Ketogenic diet - a connection between mitochondria and diet

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This article is written by Dr Gabriela Segura, Consultant Cardiologist, and published here with her permission. Mitochondria are an essential part of good cardiac function.

Numbers in square brackets refer to references at the bottom of the article.



Ketosis is an often misunderstood subject. Its presence is thought to be equal to starvation or a warning sign of something going wrong in your metabolism. But nothing could be farther from the truth, except if you are an ill-treated type 1 diabetic person.[1] Ketones – contrary to popular belief and myth – are a much needed and essential healing energy source in our cells that come from the normal metabolism of fat.

The entire body uses ketones in a more safe and effective way than the energy source coming from carbohydrates – sugar AKA glucose. Our bodies will produce ketones if we eat a diet devoid of carbs or a low carb diet (less than 60 grams of carbs per day).[2] By eating a very low carb diet or no carbs at all (like a caveman) we become keto-adapted.

In fact, what is known today as the ketogenic diet was the number one treatment for epilepsy until Big Pharma arrived with its dangerous cocktails of anti-epileptic drugs. It took several decades before we heard again about this diet, thanks in part to a parent who demanded it for his 20-month-old boy with severe seizures. The boy’s father had to find out about the ketogenic diet in a library as it was never mentioned as an option by his neurologist. After only 4 days on the diet, his seizures stopped and never returned.[3] The Charlie Foundation was born after the kid’s name and his successful recovery, but nowadays the ketogenic diet is available to the entire world and it’s spreading by word of mouth thanks to its healing effects.

It is not only used as a healthy lifestyle, it is also used for conditions such as infantile spasms, epilepsy, autism, brain tumors, Alzheimer’s disease, Lou Gehrig’s disease, depression, stroke, head trauma, Parkinson’s disease, migraine, sleep disorders, schizophrenia, anxiety, ADHD, irritability, polycystic ovarian disease, irritable bowel syndrome, gastroesophageal reflux, obesity, cardiovascular disease, acne, type 2 diabetes, tremors, respiratory failure and virtually every neurological problem but also cancer, and conditions where tissues need to recover after a loss of oxygen.[4]

Our body organs and tissues work much better when they use ketones as a source of fuel, including the brain, heart and the core of our kidneys. If you ever had a chance to see a heart working in real time, you might have noticed the thick fatty tissue that surrounds it. In fact, heart surgeons get to see this every day. A happy beating heart is one that is surrounded by layers of healthy fat. Both the heart and the brain run at least 25% more efficiently on ketones than on blood sugar.

Ketones are the ideal fuel for our bodies unlike glucose – which is damaging, less stable, more excitatory and in fact shortens your life span. Ketones are non-glycating, which is to say, they don’t have a caramelizing ageing effect on your body. A healthy ketosis also helps starve cancer cells as they are unable to use ketones for fuel, relying on glucose alone for their growth. [5]The energy producing factories of our cells – the mitochondria – work much better on a ketogenic diet as they are able to increase energy levels in a stable, long-burning, efficient, and steady way. Not only that, a ketogenic diet induces epigenetic changes[6] which increases the energetic output of our mitochondria, reduces the production of damaging free radicals, and favours the production of GABA – a major inhibitory brain chemical. GABA has an essential relaxing influence and its favored production by ketosis also reduces the toxic effects of excitatory pathways in our brains. Furthermore, recent data suggests that ketosis alleviates pain in addition to having an overall anti-inflammatory effect. [7]

The ketogenic diet acts on multiple levels at once, something that no drug has been able to mimic. This is because mitochondria are specifically designed to use fat for energy. When our mitochondria use fat as an energetic source, its toxic load is decreased, the expression of energy producing genes are increased, its energetic output is increased, and the load of inflammatory energetic-end-products is decreased.

The key of these miraculous healing effects relies on the fact that fat metabolism and its generation of ketone bodies (beta-hydroxybutyrate and acetoacetate) by the liver can only occur within the mitochondrion, leaving chemicals within the cell but outside the mitochondria readily available to stimulate powerful anti-inflammatory antioxidants. The status of our mitochondria is the ultimate key for optimal health and while it is true that some of us might need extra support in the form of nutritional supplementation to heal these much needed energy factories, the diet still remains the ultimate key for a proper balance.

Our modern world’s staple energetic source is sugar which needs to be processed first in the cell soup before it can be passed into the energy factory of the cell- the mitochondrion. Energy sources from fat don’t require this processing; it goes directly into the mitochondria for energetic uses. That is, it is more complicated to create energy out of sugar than out of fat. As Christian B. Allan, PhD and Wolfgang Lutz, MD said in their book Life Without Bread:

Carbohydrates are not required to obtain energy. Fat supplies more energy than a comparable amount of carbohydrate, and low-carbohydrate diets tend to make your system of producing energy more efficient. Furthermore, many organs prefer fat for energy.

The fact is you get MORE energy per molecule of fat than sugar. How many chronic and autoimmune diseases have an energy deficit component? How about chronic fatigue? Fibromyalgia? Rheumatoid Arthritis? Multiple Sclerosis? Cancer? Back to Allan and Lutz:

Mitochondria are the power plants of the cell. Because they produce most of the energy in the body, the amount of energy available is based on how well the mitochondria are working. Whenever you think of energy, think of all those mitochondria churning out ATP to make the entire body function correctly. The amount of mitochondria in each cell varies, but up to 50 percent of the total cell volume can be mitochondria. When you get tired, don’t just assume you need more carbohydrates; instead, think in terms of how you can maximize your mitochondrial energy production…

If you could shrink to a small enough size to get inside the mitochondria, what would you discover? The first thing you’d learn is that the mitochondria are primarily designed to use fat for energy!

In short, let fat be thy medicine and medicine be thy fat!

You will think that with all of this information we would see ketogenic diets recommended right and left by our health care providers, but alas, that is not the case. Mainstream nutritionists recommend carbohydrates AKA sugar as the main staple of our diets. The problem with this (and there are several of them) is that in the presence of a high carb diet we are unable to produce ketones from the metabolism of fats, thus, depriving our bodies from much healing ketone production. The fact that we live in a world which uses glucose as a primary fuel means that we eat a very non healing food in more ways than one.

I have been doing the low carb diet for about a week and a half now and I must say, I am really starting to feel amazing!!! The first few days my head hurt, I felt lethargic, and my legs felt so heavy. But after I got past that, I have so much energy. I don’t get tired anymore around 3pm. The best part is, I am not constantly thinking and obsessing about food. I feel a real sense of inner calm. My skin looks better, my hair looks better too. I have been having bacon and eggs for breakfast, a pork chop or other piece of meat for lunch, and usually some pork and sometimes some green beans for dinner. I have also lost some weight! Woo hoo!!! -Angela, United States. forum.

We have been on a ketogenic diet for nearly three million years and it has made us human. It was the lifestyle in which our brains got nurtured and evolved. But not anymore, unless we all make an effort to reclaim this lost wisdom. Nowadays the human brain is not only shrinking, but brain atrophy is the norm as we age and get plagued with diseases such as Alzheimer’s disease, Parkinson’s disease, senile dementia and so forth.

In the mean time new research is starting to elucidate the key role of our mitochondria in the regulation of the cell cycle – the vital process by which a single celled fertilized egg develops into a mature organism, as well as the process by which hair, skin, blood cells, and some internal organs are renewed. In the complicated and highly choreographed events surrounding cell-cycle progression, mitochondria are not simple bystanders merely producing energy but instead are full-fledged participants.[8] Given the significant amount of energy needed to make all the nutrients required for cell division, it makes sense that some coordination existed. This long ignored and overlooked connection between the mitochondria and the cell cycle is something that is worthy of considerably more attention as we understand the role of diet in our bodies. We’ll have to take a closer look at this subject of ketosis, as it really holds the key to unlock our transformational pathways that will lead us to an outstanding healthy living.

Mitochondrial Dysfunction

Mitochondria are best known as the powerhouses of our cells since they produce the cell’s energy. But they also lead the genetic orchestra which regulates how every cell ages, divides, and dies. They help dictate which genes are switched on or off in every single cell of our organism. They also provide the fuel needed to make new brain connections, repair and regenerate our bodies.

Whether we are housewives, sportsmen or labourers, energy is a topic that concerns us all, every day and in every way. Our well being, behaviour and ability to perform the tasks put in front of us is all to do with our individual levels of energy. But how do we derive energy from the foods that we eat?

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.

Source: Christian B. Allan, PhD and Wolfgang Lutz, MD, Life Without Bread.

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 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 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 means 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 part that 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.

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 fuel that animals use to travel great distances, hunt, work, and play since fat gives more energy-packed 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 that stabilizes overexcitation and oxidative stress in the brain related to all its diseases, it also causes epigenetic changes that produce healthy and energetic mitochondria and decreasing the overproduction of damaging and inflammatory free radicals among many other things!

Mitochondria regulate cellular suicide, AKA apoptosis, so that old and dysfunctional cells which need to die will do so, leaving space for new ones to come into the scene. But when mitochondria function becomes impaired and sends signals that tell normal cells to die, things go wrong. For instance, the destruction of brain cells leads to every single neurodegenerative condition known including Alzheimer’s disease, Parkinson’s disease and so forth. Mitochondrial dysfunction has wide-ranging implications, as the health of the mitochondria intimately affects every single cell, tissue and organ within your body.

The catalysts for this destruction is usually uncontrolled free radical production which causes 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, in other words, by today’s lifestyle and 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). Mitochondrial DNA 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, leaving 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 them 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 to mitochondrial injury as the final common pathway of diseases or illnesses.

Autism, ADHD, Parkinson’s, depression, anxiety, bipolar disease, brain ageing are all linked with mitochondrial dysfunction from oxidative stress. Mitochondrial dysfunction contributes to congestive heart failure, type 2 diabetes, autoimmune disorders, ageing, 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 mtDNA which directs the production and utilization of your life energy. A cell can still commit suicide (apoptosis) even when it has no nucleus nor nDNA.

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.[9] 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. This increasees free radical production to the extreme which then leads to oxidative stress damaging our mitochondria and its DNA. As a result we get overexcitation of cells and inflammation which is at the root of Parkinson’s disease and other diseases, but also mood problems and behaviour 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.[10] They are positively influenced by a diet that is non-glycating, i.e. a low carb diet as opposed to a high carb diet which induces mitochondrial dysfunction and formation of reactive oxygen species.

Another thing that contributes to mitochondrial dysfunction is latent viral infection such as the ones of the herpes family. As I mentioned in On Viral “Junk” DNA, a DNA Enhancing Ketogenic Diet, and Cometary Kicks, most, if not all of your “junk” DNA has viral-like properties. If a pathogenic virus takes hold of our DNA or RNA, it could lead to disease or cancer.

Herpes simplex virus is a widespread human pathogen and it goes right after our mitochondrial DNA. Herpes simplex virus establishes its latency in sensory neurons, a type of cell that is highly sensitive to the pathological effects of mt DNA damage.[11] A latent viral infection might be driving the brain cell loss in neurodegenerative diseases such as Alzheimer’s disease.[12]As I speculated in Heart attacks, CFS, herpes virus infection and the vagus nerve , a latent herpes virus infection might drive more diseases than we would like to admit.

Members of the herpes virus family (i.e. cytomegalovirus and Epstein-Barr virus which most people have as latent infections!), can go after our mitochondrial DNA, causing neurodegenerative diseases by mitochondrial dysfunction. But a ketogenic diet is the one thing that would help stabilize mtDNA since mitochondria runs the best on fat fuel. As it happens, Alzheimer’s disease is the one condition where a ketogenic diet has its most potential healing effect.[4]

The role of mitochondrial dysfunction in our “modern” age maladies is a staggering one. Optimal energetic sources are essential if we are to heal from chronic ailments. It is our mitochondria which lies at the interface between the fuel from foods that come from our environment and our bodies’ energy demands. And it is a metabolism based on fat fuel, a ketone metabolism, the one which signals epigenetic changes that maximizes energetic output within our mitochondria and help us heal.

I am incredulous at how my body is responding. I think I am totally carb intolerant. I’ve struggled with extreme fatigue/exhaustion for so many years, even with improved sleep in a dark room that I can’t tell you how wonderful it is to wake up in the morning, get out of bed and not long to crawl back in, going through the day by will mostly. Also chronic long-standing intestinal issues are finally resolving. A couple of people at work have made comments to the effect that I’m a “different woman”, calmer, no more 'hyperness' under pressure, stress seems to roll off of my back as well. I’ve lost a little weight and although I don’t weigh myself, my clothes are definitely looser. I’ve had the round middle for so many years I was resigned to struggling to bend over to pull my shoes on! -Bluefyre, 56 years old, United States. forum

Ketosis – Closer Look

The presence of ketones in the blood and urine, a condition known as ketosis, has always been regarded as a negative situation, related to starvation. While it is true that ketones are produced during fasting, ketones are also produced in times of plenty, but not plenty of carbohydrates since a carb metabolism suppresses ketosis. In the absence of most carbs in the diet, ketones will form from fat to supply energy. This is true even if lots of fats and enough protein are eaten, something that is hardly a starvation condition.

As we already saw, a ketogenic diet has been proved useful in a number of diseases, especially neurological ones. Strictly speaking, a ketogenic diet is a high fat diet in which carbohydrates are either completely eliminated or nearly eliminated so that the body has the very bare minimum sources of glucose. That makes fats (fatty acids) a mandatory energetic fuel source for both the brain and other organs and tissues. If your carb intake is high, you’ll end up storing both the fat and the carbs in your fat tissue thanks to the hormone insulin. A ketogenic diet is not a high protein diet, which as it happens, can also stimulate insulin. It is basically a diet where you rely primarily on animal foods and especially their fats.

I recently had my annual blood work done (cholesterol, etc.) During the review, my doctor said that everything looked great! He then encouraged me to continue on my great ‘low fat, high fruit and veggie diet’ that I must be following! I just smiled. Next visit I’m going to tell him about my real ‘diet’. Lol -1984, United States. forum.

Among the by-products of fat burning metabolism are the so called ketone bodies – acetoacetate, β-hydroxybutyrate and acetone – which are produced for the most part by the liver. When our bodies are running primarily on fats, large amounts of acetyl-CoA are produced which exceed the capacity of the Krebs cycle, 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 readily. Their solubility also makes them easily 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.

In children who were treated with the ketogenic diet to treat their epilepsy, it was seen that they become seizure-free even long after the diet ended, meaning that not only did the diet proved to be protective, but also it modified the activity of the disease , something that no drug has been able to do.[13] In Alzheimer’s disease, as levels of ketone bodies rise, memory improves. People’s starved brains finally receive the much needed fats they need! In fact, every single neurological disease is improved on the ketogenic diet.

The benefits of a ketogenic diet can be seen as quickly as one week, developing gradually over a period of 3 weeks. There are several changes in gene expression involving metabolism, growth, development, and homeostasis among others.

The hippocampus is a region in your brain that is very vulnerable to stress which makes it lose its brain cells. The hippocampus has to do with memory, learning, and emotion. As it happens, a ketogenic diet promotes the codification of genes which creates mitochondria in the hippocampus, making more energy available. A larger mitochondrial load and more energy means more reserve to withstand much more stress.[14]

In some animal models, following a ketogenic diet, there is a 50% increase in the total number of mitochondria in the hippocampus, resulting in more brain ATP.[15] Other animal studies show how communication between brain cells in the hippocampus would remain smooth for 60% longer when exposed to a stressful stimulus compared to their counterparts who didn’t had a ketogenic diet.[16] This is very important since too much stress can damage the hippocampus and its capacity to retrieve information, making you “absent-minded” or “brain-scattered”, as well as affecting the ability of your prefrontal cortex to think and manage behavior.

A ketogenic diet also increases levels of the calming neurotransmitter – GABA - which then serves to calm down the overexcitation which is at the base of major neuro-degenerative diseases, but also anxiety and other mood problems. A ketogenic diet also increases antioxidant pathways that level the excess production of free radicals from a toxic environment. It also enhances anti-inflammatory pathways.

Ketosis also cleans our cells from proteins that act like “debris” and which contribute to ageing by disrupting a proper functioning of the cell.[17] It basically does this by what is known as autophagy which preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. This prevents degenerative diseases, ageing, cancer, and protects you against microbial infections. A ketogenic diet not only rejuvenates you, it also makes a person much less susceptible to viruses and bacterial infections.[18] This is very relevant due to the increasing number of weird viral and bacterial infections that seem to be incoming from our upper atmosphere[19] (for more information see New Light on the Black Death: The Viral and Cosmic Connection), or due to high levels of radiation that creates more pathogenic strains (see Detoxify or Die: Natural Radiation Protection Therapies for Coping With the Fallout of the Fukushima Nuclear Meltdown). Either way, we are more vulnerable than ever due to the state of our mitochondria. But we can prepare for the worst with ketosis.

Ketone-enhanced autophagy is very important because autophagy can target viruses and bacteria that grow inside cells which are very problematical.[20] Intracellular viruses and bacteria can lead to severe mitochondrial dysfunction and ketosis remains by far our best chance against them.


A Paoli, A Rubini, J S Volek and K A Grimaldi. 
Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. 
European Journal of Clinical Nutrition (2013) 67, 789–796

Ketone bodies production through intermittent fasting and the ketogenic diet is the most promising treatment for mitochondrial dysfunction.[21]The longevity benefits seen by caloric restriction research is due to the fact that our bodies shift to a fat burning metabolism within our mitochondria. With a ketogenic diet, we go into a fat burning metabolism without restricting our caloric intake.

Ketosis deals effectively with all the problems of a diet rich in carbs – the one recommended by mainstream science. Namely a ketogenic diet deals with anxiety, food cravings, irritability, tremors, and mood problems among others. It is a crime to discourage the consumption of a high fat diet considering that a ketogenic diet shrinks tumours in human and animal models, and enhances our brain’s resilience against stress and toxicity.

In addition to increasing the production of our body’s natural valium – GABA – 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 vital biochemical reactions – including the cell signalling and assisting of the ongoing DNA repair. Because the ketone body beta-hydroxybutyrate is more energy rich than pyruvate, it produces more ATP. Ketosis also enhances the production of important anti-oxidants that deal with toxic elements from our environments, including glutathione.

Mitochondria from the hippocampus of ketogenic diet-fed animals are also resistant to mtDNA damage and are much less likely to commit cell suicide –apoptosis- at inappropriate times.

As Douglas C. Wallace, PhD, Director of the Center for Mitochondrial and Epigenomic Medicine says, “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.”[21]

Keto-adaptation results in marked changes in how we construct and maintain optimum membrane (“mem-brain”) composition, not only because of the healthy fats we provide through the diet, but also because of less free radical production and inflammatory mediators, along with more production of anti-oxidants. It is really the ideal balanced state.

Moreover, you might want to keep in mind this excerpt from "Human Brain Evolution: The Influence of Freshwater and Marine Food Resources"[22]:

There are two key advantages to having ketone bodies as the main alternative fuel to glucose for the human brain. First, humans normally have significant body fat stores, so there is an abundant supply of fatty acids to make ketones. Second, using ketones to meet part of the brain’s energy requirement when food availability is intermittent frees up some glucose for other uses and greatly reduces both the risk of detrimental muscle breakdown during glucose synthesis, as well as compromised function of other cells dependent on glucose, that is, red blood cells. One interesting attribute of ketone uptake by the brain is that it is four to five times faster in newborns and infants than in adults. Hence, in a sense, the efficient use of ketones by the infant brain means that it arguably has a better fuel reserve than the adult brain. Although the role of ketones as a fuel reserve is important, in infants, they are more than just a reserve brain fuel – they are also the main substrate for brain lipid synthesis.
I have hypothesized that evolution of a greater capacity to make ketones coevolved with human brain expansion. This increasing capacity was directly linked to evolving fatty acid reserves in body fat stores during fetal and neonatal development. To both expand brain size and increase its sophistication so remarkably would have required a reliable and copious energy supply for a very long period of time, probably at least a million, if not two million, years. Initially, and up to a point, the energy needs of a somewhat larger hominin brain could be met by glucose and short – term glucose reserves such as glycogen and glucose synthesis from amino acids. As hominins slowly began to evolve larger brains after having acquired a more secure and abundant food supply, further brain expansion would have depended on evolving significant fat stores and having reliable and rapid access to the fuel in those fat stores. Fat stores were necessary but were still not sufficient without a coincident increase in the capacity for ketogenesis. This unique combination of outstanding fuel store in body fat as well as rapid and abundant availability of ketones as a brain fuel that could seamlessly replace glucose was the key fuel reserve for expanding the hominin brain, a reserve that was apparently not available to other land – based mammals, including nonhuman primates.

It is indisputable that a ketogenic diet has protective effects in our brains. With all the evidence of its efficacy in mitochondrial dysfunction, it can be applied for all of us living in a highly stressful and toxic environment. Ketone bodies are healing bodies that helped us evolve and nowadays our mitochondria are always busted in some way or another since the odds in this toxic world are against us. Obviously, there are going to be people with such damaged mtDNA or with mutations they were born with, who can’t modify their systems (i.e. defects on L-carnitine metabolism), but even in some of those cases, they can halt or slow down further damage. Our healthy ancestors never had to deal with the levels of toxicity that we live nowadays and nevertheless, they ate optimally. Considering our current time and environment, the least we can do is eat optimally for our physiology.

The way to have healing ketone bodies circulating in our blood stream is to do a high fat, restricted carb and moderated protein diet. Coupled with intermittent fasting which will enhance the production of ketone bodies, and resistance training which will create mitochondria with healthier mtDNA, we can beat the odds against us.

What is considered nowadays a “normal diet” is actually an aberration based on the corruption of science which benefits Big Agra and Big Pharma. If we would go back in time to the days before the modern diet became normalized by corporative and agricultural interests, we will find that ketosis was the normal metabolic state. Today’s human metabolic state is aberrant. It is time to change that.


[1] A research member of’s forum has diabetes type 1 and is doing the ketogenic diet. Under normal circumstances, diabetics (including type I) report amazing results on a low-carbohydrate diet. See Dr. Bernstein’s Diabetics Solution by Richard K. Bernstein, MD (Little, Brown and Company: 2007).

[2] It varies among each person, but the general range is between 0 and 70 grams of carbs plus moderate intake of protein, between 0.8 and 1.5 grams of protein per kg of ideal body weight. Pregnant women and children should not have their protein restricted.

[3] Ketogenic diets in seizure control and neurologic disorders by Eric Kossoff, MD, Johns Hopkins Hospital, Baltimore, Maryland. The Art and Science of Low Carbohydrate Living by Jeff S. Volek, PhD, Rd and Stephen D. Phinney, MD, PhD. Beyond Obesity, LLC , 2011.

[4] A Paoli, A Rubini, J S Volek and K A Grimaldi. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition (2013) 67, 789–796

[5] Rainer J Klement, Ulrike Kämmerer. Is there a role for carbohydrate restriction in the treatment and prevention of cancer? Nutr Metab (Lond). Oct 26, 2011; 8: 75.

[6] If the genetic code is the hardware for life, the epigenetic code is software that determines how the hardware behaves.

[7] David N. Ruskin and Susan A. Masino, The Nervous System and Metabolic Dysregulation: Emerging Evidence Converges on Ketogenic Diet Therapy. Front Neurosci. 2012; 6: 33.

[8] Finkel T, Hwang PM. The Krebs cycle meets the cell cycle: mitochondria and the G1-S transition. Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):11825-6.

[9] Matthews C.M. Nurturing your divine feminine. Proc (Bayl Univ Med Cent). 2011 July; 24(3): 248.

[10] Hipkiss AR. Energy metabolism, altered proteins, sirtuins and ageing: converging mechanisms? Biogerontology. 2008 Feb;9(1):49-55.

[11] Saffran HA, Pare JM, Corcoran JA, et al. Herpes simplex virus eliminates host mitochondrial DNA. EMBO Rep. 2007 Feb;8(2):188-93.

[12] Porcellini E, Carbone I, et al. Alzheimer’s disease gene signature says: beware of brain viral infections. Immun Ageing. 2010 Dec 14;7:16.

[13] Gasior M, Rogawski MA, Hartman AL. Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol. 2006 Sep;17(5-6):431-9.

[14] Maalouf M, Rho JM, Mattson MP. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 2009 Mar;59(2):293-315.

[15] Nylen K, Velazquez JL. The effects of a ketogenic diet on ATP concentrations and the number of hippocampal mitochondria in Aldh5a1(-/-) mice. Biochim Biophys Acta. 2009 Mar;1790(3):208-12.

[16] Bough K. Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet. Epilepsia. 2008 Nov;49 Suppl 8:91-3.

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Gabriela Segura, MD
Friday, 9 August 2013

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