Quick Study Analysis: Seed Oils and Colon Cancer

tl;dr: The recent paper analyzing the role of inflammation in colon answer is important, but doesn't show what some claim.

I think this was the first headline I saw about this paper:

Source.

The paper is:

“Integration of Lipidomics with Targeted, Single Cell, and Spatial Transcriptomics Defines an Unresolved Pro-Inflammatory State in Colon Cancer.” (Soundararajan, 2024)

Yeah, that’s a mouthful. It’s a very interesting paper from an intellectual, or academic perspective.

What Does This Paper Show?

Here’s part of the introduction of the paper:

“The western diet, low in fibre and rich in omega-6 fatty acids such linolenic [sic] acid (LA), a metabolic precursor of a arachidonic acid (AA), has been strongly linked to chronic inflammation and CRC [Colo-Rectal Cancer] development and progression, whereas the omega-3-rich diet has been proposed to have the opposite effect.”

So they’re pointing the finger at seed oil consumption there.

(“Linolenic” is a typo, surprisingly common in these sorts of papers—they meant to write “Linoleic”, as the context makes clear; linoleic (LA), but not alpha-linolenic acid (ALA), is a precursor to arachidonic acid (AA).)

I of course love seeing papers that make this connection explicit. I have been running a series on X pointing out papers that ought to mention LA that don’t, so this makes me happy.

X post.

I read the paper, and downloaded all the supplementary information, but I didn’t make a big deal about it, because the paper does not demonstrate a mechanistic connection or correlation between seed oils and colon cancer.

But, thanks to the inflammatory titles journalists love using:

Source

Note, again, “Could”. I think they do, and I think there’s solid evidence demonstrating that, but this paper isn’t part of it.

What this paper does show is that in cancer cells, compared to normal cells, there is an excessive Ω-6 inflammatory cascade taking place, which includes higher levels of both LA and AA.

Figure 1B from (Soundararajan, 2024)

And the inflammatory mediators are also upregulated.

Figure 2B from (Soundararajan, 2024)

“There is a significant increase in pro-inflammatory lipid mediators including 5-HETE and leukotrienes (LTB4, LTC4, LTD4 and LTE4) in tumours versus controls. Conversely, prostaglandins (PGD2 and PGE2) show a significant decrease in tumours relative to normal controls.”

Thus:

“Our unsupervised lipidomics landscape analysis of CRC demonstrated dysregulated lipid metabolism in colon tumours versus matched normal controls in matched sets.”

OK, that’s cool. They find that the known inflammatory pathway is indeed found in these cancer cells, and it appears to be running amok:

“While we found LTB4 and other pro-inflammatory LTs were elevated in CRC tumours, pro-resolving lipoxins (LXA4, LXB4) linked to the AA pathway, as well as other resolvins and the genes encoding their principal synthetic enzymes (ALOX15) were difficult to detect or were poorly expressed in both tumour and normal samples.”

So what seems to be missing here is what they call “class switching”, where the inflammatory pathway moves from pro-inflammation to resolution of inflammation. Hence, you have chronic inflammation: inflammation that never ends.

“Normal wound healing is represented by a transitory phase of inflammation, followed by a pro-resolution phase, with prostaglandin (PGE2/PGD2)induced ’lipid class switching’ producing inflammation-quenching lipoxins (LXA4, LXB4).”

Arachidonic Acid and Inflammation

AA is an “essential” fat; meaning it is required for life, but the body can’t make it, so it must be included in the diet. So it is like oxygen or water; but unlike, say, glucose or most saturated fats.

The reason it seems to be required is due to its role in development and inflammation.

All of this is mundane, standard science at this point (Hadley, 2016).

Too much of anything can be a problem, of course.

As Prof. Bruce Hammock noted:

“Seventy-five percent, by weight, of the drugs sold in the world work on a single pathway called the arachidonic cascade, where arachidonic acid is converted by cyclooxygenase into prostaglandins, which are strongly pro-inflammatory.” (Rice, 2020)

Diet Can Alter AA Levels

This is further mundane, standard science. Prof. Hulbert went over some of this in his guest-post on heart disease:

Guest Post: Prof. Hulbert's Response to "Beneficial Effects of Linoleic Acid on Cardiometabolic Health: an Update"

I’m not going to revisit the topic here.

Seed Oils and Colon Cancer

There’s also ample evidence that seed oils are involved in colon cancer:

A common feature of IBD [Inflammatory Bowel Disease] and CRC is that the oxidative stress is increased in the colon tissues. Previous studies showed that a variety of reactive oxygen species (ROS), including superoxide (O2−), hydroxyl (OH), peroxyl (RO2), and alkoxyl (RO) radicals, are increased in the rodent models and human patients of IBD and CRC …. These ROS species can attack polyunsaturated fatty acids (PUFAs), notably linoleic acid (LA, the most abundant PUFA in humans diet and tissues), that are incorporated in the membrane phospholipids of colon tissues, leading to formation of endogenous lipid-derived electrophiles (LDEs), such as 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), trans, trans-2,4-decadienal (tt-DDE), and epoxyketooctadecenoic acid (EKODE …). Substantial studies have shown that the levels of LDEs are increased in animal models and human patients with IBD or CRC …. In addition, previous studies have shown that the LDEs have potent effects on inflammation and tumorigenesis …. Therefore, some of the LDE compounds are implicated in the pathogenesis of IBD and CRC …. (Lei, 2021)

Again, a full review of that evidence, while something that needs to be done, is too much for a quick study analysis.

A Piece of the Puzzle

So this paper is a piece of a puzzle implicating seed oils in colon cancer. It’s not the critical piece, but it’s interesting. I wouldn’t have spent time on it if it weren’t for the reaction it has received.

But the reaction of some of the pro-seed oil propagandists is unfounded.

X post.

I requoted this with the comment:

"This is a paper about injuries from falls."

"It has ZERO to do with gravity! Gravity wasn't even involved."

"Um...."

It’s always important to understand the context of a study, and this is a misrepresentation of the evidence concerning seed oils and colon cancer, as already shown.

Someone, somewhere (we have reinvented the Tower of Babel) sent me a video claiming to “debunk” this research. I may add that in if I can find it, as he referenced some silly epidemiology to “prove” the lack of a relationship.

Conclusion

Journalism like this does science no favors. Lots of people read these headlines, see that the paper doesn’t do what the journalist claims, and presume the entire topic is bogus.

In this case it’s not, but one has to have some previous knowledge to fit the new information into the existing evidence.

If you have more interest in this topic

Nick Jikomes

interviewed the two senior authors of this study. It’s almost two hours, and it’s pretty interesting.

They also point out that the paper doesn’t prove a relationship between seed oils and colon cancer, but spend most of the interview discussing why they think there is one.

It’s well worth your time.

X post.

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References

Hadley, K. B., Ryan, A. S., Forsyth, S., Gautier, S., & Salem, N. (2016). The Essentiality of Arachidonic Acid in Infant Development. Nutrients, 8(4), Article 4. https://doi.org/10.3390/nu8040216

Lei, L., Zhang, J., Decker, E. A., & Zhang, G. (2021). Roles of Lipid Peroxidation-Derived Electrophiles in Pathogenesis of Colonic Inflammation and Colon Cancer. Frontiers in Cell and Developmental Biology, 9. https://doi.org/10.3389/fcell.2021.665591

Rice, M. E. (2020). Bruce D. Hammock: Science Should Be Fun. American Entomologist, 66(1), 14–19. https://doi.org/10.1093/ae/tmaa010

Soundararajan, R., Maurin, M. M., Rodriguez-Silva, J., Upadhyay, G., Alden, A. J., Gowda, S. G. B., Schell, M. J., Yang, M., Levine, N. J., Gowda, D., Sundaraswamy, P. M., Hui, S.-P., Pflieger, L., Wang, H., Marcet, J., Martinez, C., Bennett, R. D., Chudzinski, A., Karachristos, A., … Yeatman, T. J. (2024). Integration of Lipidomics with Targeted, Single Cell, and Spatial Transcriptomics Defines an Unresolved Pro-Inflammatory State in Colon Cancer. Gut. https://doi.org/10.1136/gutjnl-2024-332535