Acute Effects of Inorganic Nitrate Intake on Brachial and Femoral Flow-Mediated Vasodilation, and on Carotid Artery Reactivity Responses: Results of a Randomized, Double-Blinded, Placebo-Controlled Cross-Over Study in Abdominally Obese Men

Smeets, E.; Mensink, Ronald P.; Kleinloog, Jordi P. D.; Joris, Peter J.

doi:10.3390/nu14173560

Cited by 3 publications

(4 citation statements)

References 43 publications

(64 reference statements)

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“…Yet, many issues in this area, including the supplementation of antioxidants and, more recently, the ingestion of inorganic nitrate, remain inconclusive [61][62][63][64]. In a recent study, acute supplementation of nitrate for 4 h compared to chloride did not affect brachial and femoral flow-mediated dilatation, and did not change blood pressure or heart rate in abdominally obese men [65]. This trial did not provide evidence for effects of a single dose of inorganic nitrate on 4 h vascular endothelial function.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Supplementation of Sodium Nitrate vs. Sodium Chloride Increases Homoarginine Synthesis in Young Men Independent of Exercise

Tsikas

Maassen

Thorns

et al. 2022

IJMS

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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 < 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 <−> hArg + Orn, with equilibrium constant Kharg; (2) the formation of guanidinoacetate (GAA) and Orn from Arg and glycine (Gly): Arg + Gly <−> 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 < 0.0001 each).

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Section: Discussionmentioning

confidence: 99%

Short-Term Supplementation of Sodium Nitrate vs. Sodium Chloride Increases Homoarginine Synthesis in Young Men Independent of Exercise

Tsikas

Maassen

Thorns

et al. 2022

IJMS

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“…The hArg-induced effect of supplemented inorganic nitrate is unexpected, and the underlying mechanisms remain to be elucidated. They are unlikely to be dependent upon nitric oxide [61]. Very recently, hArg administration was shown to inhibit atherogenesis by modulating T-cell function [62].…”

Section: Effects Of Drugs On Endogenous Homoarginine Synthesismentioning

confidence: 99%

Homoarginine in health and disease

Tsikas

2022

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of reviewHomoarginine (hArg) is an endogenous, nonproteinogenic amino acid. It is enzymatically synthesized from L-arginine and L-lysine. Low hArg concentrations appear to be a risk factor in the renal and cardiovascular systems. This review discusses advances in-vitro and in-vivo experimental and clinical research on hArg in health and disease.Recent findingsRecent studies indicate that low circulating and low urinary concentrations of hArg are associated with morbidity and worse outcome. Although the biological activities of hArg remain still unexplored, hArg supplementation is intensely investigated as a strategy to increase hArg concentration to reach normal levels in cases of low hArg concentrations. The greatest changes in circulating hArg concentrations are observed during pregnancy and after delivery. In healthy adults, a daily dose of 125 mg hArg seems to be optimum to normalize circulating levels. Short-term supplementation of inorganic nitrate enhances hArg biosynthesis in healthy young men. Apart from hArg supplementation, dietary L-arginine and L-citrulline appear to be a promising alternative.SummaryConsiderable progress has been made in recent years, but hArg remains still enigmatic. Further research is required to explore the biological activities of hArg. Supplementation of hArg or its precursors L-citrulline/L-arginine seem to be promising strategies to prevent and overcome altered hArg synthesis.

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“…Indeed, the classification of obesity has been challenged and includes metabolically unhealthy obesity and metabolically healthy obesity according to the risk of metabolic disorders, such as the incidence of diabetes, dyslipidaemia, cardiovascular diseases and metabolic syndrome (MetS) 5,6 . Moreover, the diagnostic methods have also been updated from a simple calculation of BMI to quantification of visceral fat mass, waist circumference, body fat rate, metabolism‐related serum traits, multimetric indices and so on 5,7 . It is clear that fat distribution and volume play an important role in the alteration of metabolism‐related serum traits and the incidence of metabolic disorders.…”

Section: Introductionmentioning

confidence: 99%

“…5,6 Moreover, the diagnostic methods have also been updated from a simple calculation of BMI to quantification of visceral fat mass, waist circumference, body fat rate, metabolism-related serum traits, multimetric indices and so on. 5,7 It is clear that fat distribution and volume play an important role in the alteration of metabolism-related serum traits and the incidence of metabolic disorders. Furthermore, there is an urgent need to study and find appropriate and non-invasive methods to distinguish and predict metabolically unhealthy obesity.…”

mentioning

confidence: 99%

Fat distribution measurements by chemical shift‐encoded transition region extraction predict the risk of hyperglycaemia, dyslipidaemia and metabolic syndrome in mice

Lin

Cheng

et al. 2023

NMR in Biomedicine

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Metabolically healthy or unhealthy obesity is closely related to metabolic syndrome (MetS). To validate a more accurate diagnostic method for obesity that reflects the risk of metabolic disorders in a pre‐clinical mouse model, C57BL/6J mice were fed high‐sucrose–high‐fat and chow diets for 12 weeks to induce obesity. MRI was performed and analysed by chemical shift‐encoded fat–water separation based on the transition region extraction method. Abdominal fat was divided into upper and lower abdominal regions at the horizontal lower border of the liver. Blood samples were collected, and the glucose level, lipid profile, liver function, HbA1c and insulin were tested. k‐means clustering and stepwise logistic regression were applied to validate the diagnosis of hyperglycaemia, dyslipidaemia and MetS, and to ascertain the predictive effect of MRI‐derived parameters to the metabolic disorders. Pearson or Spearman correlation was used to assess the relationship between MRI‐derived parameters and metabolic traits. The receiver‐operating characteristic curve was used to evaluate the diagnostic effect of each logistic regression model. A two‐sided p value less than 0.05 was considered to indicate statistical significance for all tests. We made the precise diagnosis of obesity, dyslipidaemia, hyperglycaemia and MetS in mice. In all, 14 mice could be diagnosed as having MetS, and the levels of body weight, HbA1c, triglyceride, total cholesterol and low‐density lipoprotein cholesterol were significantly higher than in the normal group. Upper abdominal fat better predicted dyslipidaemia (odds ratio, OR = 2.673; area under the receiver‐operating characteristic curve, AUCROC = 0.9153) and hyperglycaemia (OR = 2.456; AUCROC = 0.9454), and the abdominal visceral adipose tissue (VAT) was better for predicting MetS risk (OR = 1.187; AUCROC = 0.9619). We identified the predictive effect of fat volume and distribution in dyslipidaemia, hyperglycaemia and MetS. The upper abdominal fat played a better predictive role for the risk of dyslipidaemia and hyperglycaemia, and the abdominal VAT played a better predictive role for the risk of MetS.

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Acute Effects of Inorganic Nitrate Intake on Brachial and Femoral Flow-Mediated Vasodilation, and on Carotid Artery Reactivity Responses: Results of a Randomized, Double-Blinded, Placebo-Controlled Cross-Over Study in Abdominally Obese Men

Cited by 3 publications

References 43 publications

Short-Term Supplementation of Sodium Nitrate vs. Sodium Chloride Increases Homoarginine Synthesis in Young Men Independent of Exercise

Short-Term Supplementation of Sodium Nitrate vs. Sodium Chloride Increases Homoarginine Synthesis in Young Men Independent of Exercise

Homoarginine in health and disease

Fat distribution measurements by chemical shift‐encoded transition region extraction predict the risk of hyperglycaemia, dyslipidaemia and metabolic syndrome in mice

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