Effects of Folic Acid Supplementation on Liver Enzymes, Lipid Profile, and Insulin Resistance in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial

BACKGROUND: Previous evidence revealed an association between folate deficiency and non-alcoholic fatty liver disease (NAFLD). This study is the first one investigating the effects of folic acid on hepatic steatosis grade, liver enzymes, insulin resistance, and lipid profile in NAFLD cases. MATERIALS AND METHODS: Sixty-six participants with NAFLD were allocated randomly to take either a placebo or one oral tablet of folic acid (1 mg) on a daily basis within eight weeks. Serum folate, homocysteine, glucose, aminotransferases, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and lipids were assessed. Ultrasonography was used for assessing the liver steatosis grade. RESULTS: The serum alanine transaminase, grade of hepatic steatosis, and aspartate transaminase significantly were decreased within both study groups; however, the between-group comparison was not statistically significant. Of note, the decrease in ALT was more pronounced in folic acid compared with the placebo group (-5.45 ± 7.45 vs. -2.19 ± 8.6 IU/L). The serum homocysteine was decreased after receiving folic acid compared to the placebo (-0.58 ± 3.41 vs. +0.4 ± 3.56 μmol/L; adjusted P = 0.054). Other outcomes did not significantly change. CONCLUSION: Supplementation with folic acid (1 mg/d) for eight weeks among cases with NAFLD did not change significantly the serum levels of liver enzymes, the hepatic steatosis grade, insulin resistance and lipid profile. However, it was able to prevent the increase in homocysteine in comparison with the placebo. Conducting further research is suggested with the longer duration and different doses of folic acid, adjusted to the genotypes of methylenetetrahydrofolate reductase polymorphism, among NAFLD patients.