In today’s episode of The Modern Vital Podcast, we will discuss one of the most important pathways for protein synthesis in the body, a pathway known as the mTOR pathway.
Our Modern Vital Fact of the Day is that mTOR is both activated and inhibited by exercise. It is inhibited in the fat and liver cells, but activated in the brain, the muscles and the heart. This is one reason why daily exercise is one of the most critical factors in extending our lifespan and our health span.
So, first off, what is mTOR? Well, it is a protein complex that plays a crucial role in the regulation of cell growth, metabolism and survival in response to various environmental signals.
mTOR stands for mechanistic target of rapamycin. You may be reminded of the drug rapamycin, which is used to keep the body from rejecting organs and bone marrow transplants by blocking certain types of white blood cells.
Rapamycin targets mTOR, which is where it gets its name. Now, as far as environmental signals, we mean particularly nutrients, energy and stress. These signals can also include growth factors, amino acids such as leucine and glucose.
Not only does mTOR regulate protein synthesis, but also autophagy and lipid metabolism. Sounds pretty important, right? By the way, autophagy is the process by which a cell breaks down and destroys old, damaged or abnormal proteins and other substances in its own cytoplasm, that fluid inside of a cell.
mTOR is located in the cytoplasm of cells and is activated by upstream signaling pathways. One common pathway is PI3K/ Akt. Now, not only does mTOR play a crucial role in cell growth and differentiation, it is also actively involved in the pathogenesis of various diseases, such as cancer, metabolic disorders like type 2 diabetes and neurological disorders.
It would be nice to know how to target mTOR from a naturopathic perspective then as part of our therapeutics, so as to derive health benefits. We’re going to discuss some ways on this podcast.
Now, I think of particular importance is the connection between insulin resistance and mTOR.
By the way, when running a fasting insulin, did you know that a level of 10 really is the beginning of insulin resistance, even though the common reference range in micro-international units per milliliter is from 5 to 23? However, if your fasting insulin is at 15 or something, it’s far from normal.
Now, one fact is that excessively activated mTOR can lead to insulin resistant tissues that are otherwise insulin sensitive, such as the muscle, liver and adipose or fat. When mTOR is chronically over-activated in these tissues, then insulin signaling and glucose uptake can be impaired.
But one question is what type of diet are these people consuming? So, most studies are done on rats.
I would imagine that most people are consuming a boatload of carbs, even when they are on a so-called healthy diet. Anyway, the idea is that exercise can be overdone and we have to prescribe exercise for the person.
The type 2 diabetic will need to exercise differently than someone with no chronic disease who consumes a modified ketogenic diet, and that’s just a fact.
The idea here is that mTOR activity can be modulated by diet and lifestyle and by our environment.
Now, of course, I recommend that you consult a naturopathic doctor on this topic.
One needs to look at caloric restriction, exercise, specific nutrients and much more. Some studies have shown that caloric restriction can inhibit mTOR activity, which could have a beneficial effect on health and longevity, and some studies demonstrate how exercise, particularly high-intensity interval training or HIIT, can activate mTOR in muscle tissue and promote muscle growth and repair.
mTOR is a protein kinase, which means that its action requires energy or ATP via a process called phosphorylation. What this also means is that activating mTOR requires energy, and so anything we can do to support our mitochondria will also support our mTOR pathway.
Now, insulin resistance is the main factor in many diseases, such as PCOS, metabolic syndrome, type 2 diabetes.
PCOS, also known as polycystic ovary syndrome, is a common hormonal disorder in women that can cause infertility and irregular periods, such as metrorrhagia, which is bleeding at irregular intervals; amenorrhea, which is the absence of menstruation; oligomennorhea, which is infrequent menstrual periods; and hypomenorrhea, which refers to light periods.
Hence, an inactive mTOR or an under-activated mTOR could be associated with irregular periods.
Just a side note, a fasting insulin must absolutely be run when working up one for metabolic syndrome.
When an individual has three or more of the following five factors, we diagnose metabolic syndrome, and these five factors are number one, central obesity measured in waist circumference, which is 40 inches for men and 35 inches for women; number two, elevated blood pressure, that is 130 over 85 or higher. Number three, high triglyceride levels, that is, 150 milligrams per deciliter or higher. And number four, low HDL cholesterol levels.
HDL is known as the good cholesterol, as it’s been shown to absorb cholesterol from the blood and carry it back to the liver. That is, less than 40 milligrams per deciliter in men and less than 50 milligrams per deciliter in women.
And then, finally, number five, elevated fasting blood glucose levels of 100 milligrams per deciliter or higher.
But why is a fasting insulin not required?
According to Johns Hopkins research, most who have metabolic syndrome also have insulin resistance.
Remember that insulin, which is released by the pancreas, helps to push our glucose into our cells so that it can be used for fuel.
By the way, potassium always rides shotgun with insulin, so having imbalances in electrolytes can also really mess this whole process up. The cells have a much more difficult time responding to insulin in those with metabolic syndrome for a variety of reasons, not to mention the mTOR pathway could probably use some serious support.
Insulin resistance can cause plaque to build up in our arteries, a process known as atherosclerosis, which then makes heart attack and stroke more likely. Insulin resistance can drive the deposition of fat in our liver, which can then progress to NAFLD, or non-alcoholic fatty liver disease, where our liver cells can become damaged and inflamed. Liver enzymes like ALT and AST run high in NAFLD and imaging studies reveal fat accumulation in the liver in spite of the person not consuming any alcohol.
Glucose metabolism can be impaired in the brain with insulin resistance because we have insulin receptors in our brain which can lead to Alzheimer’s. Insulin resistance has been associated with certain cancers, such as breast, colon and pancreatic cancer. Even sleep apnea has been associated with insulin resistance.
So basically, it goes to show that if we can get our mTOR pathway dialed in, maybe we can reverse or better control insulin resistance and be less likely to suffer from chronic disease.
Let’s talk insulin resistance a little bit more.
Our cells can become less responsive to the hormone insulin over time. Now, mind you, insulin has a pretty tall order. It’s responsible for regulating our blood sugar levels and also in promoting the uptake of glucose by cells for energy production. Some studies in mice have found that insulin resistance can impair mTOR signaling by reducing the activity of upstream signaling pathways required to activate mTOR pathways, such as PI3K/ Akt. Insulin resistance, also known as IR, is associated with reduced mTOR signaling and impaired synthesis of muscle protein, which can lead to things like sarcopenia.
So how can we activate the mTOR pathway?
Well, first of all, it’s important to note that, as you probably have gathered by now, mTOR activation is a complex process and we need to apply the Goldilocks principle, that is, we need not too little but not too much activation of mTOR. And, honestly, it depends on who you talk to and what your health goals are.
There are some people who are afraid to activate mTOR, and they make some good points. We have to find the right amount of activation for each individual and also we are still learning a lot about mTOR. Now I happen to fall more at the end of the spectrum that believes we really do need to activate mTOR on a daily basis for longevity and health.
Several ways include resistance training or weightlifting, which can activate mTOR and promote muscle protein synthesis. My personal favorite way is to strategically stack three to four sets of eight to twelve reps, each of three to four exercises, with 30 second to 60 second breaks in between, also known as intervals, under the guidance of a personal trainer.
Now, when you’re stacking the three or four exercises, you’re not taking any breaks, but it’s when you’re done with each stacked set of three sets that you take your break, and I recommend doing this under the guidance of a personal trainer, if you can, with your personal goals in mind. You can do this for 15 to 60 minutes, depending on the day.
Also, choose your kettlebell over Ketel One.
Now, diversifying one’s amino acid intake and obtaining adequate protein in the diet, especially leucine, which is an amino acid, will help promote muscle protein synthesis. Leucine has been shown to particularly activate mTOR. Eggs and dairy are a rich source of leucine for those who are vegetarian and, interestingly, so are chickpeas, brown rice and soybeans.
According to Robb Wolf, we need about 25 grams of protein or more to get the required amount of leucine and branched chain amino acids for mTOR activation and to stimulate an anabolic as opposed to a catabolic effect. A three ounce can of wild sardines from Wild Plane plus a hard boiled egg is about 24 grams of protein. The sardines are about 18 grams and the egg is about 6, so it’s pretty close. You can throw in three or four cashews, which is about another gram of protein.
Sun exposure and 25-hydroxy Vitamin D have been associated with activated mTOR and the promotion of muscle protein synthesis, though little is known about why this is, and this is why people in San Diego probably have more highly activated mTOR.
Anyway, cold water, fatty fish are also a pretty good source of vitamin D for those who live in sun deficient areas.
Mitochondrial support, such as acetyl-L-carnitine, CoQ10, glutathione, magnesium, B vitamins, these will all support the production of ATP and healthy mitochondria, which also provides energy to drive mTOR, which requires energy.
You don’t want to overactivate your mTOR, but you also don’t want to underactivate it.
The moral of the story is that your mTOR deserves to be fully activated so that you can live to your highest potential and feel awesome.
So, in summary, mTOR is a pathway that is critical to building or losing muscle mass, and insulin resistance will turn it off. Avoiding sarcopenia is key to our longevity and one of the keys to activating protein synthesis in our bodies is turning on the mTOR pathway on a daily basis.
That concludes today’s episode of The Modern Vital Podcast. We would love to hear from you. We value your feedback. If you have any questions or suggestions, please reach out to me at firstname.lastname@example.org. Also, please leave us a review here if you enjoyed this episode. We look forward to having you join us next week for another exciting episode of The Modern Vital Podcast.