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This is the story…

  • of the machinery that keeps your heart and blood vessels healthy
  • of why this machinery becomes worn-out with advancing age
  • of what modern science tells you to do to rejuvenate your heart and blood vessels

Let us inspire you!

When you were born …

your blood vessels were equipped with a sophisticated machinery to produce a miracle molecule that keeps your heart and blood vessels smooth, flexible, and healthy – the nitric oxide (NO) machinery
By that time and throughout all your childhood and adolescence, the NO machinery worked at full pace – comparable to the power of a Porsche car, keeping your heart healthy and powerful.
The Porsche in your blood vessels …

Heart attack – the major cause of mortality in the U.S.

About 600,000 people die of heart disease in the United States every year – that’s 1 in every 4 deaths.
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.

Heart attack – CDC recommendations for prevention

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 else can you do for prevention of heart attack?

The CDC recommend reduction of risk factors

Reduce cholesterol, reduce blood pressure, go exercising, quit smoking, reduce weight

All cardiovascular risk factors impair endothelium-dependent, nitric oxide (NO)-mediated vascular function.

Impaired NO-mediated vasodilation is considered by leading cardiologists as the unifying mechanism by which cardiovascular risk factors lead to the progression of heart disease.
Therefore, improving NO-mediated vasodilation confers the chance to add more protection from heart disease.

NO is formed from L-arginine –
Multiple experimental studies prove its beneficial effects

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

L-arginine –
animal studies prove anti-atherosclerotic effects

Study A: Prevention of Plaque Build-Up

L-arginine –
animal studies prove anti-atherosclerotic effects

Study B: Stopping the Progression of Plaque Build-Up

L-arginine –
animal studies prove anti-atherosclerotic effects

Study C: Reversal of Pre-Existing Plaque

Supplementation of humans with L-arginine
yields variable results

Positive studies:
  • Significant improvement in exercise endurability in patients with stable angina (6g/day) (Ceremuzynski et al.; Am J Cardiol 1997; 80:331-3)
  • Improved blood flow, enhanced walking distance, no side effects in CHF patients (5 – 12 g/day) (Rector et al.; Circulation. 1996;93: 2135-41)
  • Improved exercise capacity, no side effects in CHF patients (9g/day) (Bednarz et al.; Kardiol Pol. 2004; 60:348-53)
  • Improved exercise capacity, no side effects in patients with stable angina (6g/day) (Bednarz et al.; Int J Cardiol. 2000;75: 205-10)

Supplementation of humans with L-arginine
yields variable results

Negative studies:
VINTAGE MI Study:
  • 153 post MI (9g/day)
  • Schulman et al.; JAMA. 2006;295:58-64 No change in EF.
  • Study was ended early by the DSMB due to excess mortality in patients in the L-arginine group (6 deaths vs. 0)
Criticisms:
  • None of the deaths was related to study medication Arginine supplementation did not increase arginine plasma levels
NO PAIN Study:
  • 133 patients with peripheral arterial disease Less improvement in walking distance than with placebo
Criticisms:
  • Arginine supplement did not increase NO production, but … … it increased ornithine levels (i.e., the product of arginase metabolism of L-arginine)
  • Wilson et al.; Circulation. 2007;116:188-95

Supplementation of humans with L-arginine
yields variable results

Summary:
  • First generation arginine supplements yielded variable results in human trials;
  • Results were highly dependent on patient selection;
  • Arginine supplements failed to elevate L-arginine plasma levels, or they failed to improve NO production;
  • Pharmacokinetics of L-arginine have not been taken into account in study design.
This means that the shortness duration of the effect of L-arginine was not respected in the studies, e.g., by multiple daily doses. Measurements of arginine in blood showed that the levels had remained low even after supplement intake.

Second-generation L-arginine supplements –
Prolonged half-life supports sustained effects

Prolongation of the half-life of L-arginine by adding L-citrulline

Second-generation L-arginine supplements –
Prolonged half-life supports sustained effects

Prolongation of the half-life of L-arginine by adding L-citrulline

Second-generation L-arginine supplements

Advantage of combined L-arginine plus L-citrulline

Problems that remained to be solved:

Multiple mechanisms may cause endothelial dysfunction –
L-arginine cannot address them all

Problems that remained to be solved:
For second generation L-arginine supplements:

Multiple mechanisms may cause endothelial dysfunction –
L-arginine cannot address them all

Problems that remained to be solved:
For second generation L-arginine supplements:

Multiple mechanisms may cause endothelial dysfunction –
L-arginine alone cannot address them all

Oxidative stress is increased and inactivates NO

In healthy blood vessels, NO released from the endothelium causes relaxation of vascularsmooth muscle cells; the blood vessel dilates.
In healthy blood vessels, NO released from the endothelium causes relaxation of vascularsmooth muscle cells; the blood vessel dilates.

Third generation L-arginine:
Nitric Oxide Plus

Its effect on upregulation of NO synthase gene

Its effect on upregulation of NO synthase gene

In Summary:  Nitric Oxide Plus 24/7 has a superior effect
on increasing the production of biologically active NO

In summary:

Multiple mechanisms may cause endothelial dysfunction – L-arginine alone cannot address them all, but Nitric Oxide Plus can

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Nitric Oxide – the Miracle Molecule.

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