- Arginine is an amino acid that supports multiple metabolic and immune functions.
- A new study in mouse models linked low arginine with reduced production of a protein that helps the immune system detect threats.
- Arginine supplementation reduced colon tumors and improved flu and COVID-19 outcomes in mice.
A new study led by Rockefeller University researchers found that arginine levels may affect how the immune system recognizes cancer cells and virus-infected cells.
The researchers tested arginine supplementation in mice and learned that as arginine levels increased, cancer tumors decreased and viral infection outcomes improved.
Since arginine is relatively inexpensive, the scientists hope it could provide a low-cost addition to existing treatments if human trials confirm the findings.
The study appears in the journal Cell.
Arginine is an amino acid found in protein-rich foods such as meat, fish, dairy products, nuts, and legumes.
The body produces arginine and obtains it through food. However, cancer and viral infections such as COVID-19 can reduce its availability. These conditions may activate immune cells that produce arginase, an enzyme that breaks down arginine.
The researchers behind the new study wanted to determine whether these changes could directly affect the body’s immune response to cancer and viral infections.
First, they analyzed existing data on amino acid levels in cancer tissue and in lung tissue from mice with influenza or SARS-CoV-2 infections. Their analysis identified arginine as one of the most consistently depleted amino acids across these conditions.
Next, the researchers restricted arginine in human and mouse colorectal cancer cells. They also tested human cell lines from melanoma and breast, stomach, and pancreatic cancers.
The team measured levels of a protein called major histocompatibility complex class I (MHC-I), which helps the immune system identify infected or abnormal cells.
The researchers measured how much antigen the cancer cells displayed and how effectively CD8 T cells killed them. They also examined how arginine affected protein production.
Next, the team tested supplemented, standard, and restricted arginine diets in a mouse model of colorectal cancer.
In separate experiments, the researchers infected mice with influenza or a mouse-adapted form of SARS-CoV-2. They monitored weight loss, survival, viral levels, and lung damage.
Arginine restriction reduced MHC-I levels in human and mouse colorectal cancer cells. The researchers found similar effects in several other cancer cell lines.
In mice, arginine supplementation reduced colon tumors and improved outcomes from influenza and SARS-CoV-2, the virus that causes COVID-19.
Cancer cells with less arginine displayed fewer antigens. As a result, CD8 T cells identified and killed fewer cancer cells.
When the researchers restored arginine after 24 hours of restriction, MHC-I levels recovered within hours. The researchers found that low arginine levels caused ribosomes to stall during MHC-I production.
In the colorectal cancer experiments, mice that received additional dietary arginine developed fewer and smaller tumors, while mice that consumed less arginine developed more tumors.
Arginine supplementation also reduced weight loss and mortality in mice with influenza. The researchers observed benefits even when they started supplementation 1 day after infection.
In mice with SARS-CoV-2, supplementation reduced weight loss, viral levels, and lung damage.
Study author Sohail Tavazoie, MD, PhD, spoke with Medical News Today about the study.
“The amount of arginine that we have supplemented is equivalent to about 10 grams of arginine per day,” Tavazoie said.
His team hopes to test supplementation in people with influenza who face a high risk of severe illness.
The NIH reports that doses of 9 to 30 grams (g) may cause gastrointestinal discomfort and slightly lower blood pressure. Human trials are needed to determine whether the arginine dose Tavazoie mentioned safely and effectively improves outcomes.
Anton Bilchik, MD, PhD, a surgical oncologist, chief of medicine, and Director of the Gastrointestinal and Hepatobiliary Program at Providence Saint John’s Cancer Institute, who was not involved in this research, also spoke with MNT about the study.
“The study highlights an intriguing and potentially important role for arginine, an inexpensive and widely available amino acid,” said Bilchik.
Bilchik said most healthy people can generally tolerate 10 g daily, but the dose may pose risks for people with kidney or liver disease. He advised consulting a healthcare professional before using arginine to boost immunity.
“Patients should avoid self-prescribing supplements like arginine with the expectation of boosting immunity or improving cancer outcomes until more definitive human data are available,” he advised.
Jagdish Khubchandani, PhD, MPH, a public health professor at New Mexico State University, likewise not involved in the study, agreed that arginine could plausibly improve MHC-I production.
However, Khubchandani emphasized that researchers conducted the study in highly controlled animal models and focused on specific antiviral and antitumor conditions.
“Unless there is a human trial, the findings have little value,” he said, noting that researchers still need to establish who might benefit and under what circumstances.
He stressed that people with cardiovascular, kidney, or liver disease and pregnant people should not take this amount without medical guidance.
“We have too many diet fads and supplements that are mostly useless,” Khubchandani cautioned, adding that human testing should come next.
