title: Biochemical responses of healthy subjects during dietary supplementation with L-arginine.
abstract: Dietary supplements of L-arginine, a substrate for nitric oxide synthases, may promote formation of nitric oxide and thus may be of clinical benefit. However, the optimal level of L-arginine supplementation is unclear. The objective of this study was to evaluate the response of healthy individuals to increasing doses of L-arginine (as free acid). Twelve healthy subjects were recruited and instructed to take L-arginine for 1-week periods at daily doses of 3, 9, 21, and 30 g. At baseline and at the end of each week, 24-hour urine and fasting blood samples were collected, and weight, diastolic blood pressure, and systolic blood pressure were recorded. Samples were analyzed for L-arginine, L-citrulline, glycine, L-lysine, L-ornithine, asymmetric dimethy L-arginine, symmetric dimethy L-arginine, glucose, insulin (serum), creatinine, cGMP (urine), and total nitrates (serum and urine). Ten subjects reported adverse side effects at initial L-arginine doses of 21 g/day (five subjects) or 30 g/day (five subjects), respectively. Blood pressure and weight did not change during the supplementation period. Of the individual biochemical measures, only L-arginine, glycine, and L-ornithine concentrations changed significantly. The mean concentration of L-arginine reached a peak during supplementation at 9 g/d; however, individuals differed markedly in their response. Availability of L-arginine, relative to that of asymmetric dimethy L-arginine, increased significantly at both 9 g/day and 21 g/day. Mean values indicate that supplementation with 9 g/day of L-arginine, a dose associated with minimal adverse side effects, is sufficient to increase circulating L-arginine concentrations. However, subjects varied widely in their responses, indicating that L-arginine supplementation needs to be tailored to individuals.
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15261, USA. rwe2@pitt.edu
authors.forename: Rhobert W
authors.initials: RW
authors.lastname: Evans
authors.forename: John D
authors.initials: JD
authors.lastname: Fernstrom
authors.forename: Julie
authors.initials: J
authors.lastname: Thompson
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Morris
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
mesh_terms: D001120:Arginine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D001682:Biological Availability; D001769:Blood / Q000187:drug effects / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D002956:Citrulline / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D005998:Glycine / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008239:Lysine / Q000097:blood; D008297:Male; D009952:Ornithine / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; C487735:dimethylarginine; D002956:Citrulline; D001120:Arginine; D009952:Ornithine; D006152:Cyclic GMP; D008239:Lysine; D005998:Glycine