Sulfur Amino Acids, Energy Metabolism and Obesity

Study Overview
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Brief Summary
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The primary objective of the trial is to establish the effects of dietary sulfur amino acid (SAA) restriction on body weight, body composition and energy expenditure in humans.

Detailed Description
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Dietary SAA restriction is an established model for increasing lifespan and improving metabolic health in animal studies. Data from human studies are limited. In this study the investigators will perform an 8-week dietary intervention with SAA restriction to characterise the effects on several parameters related to metabolic health including body weight, body composition, energy expenditure, lipid profile and gene expression profiles in adipose tissue. The aim is to translate findings from previous animal experiments to humans

Official Title
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Dietary Sulfur Amino Acid Restriction, Energy Metabolism and Obesity

Conditions
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Overweight and Obesity

Intervention / Treatment
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* Other: Low SAA diet
* Other: High SAA diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants with overweight and obesity (BMI 27-35 kg/m2) Waist circumference > 80 cm for women and > 94 cm for men Exclusion Criteria: Smoking Presence of chronic disease Established co-morbidities Already on a vegan diet or have been the last month Pregnancy Breastfeeding the last 3 months Unstable body weight the last 3 months High intensity training > 3 times weekly

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low SAA diet<br>Dietary intervention | Other: Low SAA diet<br>* Diet with low content of methionine and cysteine<br>|
| Active Comparator: High SAA diet<br>Dietary intervention | Other: High SAA diet<br>* Diet with high content of methionine and cysteine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in body weight | Kilograms | At baseline, 4 and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in resting energy expenditure | Kilocalories | At baseline, 4 and 8 weeks | 
| Changes in substrate oxidation | Respiratory quotient | At baseline, 4 and 8 weeks | 
| Changes in body composition | Fat mass (kilograms) and lean mass (kilograms) | At baseline, 4 and 8 weeks | 
| Changes in plasma concentrations of SAA and related intermediates and compounds | Sulfite, thiosulfate, rhodanide, sulfate, total aminothiols (homocysteine, cysteine, glutathione gamma-glutamylcysteine, cysteinylglycine, cysteamine), and fractions of total cysteine, total glutathione and total homocysteine, cystathionine, lanthionine, homolanthionine, taurine hypotaurine, sarcosine, hydrogen sulfide, S-adenosylmethionine and S-adenosylhomocysteine | At baseline, 4 and 8 weeks | 
| Changes in urine concentrations of SAA and related intermediates and compounds | Including sulfite, thiosulfate, rhodanide, sulfate, total aminothiols (homocysteine, cysteine, glutathione gamma-glutamylcysteine, cysteinylglycine, cysteamine) | At baseline, 4 and 8 weeks | 
| Changes in concentrations of plasma lipid profile | Fatty acids, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, ApoA1, ApoB | At baseline, 4 and 8 weeks | 
| Changes in plasma makers of insulin sensitivity | Concentrations of glucose and insulin | At baseline, 4 and 8 weeks | 
| Changes in plasma concentrations of adipokines and appetite hormones | Leptin, adiponectin, gastrin, ghrelin, cholecystokinin (CCK), glucagon-like peptide (GLP-1), oxyntomodulin, gastric inhibitory peptide (GIP), peptide YY (PYY), and pancreatic peptide (PP). | At baseline, 4 and 8 weeks | 
| Changes in gene expression | mRNA of proteins involved in SAA metabolism, lipid and energy metabolism in leucocytes and subcutaneous white adipose tissue samples | At baseline, 4 and 8 weeks | 
| Vitamin status | Plasma concentrations of folate, B12 and methylmalonic acid (MMA) | At baseline, 4 and 8 weeks | 
| Changes in biomarkers related to obesity and energy metabolism | Untargeted analyses of plasma, serum and tissue concentrations | At baseline, 4 and 8 weeks | 
| Changes in fibroblast growth factor 21 (FGF21) | Serum concentrations | At baseline, 4 and 8 weeks | 
| Nitrogen balance | 24 h-urine urea nitrogen | At baseline, 4 and 8 weeks | 
| Changes in gut microbiota | Sequencing of fecal samples | At baseline, 4 and 8 weeks | 
| Changes in short chain fatty acids | Fecal concentrations | At baseline, 4 and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methionine, Cysteine, Sulfur amino acids, Dietary intervention, Plant-based diet