Sometimes it’s called ME (myalgic encephalomyelitis) or CFS (chronic fatigue syndrome). Hitting the wall, as it’s sometimes called, is often attributed to excessive workload and can certainly be caused by this. But you can reverse the argument and say that the energy production in your cells has decreased so much that you can’t perform what you previously managed without any signs of fatigue.

This doesn’t concern all cells in the body but the cells in the brain (central nervous system) that control our organs throughout the body. These parts of the body await signals from the brain to function. When the brain cells lack oxygen, the amount of energy (ATP) produced in the central nervous system cells (mitochondria) decreases, and you become mentally fatigued and ”can’t think,” which is sometimes referred to as brain fog. Therefore, brain cells cannot send out all the signals needed for your body to function fully throughout an entire workday and more.

Why a Lack of Oxygen?
Cells receive their oxygen through tissue diffusion from nearby capillaries. For cells to receive an optimal amount of oxygen, there must be a sufficient number of red blood cells in the nearby capillaries. Capillaries, consisting of a single layer of endothelial cells, receive red blood cells from the outermost and thinnest arteries called terminal arterioles. Unlike capillaries, terminal arterioles, like all arteries, have a layer of smooth muscle (tunica media) that loses its elasticity and firmness when it lacks nitric oxide (NO). For this discovery and the fact that endothelial cells provide nitric oxide (NO) to the tunica media layer, Furchgott, Ignarro, and Murad were awarded the Nobel Prize in Medicine and Physiology in 1998.

What causes the decrease or loss of nitric oxide (NO) delivery is damage to the inside of the arteries, specifically, the glycocalyx of the arteries (the outer part of endothelial cells). This happens because the molecules normally found in the glycocalyx are imbalanced due to excess sugar in the blood. In addition to reducing the delivery of nitric oxide (NO) to the smooth muscle layer (tunica media), the glycocalyx loses its negative charge. This means that the negatively charged blood cells are no longer repelled by the glycocalyx but instead start approaching the endothelial cell membranes and the openings between the endothelial cells, which is not good. When this enters behind the endothelial cells, the formation of plaque can start.

What Damages the Glycocalyx?
The fact that bacteria in the bloodstream can lead to organ failure and death has been known for a long time. In recent years, it has also been discussed that viruses can damage the inside of arteries, specifically, the glycocalyx of endothelial cells, causing viruses to stick to receptors on the endothelial cell membranes. But there’s even more written about how too much sugar in the blood (hyperglycemia) can harm the glycocalyx. This is not unreasonable, considering that our diet nowadays, especially after 1976, is dominated by carbohydrates, i.e., sugar, flour, and starch in both food and drink. Since then, we have been recommended to consume as much as 60% carbohydrates – read sugar, flour, and starch, which turn into sugar as they pass through the digestive tract, are broken down into glucose and fructose for further transport into the bloodstream, where they eventually end up after the blood has been oxygenated by the lungs. Fructose goes straight to the liver, while glucose proceeds towards the cells (where fatty acids and amino acids also follow) for energy production.

The Terminal Arterioles
They have an inner diameter of 2-10 µm. A red blood cell has a diameter of about 7-8 µm. Even though it is malleable, it has a hard time passing through a stiffened terminal arteriole with an inner diameter of 2-5 µm. Consequently, the subsequent capillary receives fewer red blood cells, reducing oxygen delivery to the cells.

Cell energy production depends on the amount of oxygen delivered by capillaries. When oxygen deliveries decrease, the cells’ ATP production decreases as well. ATP is produced from oxygen, glucose, fats, and proteins, more specifically from oxygen, glucose, fatty acids, and amino acids. If this occurs in the parts of the brain (central nervous system) responsible for controlling the body, signaling to the body’s various functions, such as thinking, pumping the heart, moving skeletal muscles, and other movements, will deteriorate.

We react somewhat differently to fatigue. Let me describe two extremes – either we rest or we exert ourselves even more. Someone who, when fatigue sets in, lies down and rests will notice that the fatigue diminishes. The ambitious person who, instead of resting, exerts extra effort to complete their workday despite fatigue will soon realize that it becomes increasingly difficult, slower, and that a headache starts to develop. You might wonder why this happens. When cell energy production is insufficient, cells start fermenting glucose. Only glucose can ferment – not fatty acids and amino acids. Unfortunately, this fermentation process can’t compensate for the loss of energy production with oxygen – far from it. Fatigue turns into something that can be called exhaustion.

To this exhaustion, add pain that can be explained as follows: When glucose is fermented to produce energy ATP, a waste product called lactic acid is formed. This is acidic, and when it enters the cell’s alkaline environment, nerves react, and you feel it as pain. The more you exert yourself, the more it hurts.

There are only two ways to get rid of the pain – either rest or restore the oxygen delivery from the arteries to the full extent. When fermentation stops, lactic acid immediately loses an H and becomes lactate, which is alkaline. Presto, and the pain disappears.

Can a Sick Glycocalyx Become Healthy?
Yes, indeed – and it can happen quickly! In principle, it may be enough to refrain from sugar, flour, and starch from 1800 until 1000 the next day. But if you continue to eat and drink carbohydrates from 1000 to 1800, it becomes very difficult to abstain from sugar, flour, and starch from 1800 to 1000 the next day because carbohydrates trigger hunger hormones, which set off signals that make you want more. It’s the notorious craving that drives you to eat or drink something even during the time you should be fasting, from 1800 to 1000 the next day. Therefore, it’s best to change your diet so that your carbohydrate intake from both food and drink is less than 33%. Then, it won’t be the least bit difficult to abstain from eating or drinking from 1800 to 1000 the next day. Water, black coffee without sugar, and tea without sugar are entirely fine as ”snacks.”

Brain fatigue can be caused by oxygen deficiency in central nervous system cells. Oxygen deficiency arises because the glycocalyx is damaged due to prolonged hyperglycemia long before you receive a diabetes diagnosis – so much so that the decreasing nitric oxide deliveries from the endothelial cells of the arteries to the tunica media cause the tunica media to stiffen. In the thinnest arteries, known as terminal arterioles, with diameters of 2-10 µm, this means that red blood cells of 7-8 µm have difficulty passing through. Consequently, the subsequent capillaries receive fewer red blood cells, and this results in less oxygen being available for diffusion through the tissues to the individual cells.

One of the potential causes of brain fatigue is thus explained, and assistance for improvement has been described.

Lasse Blomdahl, Glycocalyx and Brain Fatigue


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