Heart Disease Linked to Eating Too Much Protein

We're often told to eat more protein to maintain a healthy, balanced diet. But new research shows that eating too much could actually be bad for our health.

Protein is an essential macronutrient and is important for growing and maintaining muscle mass. It has also been shown to reduce cravings and boost our metabolism. However, the amount of protein that our bodies actually need to fulfill these functions is much lower than modern marketing would have you believe.

All proteins are made of a string of individual units called amino acids, like beads on a string. Each amino acid has its own distinct properties and is present in varying levels from different protein sources.

In a new study, published in the journal Nature Metabolism, researchers found that eating too much of one particular amino acid, called leucine, may increase our risk of cardiovascular disease.

"We initially became interested in this topic since high protein diets are popular with both clinicians, nutritionists and the public for weight loss, building of muscle mass, and overall metabolic health," co-author Babak Razani, Professor of Cardiology and Director of the Center for Immunometabolism at University of Pittsburgh School of Medicine, told Newsweek. "But there have been large and well-done epidemiological studies (mostly based on dietary questionnaires) that show increased protein intake correlates with cardiovascular disease."

In 2020, Razani's team published a paper using mice to show that high protein diets were associated with an increased risk of atherosclerosis, the buildup of fats, cholesterol and other substances in and on the artery walls.

"We went further to show the exact mechanism which involved the following: protein intake results in flooding of the bloodstream with amino acids," it said. "Immune cells called macrophages, which are a significant driver of atherosclerosis, uptake the amino acids, [which is sensed by] an important [molecule] called mTOR. mTOR initiates deleterious signaling pathways in macrophages that result in dysfunction and in turn exacerbation of atherosclerosis."

In other words, high protein diets can activate a molecular machine called mTOR, which triggers our immune cells and increases the buildup of fats and cholesterol in our artery walls.

"In the current study, we test this protein-amino acid-immune cell response in actual human studies and find that just like our animal studies, human immune cells respond in exactly the same way," Razani said.

One amino acid in particular seemed to be driving this signaling pathway.

"We found that even though many amino acids increase in the blood stream after protein ingestion, it is predominantly leucine that activates mTOR and the deleterious signaling pathways in macrophages, the immune cells which are the key driver of atherosclerosis (or cardiovascular disease)," Razani said.

But how much protein do you need to eat to trigger this response?

"We used different doses of protein in the form of smoothies or mixed meals to get an approximation of the level of protein ingestion it takes to activate our immune cells," Razani said. "That turns out to be around 22 percent [of total] kilocalories intake. Just for context, the USDA recommends a balanced diet of 15 percent kilocalories protein together with healthy fats and complex carbohydrates, which is largely mirroring a Mediterranean diet."

Of course, different protein sources will differ in their concentration of leucine.

"Some animal protein like whey, which many protein powders in nutrition stores are composed of, do have higher leucine content," Razani said. "But in aggregate [i.e. in whole meats], the difference in leucine content of animal protein over plant protein is not very significant.

"The more complicated question lies in how these proteins are digested, absorbed, and the kinetics by which leucine enters our bloodstream. This is an issue that could really differentiate the leucine effect on our immune cells and atherosclerosis. We are working on this as we speak."

More work is also needed to understand the true impact of dietary protein on human health.

"Clearly, long-term human studies are needed to impact dietary guidelines but the take-home message is that blindly eating more protein in your diet for overall metabolic health is not a cure-all," Razani said. "As a cardiologist, I still recommend people to abide by USDA nutrition recommendations which closely follow the Mediterranean diet, with roughly 15 percent kilocalories of daily dietary protein coupled with healthier fats and complex carbohydrates, and constitutes one of the most balanced diets for the vast majority.

"In addition, do not take the results of our study to drastically change your diet without consulting with a physician, especially if you already suffer from cardiovascular disease. Our study should increase conversation on this topic and stimulate the nutrition, metabolism, and medical community to conduct mechanistic studies such as this to arrive at a more comprehensive understanding of our diet's role in heart health."

Update 02/23/2024 13:29 ET: This article was updated to include additional details on Professor Razani's position at the university.