{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:46:36Z","timestamp":1791193596628,"version":"4.1.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2007,7,10]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    <jats:sc>l<\/jats:sc>\n                    -Arginine is the precursor of endothelium-derived nitric oxide, an endogenous vasodilator.\n                    <jats:sc>l<\/jats:sc>\n                    -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\n                    <jats:sc>l<\/jats:sc>\n                    -arginine on vascular reactivity and functional capacity in patients with PAD.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    The Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) study was a randomized clinical trial of oral\n                    <jats:sc>l<\/jats:sc>\n                    -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.\n                    <jats:sc>l<\/jats:sc>\n                    -Arginine supplementation significantly increased plasma\n                    <jats:sc>l<\/jats:sc>\n                    -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\n                    <jats:sc>l<\/jats:sc>\n                    -arginine- and placebo-treated patients, the improvement in the\n                    <jats:sc>l<\/jats:sc>\n                    -arginine-treated group was significantly less than that in the placebo group (28.3% versus 11.5%;\n                    <jats:italic>P<\/jats:italic>\n                    =0.024).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    In patients with PAD, long-term administration of\n                    <jats:sc>l<\/jats:sc>\n                    -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\n                    <jats:sc>l<\/jats:sc>\n                    -arginine-treated group. As opposed to its short-term administration, long-term administration of\n                    <jats:sc>l<\/jats:sc>\n                    -arginine is not useful in patients with intermittent claudication and PAD.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.106.683656","type":"journal-article","created":{"date-parts":[[2007,6,25]],"date-time":"2007-06-25T21:05:01Z","timestamp":1182805501000},"page":"188-195","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":200,"title":["<scp>l<\/scp>\n                    -Arginine Supplementation in Peripheral Arterial Disease"],"prefix":"10.1161","volume":"116","author":[{"given":"Andrew M.","family":"Wilson","sequence":"first","affiliation":[{"name":"From the Division of Cardiovascular Medicine (A.M.W., R.H., N.N., J.P.C.) and Department of Biostatistics (N.B.), Stanford University School of Medicine, Stanford, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Harada","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine (A.M.W., R.H., N.N., J.P.C.) and Department of Biostatistics (N.B.), Stanford University School of Medicine, Stanford, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Nair","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine (A.M.W., R.H., N.N., J.P.C.) and Department of Biostatistics (N.B.), Stanford University School of Medicine, Stanford, Calif."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naras","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine (A.M.W., R.H., N.N., J.P.C.) and Department of Biostatistics (N.B.), Stanford University School of Medicine, Stanford, 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