Cited by 241Peripheral Artery Disease ManagementNitric Oxide and Endothelin EffectsCardiovascular Health and Disease Prevention

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l -Arginine Supplementation in Peripheral Arterial Disease: No Benefit and Possible Harm

Wilson, Andrew M., Harada, Randall, Nair, Nandini, Balasubramanian, Naras, Cooke, John P.·2007·Circulation

DOI 10.1161/circulationaha.106.683656

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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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Authors: Wilson, A. M., Harada, R., Nair, N., Balasubramanian, N., & Cooke, J. P.
Affiliations: Stanford Medicine (US)
ORCID: Wilson, Andrew M.
Nair, Nandini
Cooke, John P.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2007-07-10
Volume: 116
Issue: 2
Pages: 188-195
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.106.683656
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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l -Arginine Supplementation in Peripheral Arterial Disease: No Benefit and Possible Harm

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