Researchers at the University of Pittsburgh School of Medicine have found a biological mechanism by which a high-protein diet increases the risk of atherosclerosis. The results were published in Nature Metabolism.
The study, which combined small human trials with experiments on mice and cells in petri dishes, showed that consuming more than 22% of dietary calories from protein could increase activation of immune cells that play a role in atherosclerotic plaque formation. Due to which the disease increases. risk. Furthermore, scientists showed that one amino acid – leucine – plays a disproportionate role in driving the pathological pathways associated with atherosclerosis, or hardened, hardened arteries.
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“Our study shows that increasing your protein intake in the pursuit of better metabolic health is not a panacea. You could be causing real damage to your arteries,” said senior and co-corresponding author Babak Razani, MD, PhD, professor . of Cardiology at Pitt. “Our hope is that this research will start a conversation about ways to modify diet in precise ways that can impact body function at the molecular level and reduce disease risks.”
According to a survey of the average American diet over the past decade, Americans generally consume too much protein, mostly from animal sources. Furthermore, almost a quarter of the population gets more than 22% of all daily calories from protein alone.
Razani says this trend is likely driven by the popular idea that dietary protein is essential for a healthy life. But his and other groups have shown that over-reliance on protein may not be such a good thing for long-term health.
Following their 2020 research, in which Razani’s lab first showed that excess dietary protein increases the risk of atherosclerosis in mice, their next study in collaboration with Bettina Mittendorfer, PhD, a metabolism expert at the University of Missouri, Columbia, took a deeper look. Studied. Possible mechanisms and their relevance to the human body.
To arrive at the answer, Razani’s lab, led by first-author Jiangyu Zhang, Ph.D. and Divya Kapoor, MD, worked closely with Mittendorfer’s group to combine their expertise in cellular biology and metabolism and perform a series of different experiments. Models – from cells to mice to humans.
“We have shown in our mechanistic studies that amino acids, which are actually the building blocks of proteins, can trigger disease through specific signaling mechanisms and then also alter the metabolism of these cells,” Mittendorfer said. “For example, small immune cells in the vessels called macrophages can trigger the development of atherosclerosis.”
Based on preliminary experiments in healthy human subjects to determine the timeline of immune cell activation after consumption of a protein-rich meal, the researchers simulated similar conditions in mice and human macrophages, immune cells that specifically secrete amino acids. Are sensitive to. Protein.
Their work showed that consuming more than 22% of daily dietary calories through protein could negatively impact the macrophages that are responsible for clearing cellular debris, leading to a “graveyard” of those cells inside the vessel walls. “Accumulates and over time atherosclerotic plaques get worse. , Interestingly, analysis of circulating amino acids revealed that leucine – an amino acid rich in animal-derived foods such as beef, eggs and milk – is primarily responsible for the abnormal macrophage activation and atherosclerosis risk that individual Suggests a potential opportunity for further research on dietary modification. , or “precision nutrition.”
Razani notes that many questions remain to be answered, primarily: what happens when a person consumes 15% of daily calories from protein and 22% of daily calories from protein as recommended by the USDA, and if There is no ‘sweet’ ‘spot’ to maximize the benefits of protein – such as muscle gains – while avoiding triggering the molecular cascade of harmful events that lead to heart disease.
The findings are particularly relevant in hospital settings, where nutritionists often recommend protein-rich foods for the sickest patients to maintain muscle mass and strength.
“It’s probably wrong to blindly increase protein load,” Razani said. “Instead, it is important to look at diet holistically and suggest balanced meals that will not inadvertently aggravate cardiovascular conditions, especially in people at risk for heart disease and vessel disorders.”
Razani also noted that these findings suggest that differences in leucine levels between diets rich in plant and animal proteins may explain differences in their effects on cardiovascular and metabolic health. “The potential for this type of mechanistic research to inform future dietary guidelines is quite exciting,” he said.
