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/m2 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 (SAAhigh, total diet SAA ~ 50-60 mg/kg body weight/day; SAAlow, total diet SAA ~ 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 SAAlow diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders. Trial registration ClinicalTrials.gov: NCT04701346, Registration date: January 8th, 2021.

Department of Biostatistics Institute of Basic Medical Sciences University of Oslo Oslo Norway

Department of Internal Medicine and CARIM School of Cardiovascular Diseases Maastricht University Maastricht The Netherlands

Department of Nutrition Institute of Basic Medical Sciences University of Oslo Sognsvannveien 9 0372 Oslo Norway

Department of Pediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Pharmacology University of Oxford Oxford UK

Department of Physiology Faculty of Medicine University of Alexandria Alexandria Egypt

Department of Sports Science and Physical Education Faculty of Health and Sport Sciences University of Agder Kristiansand Norway

The Lipid Clinic Oslo University Hospital Oslo Norway

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

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ClinicalTrials.gov
NCT04701346