Hypertriglyceridemic Waist, Overweight
Conditions
Keywords
arginine, supplementation, metabolic syndrome, nitric oxide
Brief summary
The purpose of this study is to compare the metabolic fate of two oral forms of L-Arginine in healthy subjects featuring metabolic syndrome related risk factors
Detailed description
The study is a randomized crossover study including 16 healthy subjects with risk factors for metabolic syndrome and 16 healthy control subjects. According a double crossover design, each subject received two oral forms of L-arginine (A and B) in random order, and participated in a exploration day on the first day of arginine administration and after one week of supplementation with this arginine form. The two weeks of arginine supplementation were separated by a washout period of 2 weeks at least. Each exploration extended over 24 hours after administration of the first arginine dose. Blood tests were performed at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 h after administration of the first dose. During explorations after the supplementation period, we also collected urine (0, 2, 4, 8, 12, 24 h after the first dose).
Interventions
DIETARY_SUPPLEMENTA form Arginine
3 capsules containing 0.5g of A form of L-arginine (1.5g) 3 times daily (4.5g per day) for 1 week
DIETARY_SUPPLEMENTB form Arginine
3 capsules containing 0.5g of B form of L-arginine (1.5g) 3 times daily (4.5g per day) for 1 week
Sponsors
Institut de Recherche Pierre Fabre
Hospital Avicenne
Adeprina
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy subjects with 'Hypertriglyceridemic waist' : Inclusion Criteria: * Age between 18 to 60 years old * Overweight (BMI between 25 and 30 kg/m²) * 'Hypertriglyceridemic waist' (waist circumference \> 94cm for men or \> 88cm for women and fasting triglyceride levels \> 150 mg/dL)
Exclusion criteria
* Obesity (BMI\> 30 kg / m²) * Cardiac or vascular diseases * Diabetes * Thyroid disease * Systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 90 mmHg * Tobacco consumption \> 6 cigarettes per week * Alcohol consumption\> 3 drinks per day * Any medication (except contraceptive treatment) or dietary supplement intake that could not be arrested more than a week before the first visit for the duration of the study. * Persons under guardianship * Pregnancy (positive beta-hCG blood test) * Positive serology HBsAg AcHbc, HCV and HIV * Hemoglobin \< 14 g/dl (for men) or \<12 g / dl (for women) * Participation in a clinical trial within 6 months preceding the study Healthy control subjects : Inclusion Criteria: * Age between 18 to 60 years old * Normal weight (BMI between 18.5 and 25 kg/m²) * Waist circumference \< 94cm for men or \< 88cm for women and fasting triglyceride levels \< 150 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimate of total conversion of a dose of oral arginine into NO | Repeated measurement for 24h before (day 0) and after supplementation (day 8) for each treatment | This assessment uses labelled arginine (\[15N2-(guanido)\]-arginine) for the first dose of arginine taken in the morning, and measurements of 15NO3 in urine for 24h. After administration of 15N-arginine, for each urine collection, we determined the nitrate excretion (from measurement of diuresis and nitrate concentration, by reactive chemiluminescence) and isotope 15N enrichment of nitrate ion (by microdiffusion technique and elementary analyzer connected to an isotope mass spectrometerEA-IRMS), to establish, by the principle of isotopic dilution, the total quantities of nitrate specifically from the ingested arginine. The sum of this excretion relative to the ingested dose determined the relative conversion of ingested arginine into NO. |
| Estimate of kinetic profiles of plasma arginine concentrations over 24 hours | Repeated measurement for 24h before (day 0) and after supplementation (day 8) for each treatment | Plasma AA concentrations were determined using an ultra-performance liquid chromatography-mass spectrometry system as previously described (Haque and al., 2012). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative analysis of plasma markers of endothelial function | Before supplementation (day 0) and after supplementation (day 8) for each treatment | Fasting plasma concentrations of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1), E-Selectin, P-Selectin, Plasminogen activator inhibitor-1 (PAI-1), will be determined using two custom mixed assay kits with antibody-coated beads using the Luminex xMAP technology platform for multiplexing of immunochemical bioassays. In addition, we also have plasma concentrations of nitrite, a marker of of NO production (by reactive chemiluminescence) and other associated markers (3-nitrotyrosine, nitrosothiols, cGMP, in particular ANP, by immunochemistry). |
| Estimate of kinetics use of arginine for NO and urea synthesis | Repeated measurement for 24h after supplementation (day 8) for each treament | After administration of 15N-arginine, we measured 15N isotopic enrichment of arginine and citrulline (by mass spectrometry coupled with gas chromatography), of plasma and urinary urea (by separation, by ion exchange, and EA-IRMS) as well as the plasma and urine concentrations in urea. These data and those of arginine and citrulline concentrations provided, by the principle of isotopic dilution, the plasma appearance of ingested arginine and the plasma appearance and urinary excretion of products of its metabolism in NO synthase and arginase ways. These data were then subjected to a compartmental modeling work to establish the metabolic flow in these ways. |
| Other quantitative analysis | Before supplementation (day 0) and after supplementation (day 8) for each treatment | * Fasting Asymmetric Dimethyl-L-Arginine (ADMA) concentrations were measured by an enzyme-linked immunosorbent assay. * The fasting lipid profile (triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol) was measured and were assayed using classical clinical biochemical analyzers. * The fasting insulin and glucose were assayed using classical clinical biochemical analyzers. * Fasting metabolomic analysis |
Countries
France
Outcome results
None listed