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 Olsen; Amany Elshorbagy; Viktor Kozich; Marleen van Greevenbroek; Bente Ovrebo; Magne Thoresen; Helga Refsum; Kjetil Retterstol; Kathrine J. Vinknes

doi:10.1186/s12967-021-02824-3

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 Olsen^*, Amany Elshorbagy, Viktor Kozich, Marleen van Greevenbroek, Bente Ovrebo, Magne Thoresen, Helga Refsum, Kjetil Retterstol, Kathrine J. Vinknes

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Dietary sulfur amino acid (SAA) restriction is an established animal model for increasing lifespan and improving metabolic health. Data from human studies are limited. In the study outlined in this protocol, we will evaluate if dietary SAA restriction can reduce body weight and improve resting energy expenditure (REE) and parameters related to metabolic health.

Method/design: Men and women (calculated sample size = 60), aged 18-45 years, with body mass index of 27-35 kg/m(2) will be included in a double-blind 8-week dietary intervention study. The participants will be randomized in a 1:1 manner to a diet with either low or high SAA. Both groups will receive an equal base diet consisting of low-SAA plant-based whole foods and an amino acid supplement free of SAA. Contrasting SAA contents will be achieved using capsules with or without methionine and cysteine (SAA(high), total diet SAA similar to 50-60 mg/kg body weight/day; SAA(low), total diet SAA similar to 15-25 mg/kg body weight/day). The primary outcome is body weight change. Data and material collection will also include body composition (dual X-ray absorptiometry), resting energy expenditure (whole-room indirect calorimetry) and samples of blood, urine, feces and adipose tissue at baseline, at 4 weeks and at study completion. Measures will be taken to promote and monitor diet adherence. Data will be analyzed using linear mixed model regression to account for the repeated measures design and within-subject correlation.

Discussion: The strength of this study is the randomized double-blind design. A limitation is the restrictive nature of the diet which may lead to poor compliance. If this study reveals a beneficial effect of the SAA(low) diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders.

Original language	English
Article number	153
Number of pages	11
Journal	Journal of Translational Medicine
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s12967-021-02824-3
Publication status	Published - 15 Apr 2021

Keywords

Adipose tissue
Cysteine restriction
Dietary intervention
Gene expression
Metabolic health
Methionine restriction
Obesity
Plasma biomarkers
Sulfur amino acids
Translational research
PREVENTION
CYSTEINE
RISK
METHIONINE RESTRICTION
PLASMA
LIFE-STYLE
ADIPOSE-TISSUE

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Stolt, E., Olsen, T., Elshorbagy, A., Kozich, V., van Greevenbroek, M., Ovrebo, B., Thoresen, M., Refsum, H., Retterstol, K., & Vinknes, K. J. (2021). 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. Journal of Translational Medicine, 19(1), Article 153. https://doi.org/10.1186/s12967-021-02824-3

@article{65f8d5448c5a4ff7a6a41536896876a1,

title = "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",

abstract = "Background: Dietary sulfur amino acid (SAA) restriction is an established animal model for increasing lifespan and improving metabolic health. Data from human studies are limited. In the study outlined in this protocol, we will evaluate if dietary SAA restriction can reduce body weight and improve resting energy expenditure (REE) and parameters related to metabolic health.Method/design: Men and women (calculated sample size = 60), aged 18-45 years, with body mass index of 27-35 kg/m(2) will be included in a double-blind 8-week dietary intervention study. The participants will be randomized in a 1:1 manner to a diet with either low or high SAA. Both groups will receive an equal base diet consisting of low-SAA plant-based whole foods and an amino acid supplement free of SAA. Contrasting SAA contents will be achieved using capsules with or without methionine and cysteine (SAA(high), total diet SAA similar to 50-60 mg/kg body weight/day; SAA(low), total diet SAA similar to 15-25 mg/kg body weight/day). The primary outcome is body weight change. Data and material collection will also include body composition (dual X-ray absorptiometry), resting energy expenditure (whole-room indirect calorimetry) and samples of blood, urine, feces and adipose tissue at baseline, at 4 weeks and at study completion. Measures will be taken to promote and monitor diet adherence. Data will be analyzed using linear mixed model regression to account for the repeated measures design and within-subject correlation.Discussion: The strength of this study is the randomized double-blind design. A limitation is the restrictive nature of the diet which may lead to poor compliance. If this study reveals a beneficial effect of the SAA(low) diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders.",

keywords = "Adipose tissue, Cysteine restriction, Dietary intervention, Gene expression, Metabolic health, Methionine restriction, Obesity, Plasma biomarkers, Sulfur amino acids, Translational research, PREVENTION, CYSTEINE, RISK, METHIONINE RESTRICTION, PLASMA, LIFE-STYLE, ADIPOSE-TISSUE",

author = "Emma Stolt and Thomas Olsen and Amany Elshorbagy and Viktor Kozich and {van Greevenbroek}, Marleen and Bente Ovrebo and Magne Thoresen and Helga Refsum and Kjetil Retterstol and Vinknes, {Kathrine J.}",

note = "Funding Information: 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), and Institute of Basic Medical Sciences, University of Oslo. The funding agencies had no role in development of the study protocol. Funding Information: The authors wish to thank chef Johannes Gr?dal for expert help in designing menus and recipes for meal plans used in this trial. Any significant changes to the protocol outlined above must be written in a formal amendment and approved by Regional Committee for Research Ethics South-East. Protocol amendments will be communicated and explained in any published manuscripts and also be noted at www.clinicaltrials.gov. Trial results will be published in academic journals and at www.clinicaltrials.gov in addition to communication at academic conferences. In addition, the team is collaborating with a cluster of academic and industry organizations through Future Foods (www.fremtidsmat.no) where results will be disseminated for potential development of healthy and sustainable foods. Future Foods is not involved in the design, conduct or interpretation of the study. If successful, the study team will contact relevant patient organizations for communication of results. The trial team will review topics suggested for presentation or publication. Lead author(s) will be determined by principal investigators. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = apr,

day = "15",

doi = "10.1186/s12967-021-02824-3",

language = "English",

volume = "19",

journal = "Journal of Translational Medicine",

issn = "1479-5876",

publisher = "BioMed Central Ltd",

number = "1",

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Stolt, E, Olsen, T, Elshorbagy, A, Kozich, V, van Greevenbroek, M, Ovrebo, B, Thoresen, M, Refsum, H, Retterstol, K & Vinknes, KJ 2021, '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', Journal of Translational Medicine, vol. 19, no. 1, 153. https://doi.org/10.1186/s12967-021-02824-3

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. / Stolt, Emma; Olsen, Thomas; Elshorbagy, Amany et al.
In: Journal of Translational Medicine, Vol. 19, No. 1, 153, 15.04.2021.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Sulfur amino acid restriction, energy metabolism and obesity

T2 - a study protocol of an 8-week randomized controlled dietary intervention with whole foods and amino acid supplements

AU - Stolt, Emma

AU - Olsen, Thomas

AU - Elshorbagy, Amany

AU - Kozich, Viktor

AU - van Greevenbroek, Marleen

AU - Ovrebo, Bente

AU - Thoresen, Magne

AU - Refsum, Helga

AU - Retterstol, Kjetil

AU - Vinknes, Kathrine J.

N1 - Funding Information: 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), and Institute of Basic Medical Sciences, University of Oslo. The funding agencies had no role in development of the study protocol. Funding Information: The authors wish to thank chef Johannes Gr?dal for expert help in designing menus and recipes for meal plans used in this trial. Any significant changes to the protocol outlined above must be written in a formal amendment and approved by Regional Committee for Research Ethics South-East. Protocol amendments will be communicated and explained in any published manuscripts and also be noted at www.clinicaltrials.gov. Trial results will be published in academic journals and at www.clinicaltrials.gov in addition to communication at academic conferences. In addition, the team is collaborating with a cluster of academic and industry organizations through Future Foods (www.fremtidsmat.no) where results will be disseminated for potential development of healthy and sustainable foods. Future Foods is not involved in the design, conduct or interpretation of the study. If successful, the study team will contact relevant patient organizations for communication of results. The trial team will review topics suggested for presentation or publication. Lead author(s) will be determined by principal investigators. Publisher Copyright: © 2021, The Author(s).

PY - 2021/4/15

Y1 - 2021/4/15

N2 - Background: Dietary sulfur amino acid (SAA) restriction is an established animal model for increasing lifespan and improving metabolic health. Data from human studies are limited. In the study outlined in this protocol, we will evaluate if dietary SAA restriction can reduce body weight and improve resting energy expenditure (REE) and parameters related to metabolic health.Method/design: Men and women (calculated sample size = 60), aged 18-45 years, with body mass index of 27-35 kg/m(2) will be included in a double-blind 8-week dietary intervention study. The participants will be randomized in a 1:1 manner to a diet with either low or high SAA. Both groups will receive an equal base diet consisting of low-SAA plant-based whole foods and an amino acid supplement free of SAA. Contrasting SAA contents will be achieved using capsules with or without methionine and cysteine (SAA(high), total diet SAA similar to 50-60 mg/kg body weight/day; SAA(low), total diet SAA similar to 15-25 mg/kg body weight/day). The primary outcome is body weight change. Data and material collection will also include body composition (dual X-ray absorptiometry), resting energy expenditure (whole-room indirect calorimetry) and samples of blood, urine, feces and adipose tissue at baseline, at 4 weeks and at study completion. Measures will be taken to promote and monitor diet adherence. Data will be analyzed using linear mixed model regression to account for the repeated measures design and within-subject correlation.Discussion: The strength of this study is the randomized double-blind design. A limitation is the restrictive nature of the diet which may lead to poor compliance. If this study reveals a beneficial effect of the SAA(low) diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders.

AB - Background: Dietary sulfur amino acid (SAA) restriction is an established animal model for increasing lifespan and improving metabolic health. Data from human studies are limited. In the study outlined in this protocol, we will evaluate if dietary SAA restriction can reduce body weight and improve resting energy expenditure (REE) and parameters related to metabolic health.Method/design: Men and women (calculated sample size = 60), aged 18-45 years, with body mass index of 27-35 kg/m(2) will be included in a double-blind 8-week dietary intervention study. The participants will be randomized in a 1:1 manner to a diet with either low or high SAA. Both groups will receive an equal base diet consisting of low-SAA plant-based whole foods and an amino acid supplement free of SAA. Contrasting SAA contents will be achieved using capsules with or without methionine and cysteine (SAA(high), total diet SAA similar to 50-60 mg/kg body weight/day; SAA(low), total diet SAA similar to 15-25 mg/kg body weight/day). The primary outcome is body weight change. Data and material collection will also include body composition (dual X-ray absorptiometry), resting energy expenditure (whole-room indirect calorimetry) and samples of blood, urine, feces and adipose tissue at baseline, at 4 weeks and at study completion. Measures will be taken to promote and monitor diet adherence. Data will be analyzed using linear mixed model regression to account for the repeated measures design and within-subject correlation.Discussion: The strength of this study is the randomized double-blind design. A limitation is the restrictive nature of the diet which may lead to poor compliance. If this study reveals a beneficial effect of the SAA(low) diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders.

KW - Adipose tissue

KW - Cysteine restriction

KW - Dietary intervention

KW - Gene expression

KW - Metabolic health

KW - Methionine restriction

KW - Obesity

KW - Plasma biomarkers

KW - Sulfur amino acids

KW - Translational research

KW - PREVENTION

KW - CYSTEINE

KW - RISK

KW - METHIONINE RESTRICTION

KW - PLASMA

KW - LIFE-STYLE

KW - ADIPOSE-TISSUE

U2 - 10.1186/s12967-021-02824-3

DO - 10.1186/s12967-021-02824-3

M3 - Article

C2 - 33858441

SN - 1479-5876

VL - 19

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

IS - 1

M1 - 153

ER -