Short-Term Supplementation of Sodium Nitrate vs. Sodium Chloride Increases Homoarginine Synthesis in Young Men Independent of Exercise
Creators: name: Tsikas, Dimitrios
name: Maassen, Norbert
name: Thorns, Antonie
name: Finkel, Armin
name: Lützow, Moritz
name: Röhrig, Magdalena Aleksandra
name: Blau, Larissa Sarah
name: Dimina, Laurianne
name: Mariotti, François
name: Beckmann, Bibiana
name: Shushakov, Vladimir
name: Jantz, Mirja
Publisher: name: Basel : Molecular Diversity Preservation International
Year: 2022
Subjects: subject: amino acids
subject: guanidinoacetate
subject: homoarginine
subject: inorganic nitrate
subject: malondialdehyde
subject: oxidative stress
subject: power
subject: sports
subject: supplementation
subject: Dewey Decimal Classification::500 | Naturwissenschaften::570 | Biowissenschaften, Biologie
subject: Dewey Decimal Classification::500 | Naturwissenschaften::540 | Chemie

description: The aim of the study was to investigate the effects of short-term oral administration of inorganic nitrate (NaNO3; n = 8) or placebo (NaCl; n = 9) (each 0.1 mmol/kg body weight/d for 9 days) on plasma amino acids, creatinine, and oxidative stress in healthy young men. At baseline, the plasma concentrations of amino acids did not differ between the groups. At the end of the study, the plasma concentrations of homoarginine (hArg; by 24%, p = 0.0001), citrulline and ornithine (Cit/Orn; by 16%, p = 0.015), and glutamine/glutamate (Gln/Glu; by 6%, p = 0.0003) were higher in the NaNO3 group compared to the NaCl group. The plasma concentrations of sarcosine (Sarc; by 28%, p &lt; 0.0001), tyrosine (by 14%, p = 0.0051), phenylalanine (by 8%, p = 0.0026), and tryptophan (by 8%, p = 0.0047) were lower in the NaNO3 group compared to the NaCl group. These results suggest that nitrate administration affects amino-acid metabolism. The arginine/glycine amidinotransferase (AGAT) catalyzes two reactions: (1) the formation of l-homoarginine (hArg) and l-ornithine (Orn) from l-arginine (Arg) and l-lysine (Lys): Arg + Lys &lt;−&gt; hArg + Orn, with equilibrium constant Kharg; (2) the formation of guanidinoacetate (GAA) and Orn from Arg and glycine (Gly): Arg + Gly &lt;−&gt; GAA + Orn, with equilibrium constant Kgaa. The plasma Kgaa/KhArg ratio was lower in the NaNO3 group compared to the NaCl group (1.57 vs. 2.02, p = 0.0034). Our study suggests that supplementation of inorganic nitrate increases the AGAT-catalyzed synthesis of hArg and decreases the N-methyltransferase-catalyzed synthesis of GAA, the precursor of creatine. To our knowledge, this is the first study to demonstrate elevation of hArg synthesis by inorganic nitrate supplementation. Remarkably, an increase of 24% corresponds to the synthesis capacity of one kidney in healthy humans. Differences in the association between plasma concentrations of amino acids in the NaNO3 and NaCl groups suggest changes in amino-acid homeostasis. Plasma concentrations of the oxidative stress marker malondialdehyde (MDA) did not change after supplementation of NaNO3 or NaCl over the whole exercise time range. Plasma nitrite concentration turned out to be a more discriminant marker of NaNO3 ingestion than plasma nitrate (area under the receiver operating characteristic curve: 0.951 vs. 0.866, p &lt; 0.0001 each).