MTHFR and Fatty Liver
Fatty Liver Disease isn’t Just an Alcohol Issue
It turns out that alcohol isn’t the only culprit when it comes to fatty liver disease (FLD). Elevated homocysteine levels are associated with non-alcoholic fatty liver disease (NAFLD), an often silent but serious disease that causes fat in the liver and inflammation that can lead to permanent damage. The condition is a common cause of abnormal liver function, and it’s on the rise in both developed and developing countries.
Since the MTHFR enzyme plays a role in regulating homocysteine, a recent Turkish study looked for correlations between MTHFR variants and NAFLD. The study included 286 patients comprised of 136 healthy control subjects and 150 with FLD. Researchers excluded patients with significant alcohol use and other contraindicated conditions from the study. Each patient had their liver function tested, and ultrasounds of their livers were performed. An experienced radiologist graded the presence and stage of fatty liver disease as mild, moderate, or severe.
Researchers also performed genetic testing, specifically looking for the MTHFR C677T and A1298C variants. These mutations decrease MTHFR enzyme function, causing a rise in homocysteine levels. The increased homocysteine can lead to free radicals that cause oxidative stress, resulting in inflammation and liver damage.
Since vitamin B12 and folic acid levels can affect homocysteine levels, the researchers were surprised to find that the levels of these nutrients didn’t differ much across groups. Still, they did find significantly higher homocysteine levels in the severe NAFLD group than the control and mild NAFLD groups.
As expected, they did find that both the MTHFR C677T and A1298C mutations were more common in NAFLD patients than the healthy control group. Both of these mutations were about equally common in the NAFLD groups.
While this most recent study does supports one prior study, the literature on correlations between these MTHFR variants and NAFLD has been inconclusive, possibly due in part to different techniques. Still, the authors use previous research to speculate that insulin may be involved in the link between elevated homocysteine and FLD. Insulin is a common factor in metabolic disorders, and there’s evidence that NAFLD is linked to metabolic syndrome. Insulin has been shown to affect homocysteine processing in rats, and in a study of obese adolescents, insulin levels were significantly higher in kids with a homozygous (double) C677T mutation.
This particular study is limited by the fact that lifestyle factors affecting homocysteine levels – such as smoking and exercise – weren’t asked of participants. While a link is suggested, more and larger studies can help clarify the role of MTHFR gene mutations in NAFLD. In the meantime, a simple genetic test can help doctors determine who may be susceptible. Advising those patients to make lifestyle changes early on can reduce their future risk of fatty liver disease.