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/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

Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study

“…Triangulation of the evidence coming not only from observational studies but also from well-designed randomized controlled trials (RCTs) and genetic studies is required to demonstrate whether lower plasma methionine and tCys concentrations could be effective in preventing or reducing excessive adiposity at a population level. While an ongoing RCT may soon provide important insights [ 78 ], to date only a few studies have investigated whether genetic variants associated with plasma SAA concentrations are also associated with obesity, and focused on the methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism as determinant of plasma tHcy concentrations [ 10 ]. However, these analyses were not able to discriminate whether the causal factor is likely tHcy or one of its metabolic derivatives, and further analyses examining more polymorphisms in relation to all plasma SAA concentrations are needed.…”

The association of fasting plasma thiol fractions with body fat compartments, biomarker profile, and adipose tissue gene expression

“…Evidence from transgenic and dietary animal models suggests that increased cysteine availability is potentially obesogenic (Hasek et al 2013 ; Elshorbagy 2014 ; Niewiadomski et al 2016 ; Wanders et al 2018 ). Collectively, these findings have lately led to human dietary interventions designed to reduce dietary sulfur amino acid intake with the aim of improving body adiposity and metabolic health (Olsen et al 2018 , 2020a ; Stolt et al 2021 ).…”

Ruminococcaceae_UCG-013 Promotes Obesity Resistance in Mice

“…The results of a 16-week randomized controlled trial indicate that a methionine-restricted diet increases fat oxidation [ 47 ]. Sulfur amino acid (SAA) restricted diets reduced plasma methionine, cystathionine, and urinary total cysteine levels in adipose tissues, increased serum fibroblast growth factor 21 (FGF21) levels and altered the expression of gene products in subcutaneous adipose tissues [ 48 ]. A low SAA diet is likely to have beneficial effects on body composition and metabolic health, thus, opening up new strategies for preventing and treating overweight, obesity, and their associated diseases.…”