High-protein diets may help some people lose weight and build muscle, but a new study in mice suggests a downside: more plaque in the arteries.
Further, the new research shows that high-protein diets spur unstable plaque—the kind most prone to rupturing and causing blocked arteries. More plaque buildup in the arteries, particularly if it’s unstable, increases the risk of a heart attack.
“There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years,” says senior author Babak Razani, an associate professor of medicine at the Washington University School of Medicine in St. Louis. “But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health.”
High-Protein Diets
The researchers studied mice fed a high-fat diet to deliberately induce atherosclerosis or plaque buildup in the arteries. According to Razani, mice must eat a high-fat diet to develop arterial plaque. Therefore, some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.Unstable Plaques
“This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques,” Razani says. “In other words, our study shows how and why dietary protein leads to the development of unstable plaques.”Plaque contains a mix of fat, cholesterol, calcium deposits, and dead cells. Past work by Razani’s team and other groups has shown that immune cells called macrophages work to clean up plaque in arteries. But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.
Focus on Amino Acids
To understand how high dietary protein might increase plaque complexity, Razani and his colleagues studied the path protein takes after it has been digested—broken down into its original building blocks, called amino acids.Razani and his team found that excess amino acids from a high-protein diet activate a protein in macrophages called mTOR, which tells the cell to grow rather than go about its housecleaning tasks. The signals from mTOR shut down the cells’ ability to clean up the toxic waste of the plaque, and this sets off a chain of events that results in macrophage death.
The researchers found that certain amino acids, especially leucine and arginine, were more potent in activating mTOR than other amino acids. These amino acids were also more likely to derail macrophages from their cleanup duties, thus leading to cell death.
“This work not only defines the critical processes underlying the cardiovascular risks of dietary protein, but also lays the groundwork for targeting these pathways in treating heart disease,” he says.
Support for the work came from the National Institutes of Health, the American Diabetes Association, the Washington University Diabetic Cardiovascular Disease Center and Diabetes Research Center, the Washington University Mass Spectrometry Core, and the Foundation for Barnes-Jewish Hospital.
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