Betaine for nonalcoholic fatty liver disease

Abstract

Based on animal studies and pilot studies in humans, betaine, a methyl donor for the remethylation of homocysteine, may be a therapeutic agent for nonalcoholic steatohepatitis (NASH). We evaluated the safety and efficacy of betaine for patients with NASH and whether betaine positively modified factors postulated to be "second hits" and underlying mechanisms of NASH. We conducted a randomized placebo-control study of 55 patients with biopsy-proven NASH who received either oral betaine (20 g daily) or placebo for 12 months. Pre-and posttreatment variables were analyzed using the paired t test or Wilcoxon rank test. Treatment groups were comparable at baseline. Of the 35 patients (17 betaine, 18 placebo) who completed the study, 34 patients (16 betaine, 18 placebo) underwent posttreatment liver biopsy. Patients randomized to betaine had a decrease in steatosis grade. No intra-or intergroup differences or changes in nonalcoholic fatty liver disease activity score or fibrosis stage were noted. Elevations of insulin, glucose, and proinflammatory cytokines and the reduced antioxidant status noted in NASH patients did not improve with betaine therapy. The antiinflammatory agent adiponectin was significantly reduced in both groups and did not change with therapy. Lastly, S-adenosylhomocysteine was approximately twice normal and was not reduced by betaine therapy. Conclusion: Compared to placebo, betaine improved hepatic steatosis and may protect against worsening steatosis. High-dose betaine supplementation failed to reduce S-adenosylhomocysteine and did not positively affect any of the second hit mechanisms postulated to contribute to NASH that we studied. Although betaine has been proven effective in treating hepatic steatosis in several animal models, translating novel therapeutic options noted in animal studies to humans with NASH will prove challenging.

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

“…Predictors of histological response to antioxidants are unclear: weight loss, circulating oxidative stress markers or vitamin E deficiency do not predict histological response [49, 95,96,100]. There was no significant publication bias (ESM Fig.…”

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

“…Two RCTs were conducted to confirm the effect of betaine on NAFLD/NASH; however, one involved a combination therapy with other drugs, and in the other, betaine monotherapy did not show beneficial efficacy against NAFLD/NASH [102]. Several cohort studies were conducted to confirm the usefulness of liver transplantation for end-stage NASH cirrhotic patients.…”

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

“…In addition to these histological improvements, the therapy for 1 year was safe and well tolerated. A recent (2009) follow-up study by the same group utilized a randomized, placebo-controlled protocol with 55 patients with biopsy-proven NASH [59]. After 1 year of oral betaine supplementation (20 g/day) or placebo, betaine-supplemented patients showed a decrease in hepatic steatosis.…”