maritech organic fucoidans - marinova · benefits and bioactivities. this range includes highly...
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MARITECH® ORGANIC FUCOIDANSTHE SCIENCE
Dr J. Helen FittonChief Scientist, Marinova Pty Ltd
PAGE 2 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
About 3The author 3
The company 3Maritech® fucoidan range 4
Overview 4 Characterisation 5
Pure source 5Zero-waste manufacturing 5
Maritech® extraction process 6Bioactivities 8
Overview 8 Anti-cancer 9
Immune modulation 16Gut and digestive health 18Viral inhibition 21
Anti-inflammation 22Regulatory 24 Safety 24
Global acceptance 25Quality and certifications 25
References 26
CONTENTS
INTRODUCTIONFucoidans are non-gelling, fucose-rich sulfated polysaccharides found primarily in brown
seaweed. They are highly bioactive compounds that play a pivotal role in protecting
seaweed from water-borne pathogens and other environmental challenges. Extensive
research has shown that fucoidan extracts impart significant beneficial effects in a wide
range of human health settings.
This white paper explores the science behind fucoidan, with a particular focus on
the latest research supporting the use of Maritech® fucoidan extracts in immune
modulation, gut and digestive health, viral inhibition, anti-inflammation and integrative
oncology applications.
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 3
Dr Helen Fitton is Marinova’s Chief Scientist and an
Adjunct Senior Researcher at the University of Tasmania.
With more than 20 years experience in commercially-
focussed research and development, Dr Fitton is
recognised as a world-leading authority on fucoidan
compounds. Her area of expertise lies in polymers
for biomedical applications, with a focus on natural
polysaccharides from marine macroalgae. Dr Fitton
holds a BSc (Hons) in Biochemistry from the University of
Manchester, a MSc in Mineralised Tissues from University
College London and a PhD in Applied Chemistry from
Aston University.
To date, Dr Fitton has been a key contributor to 35
published research papers and 3 book chapters, as well
as the reviewer of countless fucoidan and macroalgae-
focussed research papers. Dr Fitton has been instrumental
in developing Marinova’s portfolio of Maritech® fucoidan
extracts and has led the science in creating effective new
products for use in a range of nutritional, pharmaceutical,
medical device and dermatological applications.
ABOUTThe author
The company
INTRODUCTION
Marinova is a progressive Australian biotechnology
company dedicated to the research, development
and manufacture of high purity fucoidan extracts for
use in pharmaceutical, nutritional and dermatological
applications.
With world-class extraction facilities and research
laboratories located in Tasmania, Australia, Marinova
is recognised globally for its commitment to innovation
and expertise in fucoidan science. The company is a
GMP, ISO9001 and HACCP accredited manufacturer
and the only producer of high purity, certified organic
fucoidan. Marinova exports its fucoidan extracts to more
than 25 countries across the globe and is the world’s
leading fucoidan supplier to research institutions and
nutraceutical and pharmaceutical companies.
Maritech® fucoidans are unique, high purity ingredients
that are non-toxic and safe for human ingestion. They
have been extensively researched and shown to impart
a range of beneficial bioactivities. Maritech® fucoidans
are particularly well known for their efficacy in anti-
cancer, anti-viral, immune modulation, gut health, anti-
inflammation and anti-aging applications.
Marinova produces its lead fucoidan ingredients
from two species of certified organic, wild grown
macroalgae:
Undaria pinnatifida: commonly called wakame or
mekabu, this is an edible seaweed that grows in the
pristine ocean waters of Patagonia and Tasmania. It
yields a fucoidan extract which is highly acetylated and
rich in galactose.
Fucus vesiculosus: commonly called bladderwrack, this
species grows in the clear northern hemisphere waters
of Nova Scotia and Brittany. It yields a fucoidan extract
with a very high fucose content that is not acetylated.
Fucoidans have different chemical structures and
bioactivities depending upon the species of seaweed
from which they are derived, and the method by which
they are extracted.1,2,3,4 From the Undaria and Fucus
species of seaweeds, Marinova has created a range
of high purity fucoidan ingredients, each with distinct
benefits and bioactivities.
This range includes highly refined compounds for
medical research and pharmaceutical development
through to certified organic fucoidan extracts for
nutritional and personal care applications. Included
in the Maritech® range are extracts that contain both
fucoidan and antioxidant-rich algal polyphenols.
MARITECH® FUCOIDAN RANGEOverview
PAGE 4 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 5
MARITECH® FUCOIDAN RANGECharacterisation Pure source
Zero-waste manufacturing
MARITECH® FUCOIDAN RANGEOverview
Fucoidans are highly branched, complex polysaccharides
of varying size, typically with a high molecular weight.
Fucoidans are characterised chemically using validated
assays that quantify the sulfation, acetylation, molecular
weight and the content of sugars in the carbohydrate
‘backbone’.
+ Figure 1: typical section of a fucoidan compound
Like fucoidan, algal polyphenols are complex
structures. The type of polyphenol found in Fucus
vesiculosus is a polymeric form of phloroglucinol.5 The
polyphenol content of Maritech® extracts is determined
using a validated colorimetric assay.
+ Figure 2: typical section of polyphloroglucinol
Marinova is a fervent protector of the world’s marine
environment and exemplifies sustainable practices in
every element of its business. Marinova only sources
wild grown, certified organic brown macroalgae from
the world’s purest ocean waters. This includes the
cool, pristine ocean waters of Patagonia, Nova Scotia,
Brittany and Tasmania.
All seaweeds are sourced using best practice
environmental standards. The macroalgae used by
Marinova is hand-harvested in line with its seasonal growth
cycle to minimise disruption to the environment and
ensure sustainable growth. Once harvested, the seaweed
is immediately dried to retain the natural bioactivity of
fucoidan.
Marinova is continuously implementing new initiatives to
ensure sustainability and protection of the environment.
Since establishing its state-of-the-art extraction facility,
the company has succeeded in diverting all seaweed
residues away from unproductive landfill and into new,
value-added products. Seaweed not utilised for the
extraction of high purity fucoidan extracts is sold by
Marinova into the gourmet and wholefoods sectors.
Both liquid and solid by-products of the extraction
process are captured and converted into nutrient-
rich organic additives for the horticultural sector. As a
result of these initiatives, the company is on the cusp of
becoming a legitimate zero-waste manufacturer.
PAGE 6 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
The high purity of Maritech® fucoidan is attributed to
the unique, proprietary Maritech® extraction process,
developed and used exclusively by Marinova. The
aqueous extraction and purification process utilises
advanced physical filtration methods to separate
and purify fucoidan without the use of harsh organic
solvents. This solvent-free technology, and the
exceptional quality of the seaweeds, are the reasons
that Marinova stands alone as the only manufacturer of
certified organic, high purity fucoidan.
The Maritech® process creates efficacious, high purity
fucoidan extracts that are:
• Certified organic
• Non-GMO accredited
• Solvent-free
• Kosher and Halal certified
• Nature-identical
• Highly bioavailable
MARITECH® FUCOIDAN RANGEMaritech® extraction process
MARITECH® ORGANIC FUCOIDANS 2017 WHITE PAPER | PAGE 7
MARITECH® FUCOIDAN RANGEMaritech® extraction process
PAGE 8 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
Studies undertaken by Marinova and independent
research groups around the world have investigated
the efficacy of fucoidan in a diverse range of
indications and clinical settings. Marinova has a very
active research program. It is continually engaging with
leading international universities and research institutions
to investigate the beneficial properties of Maritech®
fucoidan extracts in various human health settings.
Marinova’s in vitro research, animal studies and human
clinical trials are currently focussed on the key health
indications below:
BIOACTIVITIESOverview
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 9
Cancer and fucoidan
Fucoidan is particularly well known - and widely utilised
- for its anti-cancer properties. Extensive research
has been undertaken in this field, demonstrating
the potential for fucoidan to be used alongside
conventional treatments.3,6,7
In various studies, fucoidan has been found to:
• slow tumour metastasis
• enhance therapeutic effects of conventional
therapy
• reduce side effects of chemotherapy
• defend against treatment-related weight loss
and muscle loss
Directly affecting cancer cells
Fucoidan can directly affect cancer cells via cellular
pathways that involve the activation of NF-κβ. This
activation is mediated by PI3K/Akt and ERK signaling
pathways.7
Recent research indicates that fucoidan may also
induce programmed cell death (known as apoptosis)
in breast and colon cancer cells by modulating the
endoplasmic reticulum stress cascades.8
Maritech® fucoidan has been shown to cause cell
cycle arrest in the first growth phase (G1) of a HCT116
human colon cancer cell line.9 By halting the cell cycle
process in this way, the colon cancer cells are unable to
divide and spread.
Maritech® fucoidan has also been shown to induce
DNA damage as measured by ɣH2AX positive cells in a
HCT116 human colon cancer line.9 This disrupts the ability
of the cancer cells to grow and metastasise. Importantly,
the study results showed that Maritech® fucoidan did not
cause damage to normal healthy cells.
BIOACTIVITIESAnti-Cancer
BIOACTIVITIESOverview
CEL
L C
OUN
T %
G1 CELL CYCLE ARREST OF HCT116 COLON CANCER CELLS
TIME (HOURS)
60
45
30
15
00 24 48 72
• G1 • S • G2
POSI
TIV
E C
ELLS
%
DNA DAMAGE CAUSED IN HCT116 COLON CANCER CELLS
TREATMENT
CONTROL MARITECH® FUCOIDAN
100
80
60
40
20
0
POSI
TIV
E C
ELLS
%
NO DAMAGE IN NORMAL HUMAN FIBROBLASTS
TREATMENT
20
15
10
5
0 CONTROL MARITECH® FUCOIDAN
PAGE 10 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
Using the immune system
In vitro experiments and animal studies have shown
that fucoidan exerts anti-cancer activity by activating
immune cells and stimulating the production of anti-
cancer cytokines.6
Recent research indicates that fucoidan affects
macrophages, a type of white blood cell that engulfs
and destroys pathogens. In tumours, macrophages can
become damaging by secreting chemical messengers,
chemokine CCL22, that allow tumours to grow. By
suppressing chemokine CCL22, fucoidan is able to
switch macrophages back into a ‘healthy’ form.10 This,
in turn, inhibits the migration and growth of cancer cells
and the recruitment of CD4+ T lymphocytes.
Blocking chemical messages to cancer Fucoidan has been shown to effectively block chemical
messages to tumours by interfering with the binding
between the cellular receptor CXCR4 and chemokine
CXCL12 (or SDF-1).11,12
In additional research, fucoidan extracts from
Saccharina latissimi and Fucus vesiculosus were shown
to bind to CXCL12 and prevent binding to the CXCR4
cellular receptor. In doing so, fucoidan prevented
downstream effects, including the secretion of matrix-
degrading enzymes necessary for metastasis.13
Reducing pre-cursors to cancer The occurrence of cancer is often linked to chronic
inflammation. In pre-clinical studies, Maritech®
fucoidan has been shown to significantly reduce gut
inflammation and colitis by inhibiting key inflammatory
enzymes expressed in the gastrointestinal tract,
including COX-1, COX-2 and LOX-15.14
In a mouse model, orally ingested Maritech® fucoidan
was found to significantly reduce the clinical symptoms,
pathology and cytokine elevations of acute colitis.15
By doing so, Maritech® fucoidan shows promise as a
preventative for a number of gastrointestinal disorders
and cancers which are closely associated with chronic
gastrointestinal inflammation.
In addition, Maritech® fucoidan may play a preventative
role in Helicobacter pylori-induced diseases and gastric
cancer. Helicobacter pylori is the primary cause of
chronic stomach inflammation, peptic ulcer diseases
and gastric cancers in humans. In a cellular model
designed to mimic the natural infection of this ulcer-
causing bacteria, Maritech® fucoidan effectively
dislodged Helicobacter pylori from human gastric
epithelial cells and reduced adhesion by up to 55%.16
BIOACTIVITIESAnti-cancer
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 11
BIOACTIVITIESAnti-cancer
PAGE 12 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
Fucoidan research in various cancer types: Fucoidan research has demonstrated multi-faceted anti-
cancer activity across a wide range of tumour types:
Colorectal cancer In recent research, fucoidan was shown to inhibit the
growth of a colon cancer cell line via inhibition of
T-cell originated protein kinase (TOPK). In this study,
fucoidan was also orally administered to mice and
found to suppress the growth of human colorectal
tumours through the same pathway.17 Results show the
potential for fucoidan to be used as a complementary
therapy to improve the effectiveness of current cancer
treatments. As previously discussed, Maritech® fucoidan
has been shown to induce DNA damage and cause
cell cycle arrest in the first growth phase of a HCT116
human colon cancer cell line.9 This action disrupts the
ability for the cancer cells to divide and spread.
Lung cancer In a lung cancer mouse model, fucoidan down-
regulated the expression of a number of key markers
associated with tumour development, spread
and proliferation.18 These markers included matrix
metalloproteinases, NF-κβ and vascular endothelial
growth factor. The orally ingested fucoidan was shown
to reduce lung masses and lessen weight loss.
Liver cancer In an in vitro study, fucoidan inhibited the growth of liver
cancer cells through the AMPK-associated suppression
of fatty acid synthesis and cell cycle G1/S transition.19 In
further in vitro research, fucoidan increased the activity
of tumour suppressor proteins p53 and p38 MAPK, which
directly inhibits the proliferation of hepatic tumour cells
and induces apoptosis.20
Oral cancers Fucoidan reduced the growth of oral cancer
cells and caused cell death in an in vitro study of
mucoepidermoid carcinoma, a type of oral cancer.21
In this research, fucoidan decreased cell proliferation
and induced caspase-dependent apoptosis via down-
regulation of the extracellular signal-regulated kinase
ERK1/2.
Breast cancer Extensive research demonstrates the effects of fucoidan
on breast cancer in animal models.3,6 Maritech® fucoidan
has been shown to significantly improve the effectiveness
of tamoxifen, a common chemotherapy used in breast
cancer. In a mouse model, orally ingested Maritech®
fucoidan reduced breast cancer tumour growth by up to
an additional 26% when taken alongside tamoxifen.22
BIOACTIVITIESAnti-cancer
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 13
Prostate cancer Fucoidan has been shown to induce cell death in an
in vitro study of PC-3 human prostate cancer cells.23 In
the study, fucoidan was shown to activate apoptosis
through the use of both intrinsic and extrinsic pathways.
Fucoidan has also been found to inhibit growth and
induce apoptosis in DU145 human prostate cancer cells
involving the PI3K/Akt signaling pathway.24
Ovarian cancer Maritech® fucoidan has been shown to decrease the
growth of a TOV-112D human ovarian cancer cell line.
In a mouse model, the ingestion of Maritech® fucoidan
decreased the growth of this tumour line by up to 33%.25
Cervical cancer Maritech® fucoidan has been shown to reduce the growth
of a HeLa human cervical cancer cell line. Ingestion of
Maritech® fucoidan was found to decrease the growth of
this tumour line by up to 70% in a mouse model.25
Pancreatic cancer Fucoidan decreased the ability for pancreatic cancer
cells to secrete matrix-degrading enzymes required to
metastasise and spread in an in vitro model.26 In addition,
fucoidan was shown to interfere with the binding of
chemokines to the cellular receptor CXCR4.13 Inhibition
of CXCR4 has been shown in an animal model to reduce
pancreatic tumour growth and metastases.27 Fucoidan
also demonstrated potential to reduce the effects of
acute pancreatitis due to its ability to block selectins.28
BIOACTIVITIESAnti-cancer
BIOACTIVITIESAnti-cancer
CHA
NG
E IN
TUM
OUR
GRO
WTH
(M
M2 )
DECREASED GROWTH OF TOV-112D HUMAN OVARIAN CANCER CELL LINE
TIME (DAYS)
- UNTREATED- MARITECH® UNDARIA- MARITECH® FUCUS
0.4
0.3
0.2
0.1
00 7 14 21 28
PAGE 14 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
BIOACTIVITIESAnti-cancer Maritech® fucoidan and chemotherapy efficacy
In pre-clinical studies, Maritech® fucoidan has been
shown to improve the effectiveness of a number of
common chemotherapies. In vitro studies showed
strong synergistic activity between Maritech® fucoidan
and both paclitaxel and tamoxifen, as well as additive
activity between Maritech® fucoidan and topotecan.25
In further pre-clinical research, Maritech® fucoidan has
been shown to considerably improve the efficacy of
tamoxifen towards breast cancer. In a mouse model,
ingestion of Maritech® fucoidan decreased breast
cancer tumour growth by up to an additional 26%
when taken alongside tamoxifen.22
These findings have been echoed in earlier studies, in
which fucoidan from the seaweed species Cladosiphon
okamuranus showed synergistic effects with three
chemotherapy agents in breast cancer cell lines.29 In
other research, Undaria pinnatifida fucoidan was found
to increase the efficacy of the cancer drug lapatinib
and reduce morbidity in a melanoma model.30
Fucoidan has also greatly increased the efficacy of the
chemotherapy drug etoposide in human malignant
lymphoid cell lines.31
Safety of Maritech® fucoidan with chemotherapy
It is important for patients and their physicians to be
confident that any supplements taken during cancer
therapy are safe and do not cause clinically significant
adverse effects or interactions. Both in vitro tests and
human clinical studies have demonstrated the safety
of Maritech® fucoidan when used in combination with
chemotherapy.
A human clinical study investigated the
pharmacokinetics of Maritech® fucoidan on two
hormone therapies, tamoxifen and letrozole, commonly
used in the treatment of breast cancer.32 Results
showed that the ingestion of Maritech® fucoidan
caused no adverse effects and no significant changes
in steady-state plasma concentrations of letrozole,
tamoxifen or tamoxifen metabolites. Additional toxicity
monitoring showed that all parameters measured
over the study period remained unaffected by
fucoidan. These results demonstrate the safety of taking
Maritech® fucoidan alongside letrozole and tamoxifen.
A separate in vitro study evaluated drug interactions
between fucoidan and the chemotherapy drugs
paclitaxel, tamoxifen and topotecan in a range of
cancer cell lines.25 Five hepatic metabolism phase
II pathways involved in chemotherapy action were
evaluated — GST, QOR, COMT, UDP and UGT. These key
enzyme pathways are required for the effective uptake
and action of chemotherapy. Results showed that
Maritech® fucoidan did not interfere with these enzyme
pathways at physiologically relevant concentrations.
These findings demonstrate the safety of fucoidan
as an adjunct to cancer therapy.
% R
EDUC
TIO
N IN
TUM
OUR
SIZ
E
CO
MPA
RED
TO
UN
TREA
TED
IMPROVED EFFECTIVENESS OF TAMOXIFEN IN ZR-75 HUMAN BREAST CANCER TUMOUR
TREATMENT
50
37.5
25
12.5
0 TAMOXIFEN TAMOXIFEN + TAMOXIFEN + MARITECH® MARITECH® UNDARIA FUCUS
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 15
BIOACTIVITIESAnti-cancer Reducing chemotherapy side-effects
Research shows that fucoidan has the potential to
assist in alleviating the following side effects that are
common during chemotherapy treatment:
Inflammation
• Raised inflammatory levels are often seen in late
stage cancer as a side effect of chemotherapy. In a
clinical trial, 4 g of fucoidan was administered daily
to 20 patients with advanced cancer. Results showed
that fucoidan significantly reduced proinflammatory
cytokines, including interleukin-1β (IL-1β), interleukin- 6
(IL-6) and tumour necrosis factor-α (TNF-α) after 2
weeks.33
Fatigue
• In a clinical study involving patients with resectable
colon cancer, the daily ingestion of 4.05 g of fucoidan
led to a reduction in fatigue and patients were able to
tolerate more rounds of chemotherapy.34
• Fucoidan has also been shown to reduce fatigue
levels in a mouse model, involving the equivalent of
a human dose of 1.5 g of fucoidan per day.35 In this
model, reduced fatigue was associated with increased
levels of serum glucose and decreased levels of serum
lactate, ammonia and triglyceride levels.
Joint pain
• In an osteoarthritis study, patients who ingested
1 g of Maritech® fucoidan daily achieved a 52%
reduction in their osteoarthritis symptoms.36
• In a recent breast cancer study investigating the
effects of Maritech® fucoidan on chemotherapy,
20% of patients experienced a reduction in joint
pain. This is thought to be associated with a
reduction in systemic inflammation.32
Gastrointestinal impairment
• In a colitis mouse model, the oral ingestion of
Maritech® fucoidan was shown to be effective in
reducing inflammation in the gut.15
• Fucoidan has been shown to be highly effective in
restoring mucosal immunity in the gut. As demonstrated
in a cyclophosphamide-induced mucositis mouse
model, fucoidan enhanced the expression of IgA
antibodies (essential for mucosal immune function) and
reversed cyclophosphamide-induced damage.37
• In an animal model, fucoidan prevented changes
to the levels of gastric hormones gastrin and
serotonin – a common side effect of chemotherapy.
These findings suggest that fucoidan may assist in
maintaining normal gastrointestinal function during
cancer treatment.38
Weight loss and muscle wasting
• Fucoidan effectively addressed a reduction in
appetite, skeletal muscle atrophy and systemic
inflammation in a bladder cancer mouse model.39
• Fucoidan shows promise as a preventative agent
for minimising weight loss symptoms and reducing
tumour growth during chemotherapy treatment.
As demonstrated in a Lewis lung cancer model,
fucoidan reduced cachectic symptoms and
inhibited the metastasis of lung carcinoma by
down-regulating metastatic factors VEGF and matrix
metalloprotease enzymes.18
PAGE 16 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
BIOACTIVITIESImmune modulationExtensive research undertaken on the immuno-
modulatory properties of fucoidan shows a range of
beneficial effects including:
• Boosting the immune response
• Activating Natural Killer cells and cytotoxic T cells
• Mobilising stem cells
• Dampening allergic responses
Boosting key immune cells In a clinical study involving healthy normal subjects,
Maritech® fucoidan demonstrated its ability as an immune-
priming agent by increasing cytotoxic T cell and Natural
Killer cell levels after 3 days.40 Over the 28 day study period,
there was a continual increase in phagocytic activity of
monocytes and granulocytes, as well as a reduction in
the levels of inflammatory cytokine IL-6. Such an increase
in immuno-modulatory activity may be useful as a
preventative for infections such as seasonal colds and flu.
In a further study, Maritech® fucoidan extracts
significantly enhanced the immune function of cancer-
affected mice. The key immune marker Immunoglobulin
G (IgG) was significantly modulated, showing a 500%
increase relative to controls after 1 week.25
IgG is the main type of human antibody and helps
control infections by binding to pathogens (such as
viruses and bacteria) and alerting circulating immune
cells. It is often suppressed in cancer patients.
Mobilising stem cells
The ingestion of Maritech® fucoidan has been
shown to increase the number and release of CD34+
haemopoeitic stem cells after 3 days.41 Maritech®
fucoidan also demonstrated a marked increase in
chemokine receptors, SDF-1 and CXCR4, on stem cells
which may increase their availability to tissues.
These findings have been echoed in animal studies,
in which fucoidan was shown to increase the levels of
SDF-1 chemokine receptors to promote the release of
stem cells.11
Reducing allergic responses
Research has found that fucoidan can reduce allergic
responses through oral ingestion42 and even topical
application.43 In an in vitro study, fucoidan was shown
to suppress the production of IgE antibodies from both
healthy subjects and subjects with allergic dermatitis.44
IGG
EXP
RESS
ION
INCREASE IN IGG EXPRESSION
TIME (DAYS)
60
53.75
47.5
41.25
350 3 28
• MARITECH® UNDARIA• MARITECH® FUCUS
INCREASE IN PHAGOCYTIC ACTIVITY
% O
F A
CTI
VATE
D C
ELLS
TIME (DAYS)
0 7 28
1800
1450
1100
750
400
• MONOCYTES• GRANULOCYTES
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 17
BIOACTIVITIESImmune modulation
PAGE 18 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
Maritech® fucoidans are the only high purity, certified
organic fucoidans with demonstrated potential in gut
and digestive health applications. Comprehensive
research suggests a range of gastrointestinal benefits
from fucoidan including:
• Protecting gut flora from antibiotics
• Maintaining the balance of good and bad bacteria
• Reducing gut inflammation
• Reducing the growth of yeasts and fungus
• Inhibiting viruses and bacteria
• Protecting against liver disease and fibrosis
Protecting gut flora from antibiotics
An unwanted side effect of antibiotic use is the reduction
of beneficial bacteria in the gut. Human and animal
studies have linked antibiotic-induced changes in the
composition of gut flora to a number of negative health
outcomes, including obesity and diabetes mellitus.45
Evidence shows that Maritech® fucoidan has protective
effects on beneficial gut bacteria during antibiotic use.
Importantly, research also demonstrates that Maritech®
fucoidan does not interfere with the treatment action of
the antibiotic in fighting harmful bacteria.9
In an in vitro study involving the common antibiotic
gentamicin, Maritech® fucoidan was shown to protect
the levels of good Escherichia coli bacteria which
naturally reside in the human gut.9 In the same study,
Maritech® fucoidan was shown to have no impact
on the action of gentamicin against pathogenic
Staphylococcus aureus bacteria. This study reinforces
the protective benefits of fucoidan on good bacteria
during antibiotic use, whilst still enabling full antibiotic
activity against bad bacteria.
Reducing gut inflammation and colitis
In a series of pre-clinical studies, Maritech® fucoidan has
been shown to significantly reduce gut inflammation
and colitis by inhibiting key inflammatory enzymes
expressed in the gastrointestinal tract, including LOX-
15, COX-1 and COX-2.14 In a mouse model, Maritech®
fucoidan was found to significantly reduce the clinical
symptoms, pathology and cytokine elevations of acute
colitis.15
Maritech® fucoidan shows promise as a preventative
for a number of gastrointestinal disorders, including
cancers which are closely associated with chronic
gastrointestinal inflammation.
BIOACTIVITIESGut and digestive health
PROTECTION OF GOOD ESCHERICHIA COLI BACTERIA
ABS
ORB
AN
CE
(OD
600)
0 1 2 3 4 5 6 7 8 9 10
1.2
1.0
0.8
0.6
0.4
0.2
0.0
GENTAMICIN μg/mL
• GENTAMICIN + MARITECH® FUCOIDAN (250 μg/mL)• GENTAMICIN
• GENTAMICIN + MARITECH® FUCOIDAN (250 )• GENTAMICIN
ANTIBIOTIC ACTIVITY ON STAPHYLOCOCCUS AUREUS BACTERIAA
BSO
RBA
NC
E (O
D60
0)
0 1 2 3 4 5 6 7 8 9 10
1.2
1.0
0.8
0.6
0.4
0.2
0.0
GENTAMICIN μg/mL
• GENTAMICIN + MARITECH® FUCOIDAN (250 μg/mL)• GENTAMICIN
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 19
Maintaining the balance of beneficial and harmful bacteria
Recent research has demonstrated that fucoidan can
balance the composition of gut flora by promoting the
growth of naturally-occurring beneficial bacteria and
reducing the growth of harmful bacteria.
In a series of animal studies,46,47 dietary fucoidan has
been shown to:
• Increase the abundance of beneficial bacteria,
Lactobacillus and Ruminococcaceae, that naturally
reside in the gut
• Decrease the abundance of potentially harmful
bacteria, Peptococcus and Enterobacteriaceae, that
can grow opportunistically to cause gastrointestinal
problems and infections throughout the body
• Significantly decrease the inflammatory response
and antigen load of gut microbiota
Together, these results demonstrate the potential for
fucoidan to balance the composition of good and bad
bacteria in the gut for digestive benefit.
Inhibiting the adhesion of H.pylori and E.coli bacteria
Maritech® fucoidan has been shown to effectively
inhibit the adhesion of the pathogenic bacteria,
Helicobacter pylori and Escherichia coli (E.coli), to
human cells. Helicobacter pylori is the primary cause
of chronic stomach inflammation, peptic ulcers and
gastric cancers.
In a cellular model designed to mimic the natural
infection of Helicobacter pylori, Maritech® fucoidan
dislodged the ulcer-causing bacteria from human gastric
epithelial cells and reduced adhesion by up to 55%.16
Maritech® fucoidan also inhibited the adhesion of E.coli
bacteria to human epithelial cells by up to 72%.14 This
study mimicked the adhesion of E.coli to epithelial cells
that line human oral tracts, genitourinary tract and skin.
Pathogenic strains of E.coli can cause intestinal infection,
diarrhoea, abdominal pain and fever.
BIOACTIVITIESGut and digestive health
+ LACTOBACILLUS+ RUMINOCOCCACEAE
- PEPTOCOCCUS- ENTEROBACTERIACEAE
BIOACTIVITIESGut and digestive health
HELICOBACTER PYLORI ESCHERICHIA COLI
% A
DHE
REN
T H.
PYLO
RI R
ECO
VER
ED
% A
DHE
REN
T E.
CO
LI R
ECO
VER
ED
6
5
4
3
2
1
0
100
80
60
40
20
0
UNTREATED MARITECH® MARITECH® FUCUS UNDARIA
UNTREATED MARITECH® MARITECH® FUCUS UNDARIA
PAGE 20 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
Reducing the occurrence of gastric ulcersFucoidan has demonstrated effectiveness in healing gastric
ulcers and reducing ulcer-induced pain. In a randomised
double blind human study, patients who ingested fucoidan
in combination with conventional therapy reported a
significant improvement in gastric ulcers and abdominal
pain.48 Fucoidan has also demonstrated effectiveness in
an animal model by reducing the occurrence of aspirin-
induced gastric ulcers.49
Inhibiting viral infectionsFucoidan is a highly effective inhibitor of viruses that
can infect the gastrointestinal system. In a number of in
vitro studies, Maritech® fucoidan has been specifically
shown to:
• Inhibit adhesion and block entry of viruses into host
cells50
• Directly inhibit multiple strains of influenza which
multiply in gut mucosa, including Avian influenza A
H5N3 (bird flu)51 and H1N1 (swine flu)52
• Prevent the infection of herpes simplex viruses 1
& 253 which can affect microbial diversity and
influence inflammatory bowel disease54
Reducing the growth of yeasts and fungus Maritech® fucoidan has been shown to effectively
inhibit the growth of fungus and yeast strains associated
with compromised digestive function.
In an in vitro study, Maritech® fucoidan inhibited
the formation of biofilm for the fungus species,
Aspergillus brasiliensis, and yeast species, Candida
albicans.55 Biofilm formation is the process by which
microorganisms attach to a surface and cultivate.
Whilst naturally found in the human gastrointestinal
tract, Aspergillus brasiliensis and Candida albicans
species have the ability to overgrow and cause
digestive problems, particularly in people who are
immunocompromised.
Protecting against liver disease and fibrosisResearch has demonstrated that fucoidan can have
a marked protective effect on the liver. Studies have
shown that fucoidan not only protects against damage
in toxicity models of liver disease, including CCL4 and
Con A,56,57 but also in alcohol-induced58 and non-
alcohol-induced fibrosis.59,60 In addition, fucoidan
has been found to be beneficial in the treatment of
patients with chronic hepatitis C, HCV-related cirrhosis
and hepatocellular carcinoma.61
BIOACTIVITIESGut and digestive health
REDUCTION IN GROWTH OF ASPERGILLUS BRASILIENSIS
% A
SPER
GIL
LUS
BRA
SILI
ENSI
S BI
OFI
LM G
ROW
TH
FUCOIDAN μg/mL
1 10 20 30 40 50 60 70 80 90 100
100
80
60
40
20
0
• MARITECH® UNDARIA• MARITECH® FUCUS
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 21
Fucoidan exhibits powerful anti-viral properties, with
potential application in a range of therapeutic settings.
Research demonstrates that fucoidan can prevent
infection by blocking the entry of viruses into cells and
inhibiting the adhesion of viruses to host cells.
Influenza
Both in vitro and animal studies have demonstrated the
anti-viral activity of fucoidan against influenza viruses.
Fucoidan has been proven to inhibit multiple influenza
strains, including H1N1 (swine flu),52 Parainfluenza62
and Avian influenza A (bird flu) strains H5N1, H5N3 and
H7N2.51,63
Herpes Maritech® fucoidan has been shown to be a potent
inhibitor of clinical strains of the herpes simplex virus
by preventing entry into cells. This includes effective
inhibition of HSV1 (cold sore virus) and HSV2 (genital
herpes) strains.53 Maritech® fucoidan has also been
shown to strongly inhibit the activity of herpes viruses
HSV1, HSV2 and HCMV on human fibroblast cells.50
Additional research demonstrates that orally ingested
fucoidan can protect against the infection of HSV1 as
well as increase the production of viral antibodies.64
Other common viruses
Fucoidan has been shown to exhibit anti-viral activity
against the measles virus,65 Newcastle virus66 and
canine distemper.67 Clinically, fucoidan has also
reduced pro-viral loads in patients with human T
lymphotropic virus type 1 (HTLV-1)68 and showed
benefits for patients with chronic hepatitis C.61
BIOACTIVITIESViral inhibition
BIOACTIVITIESGut and digestive health
INHIBITION OF HERPES VIRUSES
HERP
ES V
IRUS
SI50 SELECTIVITY INDEX
0 800 1600 2400 3200
• STANDARD ANTI-VIRAL TREATMENT• TREATMENT WITH MARITECH® FUCOIDAN
PAGE 22 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
Fucoidan is well known - and continues to be studied -
for its profound anti-inflammatory properties. Research
shows that fucoidan has potential benefits in addressing
systemic and local inflammation through its ability
to block selectins, reduce cytokine levels and inhibit
inflammatory enzymes.
Addressing systemic inflammation
Fucoidan has been shown to inhibit selectins and
reduce the potential for systemic inflammation.
The selectin blockade mechanism of fucoidan has
been widely reported and reviewed.1 Cancer is one
condition which uses L-selectins and P-selectins to
metastasise to other tissue sites. Fucoidan has been
shown in animal studies to inhibit this selectin-induced
inflammatory process.69
Reducing gut inflammation and colitis Maritech® fucoidan has been shown to reduce gut
inflammation and colitis by inhibiting key inflammatory
enzymes expressed in the gastrointestinal tract,
including LOX-15, COX-1 and COX-2.14 In a colitis mouse
model, orally-ingested Maritech® fucoidan reduced
cumulative histological disease scores of ulcerative
colitis by up to 36% and significantly lowered cytokine
levels in the colon.15 Weight loss, a common and often
undesirable side effect of colitis, was also reduced by
more than 50%.
Combatting skin inflammation
Fucoidan has been shown to impart anti-inflammatory
benefits when applied topically. Research has
demonstrated that fucoidan can limit allergy-induced
inflammation and can be as effective as cortisone in
combatting allergic dermatitis.43
In a series of clinical studies, Maritech® fucoidan was
found to significantly reduce erythema and water loss
from the skin both before and after exposure to UVA and
UVB.70 In vitro models have also shown that Maritech®
fucoidan can effectively inhibit glycation and degrading
enzymes, elastase and collagenase.71 It can also induce
the expression of the ‘anti-aging’ protein SIRT1.14
Improving osteoarthritis symptoms
Maritech® fucoidan has been shown to reduce the
symptoms of osteoarthritis in a human clinical study.36
Osteoarthritis is a degenerative disease that involves
the painful degradation of joint function. In this study,
patients who ingested 1 g daily of Maritech® fucoidan
achieved a 52% reduction in osteoarthritis symptoms.
Similar results have been demonstrated in an animal
model, in which fucoidan inhibited the development of
osteoarthritis in rats.72
BIOACTIVITIESAnti-inflammation
Cytokine % change (p-value)
IL-1α -55.9 (0.0002)IL-1β -51.2 (<0.0001)IL-10 -62.2 (<0.0001)MIP-1α -46.5 (0.0004)MIP-1β -60.0 (0.0037)G-GSF -80.6 (<0.0001)GM-GSF -51.0 (<0.0001)
Effect of oral fucoidan on colon-derived cytokine levels.
Fucoidan treatment stabilises structural changes to the gut caused by colitis.
FUC
OID
AN
TR
EATM
ENT
CO
LITI
S C
ON
TRO
LH
EALT
HY
CEL
LS
100X 400XPC 400XDC
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 23
BIOACTIVITIESAnti-inflammation
PAGE 24 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
The safety of fucoidan is widely supported by several
lines of evidence including multiple human clinical trials,
animal studies and in vitro research. This is unsurprising
given the long history of seaweed consumption and use
of fucoidan for therapeutic purposes, particularly in Asian
cultures. Extensive literature has been published in this
area, including 2,500 preclinical in vitro and in vivo studies
on seaweed and over 1,600 studies involving fucoidan.
Comprehensive clinical testing and a full safety
toxicity dossier confirms that Maritech® fucoidan is
safe for human and animal consumption and topical
application.25,32,36,41,73,74 Maritech® fucoidan ingredients
from the Undaria pinnatifida and Fucus vesiculosus
species of seaweed have attained FDA notified GRAS
(Generally Recognised As Safe) status. They have been
deemed safe for ingestion as a food ingredient at rates
of up to 250 mg per day.
A recent preclinical assessment demonstrated that
Maritech® fucoidan does not compromise the activity
of chemotherapy drugs and is safe to use in a range
of cancer treatment regimes.25 The study evaluated
drug interactions of fucoidan alone and in combination
with chemotherapy drugs paclitaxel, tamoxifen
and topotecan. Results showed that Maritech®
fucoidan did not interact with key enzyme pathways
used by chemotherapy at physiologically relevant
concentrations, thereby validating the safety of
Maritech® fucoidan as an adjunct to cancer therapy.
Additional research has shown the safety of
administering Maritech® fucoidan to breast cancer
patients alongside conventional hormone treatments.32
Results found that Maritech® fucoidan caused no
adverse effects or significant changes in steady-state
plasma concentrations of letrozole, tamoxifen or
tamoxifen metabolites. Toxicity monitoring also showed
no significant differences in all parameters measured
over the study period.
Supporting these clinical observations, Marinova has
investigated the effects of Maritech® fucoidan on
isolated cells in culture. 100% viability was maintained
at very high fucoidan concentrations in a typical cell
culture system. Maritech® Undaria pinnatifida fucoidan
was found to be non-toxic at 5,175 μg/mL and Maritech®
Fucus vesiculosus fucoidan was found to be non-toxic at
632 μg/mL. This extensive portfolio of research attests to
the safety and tolerability of Maritech® fucoidan.
REGULATORYSafety
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 25
REGULATORYSafety
REGULATORYGlobal acceptance
Quality and certifications
All Maritech® fucoidan extracts have global regulatory
and safety acceptance including:
• USA: Generally Recognised as Safe (GRAS)
• Australia: Therapeutic Goods Association (TGA)
listable ingredients
• Canada: Health Canada NHP compliant
• Europe: Novel Foods approval
• China: Compliant with Algae Product requirements
• Korea: KFDA (Korea Food and Drug Administration)
registered
With world-class extraction facilities and research
laboratories located in Tasmania, Australia, Marinova
manufactures superior fucoidan products under
adherence to the most rigorous systems of quality
control. The company has vertically integrated
operations and a comprehensive certified organic
supply chain. Marinova exports its products to more
than 25 countries around the globe and is the leading
supplier of high purity fucoidan to the research,
nutraceutical and pharmaceutical sectors.
Marinova’s solvent-free Maritech® extraction process
enables the company to produce and supply
high quality fucoidan extracts with the following
accreditations:
• Certified organic
• Non-GMO
• Kosher
• Halal
• Made in Australia under GMP
• ISO9001 and HACCP
• Solvent-free
• Safe and non-toxic
PAGE 26 | MARITECH® ORGANIC FUCOIDANS - THE SCIENCE
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13. Schneider T, Ehrig K, Liewert I, Alban S. Interference with the CXCL12/CXCR4 axis as potential antitumor strategy: superiority of a sulfated galactofucan from the brown alga Saccharina latissima and Fucoidan over heparins. Glycobiology. 2015.
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18. Huang TH, Chiu YH, Chan YL, Chiu YH, Wang H, Huang KC, et al. Prophylactic Administration of Fucoidan Represses Cancer Metastasis by Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs) in Lewis Tumor-Bearing Mice. Mar Drugs. 2015;13(4):1882-900.
19. Kawaguchi T, Hayakawa M, Koga H, Torimura T. Effects of fucoidan on proliferation, AMP-activated protein kinase, and downstream metabolism- and cell cycle-associated molecules in poorly differentiated human hepatoma HLF cells. Int J Oncol. 2015;46(5):2216-22.
20. Min EY, Kim IH, Lee J, Kim EY, Choi YH, Nam TJ. The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines. Int J Oncol. 2014;45(1):47-56.
21. Lee HE, Choi ES, Shin JA, Lee SO, Park KS, Cho NP, et al. Fucoidan induces caspase-dependent apoptosis in MC3 human mucoepidermoid carcinoma cells. Experimental and therapeutic medicine. 2014;7(1):228-32.
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27. Saur D, Seidler B, Schneider G, Algul H, Beck R, Senekowitsch-Schmidtke R, et al. CXCR4 expression increases liver and lung metastasis in a mouse model of pancreatic cancer. Gastroenterology. 2005;129(4):1237-50.
28. Carvalho AC, Sousa RB, Franco AX, Costa JV, Neves LM, Ribeiro RA, et al. Protective effects of fucoidan, a P- and L-selectin inhibitor, in murine acute pancreatitis. Pancreas. 2014;43(1):82-7.
29. Zhang Z, Teruya K, Yoshida T, Eto H, Shirahata S. Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in MDA-MB-231 and MCF-7 breast cancer cells. Mar Drugs. 2013;11(1):81-98.
30. Thakur V, Lu J, Roscilli G, Aurisicchio L, Cappelletti M, Pavoni E, et al. The natural compound fucoidan from New Zealand Undaria pinnatifida synergizes with the ERBB inhibitor lapatinib enhancing melanoma growth inhibition. Oncotarget. 2017.
31. Philchenkov A, Zavelevich M, Imbs T, Zvyagintseva T, Zaporozhets T. Sensitization of human malignant lymphoid cells to etoposide by fucoidan, a brown seaweed polysaccharide. Exp Oncol. 2007;29(3):181-5.
32. Tocaciu S OL, Lowenthal R, Peterson G M, Patel R, Shastri M, McGuinness G, Olesen I, Fitton J H The effect of Undaria pinnatifida fucoidan on the pharmacokinetics of letrozole and tamoxifen in patients with breast cancer. Integrative Cancer Therapies. 2016;2016.
33. Takahashi H, Kawaguchi M, Kitamura K, Narumiya S, Kawamura M, Tengan I, et al. An Exploratory Study on the Anti-inflammatory Effects of Fucoidan in Relation to Quality of Life in Advanced Cancer Patients. Integrative Cancer Therapies. 2017:1534735417692097.
34. Ikeguchi M, Yamamoto M, Arai Y, Maeta Y, Ashida K, Katano K, et al. Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer. Oncology letters. 2011;2(2):319-22.
35. Chen YM, Tsai YH, Tsai TY, Chiu YS, Wei L, Chen WC, et al. Fucoidan supplementation improves exercise performance and exhibits anti-fatigue action in mice. Nutrients. 2015;7(1):239-52.
36. Myers SP, O’Connor J, Fitton JH, Brooks L, Rolfe M, Connellan P, et al. A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis. Biologics. 2010;4:33-44.
37. Zuo T, Li X, Chang Y, Duan G, Yu L, Zheng R, et al. Dietary fucoidan of Acaudina molpadioides and its enzymatically degraded fragments could prevent intestinal mucositis induced by chemotherapy in mice. Food & function. 2015;6(2):415-22.
38. Song MY, Ku SK, Kim HJ, Han JS. Low molecular weight fucoidan ameliorating the chronic cisplatin-induced delayed gastrointestinal motility in rats. Food Chem Toxicol. 2012;50(12):4468-78.
39. Chen MC, Hsu WL, Hwang PA, Chen YL, Chou TC. Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice. Oncotarget. 2016.
40. Myers SP, O’Connor J, Fitton JH, Brooks L, Rolfe M, Connellan P, et al. A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex. Biologics. 2011;5:45-60.
41. Irhimeh MR, Fitton JH, Lowenthal RM. Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells. Exp Hematol. 2007;35(6):989-94.
MARITECH® ORGANIC FUCOIDANS - THE SCIENCE | PAGE 27
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Th2 immune responses by Mekabu fucoidan from Undaria pinnatifida sporophylls. International Archives of Allergy and Immunology. 2005;137(4):289-94.
43. Yang JH. Topical Application of Fucoidan Improves Atopic Dermatitis Symptoms in NC/Nga Mice. Phytother Res. 2012.
44. Iwamoto K, Hiragun T, Takahagi S, Yanase Y, Morioke S, Mihara S, et al. Fucoidan suppresses IgE production in peripheral blood mononuclear cells from patients with atopic dermatitis. Arch Dermatol Res. 2010;303(6):425-31.
45. Yallapragada S, Nash C, Robinson D. Early-Life Exposure to Antibiotics, Alterations in the Intestinal Microbiome, and Risk of Metabolic Disease in Children and Adults. Pediatric Annals. 2015;44(11):265-9.
46. Shang Q, Shan X, Cai C, Hao J, Li G, Yu G. Dietary fucoidan modulates the gut microbiota in mice by increasing the abundance of Lactobacillus and Ruminococcaceae. Food & function. 2016;7(7):3224-32.
47. Walsh AM, Sweeney T, O’Shea CJ, Doyle DN, O’Doherty JV. Effect of dietary laminarin and fucoidan on selected microbiota, intestinal morphology and immune status of the newly weaned pig. Br J Nutr. 2013;110(9):1630-8.
48. Juffrie M RI, Damayanti W, Djumhana A, Ahmad H. The Efficcay of Fucoidan on Gastric Ulcer. Indonesian Journal of Biotechnology 2006;11(2):908-13.
49. Choi JI, Raghavendran HR, Sung NY, Kim JH, Chun BS, Ahn DH, et al. Effect of fucoidan on aspirin-induced stomach ulceration in rats. Chem Biol Interact. 2010;183(1):249-54.
50. Research performed by National Institute of Health, USA. 51. Synytsya A, Bleha R, Synytsya A, Pohl R, Hayashi K, Yoshinaga K, et al.
Mekabu fucoidan: structural complexity and defensive effects against avian influenza A viruses. Carbohydr Polym. 2014;111:633-44.
52. Hayashi T, Hayashi K, Kanekiyo K, Ohta Y, Lee J-B. Promising antiviral Glyco-molecules from an edible alga. In: Torrence PF, editor. Combating the Threat of Pandemic Infl uenza: Drug Discovery Approaches,. Hoboken, New Jersey: John Wiley & Sons; 2007. p. 166-82.
53. Thompson KD, Dragar C. Antiviral activity of Undaria pinnatifida against herpes simplex virus. Phytotherapy Research. 2004;18(7):551-5.
54. Wang W, Jovel J, Halloran B, Wine E, Patterson J, Ford G, et al. Metagenomic Analysis of Microbiome in Colon Tissue from Subjects with Inflammatory Bowel Diseases Reveals Interplay of Viruses and Bacteria. Inflamm Bowel Dis. 2015;21(6):1419-27.
55. Research performed by Blutest, Scotland.56. Hayashi S, Itoh A, Isoda K, Kondoh M, Kawase M, Yagi K. Fucoidan partly
prevents CCl4-induced liver fibrosis. Eur J Pharmacol. 2008;580(3):380-4. 57. Li J, Chen K, Li S, Liu T, Wang F, Xia Y, et al. Pretreatment with Fucoidan
from Fucus vesiculosus Protected against ConA-Induced Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis. PLoS One. 2016;11(4):e0152570.
58. Lim JD, Lee SR, Kim T, Jang SA, Kang SC, Koo HJ, et al. Fucoidan from Fucus vesiculosus protects against alcohol-induced liver damage by modulating inflammatory mediators in mice and HepG2 cells. Mar Drugs. 2015;13(2):1051-67.
59. Kawano N, Egashira Y, Sanada H. Effects of Various Kinds of Edible Seaweeds in Diets on the Development of D-Galactosamine-Induced Hepatopathy in Rats. Journal of Nutritional Science and Vitaminology. 2007;53(4):315-23.
60. Kim MJ, Jeon J, Lee JS. Fucoidan prevents high-fat diet-induced obesity in animals by suppression of fat accumulation. Phytother Res. 2014;28(1):137-43.
61. Mori N, Nakasone K, Tomimori K, Ishikawa C. Beneficial effects of fucoidan in patients with chronic hepatitis C virus infection. World J Gastroenterol. 2012;18(18):2225-30.
62. Taoda N, Shinji E, Nishii K, Nishioka S, Yonezawa Y, Uematsu J, et al. Fucoidan inhibits parainfluenza virus type 2 infection to LLCMK2 cells. Biomed Res. 2008;29(6):331-4.
63. Makarenkova ID, Deriabin PG, L’Vov D K, Zviagintseva TN, Besednova NN. [Antiviral activity of sulfated polysaccharide from the brown algae Laminaria japonica against avian influenza A (H5N1) virus infection in the cultured cells]. Voprosy virusologii. 2010;55(1):41-5.
64. Hayashi K, Nakano T, Hashimoto M, Kanekiyo K, Hayashi T. Defensive effects of a fucoidan from brown alga Undaria pinnatifida against herpes simplex virus infection. Int Immunopharmacol. 2008;8(1):109-16.
65. Morán-Santibañez K, Cruz-Suárez LE, Ricque-Marie D, Robledo D, Freile-Pelegrín Y, Peña-Hernández MA, et al. Synergistic Effects of Sulfated Polysaccharides from Mexican Seaweeds against Measles Virus. BioMed research international. 2016;2016.
66. Elizondo-Gonzalez R, Cruz-Suarez LE, Ricque-Marie D, Mendoza-Gamboa E, Rodriguez-Padilla C, Trejo-Avila LM. In vitro characterization of the antiviral activity of fucoidan from Cladosiphon okamuranus against Newcastle Disease Virus. Virol J. 2012;9:307.
67. Trejo-Avila LM, Morales-Martinez ME, Ricque-Marie D, Cruz-Suarez LE, Zapata-Benavides P, Moran-Santibanez K, et al. In vitro anti-canine distemper virus activity of fucoidan extracted from the brown alga Cladosiphon okamuranus. Virusdisease. 2014;25(4):474-80.
68. Araya N, Takahashi K, Sato T, Nakamura T, Sawa C, Hasegawa D, et al. Fucoidan therapy decreases the proviral load in patients with human T-lymphotropic virus type-1-associated neurological disease. Antivir Ther.16(1):89-98.
69. Gassmann P, Kang ML, Mees ST, Haier J. In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell--endothelial cell interaction. BMC Cancer. 2010;10:177.
70. Research performed by Farcoderm Srl, Italy.71. Research performed and sponsored by Marinova Pty Ltd.72. Lee DG, Park SY, Chung W, Park JH, Hwang E, Mavlonov GT, et al.
Fucoidan Prevents the Progression of Osteoarthritis in Rats. Journal of medicinal food. 2015;18(9):1032-41.
73. Myers SP, Mulder AM, Baker DG, Robinson SR, Rolfe MI, Brooks L, et al. Effects of fucoidan from Fucus vesiculosus in reducing symptoms of osteoarthritis: a randomized placebo-controlled trial. Biologics. 2016;10:81-8.
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