown to be
immunomodulating through upregulation of tumor necro-
sis factor-α (TNF-α) and interferon-γ (IFN-γ), and down-
regulation of interleukin-10 (IL-10), as well as inducing
apoptosis in the SEC cells.37 Elevated levels of antioxi-
dant enzymes such as superoxide dismutase, glutathione
peroxidase, catalase, and glutathione-S-transferase, in
blood and liver of MGN-3-treated animals comparable to
the normal levels were observed.38 The effects of MGN-3
treatment were more pronounced in mice that were treated
earlier rather than later.
NOD-scidIL-2Rgnull mice inoculated with neuro-
blastoma cells were treated with intravenous NK
cellular therapy using either fresh NK cells or NK cells
activated with MGN-3 overnight. The mice treated with
MGN-3 activated NK cells had upregulated NK cell
activation markers, significant neuroblastoma growth
inhibition, and higher survival rate compared to control
Synergistic Effects With Chemotherapeutic Agents. Female
Swiss albino mice inoculated with Ehrlich ascites carci-
noma cells were treated with paclitaxel only, MGN-3 only,
or MGN-3 plus paclitaxel. Tumor volumes were signifi-
cantly suppressed in MGN-3 plus paclitaxel group (88%
smaller relative to controls), compared with paclitaxel only
group (77%), and MGN-3 only group (59%).40
MGN-3 may also potentially protect against the adverse
effects of chemotherapeutic agents. Sprague-Dawley
derived albino rats fed with MGN-3 were healthier, gained
weight, and had a lower incidence of diarrhea and gross
intestinal pathology, after being administered a dose of
either cisplatin or doxorubicin, compared with control.35
Similarly, MGN-3 given either orally or intraperitoneally
to BALB/c female mice was shown to protect them from
severe weight loss associated with the injection of
Table 1. Characteristics of the Included In Vitro Studies.
No. Study Target Cell MGN-3 (μg/mL) Combined Agent Duration Outcomes
1 Ghoneum et al
(2000)27–Abstract only
Squamous cell carcinoma
Not specified Nil 72 h 30% decrease in cell number after 48 h and
50% decrease at 72 h of culture as compared
with control. Increases in intracellular levels
of IL-10 and 12, but not INF-γ
2 Ghoneum and Gollapudi
Human leukemic cells
(HUT 78)
100, 300, 1000 Agonistic anti-CD95
3-24 h 200% increase in apoptotic cells pretreated
with MGN-3 compared with control
3 Ghoneum and Gollapudi
Human breast cancer cells
(BCC) MCF-7, ZR-75,
100, 500, 1000 Saccharomyces
cerevisiae at a cell to
yeast ratio of 1:10
2 h Dose-dependent effects of accelerated yeast
phagocytosis by MCF-7 cells and enhanced
apoptosis of cancer cells MCF-7 (2-fold),
ZR-75 (2.5-fold), and HCC70 (1.8-fold) by
MGN-3, compared with control
4 Ghoneum and Gollapudi
Monolayer BCC MCF-7
and nontumorigenic
breast epithelial (MCF-
100 S cerevisiae at a cell to
yeast ratio of 1:10
1-4 h MGN-3 increased the yeast-phagocytosis of
MCF-7 cells by 2-fold, and enhanced yeast-
induced apoptosis compared with control.
No phagocytosis of yeast by MCF-10A cells
5Gollapudi and Ghoneum,
Human BCC MCF-7 and
100, 500, 1000 Daunorubicin (1 × 10−9
to 1 × 10−6 M)
3 days MGN-3 increased susceptibility of MCF-7 (5.5-
fold) and HCC70 (2.5-fold) to daunorubicin.
Increased accumulation of daunorubicin in
the cancer cells were observed
6 Ghoneum and Gollapudi
Human multiple myeloma
(U266) cells
50 or 100 Curcumin (2.5-10 μM) 3 days 87% decrease in cell number and a 2.6-fold
increase in the percentage of apoptotic
U266 cells by 100 μg/mL MGN-3 plus 10 μM
curcumin. The effect was dose dependent
7 Ghoneum et al (2014)33 Nonmetastatic human
BCC (MCF-7) and
metastatic murine BCC
100, 250, 500,
600, 750,
Paclitaxel (1 × 10−1 to 1
× 10−6 M)
24, 48 h MGN-3 increased the susceptibility of both
types of cancer cells to paclitaxel by over
100-fold; achieved through DNA damage,
enhanced apoptosis, and inhibition of cell
proliferation in 4T1 cells
8 Pérez-Martínez et al
Erythroleukemia (K562);
Jurkat T lymphoid
leukemia; Ewing sarcoma
(A673); neuroblastoma
100 NK cells Overnight MGN-3 stimulated NK cells induced a higher
expression of the activation associated
receptors CD25 and CD69; increased NK
cell cytotoxic activity against all cell lines
tested; and promoted NK cell expansion
Ooi et al 5
Case Reports
The included case reports42-48 narrated a total of 14 success-
ful MGN-3-treated clinical cases. The patient characteris-
tics and outcomes are summarized in Table 3.
Most patients were older than 50 years with only 2
patients of younger age, and 2 patients with age unreported.
Typ es of primary cancer in these cases include leukemia
(2), prostate (1), breast (1), colorectal (2), pancreas (1),
liver (3), lung (2), skin (1), and ovary (1). Most patients
started taking MGN-3 either in conjunction with conven-
tional cancer treatment, or after completion of conventional
treatment. Dosages of MGN-3 reported in these cases were
Table 2. Characteristics of the Included In Vivo Studies.
No. Study Animal Model MGN-3 Dosage Combined Agent Duration Outcomes
1 Jacoby et al (2001)35 Sprague-Dawley derived albino
Daily oral dosing of 5 or 50 mg/kg 1 × intraperitoneal (IP) dose
of cisplatin or doxorubicin
on day 3
11 days Rats receiving MGN-3 were healthier;
gained weight and had a lower
incidence of diarrhea and gross
intestinal pathology compared with
2 Endo and Kanbayashi
BALB/c female mice 0.1 mL at 10 mg/mL in water or by
IP daily 1 wk before cisplatin
Single shot of cisplatin (0.1
mL at the concentration
of 15 mg/kg)
28 days MGN-3 (both orally and IP) showed
accelerated protection against
severe loss of body weight of mice
due to cisplatin. The result was
statistically significant
3 Badr El-Din et al
Female Swiss albino mice
inoculated with Ehrlich
ascites carcinoma (EAC) cells,
bearing solid tumors
MGN-3 dissolved in 0.9% saline
given via IP or intratumoral
injections at 40 mg/kg body
weight (BW) daily for 5 wk
Nil 5 wk MGN-3 significantly delayed growth
in both tumor volume (63.27%) and
tumor weight (45.2%) compared
with control, through increased
apoptosis of EAC cells (1.8-
fold), influenced plasma cytokine
production, downregulated immune
suppressing cytokine IL-10, and
increased NK cells activity. No
adverse side effects due to MGN-3
treatment were observed
4 Noaman et al (2008)38 Female Swiss albino mice
inoculated with EAC cells,
bearing solid tumors
MGN-3 dissolved in 0.9% saline
given via IP at 25 mg/kg BW, 6
times a week from day 4 or day
11 after inoculation and end at
day 25
Nil 25 days MGN-3 suppressed the growth
of tumors; normalized lipid
peroxidation level, augmented
glutathione contents, and enhanced
antioxidant enzymes activity in
blood, liver, and tumor tissue. More
pronounced effects were observed
when treated by MGN-3 as early
as day 4
5 Pérez-Martínez et al
NOD-scidIL-2Rgnull mice
injected intravenously (IV)
with NB-1691luc 2 × 105
neuroblastoma cells
100 μg/mL overnight for activation
of NK cells
NK cells (fresh or MGN-3
activated). NK cellular IV
therapy began 7 days after
tumor cells inoculation,
twice a week for 4 wk
4 wk MGN-3 stimulated NK cells
inhibited neuroblastoma growth
and increased survival compared
with control. The results were
statistically significant
6 Badr El-Din et al
Male Wistar rats 1 dose of 40 mg/kg BW via IP
injection every other day a total
of 8 mo
Orally administered
carcinogenic MNNG
nitrosoguanidine) at 200
mg/kg BW daily for 2
8 mo MGN-3 significantly lowered
incidence of dysplasia and gastric
cancer when combined with
MNNG; effects observed include
suppression of Ki-67 tumor marker,
upregulation of apoptotic gastric
cancer cells via mitochondrial-
dependent pathway, and protection
against decrease in lymphocyte
7 Badr El-Din et al
Female Swiss albino mice
inoculated with EAC cells,
bearing solid tumors
1 dose of 40 mg/kg BW via IP
injection every other day
starting from day 8 until day 30
Paclitaxel at a dose of 2 mg/
kg BW every other day
starting from day 8 until
day 30
30 days MGN-3 plus paclitaxel significantly
suppressed tumor volume (88%)
compared with paclitaxel only
(77%) or MGN-3 only (59%).
Inhibition of tumor growth was
associated with reduced cancer
cell proliferation, increased DNA
damage and apoptosis
8 Badr El-Din et al
Male albino rats 25 mg/kg BW 5 times/week IP
for 2 wk prior to receiving
carcinogens and continued for
20 wk
Carcinogenic NDEA (N-
nitrosodiethylamine) (200
mg/kg BW) single dose
IP, plus promoter CCl4
(3 mL/kg BW) weekly
subcutaneously for 6
20 wk MGN-3 inhibited
hepatocarcinogenesis induced by
NDEA and CCI4 via induction of
apoptosis and inhibition of cancer
cell proliferation; maintained AST,
ALT, ALP, and gamma-GT levels
close to normal values
6 Integrative Cancer Therapies
Table 3. Patient Characteristics and Outcomes of the Included Clinical Case Reports.
No. Report Patient, Age Cancer
Conventional and Adjunct
Treatment MGN-3 Dosage Outcomes
1 Ghoneum and Brown
Male, 39 y Acute myelogenous
Chemotherapy 3 g/d after
White blood cells (WBCs) count at 5.6 ×
109/L after completion of chemotherapy
and maintained. NK activity increased
from 7.9 LUs to 113 LUs after 1 wk of
MGN-3 and maintained at high level for
4 y at the point of reporting
Male, 52 y Acute myelogenous
No conventional
3 g/d WBCs count at 18.7 × 109/L
pretreatments. Reduced to 11 × 109/L
after 1 mo. Condition stable for 4 y at
the point of reporting
Male, age
Prostate cancer Hormonal therapy 3 g/d after
Prostate-specific antigen (PSA) level at
0.1 after hormonal therapy. PSA level
remained within normal range for 4 y at
the point of reporting
Female, age
Recurrence breast
Surgery and
3 g/d after
completion of
NK cell activity increased 2-fold from
baseline (16.4 LUs) after 1 wk. Further
increased to 128 LUs and remained
high 4 y at the point of reporting.
No evidence of recurrence seen in
computed tomography (CT) scans or
2 Kawai (2004)42 Female, 64 y Umbilical metastasis of
recurrent colorectal
cancer (Sister Mary
Joseph’s Nodule
5-Fu 500 mg, Isovorin 250
mg (10A), Topotecin 40
mg administered once a
week from 19th month
3 g/d for first
18 mo; 6 g/d
Patient survived 2 y and 2 mo since
detection (typical survival time: 2 wk to
11 mo) and was still alive at the time of
reporting. MGN-3 helped to prolong life
and improved quality of life
3 Kaketani (2004)43 Male, 64 y Terminal pancreatic
cancer with distant
Oral anticancer drugs
(Furtulon 1200 mg/time
and Endoxan 200 mg/
ACM π water (MRN-
100A) 300 mL/d
6 g/d Initial prognosis was 3 mo of life. 5 mo
after treatment, CT images showed
pancreatic cancer to be unmeasurable
and reduced liver metastasis similarly.
Endoscopy 12 mo after treatment
showed almost no abnormality. Patient
survived 17 mo with a normal life and
died of hematemesis not related to
4 Okamura (2004) 44 Male, 67 y Liver cancer with
intestinal metastasis
1 y of treatment at
another hospital
Intravenous (IV) infusion
of Bio-reproducing
Protein (BRP) once
every 4 wk
3 g/d
for 157 days
Initially pronounced to have 1 mo to live.
The general condition, tumor markers,
and immunocompetence improved
after 2 y. Patient entered 7th year of
treatment at the time of reporting living
a normal working life and received
treatment on outpatient basis
Male, 65 y Liver cancer Conventional treatment
at 2 other medical
institutions previously
IV infusion of BRP once
every 4 wk
3 g/d for 72 days Liver cancer marker and
immunocompetence improved after 6
mo. Liver function markers raised initially
and decreased at 1 y, with jaundice
disappeared, appetite improved, no
pain occurred through to 1 y 11 mo of
Female, 71 y Liver cancer Initial treatment at
another hospital with
poor results
IV infusion of BRP once
every 4 wk
3 g/d for 392
Hepatic tumor markers decreased after
6 mo of treatment. Clinical symptoms
improved and jaundice disappeared
Female, 76 y Lung cancer
spread through both
lung fields)
Initial treatment at
another hospital with
no improvement
IV infusion of BRP once
every 4 wk
3 g/d for 128
Lung tumor maker (tissue polypeptide
antigeny [TPA]) decreased after
4 mo. Coughing decreased.
Immunocompetence (TK activity)
gradually improved
Male, 58 y Colorectal cancer with
liver metastasis
Underwent surgery at
another hospital
IV infusion of BRP once
every 4 wk
3 g/d for 77 days Liver function (glutamic-pyruvic
transaminase [GPT]) improved rapidly
and immunocompetence (TK activity)
stabilized after 1 mo of treatment.
Patient continued to work with no
subjective symptoms at the time of
Ooi et al 7
3 g/d, 6 g/d, and 45 mg/kg per body weight (BW), adminis-
tered orally. In some cases, MGN-3 was combined with
other forms of complementary therapies, including ACM π
water,43 Bio-reproducing Protein (BRP),44 and mistletoe
In nonterminal cancer cases, reported results were:
improvements in tumor markers, immunocompetence pro-
file, and initial symptoms44; patient conditions were stable
with no sign of cancer recurrence at follow-up48; and
patients showed improved quality of life (QoL) reported as
subjective improvements in sleep, appetite, digestion, phys-
ical activity and decrease in anxiety and pain; reduced
adverse effects during chemotherapy, and cancer remis-
sion.46,47 In one self-treated case, the patient refused further
conventional treatment for metastatic lung tumor after the
initial removal of his skin lesion. The metastatic lung tumor
became undetectable after 34 months of self-treatment with
MGN-3.45 In 3 cases of terminal cancer with poor progno-
sis, the patients were reported to be able to survive much
longer beyond the initial estimated lifespans with improved
QoL, and even normal working lives.42-44
Clinical Studies
Eleven clinical studies were included in this review. Among
the 11 clinical studies, 5 are nonrandomized, pre-post inter-
vention studies,48,50,51,57,58 and 6 are randomized controlled
trials (RCTs).49,52-56 The characteristics of these studies are
summarized in Table 4 (nonrandomized studies) and Table
5 (RCTs).
Nonrandomized, Pre-post Intervention Studies. The immuno-
modulating effects of MGN-3 were examined by Ghoneum
and Brown.48 Thirty-two cancer patients (various malignan-
cies) with depressed NK cell activity post conventional can-
cer treatment were treated with MGN-3 for 2 weeks. A
significant increase in NK cell activity up to tenfold was
observed. Increase in NK cell granularity and binding
capacity, improvement in T and B cell proliferation in vivo,
and improvement in tumor-associated antigens were
observed in a selected number of patients.48 Similarly,
Tsunekawa50 reported normalization of NK cell activity and
improvement in white blood cell (WBC) count in a small
study of 16 cancer patients. These were patients with vari-
ous malignancies who went through conventional cancer
treatment before starting the MGN-3 therapy for 6 months.
No subjective or objective adverse effects were recorded.
In another study, however, no substantial change in NK
cell counts was observed in 22 cancer patients after taking
MGN-3 for 2 months.51 Instead, an increase in the T helper
(Th) lymphocytes to T regulatory (Treg) lymphocytes
(CD4+ CD25+) ratio (Th:Treg) was recorded, demonstrat-
ing the effect of anticancer immunity restoration of the
MGN-3 therapy. Nonetheless, due to the small number of
patients, the results were not statistically significant.51 More
recently, Golombick et al57 reported that the combination
therapy of MGN-3 and curcumin helped 20 patients with
early B-cell lymphoid malignancies to delay disease pro-
gression by increasing neutrophil count and reducing the
raised erythrocyte sedimentation rate (ESR). No significant
change in NK cell counts was detected. Again, results from
this study lack statistical power.
No. Report Patient, Age Cancer
Conventional and Adjunct
Treatment MGN-3 Dosage Outcomes
5 Markus et al (2006)45 Male, 68 y Metastatic
of the skin with
multiple pulmonary
Wide local excision for
removal of the skin
Patient refused further
conventional treatment
for pulmonary nodules
with unknown
Lung masses steadily decreased in size by
serial imaging and became undetectable
after 34 mo of MGN-3 therapy
6 Hajto et al (2015)46 Female. 28 y Left ovary sarcoma
and endometrium
sarcoma with a
metastasis in the
right ovary
Removal of left ovary
followed with
hysterectomy and
Chemotherapy with a
CYVADIC protocol
commenced 4 wk after
second surgery
Started 0.75 ng/kg
mistletoe lectin twice a
week since 3rd cycle of
45 mg/kg given
twice a week
started at
3rd cycle of
A rapid improvement of quality of
life was observed after starting the
immunotherapy (lectin + MGN-3).
Patient was better able to tolerate the
next 3 cycles of chemotherapy. At the
time of reporting, the patient was tumor-
free after 5 y
7 Hajto et al (2016)47 Female, 74 y Inoperable lung
4 cycles carboplatin and
paclitaxel. Second-line
treatment with 75 mg/d
erlotinib (Tarceva)
given for 7 mo. 0.75 ng/
kg mistletoe lectin given
twice weekly
45 mg/kg given
twice a week
After a treatment for 7 mo, a nearly
complete remission (CR) of the primary
tumor and CR of all metastases was
established. The quality of life was
excellent and the patient was able to
work 100%
Table 3. (continued)
8 Integrative Cancer Therapies
The QoL improvement effects of MGN-3 were studied
by Hajto et al.58 A total of 35 patients with various malig-
nancies were administered a combination of mistletoe lectin
and MGN-3 as a complementary therapy for a minimum of
6 months during or after conventional cancer treatment.
Patients responded to a custom binary-response question-
naire with 8 questions regarding various aspects of their
QoL after treatment, including pain, anxiety, physical activ-
ity, appetite, and sleep, reporting a subjective improvement
of physical activity and decrease in side effects as the most
important benefits of the complementary therapy.58
Randomized Controlled Studies. The QoL improvement
effects of MGN-3 were previously studied in a large RCT
with 205 progressive cancer patients in late stages (III-IV)
of various malignancies.49 Checking patient QoL by obser-
vation and enquiry during the study using a custom grading
scale, Takahara and Sano49 reported that, patients who
received MGN-3 plus standard complementary and alterna-
tive therapy (CAT) achieved a higher survival rate (54.2%
vs 35.8%) and a better appetite than the control group who
received only standard CAT. There was no clear difference
between groups in terms of percentage changes in increas-
ing and decreasing NK activity, but the MGN-3 + CAT
group had a higher percentage of patients with unchanged
NK activity compared with the CAT only group.49 It was
unclear whether this study was sufficiently blinded.
The RCT by Bang et al52 can be regarded as the first
clinical evidence for the antitumor efficacy of MGN-3. The
participants of this 3-year RCT consisted of 68 patients with
liver cancers of stage I or II. A higher survival rate after the
second year (35% vs 6.7%) and lower recurrence of the dis-
ease (31.6% vs 46.7%) for liver cancer patients taking
MGN-3, compared with the controls, were the results of
MGN-3 applied in conjunction with conventional cancer
treatment in 38 patients.52 Thirty patients receiving only
conventional therapies were assigned as controls. Significant
decreases in the tumor marker level (α-fetoprotein [AFP]),
and tumor volumes, as compared with baseline, were also
observed in the MGN-3 group whereas the control group
Table 4. Characteristics of the Included Nonrandomized Clinical Studies.
No. Study N Cancer Type Duration MGN-3 Dosage
Conventional and
Adjunct Treatment Outcome Measurement Outcomes
1 Ghoneum
and Brown
32 Prostate, breast, multiple
myeloma, leukemia
2 wk
to 4 y
Orally at 3 g/d Most patients went
through conventional
treatment before
NK cells activity; NK
granularity; in vivo T
and B cells proliferation;
antigens (TAA)
Increased in NK cells
activity (10×); NK cell
granularity and binding
capacity; T and B cells
proliferation. Improved
TAA measurements in
selected patients. Follow-up
results of 4 patients were
2 Tsunekawa
16 Various malignancies 6 mo Orally at 3 g/d Patients went through
surgery, irradiation
therapy, and/
or chemotherapy
treatment before
Body height and weight,
leukocyte count and
subsets, NK cell
activity, tumor markers,
adverse reactions, and
No subjective or objective
adverse effects.
Improvement in leukocyte
count and subsets,
increased and normalized
NK cell activity after
3 Lissoni et al
22 Various malignancies 2 mo Orally at 2 g/d
1st mo, and 1
g/d 2nd mo
Only supportive care
for pain, vomit,
nausea, and neoplastic
Total lymphocytes, T
lymphocytes (CD3+,
CD4+, CD8+), T helper
(Th), T regulatory
(Treg), NK cells
Non–statistically significant
increase in the mean
number of Th cells and
decrease in Treg cell.
Th/Treg mean ratio
significantly enhanced
4 Golombick et
al (2016)57
20 Early B-cell lymphoid
gammopathy of
significance [MGUS],
smoldering multiple
myeloma [SMM],
chronic lymphocytic
leukemia [CLL])
6 mo Orally at 2 g/d 6 g/d of curcumin FBC, paraprotein, free
light chains/ratio,
C-reactive protein
(CRP) erythrocyte
rate (ESR) rate, B2
microglobulin, sIgGs,
and surface leukocyte
Increased neutrophil count
in 80% of MGUS/SMM
patients. Reduction in
raised ESR in 40% of the
MGUS/SMM patients
5 Hajto et al
35 Various malignancies
(mostly stage II-IV)
6 mo Orally between
12 and 45 mg/
kg twice a
Conventional oncologic
0.5-1.0 ng/kg mistletoe
lectin given twice a
Quality of life
questionnaire (pain,
anxiety, physical
activity, appetite,
sleep, digestion, side
effect, self-perceived
Improvement of physical
activity and decrease of side
effects during conventional
Ooi et al 9
showed no significant changes in either AFP or tumor
MGN-3 was shown to reduce chemotherapy-induced
side effects among breast cancer patients who were under-
going 6 cycles of chemotherapy in another RCT with 50
patients.54 MGN-3 was given to 25 patients 1 week before
and 1 week after each cycle of chemotherapy, with the con-
trol group receiving only chemotherapy. Side effects were
assessed by a custom questionnaire given to patients at the
start of each cycle. Significant reductions in tiredness,
increased appetite, no anti-emetic needs, and reduced hair
loss compared with the control group were reported.54
In cervical cancer patients undergoing chemoradiother-
apy, MGN-3 was shown to be better than placebo in reduc-
ing the diarrheal side effect in a clinical trial reported by
Itoh et al., using a custom symptom scoring system.55
Adverse events were graded by the National Cancer Institute
scale (Common Terminology Criteria for Adverse Events
[CTCAE] v3.0). Only 2 patients in the MGN-3 group devel-
oped grade 2 (moderate) events during chemotherapy, with
the control group tending to develop adverse events of
higher grades than did the MGN-3 group.55 Patients taking
MGN-3 also showed less decrease in WBC count. However,
the results from this pilot trial with only 20 patients were
not significant due to the lack of statistical power.55
For patients with chronic fatigue syndrome (CFS) due to
cancer or cancer treatment, MGN-3 plus Oncothermia was
shown to be able to reduce the CFS symptoms in an RCT
with 50 CFS patients diagnosed with various malignan-
cies.56 The 25 patients who received 3 g/d of MGN-3 and
Oncothermia once a week had significantly lower mean
scores of Chalder Fatigue Questionnaire (CFQ) compared
Table 5. Characteristics of the Included Randomized Controlled Clinical Studies.
No. Study No. of Patients Cancer Type Duration MGN-3 Dosage
Conventional and
Adjunct Treatment Outcome Measurement Outcomes
1 Takahara and Sano
(2004) 49
205 (MGN-3: 96,
Control: 109)
18 mo Orally at 3 g/d Complementary and
alternative therapy and
anticancer drugs
NK cells activity,
survival rate; custom
quality of life scoring
on pain, malaise,
nausea, and appetite
MGN-3 group achieved
higher survival rate
and better appetite
than control group
2 Bang et al (2010)52 68 (MGN-3: 38,
Control: 30)
carcinoma (stages
I and II)
3 y Orally at 1
g/d for 12
mo during
Transarterial oily
(TOCE) or TOCE and
percutaneous ethanol
injection treatment
Overall response
to treatment,
α-fetoprotein (AFP)
levels, tumor volume,
recurrence, and
MGN-3 group showed
lower recurrence,
higher survival
after 2nd year, and
significantly lower
AFP change compared
with control
3 Cholujova et al
48 (MGN-3: 32,
Placebo: 16)
Multiple myeloma 3 mo Orally at 2 g/d Alternating courses
of chemotherapy:
alkylating agents,
anthracyclines, and
analysis; NK cells
activity; and cytokine
Increased NK activity,
myeloid DCs level,
and augmented
concentrations of Th
cell type 1-related
cytokines in MGN-3
group compared with
placebo group
4 Masood et al
50 (MGN-3: 25,
Control: 25)
Breast cancer 6 mo Orally at 3 g/d
1 wk before
and 1 wk
after each
6 cycles of
Chemotherapy induced
side effects (tiredness,
anorexia, vomiting,
and hair loss)
MGN-3 group
experienced significant
reduction in tiredness;
increased appetite; no
antiemetic needs; and
less hair fall compared
with control group
5 Itoh et al (2015)55 20 (MGN-3: 10,
Placebo: 10)
Cervical cancer 3 wk Orally at 3
g/d during
Radiation therapy:
combination of
radiation therapy and
Chemotherapy: cisplatin
and 5-fluorouracil
side effects of
(diarrhea, nausea,
vomiting, loss of
appetite, safety);
WBC count; NK cell
MGN-3 group showed
less diarrhea, less
decrease in WBC
count & less adverse
events, but results
were not significant
due to lack of
statistical power
6 Petrovics et al
50 (MGN-3: 25,
Control: 25)
malignancies with
chronic fatigue
6 mo Orally at 3 g/d
for 24 wk
Oncothermia for MGN-
3 group only
Chemo- or radiotherapy
as routine care
Quality of life score
pain score (visual
analogue scale [VAS]),
body pH level, blood
abnormalities, ECG,
blood test, fatigue
scale (Chalder Fatigue
MGN-3 group showed
changes in body pH
level to be less acidic.
Average of CFQ
score was significantly
reduced in MGN-3
group compared with
no change in control
10 Integrative Cancer Therapies
with baseline after 6 months of treatment. No significant
change in mean CFQ scores was recorded in the control
group who received only conventional chemo or radiother-
apy treatment.56
The effects of MGN-3 on innate immunity were studied
by Cholujova et al53 in an RCT with 48 multiple myeloma
patients (MGN-3 group, 32; placebo, 16). Detailed blood
analyses were performed before and during the 3 months of
treatment. Significant increase in NK activity, myeloid den-
dritic cell level, and augmented concentrations of Th cell
type 1-related cytokines were observed in the MGN-3
group. No significant change in the placebo group was
observed. Hence, MGN-3 clearly improved the innate
immunity profile of the patients compared with placebo.53
Risk of Bias Assessment. We have assessed the risk of bias of
the included RCTs using the Cochrane Risk of Bias tool.59
The results of the assessment are summarized in Figures 2
and 3. Because of insufficient information provided on ran-
domization and blinding, most included RCTs have unclear
risk in at least one or more items in selection bias, perfor-
mance bias, and detection bias. Only the study by Itoh
et al.55 is considered low risk in these items. Notwithstand-
ing, this study has a high risk of attrition bias due to a high
percentage of participants being excluded from assessment
(30%).55 The risks of attrition bias and reporting bias are
low in most other studies except the study by Masood el
al,54 which has unclear risk of bias across all items of assess-
ment due to insufficient detail in published information. We
assess the study by Takahara and Sano49 to have a high risk
in other bias. It was conducted by a commercial hospital
specialized in CAT for cancer patients, thus the risk of bias
cannot be excluded due to conflict of interest. With industry
influence being a potential source of other bias, only the
study by Petrovics el al56 provided disclosure on funding
and clarified the roles of industry partners in the study,
which the other studies did not.
Current evidence supports MGN-3 to be a BRM. MGN-3 is
an evidence based and standardized arabinoxylan concen-
trate from plant origin which, similar to bacterial pathogen
associated molecular pattern molecules, can stimulate the
body’s natural immune system to protect against cancer
growth.46 The effect of MGN-3 in upregulating the cyto-
toxic activities of NK cells, by multiple-fold, has been
most prominently demonstrated.34,48-50,53 The anticancer
effect of NK cells is the subject of intense current research
and NK cell immunotherapy is being touted as the future of
cancer immunotherapy.4 Effectiveness of NK activity has
been associated with good prognosis in patients with meta-
static cancers.60,61 This may explain the life-prolongation
effect of MGN-3 as reported in a number of clinical stud-
ies49,52 and case reports.42-44 However, MGN-3 treatment
does not increase the absolute NK cell counts as noted in
clinical studies,51,57 which is a limitation. Cancer patients
with low NK cell counts (<0.15 × 109/L) tend to have lower
survival rates,62,63 indicating that lower basic level of natu-
ral antitumor activity can reduce the efficacy of a BRM.
While they may benefit from the upregulated NK activity
with MGN-3 treatment to a certain extent,49 combining NK
cellular therapy64 with MGN-3 may further improve prog-
nosis in these patients; an approach that warrant future
clinical investigation.34
Other immunomodulatory effects of MGN-3 include the
following: increase susceptibility of cancer cells to undergo
apoptosis mediated by CD95 death receptors28; influence
plasma cytokine production (upregulated TNF-α and IL-12,
while downregulating IL-10)37; enhance the activity of anti-
oxidant enzymes38; improve T and B cell proliferation48;
improve Th cell concentration,51,53 downregulate Treg
cells51; and activate dendritic cells.13,22,53 These effects have
been presented in depth by Ghoneum65 in a recent review,
supporting the use of MGN-3 as an effective BRM in cancer
MGN-3 has been tested in clinical trials as an adjunct
therapy during conventional chemo- and radiotherapy with
effects that include (1) improvement of immunoprofile,53,55
Figure 2. Risk of bias summary: Review authors’ judgements
about each risk of bias item for each included study.
Ooi et al 11
(2) reduction of side effects (diarrhea, nausea, pain, tired-
ness, anorexia, and vomiting),52,54-56,58 and (3) improvement
in treatment outcomes.52 Outcome improvement and reduc-
tion of side effects have been mostly attributed to an
improved balance of the innate immune system. However,
MGN-3 has also been shown to work synergistically with
daunorubin31 and paclitaxel33,40 in preclinical studies, as
well as transarterial oily chemoembolization (TOCE) and
percutaneous ethanol injection treatment (PEIT) for liver
cancer treatment in a clinical trial,52 by sensitizing the can-
cer cells to these agents. More research is needed to explore
such synergistic effects with other chemotherapeutic agents
and radiation therapy to fully explore the potential of
MGN-3 as a combination therapy in conventional cancer
As a follow-up therapy after conventional cancer treat-
ment, MGN-3 has demonstrated effects in restoring weak-
ened immunoprofile,48-51 improving QoL and survival rate
of late-stage cancer patients,49 as well as reducing recur-
rence.52 Such results are consistent with the clinical experi-
ences reported in the published case reports.42-47 As such,
MGN-3 may also be considered as part of the follow-up
care after conventional cancer treatment.
No adverse reaction was reported in studies that explic-
itly monitored potential MGN-3 induced adverse effects in
vivo37 and in a clinical study.50 No adverse event due to
MGN-3 was reported in any of the included clinical trials or
clinical case reports. Furthermore, the safety MGN-3 has
been studied in a series of animal studies. The median lethal
dose (LD50) of MGN-3 is more than 36 g/kg, and the “no
observed adverse effect level (NOAEL)" is 200 mg/kg/d or
higher.66 Therefore, typical MGN-3 dosages of 3 to 6 g/d or
45 mg/kg BW/d are extremely safe.
At present, there is no study on the pharmacokinetics of
MGN-3 and the achievable level of MGN-3 in serum is
unknown (personal email communication with Dr Mamdooh
Ghoneum at Charles Drew University of Medicine and
Science on August 4, 2017). Since concentrations of
MGN-3 used in some of in vitro studies were very high
(500-1000 μg/mL),28,29,31,33 it is unclear whether these con-
centrations can be of clinical relevance. Although the
MGN-3 dosages (5-50 mg/kg/BW) used for in vivo stud-
ies34,35,37-41 were more closely matched to the typical dosage
used in human studies, without understanding of the phar-
macokinetics of MGN-3, questions remain whether the
higher bioavailability via intraperitoneal injection in some
animal studies36-41 can be applicable to humans.
The clinical research on MGN-3 is still at its early stage
with only a small number of RCTs available in the litera-
ture. Most of them are small pilot trials with limited partici-
pants (N < 100) and short duration (<=6 months). At the
moment only one RCT is available to support clinical evi-
dence.52 The other RCT that has adequate size (N = 205)
and duration (18 months)49 suffers from methodological
limitations including inadequate blinding, no placebo con-
trol, and potential risk of bias due to conflict of interest.
Hence, large, well-designed, long-term placebo-controlled
RCTs are needed to further evaluate the effects of MGN-3
as a complementary therapy to support conventional cancer
Current evidence from preclinical studies, clinical case
reports, and small clinical trials suggests that MGN-3 can
be an effective BRM to complement the conventional can-
cer treatment through upregulating the patient’s immune
system, especially in boosting the NK cell activity. MGN-3
appears safe in its application with no adverse event reported
to date. It may be used as a complementary immune therapy
to reduce side effects, improve treatment outcomes, and
enhance long-term survival rate. The combination of
MGN-3 with new biological targeting treatments may open
new perspectives in the tumor therapy. Nevertheless, we
call for additional study into the pharmacokinetics of MGN-
3, as well as more well-designed RCTs to confirm its
Figure 3. Risk of bias graph: Review authors’ judgements about each risk of bias item presented as percentages across all included
12 Integrative Cancer Therapies
efficacies and strengthen the evidence to support its clinical
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
1. Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer
incidence and mortality rates and trends—an update. Cancer
Epidemiol Biomarkers Prev. 2016;25:16-27.
2. Sudhakar A. History of cancer, ancient and modern treatment
methods. J Cancer Sci Ther. 2010;1:1-4.
3. Qiao J, Liu Z, Fu YX. Adapting conventional cancer treat-
ment for immunotherapy. J Mol Med (Berl). 2016;94:
4. Kuroki M, Miyamoto S, Morisaki T, et al. Biological
response modifiers used in cancer biotherapy. Anticancer
Res. 2012;32:2229-2233.
5. Zugazagoitia J, Guedes C, Ponce S, Ferrer I, Molina-Pinelo
S, Paz-Ares L. Current challenges in cancer treatment. Clin
Ther. 2016;38:1551-1566.
6. Biemar F, Foti M. Global progress against cancer-challenges
and opportunities. Cancer Biol Med. 2013;10:183-186.
7. Biobran MGN-3—an overview. https://biobran.
org/overview. Accessed May 18, 2017.
8. Miura T, Chiba M, Miyazaki Y, Kato Y, Maeda H. Chemical
structure of the component involved in immunoregulation.
In: BioBran/MGN-3 (Rice Bran Arabinoxylan Coumpound):
Basic and Clinical Application to Integrative Medicine. 2nd ed.
Tokyo, Japan: BioBran Research Foundation; 2013:14-22.
9. Paterson A. Therapeutic properties of biobran MGN-3.
peutic-properties-of-biobran-mgn-3. Posit Heal. Published
September 2002. Accessed September 19, 2017.
10. Tazawa K. BioBran/MGN-3 (Rice Bran Arabinoxylan
Compound): Basic and Clinical Application to Integrative
Medicine. 2nd ed. Tokyo, Japan: BioBran Research
Foundation; 2013.
11. Ghoneum M, Hamilton J, Gollapudi S. Modified arabinox-
ylan rice bran (MGN-3/biobran), potentiates chemotherapy-
induced apoptosis in human breast cancer cells. J Nutr.
12. Badr El-Din N, Noaman E, Ghoneum A, Ghoneum M. Rice
bran supplement (MGN-3/Biobran) suppresses tumor growth
via modulating cytokine production and increasing apop-
totic level in ehrlich carcinoma-bearing mice. Clin Immunol.
13. Cholujova D, Jakubikova J, Sulikova M, et al. The effect of
MGN-3 arabinoxylan on natural killer and dendritic cells in
multiple myeloma patients. Haematologica. 2011;96(suppl
14. Badr El-Din NK, Fattah SMA, Pan D, Tolentino L, Ghoneum
M. Chemopreventive activity of BioBran/MGN-3, an ara-
binoxylan from rice bran, against chemical induction of
gastric dysplasia and adenocarcinoma in rats. Cancer Res.
2014;74(19 Suppl):Abstract 234.
15. Badr El-Din NK, Ali DA, Alaa El-Dein M, Ghoneum M.
Biobran/MGN-3, arabinoxylan from rice bran, sensitizes
breast adenocarcinoma tumor cells to paclitaxol in mice.
Cancer Res. 2015;75(15 Suppl):Abstract 5312.
16. Giese S, Sabell GR, Coussons-Read M. Impact of ingestion of
rice bran and shitake mushroom extract on lymphocyte func-
tion and cytokine production in healthy rats. J Diet Suppl.
17. Ghoneum M, Badr El-Din NK, Fattah SMA, Tolentino L.
Arabinoxylan rice bran (MGN-3/Biobran) provides protec-
tion against whole-body γ-irradiation in mice via restoration
of hematopoietic tissues. J Radiat Res. 2013;54:419-429.
18. Ghoneum M, Jewett A. Production of tumor necrosis factor-
alpha and interferon-gamma from human peripheral blood
lymphocytes by MGN-3, a modified arabinoxylan from rice
bran, and its synergy with interleukin-2 in vitro. Cancer
Detect Prev. 2000;24:314-324.
19. Ghoneum M, Agrawal S. MGN-3/Biobran enhances genera-
tion of cytotoxic CD8+ T cells via upregulation of DEC-205
expression on dendritic cells. Int J Immunopathol Pharmacol.
20. Ghoneum M, Agrawal S. Activation of human monocyte-
derived dendritic cells in vitro by the biological response
modifier arabinoxylan rice bran (MGN-3/Biobran). Int J
Immunopathol Pharmacol. 2011;24:941-948.
21. Ghoneum M, Abedi S. Enhancement of natural killer cell
activity of aged mice by modified arabinoxylan rice bran
(MGN-3/Biobran). J Pharm Pharmacol. 2004;56:1581-1588.
22. Cholujova D, Jakubikova J, Sedlak J. BioBran-augmented
maturation of human monocyte-derived dendritic cells.
Neoplasma. 2009;56:89-95.
23. Hajtó T, Adámy A, Langmár Z, et al. Enhanced effectiveness of
conventional oncotherapy with plant immunomodulators: over-
view of recent advances. Adv Med Plant Res. 2013;1:56-65.
24. Tan BL, Norhaizan ME. Scientific evidence of rice by-prod-
ucts for cancer prevention: chemopreventive properties of
waste products from rice milling on carcinogenesis in vitro
and in vivo. Biomed Res Int. 2017;2017:1-18.
25. Zhang S, Li W, Smith CJ, Musa H. Cereal-derived arabinox-
ylans as biological response modifiers: extraction, molecular
features, and immune-stimulating properties. Crit Rev Food
Sci Nutr. 2015;55:1035-1052.
26. Meshitsuka K. A case of stage IV hepatocellular carcinoma
treated by KM900, Biobran, and psychotherapy has presented
significant good results. Pers Med Universe (Japanese Ed.)
27. Ghoneum M, Tachiki K, Ueyama K, Makinodan T, Makhijani
N, Yamaguchi D. Natural biological response modifier
(MGN-3) shown to be effective against tumor cell growth.
Paper presented at the 8th International Congress on Anti-
Aging & Biomedical Technologies; December 14, 2000; Las
Vegas, NV.
28. Ghoneum M, Gollapudi S. Modified arabinoxylan rice bran
(MGN-3/Biobran) sensitizes human T cell leukemia cells
Ooi et al 13
to death receptor (CD95)-induced apoptosis. Cancer Lett.
29. Ghoneum M, Gollapudi S. Modified arabinoxylan rice
bran (MGN-3/Biobran) enhances yeast-induced apopto-
sis in human breast cancer cells in vitro. Anticancer Res.
30. Ghoneum M, Gollapudi S. Synergistic role of arabinoxylan
rice bran (MGN-3/Biobran) in S. cerevisiae-induced apopto-
sis of monolayer breast cancer MCF-7 cells. Anticancer Res.
31. Gollapudi S, Ghoneum M. MGN-3/Biobran, modified arabi-
noxylan from rice bran, sensitizes human breast cancer cells
to chemotherapeutic agent, daunorubicin. Cancer Detect
Prev. 2008;32:1-6.
32. Ghoneum M, Gollapudi S. Synergistic apoptotic effect of
arabinoxylan rice bran (MGN-3/Biobran) and curcumin (tur-
meric) on human multiple myeloma cell line U266 in vitro.
Neoplasma. 2011;58:118-123.
33. Ghoneum M, Badr El-Din NK, Ali DA, El-Dein MA.
Modified arabinoxylan from rice bran, MGN-3/Biobran, sen-
sitizes metastatic breast cancer cells to paclitaxel in Vitro.
Anticancer Res. 2014;34:81-88.
34. Pérez-Martínez A, Valentín J, Fernández L, et al. Arabinoxylan
rice bran (MGN-3/Biobran) enhances natural killer cell-medi-
ated cytotoxicity against neuroblastoma invitro and invivo.
Cytotherapy. 2015;17:601-612.
35. Jacoby HI, Wnorowski G, Sakata K, Maeda H. The effect of
MGN-3 on cisplatin and doxorubicin induced toxicity in the
rat. J Nutraceut Funct Med Foods. 2001;3:3-11.
36. Endo Y, Kanbayashi H. Modified rice bran beneficial for
weight loss of mice as a major and acute adverse effect of
cisplatin. Pharmacol Toxicol. 2003;92:300-303.
37. Badr El-Din NK, Noaman E, Ghoneum M. In vivo tumor
inhibitory effects of nutritional rice bran supplement MGN-3/
Biobran on ehrlich carcinoma-bearing mice. Nutr Cancer.
38. Noaman E, Badr El-Din NK, Bibars MA, Mossallam AAA,
Ghoneum M. Antioxidant potential by arabinoxylan rice bran,
MGN-3/biobran, represents a mechanism for its oncostatic
effect against murine solid Ehrlich carcinoma. Cancer Lett.
39. Badr El-Din NK, Fattah SMA, Pan D, Tolentino L, Ghoneum
M. Chemopreventive activity of MGN-3/Biobran against
chemical induction of glandular stomach carcinogenesis in
rats and its apoptotic effect in gastric cancer cells. Integr
Cancer Ther. 2016;15:NP26-NP34.
40. Badr El-Din NK, Ali DA, Alaa El-Dein M, Ghoneum M.
Enhancing the apoptotic effect of a low dose of paclitaxel
on tumor cells in mice by arabinoxylan rice bran (MGN-3/
Biobran). Nutr Cancer. 2016;68:1010-1020.
41. Badr El-Din NK, Ali DA, Othman R, Ghoneum M. Prevention of
hepatocarcinogenesis in rats by arabinoxylan rice bran, MGN-3/
Biobran. Cancer Res. 2016;76(14 Suppl):Abstract 5259.
42. Kawai T. One case of a patient with umbilical metastasis
of recurrent cancer (Sister Mary Joseph’s Nodule, SMJN)
who has survived for a long time under immunomodula-
tory supplement therapy. Clin Pharmacol Ther. 2004;14:
43. Kaketani K. A case where an immunomodulatory food was
effective in conservative therapy for progressive terminal
pancreatic cancer. Clin Pharmacol Ther. 2004;14:273-279.
44. Okamura Y. The clinical significance of modified arabinox-
ylan from rice bran (BioBran/MGN-3) in immunotherapy for
cancer. Clin Pharmacol Ther. 2004;14:289-294.
45. Markus J, Miller A, Smith M, Orengo I. Metastatic heman-
giopericytoma of the skin treated with wide local excision and
MGN-3. Dermatol Surg. 2006;32:145-147.
46. Hajto T, Baranyai L, Kirsch A, Kuzma M, Perjési P. Can a
synergistic activation of pattern recognition receptors by plant
immunomodulators enhance the effect of oncologic therapy?
Case Report of a patient with uterus and ovary sarcoma. Clin
Case Reports Rev. 2015;1(10):235-238.
47. Hajto T, Horváth A, Baranyai L, Kuzma M, Perjési P. Can
the EGFR inhibitors increase the immunomodulatory effects
of standardized plant extracts (mistletoe lectin and arabonox-
ylan) with clinical benefit? Case report of a patient with lung
adenocarcinoma. Clin Case Rep Rev. 2016;2:456-459.
48. Ghoneum M, Brown J. NK Immunorestoration and cancer
patients by BioBran/MGN-3, a modified aracbynoxylan rice
bran (study of 32 patients followed for up to 4 years). In: RM
Klatz & R Goldman, eds. Anti-Aging Medical Therapeutics,
Vol III. Marina del Rey, CA: Health Quest; 1999:217-226.
49. Takahara K, Sano K. Life prolongation and QOL improve-
ment effect of modified arabinoxylan from rice bran
(BioBran/MGN-3) for progressive cancer. Clin Pharmacol
Ther. 2004;14:267-271.
50. Tsunekawa H. Effect of long-term administration of immuno-
modulatory food on cancer patients completing conventional
treatments. Clin Pharmacol Ther. 2004;14:295-302.
51. Lissoni P, Messina G, Brivio F, et al. Modulation of the
anticancer immunity by natural agents: inhibition of T regu-
latory lymphocyte generation by arabinoxylan in patients
with locally limited or metastatic solid tumors. Cancer Ther.
52. Bang MH, Van Riep T, Thinh NT, et al. Arabinoxylan rice
bran (MGN-3) enhances the effects of interventional thera-
pies for the treatment of hepatocellular carcinoma: a three-
year randomized clinical trial. Anticancer Res. 2010;30:
53. Cholujova D, Jakubikova J, Czako B, et al. MGN-3 arabinox-
ylan rice bran modulates innate immunity in multiple myeloma
patients. Cancer Immunol Immunother. 2013;62:437-445.
54. Masood AI, Sheikh R, Anwer RA. “Biobran MGN-3”; effect
of reducing side effects of chemotherapy in breast cancer
patients. Prof Med J. 2013;20:13-16.
55. Itoh Y, Mizuno M, Ikeda M, et al. A randomized, double-
blind pilot trial of hydrolyzed rice bran versus placebo for
radioprotective effect on acute gastroenteritis secondary to
chemoradiotherapy in patients with cervical cancer. Evid
Based Complement Alternat Med. 2015;2015:947390.
56. Petrovics G, Szigeti G, Hamvas S, Máté Á, Betlehem J, Hegyi
G. Controlled pilot study for cancer patients suffering from
chronic fatigue syndrome due to chemotherapy treated with
BioBran (MGN-3-Arabinoxylan) and targeted radiofrequency
heat therapy. Eur J Integr Med. 2016;8:29-35.
57. Golombick T, Diamond TH, Manoharan A, Ramakrishna R.
Addition of rice bran arabinoxylan to curcumin therapy may
14 Integrative Cancer Therapies
be of benefit to patients with early-stage B-cell lymphoid
malignancies (monoclonal gammopathy of undetermined sig-
nificance, smoldering multiple myeloma, or stage 0/1 chronic
lymphocytic leukemia). Integr Cancer Ther. 2016;15:183-189.
58. Hajto T, Horvath A. Improvement of quality of life in tumor
patients after an immunomodulatory treatment with standard-
ized mistletoe lectin and arabinoxylan plant extracts. Int J
Neurorehabil. 2016;3(2):2-4.
59. Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane
Collaboration’s tool for assessing risk of bias in randomised
trials. BMJ. 2011;343:d5928.
60. Takeuchi H, Maehara Y, Tokunaga E, Koga T, Kakeji Y,
Sugimachi K. Prognostic significance of natural killer cell
activity in patients with gastric carcinoma: a multivariate
analysis. Am J Gastroenterol. 2001;96:574-578.
61. Pasero C, Gravis G, Granjeaud S, et al. Highly effective NK
cells are associated with good prognosis in patients with met-
astatic prostate cancer. Oncotarget. 2015;6:14360-14373.
62. Kim JK, Chung JS, Shin HJ, et al. Influence of NK cell count
on the survival of patients with diffuse large B-cell lymphoma
treated with R-CHOP. Blood Res. 2014;49:162-169.
63. He L, Zhu H-Y, Qin S-C, et al. Low natural killer (NK)
cell counts in peripheral blood adversely affect clinical out-
come of patients with follicular lymphoma. Blood Cancer J.
64. Berrien-Elliott MM, Romee R, Fehniger TA. Improving
natural killer cell cancer immunotherapy. Curr Opin Organ
Transplant. 2015;20(6):671-680.
65. Ghoneum M. From bench to bedside: The growing use of
arabinoxylan rice bran (MGN-3/Biobran) in cancer immuno-
therapy. Austin Immunol. 2016;1(2).
66. The safety of Biobran/MGN-3. In: BioBran/MGN-3 (Rice
Bran Arabinoxylan Coumpound): Basic and Clinical
Application to Integrative Medicine. 2nd ed. Tokyo, Japan:
BioBran Research Foundation; 2013:9-13.
... Rice bran arabinoxylan compound (RBAC) is a specific blend of hemicelluloses extracted from rice bran with enzymes from shiitake mushrooms (Lentinus edodes mycelia). Research has shown that RBAC possesses strong immunomodulating properties with clinical applications in cancer treatment (Ooi et al. 2018;Ghoneum 2016). As such, RBAC is used among cancer patients as an immunomodulator to support weakened immune function during and after conventional cancer treatment (Paterson 2002). ...
... As such, RBAC is used among cancer patients as an immunomodulator to support weakened immune function during and after conventional cancer treatment (Paterson 2002). RBAC has been shown to be a safe and effective plant-based BRM with immunomodulating and anti-inflammatory properties that can improve cancer patients' QoL (Ooi et al. 2018). ...
... Improved QoL using RBAC among cancer patients has been documented in many case studies (Ooi et al. 2018). The reported benefits include subjective improvement in sleep, appetite, digestion, physical activity, decreased anxiety, pain, and reduced adverse effects during cancer therapy. ...
Being diagnosed with cancer is an emotionally traumatic event that adversely affects a patient’s sense of overall function and wellbeing. Inflammation is a hallmark of cancer, with the inflammatory process aiding the proliferation and survival of malignant cells, suppressing the adaptive immune response while promoting tumour metastasis. Research has shown that rising systemic inflammation inversely correlates with the patients’ reported quality of life (QoL) and is a vital underlying mechanism leading to poor prognostic outcomes in advanced cancer. Chronic inflammation alongside cancer treatment regimens also contributes to microglial activation in the central nervous system, causing neuroinflammation. This leads to behavioural comorbidities such as depression, anxiety, fatigue, cognitive impairment, and neuropathic pain, which also adversely affect the QoL. Cancer-related malnutrition due to the activation of systemic inflammation is also a predictive factor for poor QoL. Hence, targeting inflammation is a promising approach to enhancing cancer patients’ QoL and improving treatment outcomes. Rice bran arabinoxylan compound (RBAC) is used among cancer patients to support weakened immune function during and after conventional cancer treatment. RBAC has been shown to be a safe and effective plant-based biological response modifier with immunomodulating and anti-inflammatory properties that can improve QoL. RBAC modulates the immune and inflammatory responses via direct absorption into the bloodstream and indirect modulation of gut microbiota. Numerous case studies and clinical trials have demonstrated improved QoL using RBAC among cancer patients. However, further research is required to substantiate the effect of RBAC on the QoL of cancer patients using validated instruments.KeywordsBiobranImmunomodulatorInflammationBehavioural comorbiditiesQLQ-C30FACT-G
... First, a clinical case study showed prolonged survival of the patient with malignant hemangiopericytoma who only took BioBran after surgery (Markus et al. 2006). Second, a recent review article by Ooi et al. documented the evidence-based complementary or alternative therapy using BioBran for conventional cancer treatment (Ooi et al. 2018). These papers show the multifaceted functions of BioBran, affirming its recommendation as adjuvant anticancer therapy and an immune checkpoint therapy. ...
Major lifestyle-related chronic diseases, including cancer and Alzheimer’s disease, are the consequences of long-term micro-inflammation in any microenvironment in our body with a latency of 10–20 years. Inflammation is an immune response triggered by leucocytes, such as macrophages and neutrophils, producing and spreading reactive oxygen species in response not only to pathogens but also to self-structural substances, even DNA. Such oxidative stress affects host cells, so-called friendly-fire. One of the worthiest preventive strategies for lifestyle-related diseases is suppression or downregulation of friendly-fire attacks not by drugs but by potent food supplements. Research conducted by the lead author has confirmed the partially absorbed Biobran with its derivatives in mouse blood after oral intake. The uptake of Biobran may be through Peyer’s patches in the small intestines. Further experimentation also demonstrated that both oral intake and parenteral administration of Biobran in mice induced comparable protective effects against the adverse effects of anticancer drugs, which are potent oxidants and even carcinogenic. Hence, the antioxidant, immunomodulating, and anti-inflammatory effects of BioBran can attenuate the “friendly-fire” in lifestyle-related chronic diseases in adulthood and aging.KeywordsEvidence-basedOral supplementBiobranAntioxidantImmune modulationLifestyle diseasesPreventive medicine
... Briefly, experiments from various in vitro and in vivo studies demonstrated that NK cells stimulated with RBAC had increased granularity with improved cytotoxic activity against pathogens and malignant cells (Ghoneum 2014). The evidence is further supported with positive results from clinical case reports and human trials (Ooi et al. 2018). ...
Rice bran arabinoxylan compound (RBAC) is a functional food produced from hydrolysed rice bran denatured with shiitake mushroom enzymes. RBAC demonstrates strong immunomodulatory properties, particularly for enhancing the natural killer cell activity. Additionally, RBAC can augment phagocytic cellular functions by promoting the growth of macrophage and neutrophil antimicrobial/antitumour phenotypes. Research has also shown that RBAC can modulate the production of many cytokines, including tumour necrosis factor-alpha (TNF-α), interferons (IFN-γ and IFN-λ), and interleukins (IL-2 and IL-12) which have antitumour applications. Moreover, RBAC is an inducer for the maturation and activation of dendritic cells (DCs), which plays a crucial role in priming the adaptive immune response against invading pathogens and cell mutations. As DCs are antigen-presenting cells that activate the T lymphocytes, stimulation of DCs by RBAC can induce CD4+ T cell proliferation and inhibit the immunosuppressing Treg cells in patients with underactive immune responses. While not an antioxidant in its own right, RBAC has also been shown to augment the body’s natural antioxidant defence mechanisms against free radicals. RBAC also shows antiangiogenesis effects in blocking the vascular endothelial growth factor pathway and thus inhibiting tumour development. Overall, RBAC is a potent antiproliferative food supplement with strong evidence showing that it can arrest tumour proliferation.KeywordsNutraceuticalsAntitumourMacrophagesCytokinesDendritic cellsT lymphocytesOxidative stressVEGF
... AX exhibits many bioactive characteristics, including antioxidant, fermentable, and prebiotic properties, glucose-and lipid-regulating effects, and immune-modulating potentials (4,5). AX has been described as an efficient immunomodulator for synergistic or complementary cancer treatment (6). Chlorogenic acid (CA), a hydroxycinnamic acidderived phenolic compound, is widely distributed in many plant foods, including vegetables, fruits, and herbal remedies (7). ...
Full-text available
Dietary non-starch polysaccharides and phenolics are usually ingested at the same time. They are both regarded as prebiotics, and they regulate the intestinal microbiota through various mechanisms. Notably, however, reports of their combined or synergistic effects are rare. Arabinoxylan (AX), a polysaccharide, and chlorogenic acid (CA), a polyphenol, are widely consumed, and their effects on the microbiota have previously been discussed. In the present study, they were given to dextran sulfate sodium (DSS)–treated mice, separately and together, and the intestinal microbiota were investigated by high-throughput sequencing. The data showed that CA attenuated body weight loss, colon shortening, and histological damage in DSS-treated mice, while neither AX nor the AX+CA combination exhibited any ameliorating potential. AX+CA had less of a modulating effect on intestinal microbiota profiles than did CA. AX+CA administration increased the relative abundance of Flavonifractor, Coprobacillus , and Clostridium_XlVa , and decreased the abundance of Robinsoniella and Lactobacillus . Compared to AX and CA, AX+CA contributed to a more complicated shift in the biological functions of the intestinal microbiotaAX seemed to weaken the beneficial effects of CA, at least in the present experimental model of DSS-induced colitis. The combined effects and mechanisms of dietary polysaccharides and phenolic compounds on the intestinal microbiota and on overall health still need to be further investigated.
Full-text available
Most diseases are preventable, and they are related to what we eat. Moreover, most doctor visits are for lifestyle-based diseases, which means they can be prevented by adopting a healthy lifestyle. Treating the causes of illness rather than symptoms of the disease is not only safer and cheaper, but it can work better. In this context, the Special Issue on “Nutraceuticals in Immune System” for the journal Molecules was launched in January 2020. Soon after that, the world was ravaged by the COVID-19 pandemic causing a grave health threat. Paradoxically, the immune system can be both friend and foe of COVID-19. The COVID-19 manifests only mild to moderate symptoms for most infected people who recover without hospitalisation, demonstrating the proper functioning of the immune system in fighting such an infection. For some, however, the overactivation of the immune response causing “cytokine storm” has dire consequences, with severe respiratory failure leading to multiple organ failure, which could be fatal. In fact, most deaths from COVID-19 came from organ inflammation due to undesirable immune system responses. As such, the COVID-19 is a good case in point, demonstrating the importance of a healthy immune system. Nutraceuticals are products derived from food sources with health benefits in addition to the basic nutritional values. Many of them can positively affect and enhance the immune system, which is particularly pertinent in the current turbulent times of COVID-19. Not surprisingly, nutraceutical sales rose dramatically during the pandemic period. However, much research is still needed to understand how natural products interact with the immune system to clarify their chemical compositions, mechanisms of action and effects on health and illnesses. This Special Issue provided an open forum for researchers to share their research findings in the growing interest of nutraceuticals. We received an overwhelming response with a total of 33 submissions, of which only nine original research papers and ten reviews were accepted after rigorous peer-review. The included articles research into natural substances of interest in nutraceuticals ranging from herbal medicine to vitamins to microbiota-derived metabolites. The investigated immune-related responses include cancer, neurological diseases, gastroenterological disorders, inflammatory conditions, and infections. We thank the publisher for this excellent opportunity to serve the research community. As academic editors for this Special Issue, it is our pleasure to review these insightful manuscripts first-hand. We thank all the authors for their contributions. The collected works represent our current understanding and latest findings of nutraceuticals in immune system, which we hope will continue to inspire knowledge quests into the field of nutraceuticals.
Radiotherapy is an established modality in cancer treatment alone or in combination with other modalities such as surgery and chemotherapy. Although radiotherapy is employed to improve the quality of life (QoL), its association with several side effects remains a clinical challenge. Several studies have shown that treatment-related symptoms and side effects increased in general during radiotherapy due to inflammation and cytotoxic damage, eventually leading to unnecessary treatment interruptions or delays. Studies have shown that prolonged radiotherapy treatment time is associated with worse overall survival and poor quality of life among cancer patients undergoing treatment. This chapter explores the benefits of using rice bran arabinoxylan (Biobran) as a supportive treatment for cancer patients undergoing radiotherapy. This chapter also aims to analyze its impact on clinical outcomes based on several factors, including, but not limited to, hematologic parameters, nutritional status, treatment-related toxicities, and QoL. As of writing, only a few articles have been published on rice bran arabinoxylan’s effects on cancer patients undergoing radiotherapy.KeywordsRadiotherapyCancer treatmentRice bran arabinoxylanBiobran
Integrative oncology is a branch of integrative medicine that combines the treatment of cancer patients with complementary and conventional modalities. It aims to enhance the effect of conventional treatments and optimize the quality of life and emotional health of cancer patients. Carcinogenesis involves the transformation of normal cells into cancer cells through random damage to control genes, leading to uncontrolled growth, proliferation, and invasion of cancer cells into normal tissues. While chemotherapy and bio-targeted therapy address cancer spread from the initial tumor, surgery and radiotherapy deal with the growing mass, and immunotherapy addresses those cancer cells that knock out the immune system’s ability to recognize them. Conventional cancer management targets early-stage cancer with curative intent and late-stage cancer with palliative intent. Complementary modalities in cancer management encompass mind/body practices, natural products, and lifestyle modification. When diet therapy and nutraceutical medicine are used in cancer management, it is referred to as nutritional oncology. Modified rice bran arabinoxylan is a nutraceutical that has been shown to improve the quality of life in breast cancer patients, reduce the chemotherapy side effects, enhance the response rate to chemotherapy in liver cancer, provide radioprotective effects in cervical cancer, augment immunity in multiple myeloma, and prolong survival of patients in many case studies. Integrative oncology has emerged as a new field of medical practice to improve cancer patients’ survival and quality of life.KeywordsIntegrative medicineComplementary therapyNatural productsLifestyle modificationNutritional oncologyEvidence-based integration
There is accumulating evidence that rice bran extracts have profound effects on mediating inflammation, with the therapeutic potential of rice bran widely explored in several chronic inflammatory conditions including asthma, diabetes, obesity, dermatitis, arthritis, liver injury, neuroinflammation, and cancer. However, rice bran extracts are often poorly characterised, making it difficult to ascertain which constituents of the extract are contributing to the observed anti-inflammatory properties. Despite this drawback, rice bran arabinoxylans (AXs), or AX-derived compounds such as ferulic acid and feruloylated oligosaccharides, have been identified as principal anti-inflammatory agents in rice bran extracts. Moreover, AX-induced patterns of anti-inflammatory effects involving changes in transcription factor regulation, gene transcription, enzyme activity, or inflammatory cytokine/mediator secretion are beginning to emerge in the research literature. Given the body of published research primarily utilises modified rice bran AX, commonly known as Biobran or MGN-3, there is ample scope to explore a wider range of non-modified rice bran AXs as anti-inflammatory agents in future work. Exploiting the emerging anti-inflammatory properties of rice bran AXs to develop potential treatments or prophylactic therapies for inflammatory diseases is an exciting prospect that warrants further investigation.KeywordsInflammationAnti-inflammatoryArabinoxylanRice branBiobranMGN-3
Hemicelluloses, a major component of plant cell walls, are a non-cellulosic heteropolysaccharide composed of several distinct sugars that is second in abundance to cellulose, which are one of the most abundant and cheapest renewable resources on earth. Hemicelluloses structure is complex and its chemical structure varies greatly among the different plant species. In addition to its wide use in production of feed and other chemical materials, hemicelluloses are known for its remarkable biological activities that remain largely underutilised to date. Therefore, comprehensive investigations of hemicelluloses structural and biological properties would be helpful for achieving rational utilisation and high-value conversion of this underutilised substance into agents with enhanced health benefits for incorporation in drugs and health foods. In this review, details of diverse research initiatives that have enhanced our understanding of hemicelluloses properties are summarised, including hemicelluloses sources, extraction and purification methods, structural characteristics and biological activities. Furthermore, hemicelluloses structure-activity relationships and new directions for future hemicelluloses research studies are discussed.
Full-text available
Cancer is a significant global health concern affecting men and women worldwide. Although current chemopreventive drugs could inhibit the growth of cancer cells, they exert many adverse side effects. Dietary factor plays a crucial role in the management of cancers and has drawn the attention of researchers to be used as an option to combat this disease. Both in vitro and in vivo studies showed that rice and its by-products display encouraging results in the prevention of this disease. The mechanism of anticancer effect is suggested partly through potentiation of bioactive compounds like vitamin E, phytic acid, γ -aminobutyric acid (GABA), γ -oryzanol, and phenolics. Nevertheless, the bioactivity of rice and its by-products is still incompletely understood. In this review, we present the findings from a preclinical study both in in vitro and in animal experiments on the promising role of rice by-products with focus on cancer prevention.
Full-text available
Introduction: Although modern therapies for cancer have improved life expectancy, the management of disease and improvement of quality of life (QoL) of patients, especially managing cancer-related pain and chronic fatigue syndrome are still limited. We demonstrate the efficacy of a combined therapy to treat cancer patients suffering from CFS. The effects of a combined therapy in cancer patients suffering from CFS was evaluated. NK cells were stimulated, additional tumour treatment together with targeted radiofrequency therapy (Oncothermia). Methods: SIXTY patients with CFS (due to suffering from any type of cancer) were recruited, (according to the Centres for Disease Control 1994 criteria) attending an outpatient specialist CFS service for controlled pilot study. A total of 25 participants were given oral BioBran (MGN-3-Arabinoxylane), + Oncothermia, for six months, equivalent control group has not received this complex (BioBran+Oncothermia) treatment, they received chemo-,radiotherapy treatment. Results: The whole body pH status showed strong tissue acidity before the treatment, but the BioBran group changed the tissue pH status. The most important finding was that the average of CFQ score was significantly reduced after the treatment, and in control group the CFQ scores did not change significantly. Conclusion: The findings support a specific therapeutic effect of the complex BioBran+ Oncothermia therapy in CFS of cancer patients improving their QoL, enhancing NK activity in synergy. Keywords: Chronic fatigue syndrome, BioBran (MGN-3-Arabinoxylane), Oncothermia, Complementary Medicine, EORTC QLQ-C30 (version 3), QoL, VAS, NK activity
Full-text available
In this study, we examine the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the apoptotic effect of paclitaxel (Taxol) at low concentration [2 mg/kg body weight (BW)] in animals bearing Ehrlich ascites carcinoma (EAC) cells and elucidate its mechanisms of action. On Day 8 following tumor cells inoculation, mice bearing tumors were administered MGN-3 alone (40 mg/kg BW), paclitaxel alone, or MGN-3 plus paclitaxel. On Day 30 post-tumor inoculation, we observed significant suppression of tumor volume (TV) with paclitaxel alone (59%), MGN-3 alone (77%), and MGN-3 plus paclitaxel (88%). Inhibition of tumor growth post-treatment with both agents, as compared with either treatment alone, was associated with a decrease in cell proliferation, a marked increase in the sub-G0/G1 population, an increase in DNA damage and apoptosis of tumor cells, and a significant maximization of the apoptosis index (AI)/proliferation index (PrI) ratio. Histopathological and electron microscopy examination of the combined treatment group showed an increase in the degenerative regions of the solid tumor tissue and abundant apoptotic cells. These data suggest that MGN-3 supplementation enhances tumor cell demise in the presence of a low dose of chemotherapeutic agent via apoptotic mechanism.
Full-text available
Hypothesis Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies.
Full-text available
In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer.
Objective: The aim of study was to assess the effect of Biobran in reducing of chemotherapy induced side effects in termsof tiredness, anorexia, vomiting and hair loss and quality of life in terms of weight loss. Setting: Radiotherapy Department, NishtarHospital Multan. Material and Methods: Fifty patients of breast cancer were enrolled randomly in two groups. Group-A patients weregiven 3 gram dose of Biobran MGN-3 per day one week before and one week after chemotherapy. Group-B patient were givenchemotherapy alone. Total six cycles of chemotherapy were given. No multivitamin or food supplements were given during this study.Chemotherapy induced side effects (tiredness, anorexia, and vomiting, hair loss) were assessed by questionnaire to the patients beforestart of each cycle. Weight was checked before each cycle to assess weight gain or loss. White blood cells were checked by completeblood count just before and one week after chemotherapy. Results: Between six months, 50 patients were enrolled in RadiotherapyDepartment, Nishtar Hospital Multan. There was a significant reduction in tiredness and anorexia in group-A patients. 20 (80%) patients ofgroup-A felt increase in their diet and no tiredness without any appetizer or multivitamin. But group-B patients demanded for appetizer dueto severe anorexia after chemotherapy except 3 (12%) patients who didn’t use any appetizer or food supplement. In group-A, 15 (60%)patients didn’t need any anti-emetic as compared to group-B all patient (100%) experienced severe nausea during and afterchemotherapy. Group-A patients experienced less hair fall 7 (28%) patients as compared to other group which is 25 (100%) patients.Conclusions: The study showed that, by helping to optimize the immune system, Biobran MGN-3 can not only help maximize treatmentsuccess, but also minimize treatment side effects and improve quality of life during treatment and in recovery.
Objective: Hepatocellular carcinoma is one of the most common cancers in the world and one of the most lethal. MGN-3/Biobran, derived from rice bran hemicelluloses, has been reported to possess a strong anticancer effect against several neoplasms. In the current study, we examined the protective effect of MGN-3/Biobran against N-nitrosodiethylamine (NDEA) and carbon tetrachloride (CCl4)-induced hepatocarcinogenesis in rats and studied the molecular mechanisms underlying its effect. Materials and Methods: Male albino rats received carcinogen NDEA (200 mg/kg body weight) single dose i.p. plus promoter CCl4 (3 ml/kg b.w.) weekly s.c. for 6 weeks. Another group of rats were treated with MGN-3/Biobran (25mg/Kg b.w.) 5 times/week i.p. for 2 weeks prior to receiving carcinogens and continued for 20 weeks. Tumor incidence, histopathology, body and liver weight, liver marker enzymes, cell cycle progression, cell proliferation and apoptotic-related markers at mRNA and protein expression levels were quantitatively determined. Results: Rats exposed to carcinogens alone showed loss of liver architecture, and proliferative and neoplastic changes. This group also showed marked decrease in body weight, increase in liver weight, and elevation in the levels of hepatic diagnostic markers: serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (gamma GT). In contrast, rats pretreated with MGN-3/ Biobran and subsequently exposed to carcinogens showed significant reduction in liver tumor incidence, marked decrease in the percentage of pre-neoplastic foci in hepatic parenchyma, and inhibition in the development of hepatocellular carcinoma. MGN-3/ Biobran treatment also maintained AST, ALT, ALP, and gamma GT levels close to normal values. In addition, MGN-3/Biobran treatment was associated with marked increase in both the cell cycle sub-G0/G1 population and AnnexinV-binding. The molecular studies at mRNA and protein expression levels in the liver tissues demonstrated that MGN-3/ Biobran reversed carcinogen induced suppression in the level of IkappaB-alpha (IκB-α), downregulated the expression of the nuclear factor kappa-B (NF-κBp65) and Bcl2, upregulated the expression of p53, Bax, caspases-3 and markedly increased Bax/Bcl2 ratio. Conclusion: This study concluded that MGN-3/ Biobran inhibited hepatocarcinogenesis induced by NDEA and CCI4 via induction of apoptosis and inhibition of cancer cell proliferation. MGN-3/ Biobran may be a promising chemopreventive agent for liver carcinogenesis. Biobran /MGN-3 was provided by Daiwa Pharmaceutical Co., Ltd. Tokyo, Japan. Citation Format: Nariman K. Badr El-Din, Doaa A. Ali, Reem Othman, Mamdooh Ghoneum. Prevention of hepatocarcinogenesis in rats by arabinoxylan rice bran, MGN-3/Biobran. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5259.
Background: In the last decades a special attention has been focused on the role of disturbed immune balance in the behavioral co-morbidities of tumor patients. The prognostic significance of malignant tumor-induced imbalance in the innate immune system is well known. The innate system uses a limited number of Pattern Recognition Receptors (PRR) to recognize conserved Pathogenic Associated Molecular Pattern (PAMP) structures expressed by microbes but not by host. Growing experiences suggest that the improvement of tumor induced disturbance of immune balance by using standardized plant PAMP like preparations goes often together with a better quality of life (QoL). Methods: In this study tumor patients were treated with standardized plant immunomodulators (mistletoe lectin and arabinoxylan) which were shown to activate the type-1 natural immune cells against cancer. After at least a therapy for six months the patients were asked about their QoL using questionnaires. Results: The following answers were received from the 35 patients: Decrease of pains: 17%, improvement of anxiety: 40%, Increase of physical activity: 71%, Improvement of appetite: 66%, Improvement of sleep: 40%, improvement of digestion: 43%, decrease of side effects during oncotherapy: 71%, beneficial judgement of the progress of disease based on clinical findings: 46%. As shown, the most important effects were the improvement of physical activity and decrease of side effects during conventional oncotherapy. Conclusion: Present results may support the relationship between tumor induced disturbance of immune balance and the tumor induced behavioral co-morbidities. Further clinical investigations are necessary to proof this hypothesis.