by Nils Osmar. October 3, 2022. Medical Disclaimer
In a recent animal study, the amino acid leucine was found to reverse antherosclerosis and lower total cholesterol levels. See study: Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice
Some people in our community avoid leucine, which is found mainly in animal foods, because it activates mTOR (the growth pathway) and temporarily shuts off AMPK (the longevity pathway) after we eat foods containing it. While I agree that it’s good to take breaks from mTOR activation, I personally see no reason to avoid foods with leucine.
What makes sense to me is to use intermittent fasting or time restricted eating to alternate between stretches of mTOR and AMPK activation.
These days, I’m eating all of my meals within about 5 hours a day. I start fasting after dinner, and don’t eat again till around 2 the next afternoon. During those 5 hours, I eat ample protein and am not afraid of activating mTOR. In fact, activating it is my goal. During the other 19 hours, I’m eating nothing, so mTOR will switch off and AMPK will become activated (along with a light level of autophagy, which cleans debris from our cells).
Other approaches, like alternate day fasting, provide even longer stretches of AMPK activation.
See study: “Intermittent Fasting Activates AMP-Kinase”
Interestingly, an ITP study looked at leucine found that while it does not extend lifespan, it doesn’t shorten it either. So the notion that we should avoid foods high in leucine because activating mTOR could shorten the lifespan is not supported by the ITP.
Some mTOR activation is in fact necessary to prevent sarcopenia and keep the immune system strong. (Animals who are fed very low protein, low leucine diets have depressed immune function. Their immune systems are so poor they could never survive, much less have extended lifespans, outside of the protected environment of the lab.) See article: “Protein Malnutrition Impairs the Immune Response“
Leucine and muscle growth
Aging people are faced with the reality that our muscles start shrinking as we age. Eating too little protein and leucine is a particularly dangerous approach for the older population. We can learn also from studies focusing on bodybuilders. Here’s a quote from a study called Evidence-based recommendations for natural bodybuilding contest preparation: nutrition and supplementation
A relatively recent concept with potential application to meal frequency is that a certain minimum dose of leucine is required in order to stimulate muscle protein synthesis.
Norton and Wilson  suggested that this threshold dose is approximately 0.05 g/kg, or roughly 3 g leucine per meal to saturate the mTOR signaling pathway and trigger MPS. A related concept is that MPS can diminish, or become ‘refractory’ if amino acids are held at a constant elevation.
Evidence of the refractory phenomenon was shown by Bohé et al. , who elevated plasma amino acid levels in humans and observed that MPS peaked at the 2-hour mark, and rapidly declined thereafter despite continually elevated blood amino acid levels.
For the goal of maximizing the anabolic response, the potential application of these data would be to avoid spacing meals too closely together. In addition, an attempt would be made to reach the leucine threshold with each meal, which in practical terms would be to consume at least 30–40 g high-quality protein per meal.
In relative agreement, a recent review by Phillips and Van Loon  recommends consuming one’s daily protein requirement over the course of three to four isonitrogenous meals per day in order to maximize the acute anabolic response per meal, and thus the rate of muscle gain.
Most elderly people aren’t bodybuilders, but the same principles apply to muscle growth in both groups, particularly since the activation of mTOR in response to protein is inversely correlated with aging.
This article is not intended as, and should not be taken as, medical advice.
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