So I've been doing a bit of reading in Pubmed about Arginine therapy/supplementation and its various drawbacks, esp. for long term administration. It really looks like it does not work. Citrulline, a pre-cursor to Arginine, looks very promising without
any (?) of the drawbacks. Anyone have any experience or words of wisdom to share? I've pasted a few abstracts below. Thanks,
-Malbec
Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):275-90.Click here to read Links
Therapeutic use of citrulline in cardiovascular disease.
L-citrulline is the natural precursor of L-arginine, substrate for nitric oxide synthase (NOS) in the production of NO. Supplemental administration L-arginine has been shown to be effective in improving NO production and cardiovascular function in cardiovascular diseases associated with endothelial dysfunction, such as hypertension, heart failure, atherosclerosis, diabetic vascular disease and ischemia-reperfusion injury, but the beneficial actions do not endure with chronic therapy. Substantial intestinal and hepatic metabolism of L-arginine to ornithine and urea by arginase makes oral delivery very ineffective. Additionally, all of these disease states as well as supplemental L-arginine enhance arginase expression and activity, thus reducing the effectiveness of L-arginine therapy. In contrast, L-citrulline is not metabolized in the intestine or liver and does not induce tissue arginase, but rather inhibits its activity. L-citrulline entering the kidney, vascular endothelium and other tissues can be readily converted to L-arginine, thus raising plasma and tissue levels of L-arginine and enhancing NO production. Supplemental L-citrulline has promise as a therapeutic adjunct in disease states associated with L-arginine deficiencies.
PMID: 17214603
A study in humans has shown that oral administration of L-citrulline at 3.8 g/m2 body
surface, resulted in a 227% peak increase in plasma L-arginine levels at 4 h, compared
with a 90% peak increase with the same dose of L-arginine (43). Furthermore, the area
under the curve plot of L-arginine plasma concentration vs. time was 3 fold larger for L-
citrulline, and the elevation in L-arginine levels was more persistent following L-citrulline
administration. Thus, acute oral administration of L-citrulline appears to be considerably
more efficient raising plasma levels of L-arginine than L-arginine itself. Additionally, a
recent study in children and young adults showed that five oral doses of L-citrulline every
12 hours (1.9 g/m2/dose) for a total dose of 9.5 g/m2 resulted in 57 and 85% increases in
mean plasma levels of L-arginine and L-citrulline, respectively (78).
(Lost the reference to this one, sorry, I'll check it again).
and:
Br J Nutr. 2008 Apr;99(4):855-62. Epub 2007 Oct 22.Click here to read Links
Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study.
Previous experimental studies have highlighted that citrulline (CIT) could be a promising pharmaconutrient. However, its pharmacokinetic characteristics and tolerance to loading have not been studied to date. The objective was to characterise the plasma kinetics of CIT in a multiple-dosing study design and to assess the effect of CIT intake on the concentrations of other plasma amino acids (AA). The effects of CIT loading on anabolic hormones were also determined. Eight fasting healthy males underwent four separate oral loading tests (2, 5, 10 or 15 g CIT) in random order. Blood was drawn ten times over an 8 h period for measurement of plasma AA, insulin and growth hormone (Gh). Urine samples were collected before CIT administration and over the next 24 h. None of the subjects experienced side effects whatever the CIT dose. Concerning AA, only CIT, ornithine (ORN) and arginine (ARG) plasma concentrations were affected (maximum concentration 146 (sem 8) to 303 (sem 11) micromol/l (ARG) and 81 (sem 4) to 179 (sem 10) micromol/l (ORN); time to reach maximum concentration 1.17 (sem 0.26) to 2.29 (sem 0.20) h (ARG) and 1.38 (sem 0.25) to 1.79 (sem 0.11) h (ORN) according to CIT dose). Even at high doses, urinary excretion of CIT remained low ( < 5 %). Plasma insulin and Gh were not affected by CIT administration. Short-term CIT administration is safe and well-tolerated. CIT is a potent precursor of ARG. However, at the highest doses, CIT accumulated in plasma while plasma ARG levels increased less than expected. This may be due to saturation of the renal conversion of CIT into ARG.
PMID: 17953788
