News release

From: Springer Nature

Investigating the potential effects of high protein intake

A high-protein diet and the resulting elevation in the amino acid leucine may contribute to atherosclerosis in mice, a study published in Nature Metabolism suggests. The paper, which also includes data from experiments in humans examining the effects of excess dietary proteins, provides insight into the potentially adverse effects of exceeding the recommended dietary protein intake.

While protein is a necessary macronutrient, people in Western societies consume around a third more protein than the recommended daily allowances on average. Previous research in animal models has linked excess protein to atherosclerosis (thickening and stiffening of arteries), and observational studies have associated excess protein with adverse cardiovascular events. However, current mechanistic studies investigating these relationships are limited.

Babak Razani and colleagues conducted two controlled experiments in humans using graded amounts of protein intake in a total of 23 male and female participants whose body mass index was classed as overweight. The first experiment involved 14 participants ingesting two 500-kilocalorie liquid meals, which on the first occasion was very high in protein and on the second was very low in protein. The second experiment involved 9 participants consuming a 450-kilocalorie standard meal on two occasions with either 16 grams of protein or 25 grams of protein. The authors took blood samples before and following both experiments at 1 and 3 hours after ingestion.

Based on these experiments, the authors suggest that dietary protein in excess of 25 grams per meal increases levels of the amino acid leucine in the circulation, which can affect monocytes and macrophages (cells that are part of the immune system). In subsequent cell based experiments the authors show that leucine is the predominant amino acid that can activate mTOR (which regulates many cell functions, such as proliferation, autophagy and apoptosis) in these cells. In a follow-up experiment in mice, the authors used three equivalent diets (high, moderate and low protein) and found that an ingestion of protein in excess of 22% of their dietary energy requirements also increased levels of leucine in circulation, affecting the immune cells and activating mTOR. The authors further show that increased levels of leucine are sufficient to promote atherosclerosis in male mice, even in the absence of high-protein diets. The authors suggest that their findings may have implications for understanding the effects of high-protein diets on cardiovascular events. However, they conclude that further research is needed to evaluate all the potential effects of differing protein intakes.