The Pharmacodynamics of L-Arginine
Open accessAbstract
L-arginine is a precursor for nitric oxide (NO) synthesis. NO is a ubiquitous mediator that is formed by a family of enzymes named NO synthases. In the brain, NO acts as a neurotransmitter; in the immune system, NO acts as a mediator of host defense; and in the cardiovascular system, NO mediates the protective effects of the intact endothelium, acting as a vasodilator and endogenous antiatherogenic molecule. About 5 g of L-arginine is ingested each day in a normal Western diet. L-arginine plasma levels are not significantly reduced in most disease conditions, except 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 subjects 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 of subjects receiving L-arginine than those receiving placebo. Recently it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of L-arginine metabolism by NO synthase, may determine a subject's response to L-arginine supplementation. L-arginine appears to exert no effect in subjects with low ADMA levels, whereas in subjects with high ADMA levels, L-arginine restores the L-arginine/ADMA ratio to normal levels 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.
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The ratio of l-arginine to ADMA appears to be a better indicator of cardiovascular risk.
“As pointed out above, the ratio of l-arginine to ADMA appears to be a better indicator of cardiovascular risk (28, 103, 104, 606, 1050).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [103]
When ADMA levels are low, effects of exogenous l-arginine are limited; therapy seems more beneficial in patients with higher ADMA levels, in which treatment increases l-arginine/ADMA ratios and improves endothelial function.
“It has been noted that when ADMA levels are low, the effects of exogenous l-arginine are limited; however, the therapy seems to be more beneficial in patients with higher ADMA levels, in which the treatment increases the l-arginine/ADMA ratios and improves endothelial function (103).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [103]
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- Authors
- Böger, R. H.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Böger, Rainer H.
- ORCID
- Böger, Rainer H.
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 137
- Issue
- 6
- Pages
- 1650S-1655S
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2115875498
- Cited by
- 221
- References
- 61
- Citations by year
- 2026: 14 · 2025: 9 · 2024: 11 · 2023: 12 · 2022: 10 · 2021: 10 · 2020: 14 · 2019: 12 · 2018: 14 · 2017: 11 · 2016: 16 · 2015: 11 · 2014: 12 · 2013: 13 · 2012: 12
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Herzstiftung
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology › Biochemical effects in animals
- Keywords
- L-arginine, nitric oxide, nitric oxide synthase, asymmetric dimethylarginine, endothelial function, cardiovascular disease, dietary supplementation, pharmacodynamics, dose-response relationship, end-stage renal disease, vasodilation, antiatherogenic effects
- MeSH terms
- Arginine, Cardiovascular Diseases, Humans, Nitric Oxide
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