A ketogenic diet — which provides 99% of calories from fat 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 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 an important first step toward possible clinical trials in humans. The keto diet has become increasingly popular as celebrities, including Gwyneth Paltrow, Lebron James, and Kim Kardashian, have touted it as a weight-loss regimen. However, long-term clinical studies in humans are still necessary to validate the anecdotal claims of keto’s health benefits. In the study, published on 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 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. Vishwa Deep Dixit, lead author, Zedtwitz Professor of Comparative Medicine and of Immunobiology, Yale School of Medicine, explained: “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, they consume more fat than they can burn, and develop diabetes and obesity. They lose the protective gamma delta T-cells in the fat. 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”. There are good reasons to pursue further study: According to the Centers for Disease Control, approximately 84 million American adults — or more than one out of three — have prediabetes
This condition would put 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. 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. Previously, the team found that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal influenza A infection and disease. Ketogenic feeding resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby enhancing antiviral resistance. Emily Goldberg, the postdoctoral fellow in comparative medicine who discovered that the ketodiet expands gamma-delta T cells in mice, commented: “Obesity and type 2 diabetes are lifestyle diseases; diet allows people a way to be in control. Our findings highlight the interplay between metabolism and the immune system, and how it coordinates maintenance of healthy tissue function. If the ideal length of the diet for health benefits in humans is a subject for later studies, discovering that keto is better in small doses is good news.
After all, who wants to be on a diet forever?”
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Goldberg EL et al. Nature Metabolism 2020 Jan 20.
Goldberg EL et al. Sci Immunol. 2019 Nov 15;4(41).
Schreck KC et al. Nutr Neurosci. 2019; 22(7):522-27.
Lima RCP et al. Food Funct. 2017 Apr; 8(4):1519-25.