Ketogenic diet provides greatest health benefits for treating obesity

A diet that severely limits carbohydrates but is high in fat has the greatest health benefits for people with obesity compared to a Mediterranean diet or a low-fat diet, according to a clinical trial publishing August 27 in the Cell Press journal Cell Metabolism. After following a ketogenic (or "Keto") diet for four to five months, about 50% of a group of participants with obesity and prediabetes no longer met the criteria for prediabetes. 

We know weight loss can improve metabolic health in people who are obese. Our data suggest that if you have high liver fat content and prediabetes, reducing carbohydrate intake can have important therapeutic effects on metabolism beyond just weight loss alone." 

Samuel Klein, study's corresponding author, Washington University School of Medicine in St. Louis, Missouri

It is estimated that some 40% of American adults have obesity. Healthcare providers commonly recommend low-fat, low-carbohydrate, or Mediterranean diets to promote weight loss, but it has been unclear if any of these diets provide additional metabolic benefits beyond weight loss itself, or if one offers greater health benefits than the others. 

The three popular diets differ significantly in their major nutrient composition. For example, a low-carbohydrate diet, also known as Atkins or ketogenic diet, severely restricts carbohydrate intake, while a low-fat diet can source as much as 70% of its energy from carbohydrates. A Mediterranean diet contains mostly plant-based foods, such as vegetables, olive oil, and nuts, with moderate amounts of fish and dairy, while a ketogenic diet can include foods high in saturated fat, including animal products. 

To understand the diets' metabolic effects in people, Klein and his team conducted a clinical trial with 42 participants who had obesity, prediabetes, and fatty liver disease. The researchers randomly assigned them to one of three diet groups: a ketogenic diet, a Mediterranean diet, or a low-fat, plant-forward diet. The participants received all of their food from the research team and met weekly with a dietitian to help them adhere to their assigned diets.

In the study, the ketogenic diet provided only 4% of calories from carbohydrates and 73% from fat. The Mediterranean diet had 50% of its calories from carbohydrates and 35% from fat. The plant-forward diet sourced 70% of calories from carbohydrates and 15% from fat. 

The team tailored each participant's calorie intake so that everyone lost about 10% of their body weight, which took about four to five months. 

By the end of the trial, all three diets led to a significant reduction in the participants' body fat. Their bodies also became more sensitive to insulin, improving their ability to regulate blood sugar.

But the ketogenic diet produced the greatest improvements in several markers of liver and metabolic health. Participants' liver fat decreased by an average of 67% in the ketogenic group, compared with 45% in both the Mediterranean and the plant-forward groups.

When the team monitored the participants' metabolic activities over 24 hours by testing their blood throughout, they found that the ketogenic diet group had the largest increase in glucagon, which is a hormone that promotes fat loss in the liver. That group also experienced the greatest reduction in blood insulin levels, which also reduces fat content in the liver, compared to the other two groups.

"The most surprising finding was that participants in the ketogenic diet group didn't experience an increase in blood fat or cholesterol levels despite consuming the most fat," says Max Petersen, the study's first author at Washington University School of Medicine. 

Following the weight-loss intervention, about 50% of participants in the ketogenic group no longer met the criteria for prediabetes, compared with 29% in the Mediterranean group and 7% in the plant-forward group. 

"GLP-1-based medications have revolutionized the therapy of obesity. We now have a very effective pharmacotherapy for achieving significant weight loss," Petersen says. "But in addition, our study shows that the specific composition of the diet can give you added benefits." 

This work was supported by the National Institutes of Health and the Foundation for Barnes-Jewish Hospital.