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Does a high protein intake increase cardiovascular disease risk?

Protein is one of the most talked about nutrients. Many products nowadays have added protein. Although this is mostly marketing driven there is also evidence that more protein is often considered better, at least up to a point. However, occasionally we also read reports that a higher protein intake may be detrimental for health. And recently a study received disproportional attention in the media after linking a high protein intake to cardiovascular disease risk. Here we will take a closer and more critical look at the study.

Theoretical effect of dietary protein and atherosclerosis

Protein intake: good for muscle, bad for the heart?

Protein is recognised as an important component of the diet to support training adaptations, as well as to help maintain muscle mass during ageing. However, some researchers have suggested a higher protein intake may promote atherosclerosis, the deposition of plaque in the arteries, contributing to cardiovascular disease (CVD) risk.


The new study has led to headlines in popular media, such as:

  • “Eating this much protein can be bad for your heart health”

  • “Why high-protein diets may lead to atherosclerosis”

  • “Study discovers molecular mechanism that could explain why eating too much protein is bad for your arteries”


This suggestion comes from research in animals where protein-derived amino acids activate signalling pathways in immune cells. Specifically, amino acids activate the mTORC1 (mechanistic target of rapamycin complex 1) signalling pathway in immune cells called monocytes/macrophages. When the mTORC1 signalling pathway is activated in immune cells, it can interfere with the body’s natural clearing of dysfunctional or damaged cells, known as autophagy. This interference has been linked with atherosclerosis and increased CVD risk.


Considering CVD is the leading cause of death globally, understanding if there is a link with protein intake would be very important for nutrition guidelines.

How was this new study conducted?

The new study (1), published in Nature Metabolism, aimed to bridge the gap between correlations in rodent studies to the implications for human physiology. To achieve this, the researchers conducted a series of studies in human participants, cultured cells, and mice.


The researchers recruited n=23 adults with overweight or obesity (mean BMI ~28 kg/m2). In one study, 14 participants consumed a drink containing 10% (13g) or 50% (63g) protein. In another study, 9 participants either consumed a meal containing 15% (17g) or 22% (25g) protein. In both studies, blood samples were taken before and after the drink or meal (up to 3 hours afterwards).


The researchers were primarily interested in the activation of mTORC1 signalling in immune cells (monocytes/macrophages). A signalling protein (ribosomal S6) was used as a read out for mTORC1 activity, with a greater signal indicating a greater activation.

What did the new study find?

The new study found a greater activation of mTORC1 signalling in monocytes with a higher protein intake. This activation was more pronounced with the 50% protein drink but was also seen with the 22% protein meal.


As would be expected, blood amino acid concentrations were greater with higher protein intakes. But the authors wanted to see which amino acid(s) were activating mTORC1 signalling. Treating cultured human immune cells with different amino acids (in a Petri dish) revealed leucine to have the greatest effect on mTORC1 activity – an effect commonly observed in skeletal muscle. In an additional study, this time in mice, the authors suggest greater mTORC1 activation with leucine contributed to atherosclerosis in mice consuming a higher vs. lower protein diet for 8 weeks.


Overall, the authors concluded that a high protein intake causes mTORC1 activation, inhibits immune cell regulation, and promotes atherosclerosis. A bold conclusion based on short-term human data (<3 hours) and some longer-term mice data.

Why are these conclusions nonsense?

Findings from this study by Zhang et al. show an acute effect of protein intake on cell signalling in humans that has previously only been seen in animal studies. Although this study provides another piece to the jigsaw, there remains no data in humans showing high protein intakes cause CVD-related events. Some studies have found an association between protein intake and CVD risk in humans, but the association appears to be different for animal- vs plant-based protein (2).


“… there remains no data in humans showing high protein intakes cause CVD-related events”


The main outcome of the human studies from Zhang et al. was an increased cell signalling after a higher vs. lower protein intake. This study only looked at signalling and only at short-term changes (<3 hours). This study is an example of drawing wider conclusions beyond the outcomes that were measured. This leads us to question: was everything relevant measured? Or could there be confounding factors?


Let’s take the analogy of the wheels of a car. If worn out tyres represents CVD and getting in the car represents the activation of mTORC1 signalling, there are many other steps from getting in the car that may be contributing to the tyres becoming worn out. You would first have to start the engine, make sure you have enough petrol, and start driving. Then you have the road surface that you are driving on. If this is not measured, does it mean it is not important? There is also the driving distance, which would have a much greater influence than just getting in the car. Also, if you were to regularly replace the tyres, you would not expect getting in the car to have much of an affect at all. Whether a higher protein intake increases CVD risk (worn out tyres) depends on more than just mTORC1 signalling (getting in the car).


As we have discussed previously, extrapolating short term signalling data to predict longer term outcomes can be misleading. Especially considering only one signalling protein (ribosomal S6) of many signalling proteins was studied in the human experiments. Therefore, how can we conclude short-term signalling will cause to atherosclerosis or CVD risk in humans?

So, where does this leave us for protein intake and CVD risk?

In conclusion, this study shows that a higher protein intake increases mTORC1 signalling in immune cells. It does not tell us that this activation will promote atherosclerosis in humans. And it does not tell us that atherosclerosis from a higher protein intake will cause, or even increase the risk of, a CVD-related event.


The science publication over concluded and the media articles that followed from this exaggerated the message. And because it makes attractive and spectacular headlines this disinformation reaches far more people than it deserves. If you catapult this type of information into the world, the context and the evidence that does not support the message should be considered


There are many risk factors for CVD, including low physical activity, obesity, and older age. In addition, the quantity and source of protein, as well as the amount of other nutrients will likely influence the effect of protein intake on CVD-related markers. In the absence of causational data, there is currently no reason to change daily or per meal nutrition guidelines.


  1. Zhang X, Kapoor D, Jeong SJ, et al. Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk. Nat Metab. 2024 6(2):359-377. PMID: 38409323.

  2. Qi X, Shen P. Associations of dietary protein intake with all-cause, cardiovascular disease, and cancer mortality: A systematic review and meta-analysis of cohort studies. Nutr Metab Cardiovasc Dis. 2020 30(7):1094-1105. PMID: 32451273.


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