Dietary Allowance of Methyl Donor Nutrients to Minimize Risks of Non-alcoholic Fatty Liver Progression

Dietary Allowance of Methyl Donor Nutrients to Minimize Risks of Non-alcoholic Fatty Liver Progression

Dietary Allowance of Methyl Donor Nutrients to Minimize Risks of Non-alcoholic Fatty Liver Progression: Novel Diagnostic and Therapeutic Markers in Metabolomics of Gut Microbiome/Host Methyl Nutrition and the Working Mechanisms

Investigate the methyl donors requirement of NAFLD patients to correct the malnutrition, lipid-toxicity, microbiota dysfunction, and metabolomics biomarkers.

Folate/choline/betaine, service as a methyl-donor nutrients, are essential nutrients involving in hepatic one-carbon and bioenergetic metabolism. Methyl-donor nutrients deficiency cause liver and muscle dysfunction as result of non-alcoholic fatty liver diseases (NAFLD) and its progressive lesions of steatohepatitis (NASH), fibrinogen cirrhosis and hepatoma. As methyl-donor nutrients intakes in Taiwanese population are highly insufficient, the dietary requirement of methyl-donor nutrients upon genetic, epigenetic and microbiota interaction to prevent or/and co-therapy of NAFLD progression is currently not known. In this study, we investigate whether intervention of methyl-donor nutrients improve or retard NAFLD progress. NAFLD patients are randomly divided into three groups and received placebo, folic acid, or choline, respectively. From first day to ten day, interventions are given double recommended daily intake dose of folic acid or double adequate Intakes dose of choline, then continuing with four times, and eight times dose for every 10 days. All supplements solve in cranberry juice. At the end of every ten days intervention prior, interventions are measurement of weight and body fat, and collection of blood and feces. The primary outcome measures are described to decreased body weight or body fat, improvement of liver function and fatty liver, and increasing methyl-donor nutrients levels.

In this study, we divide intervention group into two groups which received folic acid (FA) or choline chloride (CC) supplement. Each subgroups contain 20 subjects, including 10 men and women. According to Recommended Daily Nutrient Allowance, FA recommended intake is 400 ug / day and choline recommended intake in men and women is 450 and 390 mg / day. From phase 1 to phase 3 stage, for every 10 days, subjects are given 2-fold, 4-fold and 8-fold recommended intake dose of FA or CC. All supplement solve in 240 ml cranberry juice.

To estimate hepatic fat content, interventions are detected fat content in liver by using MRI or abdominal ultrasound. We assume changing liver fat proportion after finishing intervention.

To estimate liver dysfunction, we detect biochemical markers in plasma, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and glutamyl transpeptidase. After finishing intervention, we assume improving liver function.

Body fat percentage are measured by using electronic body fat meter. Body fat percentage change after intervention.

Folate and choline concentration in plasma are detected to refer methyl nutrients levels. Methyl nutrients levels change after finishing intervention.

Inclusion Criteria: NAFLD/NASH patients Folate levels in plasma < 6 ng/mL or choline levels in plasma < 5 micromol per liter Folate intake < estimated average requirement or choline intake < 50% adequate Intakes Homocysteine levels in plasma > 9 micromol per liter Exclusion Criteria: Asymptomatic carrier of hepatitis B and C Liver disease except NAFLD Taking drugs that causes fatty liver Inflammation about stomach or intestines Pregnancy Cancer except liver cancer Heart disease, vascular disease, or psychosis Intake alcohol over 100 g or unaccessible intake alcohol