Many people might choose to follow a diet high in protein content to lose weight and build muscle mass. But a new study in mice suggests that such a diet could put cardiovascular health at risk.
“There are clear weight loss benefits to high protein diets, which has boosted their popularity in recent years,” says Dr. Babak Razani, an associate professor of medicine from Washington University School of Medicine in St. Louis, MO.
“But,” he adds, “animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems.”
That is why Dr. Razani and his colleagues decided to try to find out whether high protein diets might actually influence cardiovascular health directly by facilitating the buildup of plaque inside the arteries.
“We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health,” explains Dr. Razani.
He and his team conducted their study in mouse models, and they have now published their findings in the journal Nature Metabolism.
In the study, the researchers fed mice a high fat diet. They explain that mice require a high fat diet in order to develop arterial plaque in the first place.
But while some of the mice received a diet that was high in fat and proteins, others received a high fat diet with a low protein content. This allowed the investigators to pinpoint any differences.
“A couple of scoops of protein powder in a milkshake or a smoothie adds something like 40 grams (g) of protein — almost equivalent to the daily recommended intake,” notes Dr. Razani.
“To see if protein has an effect on cardiovascular health, [in our study] we tripled the amount of protein that the mice receive in the high fat, high protein diet — keeping the fat constant. Protein went from 15% to 46% of calories for these mice,” he explains.
Dr. Razani and his team soon found that the rodents that had fed on the high fat, high protein diet had not just developed atherosclerosis — a condition characterized by the buildup of arterial plaque — but that this was significantly worse than in the mice that had eaten the high fat, low protein diet.
While the mice in the high fat, high protein diet did not gain any weight despite ingesting lots of fats, they developed approximately 30% more plaque in the arteries compared with the mice on the high fat but low protein diet.
Moreover, the kind of plaque that built up in these mice’s arteries tended to be what researchers call “unstable” plaque — plaque that is thinner, and may break off the arterial wall easily, increasing the risk of blockages and, potentially, a heart attack.
“This study is not the first to show a telltale increase in plaque with high protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques,” Dr. Razani emphasizes.
“In other words, our study shows how and why dietary protein leads to the development of unstable plaques,” he continues.
Mammal bodies, the researchers explain, actually have a first-line defense against arterial plaque. A type of white blood cells called “macrophages” usually “pick up” on the presence of these deposits and remove them.
However, sometimes they are unequal to the task. When this happens, macrophages die, leaving arterial plaque to continue to build up.
“In mice on the high protein diet, their plaques were a macrophage graveyard,” Dr. Razani says, commenting on what he and his team found.
The researchers also looked into the mechanism through which dietary protein may contribute to the creation of unstable arterial plaque.
To do so, they looked at what happens following the digestion of dietary protein — once, that is, it breaks down into the amino acids that have formed it.
The team found that the excess amino acids derived from a diet with a high protein content actually activate another protein — called mTOR — that is present in macrophages.
When mTOR becomes active, it sends a signal to the macrophage to focus on growing rather than identifying and cleaning up plaque buildup. Eventually, the abnormal growth process leads to macrophage death.
Two specific amino acids — called leucine and arginine — were the main players when it came to incapacitating macrophages, explain Dr. Razani and his colleagues.
But knowing this may also help us understand which foods people should avoid. For instance, “[l]eucine is particularly high in red meat, compared with, say, fish, or plant sources of protein,” notes the researcher.
And the understanding that some amino acids derived from dietary protein might be more harmful than others could also inform further research around diet and cardiovascular health
“A future study might look at high protein diets with different amino acid contents to see if that could have an effect on plaque complexity,” says Dr. Razani.
“Cell death is the key feature of plaque instability. If you could stop these cells from dying, you might not make the plaque smaller, but you would reduce its instability,” he notes.
So going forward, the researchers suggest that looking more closely at these mechanisms could also lead to the development of better treatments for cardiovascular problems.
“This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease,” says Dr. Razani.