arginine blood pressure

© Arginine Benefits LLC, 2013Author: Dr. Rainer Böger

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 heart‘s contractile force


About 600,000 people die of heart disease in the United States every year – that’s 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.

The Art of Staying Healthy

Source: Centers for Disease Control 2014www.cdc.gov/heartdisease/facts.htm


The Scope of the Problem



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. Don’t smoke. If you smoke, quit as soon as possible.

What the CDC Promotes



Mortality of acute heart attack drops, … butoverall numbers of heart disease are constant


Source: CDC/NCHS, Health, United States, 2012http://www.cdc.gov/nchs/data/hus/hus12.pdf

Heart disease death rates fall - but the number of diseased people is stable

or

Cardiology is good at treatment - but falls short in prevention.


The Scope of the Problem: Hypertension



The Scope of the Problem: Heart Failure



What Can Be Done



Nitric Oxide (NO) is the most important protective mediator of the arterial wall.

It is generated from the amino acid precursor,

L-arginine.

NO promotes vasodilation and arterial elasticity.

Dr. Louis J. IgnarroNobel Laureate in 1998

for the discovery of nitric oxide

The Miracles of Nitric Oxide

NO SynthaseL-Arginine

N O

L-CitrullineO2

NADPH NADP


NO – an endogenous anti-atherosclerotic molecule:

anti-atherosclerotic anti-oxidant vasodilator anti-thrombotic anti-proliferative anti-inflammatory anti-oxidant.

The Potential of Nitric Oxide

NO

vasodilation

platelet aggregation

monocyte adhesionsmooth muscle cell

proliferation

superoxide radicalelaboration

LDL oxidation

O2–

Source: Böger et al., Atherosclerosis 1996; 127: 1-11


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

The Potential of L-Arginine

Dr. John P. CookePioneer of L-arginine research

Cooke et al. Circulation 1991

Tsao et al. Circulation 1994

Böger et al.Atherosclerosis 1995

Böger et al. Atherosclerosis 1995

Böger et al. Atherosclerosis 1998

Cooke et al. 1991, 1992; Böger et al. 1995, 1997; Candipan et al. 1996



Böger et al., Atherosclerosis 1995; 117: 273 – 284

Study A: Prevention of Plaque Build-Up

Design:

0 8 weeks

Control

Cholesterol

Cholesterol + L-Arginine

Results:

Cholesterol

Cholesterol; treated with L-arginineCONTROL CHOLESTEROL

0

5

10

15

20

25

30

35

40

45

50

55

60

Ca

roti

d i

nti

ma

l p

laq

ue

are

a

[%

of

tota

l in

tim

a]

*

CHOL.

+ L-ARGININE

#

(0)

A. carotis

-80%



Böger et al., Circulation 1997; 96: 1282-1290

Study B: Stopping the Progression of Plaque Build-Up

Design:

0 10 weeks

Control

Cholesterol

Results:

164


Cholesterol

Cholesterol + Lovastatin

Control

0 weeks164

Inti

mal

pla

qu

e ar

ea(c

aro

tid

art

ery)

[%

]

0

50

40

30

20

10

-92%

„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.“



Candipan et al., Arterioscler. Thromb. Vasc. Biol. 1996; 16: 44-50

Study C: Reversal of Pre-Existing Plaque

Design:

0 18 weeks

Cholesterol

Results:

2310

Cholesterol


0 weeks1610

Inti

mal

pla

qu

e ar

ea(c

aro

tid

art

ery)

[%

]

0

75

60

45

30

15

„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 “

Cholesterol

1814


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.

The Promises of L-Arginine


CONTRACONTRA

PROPROL-Arginine caused improvements of coronary and systemic vascular endothelial function in human subjects in vivo.

The L-Arginine Paradox

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.


ADMAADMAAn endogenous inhibitor of NO synthase displaces L-arginine from the enzyme‘s catalytic site and blocks NO production.

The L-Arginine Paradox:Solution

1000100101.1.010

20

40

60

100

80

L-Arginine [µmol/L]

NO

Sy

nth

esi

s R

ate

[%

]

2.9 µMKm =

50%

1000100101.1.010

20

40

60

100

80

L-Arginine [µmol/L]

NO

Sy

nth

esi

s R

ate

[%

]

50%

In vitro:without ADMA

In patientswith high ADMA


ADMA Predicts Mortality

Total mortality

HR = 1.21 (1.07-1.37) per SD increment (0.13 µmol/l)P = 0.003

3,320 study participants from the general

population;

10 years of follow-up

Multivariate model adjustedfor established CV riskfactors included in the FRSplus BNP, renin, Hcys, CRP,urinary albumin excretion.

The Framingham Offspring StudyBöger et al. Circulation 2009


The L-Arginine / ADMA Balance

ADMAL-Arginine

NO

Normal L-Arginine/ADMA Balance:> 100 : 1

The physiological model was constructed based

upon data from the prospective Framingham

Offspring Study, the Gutenberg Health Study, the

Gotenberg Women‘s Study, the SHIP Study, and

others, totalling over 20,000 study participants.

Böger et al. Circulation 1998Leong et al. ATVB 2008…


The L-Arginine / ADMA Balance

0

0,5

1

1,5

2

2,5

3

3,5

4

Q1

Q2

Q3Q4

ADMA QuartilesQ1Q2

Q3Q4

L-ArginineQuartiles

Hazard Ratios for Mortality (Multivariable Model)

The Framingham Offspring StudyBöger et al. Circulation 2009

4th

L-arginineADMA

> 100

L-arginineADMA

< 30

3rd2nd1st

4th

3rd

2nd

1st


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!


In our recent epidemiological survey (2012/2013) 2 out of 3 subjects had high ADMA levels, justifying dietary L-arginine supplementation.

Normal range for ADMA: 0.2 – 0.7 µmol/l.

The Complexities of L-Arginine

Dr. Rainer H. BögerInventor of Arginine Cardio

Senior Medical and Scientific Advisor

Low (<0.2)

Normal(0.2 – 0.7)

Elevated (0.7 – 1.0)

Highly elevated (> 1.0)

Source: Prof. Rainer H. BögerData on file


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.“



Controversy B: Some Clinical Studies with L-Arginine failed to show Benefit

Schulman et al., J. Am. Med. Assoc. 2006; 295: 58-64

• 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.

PlaceboArginine

baseline

6 months0

20

40

60

80

100

120

L-a

rgin

ine

[µm

ol/

l]



Controversy B: Some Clinical Studies with L-Arginine failed to show Benefit

Wilson et al., Circulation 2007; 116: 188-195

• 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.


L-Citrulline is converted into L-arginine after intestinal absorption.This results in prolonged elevation of L-arginine blood levels.

The Wisdom of L-Arginine: Step 1

Prolong the Half-Life of L-Arginine


Longer half-life of L-arginine blood levelsEnables twice daily administration and results in build-up of L-arginine levelsImproved bioavailability of L-citrulline over L-arginine


Advantages of combined L-arginine plus L-citrulline


The individual dose of L-arginine is dependent on

baseline L-arginine in plasma

AND

ADMA in plasma.


Find the Right Dose in each Individual

Assess L-arginine and ADMA Supplement with Arginine Cardio


Arginine Cardio is more than just L-arginine plus L-citrulline.

It combines other ingredients that strongly support the beneficial actions of nitric oxide.


Use the Complete Formula for the Heart and Arteries

ResveratrolCoQ10Vitamin D3L-TaurineB vitaminsMagnesiumCurcuminVitamin D3Vitamin CFolic Acid

arginine blood pressure

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