Keto diets: Are their metabolic effects only due to caloric restriction?

Ketogenic diets have become very popular during the last few years, primarily as a dietary strategy for weight loss. Hence, most studies have focused on determining the effects of a ketogenic diet (KD) in this context. However, this makes keto-specific effects hard to tease out, since weight loss itself causes^[1] an improvement in several metabolic parameters and disease risk markers. This problem is further compounded because keto diets can result^[2] in spontaneous calorie restriction even if the diet isn’t explicitly meant to cut calories.

The current study was designed to address these concerns by contrasting the metabolic effects of an isocaloric keto diet with a control diet higher in carbohydrate, under energy balance, and in a highly controlled inpatient setting. Some results of this study have been published^[3] before and covered in NERD #22, Volume 2, showing that a keto diet slightly increased energy expenditure, but didn’t lead to a higher loss of body fat compared to the control diet, as the diets were calorie-matched. This was a major ding against the carbohydrate-insulin hypothesis of obesity, which predicts that a sharp drop in carbohydrate intake should drive a drop in insulin secretion, in turn leading to increased fat loss—all other factors being equal. In the study under review, the authors followed up by shifting their focus from the effects on energy balance and storage to changes in glucose and lipid metabolism, as well as inflammatory markers.

Ketogenic diets usually result in calorie restriction in free-living scenarios, making it difficult to tell if their metabolic effects are due to the diet alone or are confounded by weight loss. The current study examined the effects of a ketogenic diet compared to a control diet higher in carbohydrate on glucose and lipid metabolism, and metabolic and inflammation markers under calorie-matched conditions.