A ketogenic diet — which provides 99% of calories from fat and protein and only 1% from carbohydrates — produces health benefits in the short term, but negative effects after about a week, Yale researchers found in a study of mice.
The researchers say their results “offer early indications that the keto diet could, over limited time periods, improve human health by lowering diabetes risk and inflammation. They also represent a valuable first step toward possible clinical trials in humans”.
In the Yale study, published in the Jan. 20 issue of Nature Metabolism, researchers found that the positive and negative effects of the diet both relate to immune cells called gamma delta T-cells, tissue-protective cells that lower diabetes risk and inflammation.
A keto diet tricks the body into burning fat, said lead author Vishwa Deep Dixit (pictured above) of the Yale School of Medicine. When the body’s glucose level is reduced due to the diet’s low carbohydrate content, the body acts as if it is in a starvation state — although it is not — and begins burning fats instead of carbohydrates. This process in turn yields chemicals called ketone bodies as an alternative source of fuel. When the body burns ketone bodies, tissue-protective gamma delta T-cells expand throughout the body.
This reduces diabetes risk and inflammation, and improves the body’s metabolism, said Dixit, the Waldemar Von Zedtwitz professor of comparative nedicine and of Immunobiology. After a week on the keto diet, he said, mice show a reduction in blood sugar levels and inflammation.
But when the body is in this “starving-not-starving” mode, fat storage is also happening simultaneously with fat breakdown, the researchers found. When mice continue to eat the high-fat, low-carb diet beyond one week, Dixit said, they consume more fat than they can burn, and develop diabetes and obesity.
“They lose the protective gamma delta T-cells in the fat,” he said.
The researchers say long-term clinical studies in humans are still necessary to validate the anecdotal claims of keto’s health benefits.
“Before such a diet can be prescribed, a large clinical trial in controlled conditions is necessary to understand the mechanism behind metabolic and immunological benefits or any potential harm to individuals who are overweight and pre-diabetic,” Dixit said.
The Yale team acknowledges that there are very good reasons to study the potential health benefits of the keto diet and other nutritional interventions. It cites Centers for Disease Control data, which shows that approximately 84 million American adults — or more than one out of three — have prediabetes (increased blood sugar levels), putting them at higher risk of developing type 2 diabetes, heart disease, and stroke. More than 90% of people with this condition don’t know they have it.
“Obesity and type 2 diabetes are lifestyle diseases,” Dixit said. “Diet allows people a way to be in control.”
With the latest findings, the researchers say they now better understand the mechanisms at work in bodies sustained on the keto diet, and why the diet may bring health benefits over limited time periods.
“Our findings highlight the interplay between metabolism and the immune system, and how it coordinates maintenance of healthy tissue function,” said Emily Goldberg, the postdoctoral fellow in comparative medicine who discovered that the keto diet expands gamma-delta T cells in mice.
If the ideal length of the diet for health benefits in humans is a subject for later studies, Dixit said, discovering that keto is better in small doses is good news, he said: “Who wants to be on a diet forever?”
The research was funded in part by grants from the National Institutes of Health.
Main image: Vishwa Deep Dixit of the Yale School of Medicine