Ketogenic Diet Suppresses Brain Inflammation

Ketogenic diets are extremely low in calories and high in healthy fats, and can result in weight loss, lower cholesterol levels, and improved insulin sensitivity, according to Healthline. This diet is also recommended as a therapy for patients with epilepsy and neurological disorders.

A new study published by Nature Communications found that ketogenic diets may lower inflammation in the brain, which could explain why it benefits patients with neurological conditions.

These findings could lead to novel therapies that reduce brain inflammation after stroke, brain trauma, or other diseases—including diabetes—by mimicking the effects of the diet, according to the study.

“It's a key issue in the field—how to suppress inflammation in the brain after injury,” said senior author Raymond Swanson, MD.

In the study, the researchers discovered how the diet reduces brain inflammation. They also found a protein that links the effects of the diet to inflammatory genes, which could be inhibited to mimic the anti-inflammatory effects, according to the study.

“The ketogenic diet is very difficult to follow in everyday life, and particularly when the patient is very sick,” Dr Swanson said. “The idea that we can achieve some of the benefits of a ketogenic diet by this approach is the really exciting thing here.”

The authors report that the ketogenic diet changes how the body uses energy. Without carbohydrate-derived sugars, the body breaks down fat as an alternative fuel.

In rodent models, ketogenic diets are known to reduce inflammation, improve outcomes after a brain injury, and can lengthen lifespan; however, these findings have yet to be widely established in humans due to the difficulty of maintaining ketosis, according to the study.

In the new study, the authors used 2-deoxyglucose (2DG) to inhibit glucose metabolism and induce a ketogenic state. The investigators found that 2DG reduced inflammation in rats and cell lines to nearly control levels, according to the study.

“I was most surprised by the magnitude of this effect, because I thought ketogenic diets might help just a little bit,” Dr Swanson said. “But when we got these big effects with 2DG, I thought wow, there’s really something here.”

The authors also found that lowered glucose metabolism coincided with a reduced a barometer of energy metabolism. This action then activated the CtBP protein, which suppresses inflammatory genes, according to the authors.

The investigators then designed a drug-like peptide that inhibits CtBP to become inactive, forcing the protein to block inflammatory gene activity. These findings suggest that a peptide could be used to provide ketogenic benefits without dietary changes.

The results may be applicable for other conditions besides brain-related inflammation. In patients with diabetes, excess glucose is linked to inflammation that can lead to heart disease. The study may provide a new approach to block excess glucose from triggering an inflammatory response, according to the study.