Dietary Interventions Evaluating Transport of Uric Acid Across the Tubules

Study Overview
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Brief Summary
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The purpose of the study is to determine whether low fat dairy diet reduces serum uric acid levels.

Detailed Description
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Uric acid plays a role not only in the pathogenesis of gout but is also a predictor of cardiovascular disease, hypertension and renal disease in man. We have identified the human urate ion channel transporter (hUAT), located in the proximal convoluted tubule of the kidney that is involved in both the secretion and reabsorption of urate across the tubule. This channel has a unique lectin binding site that in in-vitro studies, has been found to be modulated by glucose, galactose and lactose. We have also identified a mutation (G/A polymorphism) in our laboratory, that in in-vitro studies has demonstrated diminished hUAT channel activity. Cross-sectional studies have earlier shown that uric acid levels vary with serum glucose levels. Studies have also reported that a low-fat dairy diet reduces the incidence of gout, while others have shown that this diet reduces blood pressure significantly when compared with a non-dairy diet. We hypothesize that the effect of blood glucose levels in lowering uric acid levels is through the regulation of hUAT channel activity. We also hypothesize that a low-fat dairy diet reduces serum uric acid levels through hUAT regulation leading to a decrease in the incidence of gout and a reduction in blood pressure levels. In our proposed randomized, controlled, cross-over trial in healthy adult volunteers, we aim to study the effect of a low-fat dairy diet and a non-dairy diet on serum uric acid levels, the renal fractional excretion of uric acid and blood pressure. We will also study the effect of an acute intravenous infusion of glucose on these parameters. DNA analysis for hUAT mutations of study subjects will be done to assess if there is a blunted response of hUAT activity in subjects with the polymorphism as compared to normal individuals.

Official Title
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Dietary Interventions Evaluating Transport of Uric Acid Across the Tubules

Conditions
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Healthy

Intervention / Treatment
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* Behavioral: Low fat dairy diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Healthy adult volunteers Coronary artery disease Glucose intolerance or Diabetes(a fasting blood sugar of less than 100 mg/dl as per the American Diabetes Association guidelines) CHF Gout Lactose intolerance Milk allergy Women who are pregnant or lactating Subjects who are on any medications except birth control pills Subjects who drink more than 3 servings of beer or liquor per week. Normal blood pressure ( less than 120 mmHg systolic and 80 mmHg diastolic) Normal serum UA levels Normal renal funcion (calculated GFR >90ml/min) Exclusion Criteria: • Coronary artery disease Glucose intolerance or Diabetes(a fasting blood sugar of less than 100 mg/dl as per the American Diabetes Association guidelines) CHF Gout Lactose intolerance Milk allergy Women who are pregnant or lactating Subjects who are on any medications except birth control pills Subjects who drink more than 3 servings of beer or liquor per week

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Behavioral: Low fat dairy diet|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lowering of serum uric acid levels |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lowering of the fractional excretion of uric acid and blood pressure |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uric acid, Dairy, Diet