Mice fed a diet rich in oleic acid, the main fat in olive oil, developed pancreatic tumors faster than animals on other diets. Mice fed fish oil had about half as much disease. The results come from a Yale School of Medicine team and appeared in Cancer Discovery, the American Association for Cancer Research journal, on April 29.
“It’s really the type of fat that you’re consuming, not just total fat content,” said Christian Felipe Ruiz, PhD, lead author and an associate research scientist in Yale’s Department of Genetics. “We found that some fats promote cancer, as we would expect, while other fats are really good at suppressing cancer.”
Twelve diets, same calories
The cancer in question is pancreatic ductal adenocarcinoma, or PDAC, the most common form of pancreatic cancer. Only about 13% of people diagnosed with it live five years. Ruiz noted that more than 65,000 people in the US are expected to be diagnosed this year, with over 50,000 deaths. Treatment options for advanced disease are limited, he said, so “prevention strategies are sorely needed.”
High-fat diets have been tied to greater PDAC risk before, but nobody had pinned down why. Senior author Mandar Deepak Muzumdar, MD, an associate professor of genetics and internal medicine at Yale, led work to answer that. The team built 12 high-fat diets with identical calories. Only the source of fat changed, and the mix was meant to resemble how Americans eat today.
That differs from older experiments, Ruiz said. Many gave mice a single fat at very high levels, often with 60% of calories from lard, which looks little like a human diet and makes individual fatty acids hard to separate.
What happened in the mice
The animals carried a genetic mutation that produces a disease close to human PDAC. Tumors came faster on diets high in oleic acid, a monounsaturated fat (MUFA) that also occurs in high-oleic safflower and sunflower oils, peanuts and lard. Polyunsaturated fats (PUFAs) slowed the cancer, and omega-3s from fish oil did so most strongly.
“When we fed mice diets enriched with fish oil, we saw a 50% reduction in disease compared with mice fed a standard fat diet,” the researchers said. Raising the MUFA to PUFA ratio raised disease burden. Lowering it cut disease burden.
The team traced this to ferroptosis, a form of programmed cell death triggered by lipid oxidation. PUFAs oxidize more easily, which leaves cancer cells more exposed to dying. “Monounsaturated fats really protect the cancer cells from lipid oxidation,” Ruiz explained.
Oleic acid had a surprising role given its name as a heart-healthy fat. “It’s traditionally been considered a healthy type of fat for cardiovascular health,” Ruiz said.
Limits and next steps
Oleic acid’s cancer-promoting effect was pronounced in male mice and largely missing in females. PUFAs reduced cancer in both sexes. Ruiz said this adds to evidence that biological sex can shape the metabolic pathways behind cancer.
No one has replicated the work in people. The findings may matter most for those at higher risk, including people with chronic pancreatitis, obesity, late-onset diabetes or a family history of the disease. Ruiz said clinicians often hear the question of what to change in diet to prevent cancer. “Right now, we don’t have clear answers, but this study begins to shed light.”
The group plans to test whether changing dietary fat could help people who already have pancreatic cancer, and whether the MUFA to PUFA ratio in blood could flag risk early. The work was supported by the National Institutes of Health and Yale University, among others. People worried about their own diet should speak to their doctor.
Sources
- The Type of Fat—Not the Amount—Fuels Pancreatic Cancer
- One fat helped pancreatic cancer grow while another cut disease in half
Sources
- The Type of Fat—Not the Amount—Fuels Pancreatic Cancer | Yale…
- One fat helped pancreatic cancer grow while another… | ScienceDaily
