Seed oil debate heats up: Study links omega-6 fat to breast cancer subtype growth

Researchers have discovered that linoleic acid drives the growth of a hard-to-treat “triple negative” breast cancer subtype. The substance is an omega-6 fatty acid found in seed oils and animal products. The preclinical study suggests a need for dietary guidance for those suffering from the disease.

While public figures like US Health and Human Services Secretary Robert F. Kennedy Jr. call for eliminating seed oils due to their alleged links to inflammation and disease, researchers at Weill Cornell caution against blanket statements. Their new study suggests that linoleic acid’s impact depends on individual biology — especially in cancer patients — highlighting the need for precision nutrition rather than dietary dogma. 

It found linoleic acid activates the nutrient-sensing growth pathway in tumor cells called the mTORC1 by binding to the FABP5 protein, which is abundant in triple-negative tumor cells.

The study also found increased levels of FABP5 and linoleic acid in tumors and blood samples from newly diagnosed triple-negative patients. The discovery could lead to new dietary and pharmaceutical strategies against breast and other cancers.

Nutrition Insight speaks to Dr. John Blenis, a pharmacologist, and Nikos Koundouros, a postdoctoral associate at Weill Cornell Medicine, to learn more.

There’s a lot of debate about seed oils being inflammatory or causing obesity. How does your research fit into this controversy?
Blenis: It is important to remember that linoleic acid, despite its abundance in seed oils and inflammatory properties, it is an essential nutrient and completely removing it from one’s diet could have adverse effects. That being said, as the ‘Western’ diet has shifted toward overconsumption of high-fat, ultra-processed foods since the 1950s, linoleic acid intake has become excessive, and it is now the most abundant polyunsaturated fat in our diet. Linoleic acid, found in seed oils, fuels tumor growth in a hard-to-treat breast cancer subtype by activating a key nutrient-sensing pathway.Our research certainly supports the notion that dietary linoleic acid intake needs to become more moderate and ideally consumed in near-equal ratios with omega-3 polyunsaturated fatty acids, which predominantly have anti-inflammatory properties. Moreover, certain patient populations — specifically those with triple-negative breast cancer and high expression of FABP5 — might be more susceptible to the adverse effects of excessive linoleic acid intake.

How does linoleic acid activate the mTORC1 pathway, and why is this effect unique to this subtype?
Koundouros: We discovered that a lipid-binding protein called FABP5 is essential for linoleic acid to activate mTORC1. Linoleic acid binds to FABP5, which then directly interacts with mTORC1 to regulate complex formation, substrate binding, and subcellular localization — processes that are obligatory for complete mTORC1 activation. Breast cancer is a heterogeneous disease and is broadly stratified into four main clinical subtypes on the basis of expression of hormone receptors or lack thereof, each with distinct molecular characteristics and therapeutic sensitivities. Interestingly, levels of FABP5 were significantly higher in triple-negative compared to receptor-positive breast cancers. This core finding is what prompted us to explore the effects of linoleic acid in triple-negative breast cancer specifically.

What do your findings suggest about the role of linoleic acid in cancer growth, and how might they impact dietary recommendations for breast cancer patients?
Blenis: The key takeaway from our findings is that linoleic acid promotes breast cancer growth but in a very specific context and disease setting. This is an important distinction: for the last several decades, studies exploring the effects of dietary fat intake on breast cancer risk have been inconsistent. A possible explanation for this inconsistency is that patients are often not stratified based on cancer subtype or genetic biomarkers in these studies. One size does not fit all when thinking about the interplay between dietary fat intake and disease risk, and our study emphasizes this by elucidating the specific mechanism through which triple-negative breast cancers respond to linoleic acid.

The study suggests precision nutrition could guide treatment, especially for patients with high levels of the FABP5 protein.While it is still too early to give definitive nutritional recommendations to cancer patients, there has been a shift over the last ten years in our understanding of how dietary habits can impact the efficacy of cancer therapies and their side effects. In the short term, our study indicates that it may be worth revisiting previous nutritional studies and reanalyzing how the risk and progression of specific breast cancer subtypes are affected by dietary fat intake. Looking to the future, our study reveals an important perspective on how the interaction between linoleic acid intake and breast cancer needs to be studied, and future nutritional studies might consider stratifying patients on the basis of FABP5 expression and triple-negative status from the outset.

Do you think FABP5 could be used as a biomarker to help tailor treatments or dietary advice for cancer patients in the future?
Koundouros: We certainly believe that FABP5 could be an exciting and useful biomarker to help match cancer patients with specific dietary interventions. Moreover, FABP5’s direct regulation of mTORC1 signaling also raises the prospect of combining nutrition with existing therapies that target mTOR signaling but have otherwise been hindered by small therapeutic windows or poor tolerability. These insights could eventually lead to the full integration of precision nutrition and drug interventions in a cancer patient’s journey.

What’s next for your research on linoleic acid, and are there any new findings we should be aware of?
Blenis: An area of research we are actively exploring and are very excited about is the implications of excessive linoleic acid consumption as part of the “Western diet” on “unhealthy aging.” It is becoming increasingly appreciated that poor nutrition can hasten the onset of aging comorbidities like chronic systemic inflammation (often referred to as ‘inflammaging’), obesity, and frailty. Our current efforts are directed toward therapeutically exploiting our proposed FABP5-mTORC1 signaling pathway to hopefully mitigate the onset of these chronic morbidities.

Seed oil debate

Kennedy has claimed that restaurants “unknowingly poison” consumers with seed oils while critiquing the rise of fast foods that no longer use beef tallow. Nutrition Insight looked at arguments from researchers opposing this stance while sharing insights on consumer perceptions about seed oils.

A recent study of dietary habits suggests that eating more plant oils and less butter could lead to better health. More than 200,000 people were tracked for over 30 years, and those consuming more seed oils like soybean and canola next to olive oil had lower mortality than those consuming high butter.