The ketogenic diet -- which provides anywhere from 75% to 99% of calories from fat, moderate protein intake, and only 1% to 5% of calories from carbohydrates to achieve a state of fat-burning ketosis -- is claimed to deliver health benefits in the short term but can have negative effects after about a week, researchers from the Yale School of Medicine found in a study of mice.
The study, published in the journal Nature Metabolism, offered early indications that the keto diet could, over limited time periods, improve human health by lowering diabetes risk and inflammation.
“A keto diet tricks the body into burning fat,” said lead author Vishwa Deep Dixit and professor of comparative medicine and of immunobiology at the Yale School of Medicine.
According to Dixit, 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 Medicine and of Immunobiology. After a week on the keto diet, he said, mice show a reduction in blood sugar levels and inflammation.
But, according to researchers, when the body is in this “starving-not-starving" mode, fat storage is also happening simultaneously with fat breakdown.
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 explained.
"Our findings highlight the interplay between metabolism and the immune system, and how it coordinates maintenance of healthy tissue function," added Emily Goldberg, the postdoctoral fellow in comparative medicine who discovered that the keto diet expands gamma-delta T cells in mice.
Human clinical trials needed
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.
And there are good reasons to pursue further study, noted researchers. According to the Centers for Disease Control, 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.
‘Who wants to be on a diet forever?’
With the latest findings, researchers 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.
Dixit noted that type 2 diabetes and obesity are both 'lifestyle diseases' and a diet such as keto “allows people a way to be in control."
Discovering that the keto may not be a long-term health strategy and is better in small doses is good news, Dixit said, because "Who wants to be on a diet forever?"
The research was funded in part by grants from the National Institutes of Health.