1. The complete formula to Enhance nitric oxide Reduce inflammation
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
This power point presentation and all the comments have been prepared by Dr. Rainer Böger MD, Professor and Head of research in alternative medicine at the University of Hamburg, Germany. He has researched arginine for over 24 years as to its effects of the body’s cardiovascular system and heart. He has published over 120 peer reviewed scientific papers on arginine. The next scientist to him has produced less than half of that number. The web site evaluates doctors worldwide according to their works. He is number # 1 on that list. Arginine Cardio was formulated based on his 24 years of research and his 100 published papers. Arginine Cardio can affect the health of the adult public more than any other product. There have been studies of over 200,000 people over 20 to 25 years that have established that over 50% of the public worldwide will get cardiovascular disease in their life time. Arginine Cardio can stop the disease and even reverse it. Your patients will be well served to start a regiment of Arginine Cardio, they will live longer and will have much less disease in their life time. This power point is based on science and research of 24 years and will establish these claims.

2. The Art of Staying Healthy
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.
Source: Centers for Disease Control 2014

3. The Scope of the Problem
This map shows the incidence of death from heart disease in the US in the years by county. The dark red areas are counties with the highest cardiac death rates = high-risk areas in the US. Today about 1,000,000 people die from heart disease every year. That is the same as 3 jumbo jets crashing every day with no survivors.
Source: Centers for Disease Control 2014

4. What the CDC Promotes Early Action is Key Americans at Risk
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.
These are three key quotations from the CDC. The wording is original CDC language. These statements prove that it is US government policy to support identification of people at high risk of heart disease, to promote early action – prevention! – and to support a change of lifestyle and eating habits for the maintenance of heart health. Arginine Cardio is 100% in line with these governmental statements!
Source: Centers for Disease Control 2014

5. Mortality of acute heart attack drops, … but
overall numbers of heart disease are constant
These are original graphics taken from the CDC website. The one on the left shows that the mortality of acute heart attack is continuously decreasing over the last decade both in men and in women. However, this means that more people survive heart attack, and they are prone to develop long-term complications of heart disease, like heart failure, chronic ischemia of the heart, restenosis, arrhythmias, etc.
The graph on the right shows that the total number of people in each age group (both in men and in women) affected by heart disease has not changed during the last decade – this supports that view that more people survive their first heart attack, but the prevalence of heart disease as a whole has not changed at all during this time.
Source: Centers for Disease Control 2014
Source: CDC/NCHS, Health, United States, 2012
Heart disease death rates fall but the number of diseased people is stable or
Cardiology is good at treatment but falls short in prevention.

6. The Scope of the Problem: Hypertension
Geographical map by the CDC showing the prevalence of high blood pressure in the 50 states of the US. High blood pressure is one of the most important risk factors for heart disease, and the geographical distribution of high blood pressure in the US is amazingly similar to the geographical distribution of heart disease deaths (see slide 3).
Source: Centers for Disease Control 2014

7. The Scope of the Problem: Heart Failure
When people survive their first heart attack, the majority of them develops heart failure, i.e. the inability of the heart muscle to contract, due to scarring and remodeling of the heart muscle. Again, the geographical distribution of the prevalence of heart failure in the US follows very closely the one of heart attack and hypertension, the two major causes of heart failure in the US. Data are from the US Centers for Disease Control.
Source: Centers for Disease Control 2014

8. What Can Be Done Source: Centers for Disease Control 2014
The American Heart Association’s official mission “Heart 360” is the key initiative to increase alertness and improve heart health in the US. Arginine Cardio is in full compliance with this initiative and supports it. By understanding how the lack of nitric oxide – the major protective molecule in human blood vessels – can be reversed by L-arginine and L-citrulline (two major ingredients of Arginine Cardio), we contribute an important part to improve heart health.
It is highly relevant to understand that 200,000 heart deaths can be prevented each year, specifically in younger people, both in black and white individuals. Arginine Cardio has been shown to work in these people, by restoring the ability of the blood vessels to make nitric oxide.
Source: Centers for Disease Control 2014

9. for the discovery of nitric oxide
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-arginine.
NO promotes vasodilation and arterial elasticity. O2
L-Citrulline
Nitric oxide is made by the inner cell lining of the arterial wall (the endothelial cells) from the amino acid precursor, L-arginine. This discovery, which significantly changed the approach of the whole field of cardiology towards the understanding of atherosclerosis and its prevention, was awarded the Novel Prize of Medicine and Physiology in Three researchers from the US received the award: Dr. Louis Ignarro (photo) from Los Angeles, Dr. Robert Furchgott from New York, and Dr. Ferid Murad from Stanford.
L-Arginine
NO Synthase O N
NADPH
NADP
Dr. Louis J. Ignarro
Nobel Laureate in 1998
for the discovery of nitric oxide

10. The Potential of Nitric Oxide
NO – an endogenous anti-atherosclerotic molecule:
anti-atherosclerotic
anti-oxidant
vasodilator
anti-thrombotic
anti-proliferative
anti-inflammatory
anti-oxidant. NO
vasodilation
platelet aggregation
monocyte adhesion
smooth muscle cell
proliferation
superoxide radical
elaboration
LDL oxidation O 2 –
Nitric oxide is a versatile mediator in the vascular wall. It not only promotes vasodilation – increasing the elasticity of the arteries and their ability to adjust blood flow velocity to changes in physiological requirements in the various organs and tissues – but it also interacts with a variety of cells and molecules in the blood stream:
Nitric oxide inhibits platelet aggregation (which is the initial event in arterial thrombosis as it occurs in heart attack), it inhibits the adhesion and immigration of leukocytes into the vascular wall (cells that induce local inflammation in the vascular wall, take up cholesterol and form soft plaque if not inhibited by endothelial nitric oxide). Nitric oxide reduces the proliferation of vascular smooth muscle cells (studies have shown that nitric oxide prevents restenosis after angioplasty when applied locally or systemically), and nitric oxide inhibits the production of oxygen free radicals and reduces oxidation of LDL cholesterol, thereby reducing tissue damage to the vascular wall.
Source: Böger et al., Atherosclerosis 1996; 127: 1-11

11. Pioneer of L-arginine research
The Potential of L-Arginine
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
Dr. John P. Cooke
Pioneer of L-arginine research
Cooke et al. 1991, 1992; Böger et al. 1995, 1997; Candipan et al. 1996
Many experimental studies were published in the 1990’s using various animal models of atherosclerosis to prove that supplementation with L-arginine improves NO-mediated vasodilation and protects from the development of plaque or halts the progression of pre-existing plaque. This research was pioneered by Professor John P. Cooke (Mayo Clinic, then Stanford University, now Houston Methodist Medical Center).
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

12. * The Potential of L-Arginine Study A: Prevention of Plaque Build-Up
Design:
Cholesterol + L-Arginine
Cholesterol
Control 8
weeks
CONTROL
CHOLESTEROL 5 10 15 20 25 30 35 40 45 50 55 60
Carotid intimal plaque area
[% of total intima] *
CHOL.
+ L-ARGININE #
(0)
A. carotis
Results:
This animal study in cholesterol-fed rabbits that was performed by Professor Böger’s research team in Germany showed that dietary supplementation with L-arginine from the beginning slows the development of atherosclerotic plaque by 80%. Rabbits were fed a high cholesterol diet for 8 weeks; their plaque build-up in the carotid artery was about 45%. Another group of rabbits with high cholesterol received L-arginine in drinking water; their plaque build-up was only 9.5%. This study was designed as a prevention study; the animals received L-arginine from the very beginning.
Cholesterol
Cholesterol; treated with L-arginine
-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 4 10 16
weeks
Results: 50
The second study by Professor Böger and his colleagues was different in design. In the first phase, rabbits were fed a high cholesterol diet for 4 weeks. Plaque build-up amounted to about 15% by that time. Then, the animals were randomly assigned to three groups – all groups continued to receive a high cholesterol diet for another 12 weeks. One group received cholesterol-rich food only, the second group received L-arginine in addition, and the third group was treated with the cholesterol-lowering drug, lovastatin. After a total of 16 weeks, plaque build-up was analyzed again. It turned out that L-arginine supplementation completely stopped further plaque growth. The inhibitory effect of the potent cholesterol-lowering drug lovastatin was not as complete as the one of L-arginine. 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
Intimal plaque area
(carotid artery) [%]
-92% 20 10 4 16
weeks
Böger et al., Circulation 1997; 96:

14. The Potential of L-Arginine
Study C: Reversal of Pre-Existing Plaque
Design:
Cholesterol
Cholesterol
Cholesterol + L-Arginine
Cholesterol 10 18 23
weeks
Results: 75
Professor Cooke chose a different design in this animal study. First, all rabbits received a cholesterol-enriched diet for 10 weeks. This caused about 30% plaque build-up in the carotid arteries. At that time, the animals were split into one group that was continued on cholesterol-rich food only for another 13 weeks, and the other group received the same cholesterol-rich food and L-arginine in addition. After 4, 8, and 13 weeks of treatment, animals were analyzed for plaque progression. The results clearly indicate that the build-up of plaque was not only stopped, but reversed by L-arginine. When a subgroup of animals that were treated with L-arginine had the arginine withdrawn after 8 weeks, their plaque growth resumed, and only five weeks later, their plaque size had caught up with the group that had never received L-arginine. This study proved that A) L-arginine can cause regression of pre-existing plaque in the arteries; and B) upon withdrawal of L-arginine plaque progression resumes. Atherosclerosis is a chronic disease that needs continuous treatment; dietary L-arginine acts for prevention of plaque growth, but it does so only for as long as it is taken up with the diet on a continuous basis. 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 10 14 18 16
weeks
Candipan et al., Arterioscler. Thromb. Vasc. Biol. 1996; 16: 44-50

15. 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.
Studies in human subjects have shown that the same vascular protective effects that were found in animal experiments can be reproduced in humans. L-arginine restores arterial elasticity by enhancing endothelial NO-dependent vasodilation. It improves blood flow to important organs and muscles even in patients with severely impaired blood flow. L-arginine improves cerebral autoregulation of blood flow and can thereby enhance memory function of the brain. In athletes like in patients with vascular diseases, L-arginine can help to increase blood flow to the exercising muscles, thereby enabling the muscle to use energy in a more efficient manner and helping recovery of muscle after exercise – the metabolic products like lactic acid are being washed out of the tissues more quickly, and re-oxygenation is accelerated. Many patients with high blood pressure have experienced a reduction of blood pressure levels, sometimes even allowing them to have their antihypertensive drug dosage reduced by their doctors. Supplementation of L-arginine has been shown to improve the clinical symptoms of coronary artery disease, chronic heart failure, peripheral arterial disease, and erectile dysfunction.

16. PRO CONTRA The L-Arginine Paradox
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.
The “L-arginine paradox” has been a term coined to describe the apparent discrepancy between the fact that blood levels of L-arginine appear to be sufficiently high in most patients, and the clinical observation that dietary L-arginine supplementation does improve symptoms of vascular disease. Biochemically, the enzyme NO synthase needs much less L-arginine in order to function properly than what the usual blood levels of this amino acid are. However, such biochemical analyses are being done in the laboratory under experimental conditions, and scientists have put forward the hypothesis that such “in vitro” conditions may not adequately mirror the medical conditions in a patient.

17. ADMA The L-Arginine Paradox:Solution
An endogenous inhibitor of NO synthase displaces L-arginine from the enzyme‘s catalytic site and blocks NO production.
In vitro:
without ADMA
In patients
with high ADMA
100
100 80 80
Indeed, in the 1990’s an endogenous, competitive inhibitor of NO production from L-arginine has been discovered in human blood. This is Asymmetric DiMethylArginine (ADMA) – a molecule that is very similar in structure to L-arginine, that binds to the enzyme NO synthase just like L-arginine, but that cannot be converted into NO, thus inhibiting the enzyme’s activity and reducing NO production rate.
This slide shows on the left the relationship between L-arginine concentration and NO production rate by the enzyme NO synthase. The area shaded in blue marks the usual plasma concentration range of L-arginine in humans. It is apparent that the NO synthesis rate is at its maximum at usual plasma levels of L-arginine – thus, adding more L-arginine from a dietary supplement should not work.
The graph to the right depicts the true situation in vivo: In the presence of the competitive inhibitor, ADMA, the curve is shifted to the right (this is a very basic characteristic of any competitive inhibitor of any enzyme throughout biochemistry). Now, the NO synthesis rate at usual L-arginine plasma concentration is only some 50-60% of its maximum, so that an increase of L-arginine blood levels will increase the synthesis rate of NO. Conclusion: The presence of ADMA in human blood explains why L-arginine improves NO-mediated vascular function. The presence of ADMA explains the apparent “L-arginine paradox”. 60 60
NO Synthesis Rate [%]
NO Synthesis Rate [%]
50%
50% 40 40 20 20 K m =
2.9 µM
.01 .1 1 10
100
1000
.01 .1 1 10
100
1000
L-Arginine [µmol/L]
L-Arginine [µmol/L]

18. ADMA Predicts Mortality
3,320 study participants from the general population;
10 years of follow-up
Total mortality
HR = 1.21 ( ) per SD increment (0.13 µmol/l)
P = 0.003
Multivariate model adjusted
for established CV risk
factors included in the FRS
plus BNP, renin, Hcys, CRP,
urinary albumin excretion.
Multiple large, prospective trials have accumulated evidence that ADMA is a diagnostic marker of the risk of cardiovascular events and mortality in humans. These studies have been performed in multiple countries in a total of more than 20,000 people with 8 – 25 years of follow-up. This slide shows the association between ADMA blood levels and mortality risk during 10 years of follow-up in the famous Framingham Heart Study. The bold line shows that mortality risk increases with increasing ADMA; this risk association is independent of all traditional risk factors, such as blood pressure, cholesterol, smoking status, diabetes status, sex, C-reactive protein, and more. In fact, a minor increase in plasma ADMA concentration from 0.5 to 0.8 µmol/l results in a 50% increase in mortality risk over the subsequent 10 years.
The Framingham Offspring Study
Böger et al. Circulation 2009

19. Normal L-Arginine/ADMA Balance:
The L-Arginine / ADMA Balance NO
Normal L-Arginine/ADMA Balance:
> 100 : 1
L-Arginine
ADMA
Data from the Framingham Study also show that the ratio of L-arginine to ADMA is important. When both are in a physiological balance (which, numerically, is at 100:1 or higher), the NO synthase is able to generate NO. Any reduction in L-arginine or increase in ADMA will reduce this ratio to levels below 100, and result in an increased cardiovascular risk.
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 1998
Leong et al. ATVB 2008 …

20. The L-Arginine / ADMA Balance
0,5 1
1,5 2
2,5 3
3,5 4 Q1 Q2 Q3 Q4
ADMA Quartiles
L-Arginine
Quartiles
Hazard Ratios for Mortality (Multivariable Model)
L-arginine
ADMA
< 30
L-arginine
ADMA
> 100
This graph depicts the original data from the Framingham Heart Study to prove what was shown schematically in the preceding slide. When ADMA is low and L-arginine is high, the ratio is 100:1 or above, and mortality risk is low. Any decrease in L-arginine or any increase in ADMA likewise cause a reduction in L-arginine/ADMA ratio, which is associated with an increased mortality risk. In this study, an L-arginine/ADMA ratio of 30 or lower was associated with a 3.5-fold excess in mortality risk.
4th
3rd
2nd
1st
2nd
3rd
1st
4th
The Framingham Offspring Study
Böger et al. Circulation 2009

21. 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!
A dried blood spot test has been developed to facilitate measurement of L-arginine and ADMA and thus allow to calculate the L-arginine/ADMA ratio in any individual. The test, which is patented in the US and in Europe, is being submitted for FDA approval. It can be used in clinical field studies now, and it will be available in the near future for diagnostic use in the US.

22. Inventor of Arginine Cardio Senior Medical and Scientific Advisor
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.
Normal range for ADMA: 0.2 – 0.7 µmol/l.
Low (<0.2)
Highly elevated
(> 1.0)
Normal
(0.2 – 0.7)
Professor Böger from Hamburg, Germany, who invented this test, has performed an epidemiological survey with the test. The results show that 67% of individuals who participated had high ADMA levels – justifying the prescription of a dietary L-arginine supplement.
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

23. The Controversies of L-Arginine
Controversy A: L-Arginine has a short half-life
Professor Böger has also spent 20+ years of research on L-arginine supplementation. His studies show that L-arginine alone is not suitable as a dietary supplement because of its short half-life in blood. With a mean half-life of only about 80 minutes, pure L-arginine must be ingested every 3-4 hours to maintain stable, elevated blood levels throughout the day (and night!). For prevention, a stable, elevated L-arginine level in blood is required, because the study showed that the vascular effects of L-arginine very closely followed its plasma concentration time course.
Many doctors claim that clinical studies with L-arginine have not unequivocally proven its benefits. This is correct. However, careful reading unveils that many studies with L-arginine had major flaws in study design:
Most studies have used pure L-arginine for dietary supplementation. Despite its short half-life, once-daily or twice-daily dosing was performed … which is clearly not enough to maintain elevated L-arginine blood levels.
All studies have included patients irrespectively of their ADMA blood levels. However, clinical and experimental research proved that individuals with elevated ADMA profit more from dietary L-arginine than those whose ADMA is low or normal. No statin drug would have been prescribed to individuals with low cholesterol, no anti-hypertensive drug would have been prescribed to individuals with low or normal blood pressure.
„The vascular effects of L-arginine are closely correlated with its plasma concentrations.
[…] Terminal elimination half-life for L-arginine was calculated as ± 9.1 min and
79.5 ± 9.3 min after intravenous and oral administration, respectively.“

24. 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
Placebo
Arginine
baseline
6 months 20 40 60 80
100
120
L-arginine [µmol/l]
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.
This clinical study by Schulman and co-workers received high media coverage because it was sponsored by the NIH and its results were published in the Journal of the American Medical Association. 150 patents who had had a myocardial infarction were randomly assigned to L-arginine or placebo for 6 months. The study was terminated early because of a presumed over-mortality in the L-arginine group
However:
None of the deaths could be causally related to L-arginine.
The L-arginine blood levels were not higher in the L-arginine group than in the placebo group after 6 months of treatment.
The major endpoint of the study was change in cardiac ejection fraction, which is not directly related to NO function. Thus, it is unclear how failure to reach the primary endpoint is supposed to prove lack of efficiency of L-arginine.
Schulman et al., J. Am. Med. Assoc. 2006; 295: 58-64

25. 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.
This study by Professor John Cooke and his team at Stanford University again failed to prove clinical benefit of L-arginine supplementation. Patients with peripheral arterial disease of the legs were treated for 6 months with L-arginine or placebo. Unexpectedly, L-arginine did not improve walking distance.
However:
There was no increase in L-arginine or L-citrulline blood levels in this study; by contrast, the blood levels of L-ornithine increased. These data show that pure L-arginine again failed to build up significant plasma levels when administered twice daily in human subjects. Further, pure L-arginine is known to be converted to L-ornithine by the enzyme arginase in the intestinal mucosa, which results in a limited bioavailability of L-arginine.
The investigators did not measure ADMA in their patients although preceding studies had shown that not all patients with arterial disease have high ADMA levels.
Thus, this study shows once again that L-arginine cannot be effective in improving clinical symptoms of arterial disease when patients are poorly selected, and when no provisions are taken to ensure stable elevated L-arginine levels in blood over prolonged periods of time.
Wilson et al., Circulation 2007; 116:

26. 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.
After animal experiments and early clinical studies had revealed that dietary L-citrulline causes an elevation of L-arginine blood levels, too, Professor Böger and his team performed this clinical trial to show that a combination of L-arginine plus L-citrulline leads to a higher and more sustained elevation of L-arginine in human blood than L-arginine alone. After 12 hours – which is the relevant time point for twice daily intake – plasma L-arginine was still significantly elevated when combined L-arginine plus L-citrulline was administered, whereas L-arginine blood levels were completely back to baseline after administration of L-arginine only.

27. 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
Kinetic modeling in this slides reveals the significance of this finding for long-term dosing of L-arginine plus L-citrulline. With each dose, L-arginine blood levels build up higher. Actual plasma concentration measurement after six weeks of twice daily administration proved that the kinetic model exactly mirrored clinical reality: After six weeks, pre-dose L-arginine level had doubled (from a mean 80 µmol/l at baseline to 160 µmol/l). This graph shows why an arginine product must be sustained in the system for at least 12 hours, such as in Arginine Cardio. Arginine Cardio was designed for a 12 hour sustained titration of converting arginine into Nitric Oxide, none of the current products can do that, including Proargi9 plus and L-arginine plus. With each dose of Arginine Cardio, L-arginine blood levels build up higher. Actual plasma concentration measurement after six weeks of twice daily administration proved that the kinetic model exactly mirrored clinical reality: After six weeks, pre-dose L-arginine level had doubled (from a mean 80 µmol/l at baseline to 160 µmol/l).

28. 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.
In conclusion of everything mentioned before, an individual’s need for L-arginine is determined by
the baseline L-arginine concentration in plasma
The concentration of ADMA, a cardiovascular risk marker and inhibitor of nitric oxide, in plasma
The presence or absence of cardiovascular disease or risk factors
L-Arginine Cardio is an L-arginine /L-citrulline formula specifically designed to help prevent or treat heart disease. It has been proven in scientific studies to overcome the inhibitory effects of ADMA on nitric oxide production. It is the only L-arginine supplement for heart health that is fully supported by scientific data.
Besides the use of combined L-arginine plus L-citrulline in their optimal proportion (as is provided by Arginine Cardio), it is useful to identify each patient’s individual needs by measuring L-arginine and ADMA blood levels. The best time to do this is in 90 days from the start of taking Arginine Cardio. At that time it can be determined if the patient is absorbing L-arginine efficiently. We can send the kits out and you can take the blood sample and send it to us and we can process the blood sample and send the results to you. The cost is $ Soon we will be able to get the results from a laboratory location in the US. Some of your patients should have the tests done before the L-arginine supplementation, if your current tests cannot reveal their current state as to cardiovascular disease. If a patient has a family history of cardiovascular disease and problems he or she is a good candidate for the test ahead of the supplementation.
Assess L-arginine and ADMA
Supplement with Arginine Cardio

29. 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 C
Folic Acid
Arginine Cardio is more than just an arginine supplement. It is the supplement with the highest ratio of L-arginine to L-citrulline, which guarantees its long-term action and efficacy in enhancing blood flow.
However, in designing the formula we have gone far beyond that:
We have added a total of 10 more ingredients which were specifially selected based on scientific data proving that these ingredients support the heart’s function. Arginine Cardio not only increases the blood flow to the myocardium, it also helps the heart muscle cells to utilize the nutrients and oxygen that come with the blood stream into energy, into contractile force.