Dr. Ann de Wees Allen is one of only three arginine biochemists in the world that has actually researched Larginine for 10-20 years. A safe Larginine product must be formulated by an arginine biochemist to prevent unacceptable Larginine formulations. The scientist who designed L-Arginine formulas must be proficient in the field of bio-chemistry and the study of metabolic pathways taken by larginine, NO, GH and anti-aging hormones.
If you are considering purchasing a Larginine formula other than LarginineM2, we suggest you research the product and find out if it has had 10 years of safe use in humans. Inappropriate forms of arginine can not only block the benefits of Larginine, but can also cause serious side effects.
According to independent studies, L-citrulline is not an appropriate ingredient in an L-arginine formulation:
“Conversion of citrulline to arginine occurs primarily within the kidney. Increased mortality (death) risk ratio observed after citrulline is included in the Cox regression analysis reflects the effects of renal dysfunction on arginine bioavailability.”
“Citrulline levels trended higher in Sickle Cell Disease (SCD) patients with pulmonary hypertension and correlated with rising creatinine levels (Spearman = 0.51; P<.001).”
Dysregulated Arginine Metabolism, Hemolysis-Associated Pulmonary Hypertension, and Mortality in Sickle Cell Disease. JAMA.2005;294:81-90
The use of Citrulline in an L-arginine formulation causes inherent problems, including depletion of L-arginine.
According to The Arginine Paradox (Folia Pharmacol. Japan Vol. 119 7-14:2002 Department of Pharmacology, Teikyo University School of Medicine) :
L-Arginine has attracted major interest because it has been identified as the natural substrate of nitric oxide synthase and is now recognized as a major player in the regulation of biological function.
The arginine paradox refers to the phenomenon that exogenous L-arginine causes NO-mediated biological effects despite the fact that nitric oxide synthases (NOS) are theoretically saturated with the substrate L-arginine.
There have been several explanations for this phenomenon, although none of them can explain the arginine paradox fully:
- L-arginine-induced insulin, which has vasodilatory actions.
- Neither extracellular nor intracellular concentration determines the NOS activity but rather the L-arginine amount transported across the plasma membrane may do so.
- Endogenous NOS inhibitors reduce the enzyme sensitivity to L-arginine. These inhibitors include, NG, NG-dimethyl-L-arginine, L-citrulline, argininosuccinic acid and agmatine.
- Intracellular L-citrulline, an NOS product, is a potent inhibitor of NOS so that the cells may need extra L-arginine to compete with L-citrulline inhibition .
Further evidence against the use of L-citrulline is the the 2005 Alternative Medicine Review reported that L-arginine, and not L-citrulline is the appropriate amino acid for oral supplementation:
“The amino acid L-arginine is the preferred substance for oral supplementation to enhance nitric oxide synthesis.”
“The mechanism by which L-arginine works is by providing the substrate for nitric oxide synthesis in vascular endothelial cells, which in turn creates cyclic GMP in the underlying vascular smooth muscle cells.”
“L-arginine overcomes ADMA's nitric oxide inhibition.”
“Some supplement companies are marketing L-citrulline – a by-product of the arginine-to-nitric oxide pathway – as a substance to increase nitric oxide synthesis in vascular endothelial cells.”
“Citrulline does not directly convert to nitric oxide, but instead is recycled to L-arginine (an ATP-dependent process), which then converts to nitric oxide.”
The Nobel Prize in Physiology/Medicine 1998 was awarded to doctors Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad for their discoveries concerning "the nitric oxide as a signalling molecule in the cardiovascular system".
As reported in the 2005 Alternative Medicine Review , “Ferid Murad, MD, PhD, Nobel-prize winner for his research on nitric oxide, has said the use of L-citrulline to increase nitric oxide is only marginally effective .”
The Alternative Medicine Review conclusion is . . .toss out the citrulline, and utilize
L-arginine. “Change bad medicine to good medicine and ignore the hype.”
© 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 4 December 2005.
These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease. For counsel on injuries or disease, we recommend that you see a health professional who can help you make responsible decisions concerning your specific health concerns.
