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Monday, 25 September 2017
Ketogenic diet prevents inflammation
The high-fat, low-carbohydrate regimen of ketogenic diets changes the way the body uses energy. In response to the shortage of carb-derived sugars such as glucose, the body begins breaking down fat into ketones and ketoacids, which it uses as alternative fuels.
In rodents, ketogenic diets and caloric restriction reduce inflammation, improve outcomes after brain injury, and extend lifespan. These benefits have not been confirmed in human.
Ketogenic diets can modulate the inflammatory response in rodents.
Researchers used a small molecule known as 2-deoxyglucose, 2DG, to block glucose metabolism and produce a ketogenic state in rats and controlled laboratory cell lines.
The team found that 2DG could bring inflammation to control levels. Reduced glucose metabolism lowered a key barometer of energy metabolism – the NADH/NAD+ ratio which in turn activated a protein called CtBP that acts to suppress activity of inflammatory genes. Researchers designed a drug-like peptide molecule that blocks the ability of CtBP to enter its inactive state – essentially forcing the protein to constantly block inflammatory gene activity and mimicking the effect of a ketogenic state.
Peptides, which are small proteins, don't work well themselves as drugs because they are unstable and people make antibodies against them. But other molecules that act the same way as the peptide could provide ketogenic benefits without extreme dietary changes. Excess glucose in people with diabetes, is associated with a pro-inflammatory state that often leads to atherosclerosis; the buildup of fatty plaques that can block key arteries.
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