For years, the common assumption has been simple: eating less fat may help lower cancer risk. New research suggests the picture is much more complicated.
Scientists report that when it comes to pancreatic cancer, the specific type of fat in the diet may be more important than the total amount consumed.
The findings, published in Cancer Discovery, a journal of the American Association for Cancer Research, indicate that different fats can have dramatically different effects on cancer development.
"It's really the type of fat that you're consuming, not just total fat content," says Christian Felipe Ruiz, PhD, an associate research scientist in Yale School of Medicine's Department of Genetics and lead author of the study. "Depending on the type of fat that you consume, it can go completely different ways. We found that some fats promote cancer, as we would expect, while other fats are really good at suppressing cancer."
Oleic Acid Linked to Faster Tumor Growth
One of the study's most unexpected findings involved oleic acid, the primary fatty acid found in olive oil.
Researchers found evidence that oleic acid may encourage tumor growth in pancreatic cancer, a result that surprised the team because of the fatty acid's long-standing reputation as a heart-healthy dietary fat.
"It's traditionally been considered a healthy type of fat for cardiovascular health," Ruiz says.
The cancer examined in the study was pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer and one of the deadliest cancers overall. Only about 13% of people diagnosed with PDAC survive for five years.
"More than 65,000 people are expected to be diagnosed with PDAC in the U.S. this year, with over 50,000 deaths," Ruiz notes. "At the moment, effective treatment options are limited, especially for advanced disease. Therefore, prevention strategies are sorely needed to move the needle on PDAC mortality."
Although previous research has linked high-fat diets to a greater risk of PDAC, scientists have struggled to identify exactly how dietary fat influences the disease. The new study, led by senior author Mandar Deepak Muzumdar, MD, associate professor of genetics and of internal medicine at YSM, sought to answer that question.
Muzumdar is also a member of Yale Cancer Center and the Yale Cancer Biology Institute at West Campus.
Comparing Different Types of Dietary Fat
To isolate the effects of specific fats, the researchers created 12 different high-fat diets. Each diet contained the same number of calories, with the only difference being the source of fat. The diets were designed to reflect common patterns of fat consumption in the modern American diet.
According to Ruiz, many earlier studies relied on a simpler approach.
For decades, researchers commonly "gave mice very high levels of fat in their diet, often using a single fat source." In many cases, those diets derived 60% of calories from lard, which does not accurately reflect typical human eating habits and makes it difficult to determine the effects of individual fatty acids.
"Exactly what components of dietary fat cause cancer has remained a mystery," Ruiz adds.
The results were striking. Mice carrying a genetic mutation that produces a disease closely resembling human PDAC developed tumors more rapidly when fed diets 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, diets rich in polyunsaturated fatty acids (PUFAs) slowed cancer development. The strongest protective effects were seen with omega-3 fatty acids, including those found in fish oil.
"When we fed mice diets enriched with fish oil, we saw a 50% reduction in disease compared with mice fed a standard fat diet."
How Dietary Fats Affect Cancer Cell Survival
The findings led researchers to investigate ferroptosis, a form of programmed cell death caused by lipid oxidation.
When fatty acids become part of pancreatic cell membranes, their chemical characteristics influence how easily those cells can be damaged by oxidation. PUFAs are more prone to oxidation, making cancer cells more vulnerable to ferroptosis and death. MUFAs are more resistant to oxidation, helping protect cancer cells from this process.
"Monounsaturated fats really protect the cancer cells from lipid oxidation," Ruiz explains. "Because oxidation is reduced, they're less likely to undergo ferroptosis."
The researchers observed a direct relationship between fat composition and disease severity.
"When we increased the ratio of MUFAs to PUFAs in the diet, disease burden increased. Conversely, when we decreased the ratio, disease burden was reduced."
Source: ScienceDaily
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