BLOG

By E. Dylan Mayer

I recently came across an article talking about the surprising antitumor effects of polyunsaturated fatty acids (PUFAs) during acidosis (when there is too much acid in the body fluids – opposite of alkalosis). This is surprising in view of the well-known fact that cancer cells require fatty acids (FAs) to support tumor growth (tumorigenesis) and cancer progression. FAs sustain membrane biosynthesis during rapid proliferation and provide an important energy source during conditions of metabolic stress.

In an animal study, researchers found that omega-3, as well as omega-6 polyunsaturated fatty acids, selectively induced ferroptosis (programmed cell death linked to oxidation of certain fatty acids) in cancer cells when there is an excess of fatty acids in the blood. During acidosis, the cancer cells feed on these PUFAs, but due to them being unable to store them correctly, they end up oxidizing and poisoning themselves from within.

During acidosis, the cancer cells replace glucose with lipids as an energy source in order to multiply. Going off previous studies, researchers went on to study the effects of various fatty acids on tumors and found that the tumor cells behaved completely different depending on the fatty acids available to them. Docosahexaenoic acid (DHA), an omega-3 PUFA found commonly in some fish and mussels was found to poison cancer cells and significantly slow mouse tumor growth when compared with a monounsaturated FA-rich diet.

These researchers also found that using a lipid metabolism inhibitor such as diacylglycerol acyltransferase inhibitors (DGATi) can magnify this processing of overwhelming the cancerous cells. In the animal trials, the researchers administered a DHA-enriched diet to mice with tumors, drastically slowing tumor development in the animals on the DHA diet compared to those who were given a conventional diet.

Even though many spectacular observations in mouse models of disease, including tumor models often get “lost in translation”, in other words, are not reproducible in humans, the findings of this study are intriguing. Fish is not a habitually consumed food in the United States, compared to red meat and chicken, creating a potential for omega-3 deficits in our diet. Comparing previous studies to more recent studies, our omega-3 fatty acid intake has significantly increased from about 160mg/day (10mg-20mg from EPA and DHA, the rest from ALA), to 41mg of EPA and 72mg of DHA in adults aged 19 years and up. To put this into perspective, according to the NIH, flaxseed oil, chia seeds, walnuts, salmon, herring, canola oil, sardines and mackerel have the highest levels of omega-3s – and this is shared between three types of omega-3s, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA).

It is already well-known that PUFAs have extensive beneficial effects on our health, such as repressing lipogenesis and increase resolvins and protectin generation, leading to reduced inflammation. The consumption of omega-3 fatty acids is recommended to optimize cardiovascular as well as brain health. While it is most commonly consumed in the form of fish (primarily salmon and smaller fish, such as sardines, mackerel, anchovies and mussels) or fish oil supplements, these fatty acids actually originate from algae, which the smaller fish feed on and take it up the food chain. This is interesting as there is also evidence that suggests farmed salmon has a higher ratio of omega-6/omega-3 (less healthy) than that of wild salmon. I’d be willing to guess that is due to the farmed salmon’s diet being vastly different from that of their wild counterparts.

Going back to DHA’s antitumor effects in mouse models, this research opens the doors for more effective treatment options of cancerous tumors in humans. One question remains is the need for acidosis to transform the omega-3 fatty acids into cancer fighting molecules. Even not investigated in this study, is it possible that a ketogenic diet is required to produce this effect in humans. Another limitation that the authors of the study mention is the fact that it was done in mouse tumor models, and performed in 3D cancer spheroids (these are micro-sized cellular aggregates that have been widely used to generate models of different cancer types in vitro). It raises the question if the concentration of bioactive omega-3 PUFAs that can be reached in humans is sufficient to produce the antitumor effects.
I’m optimistic that with both the finding that during acidosis, omega-3s become poisonous for cancer cells, as well as that lipid metabolism inhibitors can enhance the effect of overwhelming cancerous tumor cells with PUFAs, that this kind of nutrition-based science is able to improve cancer treatments in the future.

E. Dylan Mayer is a graduate from the University of Colorado at Boulder, with a major in Neuroscience and minor in Business. He is currently completing his master’s degree in Human Nutrition from Columbia University. Dylan is fascinated by the close interactions between nutrition, exercise and human health, especially with regard to the brain-gut-microbiome system – and regularly posts his content on his Instagram (@mayerwellness).