A study led by Rutgers researchers and published in Science Advances found that mice given a low protein diet experienced slower liver tumor growth and fewer cancer related deaths. The findings revealed how a liver that cannot properly handle metabolic waste can unintentionally create conditions that support cancer development.

Liver Cancer Risk and the Growing Burden of Liver Disease

Liver cancer is among the most lethal primary cancers in the United States. The disease has a five year survival rate of roughly 22%. According to the American Cancer Society, 42,240 new cases were expected in 2025, along with 30,090 deaths.

Even more people live with liver conditions that increase cancer risk. About 1 in 4 adults in the United States has fatty liver disease. This condition, along with viral hepatitis and heavy alcohol consumption, can lead to cirrhosis and significantly raise the likelihood of developing liver cancer.

“If you have liver disease or damage that prevents your liver from functioning correctly, you should seriously consider reducing your protein intake to lower the risk of developing liver cancer,” said the study’s senior author, Wei-Xing Zong, a distinguished professor at the Rutgers Ernest Mario School of Pharmacy and a member of the Cancer Metabolism and Immunology Program at Rutgers Cancer Institute, the state’s only NCI-designated Comprehensive Cancer Center.

How Protein Metabolism Can Produce Toxic Ammonia

When the body breaks down protein, nitrogen from that process can be converted into ammonia. Ammonia is toxic to both the brain and the body. Normally, the liver converts ammonia into a safer compound called urea, which is then removed from the body in urine.

“The clinical observation that the liver’s ammonia-handling machinery is usually impaired in liver cancer patients is decades old,” Zong said. “The question that has remained unanswered until now is whether this impairment and the resulting ammonia buildup are a consequence of the cancer or a driver of the tumor growth.”

Study Reveals How Ammonia Can Fuel Tumor Growth

To determine whether ammonia buildup actually contributes to cancer development, Zong and his colleagues designed an experiment in mice. They first induced liver tumors while keeping the animals’ ammonia processing system intact.

Next, the researchers used gene editing tools to shut down key enzymes responsible for processing ammonia in some of the mice. Other mice retained normal ammonia processing. The scientists then compared tumor growth and survival between the two groups.

The difference was clear. Mice that could not properly process ammonia accumulated higher levels of the toxin. These animals developed larger tumor burdens and died much faster than mice whose ammonia handling systems were still functioning.

Further analysis showed where the excess ammonia was going. Researchers discovered that it was being incorporated into compounds that cancer cells rely on to grow and multiply.

“The ammonia goes into amino acids and nucleotides, both of which tumor cells depend on for growth,” said Zong.

Low Protein Diet Slowed Liver Tumors in Mice

After identifying this metabolic pathway, the team explored a practical strategy that might reduce ammonia buildup. They tested whether lowering protein intake could limit the supply of nitrogen that ultimately forms ammonia.

The results were dramatic. Mice fed a low protein diet showed significantly slower tumor growth and survived much longer than animals that consumed normal amounts of protein.

For people with healthy livers, high protein intake is generally not a concern because the liver can efficiently convert ammonia into urea. However, the findings may be important for people who already have liver damage or diseases that affect liver function.

Dietary Decisions Should Be Discussed With Doctors

Experts caution that diet changes should be made carefully and with medical guidance. Cancer treatment guidelines often recommend higher protein intake to help patients maintain muscle mass and strength during therapy.

Zong said the right approach will likely depend on a person’s specific health situation and liver function. For patients whose bodies struggle to eliminate ammonia, lowering protein intake could potentially be beneficial.

“Reducing the protein consumption may be the easiest way to get ammonia levels down,” Zong said.