The negative effects of excess activation of the mTOR pathway can lead to cancer, insulin resistance, diabetes, Alzheimer’s, etc. Meanwhile, if we always keep it inhibited, we would affect the creation of tissue, muscle, bone, and cell repair – leading to sarcopenia, osteoporosis, weakness… and these are the problems of an over-activation of the AMPk pathway.
In this second part of the articles dedicated to the AMPk and mTOR metabolic pathways, we will try to give some ideas on how to balance these two pathways to get the best out of each of them. At Neolife, we know how to help you with these strategies adapted to your situation and your state of health so that you have an optimal quality of life and state of health.
Dr. Alfonso Galán González – Neolife Medical Team
High-intensity exercise, or exercise at high-intensity intervals, such as HIIT, has been shown to activate the AMPk pathway, while strength (weight) training activates the mTOR pathway.
In this second part of the articles dedicated to the AMPk and mTOR metabolic pathways, we will try to give some ideas on how to balance these two pathways to get the best out of each one.
Scientific interest in them has been increasing in recent years, as shown by the number of articles published in Pubmed when you search for mTOR:
And for AMPk:
We mentioned in the previous article that the negative effects of excess activation of the mTOR pathway can lead to cancer, insulin resistance, diabetes, Alzheimer’s, Parkinson’s, etc. Meanwhile, if we always keep it inhibited, we would affect the creation of tissue, muscle, bone, and cell repair – leading to sarcopenia, osteoporosis, weakness… and these are the problems of an over-activation of the AMPk pathway – mTOR’s “antagonistic” pathway.
Thus, we do not want to develop diabetes, neurodegenerative and cardiovascular diseases, or cancer; however, we also do not want to lose bone mass or muscle mass, which we need in order to have an adequate metabolic rate to promote the burning of fat and glucose.
Life in industrialized society almost inevitably leads us to an excess of mTOR activation, as we have plenty of food, we can eat as many times a day as we want (always maintaining high sugar levels with the consequent release of insulin), and we have sedentary jobs not needing to undertake physical activity to get our food. As we have seen, these are the things that inhibit AMPk pathway activation and that may be the cause of the increase in metabolic diseases in recent decades. Obviously, if we think about how the first humans lived, we can see that inevitably there was an alternation between exercise and rest, between eating and fasting…
Currently, we could say that we have to “simulate” all of that in order to improve our state of health and get the benefits of both metabolic pathways while avoiding the negative effects at the same time.
I hope I have been able to convey that neither of the pathways is good or bad; it is a balance between the two that will lead us to greater longevity, a life free of disease, to avoid the loss of muscle mass and bone mass, etc.
How do we balance both pathways?
Alluding to the 4 fundamental pillars of treatment of Age Management Medicine and of Neolife (which we can expand to many more, but for educational and practical purposes we will reduce to 4) which are nutrition, exercise, supplementation, and hormonal balance, we will briefly explain what can be done.
- Nutritional strategies:
The intermittent fasting that we hear about everywhere and about which we have written on our blog on other occasions is a simple technique that will activate the AMPk pathway. We recommend fasts of at least 12h to bring about activation (usual and moderately bearable strategies go up to 14-16h). From that time, the glycogen of the liver already begins to mobilize itself, glucose and insulin in blood lower, and the secretion of hormones increases – such as cortisol, adrenaline, noradrenaline, growth hormone,– as well as the biogenesis of more mitochondria to optimize energy gathering and production.
Meals should preferably be low in carbohydrates and have a low or medium glycemic index (this measures how fast and how many carbohydrates in a food get into the blood in the form of glucose). In order to activate the mTOR pathway after training, to take advantage of the conditions when the workout is over and promote muscle development, it is important for food to be rich in proteins and carbohydrates and for it to have a high glycemic load (white rice, potatoes, pasta, etc.).
- Training strategies:
As we have already mentioned, high-intensity exercise, or exercise at high-intensity intervals, such as HIIT, has been shown to activate the AMPk pathway, while strength (weight) training activates the mTOR pathway. We recommend alternating both forms of training throughout your weekly exercise routine to promote – on the one hand – carbohydrate metabolism, energy collection, fat burning, and mitochondrial biosynthesis, and – on the other – muscle development. We must stop to think here about how intimately related the two pathways are, despite their “antagonistic ” effects. As we develop more muscle, we will have more peripheral insulin receptors, which will favor AMPk action in terms of improving insulin resistance; and those muscles that are more developed because of mTOR activation will be more efficient when producing energy because they have higher mitochondrial density thanks to the activation of the AMPk pathway.
There are several supplements that help us to activate these pathways in addition to the drugs already mentioned like metformin for the AMPk pathway and rapamycin for the mTOR pathway.
Alpha-lipoic acid, resveratrol, quercetin, EGCG from green tea, berberine, turmeric, anthocyanins from blueberries, zinc, carnitine, virgin olive oil, fish oil (omega 3), ginseng, cinnamon, astragalus, Coenzyme Q10, red rice yeast, and apigenin all activate the AMPk pathway.
As for activating the mTOR pathway, it is a good idea to use amino acids such as leucine, whey protein, and hydrolyzed carbohydrates, which lead to an insulin peak that activates this pathway during strength training. Testosterone also activates the mTOR pathway (Basualto-Alarcón C et al. 2013).
With this we hope to have given you a bit of a better understanding of these important metabolic pathways and how to use them to your benefit. At Neolife, we know how to help you with these strategies adapted to your situation and your state of health so that you have an optimal quality of life and state of health.
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