STAY
Sulfur amino acids, energy metabolism and obesity
Research over the last decade suggests that methionine and cysteine, two dietary sulfur amino acids that are abundant in proteins from animal sources, play a role in development of obesity and related metabolic diseases. In rodents, experiments with diets low in methionine and cysteine content result in improved glucose and lipid metabolism and reduced body fat. In human observational studies, circulating total cysteine linearly correlates with fat mass, independent of other sulfur amino acids.
The overall aim of the STAY project has been to study the relevance of dietary, circulating and urinary sulfur amino acids and related compounds in obesity and related co-morbidities in humans using interventional and observational data.
We implemented a dietary intervention study (doi.org/10.1186/s12967-021-02824-3) in participants with overweight and obesity to evaluate the effects of a plant-based diet low in methionine and cysteine on body weight, body composition, and energy balance, as well as obesity-related blood markers (glucose and lipid metabolism, amino acids, fatty acids). Results of the primary outcome and some secondary outcomes were published in January 2024. We show that an 8-week intervention with a sulfur amino acid-restricted, plant-based diet in adults with overweight and obesity (n = 59) led to a decrease in body weight and serum leptin concentrations, and an increase in plasma ketone bodies compared to controls. The diet also affected plasma and urine sulfur metabolites, and gene expression in white adipose tissue (doi. 10.1186/s12967-023-04833-w).
In addition, we have used data from a large Dutch population study (The Maastricht Study) to investigate associations of dietary, circulating and urinary methionine and cysteine with body fat and disease. The first article (doi: 10.1007/s00394-022-03041-4) shows associations of plasma concentrations of methionine and cysteine with different fat depots; plasma methionine was positively associated with liver fat, while plasma cysteine was associated with greater general, central and peripheral adiposity. The second paper from The Maastricht Sstudy (doi:10.1016/j.tjnut.2023.05.008) show that a significant dietary determinant of plasma sulfur amino acids was protein intake, particularly from animal sources, which was associated with higher plasma cysteine levels.
We have also developed new laboratory method for the quantification of specific biomarkers in sulfur amino acid metabolism − urinary sulfate. The method was developed at Charles University, Prague, and has been applied on samples from the dietary intervention study and The Maastricht Study.
This project has generated new insight into the role of methionine and cysteine in human obesity and obesity-related diseases, and the extent to which their restriction by a plant-based diet can facilitate weight loss and improve metabolic health.
Consortium
| Partner Organization | Partner Country |
|---|---|
| Charles University-First Faculty of Medicine | Czech Republic |
| Maastricht University | The Netherlands |
| University of Oxford | UK |
Highlights
In the STAY project we have implemented a double-blind randomized controlled dietary intervention study in participants with overweight and obesity to evaluate the effects of a plant-based diet low in methionine and cysteine on body weight, body composition, and energy balance, as well as obesity-related blood markers (doi: 10.1186/s12967-021-02824-3). Results of the primary outcome and some secondary outcomes studies indicate effects on body weight and on several biomarkers in plasma and urine. We show that the intervention led to a decrease in body weight (20 % greater than in controls) and serum leptin concentrations, and an increase in plasma ketone bodies (doi: 10.1186/s12967-023-04833-w.) in individuals with overweight or obesity (n = 59). The diet also affected plasma and urine sulfur metabolites, and gene expression in white adipose tissue (in review).
Using data of The Maastricht Study, a population-based cohort study, plasma methionine was positively associated with liver fat, while plasma cysteine was associated with greater general, central and peripheral adiposity (doi: 10.1007/s00394-022-03041-4.). Furthermore, a significant dietary determinant of plasma sulfur amino acids was protein intake, particularly from animal sources, which was associated with higher plasma cysteine levels (doi: 10.1016/j.tjnut.2023.05.008.)
Products
Author: Emma Stolt*, Thomas Olsen*, Amany Elshorbagy*, Viktor Kozich*, Marleen van Greevenbroek*, Bente Øvrebø, Magne Thoresen, Helga Refsum*, Kjetil Retterstøl*, Kathrine J. Vinknes*
Link: https://doi.org/10.1186/s12967-021-02824-3
Author: Tore EC*, Elshorbagy AK*, Bakers FCH, Brouwers MCGJ, Dagnelie PC, Eussen SJPM, Jansen JFA, Kooi ME, Kusters YHAM, Meex SJR, Olsen T,* Refsum H*, Retterstøl K*, Schalkwijk CG, Stehouwer CDA, Vinknes KJ*, van Greevenbroek MMJ.*
Link: https://doi.org/10.1007/s00394-022-03041-4
Author: Nichenametla SN, Mattocks DAL, Cooke D, Midya V, Malloy VL, Mansilla W, Øvrebø B*, Turner C, Bastani NE*, Sokolová J*, Pavlíková M*, Richie JP Jr, Shoveller AK, Refsum H*, Olsen T*, Vinknes KJ*, Kožich V*, Ables GP.
Link: https://doi.org/10.1111/acel.13739
Author: Tore EC, Eussen SJPM, Bastani NE, Dagnelie PC, Elshorbagy AK, Grootswagers P, Kožich V, Olsen T, Refsum H, Retterstøl K, Stehouwer CD, Stolt ETK, Vinknes KJ, van Greevenbroek MMJ
Magazine: The Journal of Nutrition
Link: https://doi.org/10.1016/j.tjnut.2023.05.008
Author: Olsen T, Stolt E, Øvrebø B, Elshorbagy A, Tore EC, Lee-Ødegård S, Troensegaard H, Johannessen H, Doeland B, Vo AAD, Dahl AF, Svendsen K, Thoresen M, Refsum H, Rising R, Barvíková K, van Greevenbroek M, Kožich V, Retterstøl K, Vinknes KJ
Magazine: Redox Biology
Link: https://doi.org/10.1016/j.redox.2024.103192
Communication & Dissemination Activities
| Target group | Authors | Means of communication |
|---|---|---|
| Members from food industry and academic institutions with a interest in sustainable and healthy food patterns and products | Thomas Olsen and Kathrine J Vinknes Sulfur amino acids, energy metabolism and obesity – STAY. Member meeting in Future Food (Fremtidsmat). Virtual November 2020. | Oral presentation |
| Scientists in the field of diet and diabetes | Thomas Olsen and Kathrine J Vinknes Sulfur amino acids, energy metabolism and obesity – STAY. Oslo Diabetic Research Centre, OUS. Virtual February 2022. | Oral presentation |
| Scientists in the field of diet and diabetes | Elena Tore. Distinct associations of plasma methionine and cysteine with regional fat distribution: CODAM and The Maastricht study. The 38th International Symposium on Diabetes and Nutrition, Virtual, 2021 | Poster presentation |
| Scientists in the field of diet and diabetes | Elena Tore. Distinct associations of plasma methionine and cysteine with regional fat distribution: CODAM and The Maastricht study. The European Association for the Study of Diabetes conference, Virtual, 2021 | Oral presentation |
| Scientists and students in the aging field | Thomas Olsen. Aging Science Talks (virtual), October, 2021 | Invited oral presentation |
| Scientists in the field of diet and diabetes | Elena Tore. Distinct associations of plasma methionine and cysteine with regional fat distribution: CODAM and The Maastricht study. The Annual Dutch Diabetes Research Meeting (Nederlandse Vereniging voor Diabetes Onderzoek), Virtual, 21 January 2022 | Oral presentation |
| Scientists and researchers in the aging field | Thomas Olsen and Kathrine J Vinknes. Sulfur amino acids and metabolic outcomes – Preliminary data, challenges, and experiences from human clinical intervention studies, OFAS Symposium for Healthy Aging, Virtual, December 2021 | Invited oral presentation |
| Scientists in the field of nutrition | Emma Stolt and Kathrine Vinknes, "Sulfur amino acid restriction, energy metabolism and obesity: Preliminary results from an 8-wk randomized controlled dietary intervention", Throne Holst Symposium at Institute of Basal Medical Sciences, Univesity of Oslo. May 2022 | Poster presentation |
| Food industry and academic institutions with interest in sustainable and healthy food patterns and products | Kathrine Vinknes, "Sulfur amino acid restriction, energy metabolism and obesity: Preliminary results from an 8-wk randomized controlled dietary intervention", Member meeting in Future Food, Oslo May 2022 | Oral presentation |
| People and consultants in the field of environmental management | Kathrine Vinknes, "Sulfur amino acids, energy metabolism and obesity", Meeting at Eco-Lighthouse, Oslo/Kristiansand November 2022 | Oral presentation |
| Scientists in the field of obesity | Elena Tore, "Distinct associations of plasma methionine and cysteine with regional fat distribution: CODAM and The Maastricht study", Annual meeting of the European Associations for the Study of Obesity (EASO), Maastricht, May 2022 | Oral presentation |
| Scientists in the field of diet and diabetes | Elena Tore, "The roles of SCD enzyme and appetite hormones in the associations of plasma cysteine with obesity and insulin resistance: The Maastricht Study", Annual meeting of the Diabetes and Study Group of the European Associations for the Study of Diabetes, Athens, June 2022 | Oral presentation (awarded best meeting presentation) |
| Scientists in the field of obesity | Elena Tore, "The roles of SCD enzyme and appetite hormones in the associations of plasma cysteine with obesity and insulin resistance: The Maastricht Study", Annual meeting of the European Associations for the Study of Diabetes, Stockholm, September 2022 | Short oral presentation |
| Scientists in the field of diet and diabetes | Elena Tore, "The SCD enzyme and ghrelin mediate the associations of plasma cysteine with obesity and insulin resistance: The Maastricht Study", Annual meeting of the Dutch Associations for Diabetes Research (Nederlandse Vereniging voor Diabetes Onderzoek, Wageningen November 2022 | Oral presentation |
| Scientists with interests in the field of nutrition | Kathrine Vinknes, "Sulfur amino acids, energy metabolism and obesity", Norwegian Journal of Nutrition (NTFE) Conference, Oslo, December 2022 | Oral presentation |
| Scientists and health professionals | Marleen van Greevenbroek. “Sulfur amino acids, energy metabolism and obesity - STAY” (in Dutch). 10e congres ZonMW ‘Goed Gebruik Geneesmiddelen’, Session ‘Leefstijl als medicijn’ March 2023 | Invited oral presentation & panel discussion |
| Scientists with interests in the field of nutrition | Kathrine Vinknes and Thomas Olsen. Sulfur amino acids and metabolic outcomes – experiences from translational human clinical interventions. Throne Holst Symposium, UiO. June 2023. | Oral presentation |
| Scientists and researchers in the aging field | Thomas Olsen. Dietary sulfur amino acid restriction in men and women with overweight or obesity – Evidence from a double-blind, randomized controlled dietary intervention study. Academic lecture at National Institutes of Health, US, September 2023. | Invited oral presentation |
| Scientists with interests in the field of nutrition | Thomas Olsen. Dietary sulfur amino acid restriction in men and women with overweight or obesity – Evidence from a double-blind, randomized controlled dietary intervention study. Department of Pharmacology - University of Oxford, September 2023 | Oral presentation |
| Scientists with interests in the field of nutrition | Kathrine Vinknes. The role of sulfur amino acids in obesity and metabolic health - The STAY project. The 14th European Nutrition Conference FENS 2023. November 2023. | Oral presentation |
| Scientists with interests in the field of nutrition | Emma Stolt. Effects of dietary sulfur amino acid restriction in humans: Evidence from a double-blind, randomized controlled dietary intervention study. The 14th European Nutrition Conference FENS 2023. November 2023. | Poster presentation |