A weakened immune system has long been thought to be caused by aging and poor lifestyle choices, but according to an October 2023 study.1 Nature Communications says the main reason for this weakened immune system is malfunctioning mitochondria, the powerhouses of cells, especially those found in T cells (a type of immune cell).
When mitochondria do not function properly, T cells lose the energy they need to perform their functions, leading to decreased immune system function. As a result, both acute infections and chronic diseases cannot be prevented. As reported by Medical Xpress:2
„…in the immune system, defenses against chronic infections and tumors often lead to a phenomenon called T-cell depletion. During this process, T lymphocytes gradually lose their function and the response to cancers and infections is impaired. It will…
This study found that the fatigue process is significantly influenced by mitochondria. Failure of mitochondrial respiration triggers a cascade of reactions that culminates in genetic and metabolic reprogramming of T cells, a process that causes functional fatigue. ”
The good news, confirmed in a high-profile study, is that this decline can be reversed with treatments that target mitochondrial function.
Decreased mitochondrial function can cause T cell depletion
Simply put, when the body fights an infection, immune cells called CD8+ T cells transform into cytotoxic T lymphocytes (CTLs) and destroy infected cells. This change requires changes in gene expression, cell structure, and energy use.
However, in long-term infections or cancers, T cells can become exhausted or „used up“ and lose their effectiveness. This fatigue is related to energy problems within the cells, especially within the mitochondria. Researchers are now studying how solving these energy issues could rejuvenate her exhausted T cells, thereby improving cancer treatment. Bioenergetics researcher Georgi Dinkov commented on these findings:3
„Until now, age-related decline in immune function has been explained by the concept of simple 'wasting', but when immunodeficiency occurs in young people, the cause is genetic vulnerability, alcohol It is thought to be either a lifestyle choice, such as taking drugs.
In other words, to this day, medicine does not seem to fully understand why immune function declines with age and disease, and what, if anything, can be done to prevent it.
This study shows that the direct cause of decreased immunity is fairly simple: decreased mitochondrial function (OXPHOS). When the mitochondria of T cells (immune cells produced by the thymus gland) become dysfunctional, they must rely solely on glycolysis for energy production.
Energy production from glycolysis is insufficient to support proper T cell differentiation and activity, and in fact, large amounts of reactive oxygen species (ROS) are generated when glycolysis is the predominant energy mode. This can lead to T cell damage and death. production.
This study also shows that such mitochondrial dysfunction is a necessary and sufficient condition for immunocompromise (also known as T-cell „exhaustion“) to occur, and that immunocompromise is reversible when mitochondrial function is restored pharmacologically. It has also been proven that. ”
Glucose Metabolism 101
So what is „energy production through glycolysis“ and why is it so harmful? All dietary carbohydrates are digested and broken down into glucose, a type of sugar. Glucose can then be metabolized (burned) as fuel using two different pathways, as shown below.
![Glucose Metabolism 101](https://media.mercola.com/ImageServer/public/2024/March/glucose-metabolism-101.jpg)
![Glucose Metabolism 101](https://media.mercola.com/ImageServer/public/2024/March/glucose-metabolism-101.jpg)
First, glucose is metabolized to pyruvate. Pyruvate then enters the glycolytic pathway in the cell's cytoplasm to generate lactic acid or is converted to acetyl-CoA and transported to the mitochondrial electron transport chain.
Cancer cells are well known for utilizing the glycolytic pathway. This is the same pathway that glucose passes through when mitochondrial glucose metabolism is impaired. Essentially, this is the pathway used whenever the amount of ATP that can be produced within the mitochondria reaches its limit (it is the most efficient and least damaging way to produce energy).
Downstream dangers of glycolysis
The glycolytic pathway is great when you need immediate fuel, but when this is the primary way glucose is burned, stress hormones are constantly activated, creating a state that promotes insulin resistance and diabetes. As a result, large amounts of lactic acid are produced as a waste product. Produces healthy carbon dioxide (CO) alternative products.2) and metabolic water.
Lactic acid increases reductive stress, causing a backflow of electrons within the mitochondria and increasing ROS to 3%-4%. This is 30 to 40 times more than when glucose is burned in the mitochondria. This increased ROS production is responsible for causing T cell damage and death.
Furthermore, glycolysis produces only two ATPs per glucose molecule. This is 95% less energy than would be produced if glucose was metabolized within the mitochondria.
the devil is in the details
Now, you've probably heard that sugar promotes cancer because cancer cells preferentially use glycolysis. However, it is a mistake to think that all glucose uses the glycolytic pathway. As shown above, glucose is also burned in the mitochondrial electron transport chain, which is the most efficient way to generate energy.
Therefore, when it comes to the „sugar promotes cancer“ issue, it is important to distinguish between sources of carbohydrates. Although it is technically accurate to call all carbohydrates sugars, there are fundamental differences in the sources of carbohydrates. For example, whole ripe fruits and starches, whole fruits and refined processed sugars (e.g. table sugar and high fructose corn syrup). .
Refined sugars and many starches are common sources of endotoxin production in the intestines, disrupting mitochondrial function and triggering cancer metabolism, while fructose found in whole foods typically contributes to endotoxin production. does not cause
This is one of the main differences between refined sugar and fructose from ripe fruit, and helps explain why refined sugar promotes cancer, while natural fructose does not. So, to be clear, sugar itself is not promoting cancer progression. The root cause is mitochondrial dysfunction, and fatty acid oxidation (fat is metabolized instead of glucose) is part of what causes that dysfunction.
I want to burn glucose in mitochondria.
For a long time, I believed that fat burns „cleaner“ than carbohydrates – one of the „selling points“ of the keto diet – but I've since realized that it was the opposite. When glucose is burned in the mitochondria, it burns much more cleanly than fat.
Therefore, it is important to get the macronutrient ratios correct. This is because ingested glucose constantly shuttling back and forth to the glycolytic system can promote cancer. At the same time, the ingested fat remains in fat stores rather than being used as fuel.
Ultimately, your mitochondria need to burn glucose, and to ensure this happens, you need to keep your dietary fat intake to less than 35% of your total calories. The reason is that when fat intake is too high, glucose is sent to the glycolytic system. For a detailed explanation of this metabolic switch, please see .Understanding the Randall Cycle”
If you have insulin resistance, meaning your metabolism is inflexible, that threshold can be closer to 20% or 10%. Therefore, if you have insulin resistance, you should significantly reduce your fat intake until your insulin resistance is resolved. You can then increase it to 30%.
Dysfunctional T cells and cancer cells utilize glycolysis
The reason cancer cells use the glycolytic pathway is because their mitochondria are severely dysfunctional. Mitochondria are so damaged that they cannot burn glucose. As a result, cancer cells must rely on a backup system, glycolysis, to survive. This is the true nature of the Warburg effect.
Similarly, malfunctioning mitochondria within T cells forces them to rely on glycolysis for energy production, which leads to a weakened and dysfunctional immune system.
As mentioned in the featured study, T cell depletion is a hallmark of cancer, which is not surprising given that it is all related to mitochondrial dysfunction. Cancer occurs when the mitochondria in cells are severely damaged, and as the disease progresses, the mitochondria in T cells similarly stop functioning.
Because mitochondrial dysfunction is at the heart of it all, the most effective strategy is to use metabolic therapies that address why cells are unable to oxidize (burn) sugars within the mitochondria. Once the mitochondria are repaired so that they can produce enough energy again, they no longer need to rely on glycolysis, and the cancer usually regresses and immune function is restored.
What causes mitochondrial dysfunction?
There are four main causes of mitochondrial dysfunction:
- Excessive intake of linoleic acid (LA)
- Estrogen dominance
- Exposure to electromagnetic fields (EMF)
- Endotoxin — Refined sugars and many starches are more likely to cause dysbiosis in your gut that can lead to endotoxin production. This endotoxin is one of the factors that disrupts mitochondrial function and causes the Warburg effect (cancer metabolism), where glucose is burned through glycolysis.
Although these all play major roles, I believe that excess LA and estrogen dominance are the main causes of mitochondrial dysfunction. This is primarily because LA and estrogen negatively affect the body in similar ways. They both:
- It increases free radicals that cause oxidative stress and damage the mitochondria's ability to produce energy.
- Increasing intracellular calcium uptake increases nitric oxide and superoxide, increases peroxynitrite, and also increases oxidative stress.
- It causes an increase in intracellular water, causing the body to retain water.
- Reduces metabolic rate and suppresses thyroid gland.
Almost everyone in the developing world has 10 times more LA in their tissues than their ancestors did 100 years ago. This polyunsaturated fat (PUFA) is highly sensitive to oxidative damage and generates free radicals in the body, such as reactive aldehydes, which destroy mitochondria.
These toxic metabolites of LA cause a tremendous amount of reductive stress as a result of electron accumulation within the ETC and impeding the advancement of electrons to complexes IV and V to generate ATP. Additionally, because LA is embedded in the inner mitochondrial membrane, damage can result in the leakage of protons that would normally accumulate in the mitochondrial lumen.
This proton gradient is responsible for driving the nanomotor of complex V to generate ATP. Both processes combine to shut down and ultimately prematurely destroy mitochondria. Eating starch can also feed bacteria in your intestines that produce endotoxin, which is a powerful mitochondrial poison.
solution
Finally, if you want to improve or restore mitochondrial function, here are some important solutions:
- Reduce LA intake Reduce your intake as much as possible by avoiding processed foods, seed oils, chicken, pork, seeds, and nuts.
- Make sure to consume healthy carbohydrates such as ripe fruits, raw honey, and maple syrup.
- Reducing lactic acid production and increasing carbon dioxide have opposing effects.Four For more information, see .biology of carbon dioxide”
- Reduce stress, as chronic stress promotes the release of cortisol, a powerful inhibitor of mitochondrial function and biogenesis. Progesterone is very helpful here as it is a powerful cortisol blocker. For more information, see .What you need to know about estrogen and serotonin”
- take supplements niacinamideThis is because without mitochondria, energy cannot be created. We recommend taking 50mg of niacinamide three times a day.