Low folate and B12 linked to severity of fatty liver disease

By Tim Cutcliffe

- Last updated on GMT

© iStock
© iStock
Two key B vitamins may be linked to the progression of liver fibrosis in non-alcoholic fatty liver disease (NAFLD), say researchers.

The study involving 83 patients with non-alcoholic steatohepatitis (NASH), found that blood levels of folate (vitamin B9) and vitamin B12 were inversely related to the grade of fibrosis (the formation of scar tissue) in the liver.

Furthermore, low serum B12 levels were associated with higher severity of NASH, found the research team, a collaboration between Tel-Aviv University and Nazareth Hospital EMMS, Israel.

NASH is a progressive form of NAFLD, from which cirrhosis or liver cancer can subsequently develop. NAFLD is widely known to start as simple steatosis, the accumulation of fat cells within the liver, and progress to NASH as fibrosis occurs.

“In this study, both folate and vitamin B12 serum levels were found to be significantly correlated with the liver fibrosis grade, whereas vitamin B12 status was also associated with NASH degree of activity,”​ commented co- lead researcher Dr. Abdulla Watad of Tel-Aviv University.


Although previous research has identified an association between lower levels of vitamins and chronic liver disease, this is the first study to correlate folate and B12 levels to NASH severity, explained the researcher, writing in Nutrients.

NAFLD is recognised as the most prevalent liver disease worldwide, with particularly high incidence occurring in the Middle East and South America,

“NASH is a chronic liver condition, which imposes a dramatic burden, both in epidemiological and clinical terms,​” said Watad.

“Our study demonstrated that low levels of folate (B9) and vitamin B12 can be used as independent predictors of the histological severity of NASH. Thus, these findings may have practical implications in the follow-up and prognosis assessment of NASH patients.”

Study details

The study population had an average age of 41 years and included 51 males and 32 females. Researchers analysed liver biopsies to assess the degree of steatohepatitis in the patients using the SAF (steatosis, activity, and fibrosis) scoring system. Blood levels of folate and B12 were measured and correlations calculated with the stages of progression of NAFLD and NASH activity.

The study was cross-sectional in design, so no causal conclusions can be drawn between low folate / B12 status and the development of NASH, emphasised the researchers.   

Although serum folate levels were predictive of NAFLD in this study, the scientists noted that a small open-label intervention trial using 1 mg/day of folic acid for 6 months found no improvement in fibrosis. (However, folate deficiency was only found in one patient).

Pathological mechanisms linking deficiency of the two B vitamins would need to be established in future trials, the researchers suggested.

“Further studies regarding the pathological role of low folate and B12 levels in NASH development are warranted,”​ they concluded.

Source:  Nutrients

Volume 10, issue 4, article no. 440   doi: 10.3390/nu10040440

“Folate and B12 Levels Correlate with Histological Severity in NASH Patients”

Authors:  Mahmud Mahamid, Abdulla Watad et al





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