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Protandim: PubMed.Gov Clinical Studies and More

  1. 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     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     • 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. 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       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. 3.     4. VIRGINIA  COMMONWEALTH  UNIVERSITY     Chronic  Pulmonary  Artery  Pressure  Elevation  Is  Insufficient  to  Explain  Right  Heart  Failure,  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     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. 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     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     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. 5. 8. LOUISIANA  STATE  UNIVERSITY  -­‐  SKIN  CANCER  &  MnSOD     The  Role  of  Manganese  Superoxide  Dismutase  in  Skin  Cancer,  Enzyme  Research,  March  23,   2011   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   **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. 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-­‐           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     “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. 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      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       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. 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       “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. 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. 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. 11.                                      
  12. 12.   1ST  ANNUAL  CONFERENCE:       THE  KEAP1/NRF2  PATHWAY  IN  HEALTH  AND  DISEASE,     CAMBRIDGE,  UK  JANUARY  2015                                                                                      
  13. 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        
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