Sulfur Amino Acids, Energy Metabolism and Obesity (STAY)

Dietary Sulfur Amino Acid Restriction, Energy Metabolism and Obesity

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.

Study Overview

• Status: Completed
• Conditions: Overweight and Obesity
• Intervention / Treatment: Other: Low SAA diet; Other: High SAA diet

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0372
    • Centre for Clinical Nutrition, University of Oslo/Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low SAA diet; Dietary intervention	Other: Low SAA diet; Diet with low content of methionine and cysteine
Active Comparator: High SAA diet; Dietary intervention	Other: High SAA diet; Diet with high content of methionine and cysteine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Oslo
• Collaborators: Charles University, Czech Republic; University of Oxford; Maastricht University
• Investigators: Study Director: Kjetil Dr Retterstøl, Prof. dr med, University of Oslo

Publications and helpful links

General Publications

• Stolt E, Olsen T, Elshorbagy A, Kozich V, van Greevenbroek M, Ovrebo B, Thoresen M, Refsum H, Retterstol K, Vinknes KJ. Sulfur amino acid restriction, energy metabolism and obesity: a study protocol of an 8-week randomized controlled dietary intervention with whole foods and amino acid supplements. J Transl Med. 2021 Apr 15;19(1):153. doi: 10.1186/s12967-021-02824-3.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): March 17, 2022
• Study Completion (Actual): March 17, 2022

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 5, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Actual): May 19, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Plant-based diet; Dietary intervention; Cysteine; Methionine; Sulfur amino acids
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Obesity; Overweight
• Other Study ID Numbers: 310475

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

EU privacy regulations do not permit public sharing of IPD as long as the project is ongoing. Anonymized data can be shared after the project and biobank permissions end in 2030.

The study protocol will be published.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No