Sept. 1, 2024
Hard on the Arteries
Eating too much protein can stiffen vessels.
TOPICS: Chronic Disease | Research
Designs on Aging-Ready
By Ana Gorelova
People in the United States generally consume a lot of protein, mostly from animal sources, according to a survey of their average diet over the last decade. Nearly a quarter of the population receives more than 22% of all daily calories from protein alone.
That trend is likely driven by the popular idea that dietary protein is essential to healthy living, says Babak Razani, professor of medicine at the University of Pittsburgh. But new research shows that overreliance on protein may not be good for long-term health.
Razani and other researchers found a molecular mechanism by which excessive dietary protein could increase the risk of atherosclerosis, or stiff, hardened arteries. The findings were published in Nature Metabolism in February 2024.
The study, which combined small human trials with experiments in mice and cells in a petri dish, showed that consuming more than 22% of dietary calories from protein can lead to increased activation of immune cells that play a role in atherosclerotic plaque formation, driving the disease risk.
“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,” Razani says. “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.”
"[I]t's important to look at the diet as a whole and suggest balanced meals that won't inadvertently exacerbate cardiovascular conditions."
Babak Razani, professor of medicine
Razani’s laboratory first showed that excess dietary protein increases atherosclerosis risk in mice in research from 2020. His next study delved deeper into the potential mechanism and its relevance to the human body in collaboration with Bettina Mittendorfer, a metabolism expert at the University of Missouri-Columbia.
Led by first authors Xiangyu Zhang, research assistant professor, and Divya Kapoor, at Washington University in St. Louis, Razani’s and Mittendorfer’s groups teamed up to combine their expertise.
“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,” Mittendorfer says.
Based on initial experiments in healthy human subjects to determine the timeline of immune cell activation after they ingest protein-enriched meals, the researchers simulated similar conditions in mice and in human macrophages, immune cells that are shown to be particularly sensitive to amino acids derived from protein.
Their work showed that consuming more than 22% of daily dietary calories through protein can trip up macrophages that are responsible for clearing out cellular debris. This leads to the accumulation of a “graveyard” of those cells inside the vessel walls and worsens atherosclerotic plaques over time.
An analysis found that leucine—an amino acid enriched in animal-derived foods like beef, eggs and milk—is primarily responsible for the risk, suggesting a potential avenue for further research on personalized diet modification, or “precision nutrition.” Differences in leucine levels between diets enriched in plant and animal protein might explain the differences in their effect on cardiovascular and metabolic health.
The findings are particularly relevant in hospital settings, where nutritionists often recommend protein-rich foods for the sickest patients to preserve muscle mass and strength.
“Perhaps blindly increasing protein load is wrong,” Razani says.
“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.”
Adapted from the Fall 2024 Pitt Med Magazine