How high protein diets can increase risk of heart attack

Some people may choose a high protein diet to loose weight and build muscle mass. But a new study in mice indicates such a diet may endanger cardiovascular health.

A lady eating high protein diets
Recent animal model research shows that high protein diets can have a direct effect on cardiovascular health, potentially increasing risk of heart attacks.

“There are strong weight loss benefits for high-protein diets that have increased their popularity in recent years,” says Dr. Babak Razani, associate professor of medicine at the Washington University School of Medicine in St. Louis, MO.

“However,” he adds, “animal studies and some large-scale epidemiological studies in humans have connected high-protein to cardiovascular issues.”

That is why Dr. Razani and his colleagues decided to try to find out if high protein diets could actually directly impact cardiovascular health by promoting plaque buildup inside the arteries.

“We have decided to look at whether there really is a causal link between high dietary protein and reduced cardiovascular health,” Dr. Razani says.

He and his colleagues performed their research in mouse models, and their results have now been published in the journal Nature Metabolism.

30% more arterial plaque

The researchers were fed a high fat diet to mice in the study. We demonstrate that mice require a high fat diet to initially grow arterial plaque.

However while some of the mice got a diet high in fat and protein, others were given a high fat diet low in protein. This allowed researchers to recognize any differences.

“A few scoops of protein powder in a milkshake or smoothie contain something like 40 grams (g) of protein— almost the equivalent of the recommended daily intake,” Dr. Razani says.

“To see if protein has an effect on cardiovascular health[ in our study] we tripled the amount of protein the mice get in the high-fat, high-protein diet— holding the fat constant. Protein for these mice went from 15 to 46 per cent of calories,” he says.

Dr. Razani and his team soon noticed that rodents who had fed on a high-fat, high-protein diet had not only developed atherosclerosis — a disease marked by arterial plaque accumulation— but that it was much worse than mice who had consumed a high-fat, low-protein diet.

While the mice in the high-fat, high-protein diet gained no weight despite consumption of loads of fats, they developed about 30 percent more plaque in the arteries compared to the mice in the high-fat but low-protein diets.

In addition, the kind of plaque built up in the arteries of these mice appeared to be what researchers term “unstable” plaque— a plaque that is smaller and can easily break off the arterial wall, increasing the risk of blockages and, possibly, a heart attack.

“This study is not the first to show a telltale rise in plaque with high protein diets, but it offers a deeper understanding of the effects of high protein with a detailed plaque analysis,” Dr. Razani emphasises.

“In other words, our study shows how and why dietary protein is causing dysfunctional plaques to form,” he continues.

‘A recipe for heart attack’

Mammalian bodies also have a first-line defense against arterial plaque, the researchers demonstrate. A group of white blood cells called “macrophages” normally “pick up” on the presence and remove these deposits.

We are, however, also disrespectful to the job. As this happens, macrophages die, causing the arterial plaque to build up again.

“Their plaques were a macrophage graveyard in mice on the high protein diet,” says Dr Razani, reflecting on what he and his team noticed.

Numerous dead cells in the plaque’s heart make it extremely brittle and vulnerable to rupture. When blood flows past the plaque, it puts a lot of stress on it— especially in the context of high blood pressure. This condition is a heart attack recipe.

– Dr. Babak Razani

The researchers also looked at the mechanism by which dietary protein may contribute to unstable arterial plaque formation.

To do this, they looked at what happens after the dietary protein digestion— one time, that is, this breaks down into the amino acids that have formed it.

The team found that the excess amino acids extracted from a high protein diet directly activate another protein that is present in macrophages — called mTOR.

This sends a signal to the macrophage when mTOR becomes active to focus on growing, rather than detecting and cleaning up plaque buildup. Finally the cycle of abnormal growth leads to death in the macrophage.

Future research pathways

Two particular amino acids– called leucine and arginine– were the main players when macrophages were incapacitated, Dr. Razani and his colleagues demonstrate.

Understanding this, however, can also help us understand what foods people should avoid. For example,”[ l]eucine is particularly high in red meat, relative to, say, fish or protein sources in plants,” the researcher reports.

And the knowledge that some amino acids derived from dietary protein could be more harmful than others may also lead further research into diet and cardiovascular health

“A future study would look at high protein diets with different content of amino acids to see if that might influence the production of plaques,” Dr. Razani explains.

“Cell death is a key feature of instability in plaques. If you could prevent the dying of these cells, you might not make the plaque smaller, but you would may its instability,” he says.

So the researchers suggest that looking at these pathways more closely could also lead to the development of better treatments for cardiovascular problems.

“This study not only describes the essential mechanisms underlying dietary protein’s cardiovascular risks, but also lays the groundwork for addressing these pathways in the treatment of heart disease,” says Dr. Razani.

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