Sulfur Amino Acids, Energy Metabolism and Obesity

Conditions

Overweight and Obesity

Keywords

Methionine, Cysteine, Sulfur amino acids, Dietary intervention, Plant-based diet

Brief summary

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

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

Ulalume Hernández-Arciga, Ceda Stamenkovic, Shweta Yadav, Chiara Nicoletti, Wafaa N. Albalawy et al. (44 authors)

Science Advances2025-04-165 citations

10.1126/sciadv.ads1532

DIETARY METHIONINE RESTRICTION STARTED LATE IN LIFE IMPROVES NEUROMUSCULAR FUNCTION AND PROMOTES HEALTHY AGING

Andrey A. Parkhitko, Ulalume Hernandez Arciga, Ceda Stamenkovic, Shweta Yadav, Gene P. Ables et al. (8 authors)

Innovation in Aging2024-12-01

10.1093/geroni/igae098.3650

Dietary sulfur amino acid restriction in humans with overweight and obesity: Evidence of an altered plasma and urine sulfurome, and a novel metabolic signature that correlates with loss of fat mass and adipose tissue gene expression.

Olsen T, Vinknes KJ, Barvíková K, Stolt E, Lee-Ødegård S, Troensegaard H, Johannessen H, Elshorbagy A, Sokolová J, Krijt J, Křížková M, Ditrói T, Nagy P, Øvrebø B, Refsum H, Thoresen M, Retterstøl K, Kožich V.

2024-05-173 citations

10.1016/j.redox.2024.103192

Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial

Thomas Olsén, Emma Stolt, Bente Øvrebø, Amany Elshorbagy, Elena C. Tore et al. (20 authors)

Journal of Translational Medicine2024-01-0928 citations

10.1186/s12967-023-04833-w

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

Emma Stolt, Thomas Olsén, Amany Elshorbagy, Viktor Kožich, Marleen M. J. van Greevenbroek et al. (10 authors)

Journal of Translational Medicine2021-04-1526 citations

10.1186/s12967-021-02824-3

Interventions

OTHERLow SAA diet

Diet with low content of methionine and cysteine

OTHERHigh SAA diet

Diet with high content of methionine and cysteine

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Changes in body weight	At baseline, 4 and 8 weeks	Kilograms

Secondary

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

Countries

Norway

Outcome results

None listed