Mice fed a palm oil-based shortening keto diet accumulated much higher levels of proinflammatory macrophages in multiple organs after 21 days compared to those on a coconut oil formulation, according to a peer-reviewed study published on November 13 in Science Advances.
Dietary Fat Composition Drives Inflammation
Ketogenic diets restrict carbohydrates to induce a metabolic state called ketosis, in which the body uses fat and ketone bodies as its main fuel source instead of glucose, ScienceAlert reported. While widely recognized as a strategy for weight loss, the diet was originally designed to treat epilepsy.
Researchers wanted to understand other potential therapeutic applications, which requires a detailed look at how different formulations work in the body. Physician-David Gius, director of the University of Cincinnati Cancer Center, said that previous work established that all ketogenic diets are not identical, with different fats causing distinct metabolic changes.
“Our previous studies have found that all ketogenic diets are not the same, with different fats causing different metabolic changes,” said David Gius, director of the University of Cincinnati Cancer Center, as reported by EurekAlert.
The peer-reviewed study evaluated dietary fats across living organisms and isolated cell systems, according to Bioengineer.org. The experimental outcomes showed that long-chain saturated fatty acids favored an inflammatory immune response, whereas unsaturated and medium-chain fatty acids promoted anti-inflammatory characteristics.
Mice fed Crisco accumulate more proinflammatory macrophages in hearts
To evaluate these metabolic variations systematically, researchers tested two different keto formulations on laboratory mice alongside a regular diet over a 21-day period, ScienceAlert reported. One keto diet used Crisco, a palm oil-based shortening containing about 26 percent long-chain saturated fatty acids. The other used coconut oil, featuring a similar total fat content but only 12 percent long-chain saturated fatty acids.
Mice fed the Crisco-based diet accumulated significantly higher levels of proinflammatory macrophages—specialized white blood cells that fight pathogens—in their hearts, kidneys, livers, brains, and white fat. Conversely, animals on the coconut oil keto diet showed inflammatory marker levels more similar to those fed a normal diet, UA.News reported.
“Our findings suggest that the proinflammatory effects of long-chain saturated fatty acids may emerge only beyond a critical threshold of exposure,” the authors write in Science Advances.
The authors added that the inflammatory consequences are not intrinsic to ketone metabolism, which has demonstrated anti-inflammatory effects. Instead, the response is shaped by diet composition, fatty acid availability, and cell type-specific reactions triggered by mitochondrial stress signaling and immune cell activation.
Researchers investigate ketogenic diets for cancer immunotherapy
Researchers are investigating whether ketogenic diets could be tailored to alter the microenvironments of tumors and potentially improve outcomes for cancer immunotherapy. However, this remains a controversial area of research still in the exploratory phase, with evidence stemming mainly from animal studies.
A large systematic review conducted in 2021 found no evidence that a ketogenic diet made a difference for cancer patients regarding anti-tumor effects or overall survival, as reported by ScienceAlert. To examine the issue further, scientists have launched a clinical trial at the University of Texas Health Science Center, with another site scheduled to open soon at the University of Cincinnati.
Ketogenic Diet FAQs
Do all ketogenic diets cause inflammation?
No, the study found that proinflammatory effects depend heavily on the specific type of fats used in the diet. Long-chain saturated fatty acids triggered mitochondrial stress and macrophage accumulation, while medium-chain and unsaturated fats promoted anti-inflammatory characteristics.
How long did the mouse experiments last?
The mice were fed either a Crisco-based keto diet, a coconut oil keto diet, or a regular diet for a total of 21 days before researchers measured macrophage accumulation across multiple organs.
What is the main goal of current clinical trials?
Scientists at the University of Texas Health Science Center and the University of Cincinnati are investigating whether specialized ketogenic diets can alter tumor microenvironments and potentially improve cancer immunotherapy outcomes.
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