[Health Focus] “Some fatty acids in the keto diet may increase the risk of inflammatory reactions.”

Research has shown that even in the keto diet, which significantly reduces carbohydrates and increases fat intake, a high proportion of long-chain saturated fatty acids with more than 16 carbon atoms, such as palmitic acid and stearic acid, can increase pro-inflammatory immune cells.

Dr. David Geuse's team at the University of Cincinnati Cancer Center announced in the scientific journal Science Advances on the 14th that they confirmed this fact through experiments feeding mice a keto diet with high or low content of long-chain saturated fatty acids and through human macrophage culture experiments.

The research team said that long-chain saturated fatty acids induced the activation of pro-inflammatory macrophages, but medium-chain fatty acids and unsaturated fatty acids did not cause the same changes. When evaluating the effectiveness and safety of the keto diet, it is necessary to consider not only the ratio of carbohydrates and fats, but also the type of fatty acid, period of intake, and immune response.

The ketogenic diet, also known as 'low-carb, high-fat', is a diet that significantly reduces carbohydrate intake and increases the proportion of fat intake to promote fatty acid oxidation and ketone body production in the body. It is used clinically for the treatment of various diseases, including metabolic diseases.

The research team pointed out that while some of the existing studies on the keto diet reported an effect of reducing inflammation, other studies showed inflammation and metabolic abnormalities, and the mechanism by which these conflicting results occur is still unclear.

The research team divided mice into two groups and fed them a keto diet with the same ratio of calories from fat (about 90%) but different compositions of fatty acids for 21 days or 4 months, and then conducted an experiment to analyze the heart, kidneys, liver, brain, and fat tissue.

One group was fed a Crisco-based diet containing about 26% palmitic acid (C16:0) and stearic acid (C18:0), and the other group was fed a coconut oil-based diet containing 12% palmitic acid and stearic acid.

As a result, in mice that ate a keto diet with a ratio of long-chain saturated fatty acids of about 26%, pro-inflammatory macrophages increased in various tissues, including the heart, kidneys, liver, brain, and adipose tissue. Macrophages are immune cells that remove bacteria and damaged cells, but they can also participate in inflammatory reactions.

On the other hand, in mice that ate a coconut oil-based diet containing 12% long-chain saturated fatty acids, the index of increase in pro-inflammatory macrophages did not increase.

Additionally, when mouse and human macrophages were treated with various fatty acids, palmitic acid and stearic acid changed the macrophages into a state with a strong pro-inflammatory function, while medium chain fatty acids and unsaturated fatty acids did not cause the same change.

The research team explained that this shows that the effect of the keto diet on inflammation can vary depending not only on fat intake but also on the type of fatty acid consumed.

The research team also confirmed that a specific signaling pathway (cGAS-STING), which is involved in activating immune and inflammatory responses when cells detect danger signals, is involved in this inflammatory response.

The cGAS-STING pathway and inflammasome-related signals were activated in human macrophages treated with palmitic acid, and this pathway was also activated in tissues of mice fed a keto diet rich in long-chain saturated fatty acids.

In addition, as a result of analyzing samples rich in macrophages from the kidneys of mice fed a keto diet containing 26% long-chain saturated fatty acids for 4 months, changes in mitochondria-related energy metabolism and lipid metabolism were confirmed.

The research team explained that this suggests that changes in fatty acid metabolism, such as long-chain saturated fatty acids, can affect stress signals and immune responses inside cells. Long-chain saturated fatty acids appear to induce a pro-inflammatory state by changing the metabolism of macrophages and intracellular signaling.

However, he added that the study was a dietary experiment on mice and a laboratory study using human macrophages, and was not a clinical trial to confirm whether the keto diet increases the risk of inflammation or disease in humans.

◆ Source: Science Advances, David Gius et al., "Ketogenic diets induce proinflammatory macrophage accumulation through long-chain saturated fatty acids driving cGAS-STING signaling", https://doi.org/10.1126/sciadv.aeg5542