TY - JOUR
T1 - Dietary sulfur amino acid restriction in humans with overweight and obesity
T2 - a translational randomized controlled trial
AU - Olsen, Thomas
AU - Stolt, Emma
AU - Øvrebø, Bente
AU - Elshorbagy, Amany
AU - Tore, Elena C.
AU - Lee-Ødegård, Sindre
AU - Troensegaard, Hannibal
AU - Johannessen, Hanna
AU - Doeland, Beate
AU - Vo, Anna A.D.
AU - Dahl, Anja F.
AU - Svendsen, Karianne
AU - Thoresen, Magne
AU - Refsum, Helga
AU - Rising, Russell
AU - Barvíková, Kristýna
AU - van Greevenbroek, Marleen
AU - Kožich, Viktor
AU - Retterstøl, Kjetil
AU - Vinknes, Kathrine J.
N1 - Funding Information:
Open access funding provided by University of Oslo (incl Oslo University Hospital). This project has received funding from The Research Council of Norway (Grant no: 310475) under the umbrella of the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) and of the ERA-NET Cofund HDHL INTIMIC (GA N° 727565 of the EU Horizon 2020 Research and Innovation Programme), Institute of Basic Medical Sciences, University of Oslo, and Henning och Johan Throne-Holsts stiftelse. VK and KB were supported by the Czech Ministry of Education, Sports and Youth (STAY 8F20013), institutional support was provided by Charles University (program COOPERATIO-Metabolic Disorders) and Ministry of Health DRO VFN64165.
Publisher Copyright:
© 2024, The Author(s).
PY - 2024/12/1
Y1 - 2024/12/1
N2 - Background: Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. Methods: N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. Results: SAAR led to a ~ 20% greater weight loss compared to controls (ß 95% CI - 1.14 (- 2.04, - 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. Conclusion: Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. Trial registration: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www.clinicaltrials.gov/study/NCT04701346.
AB - Background: Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. Methods: N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. Results: SAAR led to a ~ 20% greater weight loss compared to controls (ß 95% CI - 1.14 (- 2.04, - 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. Conclusion: Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. Trial registration: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www.clinicaltrials.gov/study/NCT04701346.
KW - Cysteine
KW - Dietary intervention
KW - Leptin
KW - Methionine restriction
KW - Obesity
KW - Overweight
KW - Randomized controlled trial
KW - Sulfur amino acid restriction
KW - Weight loss
U2 - 10.1186/s12967-023-04833-w
DO - 10.1186/s12967-023-04833-w
M3 - Article
SN - 1479-5876
VL - 22
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
IS - 1
M1 - 40
ER -