New research from the University of Cincinnati Cancer Center suggests that not all ketogenic diets have the same effects on the body. A ketogenic diet is high in fat and low in carbohydrates, with the goal of entering ketosis, a metabolic state in which the body burns fat and ketones for fuel instead of glucose. Many earlier studies have reported anti-inflammatory benefits from keto diets, while others have found increased inflammation and other harmful effects.
The study, led by Cancer Center Director David Gius, M.D., Ph.D., and published Nov. 13 in the journal Science Advances, found that a ketogenic diet high in long-chain saturated fatty acids can increase inflammation. Gius said the team stumbled on the finding while studying another aspect of keto diets, and that earlier work had already shown that different fats produce different metabolic changes. In the mouse experiments, mice were fed a keto diet built on Crisco, a palm oil-based shortening with about 26 percent long-chain saturated fatty acids, or a keto diet built on coconut oil, which has only 12 percent. After 21 days, the Crisco-fed mice had much higher levels of proinflammatory macrophages in their hearts, kidneys, livers, brains and white fat, while the coconut oil group looked more like mice on a regular diet.S1S2
The researchers say the inflammatory effect appears to be driven by mitochondrial stress signaling and activation of immune cells. Gius said that combined with the team's earlier publications in Science Advances (2024) and Cell Reports (2025), the results suggest several factors, including the dietary source of fat, must be considered to achieve the desired outcome. The authors add that the inflammatory consequences of keto diets are shaped by diet composition and fatty acid availability rather than by ketone metabolism itself, which has been shown to have anti-inflammatory effects.S1S2
In cancer research, Gius said ketogenic diets may alter tumor microenvironments in ways that could improve the outcomes of immunotherapy. A clinical trial is underway at UT Health San Antonio, where Gius began the research, and will open soon at the University of Cincinnati Cancer Center.S1S2
