For many years, the common assumption was simple. Reducing fat intake may reduce cancer risk. New research suggests the situation is much more complex.
Scientists report that when it comes to pancreatic cancer, the specific types of fat in your diet may be more important than the total amount you eat.
The survey results are cancer discoveryThe Journal of the American Association for Cancer Research shows that different fats can have dramatically different effects on cancer development.
“It’s not the total amount of fat that’s important, but the actual type of fat you’re consuming,” says Christian Felipe Ruiz, Ph.D., associate research scientist in the Department of Genetics at Yale School of Medicine and lead author of the study. “Depending on the type of fat you consume, its effects can be quite different. As we expected, we found that some fats promote cancer, while others are very good at inhibiting cancer.”
Oleic acid is linked to promoting tumor growth
One of the most unexpected findings of this study concerned oleic acid, the main fatty acid found in olive oil.
Researchers have found evidence that oleic acid may promote tumor growth in pancreatic cancer. The results surprised the research team, given the fatty acids’ long-standing reputation as heart-healthy dietary fats.
“Traditionally, it’s been thought of as a healthy fat for cardiovascular health,” Lewis says.
The cancer tested in the study was pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer and one of the deadliest cancers overall. The five-year survival rate for people diagnosed with PDAC is only about 13%.
“More than 65,000 people in the United States are expected to be diagnosed with PDAC this year, and more than 50,000 people will die,” Lewis points out. “Currently, effective treatment options are limited, especially for advanced disease. Therefore, preventive strategies are desperately needed to improve PDAC mortality.”
Previous studies have linked high-fat diets to an increased risk of PDAC, but scientists have struggled to pinpoint exactly how dietary fat affects the disease. This new study, led by senior author Mandar Deepak Muzumdar, MD, associate professor of genetics and internal medicine at YSM, sought to answer that question.
Muzumdar is also a member of the Yale Cancer Center and the Yale Cancer Biology Institute on West Campus.
Comparison of different types of dietary fats
To isolate the effects of specific fats, the researchers created 12 different high-fat diets. Each meal contains the same calories, the only difference being the fat source. These diets were designed to reflect common fat intake patterns in the modern American diet.
According to Ruiz, much of the previous research was based on simpler approaches.
For decades, researchers commonly “feed mice very high levels of dietary fat using a single fat source.” These diets often derive 60% of their calories from lard, which does not accurately reflect typical human eating habits and makes it difficult to determine the impact of individual fatty acids.
“Exactly which components of dietary fat cause cancer remains a mystery,” Lewis added.
The results were amazing. Mice with a genetic mutation that causes a disease similar to human PDAC developed tumors more rapidly when fed a diet rich in oleic acid. Oleic acid is a monounsaturated fatty acid (MUFA) found in foods such as olive oil, high oleic safflower oil, high oleic sunflower oil, peanuts, and lard.
In contrast, a diet rich in polyunsaturated fatty acids (PUFA) slowed cancer development. The strongest protective effects were seen with omega-3 fatty acids found in fish oil.
“When we fed mice a diet enriched with fish oil, we found a 50% reduction in disease compared to mice fed a standard fat diet.”
Effect of dietary fat on cancer cell survival
This discovery led the researchers to investigate ferroptosis, a form of programmed cell death caused by lipid oxidation.
Once fatty acids become part of pancreatic cell membranes, their chemical properties influence how easily those cells are damaged by oxidation. PUFAs are easily oxidized, making cancer cells more susceptible to ferroptosis and death. MUFAs are highly resistant to oxidation and help protect cancer cells from this process.
“Monounsaturated fats actually protect cancer cells from lipid oxidation,” Lewis explains. “Because there is less oxidation, you are less likely to develop ferroptosis.”
Researchers observed a direct relationship between fat composition and disease severity.
“Increasing the ratio of MUFA to PUFA in the diet increased disease burden. Conversely, lowering the ratio decreased disease burden.”
Male and female mice responded differently
The study also revealed differences between men and women.
The cancer-promoting effect of oleic acid was significant in male mice, but almost absent in female mice. On the other hand, PUFA reduced cancer incidence in both men and women.
Lewis said the findings add to the evidence that biological sex can influence metabolic pathways involved in cancer development and deserves further investigation.
Potential impact on cancer prevention
Although this study has not yet been replicated in humans, the findings may be particularly relevant to people at high risk for pancreatic cancer, such as those with chronic pancreatitis, obesity, late-onset diabetes, or a family history of pancreatic cancer.
“One of the most common questions clinicians receive is, ‘What should I change in my diet to prevent cancer?'” Ruiz says. “There is no clear answer at this time, but this study begins to shed light on how we can address that question.”
In the future, the researchers will investigate whether adjusting the fat composition of the diet can improve outcomes in people who already have pancreatic cancer. They also want to investigate whether the ratio of MUFA to PUFA in the bloodstream could serve as an early warning marker for pancreatic cancer risk.
The research reported in this news article was supported by the National Institutes of Health (Award T32CA193200; The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional support was provided by the Ford Foundation, the National Science Foundation, the Yale Stem Cell Center, the American Association for Cancer Research, the Department of Veterans Affairs, the Yale Women’s Health Research, the Damon Runyon Rachleff Research Foundation, the Yale Cancer Center, and the Lustgarten Foundation.
