This study investigates the impact of high protein intake on mTOR signaling in macrophages and its potential role in cardiovascular disease. The authors conducted clinical studies involving graded amounts of protein ingestion and detailed plasma amino acid analysis. They identified leucine as the key activator of mTOR signaling in macrophages and found a threshold effect where only protein intake exceeding approximately 25 grams per meal (or about 22% of total energy requirement) induces mTOR activation. In mouse models, they confirmed this threshold effect and showed that protein intake exceeding this threshold drives atherosclerosis in male mice. The study highlights a mechanistic link between high dietary protein intake and cardiovascular risk, suggesting that excessive protein intake may have adverse effects on vascular health. The findings have important clinical implications, as they provide a potential explanation for the increased cardiovascular disease mortality associated with high protein intake.This study investigates the impact of high protein intake on mTOR signaling in macrophages and its potential role in cardiovascular disease. The authors conducted clinical studies involving graded amounts of protein ingestion and detailed plasma amino acid analysis. They identified leucine as the key activator of mTOR signaling in macrophages and found a threshold effect where only protein intake exceeding approximately 25 grams per meal (or about 22% of total energy requirement) induces mTOR activation. In mouse models, they confirmed this threshold effect and showed that protein intake exceeding this threshold drives atherosclerosis in male mice. The study highlights a mechanistic link between high dietary protein intake and cardiovascular risk, suggesting that excessive protein intake may have adverse effects on vascular health. The findings have important clinical implications, as they provide a potential explanation for the increased cardiovascular disease mortality associated with high protein intake.