1.
PROTANDIM,
NRF2
ACTIVATOR
Peer-­‐Reviewed
Studies,
WWW.PUBMED.GOV
Updated
January
22,
2015
1. UNIVERSITY
OF
COLORADO
–
OXIDATIVE
STRESS
The
induction
of
human
superoxide
dismutase
and
catalase
in
vivo:
a
fundamentally
new
approach
to
antioxidant
therapy,
Free
Radical
Biology
&
Medicine
Jan.
2006
http://www.ncbi.nlm.nih.gov/pubmed/16413416
Protandim®
is
not
an
antioxidant
supplement.
It
is
an
Nrf2
Activator.
This
DNA
pathway
up
and
down
regulates
500
of
the
25,000
genes
in
our
body.
These
genes
are
called
the
survival
genes.
After
120
days,
Superoxide
Dismutase
(SOD)
increased
by
30
%
(+
/
-­‐
10%);
Catalase
increased
54%
(+/
-­‐
15%).
These
indirect
antioxidant
enzymes
neutralize
1,000,000
free
radicals
per
second
every
second.
Oxidative
Stress
levels
are
subsequently
reduced
in
every
mammal
by
an
average
of
40%
in
30
days
and
up
to
70%
in
120
days
-­‐
100%
of
the
time.
Oxidative
Stress
is
related
to
over
250
age-­‐related
diseases.
The
study
indicated
no
evidence
of
toxicity
=
Protandim
is
a
safe
nutraceutical
supplement.
2. LOUISIANA
STATE
UNIVERSITY
–
SKIN
CANCER
Protandim,
a
fundamentally
new
antioxidant
approach
in
chemoprevention
using
mouse
two-­‐stage
skin
carcinogenesis
as
a
mode,
PLoS
One,
April
2009
http://www.ncbi.nlm.nih.gov/pubmed/19384424
• The
group
without
Protandim®
all
developed
Cancer.
• In
the
group
that
received
Protandim®:
o 33%
developed
NO
Cancer
at
all
o The
remaining
developed
40%
Less
aggressive
Cancer
with
fewer,
smaller
tumors

2.
3. UNIVERSTIY
OF
COLORADO
-­‐
GLUTATHIONE
Synergistic
induction
of
heme
oxygenase-­‐1
by
the
components
of
the
antioxidant
supplement
Protandim,
Free
Radical
Biology
&
Medicine
Feb.
2009
http://www.ncbi.nlm.nih.gov/pubmed/19056485
Protandim®,
up
regulates
the
enzyme
Glutathione
by
300%
in
30
days.
Glutathione
is
the
Master
Antioxidant
in
our
bodies.
It
is
a
powerful
Anti-­‐inflammatory
agent
that
crosses
the
brain
barrier
&
gut
barrier
(very
few
things
in
our
bodies
can
do
this).
It
also
detoxifies
our
liver
&
kidneys.
This
study
explored
whether
components
of
Protandim
acted
in
a
synergistic
manner
in
certain
cells,
specifically
if
it
would
induce
heme
oxygenase.
When
each
component
was
tested
alone,
only
curcumin
showed
minimal
induction.
Together,
all
five
major
ingredients
in
Protandim®,’s
patented
formula,
produced
a
strong,
synergistic
induction
MUCH
greater
than
the
sum
of
its
parts.

3.
4. VIRGINIA
COMMONWEALTH
UNIVERSITY
Chronic
Pulmonary
Artery
Pressure
Elevation
Is
Insufficient
to
Explain
Right
Heart
Failure
http://www.ncbi.nlm.nih.gov/pubmed/19884466,
Circulation,
Nov
2009
This
study
used
a
lab
model
of
pulmonary
hypertension
in
rats
to
explore
factors
contributing
to
heart
failure
in
animals.
Pulmonary
hypertension
was
induced
in
rats
through
a
drug
and
by
creating
an
oxygen-­‐poor
environment.
• The
animals
pre-­‐treated
with
Protandim®
experienced
strong
cardio-­‐protective
effects.
• Protandim®
protected
the
animals’
hearts
by
increasing
the
expression
of
protective
genes
and
preventing
the
formation
of
scar
tissue.
• Protandim®
preserved
heart
functions
and
demonstrated
strong
cardio-­‐protective
effects
in
an
animal
model
of
lung
disease.
• Osteopontins
levels
reduced
by
more
than
50%;
heart
output
preserved
and
cardiac
fibrosis
(Harding
of
the
Arteries)
was
prevented
in
animals.
“This
study
showed
that
induction
of
Nrf2
by
Protandim®
prevents
cardiac
oxidative
stress,
preserves
HO-­‐1
and
VEGF
expression
and
myocardial
capillary
density,
and
prevents
RV
failure
without
modifying
lung
angioproliferation.
The
restoration
of
Nrf2
and
HO-­‐1
signaling
can
prevent
maladaptive
RV
remodeling
and
preserve
heart
(RV)
function.”
5. HARVARD
UNIVERSITY
–
MUSCULAR
DYSTROPHY
The
Dietary
Supplement
Protandim
Decreases
Plasma
Osteopontin
and
Improves
Markers
of
Oxidative
Stress
in
Muscular
Dystrophy
Mdx
Mice,
Journal
of
Dietary
Supplements,
June
2010
http://www.ncbi.nlm.nih.gov/pubmed/20740052
Protandim®
IMPROVES
markers
of
Oxidative
Stress
and
Fibrosis
in
muscular
dystrophy
mice.
Oxidative
damage
is
thought
to
be
a
pertinent
factor
in
the
development
of
Duchenne
Muscular
Dystrophy
(DMD),
the
most
common
and
lethal
neuromuscular
disorder
in
children.
Researchers
used
surrogate
markers
and
functional
measurers
in
a
dystrophin-­‐deficient
mouse
model
of
DMD
to
determine
whether
Protandim
provides
any
benefit.
After
six
months
on
Protandim®,
researchers
saw
a
48
%
average
decrease
in
plasma
TBARS
(oxidative
stress)
and
a
57
%
decrease
in
plasma
osteopontin
as
well
as
a
35
%
increase
in
beneficial
protective
plasma
PON1
activity.
• Osteopontin
(OPN)
is
a
pleiotropic
protein
with
important
roles
in
inflammation
and
immunity
that
has
been
suggested
as
a
candidate
biomarker
for
disease
activity
in
multiple
sclerosis
(MS)
• PON1
Paraoxonase:
An
enzyme
associated
with
high-­‐density
lipoprotein
(HDL)
that
is
believed
to
protect
against
the
oxidation
of
low-­‐density
lipoprotein
(LDL)
and
hence
to
affect
the
risk
of
coronary
artery
disease

4.
6. LOUISANA
STATE
UNIVERSITY
–
TUMOR
SUPPRESSION
IN
SKIN
CANCER
The
chemopreventive
effects
of
Protandim:
modulation
of
p53
mitochondrial
translocation
and
apoptosis
during
skin
carcinogenesis,
PLoS
One,
July
2010
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011902
Chemopreventative
Effects
of
Protandim®
Examined
Further
in
New
Peer-­‐Reviewed
Study;
Protandim's
ability
to
modulate
relationship
between
superoxide
dismutase
and
tumor
suppressor
p53
believed
responsible
for
reduction
of
skin
cancers
in
mice.
“MnSOD
is
a
highly
inducible
protein,
and
when
induced
by
dietary
compounds
such
as
Protandim®,
is
effective
in
the
suppression
of
tumor
promotion.
The
results
from
this
study
further
confirmed
and
extended
our
previous
findings
that
Protandim®
modulates
tumorigenesis
via
the
induction
of
endogenous
antioxidant
enzymes.
In
addition,
Protandim®
utilizes
multiple
mechanisms
to
modulate
cell
proliferation
and
apoptosis
in
vivo
and
in
vitro
which
both
contribute
to
tumorigenesis.
Therefore,
these
results
further
demonstrate
the
effectiveness
of
multi-­‐modal
antioxidant
base
therapies
in
chemoprevention.”
(Excerpt
from
study)
The
induction
of
MnSOD
(Manganese
Superoxide
Dismutase)
is
gaining
interest
as
an
effective
novel
mechanism
of
chemoprevention,
being
that
it
is
the
ONLY
antioxidant
enzyme
that
when
over
expressed
suppresses
tumor
formation.
MnSOD
also
has
the
ability
to
modulate
multiple
pathways
contributing
to
skin
carcinogenesis.
7. OHIO
STATE
UNIVERSITY
–
CORONARY
BYPASS
GRAFTS
Protandim
attenuates
intimal
hyperplasia
in
human
saphenous
veins
cultured
ex
vivo
via
a
catalase-­‐dependent
pathway,
Free
Radical
Biology
and
Medicine,
March
2011
http://www.ncbi.nlm.nih.gov/pubmed/21167278
This
study
examined
the
biochemical
mechanisms
that
underlie
the
ability
of
Protandim®
to
suppress
intimal
hyperplasia-­‐over-­‐proliferation
of
cells
that
line
the
vessel
wall,
a
common
adverse
event
that
limits
the
effectiveness
of
vascular
surgery.
Treatment
of
human
saphenous
veins
with
Protandim®
blocked
intimal
hyperplasia
and
reduced
cellular
proliferation
to
that
of
freshly
isolated
human
saphenous
veins.
Protandim®
prevents
the
proliferation
of
cells
that
can
cause
re-­‐blockage
of
vessels
following
coronary
artery
bypass
surgery,
stenting,
and
carotid
endarterectomy.

5.
8. LOUISIANA
STATE
UNIVERSITY
-­‐
SKIN
CANCER
&
MnSOD
The
Role
of
Manganese
Superoxide
Dismutase
in
Skin
Cancer,
Enzyme
Research,
March
23,
2011
http://www.ncbi.nlm.nih.gov/pubmed/21603266
This
study
used
a
two-­‐part
model
to
test
the
effectiveness
of
Protandim®
in
chemoprevention.
In
one
approach,
researchers
applied
an
SOD
mimetic
topically
to
mouse
skin.
In
another
approach,
Protandim®
decreased
tumor
incidence
and
multiplicity
by
33%
and
57
%
respectively.
“Protandim®
may
be
a
novel
approach
to
chemoprevention.”
9. UNIVERSITY
OF
COLORADO
–
PIVOTAL
NRF2
ACTIVATION
AND
GENE
EXPRESSION
STUDY
Oxidative
stress
in
health
and
disease:
The
therapeutic
potential
of
Nrf2
activation,
Molecular
Aspects
of
Medicine,
August
2011
http://www.ncbi.nlm.nih.gov/pubmed/22020111
**A
MUST
read
for
healthcare
professionals**
“Nrf2
is
referred
to
as
the
"master
regulator"
of
the
antioxidant
response,
modulating
the
expression
of
hundreds
of
genes,
including
not
only
the
familiar
antioxidant
enzymes,
but
large
numbers
of
genes
that
control
seemingly
disparate
processes
such
as
immune
and
inflammatory
responses,
tissue
remodeling
and
fibrosis,
carcinogenesis
and
metastasis,
and
even
cognitive
dysfunction
and
addictive
behavior.
Thus,
the
dysregulation
of
Nrf2-­‐regulated
genes
provides
a
logical
explanation
for
the
connections,
both
direct
and
indirect,
between
observable
oxidative
stress
and
perhaps
200
human
diseases
involving
these
various
physiological
processes,
each
reflecting
a
network
involving
many
gene
products.”
(Excerpt
from
Abstract)
This
study
involved
using
a
Bioassay
of
the
AREc32
cell
line
to
which
scientists
added
solutions
containing
either
Protandim®
,
sulforaphane,
bardoxolone
methyl,
or
dimethyl
fumarate.
Each
of
which
are
known
Nrf2
activators.
The
test
was
to
determine
the
extent
of
each
item’s
ability
to
activate
the
Nrf2
pathway
leading
to
gene
expression
within
the
cells.
The
tests
were
conducted
three
times.
RESULTS:
• “Luciferase
activity
is
increased
up
to
100-­‐fold
by
Protandim®
at
30
lg/ml,
the
most
potent
Nrf2
activator
that
we
have
observed.”
(p
237)
• “As
seen
here,
the
two
important
parameters
Cmax
and
FImax
are
easily
observed.
The
greatest
FImax
was
observed
with
Protandim
at
135-­‐fold”
(p
239)
• “Among
the
10
genes
most
highly
upregulated
by
Protandim®
are
a
number
of
notables
that
encode
antioxidant
and
anti-­‐inflammatory
proteins.”
(p
240)

6.
• “Pathway
analysis
of
results
shows
significant
modulation
by
Protandim®
of
pathways
involving
not
only
antioxidant
enzymes,
but
of
those
related
to
colon
cancer,
cardiovascular
disease,
and
Alzheimer
disease.”
• Of
the
66
Protandim-­‐regulated
genes
that
are
associated
with
Alzheimer
disease,
only
five
(SOD1,
NQO1,
HMOX1,
GLRX,
and
TXN)
appear
to
be
in
the
antioxidant
family.
Protandim®
upregulated
ALL
five
of
them…
(p
243)
In
addition
to
the
discussion
of
the
therapeutic
potential
of
Nrf2
activation
for
cardiovascular
disease,
colon
cancer,
and
Alzheimer’s,
the
study
discusses
the
therapeutic
potential
as
it
relates
to
other
diseases
such
as
renal
failure,
multiple
sclerosis,
type
II
diabetes,
etc.
The
study
also
includes
a
table
indicating
the
specific
genes
and
by
how
much
Protandim®
up
or
down
regulates
each
gene.
Dr.
Joe
McCord
Overview
of
Nrf2
Study-­‐https://www.youtube.com/watch?v=wzZKCyyXBME
10. UNIVERSITY
OF
COLORADO,
SCHOOL
OF
MEDICINE
–
ALCOHOL
ABUSE
AND
LUNG
INJURY
Protandim
does
not
influence
alveolar
epithelial
permeability
or
intrapulmonary
oxidative
stress
in
human
subjects
with
alcohol
use
disorders,
American
Journal
of
Physiology:
Lung
Cellular
and
Molecular
Physiology,
April
2012
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330762/
“Alcohol
use
disorders
(AUDs),
including
alcohol
abuse
and
dependence,
have
been
linked
to
the
development
of
acute
lung
injury
(ALI).
Prior
clinical
investigations
suggested
an
association
between
AUDs
and
abnormal
alveolar
epithelial
permeability
mediated
through
pulmonary
oxidative
stress
that
may
partially
explain
this
relationship.
We
sought
to
determine
if
correcting
pulmonary
oxidative
stress
in
the
setting
of
AUDs
would
normalize
alveolar
epithelial
permeability
in
a
double-­‐blinded,
randomized,
placebo-­‐controlled
trial
of
Protandim,
a
nutraceutical
reported
to
enhance
antioxidant
activity.
We
randomized
30
otherwise
healthy
AUD
subjects
to
receive
directly
observed
inpatient
oral
therapy
with
either
Protandim
(1,350
mg/day)
or
placebo.
Subjects
underwent
bronchoalveolar
lavage
(BAL)
and
blood
sampling
before
study
drug
administration
and
after
7
days
of
therapy……These
results
suggest
that
Protandim
for
7
days
in
individuals
with
AUDs
who
are
newly
abstinent
does
not
alter
alveolar
epithelial
permeability.
However,
our
work
demonstrates
the
feasibility
of
safely
conducting
clinical
trials
that
include
serial
bronchoscopies
in
a
vulnerable
population
at
risk
for
acute
lung
injury.”(Abstract)

7.
11. COLORADO
STATE
UNIVERSITY
-­‐
NRF2
AND
CORONARY
ARTERY
PROTECTION
Phytochemical
Activation
of
Nrf2
Protects
Human
Coronary
Artery
Endothelial
Cells
against
an
Oxidative
Challenge,
Oxidative
Medicine
and
Cellular
Longevity,
March
2012
http://www.ncbi.nlm.nih.gov/pubmed/22685617
Activation
of
NF-­‐E2-­‐related
factor
2
(Nrf2)
is
a
potential
therapeutic
intervention
against
endothelial
cell
oxidative
stress
and
associated
vascular
disease.
The
study
was
done
to
determine
if
treatment
with
Protandim®
would
induce
Nrf2
nuclear
localization
and
phase
II
antioxidant
enzyme
protein
in
human
coronary
artery
endothelial
cells
(HCAECs),
protecting
against
an
oxidant
challenge
in
an
Nrf2-­‐
dependent
manner.
RESULTS:
• Protandim®
treatment
induced
Nrf2
nuclear
localization,
and
HO-­‐1
(778%
of
control
±
82.25
P
<
0.01),
SOD1
(125.9%
of
control
±
6.05
P
<
0.01),
NQO1
(126%
of
control
±
6.5
P
<
0.01),
and
GR
(119.5%
of
control
±
7.00
P
<
0.05)
protein
expression
in
HCAEC
(human
artery
cells).
• Protandim®
induces
Nrf2
nuclear
localization
and
antioxidant
enzyme
expression.
Protection
of
Human
Coronary
Artery
Endothelial
Cells
HCAEC
from
an
oxidative
challenge
is
Nrf2
dependent.
12. COLORADO
STATE
UNIVERSITY
–
NRF2
AND
CARDIOMYOCYTE
PROTECTION
Upregulation
of
phase
II
enzymes
through
phytochemical
activation
of
Nrf2
protects
cardiomyocytes
against
oxidant
stress,
Free
Radical
Biology
and
Medicine,
March
2013
http://www.ncbi.nlm.nih.gov/pubmed/23201694
Oxidative
stress
has
been
linked
to
cardiovascular
disease.
The
purpose
of
the
experiments
in
this
study
was
to
determine
if
treatment
of
cardiomyocytes
with
Protandim®
would
activates
Nrf2,
induce
phase
II
detoxification
enzymes,
and
protect
cardiomyocytes
from
oxidant-­‐induced
apoptosis
in
a
Nrf2-­‐dependent
manner.
**They
wanted
to
know
if
Protandim
would
protect
heart
cells
from
oxidative
damage.
• The
result
–
“phytochemical
treatment
[with
Protandim®
]
was
found
to
be
a
more
robust
activator
of
Nrf2
than
oxidant
treatment,
supporting
the
use
of
the
phytochemicals
as
a
potential
treatment
to
increase
antioxidant
defenses
and
protect
heart
cells
against
an
oxidative
challenge.

8.
13. UNIVERSITY
OF
COLORADO
-­‐
ACUTE
MOUNTAIN
SICKNESS
AND
NRF2
ACTIVATION
Nrf2
activation:
A
potential
strategy
for
the
prevention
of
acute
mountain
sickness,
Free
Radical
Biology
and
Medicine,
Oct.
2013
http://www.ncbi.nlm.nih.gov/pubmed/23722164
“Reactive
oxygen
species
(ROS)
formed
during
acute
high
altitude
exposure
contribute
to
cerebral
vascular
leak
and
development
of
acute
mountain
sickness
(AMS).
Nuclear
factor
(erythroid-­‐derived
2)-­‐related
factor
2
(Nrf2)
is
a
transcription
factor
that
regulates
expression
of
greater
than
90%
of
antioxidant
genes,
but
prophylactic
treatment
with
Nrf2
activators
has
not
yet
been
tested
as
an
AMS
therapy.
We
hypothesized
that
prophylactic
activation
of
the
antioxidant
genome
with
Nrf2
activators
would
attenuate
high-­‐altitude-­‐induced
ROS
formation
and
cerebral
vascular
leak
and
that
some
drugs
currently
used
to
treat
AMS
symptoms
have
an
additional
trait
of
Nrf2
activation.
…….Of
nine
drugs
tested,
with
the
exception
of
dexamethasone,
only
drugs
that
showed
the
ability
to
activate
Nrf2
(Protandim,
methazolamide,
nifedipine,
amlodipine,
ambrisentan,
and
sitaxentan)
decreased
high-­‐altitude-­‐induced
cerebral
vascular
leak
in
vivo.”
(Excerpt
from
Abstract)

9.
BIOGEN
IDEC
–
NRF2
ACTIVATORS
BG-­‐12
(TECFIDERA)
AND
PROTANDIM
Nrf2
activators:
a
novel
strategy
to
promote
oligodendrocyte
survival
in
multiple
sclerosis?,
October
21,
2011
J.
Lim,
S.
van
der
Pol,
J.
Drexhage,
E.
de
Vries,
J.
van
Horssen
(Amsterdam,
NL)
Objectives:
To
investigate
the
potential
of
different
Nrf2
activators
to
boost
antioxidant
enzyme
expression
in
oligodendrocytes
and
protect
them
from
reactive
oxygen
species
(ROS)-­‐mediated
cell
death.
Background:
Oligodendrocyte
damage
and
loss
are
key
features
of
Multiple
Sclerosis
(MS)
pathology
and
oligodendrocytes
are
particularly
vulnerable
to
ROS-­‐induced
oxidative
damage
and
cell
death.
Hence,
a
potential
therapeutic
strategy
to
protect
these
cells
from
ROS-­‐mediated
damage
is
urgently
needed.
To
date,
several
compounds,
including
fumurate
derivative
BG-­‐12,
tert-­‐Butylhydroquinone
(tBHQ),
sulforaphane
(SFN)
and
protandim
have
potential
anti-­‐inflammatory
and
neuroprotective
properties.
These
compounds
are
thought
to
exert
their
protective
function
via
activation
of
the
nuclear-­‐factor-­‐E2-­‐related
factor-­‐2
(Nrf2)
transcriptional
pathway,
which
is
involved
in
the
production
of
antioxidant
enzymes
necessary
for
oxidative
stress
defense.
We
postulate
that
distinct
Nrf2
activators
boost
antioxidant
enzyme
production
in
oligodendrocytes
and
limit
ROS-­‐mediated
oligodendrocyte
cell
death.
Methods:
Primary
rat
oligodendrocytes
and
rat
and
human
oligodendrocyte
cell
lines
were
treated
with
different
concentrations
of
BG-­‐12,
tBHQ,
SFN
and
protandim.
Next,
we
analyzed
the
expression
of
Nrf2-­‐mediated
antioxidant
enzymes
by
PCR
and
Western
blot
techniques.
To
study
the
beneficial
effects
of
the
different
Nrf2
activators,
we
first
incubated
the
oligodendrocytes
with
Nrf2
activators
and
subsequently
exposed
them
to
various
concentrations
of
hydrogen
peroxide
and
measured
oligodendrocyte
cell
survival.
Results:
1.
BG-­‐12,
tBHQ,
SFN
and
Protandim
are
well-­‐tolerated
and
strongly
induce
Nrf2-­‐driven
antioxidant
enzyme
production
in
oligodendrocytes,
with
protandim
showing
the
most
potent
induction.
2.
Nrf2
activators
are
able
to
protect
oligodendrocytes
against
ROS-­‐induced
cytotoxicity.
Conclusions:
Our
findings
indicate
that
several
Nrf2
activators
are
able
to
significantly
increase
antioxidant
enzyme
production
in
oligodendrocytes.
Interestingly,
Protandim,
a
dietary
supplement
consisting
of
herbal
ingredients,
was
the
most
potent
inducer
and
therefore
may
be
the
most
suited
as
a
therapeutic
strategy.
Importantly,
Nrf2-­‐mediated
antioxidant
enzyme
expression
in
oligodendrocytes
resulted
in
enhanced
oligodendrocyte
survival
during
an
oxidative
attack.
Dr.
J.
van
Horssen
received
research
grants
from
BiogenIdec

10.
MAYO
CLINIC
–
PROTANDIM
APPROACH
TO
TREATING
OVARIAN
CANCER
Translational
Studies
of
Protandim(RTM)
as
a
Candidate
Nutraceutical
Approach
to
Treating
Ovarian
Cancer
by
Prasongsook,
Naiyarat,
M.S.,
COLLEGE
OF
MEDICINE
–
MAYO
CLINIC,
2014,
98
pages;
1555561
Abstract
Background:
Nutraceutical
approaches
are
increasing
in
cancer
patients.
We
encountered
a
recurrent
ovarian
cancer
patient
who
incurred
durable
tumorregression
and
decreasing
CA-­‐125
with
initiation
of
the
nutraceutical
Protandim,
a
combination
of
five
phytochemical
extracts
(ashwagandha,bacopa,
green
tea,
milk
thistle,
turmeric).
Preclinical
studies
were
undertaken
to
investigate
Protandim
and
its
constituent
anticancer
effects
and
underlying
mechanism(s).
Methods:
In
vitro
ovarian
cancer
models
were
used
to
assess
Protandim
effects.
Colony
forming
assays,
Hoechst
nuclear/Trypan
exclusion
staining,
immunoblotting,
and
flow
cytometric
methods
were
used
to
assess
cytotoxic
and
to
identify
mechanism
(s)
of
action.
Combined
effects
of
Protandim
components
were
assessed
by
the
methods
of
Chou
and
Talalay;
ex
vivo
myeloma
patient
model
was
used
to
assess
cancer
selectivity.
In
vivo
studies
assessed
tolerability
and
toxicity
effect
of
Protandim.
Results:
Anticancer
effects
of
Protandim
demonstrated
induction
of
necrotic-­‐morphological
cell
death.
Ex
vivo
assays
showed
Protandim
to
selectively
kill
freshly
collected
patient
myeloma
cells,
relatively
sparing
paired
patient
normal
bone
marrow
cells.
Immunoblotting
and
flow
cytometric
experiments
indicated
that
Protandim
induced
cellular
reactive
oxygen
species
(ROS)
level.
Similar
cytotoxic
effects
in
wild-­‐type
and
Rho-­‐MOLT4
cells
indicated
non-­‐mitochondrial
mediated
ROSinduction.
Assessment
of
the
combined
effects
of
Protandim
constituents
showed
antagonism
or
additivity.
In
vivo
studies
showed
no
Protandim
toxicities
in
mice.
Conclusions:
Protandim
has
promising
activity
in
ovarian
cancer
models,
associated
with
induction
of
non-­‐
mitochondrial
mediated-­‐
ROS
and
necrosis.
Protandim
is
well-­‐tolerated
in
mice,
and
has
anti-­‐
cancer
selectivity.
Further
investigations
to
more
specifically
assess
molecular
mechanism
and
in
vivo
efficacy
are
presently
underway.

11.

12.
1ST
ANNUAL
CONFERENCE:
THE
KEAP1/NRF2
PATHWAY
IN
HEALTH
AND
DISEASE,
CAMBRIDGE,
UK
JANUARY
2015

13.
22nd
Annual
World
Congress
on
Anti-­‐Aging
Medicine
December
11-­‐13,
2014
Las
Vegas,
NV
This
year’s
conference
highlights
include:
• Metabolic
Syndrome
• Hormonal
Health
• Diagnostic
Testing
and
Interpretations
• Stress
and
the
Immune
Response
• Function
Neurology
• The
Science
of
Stem
Cells
• PRP-­‐new
research
and
applications
• Clinical
and
Aesthetic
Advancements
• Skin
technology,
skin
tightening
therapies
and
procedures
• Nutrient
Strategies
• Endocrine
System
• Lifestyle
Factors
• Chronic
Stress,
Oxidative
Stress
• Lifestyle
effects
on
sex
and
stress
hormones
PRODUCT
SHOWCASE
In
addition
to
the
education
offered
at
this
event,
A4M’s
product
showcase
features
the
most
cutting
edge
products
and
services
designed
to
keep
the
frontline
physician
improving
their
patient
care
and
increasing
their
practice
revenue.
The
product
showcase
will
take
place
during
the
breaks
of
the
CME
presentations
and
will
include
demonstrations
from
diagnostic
labs,
weight
loss
management
firms,
clinics,
nutraceutical
companies,
and
compounding
pharmacies,
among
others.
Topic:
Protandim
and
Nrf2
Triggering
-­‐
a
fundamentally
different
approach
to
cellular
protection
Presented
by:
Shawn
Talbott,
PhD
Sponsored
by:
LifeVantage

14.

15.