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You	
  Are	
  What	
  You	
  Eat!	
  
David	
  Bihari	
  
Intensive	
  Care	
  Physician	
  
Prince	
  of	
  Wales	
  Hospital	
  and	
  Lismore	
  Base	
  Hospital	
  
Conflicts	
  of	
  Interest	
  
Conflicts	
  of	
  Interest	
  
•  “TPN	
  Czar”	
  of	
  Prince	
  of	
  Wales	
  Hospital	
  
•  Medical	
  representaGve	
  on	
  the	
  TPN	
  Forum	
  
•  In	
  a	
  previous	
  life,	
  performed	
  and	
  published	
  
research	
  in	
  the	
  area	
  of	
  “immunonutriGon”	
  
•  Tendency	
  to	
  believe	
  in	
  “one’s	
  own	
  bull	
  shit”!	
  	
  
You	
  Are	
  What	
  You	
  Eat	
  
•  The	
  noGon	
  that	
  to	
  be	
  fit	
  and	
  healthy	
  you	
  need	
  
to	
  eat	
  GOOD	
  FOOD!	
  
•  “Dis	
  moi	
  ce	
  que	
  tu	
  manges,	
  je	
  te	
  dirai	
  ce	
  que	
  
tu	
  es”	
  Anthelme	
  Brillat-­‐Savarin	
  1826	
  
•  1942	
  Lindahr	
  –	
  You	
  are	
  what	
  you	
  eat:	
  how	
  to	
  
win	
  and	
  keep	
  healthy	
  with	
  diet	
  
•  More	
  Catholic	
  than	
  catabolic?	
  
– TransubstanGaGon!	
  
Things	
  Your	
  Mother	
  Taught	
  You	
  
•  Eat	
  your	
  greens	
  ….not	
  
too	
  many	
  Mars	
  bars	
  …
because	
  you	
  are	
  what	
  
you	
  eat!	
  
–  Avoid	
  the	
  “Cambridge	
  
diet”	
  of	
  beer	
  and	
  crisps	
  
Crick and Watson 1952
The	
  Mediterranean	
  Diet	
  
1975
The	
  Cambridge	
  “Beer	
  and	
  Crisps”	
  Diet	
  	
  
Nutrition and exercise
Fat	
  Men	
  
Things	
  Your	
  Mother	
  Taught	
  You	
  
•  Eat	
  your	
  greens	
  ….not	
  too	
  many	
  Mars	
  bars	
  …
because	
  you	
  are	
  what	
  you	
  eat!	
  
– Avoid	
  the	
  “Cambridge	
  diet”	
  of	
  beer	
  and	
  crisps	
  
•  Don’t	
  go	
  swimming	
  on	
  a	
  full	
  stomach!	
  
– 	
  Nutrients	
  in	
  the	
  lumen	
  of	
  the	
  bowel	
  promote	
  
splanchnic	
  blood	
  flow	
  
– “Trophic	
  enteral	
  feeding”	
  :	
  10	
  –	
  30	
  mL/hour	
  
Splanchnic	
  Blood	
  Flow	
  
1909 - British lady “suffragette” (fighting for the
rights of women) put in prison and on hunger strike
The Intensivist?
“more intensive than caring”
The Dietician?
“obsessing about calories”
NutriGonal	
  Support	
  2014	
  
•  Energy	
  intake	
  may	
  not	
  be	
  so	
  important	
  
– Hypocaloric	
  enteral	
  feeding	
  is	
  widespread	
  
– Trophic	
  feeding	
  	
  
•  ResurrecGon	
  of	
  TPN	
  through	
  meta-­‐analysis	
  
(2005)	
  since	
  its	
  crucifixion	
  by	
  meta-­‐analysis	
  
(1998)	
  
•  IntroducGon	
  of	
  glutamine	
  containing	
  TPN	
  by	
  
meta-­‐analysis	
  
NutriGonal	
  Support	
  2014	
  
•  Crucifixion	
  of	
  TPN	
  –	
  EPaNIC	
  study	
  
– Not	
  enough	
  protein!	
  
•  Crucifixion	
  of	
  glutamine	
  –	
  the	
  REDOX	
  study	
  	
  
– Too	
  much	
  nitrogen	
  given	
  to	
  paGents	
  too	
  sick	
  to	
  
uGlise	
  
– Not	
  enough	
  nutriGon!	
  
•  New	
  intravenous	
  lipid	
  soluGons	
  available	
  	
  
•  Crucifixion	
  of	
  enteral	
  immune	
  modulaGng	
  
nutriGon	
  (specifically	
  arginine	
  containing	
  feeds	
  
eg.	
  “Impact”)	
  by	
  meta-­‐analysis	
  (2003)	
  
Some	
  Cult	
  Leaders	
  
The Golden Calf Phenomenon
Learning	
  from	
  the	
  Past	
  
Criminal terrorist or
political prisoner?
Lessons	
  from	
  Northern	
  Ireland	
  
“Hunger”	
  
Bobby Sands 61 days
Francis Hughes 59 days
Raymond McCreesh 61 days
Patsy O’Hara 61 days
Joseph McDonnell 61 days
Martin Hurson 44 days
Kevin Lynch 71 days
Kieran Doherty 73 days
Thomas McElwee 62 days
Micky Devine 61 days
Cause of death - infection
StarvaGon	
  in	
  hospital	
  is	
  unacceptable	
  
•  Nutrients	
  -­‐	
  unlike	
  drugs	
  -­‐	
  are	
  required	
  for	
  the	
  
maintenance	
  of	
  good	
  health,	
  survival	
  
•  10	
  IRA	
  hunger	
  strikers	
  fasted	
  to	
  death	
  over	
  a	
  mean	
  of	
  
62	
  +	
  3	
  days	
  
–  Died	
  from	
  infecGon	
  
•  Australian	
  medical	
  student	
  lost	
  in	
  Nepal	
  lived	
  for	
  42	
  
days	
  eaGng	
  only	
  snow	
  (Ann	
  Int	
  Med	
  1997)	
  :	
  lost	
  19	
  kg,	
  	
  
80	
  to	
  61	
  kg	
  
•  StarvaGon	
  is	
  not	
  the	
  same	
  as	
  criGcal	
  illness	
  
•  Malnourished	
  paGents	
  form	
  a	
  special	
  group	
  
–  Li-le	
  /me	
  to	
  waste	
  before	
  ins/tu/ng	
  support	
  	
  	
  
TreaGng	
  MalnutriGon	
  
Learning	
  from	
  the	
  Past	
  
The Refeeding Syndrome – death from
hypophosphataemia (plus hypomagnesaemia)
The	
  Refeeding	
  Syndrome	
  
•  First	
  described	
  in	
  Far	
  East	
  Japanese	
  
prisoners	
  amer	
  2nd	
  World	
  War	
  
•  Schnitker	
  et	
  al	
  Ann	
  Inter	
  Med	
  1951	
  
•  StarGng	
  to	
  eat	
  associated	
  with	
  
development	
  of	
  cardiac	
  failure	
  
–  DepleGon	
  of	
  intracellular	
  PO4,	
  Mg	
  &	
  K	
  
•  Decreased	
  secreGon	
  of	
  insulin	
  
–  Refeeding	
  with	
  CHO	
  results	
  in	
  increased	
  
insulin	
  secreGon,	
  cellular	
  uptake	
  of	
  PO4,	
  Mg	
  
and	
  K	
  
•  First	
  4	
  days	
  of	
  refeeding	
  
•  Arrhythmias,	
  sudden	
  death,	
  heart	
  failure,	
  
rhabdomyolysis,	
  seizures	
  
Conflicts	
  of	
  Interest	
  
The	
  REDOX	
  Study	
  –	
  4	
  arms	
  
" 0.35	
  Gm/kg/day	
  iv	
  glutamine	
  plus	
  30	
  Gm	
  enteral	
  
glutamine	
  	
  
" 0.5	
  Gm/kg/day	
  of	
  iv	
  dipepGde	
  alanyl-­‐glyutamine	
  
" 42.5	
  Gm	
  of	
  enteral	
  alanyl-­‐glutamine	
  and	
  glycine-­‐glutamine	
  
•  AnGoxidants	
  	
  
–  500	
  mcg	
  selenium	
  iv,	
  300	
  mcg	
  enterally	
  
–  20	
  mg	
  zinc,	
  10	
  mg	
  beta-­‐carotene	
  enterally	
  
–  500	
  mg	
  vitamin	
  E,	
  1500	
  mg	
  vitamin	
  C	
  enterally	
  
Arginine	
  as	
  an	
  Immunonutrient	
  
•  Arginine	
  (C6H14N4O2,	
  mw	
  174.20)	
  
– EssenGal	
  amino	
  acid	
  during	
  childhood	
  
– CondiGonally	
  essenGal	
  in	
  adults	
  
– Incorporated	
  into	
  protein	
  at	
  4.7%	
  per	
  mole	
  
– Found	
  in	
  meat,	
  fish,	
  dairy	
  products,	
  brown	
  rice,	
  
nuts,	
  raisons,	
  whole	
  wheat	
  
– Glutamine,	
  glutamate	
  and	
  citrulline	
  are	
  also	
  dietry	
  
sources	
  of	
  arginine	
  
•  IntesGnal	
  conversion	
  to	
  citrulline	
  
•  Renal	
  and	
  hepaGc	
  conversion	
  to	
  arginine	
  
Watermelon	
  ConsumpGon	
  and	
  Plasma	
  
Arginine	
  Levels	
  	
  
•  Collins	
  et	
  al	
  NutriGon	
  2007;	
  23:	
  261-­‐266	
  
•  Watermelon	
  is	
  a	
  rich	
  source	
  of	
  citrulline	
  
•  Controlled	
  diet	
  plus	
  0	
  /	
  780	
  g	
  /	
  1560	
  g	
  of	
  
watermelon	
  juice	
  
– Equivalent	
  to	
  1	
  g	
  and	
  2	
  g	
  citrulline	
  /	
  day	
  
•  Amer	
  3	
  weeks,	
  fasGng	
  plasma	
  arginine	
  levels	
  
increased	
  by	
  12	
  and	
  22%	
  respecGvely	
  
•  No	
  change	
  in	
  citrulline	
  levels	
  
•  18%	
  increase	
  in	
  ornithine	
  levels	
  
Arginine	
  as	
  an	
  Immunonutrient	
  
•  Number	
  of	
  supposed	
  beneficial	
  effects	
  
– Anabolic	
  secretagogue	
  sGmulaGng	
  the	
  secreGon	
  of	
  
growth	
  hormone,	
  glucagon,	
  insulin	
  and	
  IGF-­‐1	
  
– UGlized	
  in	
  the	
  synthesis	
  of	
  creaGne	
  in	
  skeletal	
  
muscle	
  	
  
•  Important	
  for	
  high	
  energy	
  creaGne	
  phosphate	
  
– Enhances	
  wound	
  healing	
  
– Enhances	
  cell	
  mediated	
  immunity	
  in	
  elecGve	
  
surgical	
  paGents	
  
– Substrate	
  for	
  the	
  formaGon	
  of	
  NO	
  
Metabolism of L-arginine by nitric oxide synthase
(NOS) and arginase
Nitric oxide synthase oxidatively degrades L-arginine into L-citrulline
and nitric oxide (NO), whereas arginase hydrolyses L-arginine to urea
and L-ornithine 
<5%
>95%
Arginine	
  in	
  Sepsis	
  
•  Role	
  of	
  nitric	
  oxide	
  (NO)	
  in	
  sepsis	
  	
  
– Key	
  mediator	
  of	
  the	
  vasodilataGon	
  
•  Appropriate	
  release	
  maintains	
  microvascular	
  blood	
  flow	
  
•  Excessive	
  release	
  associated	
  with	
  hypotension	
  
– Key	
  mediator	
  in	
  macrophages	
  and	
  white	
  cells	
  for	
  
killing	
  of	
  invading	
  microorganisms	
  
•  Excessive	
  release	
  associated	
  with	
  Gssue	
  injury?	
  
–  Splanchnic	
  mucosal	
  injury	
  
–  Myocardial	
  dysfuncGon	
  
–  Skeletal	
  muscle	
  mitochondrial	
  dysfuncGon	
  
Arginine	
  in	
  Sepsis	
  
•  The	
  Heyland	
  Hypothesis	
  
– Arginine	
  in	
  sepsis	
  may	
  be	
  contra-­‐indicated	
  since	
  it	
  
may	
  enhance	
  the	
  producGon	
  of	
  NO	
  and	
  worsen	
  any	
  
associated	
  Gssue	
  injury	
  
– Signal	
  of	
  detrimental	
  effect	
  obtained	
  from	
  studies	
  of	
  
arginine	
  containing	
  enteral	
  nutriGon	
  
– Ignores	
  the	
  evidence	
  of	
  the	
  detrimental	
  effects	
  of	
  
blocking	
  the	
  synthesis	
  of	
  NO	
  in	
  sepGc	
  shock	
  using	
  N-­‐
methyl-­‐L-­‐arginine	
  (546C88)	
  
cNOS
cNOS + iNOS
EffectofArginine
inducedNOformation
HarmfulBenefitial
Arginine / NO
availability
Optimal NO-Balance
- Hemodynamic instability
- Immune Suppression
- Cytotoxicity
- Organ dysfunction
- Microcirculation ↑
- Immune augmentation ↑
Suchner Brit J Nutrition 2001
2/22 = 9%
3/31 = 10%
0/37 = 0%
3/98 = 3%
36/296 = 12%
2/33 = 6%
28/170 = 16%
12/36 = 33%
2/43 = 5%
3/30 = 10%
6/29 = 21%
180/390 = 46%
45/176 = 26%
Heyland DK et al. Should Immunonutrition become
routine in critically ill patients? A systematic
review of the evidence. JAMA 2001; 286: 944-953
1391 “critically ill” patients studied with 322 deaths (23%)
13 studies included
Relative risk 1.18; 95%CI 0.88-1.58
A	
  Convert	
  to	
  Heylandism	
  
•  The	
  paGent	
  must	
  be	
  fed	
  
early	
  
•  The	
  paGent	
  must	
  go	
  on	
  
TPN	
  
•  The	
  paGent	
  must	
  
receive	
  glutamine	
  
•  The	
  “Maya”	
  factor!	
  
•  A	
  Killer	
  Penis	
  in	
  
Minutes	
  
–  www.libidus-­‐pill.com	
  
•  Penis	
  Enlargement	
  
Chart	
  
–  www.Penis-­‐
Enlargement-­‐Chart.com	
  



L-Arginine 500mg 60 Caps
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• Dr Vera's Formulations 
• L-Arginine 500mg 
• May assist with male infertility 
• May assist wound healing and immune
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• May assist cardiovascular health
more info...


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Bihari: You are what you eat

  • 1. You  Are  What  You  Eat!   David  Bihari   Intensive  Care  Physician   Prince  of  Wales  Hospital  and  Lismore  Base  Hospital  
  • 3. Conflicts  of  Interest   •  “TPN  Czar”  of  Prince  of  Wales  Hospital   •  Medical  representaGve  on  the  TPN  Forum   •  In  a  previous  life,  performed  and  published   research  in  the  area  of  “immunonutriGon”   •  Tendency  to  believe  in  “one’s  own  bull  shit”!    
  • 4. You  Are  What  You  Eat   •  The  noGon  that  to  be  fit  and  healthy  you  need   to  eat  GOOD  FOOD!   •  “Dis  moi  ce  que  tu  manges,  je  te  dirai  ce  que   tu  es”  Anthelme  Brillat-­‐Savarin  1826   •  1942  Lindahr  –  You  are  what  you  eat:  how  to   win  and  keep  healthy  with  diet   •  More  Catholic  than  catabolic?   – TransubstanGaGon!  
  • 5. Things  Your  Mother  Taught  You   •  Eat  your  greens  ….not   too  many  Mars  bars  … because  you  are  what   you  eat!   –  Avoid  the  “Cambridge   diet”  of  beer  and  crisps  
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  • 13. 1975 The  Cambridge  “Beer  and  Crisps”  Diet    
  • 16. Things  Your  Mother  Taught  You   •  Eat  your  greens  ….not  too  many  Mars  bars  … because  you  are  what  you  eat!   – Avoid  the  “Cambridge  diet”  of  beer  and  crisps   •  Don’t  go  swimming  on  a  full  stomach!   –   Nutrients  in  the  lumen  of  the  bowel  promote   splanchnic  blood  flow   – “Trophic  enteral  feeding”  :  10  –  30  mL/hour  
  • 18.
  • 19. 1909 - British lady “suffragette” (fighting for the rights of women) put in prison and on hunger strike The Intensivist? “more intensive than caring” The Dietician? “obsessing about calories”
  • 20. NutriGonal  Support  2014   •  Energy  intake  may  not  be  so  important   – Hypocaloric  enteral  feeding  is  widespread   – Trophic  feeding     •  ResurrecGon  of  TPN  through  meta-­‐analysis   (2005)  since  its  crucifixion  by  meta-­‐analysis   (1998)   •  IntroducGon  of  glutamine  containing  TPN  by   meta-­‐analysis  
  • 21. NutriGonal  Support  2014   •  Crucifixion  of  TPN  –  EPaNIC  study   – Not  enough  protein!   •  Crucifixion  of  glutamine  –  the  REDOX  study     – Too  much  nitrogen  given  to  paGents  too  sick  to   uGlise   – Not  enough  nutriGon!   •  New  intravenous  lipid  soluGons  available     •  Crucifixion  of  enteral  immune  modulaGng   nutriGon  (specifically  arginine  containing  feeds   eg.  “Impact”)  by  meta-­‐analysis  (2003)  
  • 23. The Golden Calf Phenomenon
  • 24. Learning  from  the  Past   Criminal terrorist or political prisoner?
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  • 26. Lessons  from  Northern  Ireland   “Hunger”   Bobby Sands 61 days Francis Hughes 59 days Raymond McCreesh 61 days Patsy O’Hara 61 days Joseph McDonnell 61 days Martin Hurson 44 days Kevin Lynch 71 days Kieran Doherty 73 days Thomas McElwee 62 days Micky Devine 61 days Cause of death - infection
  • 27. StarvaGon  in  hospital  is  unacceptable   •  Nutrients  -­‐  unlike  drugs  -­‐  are  required  for  the   maintenance  of  good  health,  survival   •  10  IRA  hunger  strikers  fasted  to  death  over  a  mean  of   62  +  3  days   –  Died  from  infecGon   •  Australian  medical  student  lost  in  Nepal  lived  for  42   days  eaGng  only  snow  (Ann  Int  Med  1997)  :  lost  19  kg,     80  to  61  kg   •  StarvaGon  is  not  the  same  as  criGcal  illness   •  Malnourished  paGents  form  a  special  group   –  Li-le  /me  to  waste  before  ins/tu/ng  support      
  • 28. TreaGng  MalnutriGon   Learning  from  the  Past   The Refeeding Syndrome – death from hypophosphataemia (plus hypomagnesaemia)
  • 29. The  Refeeding  Syndrome   •  First  described  in  Far  East  Japanese   prisoners  amer  2nd  World  War   •  Schnitker  et  al  Ann  Inter  Med  1951   •  StarGng  to  eat  associated  with   development  of  cardiac  failure   –  DepleGon  of  intracellular  PO4,  Mg  &  K   •  Decreased  secreGon  of  insulin   –  Refeeding  with  CHO  results  in  increased   insulin  secreGon,  cellular  uptake  of  PO4,  Mg   and  K   •  First  4  days  of  refeeding   •  Arrhythmias,  sudden  death,  heart  failure,   rhabdomyolysis,  seizures  
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  • 41. The  REDOX  Study  –  4  arms   " 0.35  Gm/kg/day  iv  glutamine  plus  30  Gm  enteral   glutamine     " 0.5  Gm/kg/day  of  iv  dipepGde  alanyl-­‐glyutamine   " 42.5  Gm  of  enteral  alanyl-­‐glutamine  and  glycine-­‐glutamine   •  AnGoxidants     –  500  mcg  selenium  iv,  300  mcg  enterally   –  20  mg  zinc,  10  mg  beta-­‐carotene  enterally   –  500  mg  vitamin  E,  1500  mg  vitamin  C  enterally  
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  • 45. Arginine  as  an  Immunonutrient   •  Arginine  (C6H14N4O2,  mw  174.20)   – EssenGal  amino  acid  during  childhood   – CondiGonally  essenGal  in  adults   – Incorporated  into  protein  at  4.7%  per  mole   – Found  in  meat,  fish,  dairy  products,  brown  rice,   nuts,  raisons,  whole  wheat   – Glutamine,  glutamate  and  citrulline  are  also  dietry   sources  of  arginine   •  IntesGnal  conversion  to  citrulline   •  Renal  and  hepaGc  conversion  to  arginine  
  • 46. Watermelon  ConsumpGon  and  Plasma   Arginine  Levels     •  Collins  et  al  NutriGon  2007;  23:  261-­‐266   •  Watermelon  is  a  rich  source  of  citrulline   •  Controlled  diet  plus  0  /  780  g  /  1560  g  of   watermelon  juice   – Equivalent  to  1  g  and  2  g  citrulline  /  day   •  Amer  3  weeks,  fasGng  plasma  arginine  levels   increased  by  12  and  22%  respecGvely   •  No  change  in  citrulline  levels   •  18%  increase  in  ornithine  levels  
  • 47. Arginine  as  an  Immunonutrient   •  Number  of  supposed  beneficial  effects   – Anabolic  secretagogue  sGmulaGng  the  secreGon  of   growth  hormone,  glucagon,  insulin  and  IGF-­‐1   – UGlized  in  the  synthesis  of  creaGne  in  skeletal   muscle     •  Important  for  high  energy  creaGne  phosphate   – Enhances  wound  healing   – Enhances  cell  mediated  immunity  in  elecGve   surgical  paGents   – Substrate  for  the  formaGon  of  NO  
  • 48. Metabolism of L-arginine by nitric oxide synthase (NOS) and arginase Nitric oxide synthase oxidatively degrades L-arginine into L-citrulline and nitric oxide (NO), whereas arginase hydrolyses L-arginine to urea and L-ornithine <5% >95%
  • 49. Arginine  in  Sepsis   •  Role  of  nitric  oxide  (NO)  in  sepsis     – Key  mediator  of  the  vasodilataGon   •  Appropriate  release  maintains  microvascular  blood  flow   •  Excessive  release  associated  with  hypotension   – Key  mediator  in  macrophages  and  white  cells  for   killing  of  invading  microorganisms   •  Excessive  release  associated  with  Gssue  injury?   –  Splanchnic  mucosal  injury   –  Myocardial  dysfuncGon   –  Skeletal  muscle  mitochondrial  dysfuncGon  
  • 50. Arginine  in  Sepsis   •  The  Heyland  Hypothesis   – Arginine  in  sepsis  may  be  contra-­‐indicated  since  it   may  enhance  the  producGon  of  NO  and  worsen  any   associated  Gssue  injury   – Signal  of  detrimental  effect  obtained  from  studies  of   arginine  containing  enteral  nutriGon   – Ignores  the  evidence  of  the  detrimental  effects  of   blocking  the  synthesis  of  NO  in  sepGc  shock  using  N-­‐ methyl-­‐L-­‐arginine  (546C88)  
  • 51. cNOS cNOS + iNOS EffectofArginine inducedNOformation HarmfulBenefitial Arginine / NO availability Optimal NO-Balance - Hemodynamic instability - Immune Suppression - Cytotoxicity - Organ dysfunction - Microcirculation ↑ - Immune augmentation ↑ Suchner Brit J Nutrition 2001
  • 52. 2/22 = 9% 3/31 = 10% 0/37 = 0% 3/98 = 3% 36/296 = 12% 2/33 = 6% 28/170 = 16% 12/36 = 33% 2/43 = 5% 3/30 = 10% 6/29 = 21% 180/390 = 46% 45/176 = 26% Heyland DK et al. Should Immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA 2001; 286: 944-953 1391 “critically ill” patients studied with 322 deaths (23%) 13 studies included Relative risk 1.18; 95%CI 0.88-1.58
  • 53.
  • 54. A  Convert  to  Heylandism   •  The  paGent  must  be  fed   early   •  The  paGent  must  go  on   TPN   •  The  paGent  must   receive  glutamine   •  The  “Maya”  factor!  
  • 55. •  A  Killer  Penis  in   Minutes   –  www.libidus-­‐pill.com   •  Penis  Enlargement   Chart   –  www.Penis-­‐ Enlargement-­‐Chart.com  
  • 56. 
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