Fish Oil, Fish Intake Raises Plasma Chemoresistance-Inducing Fatty Acid Levels

Dutch researchers caution against the consumption of fish oil supplements and fish in the day before and after chemotherapy exposure

Intake of fish oil supplements and certain types of fish causes an increase in plasma levels of the platinum-induced fatty acid 16:4(n-3) in healthy volunteers, research shows.

This fatty acid has previously been shown to induce resistance to chemotherapy in preclinical mouse models, an effect seen with minute quantities, explain Emile Voest, from the Netherlands Cancer Institute in Amsterdam, and co-investigators.

“Our results add to the growing awareness that not all dietary supplements are beneficial or harmless: some may interfere with treatment outcome”, they write in JAMA Oncology.

The administration of three different commercially available fish oil supplements, with 16:4(n-3) concentrations ranging from 0.80 μM to 6.27 μM, to six healthy volunteers each at a dose of either 10 mL or 50 mL resulted in “clear increases” in the plasma levels of 16:4(n-3) in all volunteers, “reaching up to 20 times the baseline levels”.

Plasma 16:4(n-3) levels normalised 8 hours after intake of the 10 mL dose, which the researchers say is the recommended daily amount, but the 50 mL dose resulted in a “prolonged” elevation.

Interestingly, the researchers noted a discrepancy between the plasma peak and the calculated 16:4(n-3) intake – 50 mL of fish oil A, for example, contained 272 nmol of the fatty acid, but after consumption, plasma levels of 400 nM were observed.

This, they say, suggests that “other fatty acids in fish oil are metabolized to 16:4(n-3) in the body.”

The levels of 16:4(n-3) in plasma also rose substantially following ingestion of 100 g of cured herring or smoked mackerel, both fish that contain high amounts of the fatty acid. By contrast, intake of 100 g of raw salmon resulted in a “small, short-lived peak” and consuming the same amount of raw tuna, which has the lowest levels of 16:4(n-3), left plasma levels unaffected.

A survey completed by 118 patients undergoing active cancer treatment showed that 30% used nutritional supplements regularly and 11% used supplements containing omega-3 fatty acids, most commonly in the form of fish oil.

While highlighting that a controlled clinical trial assessing the effects of 16:4(n-3) on chemotherapy would in their view be “unethical”, Emile Voest et al say that “until further data become available, we advise patients to temporarily avoid fish oil from the day before chemotherapy until the day thereafter.”

This advice has been adopted by the Dutch Cancer Society and the Dutch National Working Group for Oncologic Dieticians, they report.

“Although further evidence on the relation between fish consumption and chemotherapy activity is desired, we would currently also recommend to avoid herring and mackerel in the 48 hours surrounding chemotherapy exposure.”


Daenen LGM, Cirkel GA, Houthuijzen JM, et al. Increased Plasma Levels of Chemoresistance-Inducing Fatty Acid 16:4(n-3) After Consumption of Fish and Fish Oil. JAMA Oncol 2015; Advance online publication 2 April. doi:10.1001/jamaoncol.2015.0388

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