1. L-arginine as dietary supplement for improving microvascular function
Ziva Melik, Polona Zaletel, Tina Virtic, Ksenija Cankar Clin Hemorheol Microcirc. 2017;65(3):205-217. doi: 10.3233/CH-16159.
Background: Reduced availability of nitric oxide leads to dysfunction of endothelium which plays an important role in the development of cardiovascular diseases. Objective: The aim of the present study was to determine whether the dietary supplement L-arginine improves the endothelial function of microvessels by increasing nitric oxide production. Methods: We undertook experiments on 51 healthy male volunteers, divided into 4 groups based on their age and physical activity since regular physical activity itself increases endothelium-dependent vasodilation. The skin laser Doppler flux was measured in the microvessels before and after the ingestion of L-arginine (0.9 g). The endothelium-dependent vasodilation was assessed by acetylcholine iontophoresis and the endothelium-independent vasodilation by sodium nitroprusside iontophoresis. In addition, we measured endothelium-dependent and endothelium-independent vasodilation in 81 healthy subjects divided into four age groups. Results: After the ingestion of L-arginine, the endothelium-dependent vasodilation in the young trained subjects increased (paired t-test, p < 0.05), while in the other groups it remained the same. There were no differences in the endothelium-independent vasodilation after ingestion of L-arginine. With aging endothelium-independent vasodilation decreased while endothelium-dependent vasodilation remained mainly unchanged. Conclusion: Obtained results demonstrated that a single dose of L-arginine influences endothelium-dependent vasodilation predominantly in young, trained individuals.
2. The Renal Safety of L-Carnitine, L-Arginine, and Glutamine in Athletes and Bodybuilders
Dorna Davani-Davari, Iman Karimzadeh, Mohammad Mahdi Sagheb, Hossein Khalili J Ren Nutr. 2019 May;29(3):221-234. doi: 10.1053/j.jrn.2018.08.014. Epub 2018 Oct 16.
One of the major concerns about taking amino acid supplements is their potential adverse effects on the kidney as a major organ involved in the metabolism and excretion of exogenous substances. The aim of this study is to review available data about renal safety of the most prominent amino acid supplements including L-arginine, glutamine and also L-carnitine as well as creatine (as amino acid derivatives) in athletes and bodybuilders. The literature was searched by keywords such as "L-carnitine", "L-arginine", "glutamine", and "kidney injury" in databases such as Scopus, Medline, Embase, and ISI Web of Knowledge. Articles published from 1950 to December 2017 were included. Among 3171, 5740, and 1608 records after primary search in the relevant databases, 8, 7, and 5 studies have been finally included, respectively, for L-carnitine, L-arginine, and glutamine in this review. Arginine appears to have both beneficial and detrimental effects on kidney function. However, adverse effects are unlikely to occur with the routine doses (from 3 to >100 g/day). The risks and benefits of L-carnitine on the athletes' and bodybuilders' kidney have not been evaluated yet. However, L-carnitine up to 6000 mg/day is generally considered to be a safe supplement at least in healthy adults. Both short-term (20-30 g within a few hours) and long-term (0.1 g/kg four times daily for 2 weeks) glutamine supplementation in healthy athletes were associated with no significant adverse effects, but it can cause glomerulosclerosis and serum creatinine level elevation in the setting of diabetic nephropathy. Creatine supplementation (ranged from 5 to 30 g/day) also appears to have no detrimental effects on kidney function of individuals without underlying renal diseases. More clinical data are warranted to determine the optimal daily dose and intake duration of common supplemental amino acids associated with the lowest renal adverse effects in sportsmen and sports women.
3. The pharmacodynamics of L-arginine
Rainer H Böger Altern Ther Health Med. 2014 May-Jun;20(3):48-54.
L-Arginine is a precursor for nitric oxide (NO) synthesis. NO is a ubiquitous mediator that is formed by a family of enzymes called NO synthases (NOSs). In the brain, NO acts as a neurotransmitter; in the immune system, it acts as a mediator of host defense; and in the cardiovascular system, it mediates the protective effects of the intact endothelium, acting as a vasodilator and endogenous, antiatherogenic molecule. About 5 g of L-arginine are ingested each day in a normal Western diet. Plasma levels of L-arginine are not significantly reduced in most diseases, except in end-stage renal failure during hemodialysis treatment. Nonetheless, intravenous or dietary (oral) administration of relatively large doses of L-arginine has been shown to result in enhanced NO formation in individuals with impaired endothelial function at baseline. In several controlled clinical trials, long-term administration of L-arginine has been shown to improve the symptoms of cardiovascular disease. However, in other trials, L-arginine was not beneficial, and in a recent study, the authors reported higher mortality for participants receiving L-arginine than for those receiving placebo. Recently, it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of L-Arginine metabolism by NOS, may determine an individual's response to L-arginine supplementation. L-Arginine appears to exert no effect in individuals with low ADMA levels, whereas in those with high levels, L-arginine restores the L-arginine/ADMA ratio to normal and, thereby, normalizes endothelial function. In conclusion, the effects of L-arginine supplementation on human physiology appear to be multicausal and dose-related. Doses of 3-8 g/d appear to be safe and not to cause acute pharmacologic effects in humans.
