Writing in the journal Nature Cancer, researchers at Cedars-Sinai Health Sciences University conducted a Phase 1 clinical trial to improve gut health among stage 4 pancreatic cancer patients because they do not absorb nutrients well.
Half of the patients in the study maintained their weight, and the investigators found a connection between the way the bacteria in the gut responded to the glutamine and patient outcomes. Life expectancy of these patients taking glutamine and chemotherapy was more than double the average life expectancy associated with the typical standard of care.
“All the patients that did well, they reversed their cachexia,” said Dr. Neil Bhowmick, PhD, Mark Goodson Chair in Oncology Research, professor of medicine and biomedical sciences at Cedars-Sinai Cancer, and senior author of the study. “I think this had a big role to do with the fact that they had less leaky gut.”
Cachexia and leaky gut
People experiencing cachexia lose skeletal muscle, a vicious cycle of inflammation in the muscle that causes its degradation. Other muscles in the body are impacted as well.
“Your heart is a muscle. Your diaphragm is a muscle,” Dr. Bhowmick said. “So oftentimes these patients, they don’t pass away because the tumor just went out of control. They pass away because their diaphragm just got too weak to pump.”
Cachexia is not unique to pancreatic cancer, though 80% of patients with pancreatic cancer develop it.
Additionally, taking chemotherapy makes patients even weaker. They often experience leaky gut and diarrhea as a result. Glutamine is well described in the literature to help mitigate leaky gut. L-glutamine is an amino acid that occurs naturally in the body and plays an important role in digestion.
“We thought at least the patients will not feel so bad with the chemo if we give them glutamine,” Dr. Bhowmick said. “Worst case scenario, they will have better quality of life. And sure enough, that happened. They definitely had better quality of life. And what surprised the hell out of us was that the tumors actually shrank and two of the patients had a complete response [from the chemotherapy, glutamine combo].”
He added that pancreatic cancer uniquely metabolizes glutamine. It utilizes glutamine not just for energy or building blocks for proteins and nucleotides, as all cells do, but it uses it as an antioxidant.
Study details
The investigators studied 16 patients with advanced pancreatic cancer. All patients were treated with a standard chemotherapy combination of gemcitabine and nab-paclitaxel, along with clinical-grade l-glutamine supplements (30 g per day orally).
Current treatment for stage 4 pancreatic cancer is a cocktail of chemotherapy, with overall survival ranging from eight to 13 months. In this small, single-arm Phase 1 trial, patients receiving L-glutamine alongside chemotherapy had a median overall survival of 22 months, compared with historical benchmarks of roughly 8–13 months with standard treatment.
“L-glutamine supplementation appears to preserve gut barrier integrity, limit malabsorption and inhibit proinflammatory response, providing yet another possible benefit through anticachexia effects that have been previously characterized with l-glutamine administration,” the researchers wrote. “Collectively, our correlative studies suggest that intermediary metabolism, basal gut microbiome constitution and associated systemic inflammatory signature could serve as biomarkers for l-glutamine treatment.”
The researchers explained that the gut microbiome constitution at baseline and l-glutamine-driven effects on bacterial metabolism and glutamine intermediary metabolism “could serve as the basis of efficacy of the combination therapy for further testing in a randomized control trial.”
The investigators are interested in studying the impact of administrating glutamine in patients with earlier stage pancreatic cancer and in patients taking newer pancreatic cancer drugs.
“The survival rate for advanced pancreatic cancer is poor,” said Dr. Robert Figlin, MD, interim director of Cedars-Sinai Cancer in a statement. “This trial points to a potential new option for optimizing first-line chemotherapy for patients while also opening up a number of new avenues for our physician-scientists to study.”
Source: Nature Cancer. doi: 10.1038/s43018-026-01225-z. “l-Glutamine in combination with first-line gemcitabine and nab-paclitaxel in advanced pancreatic ductal adenocarcinoma: an open-label, single-arm, phase 1 GlutaPanc trial.” Authors: Jun Gong et al.
