Machine learning uncovers manganese as a key nutrient associated with reduced risk of steatotic liver disease

Liver International, vol. 44, pp. 2807–2821

Abstract

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 20%-30% of the general population and is linked to high-caloric western style diet. However, there are little data that specific nutrients might help to prevent steatosis. METHODS: We analysed the UK Biobank (ID 71300) 24 h-nutritional assessments and investigated the association between nutrient intake calculated from food questionnaires and hepatic steatosis indicated by imaging or ICD10-coding. The effect of manganese (Mn) on subgroups with risk single nucleotide polymorphism carriage as well as the effect on metabolomics was investigated. All analyses are corrected for age, sex, body mass index, Townsend index for socioeconomic status, kcal, alcohol, protein intake, fat intake, carbohydrate intake, energy from beverages, diabetes, physical activity and for multiple testing. RESULTS: We used a random forest classifier to analyse the feature importance of 63 nutrients and imaging-proven steatosis in a cohort of over 25 000 UK Biobank participants. Increased dietary Mn intake was associated with a lower likelihood of MRI-diagnosed steatosis. Subsequently, we conducted a cohort study in over 200 000 UK Biobank participants to explore the relationship between Mn intake and hepatic or cardiometabolic outcomes and found that higher Mn intake was associated with a lower risk of ICD-10 coded steatosis (OR = .889 [.838-.943], p < .001), independent of other potential confounders. CONCLUSION: Our study provides evidence that higher Mn intake may be associated with lower odds of steatosis in a large population-based sample. These findings underline the potential role of Mn in the prevention of steatosis, but further research is needed to confirm these findings and to elucidate the underlying mechanisms.

Authors 12

1. Simon Schophaus Aachen Department of Internal Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen Aachen Germany

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany

2. Kate Townsend Creasy

   University of Pennsylvania

   Affiliation as printed

   Department of Biobehavioral Health Sciences, School of Nursing University of Pennsylvania Philadelphia Pennsylvania USA

   The Perelman School of Medicine, The Institute for Translational Medicine and Therapeutics University of Pennsylvania Philadelphia Pennsylvania USA

   Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania, USA

   The Perelman School of Medicine, The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA

3. Paul‐Henry Koop Aachen Department of Internal Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen Aachen Germany

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany

4. Jan Clusmann Aachen Department of Internal Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen Aachen Germany

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany

5. Julius W. Jaeger Aachen Department of Internal Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen Aachen Germany

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany

6. Varnitha Punnuru

   University of Pennsylvania

   Affiliation as printed

   Department of Biobehavioral Health Sciences, School of Nursing University of Pennsylvania Philadelphia Pennsylvania USA

   Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania, USA

7. Alexander Hemdorff Koch Aachen Department of Internal Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen Aachen Germany

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany

8. Christian Trautwein Aachen Department of Internal Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen Aachen Germany

   Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany

9. Rohit Seth Loomba

   University of California San Diego

   Affiliation as printed

   Division of Gastroenterology, Department of Medicine University of California at San Diego San Diego California USA

   Division of Gastroenterology, Department of Medicine, University of California at San Diego, San Diego, California, USA

10. Tom Luedde

    Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty Heinrich‐Heine‐University Düsseldorf Germany

11. Kai Markus Schneider Aachen Department of Internal Medicine III

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen Aachen Germany

    Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany

12. Carolin Victoria Schneider corresponding Aachen Department of Internal Medicine III

    Universitätsklinikum Aachen · University of Pennsylvania · RWTH Aachen University

    Affiliation as printed

    Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen Aachen Germany

    The Perelman School of Medicine, The Institute for Translational Medicine and Therapeutics University of Pennsylvania Philadelphia Pennsylvania USA

    Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany

    The Perelman School of Medicine, The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA