Uric Acid Metabolism, Endothelial Function and Oxidative Stress in Vegans and Omnivores.

Study Overview
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Brief Summary
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50 vegans and 50 omnivores will be recruited at the Erasme Hospital, Brussels. Hypothesis Relative induced-hyperuricemia by the vegan diet is not associated with impaired endothelial function if vitamin B12 and folic acid levels are normal. Quantification of xanthine oxidoreductase (XOR) isoforms varies according to the diet. Omnivores present more xanthine oxidase (XO) than vegans in which the xanthine dehydrogenase (XD) isoform is more prevalent. The vegan group has more favorable oxidant, metabolic and inflammatory profiles than the omnivore group.

Detailed Description
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Non-meat eaters rise widely worldwide. This choice answers ideological, ecological or health concerns. Several vegetarian diets exist and the vegan diet is the most restricted one as it excludes all animal products, eggs and dairy. Beside benefits on health and particularly on the cardiovascular system (blood pressure, weight, lipid profile), some authors described less favorable lipid and oxidative profiles and others described an impairment in endothelial function markers in 'vegans'. These effects were attributed to low vitamin B12 and folate levels and high homocystein levels. However, vitamin B12 supplementation improved these parameters. Epidemiological studies also showed that 'vegans' disclose higher uric acid levels than other vegetarians or omnivores. Uric acid acts as an antioxidant in the plasma but can be deleterious for vascular cells leading to endothelial dysfunction. The main enzyme involved in uric acid metabolism is xanthine oxidoreductase which exists under two interconvertible isoforms. Xanthine dehydrogenase is the main form and uses nicotinamide adenine dinucleotide (NAD+) as electron acceptor and does not produce reactive oxygen species (ROS). In contrast, the other isoform xanthine oxidase uses oxygen as an electron acceptor and produces reactive oxygen species (ROS). The investigators wish to test the hypothesis that it is not uric acid per se, but which isoform of xanthine oxidoreductase which alters endothelial function. This is why the investigators wish to determine if regular 'vegans' (with normal vitamin B12 and folate levels) disclose increased uric acid levels in the presence of a reduced inflammation, oxidative stress and improved endothelial function, as compared to matched 'omnivores'. 50 vegans and 50 omnivores will be recruited at the Erasme Hospital, Brussels. Hypothesis Relative induced-hyperuricemia by the vegan diet is not associated with impaired endothelial function if vitamin B12 and folic acid levels are normal. Quantification of oxidoreductase (XOR) isoforms varies according to the diet. Omnivores present more xanthine oxidase (XO) than vegans in which the xanthine dehydrogenase (XD) isoform is more prevalent. The vegan group has more favorable oxidant, metabolic and inflammatory profiles than the omnivore group.

Official Title
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Differential Analysis of Uric Acid Metabolism, Endothelial Function, Oxidative Stress and Cardiovascular Parameters in Vegans and Omnivores.

Conditions
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Healthy, Diet Modification

Intervention / Treatment
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* Other: Endothelial function and inflammation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Vegan or omnivore diet for at least one year (matched for age, gender, BMI, socio-economic status and weight) Healthy Exclusion Criteria: Smoking Chronic treatment No allowed drugs taking Excessive alcohol consumption

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Omnivore<br> | Other: Endothelial function and inflammation<br>* Analysis of endothelial function, oxidative stress<br>|
| Vegan<br> | Other: Endothelial function and inflammation<br>* Analysis of endothelial function, oxidative stress<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of the perfusion of the microcirculation of the skin | Endothelial function assessment will be performed through analyse of the perfusion of the microcirculation of the skin in the forearm will be assessed by means of a laser Doppler imager and iontophoresis of acetylcholine and sodium nipride. Heating-induced hyperemia will be assessed after iontophoresis of inhibitor of NO synthase and saline. Units are perfusion unit. Iontophoresis is a non-invasive tool which permits to infuse molecules in the first micrometers of the skin. The used molecules are vasodilative, saline or NO synthase inhibitor. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Uric acid | Uric acid (mg/dL or SI) | 2 hours | 
| Concentration of xanthine oxidase and xanthine dehydrogenase in blood | western blot | 2 hours | 
| Measure of hemoglobin | g/l | 2 hours | 
| Measure of white blood cells, red blood cells and platelets | cells/µl of blood | 2 hours | 
| Measure of urea, creatinine, bilirubin, albumine, prealbumin, LDL, HDL, lp(a), total cholesterol, triglyceride, apolipoprotein A and B | mg/dl | 2 hours | 
| Measure of glycemia, vitamine and iron status (B3, B6, B12, C, D, E, B9, Zn, Cu, Selenium, iron, ferritin), c-reactive protein, homocystein | mg/dl | 2 hours | 
| Measure of sodium, potassium, chlore, phosphor, calcium, magnesium, HbA1c, omega 3 et 6 | mmol/l | 2 hours | 
| Measure of glomerular filtration rate | ml/min | 2 hours | 
| Measure of gamma-glutamyltransferase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatin phosphokinase, insulin, TSH | u/l | 2 hours | 
| Measure of allantoin, homocitrulline/lysine, chloro-tyrosine/tyrosine, Il-8, myeloperoxidase | Mass spectrometry and Elisa Kits | 2 hours | 
| Measure of renin, aldosterone, angiotensin 2, angiotensin converting enzyme |  | 2 hours | 
| Measure of main proteomes and metabolomes in cells incubated with sera from participants | Sera will be used for cell cultures. Theses cells will be lysed and used to analyse and compare the different proteomes / metabolomes according to the groups. We will be able to understand which protein groups are reduced or enhanced according to the diet. | 2 hours | 
| Measure of blood pressure | Systolic and diastolic blood pressure | 2 hours | 
| Measure of baroreflex sensitivity | finometer | 2 hours | 
| Measure of heart rate | finometer | 2 hours | 
| Measure of augmentation index | Assessment of the arterial stiffness | 2 hours | 
| Measure of pulse wave velocity | Assessment of the arterial stiffness | 2 hours | 
| Diet questionary | Diet History Questionnaire third version provides estimation of one year consumption of proteins, carbohydrates, lipids, micronutrient and vitamines | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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uric acid, hemodynamic parameters, endothelial function, oxidative stress and inflammation, vegan, omnivore