Tuesday, October 15, 2013

MITOCHONDRIA METABOLISM AND THE ZERO CARB DIET


I just finish reading an article published 3 days ago in “Nutrition & Metabolism” by Joseph McInnes, a German scientist. It was difficult to read by moments but some parts were very exciting for me and since I think they could also be of interest for anyone on a Zero Carb diet, I decided to bring you here a resume of the highlights. 

In the last ten years, research has revolutionized the way in which we view mitochondria. They are no longer viewed solely as cellular powerhouses; rather, mitochondria are now understood to be astonishing structures, constantly undergoing fusion and fission, and engaging in intimate interactions with other cellular structures.

Studies have implicated mitochondria in a wide variety of cellular processes, such as lipid flux, and intracellular signaling. It does not come as a surprise that an increasing number of human pathologies have been associated with functional defects in mitochondria.
The difficulty in understanding and treating human pathologies caused by mitochondrial dysfunction arises from the complex relationships between mitochondria and other cellular processes, as well as the genetic background of such diseases.
What is interesting to us, Zero-Carbers, is how all this new knowledge available nowadays help us to understand why our diet is so efficient in helping to regain health losses associated with metabolic diseases which are, as you will see, “mitochondrial-associated”.
Mitochondria are defined as energy-generating organelle of the cell, responsible for the final steps of metabolizing organic substances to produce energy (ATP). I will voluntarily omit all the scientific explanation of how the said ATP molecules are produced and concentrate on the consequences of dietary sources of energy on mitochondria functioning.
It is generally understood mitochondria produce ATP from the breakdown of sugar such as glucose. Sadly, and often omitted, is the second energy source for mitochondria: the degradation of fatty acids, which, as you know, originate from our diet or from our reserve in the adipocytes.
Fatty acids IS THE MAJOR ENERGY SOURCE in humans and this process relies on beta-oxidation in the mitochondria. Let's never forget glucose levels in our blood at any moment are very limited and our glycogen reserves are not much better for special needs.
Many defect of “burning glucose” in our mitochondria cause diseases that are, even if rare, quite serious. They have names like “mitochondrial myopathy” or “glutaric acidemia type 2” or “respiratory complex deficiency”. At the end, they have all the same origin: a genetic defect of glucose mitochondrial metabolism.
And as our cells cannot synthesize mitochondria, they have to multiply by division from old ones, a process named “fission”. They also go into a process of “fusion” when 2 mitochondria “fuse” together. This way, through the life cycle of a cell, “fusion and fission” allows the body to adjust to create to the adequate balance of the energy producing structures.
Throughout its lifetime, mitochondria can accumulate damage and debris, characterized by excessive amounts of reactive oxygen species (ROS) especially from burning sugar. One way mitochondria can dispose of such molecular debris is by segregating that part of the mitochondrion by fission, followed by the “digestion” process of “mitophagy”.
Interestingly, this process of “mitophagy” is believe to be a vital mechanism have been linked to human pathologies associated with metabolism such as ageing, cancer, neurodegenerative disease, and tissue injury and repair.
So you can understand how maintaining our mitochondria in good shape is essential for metabolic function but this process may vary among tissues because there metabolism in the liver, for example, is quite different from the one in the hearth.
So how can we maintain our mitochondria happy? With diet and nutrition. But not any diet and nutrition…
Food items have the ability to influence mitochondrial function, and in turn the effects of mitochondrial-associated diseases. As discussed, energy sources provided by diet include carbohydrates and fats. Carbohydrates are broken down by the glycolysis. Fats, on the other hand, are broken down by β-oxidation. Additionally, in the liver and kidneys, ketone bodies can be produced as a byproduct of fatty acid β-oxidation. Ketone bodies are high-energy compounds, which are transported via the blood to other tissues. Thus, they have the ability to serve as an alternative energy source for tissues in situations of impaired glucose oxidation.
Though clinical data investigating how diet influences mitochondrial function is currently quite limited, one well-studied diet associated with influencing mitochondrial function is the ketogenic diet.
As many defects in mitochondrial pathologies arise from defects in mitochondrial metabolism, especially mutations affecting proteins required for glucose oxidation, the use of ketones originating from fat oxidation have been quite useful. This process bypasses the glucose oxidation pathway and provides a glucose-independent energy source. For example, the use of ketone diet for treating epilepsy is quite effective, as this disease is known to be a defect of mitochondria in the hippocampal neurons. Sadly, many doctors still talk about “idiopathic epilepsy” meaning they have no idea of the cause of the said epilepsy…
In a mouse model of a mitochondrial myopathy, it was shown that a ketogenic diet positively affects mitochondrial function and partially relieves some effects of mitochondrial myopathies. More recently, some laboratory studies have focused on how diet composition in terms of protein, fat and carbohydrate amounts influence mitochondrial function. For example, in a Drosophila model, a high carbohydrate to protein ratio triggered the appearance of mitochondrial defects.
Therefore, by developing a diet regiment, which increases metabolic function in cases of defects in mitochondrial function, one single diet plan may have the ability to treat a wide range of mitochondrial pathologies and the ketone diet is the best example. I hope I do not have to explain to you all a ketone diet is a HIGH FAT diet…
Mitochondrial myopathies are difficult to detect, as clinical symptoms of mitochondrial disorders often present with many other effects, such as liver failure, stroke-like symptoms, diabetes or other symptoms. Some therapies to treat mitochondrial myopathies have been clinically investigated, and one treatment possibilities, such as switching to a ketogenic diet to suppress the effects of myopathies, is currently being investigated.
Type 2 diabetes arises from a complex set of factors including genetic predisposition and lifestyle and, interestingly, mitochondrial dysfunction has recently been identified within various aspects in the pathogenesis of this disease. When target cells no longer respond to insulin signals to take up glucose from the blood, it results in high blood glucose and energy-deprived tissues. Do I need to add how a ketogenic diet comes in quite useful here???
Therefore, ongoing research into therapies for other mitochondrial-associated diseases is also likely to have implications for treating certain aspects of type 2 diabetes, and vice versa.
Mitochondrial activity is also affected in cancer patients. Tumor progression is associated with increased mitochondrial respiration (due to rapidly growing cells) and therefore increased ROS production from burning glucose. With increased ROS production comes an increased risk of mutations. Again here, many research are under way using a ketogenic diet as a treatment option, especially for brain cancer.
What I found interesting here is this mitochondria dysfunction goes further in explaining the pathology of so many diseases, many of them part of the Metabolic Syndrome. It is certainly a step further then simply stating diabetes comes from insulin resistance. And when you go down and observe what is happening in the said mitochondria, there is not much more going on other then burning sugar or fat.
And it seems burning sugar in there brings up many problems while burning fat brings back everything to normal…
Denis


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