Serine Supplementation for Obese Subjects With Fatty Liver Disease
Condition: Non-alcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      In this study, the investigators aim to increase the liver tissue level of GSH in NAFLD
      patients by short-term dietary serine supplementation and improve their liver function by
      lowering the oxidative stress resulting from hepatic steatosis.
    

Detailed description: 
      There is a strong correlation between major adverse health consequences of obesity and
      development of non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by abnormal
      hepatic accumulation of triglycerides and other lipids. It has become a worldwide health
      problem that accelerates cirrhosis, type 2 diabetes mellitus (T2DM), and especially premature
      cardiovascular morbidity and mortality.

      The plasma level of glutathione (GSH) is typically depleted in individuals with metabolism
      related disorders. However, cellular GSH levels cannot be increased by supplementing GSH and
      it must be synthesized within the liver either de novo or by salvation pathway. The
      investigators found that the level of GSH is not enough to maintain and regulate the thiol
      redox status of the liver in subjects with high hepatic steatosis at fasting stage due to the
      depletion of glycine. Glycine can be synthesized via the interconversion of serine through
      serine hydroxymethyl transferases (SHMT1 and SHMT2) with concomitant conversion of
      tetrahydrofolate (THF) into 5,10-methylene-THF (CH2-THF). It has been shown that the serine
      synthesis is downregulated in patients with NAFLD and supplementation of serine has
      attenuated alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats.

      In this study, the investigators aim to increase the liver tissue level of GSH in NAFLD
      patients by short-term dietary serine supplementation and improve their liver function by
      lowering the oxidative stress resulting from hepatic steatosis.

      Ten obese patients (BMI 30 - 39.9 kg/m2) with ultrasound and CT-verified non-alcoholic fatty
      liver disease (NAFLD). Subjects will be recruited from the Swedish CArdioPulmonary bioImage
      Study (SCAPIS) in Gothenburg. The participants in this study (50-65-year-old men and women)
      are randomly recruited from the Swedish Population and Address Register. Currently, 1050
      subjects have been analyzed and 5000 additional subjects will be analyzed over the next 2
      years. By January 2015, over 2000 subjects have been analyzed. Each subject is extensively
      phenotyped over two days. This includes extensive blood samples, anthropometry, carotid and
      liver ultrasound, and a CT examination that includes coronary calcium score, CT angiography
      of coronary arteries, thoracic aorta, and assessment of epicardial fat, liver fat, and
      subcutaneous abdominal fat.

      Preliminary analysis of the first 1050 subjects indicates that approximately 20% fulfill the
      criteria for NAFLD, consistent with data in other western populations.
    

Intervention name(s): Serine supplementation
Intervention type(s): Dietary Supplement
Intervention description(s): Serine supplementation (200 mg/kg/day)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: NAFLD; NASH; Serine; Glutathione