Methionine and Cysteine Restriction in Humans

Study Overview
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Brief Summary
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The aim of this study is to examine the effect of methionine and cysteine restriction on energy and macronutrient metabolism in overweight human subjects

Detailed Description
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The sulfur-containing amino acid methionine and its downstream metabolite cysteine has been associated with fat mass in animal studies and human observational studies. Some of the proposed mechanisms include an association with lipogenesis, insulin sensitivity and disrupted energy metabolism. The overall aim of this project is to evaluate the effects of a diet low in methionine and cysteine on markers of lipids, amino acids, glucose and other biomarkers related to energy metabolism, including transcriptomic and protein expression data from adipose tissue and lymphocytes. Overweight and obese but otherwise healthy volunteers will be randomized to receive a diet either low, moderate or high in methionine and cysteine concentrations for 1 week. This is a pilot study that may be considered an extension of NCT02647970. In addition to the primary and secondary outcomes we will evaluate the feasibility of the intervention and procedures.

Official Title
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Dietary Methionine and Cysteine Restriction in Overweight Human Subjects

Conditions
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Overweight

Intervention / Treatment
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* Behavioral: Low met/cys diet
* Behavioral: Moderate met/cys diet
* Behavioral: High met/cys diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index of 25-35 kg/m2 Exclusion Criteria: High physical activity Smoking Drugs Chronic disease Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low met/cys diet<br>Dietary intervention | Behavioral: Low met/cys diet<br>* Dietary intervention with low contents of methionine and cysteine<br>|
| Experimental: Moderate met/cys diet<br>Dietary intervention | Behavioral: Moderate met/cys diet<br>* Dietary intervention with moderate contents of methionine and cysteine<br>|
| Active Comparator: High met/cys diet<br>Dietary intervention | Behavioral: High met/cys diet<br>* Dietary intervention with high contents of methionine and cysteine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma concentrations of amino acids | Measurement of biomarkers of amino acid metabolism, including plasma concentrations of methionine, cysteine and related metabolites | Baseline, Day 1, Day 3 and Day 7 (final visit) | 
| Change in protein expression activity in tissues | Measurement of protein expression and activity related to methionine and cysteine metabolism in adipose tissue and lymphocytes. | Baseline and day 7 (final visit for adipose tissue, Baseline and day 1, 3 and 7 (final visit) for lymphocytes. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma concentrations of fatty acids | Measurement of fatty acid content in plasma | Baseline, Day 1, Day 3 and Day 7 (final visit) | 
| Change in plasma activity indices of steaoryl-CoA desaturase | Calculated based onthe ratio of plasma concentrations of products and precursors | Baseline, Day 1, Day 3 and Day 7 (final visit) | 
| Change in protein expression of steaoryl CoA-desaturase in adipose tissue | Measurement of protein expression of steaoryl CoA-desaturase in adipose tissue | Baseline and Day 7 (final visit) | 
| Change in protein expression of steaoryl CoA-desaturase in lymphocytes | Measurement of protein expression of steaoryl CoA-desaturase in lymphocytes | Baseline, Day 1, Day 3 and Day 7 (final visit) | 
| Change in steaoryl CoA-desaturase activity in adipose tissue | Measurement of enzyme activity of steaoryl CoA-desaturase in adipose tissue | Baseline and Day 7 (final visit) | 
| Diet feasibility | Diet feasibility will be measured by a self-administered questionnaire | Baseline, Day 1, Day 3 and Day 7 (final visit) | 
| Diet compliance | Compliance with the diet will be measured by a self-administered questionnaire | Baseline, Day 1, Day 3 and Day 7 (final visit) | 
| Body composition | Measurement of body composition by bioimpedance and dual X-ray absorptometry | Baseline and day 7 (final visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methionine, Cysteine, Energy metabolism, Sulfur amino acids