Re: Ketogenic Diet - Path To Transformation?
Here are some basics of mitochondrial energetics that are meant highlight the difference between fat burning metabolism vs carb burning metabolism. It is taken for the most part from the LWB thread and it can serve as a useful guide and complement to the videos or other references. It will also help people understand where are some of the names coming from in the papers.
There are many man-made myths surrounding energy production in the body and which foods supply energy. Mainstream science says that carbohydrates are what mitochondria use as fuel for energy production. This process is called oxidative metabolism because oxygen is consumed in the process. The energy produced by mitochondria is stored in a chemical “battery”, a unique molecule called adenosine triphosphate (ATP). Energy-packed ATP can then be transported throughout the cell, releasing energy on demand of specific enzymes. In addition to the fuel they produce, mitochondria also create a by-product related to oxygen called reactive oxygen species (ROS), commonly known as free radicals. But what we are not told is that mitochondria were specifically designed to use fat for energy, not carbohydrate.
There are several very complicated steps in making ATP within mitochondria, but a look at 5 major parts of ATP production will be all that you need to know in order to understand how energy is created within our mitochondria and why fats are the key to optimize their function. Don’t get too focused on specific names, just try to see the whole picture.
Step 1 – Transportation of Food-Based Fuel Source into the Mitochondria
Fuel must first get into the mitochondria where all the action happens. Fuel can come from carbs or it can come from fats. Fatty acids are the chemical name for fat, and the medium and large sized fatty acids get into the mitochondria completely intact with the help of L-carnitine. Think of L-carnitine as a subway train that transports fatty acids into the mitochondria. L-carnitine (from the Greek word carnis meaning meat or flesh) is chiefly found in animal products.
Fuel coming from carbs needs to get broken down first outside the mitochondria and the product of this breakdown (pyruvate) is the one who gets transported inside the mitochondria, or it can be used to produce energy in a very inefficient way outside the mitochondria through anaerobic metabolism which produces ATP when oxygen is not present.
Step 2 – Fuel is Converted into Acetyl-CoA
When pyruvate – the product of breaking down carbs – enters the mitochondria, it first must be converted into acetyl-CoA by an enzymatic reaction.
Fatty acids that are already inside the mitochondria are broken down directly into acetyl-CoA in what is called beta-oxidation.
Acetyl-CoA is the starting point of the next step in the production of ATP inside the mitochondria.
Step 3 – Oxidation of Acetyl-CoA and the Krebs Cycle
The Krebs cycle (AKA tricarboxylic acid cycle or citric acid cycle) is the one that oxidizes the acetyl-CoA, removing thus electrons from acetyl-CoA and producing carbon dioxide as a by-product in the presence of oxygen inside the mitochondria.
Step 4 – Electrons Are Transported Through the Respiratory Chain
The electrons obtained from acetyl-CoA – which ultimately came from carbs or fats – are shuttled through many molecules as part of the electron transport chain inside the mitochondria. Some molecules are proteins, others are cofactors molecules. One of these cofactors is an important substance found mainly in animal foods and it is called coenzyme Q-10. Without it, mitochondrial energy production would be minimal. This is the same coenzyme Q10 that statins drug block producing crippling effects on people’s health. Step 4 is also where water is produced when oxygen accepts the electrons.
Step 5 – Oxidative phosphorylation
As electrons travel down the electron transport chain, they cause electrical fluctuations (or chemical gradients) between the inner and outer membrane in the mitochondria. These chemical gradients are the driving forces that produce ATP in what is called oxidative phosphorylation. Then the ATP is transported outside the mitochondria for the cell to use as energy for any of its thousands of biochemical reactions.
So that's the basics. But why is fat better than carbs?
If there were no mitochondria, then fat metabolism for energy would be limited and not very efficient. But nature provided us during our evolution with mitochondria that specifically uses fat for energy. Fat is the fueled that animals use to travel great distances, hunt, work, and play since fat gives more packed-energy ATPs than carbs. Biochemically, it makes sense that if we are higher mammals who have mitochondria, then we need to eat fat.
Whereas carb metabolism yields 36 ATP molecules from a glucose molecule, a fat metabolism yields 48 ATP molecules from a fatty acid molecule inside the mitochondria. Fat supplies more energy for the same amount of food compared to carbs. But not only that, the burning of fat by the mitochondria – beta oxidation – produces ketone bodies. These ketone bodies - acetoacetate, β-hydroxybutyrate and acetone – are produced for the most part by the cells in the liver. When our bodies are running primarily on fats, large amounts of acetyl-CoA are produced which exceed the capacity of the Krebs, leading to the making of these three ketone bodies within liver mitochondria. Our levels of ketone bodies in our blood go up and the brain readily uses them for energetic purposes. Ketone bodies cross the blood brain barrier very easily as well. Their solubility also makes them readily transportable by the blood to other organs and tissues. When ketone bodies are used as energy, they release acetyl-CoA which then goes to the Krebs cycle again to produce energy.
The increased production of acetyl-CoA generated from the ketone bodies also drives the Krebs cycle to increase mitochondrial NADH (reduced nicotinamide adenine nucleotide) which our body uses in over 450 biochemical reactions that are vital, including the cell signaling and assisting of the ongoing DNA repair. Because the ketone body beta-hydroxybutyrate is more energy rich than pyruvate, it produces more ATP as well. Ketosis also enhances the production of important anti-oxidants that deal with toxic elements from our environments, including glutathione.
According to Douglas C. Wallace (Director of the Center for Mitochondrial and Epigenomic Medicine), the longevity benefits seen in caloric restriction research is due to the fact that our bodies shift to a fat burning metabolism within our mitochondria. That is, we don't necessarily need to restrict our caloric intake as long as we are on ketosis from a high fat, moderate protein diet (and restricted in carbs of course). Alternating now and again with intermittent fasting will help us maintain good levels of ketone bodies though.
A few concepts of the role of our mitochondria will also help put things into perspective.
Mitochondria regulate cellular suicide, AKA apoptosis, so that old and dysfunctional cells which need to die do so and then new ones can come into the scene. A cell can still commit suicide (apoptosis) even when it has no nucleus along with its nuclear DNA. But when mitochondria function becomes impaired and send signals that tell normal cells to die, things go wrong. For instance, the destruction of brain cells leads to every single neurodegenerative condition including Alzheimer’s disease, Parkinson’s disease and so forth.
The catalysts for this destruction is usually uncontrolled free radical production which cause oxidative damage to tissues, fat, proteins, DNA, causing them to rust. This damage, called oxidative stress, is at the basis of oxidized cholesterol, stiff arteries (rusty pipes) and brain damage. Oxidative stress is a key player in dementia as well as autism. We produce our own anti-oxidants to keep a check on free radical production, but these systems are easily overwhelmed by a toxic environment and a high carb diet.
Mitochondria also have interesting characteristics which differentiate them from all other structural parts of our cells. For instance, they have their own DNA (referred as mtDNA) which is separate from the widely known DNA in the nucleus (referred as n-DNA), and it comes for the most part from the mother line which is why mitochondria is also considered as your feminine life force. This mtDNA is arranged in a ring configuration and it lacks a protective protein surrounding which leaves its genetic code vulnerable to free radical damage. If you don’t eat enough animal fats, you can’t build a functional mitochondrial membrane which will keep it healthy and prevent it from dying. If you have any kind of inflammation from anywhere in your body, you damage your mitochondria. The loss of function or death of mitochondria is present in pretty much every disease. Dietary and environmental factors lead to oxidative stress and thus, mitochondrial injury as the final common pathway of diseases or illnesses. Autism, ADHD, Parkinson’s, depression, anxiety, bipolar disease, brain aging is linked with mitochondrial dysfunction from oxidative stress. Mitochondrial dysfunction contributes to congestive heart disease, type 2 diabetes, autoimmune disorders, aging, cancer, and other diseases.
Whereas the nDNA provides the information your cells need to code for proteins that control metabolism, repair, and structural integrity of your body, it is the mDNA which directs the production and utilization of your life energy.
Because of their energetic role, the cells of tissues and organs which require more energy to function are richer in mitochondrial numbers. Cells in our brains, muscles, heart, kidney and liver contain thousands of mitochondria, comprising up to 40% of the cell’s mass. According to Prof. Enzo Nisoli, a human adult possesses more than ten million billion mitochondria, making up a full 10% of the total body weight. Each cell contains hundreds of mitochondria and thousands of mtDNA.
Since mtDNA is less protected than nDNA because it has no “protein” coating (histones), it is exquisitely vulnerable to injury by destabilizing molecules such as neurotoxic pesticides, herbicides, excitotoxins, heavy metals and volatile chemicals among others, tipping the balance of free radical production to the extreme and leading to oxidative stress which damages our mitochondria and its DNA. This leads to overexcitation of cells and inflammation which is at the root of Parkinson’s disease and other diseases, but also mood problems and behavior problems.
Enough energy means a happy and healthy life. It also reflects in our brains with focused and sharp thinking. Lack of energy means mood problems, dementia, and slowed mental function among others. Mitochondria are intricately linked to the ability of the prefrontal cortex –our brain’s captain- to come fully online. Brain cells are loaded in mitochondria that produce the necessary energy to learn and memorize, and fire neurons harmoniously.
The sirtuin family of genes works by protecting and improving the health and function of your mitochondria. They are positively influenced by a diet that is non-glycating, i.e. a low carb diet, since a high carb diet induces mitochondrial dysfunction and formation of reactive oxygen species.
And well, then we come back in full circle to the information presented in this thread that shows how ketosis stabilizes overexcitation and oxidative stress, increases our natural valium (GABA), makes our hippocampus (important for learning, memory and emotions) super resilient to stress, with possibly double the quantity of mitochondria when in ketosis. It also causes epigenetic changes that increases the production of healthy and energetic mitochondria and it decreases the overproduction of damaging and inflammatory free radicals among may other things.
As Douglas C. Wallace says in the Mitochondrial Energetics paper, “the ketogenic diet may act at multiple levels: It may decrease excitatory neuronal activity, increase the expression of bioenergetic genes, increase mitochondrial biogenesis and oxidative energy production, and increase mitochondrial NADPH production, thus decreasing mitochondrial oxidative stress.”
Moreover, you might want to keep in mind this excerpt from Human Brain Evolution: The Influence of Freshwater and Marine Food Resources :
Ketosis made us human :)
Here are some basics of mitochondrial energetics that are meant highlight the difference between fat burning metabolism vs carb burning metabolism. It is taken for the most part from the LWB thread and it can serve as a useful guide and complement to the videos or other references. It will also help people understand where are some of the names coming from in the papers.
There are many man-made myths surrounding energy production in the body and which foods supply energy. Mainstream science says that carbohydrates are what mitochondria use as fuel for energy production. This process is called oxidative metabolism because oxygen is consumed in the process. The energy produced by mitochondria is stored in a chemical “battery”, a unique molecule called adenosine triphosphate (ATP). Energy-packed ATP can then be transported throughout the cell, releasing energy on demand of specific enzymes. In addition to the fuel they produce, mitochondria also create a by-product related to oxygen called reactive oxygen species (ROS), commonly known as free radicals. But what we are not told is that mitochondria were specifically designed to use fat for energy, not carbohydrate.
There are several very complicated steps in making ATP within mitochondria, but a look at 5 major parts of ATP production will be all that you need to know in order to understand how energy is created within our mitochondria and why fats are the key to optimize their function. Don’t get too focused on specific names, just try to see the whole picture.
Step 1 – Transportation of Food-Based Fuel Source into the Mitochondria
Fuel must first get into the mitochondria where all the action happens. Fuel can come from carbs or it can come from fats. Fatty acids are the chemical name for fat, and the medium and large sized fatty acids get into the mitochondria completely intact with the help of L-carnitine. Think of L-carnitine as a subway train that transports fatty acids into the mitochondria. L-carnitine (from the Greek word carnis meaning meat or flesh) is chiefly found in animal products.
Fuel coming from carbs needs to get broken down first outside the mitochondria and the product of this breakdown (pyruvate) is the one who gets transported inside the mitochondria, or it can be used to produce energy in a very inefficient way outside the mitochondria through anaerobic metabolism which produces ATP when oxygen is not present.
Step 2 – Fuel is Converted into Acetyl-CoA
When pyruvate – the product of breaking down carbs – enters the mitochondria, it first must be converted into acetyl-CoA by an enzymatic reaction.
Fatty acids that are already inside the mitochondria are broken down directly into acetyl-CoA in what is called beta-oxidation.
Acetyl-CoA is the starting point of the next step in the production of ATP inside the mitochondria.
Step 3 – Oxidation of Acetyl-CoA and the Krebs Cycle
The Krebs cycle (AKA tricarboxylic acid cycle or citric acid cycle) is the one that oxidizes the acetyl-CoA, removing thus electrons from acetyl-CoA and producing carbon dioxide as a by-product in the presence of oxygen inside the mitochondria.
Step 4 – Electrons Are Transported Through the Respiratory Chain
The electrons obtained from acetyl-CoA – which ultimately came from carbs or fats – are shuttled through many molecules as part of the electron transport chain inside the mitochondria. Some molecules are proteins, others are cofactors molecules. One of these cofactors is an important substance found mainly in animal foods and it is called coenzyme Q-10. Without it, mitochondrial energy production would be minimal. This is the same coenzyme Q10 that statins drug block producing crippling effects on people’s health. Step 4 is also where water is produced when oxygen accepts the electrons.
Step 5 – Oxidative phosphorylation
As electrons travel down the electron transport chain, they cause electrical fluctuations (or chemical gradients) between the inner and outer membrane in the mitochondria. These chemical gradients are the driving forces that produce ATP in what is called oxidative phosphorylation. Then the ATP is transported outside the mitochondria for the cell to use as energy for any of its thousands of biochemical reactions.
So that's the basics. But why is fat better than carbs?
If there were no mitochondria, then fat metabolism for energy would be limited and not very efficient. But nature provided us during our evolution with mitochondria that specifically uses fat for energy. Fat is the fueled that animals use to travel great distances, hunt, work, and play since fat gives more packed-energy ATPs than carbs. Biochemically, it makes sense that if we are higher mammals who have mitochondria, then we need to eat fat.
Whereas carb metabolism yields 36 ATP molecules from a glucose molecule, a fat metabolism yields 48 ATP molecules from a fatty acid molecule inside the mitochondria. Fat supplies more energy for the same amount of food compared to carbs. But not only that, the burning of fat by the mitochondria – beta oxidation – produces ketone bodies. These ketone bodies - acetoacetate, β-hydroxybutyrate and acetone – are produced for the most part by the cells in the liver. When our bodies are running primarily on fats, large amounts of acetyl-CoA are produced which exceed the capacity of the Krebs, leading to the making of these three ketone bodies within liver mitochondria. Our levels of ketone bodies in our blood go up and the brain readily uses them for energetic purposes. Ketone bodies cross the blood brain barrier very easily as well. Their solubility also makes them readily transportable by the blood to other organs and tissues. When ketone bodies are used as energy, they release acetyl-CoA which then goes to the Krebs cycle again to produce energy.
The increased production of acetyl-CoA generated from the ketone bodies also drives the Krebs cycle to increase mitochondrial NADH (reduced nicotinamide adenine nucleotide) which our body uses in over 450 biochemical reactions that are vital, including the cell signaling and assisting of the ongoing DNA repair. Because the ketone body beta-hydroxybutyrate is more energy rich than pyruvate, it produces more ATP as well. Ketosis also enhances the production of important anti-oxidants that deal with toxic elements from our environments, including glutathione.
According to Douglas C. Wallace (Director of the Center for Mitochondrial and Epigenomic Medicine), the longevity benefits seen in caloric restriction research is due to the fact that our bodies shift to a fat burning metabolism within our mitochondria. That is, we don't necessarily need to restrict our caloric intake as long as we are on ketosis from a high fat, moderate protein diet (and restricted in carbs of course). Alternating now and again with intermittent fasting will help us maintain good levels of ketone bodies though.
A few concepts of the role of our mitochondria will also help put things into perspective.
Mitochondria regulate cellular suicide, AKA apoptosis, so that old and dysfunctional cells which need to die do so and then new ones can come into the scene. A cell can still commit suicide (apoptosis) even when it has no nucleus along with its nuclear DNA. But when mitochondria function becomes impaired and send signals that tell normal cells to die, things go wrong. For instance, the destruction of brain cells leads to every single neurodegenerative condition including Alzheimer’s disease, Parkinson’s disease and so forth.
The catalysts for this destruction is usually uncontrolled free radical production which cause oxidative damage to tissues, fat, proteins, DNA, causing them to rust. This damage, called oxidative stress, is at the basis of oxidized cholesterol, stiff arteries (rusty pipes) and brain damage. Oxidative stress is a key player in dementia as well as autism. We produce our own anti-oxidants to keep a check on free radical production, but these systems are easily overwhelmed by a toxic environment and a high carb diet.
Mitochondria also have interesting characteristics which differentiate them from all other structural parts of our cells. For instance, they have their own DNA (referred as mtDNA) which is separate from the widely known DNA in the nucleus (referred as n-DNA), and it comes for the most part from the mother line which is why mitochondria is also considered as your feminine life force. This mtDNA is arranged in a ring configuration and it lacks a protective protein surrounding which leaves its genetic code vulnerable to free radical damage. If you don’t eat enough animal fats, you can’t build a functional mitochondrial membrane which will keep it healthy and prevent it from dying. If you have any kind of inflammation from anywhere in your body, you damage your mitochondria. The loss of function or death of mitochondria is present in pretty much every disease. Dietary and environmental factors lead to oxidative stress and thus, mitochondrial injury as the final common pathway of diseases or illnesses. Autism, ADHD, Parkinson’s, depression, anxiety, bipolar disease, brain aging is linked with mitochondrial dysfunction from oxidative stress. Mitochondrial dysfunction contributes to congestive heart disease, type 2 diabetes, autoimmune disorders, aging, cancer, and other diseases.
Whereas the nDNA provides the information your cells need to code for proteins that control metabolism, repair, and structural integrity of your body, it is the mDNA which directs the production and utilization of your life energy.
Because of their energetic role, the cells of tissues and organs which require more energy to function are richer in mitochondrial numbers. Cells in our brains, muscles, heart, kidney and liver contain thousands of mitochondria, comprising up to 40% of the cell’s mass. According to Prof. Enzo Nisoli, a human adult possesses more than ten million billion mitochondria, making up a full 10% of the total body weight. Each cell contains hundreds of mitochondria and thousands of mtDNA.
Since mtDNA is less protected than nDNA because it has no “protein” coating (histones), it is exquisitely vulnerable to injury by destabilizing molecules such as neurotoxic pesticides, herbicides, excitotoxins, heavy metals and volatile chemicals among others, tipping the balance of free radical production to the extreme and leading to oxidative stress which damages our mitochondria and its DNA. This leads to overexcitation of cells and inflammation which is at the root of Parkinson’s disease and other diseases, but also mood problems and behavior problems.
Enough energy means a happy and healthy life. It also reflects in our brains with focused and sharp thinking. Lack of energy means mood problems, dementia, and slowed mental function among others. Mitochondria are intricately linked to the ability of the prefrontal cortex –our brain’s captain- to come fully online. Brain cells are loaded in mitochondria that produce the necessary energy to learn and memorize, and fire neurons harmoniously.
The sirtuin family of genes works by protecting and improving the health and function of your mitochondria. They are positively influenced by a diet that is non-glycating, i.e. a low carb diet, since a high carb diet induces mitochondrial dysfunction and formation of reactive oxygen species.
And well, then we come back in full circle to the information presented in this thread that shows how ketosis stabilizes overexcitation and oxidative stress, increases our natural valium (GABA), makes our hippocampus (important for learning, memory and emotions) super resilient to stress, with possibly double the quantity of mitochondria when in ketosis. It also causes epigenetic changes that increases the production of healthy and energetic mitochondria and it decreases the overproduction of damaging and inflammatory free radicals among may other things.
As Douglas C. Wallace says in the Mitochondrial Energetics paper, “the ketogenic diet may act at multiple levels: It may decrease excitatory neuronal activity, increase the expression of bioenergetic genes, increase mitochondrial biogenesis and oxidative energy production, and increase mitochondrial NADPH production, thus decreasing mitochondrial oxidative stress.”
Moreover, you might want to keep in mind this excerpt from Human Brain Evolution: The Influence of Freshwater and Marine Food Resources :
Ketosis made us human :)
). Bravo!
