Leucine and Muscle Protein Synthesis...Overrated?

Muscle protein synthesis in response to dietary protein depends on the post-meal availability of Essential Amino Acids in the blood flowing into the muscle. All amino acids are required for protein synthesis, as missing one or more amino acids tend to limit or even prevent protein synthesis.

For example, leucine, along with the other BCAAs isoleucine and valine, are heavily involved with initiating muscle protein synthesis. However, consuming BCAAs alone cannot enhance muscle protein synthesis for a long time if the availability of other EAA is limited. Yes, taking BCAAs or leucine can result in a quick bump in muscle protein synthesis, but it’s not as big or as long as a full meal containing more protein, more Calories, and so on.

Research on leucine, BCAAs, and EAAs have led to the concept of a “leucine threshold”, where there’s a minimum amount of leucine needed to maximize muscle protein synthesis for a meal. The suggested mechanism is as follows:

*X amount of leucine is needed to be in a meal in order to produce a big increase in blood levels of leucine (leucinemia) quickly. Higher blood leucine levels drive more muscle protein synthesis, which is better for muscle growth, recovery, and performance.

The ISSN recommends that each meal should “…strive to contain 700–3000 mg of leucine and/or a higher relative leucine content, in addition to a balanced array of the essential amino acids (EAAs).” For healthy individuals, the leucine threshold for a meal about ~ 2-3 grams, whereas individuals with anabolic resistance may need more.

The leucine threshold theory has extended to protein sources as well, where protein sources like whey, beef, chicken, and other animal sources are preferred for their high leucine content compared to plant-based protein sources. For example, 25 grams of whey contains about 2.7 g of leucine and 10.9 g total of EAAs, whereas someone would need to consume 31 g of corn protein powder or 105 g of hemp protein to get the same doses of leucine and EAA.

For the most part, we’ve stayed away from micromanaging the intake of leucine and EAAs. Instead, we’ve recommended protein intakes high enough to make it very unlikely someone isn’t getting enough leucine or EAAs, regardless of dietary pattern (e.g. vegan or omnivore). Our view is less concerned with the mechanisms of muscle protein synthesis, but rather, muscle- and health- related outcomes from various dietary and exercise practices. However, others in the space really focus on leucine intake, often advocating for ultra-specific strategies in order to “optimize” performance and health.

A recent paper published has called the leucine threshold into question, suggesting that it is reductionist based on emerging evidence.

The UK-based research group has identified a number of inconsistencies with the leucine threshold theory:

  • Muscle protein synthesis rates are not reliably predicted by leucine content in food in most adults. There’s a moderate correlation between the two for older individuals post workout.
  • Blood leucine levels are not linearly proportional to food leucine levels, e.g. 20g of whey increases blood leucine to ~400 ÎĽ mol/, while 40g of whey only goes up to 600 ÎĽ mol/L.
  • Blood leucine levels don’t reliably predict muscle protein synthesis rates between different foods (e.g. fungal protein vs whey, cooked vs raw egg, etc.)
  • Even meals with no leucine and subsequent leucinemia have increased muscle protein synthesis

My take?

I think that these findings highlight the challenge in making logical leaps from one “finding” to another. While leucine is clearly involved in muscle protein synthesis and eating more protein (upt to a point) tends to produce better muscle-related outcomes, it’s not clear these outcomes are caused by leucine specifically. It’s also not clear that altering leucine intake directly would lead to improvement in these outcomes.

To me, this is similar to the food matrix theory, which suggests that the effects of foods are the result of how each and every component of the food interact with each other in the body. It’s not just the fiber, the flavonoid, or a particular vitamin. Rather, it’s the whole food.

I don’t think this changes my protein recommendations, but maybe I won’t talk about leucine as much when describing muscle protein syntheis.

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