Eating Too Much Protein May Be Bad For Your Arteries

The study combined small human trials with experiments in mice as well as cells in a Petri dish and found that consuming over 22% of dietary calories from protein can lead to the increased activation of immune cells that play a role in the formation of atherosclerotic plaque that drives the risk of developing the disease. The researchers also showed that the amino acid leucine appeared to play a significant role in driving the pathological pathways linked to stiff and hardened arteries (atherosclerosis). 

"Our study shows that dialing up your protein intake in pursuit of better metabolic health is not a panacea. You could be doing real damage to your arteries," said senior and co-corresponding author Babak Razani, M.D., Ph.D., professor of cardiology at Pitt. "Our hope is that this research starts a conversation about ways of modifying diets in a precise manner that can influence body function at a molecular level and dampen disease risks."

Over recent decades Americans have consumed more protein, largely from animal sources, and nearly a quarter of the population receives over 22% of all daily calories from protein alone. The trend is likely due to people believing that dietary protein is essential to healthy living, but according to the researchers, overreliance on protein may not be good for long-term health. 

"We have shown in our mechanistic studies that amino acids, which are really the building blocks of the protein, can trigger disease through specific signaling mechanisms and then also alter the metabolism of these cells," Bettina Mittendorfer, Ph.D., a metabolism expert at the University of Missouri, Columbia said. "For instance, small immune cells in the vasculature called macrophages can trigger the development of atherosclerosis."

Their findings are based on initial experiments with healthy humans to determine the timeline of immune cell activation following eating protein-rich meals and simulating similar conditions in mice and human macrophages in Petri dishes which all showed that immune cells are sensitive to amino acids derived from protein. According to the researchers, consuming more than 22% of dietary calories can negatively affect macrophages responsible for clearing cellular debris leading to the accumulation of those cells in the vessel walls and the worsening of atherosclerotic plaques over time. 

Analysis of circulating amino acids revealed that leucine is primarily responsible for the abnormal macrophage activation and increased atherosclerosis risk. Leucine is found in higher levels in enriched animal-derived foods, and it was noted that level differences between diets enriched by plant and animal protein may explain their effects on cardiovascular and metabolic health. 

While many questions remain regarding different percentages of protein and whether there could be a sweet spot for maximizing the benefits of protein, the findings are relevant to those who often recommend protein-rich foods to preserve/build muscle mass and strength.

Leucine can be found in a wide range of food in varying levels such as lentils, chicken, peanuts, cottage cheese, beef, navy beans, salmon, yogurt, oats, pumpkin seeds, hemp seed, eggs, spirulina, sesame seed, soybeans, quinoa, wheat, tuna, almonds, chickpeas, broccoli, celery, yams, tomatoes, bananas, cucumber, and apples among other sources. 

"Perhaps blindly increasing protein load is wrong," Razani said. "Instead, it's important to look at the diet as a whole and suggest balanced meals that won't inadvertently exacerbate cardiovascular conditions, especially in people at risk of heart disease and vessel disorders."

"The potential for this type of mechanistic research to inform future dietary guidelines is quite exciting," said Razani.