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• Arginine Cardio
• The intelligent way of combining the best that
  nature offers for the protection of your heart
  and blood vessels.
• The complete formula to
• Enhance nitric oxide
• Reduce inflammation
• Fight oxidative stress
• Strengthen the hearts contractile force

2
The Art of Staying Healthy
About 600,000 people die of heart disease in the
United States every year thats 1 in every 4
deaths. Heart disease is the leading cause of
death for both men and women. More than half of
the deaths due to heart disease in 2009 were in
men. Coronary heart disease is the most common
type of heart disease, killing nearly 380,000
people annually. Every year about 720,000
Americans have a heart attack. Of these, 515,000
are a first heart attack and 205,000 happen in
people who have already had a heart
attack. Coronary heart disease alone costs the
United States 108.9 billion each year.
Source Centers for Disease Control
2014 www.cdc.gov/heartdisease/facts.htm
3
The Scope of the Problem
Source Centers for Disease Control
2014 www.cdc.gov/heartdisease/facts.htm
4
What the CDC Promotes
Early Action is Key About 47 of sudden cardiac
deaths occur outside a hospital. This suggests
that many people with heart disease don't act on
early warning signs. Americans at Risk High
blood pressure, high LDL cholesterol, and smoking
are key risk factors for heart disease. About
half of Americans (49) have at least one of
these three risk factors. Protect Your
Heart Lowering you blood pressure and
cholesterol will reduce your risk of dying of
heart disease. Eat a healthy diet. Take a brisk
10-minute walk, 3 times a day, 5 days a week.
Dont smoke. If you smoke, quit as soon as
possible.
Source Centers for Disease Control
2014 www.cdc.gov/heartdisease/facts.htm
5
Mortality of acute heart attack drops,
but overall numbers of heart disease are constant
Source Centers for Disease Control
2014 www.cdc.gov/heartdisease/facts.htm
Source CDC/NCHS, Health, United States,
2012 http//www.cdc.gov/nchs/data/hus/hus12.pdf
Heart disease death rates fall - but the
number of diseased people is stable or Cardi
ology is good at treatment - but falls
short in prevention.
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The Scope of the Problem Hypertension
Source Centers for Disease Control
2014 www.cdc.gov/heartdisease/facts.htm
7
The Scope of the Problem Heart Failure
Source Centers for Disease Control
2014 www.cdc.gov/heartdisease/facts.htm
8
What Can Be Done
Source Centers for Disease Control
2014 www.cdc.gov/heartdisease/facts.htm
9
The Miracles of Nitric Oxide
Nitric Oxide (NO) is the most important
protective mediator of the arterial wall. It is
generated from the amino acid precursor, L-argini
ne. NO promotes vasodilation and arterial
elasticity.
L-Citrulline
O2
NO Synthase
L-Arginine
O
N
Dr. Louis J. Ignarro Nobel Laureate in 1998 for
the discovery of nitric oxide
NADP
NADPH
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The Potential of Nitric Oxide

• NO an endogenous anti-atherosclerotic molecule
• anti-atherosclerotic
• anti-oxidant
• vasodilator
• anti-thrombotic
• anti-proliferative
• anti-inflammatory
• anti-oxidant.

Source Böger et al., Atherosclerosis 1996 127
1-11
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The Potential of L-Arginine
Dr. John P. Cooke Pioneer of L-arginine research

• L-arginine maintains vascular elasticity
• (endothelium-dependent vascular relaxation)
• and reverses build-up of soft plaque
• even in pre-existing atherosclerosis
• this effect is lost after withdrawal of
  L-arginine.
• In experimental studies, L-arginine
• Increases NO formation
• Improves vasodilation
• Inhibits platelet aggregation
• Reduces leukocyte infiltration
• Diminishes superoxide radical formation

Cooke et al. 1991, 1992 Böger et al. 1995, 1997
Candipan et al. 1996
Böger et al. Atherosclerosis 1995
Cooke et al. Circulation 1991
Tsao et al. Circulation 1994
Böger et al. Atherosclerosis 1998
Böger et al. Atherosclerosis 1995
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The Potential of L-Arginine
Study A Prevention of Plaque Build-Up
Design
Cholesterol L-Arginine
Cholesterol
Control
0
weeks
8
Results
-80
Böger et al., Atherosclerosis 1995 117 273 284
13
The Potential of L-Arginine
Study B Stopping the Progression of Plaque
Build-Up
Cholesterol L-Arginine
Design
Cholesterol
Cholesterol
Cholesterol Lovastatin
Control
Control
0
weeks
10
16
4
Results
50
40
Dietary L-arginine completely suppressed the
aggravation of intimal plaque formation during
the second part of the study Lovastatin
treatment significantly reduced the progression
of plaque formation but did not completely block
it.
30
-92
Intimal plaque area (carotid artery)
20
10
0
0
weeks
16
4
Böger et al., Circulation 1997 96 1282-1290
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The Potential of L-Arginine
Study C Reversal of Pre-Existing Plaque
Design
Cholesterol
Cholesterol
Cholesterol L-Arginine
Cholesterol
0
weeks
18
23
10
Results
75
60
This is the first demonstration that
restoration of NO activity can induce
regression of preexisting intimal lesions and
provides evidence that L-arginine therapy may be
of potential clinical benefit
45
Intimal plaque area (carotid artery)
30
15
0
0
weeks
16
10
18
14
Candipan et al., Arterioscler. Thromb. Vasc.
Biol. 1996 16 44-50
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The Promises of L-Arginine

• In clinical studies with human subjects,
  L-arginine was shown to
• Restore arterial elasticity
• Improve blood flow
• Enhance memory function
• Accelerate recovery from exercise
• Lower blood pressure
• Reduce the symptoms of
• chronic heart failure
• coronary artery disease
• peripheral arterial disease
• erectile dysfunction.

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The L-Arginine Paradox
PRO
L-Arginine caused improvements of coronary and
systemic vascular endothelial function in human
subjects in vivo.
CONTRA
Not all patients with vascular disease have low
plasma L-arginine levels. In vitro, NO synthase
is saturated with substrate at concentrations
corresponding to usual plasma levels.
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The L-Arginine ParadoxSolution
ADMA
An endogenous inhibitor of NO synthase displaces
L-arginine from the enzymes catalytic site and
blocks NO production.
In vitro without ADMA
In patients with high ADMA
100
100
80
80
60
60
NO Synthesis Rate
NO Synthesis Rate
50
50
40
40
20
20
K

m
2.9 µM
0
0
1000
100
10
1
.1
.01
1000
100
10
1
.1
.01
L-Arginine µmol/L
L-Arginine µmol/L
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ADMA Predicts Mortality
3,320 study participants from the general
population 10 years of follow-up
Multivariate model adjusted for established CV
risk factors included in the FRS plus BNP, renin,
Hcys, CRP, urinary albumin excretion.
The Framingham Offspring Study Böger et al.
Circulation 2009
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The L-Arginine / ADMA Balance
NO
Normal L-Arginine/ADMA Balance gt 100 1
ADMA
L-Arginine
The physiological model was constructed based
upon data from the prospective Framingham
Offspring Study, the Gutenberg Health Study, the
Gotenberg Womens Study, the SHIP Study, and
others, totalling over 20,000 study participants.
Böger et al. Circulation 1998 Leong et al. ATVB
2008
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The L-Arginine / ADMA Balance
4th
3rd

2nd

1st
2nd

1st
3rd

4th
The Framingham Offspring Study Böger et al.
Circulation 2009
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The ADMA Card test
The ultimate tool for assessing risk and
controlling L-arginine treatment ? measure
ADMA and arginine blood levels in just a
few drops of blood! ? send sample by surface
mail from any place to the specialized
lab! ? Know who really is in need
of arginine supplementation! ? Check
whether your status has improved during
L-arginine intake!
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The Complexities of L-Arginine
In our recent epidemiological survey (2012/2013)
2 out of 3 subjects had high ADMA levels,
justifying dietary L-arginine supplementation. No
rmal range for ADMA 0.2 0.7 µmol/l.
Low (lt0.2)
Highly elevated (gt 1.0)
Normal (0.2 0.7)
Elevated (0.7 1.0)
Dr. Rainer H. Böger Inventor of Arginine
Cardio Senior Medical and Scientific Advisor
Source Prof. Rainer H. Böger Data on file
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The Controversies of L-Arginine
Controversy A L-Arginine has a short half-life
The vascular effects of L-arginine are closely
correlated with its plasma concentrations.
Terminal elimination half-life for L-arginine was
calculated as 59.6. 9.1 min and 79.5 9.3 min
after intravenous and oral administration,
respectively.
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The Controversies of L-Arginine
Controversy B Some Clinical Studies with
L-Arginine failed to show Benefit

• 153 patients recruited within 3-21 days
• after ST elevation MI
• L-Arginine 3x3 g/d versus placebo,6 months
• Primary endpoint Composite of total mortality
• and change in ejection fraction

Study was ended early due to excess mortality in
patients in the L-arginine group. However, none
of the deaths could be causally related to
arginine. Only 56 patients total ended the study
and were included in the analysis. Further,
arginine did not succeed to increase the
arginine blood level.
Schulman et al., J. Am. Med. Assoc. 2006 295
58-64
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The Controversies of L-Arginine
Controversy B Some Clinical Studies with
L-Arginine failed to show Benefit

• 133 patients with peripheral arterial disease
• L-Arginine 3x1 g/d versus placebo during 6
  months
• Primary endpoint Change in absolute
  claudication distance at 6 mo.

Wilson et al., Circulation 2007 116 188-195
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The Wisdom of L-Arginine Step 1
Prolong the Half-Life of L-Arginine
L-Citrulline is converted into L-arginine after
intestinal absorption. This results in prolonged
elevation of L-arginine blood levels.
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The Wisdom of L-Arginine Step 1
Advantages of combined L-arginine plus
L-citrulline
Longer half-life of L-arginine blood
levels Enables twice daily administration and
results in build-up of L-arginine levels Improved
bioavailability of L-citrulline over L-arginine
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The Wisdom of L-Arginine Step 2
Find the Right Dose in each Individual
The individual dose of L-arginine is dependent on
baseline L-arginine in plasma AND ADMA in
plasma.
Supplement with Arginine Cardio
Assess L-arginine and ADMA
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The Wisdom of L-Arginine Step 3
Use the Complete Formula for the Heart and
Arteries
Arginine Cardio is more than just L-arginine plus
L-citrulline. It combines other ingredients that
strongly support the beneficial actions of
nitric oxide.
Resveratrol CoQ10 Vitamin D3 L-Taurine B
vitamins Magnesium Curcumin Vitamin D3 Vitamin
C Folic Acid