The prevalence of overweight and obesity are increasing worldwide. The World Health Organization reports that 1.9 billion people were overweight and 650 million were obese in 2016. Many people are aware that obesity leads to increased risk of chronic diseases and mortality, yet struggle to lose weight and maintain weight loss.

Research over the last decade suggests that methionine and cysteine, two dietary amino acids that are abundant in proteins from animal sources, play a role in development of obesity and related metabolic diseases. In mice and rats, diets low in methionine and cysteine content were found to improve glucose and lipid metabolism and reduce body fat. In human studies in thousands of subjects, blood levels of cysteine were found to be higher in overweight and obese individuals, in a dose-dependent manner. In the STAY project, we aim to examine whether we can achieve the beneficial findings seen in animal experiments in humans with obesity.

We will perform a dietary study in participants with obesity to evaluate the effects of a plant-based diet low in methionine and cysteine on body weight, body composition, and energy balance, as well as obesity-related blood markers (glucose and lipid metabolism, amino acids, fatty acids) and gene expression patterns. In addition, we will use data form a large Dutch population study to investigate associations of dietary, circulating and urinary methionine and cysteine with body fat and chronic disease, including diabetes. Using genetic data from this population, we will investigate if certain genes are linked to the effect of diet on body fatness. In the analytical part of the STAY project, we will use state-of-the-art methodology to assess plasma and urine sulfur amino acids and related compounds, plasma lipid and fatty acid profiles, glucose tolerance, and obesity and appetite-related hormones to increase our understanding of how methionine and cysteine are linked to increased body adiposity.

In combination, this project will help us understand the role of methionine and cysteine in human obesity and obesity related diseases, and to what extent their restriction by a plant-based diet can facilitate weight loss and improve metabolic health.

In 2021, the randomized controlled dietary intervention started (March), and so far 44 participants have completed the trial (powered for 46-60 participants). The trial protocol was published in Journal of Translational Medicine (IF 5.531). Biochemical analyses of the Dutch population was finalized early spring, and data analysis and manuscript preparation has started based on the generated data. Furthermore, continuous biomarker assessment of the biological material collected in the intervention trial are being performed in the Czech Republic.

No research results have been published yet, but there are several manuscripts in preparation. The trial protocol has been published.

Stolt, E., Olsen, T., Elshorbagy, A. et al. 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. J Transl Med 19, 153 (2021). https://doi.org/10.1186/s12967-021-02824-3