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

Abstract

AbstractDietary sulfur amino acid restriction (SAAR) improves metabolic health in animals, but in humans, SAAR has not been investigated in translational clinical trials. 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 59 humans with overweight and obesity in a double-blind, randomized controlled trial (ClinicalTrials.gov:NCT04701346). Participants were randomized to a plant-based diet low (∼2 g/d, SAAR) or high (∼5.6 g/d, control group) in sulfur amino acids. The diets were provided in full to the participants. After 8 weeks of intervention, SAAR led to a ∼20 % greater weight loss compared to controls (β (95 % CI) -1.14 (-2.04, -0.25) kg, p = 0.012). 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 processer related to structural components were downregulated. In conclusion, our study shows that SAAR leads to weight loss and metabolic benefits. Further research SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans.