Fatty liver and Vitamin B12 deficiency: Is there a connection, and what to do about it

Fatty liver disease affects millions of people worldwide, with nonalcoholic fatty liver disease (NAFLD) being the most common form. The rise in NAFLD, especially amongst children and teens, has further raised concerns. While many factors contribute to the disease, research has sparked interest in a potential link between vitamin B12 deficiency and fatty liver disease. Before we delve into the association between fatty liver and vitamin B12, let’s look at what fatty liver disease is and its symptoms

Fatty liver is a condition in which fat builds up in the liver. What makes this condition especially dangerous is that, in most people, fatty liver disease does not cause any symptoms. There are two types of fatty liver: Nonalcoholic fatty liver disease (NAFLD) and Alcoholic fatty liver disease (AFLD). AFLD occurs in people who drink large amounts of alcohol, while NAFLD occurs in people who drink little or no alcohol.

Some of the common symptoms include:

• Fatigue: Persistent tiredness or weakness.

• Abdominal discomfort: A dull ache or feeling of fullness in the upper right abdomen, where the liver is located.

• Unexplained weight loss: Losing weight without trying, especially in more advanced stages.

• Weakness: General lack of energy or muscle strength.

• Jaundice: Yellowing of the skin or eyes, indicating liver dysfunction (more common in severe cases).

• Swelling: Fluid buildup in the abdomen (ascites) or legs (edema), typically in advanced stages.

• Itchy skin: Persistent itching, often linked to liver issues.

• Confusion or difficulty concentrating: In severe cases, due to toxin buildup affecting brain function (hepatic encephalopathy).

Vitamin B12 (cobalamin) is essential for red blood cell production, DNA synthesis, and nerve function. It is naturally found in animal products like meat, eggs, and dairy. A deficiency can lead to numerous symptoms and can even progress to irreversible neurological issues if left untreated.

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A 2022studyuncovered a mechanism that leads to an advanced form of fatty liver disease, and it turns out that vitamin B12 and folic acid supplements could reverse this process.

NAFLD affects 25 per cent of all adults and is the leading cause of liver transplant worldwide. When the condition progresses to inflammation and scar tissue formation, it is known as non-alcoholic steatohepatitis (NASH).

There are limited pharmacological treatments for NASH, as scientists don’t understand the mechanics of the disease. Although scientists know that NASH is associated with elevated blood levels of an amino acid called homocysteine, they didn’t know what role, if any, it plays in the development of the disorder.

Dr Madhulika Tripathi, first author of the study, who is a senior research fellow with the Laboratory of Hormonal Regulation at Duke-NUS’ Cardiovascular & Metabolic Programme, study co-author Dr Brijesh Singh and their colleagues in Singapore, India, China and the US confirmed the association of homocysteine with NASH progression in preclinical models and humans. They found that rising homocysteine levels impair key liver proteins, particularly syntaxin 17, disrupting fat metabolism and contributing to disease progression. However, supplementing with vitamin B12 and folic acid restored syntaxin 17 function, and autophagy. It also slowed NASH progression and reversed liver inflammation and fibrosis.

“Our findings are both exciting and important because they suggest that a relatively inexpensive therapy, vitamin B12 and folic acid, could be used to prevent and/or delay the progression of NASH. Additionally, serum and hepatic homocysteine levels could serve as a biomarker for NASH severity,” Dr. Singh said.

“The potential for using vitamin B12 and folate, which have high safety profiles and are designated as dietary supplements by the US Food and Drug Administration, as first-line therapies for the prevention and treatment of NASH could result in tremendous cost savings and reduce the health burden from NASH in both developed and developing countries," Professor Paul M. Yen, Head of the Laboratory of Hormonal Regulation at Duke-NUS’ Cardiovascular & Metabolic Disorders Programme, and senior author of the study, said.

“Currently, the only treatment for patients with end-stage liver disease is to receive a transplant. The findings by Dr Tripathi and her colleagues demonstrate that a simple, affordable, and accessible intervention could potentially halt or reverse the damage to the liver, bringing new hope to those suffering from fatty liver diseases. The team’s findings underscore the value of basic scientific research, through which the scientific community continues to have a major positive impact on the lives of patients,” Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS, added.

Eating a healthy diet can also reduce fatty liver