Ketogenic nutrition in metabolic imbalances – Leptin resistance (Leptin Rx)
Initially, when I started writing this article, I intended to take and dissect each metabolic disease separately. While studying the subject, the text changed its form. I realized that what matters is to know the mechanisms by which these metabolic imbalances occur, and as I analyzed them, I realized that they all converge to one: Leptin resistance!
Thus, I prefer to define some terms and some notions, for the specialized language to be understood, and to put the spotlight on the metabolic processes involved. I will expand only on the current one.
THIS ARTICLE INCLUDES
- Basic Terms & Notions: insulin, leptin, sdr. metabolic, diabetes, obesity.
- Leptin resistance: leptin, mechanisms of action, leptin and the brain, leptin and other hormones, leptin and immunity, leptin and the locomotory system
- Solutions: aspects to consider, ketonutrition and biohacking as a solution.
Basic Terms & Notions
Insulin is the hormone released into the blood by beta-pancreatic cells when we have a blood glucose (blood glucose) higher than 110 mg / dl. Insulin helps glucose to pass from the bloodstream into the cell, bringing blood sugar back to normal. It is thus a hypoglycemic and anabolic hormone (supports the formation of tissues). Keep in mind that blood glucose counts for insulin. This is a very simplistic description of the complex role that insulin plays in the body. A more accurate definition may describe insulin as the hormone that is responsible for storing energy in the body. For a more detailed understanding, I recommend this video with the effects of insulin on the whole body, in which everything that involves the metabolism of insulin is schematically, but almost completely, represented.
Metabolic syndrome is not a disease in itself. It is rather a diagnosis that, once made, means reaching a fairly high threshold in metabolic imbalance in general. It is defined as a combination of at least 3 of the following factors: high blood pressure, low glucose tolerance, abdominal obesity, high triglycerides and low HDL. In medicine, the presence of metabolic syndrome is considered a risk factor for cardiovascular disease, diabetes and stroke.
Diabetes occurs when, due to a resistance of the receptors to the action of insulin, glucose remains in the blood. Similarly, the diagnosis (according to the American Diabetes Association) is made when the following conditions are met: symptoms + blood sugar> 200 mg / dl; fasting blood glucose> 125 mg / dl; blood glucose> 200 mg / dl 2 hours after ingestion of 75 g glucose.
Obesity is more than normal weight gain. Specifically, the diagnosis of obesity is made when the body mass index (BMI) exceeds the value of 30 kg / m2. The diagnosis of abdominal obesity is made when the abdominal circumference exceeds 80 cm in women and 94 cm in men.
Regarding leptin and leptin resistance, there are several articles and sources of information, but my main choice is Dr. Jack Kruse. He is one of the few physicians who has understood its importance and, with an enormous body of knowledge in all fields, especially quantum physics, and medical experience, manages to integrate and interconnect leptin data in the overall context of health and longevity.
In the structure of its “web” (The Quilt) formed by the main pillars necessary for the optimization of the human body, leptin occupies the 2nd place (!). You can access here a beginner’s guide to leptin rx, from which you can study in depth how much you feel like. In this article I will cover all the essential points anyway.
What is Leptin?
Leptin is a hormone produced mainly by fat cells, which coordinates the metabolism of energy in the body, through direct action, but also by coordinating the activity of other hormones.
To get along, it’s all about energy. Where there is no energy, there is no life.
Our brain monitors and coordinates the energy status of over 20 trillion cells. It is impossible for this monitoring to be done directly, exclusively through neural networks, from a space boundary. Thus, monitoring and coordination is performed indirectly, with the help of hormones.
Leptin plays exactly this role. It is the hormone that connects the brain and cells and provides information about energy, metabolism and the state of the neuro-endocrine system. Basically, it maintains energy homeostasis in the body.
Although it is known that leptin is produced by fat cells, it is important to know that we receive the first dose of leptin with the first ingestion of breast milk through colostrum. Through the information it brings to the brain, some “basic settings”, some parameters are made, some “instructions” regarding hunger and satiety are installed. Leptin has a very important role in methylation processes, a process on which genetic expression depends, and the absence of these basic settings in the first days of life can influence the appearance of epigenetic diseases.
Mecanism of action
Leptin, produced mainly in adipocytes, acts centrally – in the medial and lateral hypothalamus, or peripherally – in other tissues, through receptors. There it transmits information about the amount of energy stored as fat in the body. The information is analyzed, and from here the orders to the endocrine system and other nerve centers are given.
Leptin resistance occurs when the brain (or peripheral tissues) no longer receive the information brought by leptin.
The more adipose tissue (fat) there is, the more leptin is produced. The problem is not that we do not have enough satiety hormone, but that the body no longer responds to its signals.
The diagnosis of leptin resistance can be made clinically or by dosing the hormone “reverse T3” in the blood, but I will deepen this aspect a little later. Clinically, the symptoms that may occur are: obesity, increased appetite, craving for carbohydrates, chronic fatigue.
Organs/tissues affected by Leptin RX
The most affected organs and systems are those that need large amounts of energy to function optimally. Here we mention the nervous system, endocrine system, bone system, muscle system, reproductive system, immune system, and metabolic processes in general.
Let’s take them one at a time.
Leptin and The Brain
When there is a central type of leptin resistance, it means that the receptors for leptin in the brain, more precisely in the hypothalamus, do not respond to the signals of leptin secreted by fat cells. This means that there is enough energy stored in the form of fat, but the information does not reach the brain. The brain, not having this information, commands the other systems to continue storing energy in the form of fat. Basically, at the informational level, the brain is in a continuous hunger. It basically becomes “a fight with hunger”, but an illusory one. This happens in that “central obesity”, ie the problem is in the central nervous system (CNS). Studies show that, even in the case of exogenous administration of leptin, its effects diminish over time, a clear sign that it is a resistance, not the amount of leptin available..
Leptin and Other Hormones
Here the story is a little more complex.
Let’s start with insulin. Leptin resistance, through its mechanism, overloads the body’s task of producing insulin in the pancreas to store glucose as triglycerides in fat cells. An increased concentration of leptin causes a low secretion of amylin, also produced by beta-pancreatic cells, the same ones that secrete insulin, and, decreasing the activity of these cells, decreases the production of insulin. Thus, over time, through these mechanisms, insulin resistance occurs. This process takes place within 5-7 years. What is especially important to understand is that diabetes, which comes with associated diseases, can be prevented 5-7 years before the onset of insulin resistance (!!!). This is an extremely wide range in which we can act, if we know when, what to look for and how to intervene. Classical medicine still focuses on late-onset insulin resistance.
There is a special term, “autoimmune diabetes”, or diabetes 1.5, which occurs in the context in which there is already a context of intestinal or autoimmune diseases. They precipitate the onset of insulin resistance, ie diabetes, the difference between it and type II diabetes being only the time in which it sets in.
Then, leptin resistance, along with insulin resistance, determines adrenal resistance. The body becomes, due to hunger, to be in a permanent state of alert. It is known that, in the alert state, cortisol, the stress hormone, is secreted in the adrenal glands. After a long time, the adrenals reach exhaustion. From now on, if we do not intervene optimally, we can say that we have the perfect ingredients for chronic diseases and cancers. I invite you to read this article on adrenal exhaustion (RO). But let’s not forget where we started: from leptin!
Regarding the reproductive system, I want to mention the importance of leptin resistance in women. Sustaining a pregnancy is a process that requires massive amounts of energy. Automatically, if the energy management of the body is defective, including the reproductive organs, the pregnancy will not be sustained! There are also common conditions such as polycystic ovary syndrome (PCOS), a topic that you will find described in more detail in my article – Ketogenic Nutrition and the Endocrine System (link).
We mentioned in the laboratory diagnosis the dosage of reverse T3. It is a competitive inhibitor for thyroid hormones T3 and T4. This means that reverse T3 is in competition with thyroid hormones for the same receptors. Reverse T3 has been found to increase leptin resistance, so it blocks thyroid hormone receptors, and they have no effect. So, even if the classic thyroid profile is within its normal limits, it does not mean that everything is fine from a functional point of view. We may thus have symptoms of hypothyroidism, with decreased basal metabolism. That is, the body no longer burns fuel to support basic functions. The cause? Leptin resistance.
Leptin and The Liver
Although I presented the thyroid in the previous chapter, I want to make sure to clarify its position in this puzzle. Dr. Kruse makes an analogy: if we were talking about a car, the liver would be the engine, the thyroid would be the acceleration pedal, and leptin is the chip that makes the connection between the two.
The liver is the body’s main metabolic organ. Of the calories from food, 60% are used by the liver to support basal metabolism, ie the basic functions of the body, those functions that occur when our body is at rest, when we sleep, when we meditate. Glucagon is the hormone complementary to leptin, which releases the energy substrate from the cells for use.
The remaining 40 percent reach the tissues, much of it at the muscle level, where, if the muscle is sensitive to leptin, the energy is used properly. However, if the muscle is resistant to leptin, the energy is stored: either in the adipose tissue or back in the liver. Without going into too much detail, which you can find in Dr. Kruse’s article, I also say that when leptin resistance occurs in the liver, it no longer metabolizes carbohydrates, fats and proteins properly, thus synthesizing cholesterol molecules from carbohydrates. which can be stored in blood vessels (ie “bad cholesterol”), with low density: SdLDL, and from IDL / VLDL proteins and lipids, which, at the indication of estrogen and testosterone, reach different areas of body fat.
As a result of the leptin resistance of the liver, an insulin resistance also occurs, when the liver decides that the excess energy must be stored here as well. The fat is stored in the liver and non-alcoholic hepatic steatosis (“fatty liver”) occurs. Moreover, the hepatic cell membrane continues to suffer because DHA is no longer assimilable in the cell. There is a correlation between liver size and waist size, abdominal obesity being part of the metabolic syndrome.
Leptin and Locomotor System
Most people ignore the importance of the bone system and see the bones as static tissue. In fact, bone is one of the most active tissues. As long as we move, the bone is in a permanent remodeling, depending on the pressures and forces of traction and torsion to which it is subjected. The bone is formed to correspond to the activities of each. Leptin resistance at this level leads to osteoporosis. No wonder obesity is generally associated with osteoporosis. Leptin … Leptin, leptin, leptin.
As for the muscles, here’s a part I particularly like. At the muscular level we have some proteins: UCP3 (uncoupling proteins). These proteins allow leptin to act inside the muscle cell. They are an alternative way for the body to manage excess calories, excess energy substrate: instead of storing fuel in the form of glycogen or fat, the muscle cell converts it directly into heat, without creating ATP molecules. as an intermediate process. This is an extraordinary, very clean process, in which far fewer reactive oxygen species (ROS) are produced at the mitochondrial level. This is perhaps the most valuable secret in the whole article:
Calories do not count IF leptin sensitivity is unaffected.
Some opinions claim that mathematics is mathematics, that it is normal not to lose weight if you eat like a pig. It’s true … partially: if there is resistance to leptin.
In ketonutrition, some approaches claim that it doesn’t matter how much you eat, as long as you stay in ketosis. That’s true too, but … still partially: if you’re not resistant to leptin.
In a functional organism, this should be the first way to burn fat in the periphery: at the muscular level. Athletes who have normally trained muscles notice this effect. It is very difficult for them to gain weight.
Well, this mechanism does not work in obese people. Because these proteins do not work, muscle resistance to leptin occurs, and muscles, like the brain, are continually starved and, consequently, tired. Muscle hunger is transmitted in the intestine, from where the information is transmitted to higher centers, which continue to order the energy from food to be stored. It thus remains in a vicious circle, seemingly hopeless, in which, no matter how much we eat and whatever we do, demand exceeds supply indefinitely, even if there are resources. Kind of: we die of thirst with the water next to us. Because the translation of matter into information no longer works.
I would also like to mention that, in the absence of an energy source, the muscles, in their craving, use ALE (protein residues from fatty acid oxidation) and AGE (residues obtained from carbohydrate metabolism). This fact results in an imbalance in the ratio of omega-type fats, with resonance in bone and metabolic disorders, respectively the increase of the level of proinflammatory cytokines, with implication in degenerative diseases.
Leptin and Immune System
Leptin is also important in modulating the immune system. Elevated leptin levels are associated with increased leukocyte counts. It also increases the level of cytokines produced in visceral fat and has been found to decrease the concentration of vitamin D, which has a special role in terms of immunity. This is a subject as broad a topic as this one about leptin, which I will address on another occasion.
Although ketonutrition has a great contribution in restoring sensitivity to leptin and, therefore, the reoptimization of metabolic processes, it is not enough. Or, to put it another way, its benefits are much easier to obtain if we consider other factors.
Let’s see what this is about.
You can follow the protocol proposed by Dr. Kruse, which includes, in general, 3 steps:
- Epi-paleo Rx nutritional protocol
Personally, no matter how much appreciation and gratitude I have for his contribution, I can’t help but consider other aspects. I mean that this protocol involves and even supports the consumption of animal proteins (meat, fish, eggs). No matter how organic it is, let’s remember that any food comes bundled with information, coded, guess where, exactly in protein. Basically, we consume protein and use amino acids as a substrate, but the story does not end here. Proteins encode information. You can watch this interview or this show with Dr. Bruce Lipton – Biology of belief, in which it is highlighted that the classic perspective on cell biology changes radically, and the expression of our DNA is actually influenced by the environment we live in, ie by information which reaches the cellular level, the information brought by the proteins in the diet. Epigenetics. This vision is not difficult to understand, but difficult to accept.
Animal proteins provide information about how the animal lived, what it ate, how it felt, how it was sacrificed, etc., and usually have a lower frequency. It is useful to eat from time to time (for grounding), but this is quite rare from time to time, if we want to keep our vibration at a high level. Although Dr. Kruse generally recommends a paleo-like diet, specifically epi-paleo (from epigenetics), even if we go on the concept of paleo, ie a model of nutrition close to that used by our ancestors, even for them, meat was a luxury, and domestic animals did not exist … so zero dairy, and eggs from the nests in the trees. However, we need protein – says the theory. I reformulate what others have said and say: we do not need proteins, but amino acids! In the article Vegan Keto (Gabriel Peșa) you have information about what and how.
What is perhaps unique to this diet is the way some foods are chosen and eliminated, the selection criteria being factors such as season, freshness of fruit, geographic area, and personal purpose, all of which resonate with that Quilt of his.
- What and how you eat
What I have to mention here is the fact that I do not support, for other reasons, eating in the morning. What I recommend is, indeed, the gradual reduction of the eating interval, with a start from the classic post intermitent (Gabriel Peşa) of 16: 8 until it reaches 23: 1 (yes, with a lot of discipline, it is possible, but in time).
- Signs of reduced leptin resistance appear (in 4-6 weeks):
Craving decreases, mood is better, energy levels improve, sweating pattern changes, sleep is more restful. Only now is it recommended to introduce sports, in the form of HIIT or weightlifting (In this direction I also recommend the book Keto bodybuilding by Siim Land, which explains the role of muscle mass in metabolic processes and longevity), which are more effective in increasing / optimizing muscles compared to other sports with aerobic mechanism, which can be introduced later. Increasing muscle mass maintains the process of increasing leptin sensitivity.
It is important that this whole process is done gradually, otherwise, only short-term weight loss occurs, but in the long run, the effects in terms of aging and longevity are to our disadvantage.
Okay, that was the Kruse protocol, but let’s see what ketongenic nutrition or, more specifically, a ketogenic DIET has to say about this!
Scientific data and measurements obtained from clinical trials in patients with metabolic syndrome, diabetes or obesity are in favor of ketogenic diets. Some of the effects have been achieved with low-carb diets, but keto seems to have an advantage in terms of efficiency. Below we have described some results for each. I repeat, however, that behind the measurements, the main mechanism is leptin resistance.
Within the metabolic syndrome, it was observed, in general, the increase of glycemic values, insulin secretion and decrease of fatty acid metabolism, increase of atherogenesis and the appearance of cardiovascular diseases. A long-term ketogenic diet brings about an increase in blood ketones, results in weight loss, normalization of blood pressure and normalization of the lipid profile, which turns into a non-atherogenic profile, ie the proportion of fat in the blood is brought to normal, so atheroma plaques are more difficult to form. Basically, this is what is being tried to prevent in the metabolic syndrome: heart attacks and strokes.
In the case of diabetes, after the establishment of even a low-carb diet, both decreases in blood glucose and body weight were observed, and in the case of a ketogenic diet it was found a decrease in doses or even elimination of drug treatment. Also, there were improvements in inflammatory parameters, brain activity, blood sugar control with a decrease in acute episodes of hyper or hypoglycemia, hunger. Insulin-secreting beta-pancreatic cells do not appear to improve their function with this regimen alone, and in patients with insulin-dependent type 1 diabetes, long-term sustained ketogenic nutrition may increase the risk of hypoglycaemia. .
This subchapter is special, and those who have had the patience to get here will read some information that can not be found on mainstream keto-friendly blogs.
As an overview, after dissecting the mechanisms of leptin, we can say that “leptin receptors are a solid biochemical isolator in a world dominated by light” (Dr. Kruse). This description seems fantastic to me and has the power to remind us that we are, in fact, luminous beings, who forgot this as they sank deeper and deeper into the material world. It is fascinating to see that leptin and its receptors are the connecting points between these two intertwining worlds.
Also from Dr. Kruse:
It’s not what the sun lights that is important,
it’s what it doesn’t illuminate that is.”
Leptin is the one that transmits light signals to the lateral hypothalamus. Pam Pam.
Ha ha. So let’s reset this leptin sensitivity and …
May you let Ra be with you!
 www.gabrielpesa.com – Nutritionist, Biohacker, Antiaging Expert – the best I know of.
 Myers, Martin G Jr et al. “Obesity and leptin resistance: distinguishing cause from effect.” Trends in endocrinology and metabolism: TEM vol. 21,11 (2010): 643-51.
 Vitamin D: The Sunshine of Your Life?
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