(P13-014-23) Fish Oil Enhances the Efficacy of a Ketogenic Diet To Lower Tobacco Carcinogen-Induced Lung Cancer

Objectives: Since cancer cells typically take up more glucose than normal cells, we hypothesized that a ketogenic diet, which is very low in carbohydrate, might slow tumor growth. However, since ketogenic diets are very high in fat, and different fats might have different biological effects, we investigated whether fat types influenced the efficacy of a ketogenic diet to lower tobacco carcinogen-induced lung cancer in mice.

Methods: We placed 12 week old A/J mice on a Western diet, or ketogenic diets comprised of either palm oil, olive oil, corn oil, milk fat, fish oil, medium chain triglyceride oil, or a blend of fats typically found in a Western diet. We then intraperitoneally injected the obacco-specific carcinogen, nicotine-derived nitrosamine ketone (NNK) to these mice twice, one week apart, to initiate lung tumor formation. Lung nodules in these mice were then counted five months later.

Results: Mice that were fed the ketogenic diets had significantly (P < 0.05) lower lung nodule numbers compared to the Western diet, suggesting that glucose restriction is indeed a feasible strategy to slow tumor formation. comparing the different ketogenic diets, we found the ketogenic diet containing fish oil was significantly (P < 0.05) more effective than the rest of the ketogenic diets in reducing lung tumor formation. This increased efficacy was associated with higher plasma ß-hydroxybutyrate, lower blood glucose, and liver fatty acid expression. Taken together, fish oil appears to be unique in its ability to promote ketosis in mice fed a ketogenic diet.

Conclusions: We conclude that not all fats are created equal in the context of a ketogenic diet. Incorporation of fish oil, which is high in the omega 3 fatty acids, EPA and DHA, can increase the efficacy of a ketogenic diet in preventing the formation of NNK-induced lung tumors.

Funding Sources: This work was funded by Hecht Grant #4340 and #4717 to GK.