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Consuming over 22% of dietary calories from protein can lead to increased activation of immune cells that play a role in atherosclerotic plaque formation and drive disease risk, a new study showed.

University of Pittsburgh School of Medicine researchers discovered a molecular mechanism by which excessive dietary protein could increase atherosclerosis risk. The findings were published in Nature Metabolism.

One amino acid in particular, leucine, seems to have a disproportionate role in driving the pathological pathways linked to atherosclerosis. Amino acids, which are the building blocks of the protein, can trigger disease through specific signaling mechanisms and alter the metabolism of small immune cells in the vasculature called "macrophages" which can trigger the development of atherosclerosis.

Disproportionately high protein intake (specifically animal-based protein) can negatively affect macrophages that are responsible for clearing out cellular debris, leading to the accumulation of a "graveyard" of those cells inside the vessel walls and worsening of atherosclerotic plaques overtime.

Leucine is more prevalent in animal-derived foods like beef, eggs and milk, and is primarily responsible for abnormal macrophage activation and atherosclerosis risk. These findings suggest that differences in leucine levels between diets enriched in plant (versus animal) protein might explain the differences in their effect on cardiovascular and metabolic health.

Diets high in animal protein, like the "paleo" and "keto" diets, are gaining in popularity. This research provides evidence that these diets might trigger responses in the body that contribute to the risk of heart attack, or stroke.


mTOR (mechanistic target of rapamycin) is a protein kinase that plays a crucial role in regulating cell growth, proliferation, survival, and metabolism in response to various environmental signals, such as nutrients, energy levels, and stress. It acts as a central regulator of cellular processes by integrating signals from growth factors, amino acids, and other nutrients to control protein synthesis and cell growth.

mTOR exists in two distinct complexes: mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2). mTORC1 is particularly sensitive to amino acids, especially leucine, and is a key regulator of protein synthesis, cell growth, and autophagy (cell recycling).

While we need it early on in life to grow, high levels of mTOR in adulthood seem to be linked to a significantly higher risk of cancer, as well as premature death.

Studies show that in almost 100 percent of advanced human prostate cancers, mTOR is present in higher amounts. Similarly, higher levels of mTOR are found in breast cancer tissues and appear to be associated with advanced disease and worse overall survival rates. Simply put, if you suppress mTOR, you may reduce your risk of cancer and increase your chances of living longer.

Leucine-activated, mTOR signaling, is prevalent in high-protein, animal-based, diets.

Therefore, to lower your leucine intake (and mTOR levels), you should restrict your consumption of animal proteins. While plant foods contain small amounts of leucine, it is nothing in comparison to animal proteins.

Eating plants—and specifically cruciferous veggies—decreases mTOR activation and provides natural mTOR inhibition. Some of the best mTOR-inhibiting fruits and veggies include broccoli, green tea, soy, turmeric, grapes, onions, strawberries, blueberries, and mangoes.

Is mTOR really all that bad?

mTOR is not inherently "bad." It is a critical protein kinase that plays essential roles in regulating various cellular processes, including cell growth, proliferation, metabolism, and survival. mTOR is involved in coordinating cellular responses to changes in nutrients, energy levels, growth factors, and environmental stresses. Some studies suggest that certain plant-based proteins, particularly those high in leucine, and other essential amino acids like soy protein, can effectively stimulate mTOR and promote muscle protein synthesis to a similar extent as animal-based proteins. However, plant-based proteins also contain bioactive compounds, such as polyphenols and phytochemicals, that could modulate mTOR activity through indirect mechanisms.

mTOR is crucial for normal cellular function and is involved in many physiological processes, such as:

  • Protein Synthesis: mTOR promotes protein synthesis by phosphorylating key regulators of translation initiation and ribosome biogenesis, which are essential for building new proteins necessary for cell growth and repair.

  • Cell Growth and Proliferation: By regulating protein synthesis, mTOR controls cell growth and proliferation, ensuring that cells grow and divide appropriately in response to extracellular signals.

  • Metabolism: mTOR influences various metabolic processes, including lipid synthesis, glucose metabolism, and mitochondrial function, to meet the energy demands of growing and dividing cells.

  • Autophagy: mTOR negatively regulates autophagy, a cellular process that degrades and recycles damaged organelles and proteins to maintain cellular homeostasis and prevent cellular damage.

While mTOR is essential for normal cellular function, dysregulated mTOR signaling has been implicated in various diseases, including cancer, metabolic disorders, neurodegenerative diseases, and aging. Excessive mTOR activation can promote abnormal cell growth, tumor formation, insulin resistance, and other pathological conditions.

how much is too much?

Only protein above 25g per meal activates mTOR and has functional consequences. The amount of protein that the body can effectively digest and utilize in one meal can vary depending on factors such as individual physiology, protein source, meal composition, and overall dietary habits. However, research suggests that the body can efficiently digest and absorb roughly 25g of protein in a single meal. This is often referred to as the "anabolic threshold" for protein intake in a single meal.

As I have always personally recommended, individuals should consume approximately 1g of protein per kilogram of body weight. As it turns out, according to this study, 1.6 g of protein per kg resulting in higher mTORC1 activation than 0.8 g of protein per kg.

To summarize, eat more plant-based protein (i.e.: Mediterranean diet), and as always, everything in moderation.



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