Sickle cell, clinical trials at NIH, calling L-Arginine a "drug".

http://www.clinicaltrials.gov/ct/gui/show/NCT00056433
Purpose

>>Patients with sickle cell disease have abnormal hemoglobin (the protein in red blood cells that carries oxygen to the body). This abnormality causes red blood cells to take on a sickle shape, producing disease symptoms. Fetal hemoglobin, a type of hemoglobin present in fetuses and babies, can prevent red cells from sickling. The drug hydroxyurea increases fetal hemoglobin production in patients with sickle cell disease by making a molecule called nitric oxide. The drugs L-arginine and Sildenafil (Viagra) increase the amount or the effect of nitric oxide. This study will evaluate:<<

Edited to say, this is me speaking here: They are referring to L-Arginine as a drug.... therefore, one could conclude that it would not be on every Walmart shelf, every GNC, every internet health food site, and in some doctors office as a no script product. Another safe and therapeutic bioflavonoid that affects NO synthesis is pycnogenol, (Grape Seed Extract) and if I find anything on it and sickle cell, I will post it in this thread. Note the date on this paper.

To explain how this can be.... a paper from the NIH
Comment in:
JAMA. 2005 Nov 16;294(19):2432-3; author reply 2433-4.
JAMA. 2005 Nov 16;294(19):2433; author reply 2433-4.

Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease.

Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V, Hazen SL, Vichinsky EP, Morris SM Jr, Gladwin MT.

Department of Emergency Medicine, Children's Hospital and Research Center at Oakland, CA 94609, USA. claudiamorris@comcast.net

CONTEXT: Sickle cell disease is characterized by a state of nitric oxide resistance and limited bioavailability of l-arginine, the substrate for nitric oxide synthesis. We hypothesized that increased arginase activity and dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary hypertension, and patient outcomes.

OBJECTIVE: To explore the role of arginase in sickle cell disease pathogenesis, pulmonary hypertension, and mortality.

DESIGN: Plasma amino acid levels, plasma and erythrocyte arginase activities, and pulmonary hypertension status as measured by Doppler echocardiogram were prospectively obtained in outpatients with sickle cell disease. Patients were followed up for survival up to 49 months.

SETTING: Urban tertiary care center and community clinics in the United States between February 2001 and March 2005.

PARTICIPANTS: Two hundred twenty-eight patients with sickle cell disease, aged 18 to 74 years, and 36 control participants.

MAIN OUTCOME MEASURES: Plasma amino acid levels, plasma and erythrocyte arginase activities, diagnosis of pulmonary hypertension, and mortality.

RESULTS: Plasma arginase activity was significantly elevated in patients with sickle cell disease, with highest activity found in patients with secondary pulmonary hypertension. Arginase activity correlated with the arginine-ornithine ratio, and lower ratios were associated with greater severity of pulmonary hypertension and with mortality in this population (risk ratio, 2.5; 95% confidence interval , 1.2-5.2; P = .006). Global arginine bioavailability, characterized by the ratio of arginine to ornithine plus citrulline, was also strongly associated with mortality (risk ratio, 3.6; 95% CI, 1.5-8.3; P<.001). Increased plasma arginase activity was correlated with increased intravascular hemolytic rate and, to a lesser extent, with markers of inflammation and soluble adhesion molecule levels. CONCLUSIONS: These data support a novel mechanism of disease in which hemolysis contributes to reduced nitric oxide bioavailability and endothelial dysfunction via release of erythrocyte arginase, which limits arginine bioavailability, and release of erythrocyte hemoglobin, which scavenges nitric oxide. The ratios of arginine to ornithine and arginine to ornithine plus citrulline are independently associated with pulmonary hypertension and increased mortality in patients with sickle cell disease.

PMID: 15998894

few other commonly available supplements that are safe, non-toxic and cheap.

1: Nutrition. 2000 May;16(5):330-8. Related Articles, Links


Comment in:
Nutrition. 2000 Nov-Dec;16(11-12):1098-100.

Sickle cell anemia: a potential nutritional approach for a molecular disease.

Ohnishi ST, Ohnishi T, Ogunmola GB.

Philadelphia Biomedical Research Institute, King of Prussia, Pennsylvania 19406, USA. stohnishi@aol.com

A certain population of red blood cells in patients with sickle cell anemia has an elevated density and possesses an abnormal membrane. These "dense cells" have a tendency to adhere to neutrophils, platelets, and vascular endothelial cells, and, thus, they could trigger vasoocclusion and the subsequent painful crisis from which these patients suffer. We developed a laboratory method of preparing such dense cells and found that nutritional antioxidant supplements, hydroxyl radical scavengers, and iron-binding agents could inhibit the formation of dense cells in vitro. The concentrations at which effective nutritional supplements could inhibit dense cell formation by 50% were 4.0 mg/mL for aged garlic extract, 0.38 mg/mL for black tea extract, 0.13 mg/mL for green tea extract, 0.07 mg/mL for Pycnogenol, 930 microM for alpha-lipoic acid, 270 microM for vitamin E, 45 microM for coenzyme Q(10), and 32 microM for beta-carotene. Both an ex vivo study and a pilot clinical trial demonstrated that a cocktail consisting of daily doses of 6 g of aged garlic extract, 4-6 g of vitamin C, and 800 to 1200 IU of vitamin E may indeed be beneficial to the patients.

Publication Types:
Clinical Trial
Controlled Clinical Trial

PMID: 10793299