People whose liver is not functioning properly may be able to reduce their chances of developing liver cancer or slow the progression of the disease if it has already started by making simple changes to their diet, including reducing their protein intake.
Led by Rutgers researchers, scientific progress They found that mice fed a low-protein diet had slower liver tumor growth and fewer cancer-related deaths. The findings reveal how the liver’s inability to properly process metabolic wastes can inadvertently create conditions that promote cancer development.
Liver cancer risk and the increasing burden of liver disease
Liver cancer is one of the deadliest primary cancers in the United States. The five-year survival rate for this disease is approximately 22%. According to the American Cancer Society, by 2025 there will be 42,240 new infections and 30,090 deaths.
Many more people live with liver diseases that increase their risk of cancer. Approximately one in four adults in the United States has fatty liver disease. This condition, along with viral hepatitis and heavy alcohol consumption, can cause cirrhosis and greatly increase the chance of developing liver cancer.
“If you have liver disease or damage that prevents your liver from functioning properly, you should seriously consider reducing your protein intake to lower your risk of developing liver cancer,” said study lead author Weixin Zhong, a distinguished professor in 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 produces toxic ammonia
When your body breaks down proteins, the nitrogen produced in the process can be converted to ammonia. Ammonia is toxic to both the brain and body. Normally, the liver converts ammonia into a safer compound called urea, which is removed from the body in the urine.
“Clinical observations have been made for decades that the liver’s ammonia-handling machinery is typically dysfunctional in patients with liver cancer,” Zhong said. “A question that remains unanswered so far is whether this dysfunction and the resulting accumulation of ammonia is a consequence of cancer or whether it promotes tumor growth.”
Study reveals how ammonia promotes tumor growth
To determine whether ammonia accumulation actually contributes to cancer development, Zong and colleagues designed an experiment in mice. They first induced liver tumors while keeping the animals’ ammonia-handling systems intact.
The researchers then used gene editing tools to turn off a key enzyme responsible for processing ammonia in some mice. Other mice retained normal ammonia handling. The scientists then compared tumor growth and survival between the two groups.
The difference was obvious. Mice that couldn’t process ammonia properly accumulated higher levels of the toxin. These animals developed larger tumor burdens and died much earlier than mice whose ammonia handling system was still functioning.
Further analysis revealed where the excess ammonia was going. Researchers have discovered that it is incorporated into compounds that cancer cells rely on to grow and proliferate.
“Ammonia enters amino acids and nucleotides, both of which tumor cells depend on to grow,” Zhong said.
Low-protein diet slowed liver tumor progression in mice
After identifying this metabolic pathway, the team considered practical strategies that could reduce ammonia accumulation. They tested whether reducing protein intake could limit the supply of nitrogen, which ultimately produces ammonia.
The results were dramatic. Mice fed a low-protein diet had tumors that grew significantly slower and lived much longer than mice that received normal amounts of protein.
For people with a healthy liver, consuming more protein is usually not a cause for concern because the liver can efficiently convert ammonia to urea. However, this finding may be important for people who already have liver damage or diseases that affect liver function.
Dietary decisions should be discussed with your doctor
Experts warn that dietary changes should be made carefully and under the guidance of a doctor. Cancer treatment guidelines often recommend higher protein intake to help patients maintain muscle mass and strength during treatment.
Zhong said the appropriate approach will likely depend on an individual’s specific health status and liver function. For patients whose bodies have a hard time removing ammonia, reducing protein intake could potentially be beneficial.
“Reducing protein intake may be the easiest way to lower ammonia levels,” Zhong says.
