MCT for Health

For quite some time, one idea has been recurring throughout my posts: slowing down certain specific processes could be the solution to metabolic problems and could increase the overall metabolic rate.  This idea is supported by a number of clues.  If the main problem is an excess of the aldehyde HNE , produced after linoleic acid is released from cardiolipin by the enzyme iPLA2γ in response to oxidative stress, then the solution is to reduce oxidative stress, simply by limiting the processes that generate it. Fat burning under unfavorable conditions could be one such process.  There is absolutely nothing wrong with using stored fat to obtain energy, but under certain conditions the system becomes overloaded, generating oxidative stress. This can happen, for example, due to an overall lack of oxygen, insufficient reduced glutathione (GSH), insufficient NADPH molecules to recycle oxidized glutathione (GSSG), inadequate function of the ALDH2 enzyme , which removes the aldehy...

Recently, Georgi Dinkov commented on an interesting study on his blog, which shows that uncontrolled fat burning could damage mitochondria. Let's take a closer look at this study, considering all the facts known so far. Should we be afraid of fats or not? We must first show the position of the study authors. Quote "Unrestrained fatty acid oxidation triggers heart failure in mice via cardiolipin loss and mitochondrial dysfunction" "Collectively, these results indicate that although FAO is essential for cardiac energy production, therapeutic strategies aimed at stimulating cardiac FAO may be detrimental rather than beneficial in heart failure." Unquote So, can promoting fat burning really be harmful? Well, we already know that promoting fat burning without overeating extends the life of mice . Cells need fat burning to improve resilience . So the scientists' statement about the dangers of promoting fat burning is contradictory to these findings,  so something...

In the previous post, I showed how the omega-6 linoleic acid peroxidation product 4-hydroxy-2-nonenal (HNE) suppresses signaling of cellular energy deficiency, i.e., a shortage of ATP molecules . This forces the cell to switch into an energy-conserving metabolic mode, activate glucose fermentation or cellular senescence, or ultimately undergo apoptosis—programmed cell death. Today, we will look at another older study  (from 2014) in which researchers investigated whether fatty liver disease could be alleviated by suppressing the function of the AR enzyme, i.e., by inhibiting aldose reductase. If you have not yet heard of aldose reductase (AR, also known as aldo-keto reductase AKR1B1), I have published a large number of posts on this blog presenting studies showing that AR activation is the basis of virtually all modern chronic diseases, whether it is obesity , liver damage , or vascular endothelial damage . Today, the main activators of AR are not only elevated blood glucose l...

One of the main sensors of energy sufficiency in the cell, that is, a sufficient supply of ATP molecules, is the enzyme AMPK. It is activated whenever the amount of AMP molecules increases. But does it really work "every time"? An adequate energy supply for all cellular functions is so fundamental that we should ask whether certain substances can suppress this signaling. The cell then suffers from an energy deficit and enters various energy-conserving states, for example pseudohypoxia or cellular senescence , which is characterized by fermentative metabolism to reduce the production of reactive oxygen species (ROS, such as hydrogen peroxide), but also by the shutdown of processes that repair damaged DNA ( which is a common occurrence caused, for example, by UV radiation or ionizing radiation ). So, do we know of any substances that block AMPK activity? Yes, we certainly do. One is the well-known autooxidation product of the omega-6 fatty acid linoleic acid, a molecule called...

If you think that vegetable (seed) oils protect your blood vessels, that is probably not true . This is suggested by studies examining their effects in older age or looking at lifespan. Vegetable oils may lower cholesterol, but low cholesterol levels are associated with shorter lifespan. But what would you say to the information that simply adding 1% of a special mixture of polyunsaturated oils—specifically processed linoleic acid—to the diet causes vascular plaque to disappear in an animal model within a few weeks! However, the processing of these vegetable oils was not carried out by any industrial food company. No—the processing was performed by bacteria in the cow’s stomach! The resulting product is called CLA, conjugated linoleic acid. There are several types, but the most interesting is rumenic acid, c9,t11-CLA. Another is t10,c12-CLA, but the first one is found in butter at ten to twenty times higher levels than the second. Could it be, then, that full-fat dairy products—especia...

In this post, I will try to summarize information from previous posts and studies and supplement it with the latest insights on the effect of enzymatic hydrogen sulfide (H2S) production on metabolism. What do we already know? Intestinal permeability A high-fat diet with sugar promotes a composition of gut bacteria that produces a large amount of hydrogen sulfide. There is so much of it that this hydrogen sulfide deprives intestinal epithelial cells of ATP energy, blocks mitochondrial complex IV, and causes leaky gut . A high concentration of H2S damages metabolism. Liver With a high-fat diet containing sugar, the liver is burdened by endotoxins (LPS) from a leaky gut. These activate aldose reductase (AR), increasing the formation of H2O2 (ROS) in the liver. According to the already known scheme, this switches on fatty acid synthesis (DNL) as well as triglyceride (TG) production and activates their export further into the body , either to be burned for heat, to produce chemical energy (...

It is strange. Mechanistically, it is clear that dietary linoleic acid is associated with increased oxidative stress and odd auto-oxidation products such as 4-HNE, which is a molecule that binds to enzymes in a way that prevents them from functioning properly . It even prevents its own removal, so its concentration increases, and it should be easy to arrange a simple experiment: give one group of people more linoleic acid in the diet than the control group receives, and the result should be a clear difference. But that is not how it works. Thus, for example, when Tucker Goodrich, a well-known blogger and proponent of the theory about the harmfulness of linoleic acid, is asked on the X network to support with a human study that linoleic acid causes inflammation, he presents a study with this conclusion : "Our meta-analysis suggested that increasing dietary LA intake does not have a significant effect on the blood concentrations of inflammatory markers. However, the extent of chang...