A Slow- Compared with a Fast-Release Form of Oral Arginine Increases Its Utilization for Nitric Oxide Synthesis in Overweight Adults with Cardiometabolic Risk Factors in a Randomized Controlled Study.
Oral l-arginine supplements can have a beneficial effect on nitric oxide (NO)-related functions when subjects have cardiovascular disease risk factors.



The study was designed to determine the utilization for NO synthesis of oral l-arginine as a function of the cardiometabolic risk and the speed of absorption by comparing immediate-release arginine (IR-Arg), as in supplements, and sustained-release arginine (SR-Arg), which mimics the slow release of dietary arginine.



In a randomized, single-blind, 2-period crossover, controlled trial (1 wk of treatment, >2 wk of washout), using [(15)N-(15)N-(guanidino)]-arginine for the first morning dose, we compared the bioavailability (secondary outcome) and utilization for NO synthesis (primary outcome) of 1.5 g IR- and SR-Arg 3 times/d in 12 healthy overweight [body mass index (BMI; in kg/m(2)): 25-30] adults with the hypertriglyceridemic waist phenotype [HTW; plasma triglycerides (TGs): >150 mg/dL; waist circumference: >94 cm (men) or >80 cm (women)] and 15 healthy control adults (CON; BMI: 18.5-25; no elevated TGs and waist circumference).



Plasma oral arginine areas under the curve were lower after supplementation with SR-Arg than with IR-Arg (112 ± 52.3 and 142 ± 50.8 μmol ⋅ h/L; P < 0.01). The utilization of oral arginine for NO synthesis was 58% higher in HTW subjects than in CON subjects and higher with SR-Arg than with IR-Arg (P < 0.05 both), particularly in HTW subjects (group-by-treatment interaction, P < 0.05). In HTW subjects administered the SR form, utilization for NO synthesis was 32% higher than with the IR form and 87% higher than in CON subjects who were administered the SR form.



In overweight adults with the HTW phenotype, a slow- compared with a fast-release form of oral arginine markedly favors the utilization of arginine for NO synthesis. The utilization of low-dose, slow-release arginine for NO synthesis is higher in overweight adults with the HTW phenotype than in healthy controls, suggesting that the sensitivity of NO synthesis to the dietary arginine supply increases with cardiometabolic risk. The trial was registered at clinicaltrials.gov as NCT02352740.
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France;
Ambre
A
Deveaux
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France;
Hélène
H
Fouillet
German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; and.
Klaus J
KJ
Petzke
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France;
Dominique
D
Hermier
Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France.
Etienne
E
André
Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France.
Pierre
P
Bunouf
Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France.
Frédérique
F
Lantoine-Adam
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France;
Robert
R
Benamouzig
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France;
Véronique
V
Mathé
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France;
Jean-François
JF
Huneau
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France; francois.mariotti@agroparistech.fr.
François
0000-0002-4516-3853
F
Mariotti
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000453:epidemiology / Q000209:etiology; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D050177:Overweight / Q000150:complications / Q000378:metabolism*; D012307:Risk Factors; D055815:Young Adult
D009569:Nitric Oxide; D001120:Arginine
arginine metabolism; dietary arginine; isotopic methods; metabolic syndrome; nitric oxide