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l -Arginine Supplementation in Peripheral Arterial Disease: No Benefit and Possible Harm
Abstract
Background— l -Arginine is the precursor of endothelium-derived nitric oxide, an endogenous vasodilator. l -Arginine supplementation improves vascular reactivity and functional capacity in peripheral arterial disease (PAD) in small, short-term studies. We aimed to determine the effects of long-term administration of l -arginine on vascular reactivity and functional capacity in patients with PAD. Methods and Results— The Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) study was a randomized clinical trial of oral l -arginine (3 g/d) versus placebo for 6 months in 133 subjects with intermittent claudication due to PAD in a single-center setting. The primary end point was the change at 6 months in the absolute claudication distance as assessed by the Skinner-Gardner treadmill protocol. l -Arginine supplementation significantly increased plasma l -arginine levels. However, measures of nitric oxide availability (including flow-mediated vasodilation, vascular compliance, plasma and urinary nitrogen oxides, and plasma citrulline formation) were reduced or not improved compared with placebo. Although absolute claudication distance improved in both l -arginine- and placebo-treated patients, the improvement in the l -arginine-treated group was significantly less than that in the placebo group (28.3% versus 11.5%; P =0.024). Conclusions— In patients with PAD, long-term administration of l -arginine does not increase nitric oxide synthesis or improve vascular reactivity. Furthermore, the expected placebo effect observed in studies of functional capacity was attenuated in the l -arginine-treated group. As opposed to its short-term administration, long-term administration of l -arginine is not useful in patients with intermittent claudication and PAD.
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“Soon after its discovery in cells and tissue, ADMA was recognized as an important marker for cardiovascular disease progression (656, 829, 961, 1011, 1053, 1068).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1011]
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Metadata
- Authors
- Wilson, A. M., Harada, R., Nair, N., Balasubramanian, N., & Cooke, J. P.
- Affiliations
- Stanford Medicine (US)
- Venue
- Circulation
- Published
- 2007-07-10
- Volume
- 116
- Issue
- 2
- Pages
- 188-195
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2000796869
- Cited by
- 241
- References
- 48
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 7 · 2020: 14 · 2019: 9 · 2018: 11 · 2017: 24 · 2016: 15 · 2015: 13 · 2014: 13 · 2013: 12 · 2012: 26
- FWCI
- 16.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Royal Australasian College of Physicians
- National Health and Medical Research Council
- National Medical Research Council
- National Heart, Lung, and Blood Institute (R01 HL-63685, R01HL075774, T32HL007708, R01HL063685, P50HL083800)
- National Institute of Allergy and Infectious Diseases (P01AI050153, P01AI50153)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- arginine supplementation, peripheral arterial disease, intermittent claudication, nitric oxide, endothelial function, flow-mediated dilation, vascular compliance, citrulline, claudication distance, long-term supplementation, placebo effect
- MeSH terms
- Aged, Arginine, Brachial Artery, Female, Humans, Intermittent Claudication, Male, Middle Aged, Placebos, Prospective Studies, Peripheral Vascular Diseases, Patient Selection, Nitric Oxide Synthase, Dietary Supplements, Racial Groups
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