What is Ketosis and Is it Dangerous?

A frequent concern that comes up for some people when I talk about following a very low-carb Paleo diet is whether ketosis, ketones, or a ketogenic diet are dangerous. Unfortunately, there is a great deal of misinformation and confusion on this topic that gets passed around and results in an unsubstantiated negative perception and needless fear.

For the most part, this is due to the fact that many people (including a lot of doctors) do not understand the difference between ketosis and ketoacidosis. The two words are often mistaken for one another and most people just do not understand what ketones are or the role they play in the body. So let’s set the record straight.

Definition of Ketosis

In The Primal Blueprint, Mark Sisson describes ketosis as “a natural, normal, part of human energy production and metabolism.” If you have ever fasted or skipped several meals in a row, you have been in ketosis. You are actually in a very mild state of ketosis when you wake in the morning after going without food overnight.

Ketones are just one of the four types of fuel (carb, fat, protein, ketones) that your body can use for energy and a ketogenic diet is a diet that puts one in ketosis (typically less than 50 grams of total carbs (not net) per day in conjunction with a high amount of fat and a moderate amount of protein).

The human body evolved burning mostly fats for energy, and a small amount of glucose. However, we are capable of burning protein if we are low on glucose or glycogen (glucose that is stored in the liver and muscle). Protein can be converted into glucose by the liver, which is called gluconeogenesis.

Most cells in the human body can burn either fat or glucose. However, there are some that can run only on glucose which includes “certain brains cells, red blood cells, and kidney cells.” These cells would not function without glucose and we would perish.

It is estimated that approximately 150 to 200 grams of glucose are needed on a daily basis to keep those cells running. However, after a brief period of adaptation, research suggests that many of these cells (except red blood cells which must have a particular amount of glucose) can function just as well (if not better) on ketones, which significantly reduces your need for glucose.

After a few weeks of reducing carbs, and ultimately insulin production, and increasing the fat in your diet, your genes will receive the message that they should upregulate the biochemical hardware needed to burn ketones effectively. This is called keto-adapted. At this point, the body relies primarily on fat for energy instead of glucose, which is called fat-adapted. So to put it more simply, ketosis is a state where the body burns fat for energy instead of carbohydrates.

Our ancestors rarely had access to carbohydrates because they simply were not available like they are today. They were forced to go without them for weeks or even months at a time and existed primarily on animal protein and fat. Easy access to carbohydrates did not occur until the Agricultural Revolution. The body can only store a little bit of glucose in the form of glycogen, which gets used up very quickly.

Therefore, the circumstances demanded that we evolve a system that enabled the liver to take protein straight from our food or from the muscles and convert it into glucose if we were going to remain alive; this process is called gluconeogenesis. This system enabled us to survive and thrive as a species during brief periods of starvation or when the only food source available was protein and fat. It also enabled us to develop bigger and smarter brains that brought us to the top of the food chain.

What are Ketones?

Ketones (ketone bodies) are a byproduct of fat metabolism. They are produced when fat (fatty acids) is broken down for fuel or energy. This source of fuel can be used by your cells instead of glucose. There are three primary types known as acetoacetate, beta-hydroxybutyrate, and acetone.

In order for the liver to convert protein into glucose, a source of energy is required, therefore it uses fatty acids (fat) for this process. When cells in the liver are engaged in gluconeogenesis, they are not capable of burning off the fats completely, which results in an “energy-rich by-product” called ketones, or a ketone body.

Additionally, if all your glycogen (stored glucose) is used up and you have no food coming in (such is the case when you are fasting), then the body will start burning fat that you have stored in the body for fuel, which will produce ketones and another component of fat called glycerol will be converted into glucose through gluconeogenesis.

Ketones can also be generated with the consumption of coconut fat because coconut contains a particular type of fat called medium-chain triglycerides, that is converted directly into beta-hydroxybutyrate (our primary ketone is also known as Beta HBA) by the liver.

Astrocytes, a special type of cell in the brain (a primary class of glial cells, which are non-neuronal cells that support and assist neurons) can also produce ketone bodies with fatty acids and the amino acid leucine when glucose is scarce as well. These particular ketones possess a powerful ability to protect the neuronal network, by increasing antioxidants and decreasing free radical production in the brain, increasing the formation of new mitochondria, and preventing cell death.

Unlike fat and glucose, ketones cannot be stored in fat cells; they just travel freely throughout the bloodstream where they may be easily obtained for energy by any cell that wants or needs them. The state of ketosis occurs when ketones that are in the bloodstream accumulate to a level that is higher than what is being used up by the cells for energy, thus there is an elevated level.

If you have been consuming a diet that is moderate to high in carbohydrates, then your body is not capable of accessing those ketones for energy very efficiently, because your genes have downregulated the biochemical pathways used in this process due to the presence of carbohydrates in the diet.

Ketones that are not used by the body are excreted in the urine, stool, and breath. Until the body becomes keto-adapted, you may smell ketones on the breath, which smells something like nail polish remover or have increased levels of ketones in the urine. However, this is temporary, not a dangerous state and nothing to be alarmed about.

Once you reduce carbohydrates in your diet, then it will take a few weeks for your genes to be reprogrammed and they will become capable of burning ketones for energy efficiently, thereby accumulating and excreting less and having less need for glucose. According to nutritional consultant Nora Gedgaudas, author of Primal Body Primal Mind, this process can take anywhere from three to six weeks, which varies from person to person. She suggests that the individual transitioning to a ketogenic diet should drink plenty of water to flush ketones out through the urine, which reduces ketone breath. A dash of fresh lemon juice in your water can also help alkalize.

You can also reduce ketone breath or how quickly ketones elevate in the urine by transitioning onto a ketogenic diet slowly. Instead of dropping down to 0 to 50 grams per day immediately, begin by reducing down to 100 to 150 grams a day, then after a week or two drop down to 50 to 100 grams. After a week or two then, drop down to 0 to 50. This allows your body time to adjust slowly until your genes start upregulating your hardware for burning ketones more effectively.

The Difference Between Ketoacidosis and Ketosis

Ketoacidosis, on the other hand, is a serious and potentially life-threatening condition that primarily affects insulin-dependent type 1 diabetics, (rarely late-stage insulin-dependent type 2) but this is a completely different state than ketosis. In ketoacidosis, the levels of ketones are abnormally high and out of control due to the lack of insulin and the inability of the body to use glucose.

When insulin isn’t present, then glucose cannot be carried into the cell for energy. When the pancreas recognizes that there is no glucose getting into the cell, then it sends out the signal to convert protein into glucose, and consequently, ketones. However, since there is no insulin to deliver the glucose to the cell, the cell never receives any. So the pancreas just keeps sending the signal to make more and more ketones uncontrollably. Ketones are acidic by nature and if they are in the bloodstream at very high levels they can cause a profound imbalance in pH (a dangerous acidic state) that can result in coma and death. It isn’t really the ketones themselves that are dangerous, but the imbalance in pH that occurs. Alcoholic ketoacidosis can also occur in chronic long-term alcoholism due to dehydration impairing gluconeogenesis and causing an imbalance in pH.

Ketone levels in someone who is in ketosis are at a maximum of 8 mM, while ketone levels in someone with ketoacidosis are somewhere between 15 and 25 mM. Once you become keto-adapted, ketone levels will be more like .05 to 3.0 mm. Therefore, unless you are an active chronic alcoholic or have insulin-dependent diabetes, ketosis is completely safe. (However, you should always consult with your physician prior to undertaking any changes in diet.)

Ketoacidosis will not occur by eating a ketogenic diet because if you aren’t diabetic, you have insulin, glucagon, and other hormones to regulate the process and you are restricting glucose. It just isn’t possible to enter a state of ketoacidosis, even if you are producing just a little insulin, because it won’t allow ketones to get out of hand. Nora Gedgaudas suggests that anyone with renal disease or who is pregnant and not already keto-adapted may need to avoid a ketogenic diet. She also reports that even people with type 1 diabetes have used the ketogenic diet successfully, but it should always be done with medical supervision.

Other Unnecessary Concerns About Ketosis

Some people are concerned that they will be missing out on nutrients if they eat a ketogenic diet, (less than 50 grams of total carbs per day) but that is not the case. You can consume plenty of nutrient-rich vegetables if you stay between 20 and 50 grams per day. Many of our ancestors not only survived but thrived, quite nicely on 50 grams or less of carbs per day and the human body can still do so today. Actually, our ancestors spent a significant amount of time in ketosis, so your body will be comfortable there as well.

As a matter of fact, if given the choice, some of your cells like skeletal muscle, cardiac muscle, and some brains cells, actually favor ketones over glucose. Once you become keto-adapted, the brain can function quite well by acquiring about “75 percent of its energy from ketones.” According to Dr. David Perlmutter, author of Grain Brain, both the heart and brain run as much as 25 percent better on ketones than they do on glucose.

Ketosis typically occurs when carbohydrate consumption is between 0 and 50 total grams per day, fat consumption is increased, and protein consumption is not in excess. If you are eating between 50 and 100 total grams of carbohydrates per day, you are not going to be in a state of ketosis, but your body will be burning more ketones than the person who eats mostly carbohydrates. You will be running on a combination of mostly fats and ketones, and a little bit of glucose, which is the preferred state of the human body since it is the way we evolved.

Whereas people who eat high to moderate levels of carbs run primarily on glucose. If you are consuming more than 100 grams of carbs per day, then ketone production is reduced and the body becomes less capable of burning them for energy since insulin and glucose both suppress ketones by giving your genes the message that it should downregulate the biochemical pathways to do so.

So, you see, your genes can easily switch back and forth between these energy-producing systems or metabolic pathways depending on what types of food you are putting in your body. Eat fewer carbs and more fat and you’ll run on protein and fat. Eat lots of carbs and you’ll run on carbs. Without the ability to run on ketones, our species would have simply died off in the caveman days and we would not be having this discussion.

Other people are concerned that they will deplete muscle on a low-carb diet, but that only applies to dietary approaches that restrict calories, which is not the case on a low-carb ketogenic Paleo diet. As long as you are eating adequate protein and fat, there will be no loss of muscle. The protein in your diet (not your muscle) will be used for gluconeogenesis and lots of fat will be available to meet your daily requirements for energy.

There is a belief within the paleo/keto community that gluconeogenesis (converting protein or fat into glucose), which occurs when eating low-carb is stressful and puts an excess burden on the adrenals because it requires cortisol for the process. However, that is not completely accurate. The hormone that is called into action to prompt gluconeogenesis is glucagon (not cortisol), which is produced by the pancreas. This typically happens before blood sugar gets low enough to trigger cortisol and epinephrine. When blood sugar first begins to drop, it is glucagon that regulates blood sugar. If for some reason, glucagon does not perform the job of stabilizing blood sugar or gluconeogenesis is impaired for some other reason, then blood sugar levels drop even further and hypoglycemia is experienced. At this point then cortisol and epinephrine would be elevated.

There are a few rare genetic disorders that can impair gluconeogenesis. However, most people do not have a problem with glucagon production. People with “true” hypoglycemia have lost their ability to make glucagon. But you can experience symptoms that mimic true hypoglycemia simply because you are not eating enough animal protein and fat or you’re eating too many carbs. Additionally, Candida itself (as well as bacteria) can impair gluconeogenesis because of their ability to impair ATP production (needed for gluconeogenesis), which is often the culprit of low blood sugar.

In either case, my personal experience has shown that the solution to all these problems is to keep carb consumption low and ensure there are adequate animal protein and fat in the diet and that you don’t go too long without eating. No more than four to five hours in between meals. This will prevent blood sugar from dropping too low that would prompt elevations in cortisol and epinephrine. If you are experiencing the drop in blood sugar and the cortisol/epinephrine surge, then you aren’t eating enough animal protein or you are going too long between meals.

Some research suggests that after a period of adaptation Candida may feed on ketones and that the killing of Candida by neutrophils (white blood cells that protect us from microbes) may be impaired in ketosis. That has not been my personal experience, and no one I’ve worked with directly has made this report to me. However, that doesn’t mean it can’t happen. Some people writing in online forums believe they have had this experience with ketones. Many other people with Candida (myself included) report feeling best when running primarily on ketones.

These conflicting reports demonstrate how complex and adaptable Candida is and how the experience may vary from person to person. Still, this does not mean that one should abandon a low-carb diet and start consuming a lot of starches. Considering the fact that sugar and carbs are Candida’s preferred foods and they enable Candida to do its worst damage, and the fact that these foods are associated with so many other problems like cravings for more sugar and carbs, addiction, metabolic syndrome, and dementia, and the fact that a ketogenic diet provides so many other benefits presented in the next section, it remains clear that maintaining nutritional ketosis is the better choice even if this circumstance does occur.

Be aware of this potential for ketones to exacerbate candida, and monitor how your body responds. If you sense that a ketogenic diet is worsening your Candida, the logical course of action would be to strike a middle ground: eat a diet that does not increase either glucose or ketones too much—that is, consuming a total of around 60 to 70 grams of carbohydrate per day. That would be total carbs, not net carbs.

Benefits of Ketosis and a Ketogenic Diet

There are many studies that suggest a low-carb, ketogenic diet is a safe and effective way for the obese or overweight to lose weight and reduce body fat, as well as reverse insulin resistance, type 2 diabetes, free radical damage, LDL cholesterol, and other damage inflicted by a high carbohydrate diet in anyone.

When in a state of ketosis, you will burn stored body fat for energy and convert protein into glucose, therefore this accelerates fat burning and becomes a catalyst for losing weight in a quick and fairly comfortable manner without losing muscle.

Occasionally someone may find that they are in ketosis but are not losing weight or maybe gaining weight. It’s important to find the protein, fat, carb ratio that works right for your body.

Many people believe that if one is eating more protein than their system can use for basic maintenance and repair, then excess protein will be converted into glucose by the liver through gluconeogenesis, which can interrupt your efforts to be in ketosis since insulin will be present. So even if you are eating carbs within the 0 to 50 range, if your protein intake is too high, then you may still run more on glucose which ends up getting stored as fat. However, I am not certain this is true. Take a look here, which provides a variety of studies that suggest gluconeogenesis is a process that is driven by demand not supply.

However, even if true, what is considered to be too much protein would vary from person to person, not a number that is set in stone. Your need for animal protein will also vary depending on other factors like whether glucagon is managing your blood sugar adequately, immune health, and others.

You can reduce your need for animal protein by eating more fat, which is an important component of eating a ketogenic diet anyhow. Not only do you reduce carbohydrates, but you should eat more fat.  A ketogenic diet is high in fat, moderate in animal protein, and low in carb.

More fat consumption typically happens naturally, because you’ll find that once you start burning fat, you have an increased need to consume it, so you will just naturally gravitate towards more fat. I experienced this in my own life; after I was following a ketogenic diet for about seven or eight months and had burnt off most of my excess body fat, I began to be hungry for fat whenever meal time came around. My meals must now contain a substantial amount of fat or I don’t feel satiated.

On the other hand, it is vital that you don’t go too low on protein or protein will be taken from the muscle for gluconeogenesis, and muscle wasting would occur. For most people, there should be between four and eight ounces of protein per meal.

Furthermore, if you exercise too much or too strenuously, this prompts the liver to release its glycogen (stored glucose) into the bloodstream, and the inevitable arrival of insulin, which can also interfere in reaching or maintaining ketosis.

Additionally, a ketogenic diet is being used to successfully treat many psychiatric and neurological conditions like autism, Alzheimer’s, Parkinson’s, depression, schizophrenia, OCD, ALS (Lou Gehrig’s Disease), and seizure disorders like epilepsy; as well as cardiovascular disease, multiple sclerosis, PCOS, migraines, diabetes, and cancer. A ketogenic diet works for cancer, because it deprives cancer cells of glucose, one of its primary sources of fuel, and supports mitochondria.

To quote Dr. David Perlmutter, who was quoting Gary Taubes “ketosis is arguably not just a natural condition but even a particularly healthy one.”

A ketogenic diet activates a gene that produces a protein called brain-derived neurotrophic factor or BDNF. BDNF helps protect existing neurons, encourages connection between neurons, and creates new neurons. BDNF levels are low in Alzheimer’s patients and other neurological disorders like epilepsy, anorexia, depression, schizophrenia, OCD, and increased appetites.

Again to quote Dr. David Perlmutter, “Beta HBA (the primary ketone body) is not just a fuel – but a super fuel more efficiently producing ATP for energy than glucose” and it protects neuronal cells against toxins associated with conditions like Alzheimer’s.

Furthermore, Perlmutter states a ketogenic diet also reduces amyloid in the brain (a protein that builds up in the arteries in the brain that is associated with Alzheimer’s and other related conditions involving cognitive decline), increases the production of glutathione (a vital antioxidant for the brain), stimulates mitochondrial growth and increases metabolic efficiency.

In one study of Parkinson’s patients, they experienced symptom improvement that was comparable to drugs and surgery after being on a ketogenic diet for less than a month. Coconut oil is also being used very successfully for improving cognitive function in Alzheimer’s patients due to its high level of MCT (medium-chain triglycerides) that are rapidly converted into beta-hydroxybutyrate.

In Primal Body Primal Mind, Nora Gedgaudas explains that a ketogenic diet was the primary method of treatment for epilepsy prior to the appearance of the drug Dilantin in 1938. Furthermore, Nora states that ketones are a “far less damaging source of energy, far more stabilizing, and less excitatory” than glucose, and recent research suggests that “the more you use ketones for energy in your lifetime as opposed to glucose the longer and healthier you will live.” Like many others, she also reinforces the point that a ketogenic diet improves the performance of mitochondria (what produces energy), and increases energy levels. Nora also quotes Gary Taubes who is quoting Dr. Richard Veech, a researcher at the United States National Institutes of Health, stating that he would argue that ketosis is the “normal state of man.”

As a matter of fact, we all begin our lives in a state of mild ketosis if we are breastfed as nature intended us to be because as newborns we are supposed to be relying on mother’s milk for our diet, which is rich in fat and ketogenic. The human body does not run on carbohydrates unless carbohydrates are introduced into the diet.

Furthermore, Nora explains “ketones are a steady, long-burning, efficient fuel that we were designed to use as our primary source of fuel for most things (except in an emergency), which is when glucose gets released as a turbocharged supplemental source of energy.” But, “we always pay a price for the use of glucose as an energy source, even in low amounts.”

Emily Dean, an evolutionary psychiatrist, explains that one of the reasons the ketogenic diet may be so effective with epilepsy is because (for reasons not completely understood) it encourages the conversion of glutamate into GABA rather than aspartate. Glutamate is our primary excitatory neurotransmitter that is very important for stimulating brain cells in order to think, talk, learn new information and other tasks, but when it is in excess it is considered an excitotoxin because it results in excessive brain stimulation, cell death, brain injury, and in the most extreme cases it may result in seizures. GABA is our primary calming inhibitory neurotransmitter. GABA and glutamate are supposed to keep each other in balance, but sometimes glutamate gets out of hand due to factors like diet, toxins, nutritional imbalances, microbes, or a genetic mutation. Glutamate may be converted into GABA or aspartate. Aspartate is also an excitatory neurotransmitter that can have a similar excitotoxic effect on the brain when in excess. People with epilepsy who respond best to a ketogenic diet are found to have higher levels of GABA in the central nervous system, thus suggesting that being in ketosis maintains a balance between GABA, glutamate, and aspartate. According to Dean, “lower glucose is associated with a higher seizure threshold and less neuronal excitability.”

In Autism: Pathways for Recovery, Dr. Amy Yasko explains that glutamate incites the release of insulin, which means insulin then decreases blood glucose. However, glucose is needed to moderate glutamate at the synapses, so when insulin brings it crashing down, glutamate levels will then increase even more. So this may explain why less glucose is correlated with fewer seizures and one of the reasons a ketogenic diet favors GABA production.

Additionally, a ketogenic diet has been shown to increase the GAD enzyme, needed to convert glutamate into GABA and neurons can use ketones as a precursor to GABA.

This means that other symptoms and conditions that are associated with excess glutamate like anxiety, panic disorders, insomnia, restless leg syndrome, OCD, attention deficit, hyperactivity, slurred speech, nervousness, ALS, fibromyalgia, depression, chronic pain syndromes, chronic migraines, aggressive behavior, autism and self-stimulatory behaviors like rocking, pacing, spinning, hand flapping or other repetitive body movements or movement of objects, may also benefit from a ketogenic diet for the same reasons.

Dean and others claim that ketones leave a lot less garbage in the mitochondria than glucose when burned, which means it is more efficient for cells to make energy from ketones than it is from glucose. If our energy supply is more efficient, then it enables our brain to prevent excess glutamate and increase GABA.

In Keto Clarity by Jimmy Moore and Dr. Eric Westman, they state that a study from 2014 in Nature magazine, “found that ketogenic dieting increased microbes of the genus Bacteroides and decreased Firmicutes.” The opposite is found in people with SIBO and related conditions like IBS and GERD, so that means it is beneficial for these conditions. The Firmicutes are the ones that prefer carbohydrates. Jimmy states the opposite is also associated with obesity and that “the microbial alterations induced by the ketogenic diets were associated with reduced levels of inflammation.”

Other studies cited in Keto Clarity have shown that the ketogenic diet improves many mental health issues including bipolar and schizophrenia. One of the other contributors to this book, neuroscientist Dr. Bryan Barksdale, points out that ketones have “neuroprotective properties”—they protect brain cells.

In my opinion, a ketogenic diet (or close to it – very low carb) is the best way to address low blood sugar, sugar and carb addiction, compulsive overeating, Candida overgrowth, SIBO, or other microbes, adrenal fatigue, alcohol and drug addiction, anxiety disorders, depression, and other mental health issues or excess sympathetic nervous system activity. Carbohydrates fuel each of these conditions by disrupting or overstimulating the endocrine system and/or the brain and feeding microbes. Running primarily on ketones restores balance. Cravings for sugar and carbs and other addictive substances simply disappear and blood sugar remains stable. Not only will you overcome cravings for sugar, carbs, caffeine, and other addictive substances and have more emotional stability, but you’ll also reduce your risk of all diet-related conditions, like heart disease, type 2 diabetes, cancer, etc., simultaneously. However, it is important to note that fat is a histamine releaser, so anyone with histamine intolerance or high histamine typically does not do well by going into ketosis, but stay just under with low-carb and more animal protein.

Paleo and Ketosis in Summary

It’s important to keep in mind that the reason that a state of ketosis is effective for so many disorders, is because it reverses the damage that is inflicted on the brain and the body by the consumption of sugar, carbs, grains, legumes, refined and processed foods, etc. Therefore, the ketogenic diet can be used to help prevent these conditions just as well as improving them, by keeping the damage from occurring in the first place. If more people were eating a low-carb Paleo diet, we could significantly reduce the incidence of all these conditions.

Please be aware that being on a Paleolithic diet does not mean you have to eat a ketogenic diet or be in ketosis, it all depends on how many carbohydrates you choose to consume and the goals you are trying to achieve. A Paleo diet generally should not be above 100 or 150 grams of carbs per day, (all of which should be derived primarily from low-starch vegetables and to a lesser extent from fruits and nuts.) So, as long as you are eating Paleo-approved foods and falling somewhere in that guideline, then that is considered Paleo. You could essentially eat a high-carb diet by eating lots of fruits, sweet potatoes, and yams and still technically be within Paleo guidelines,  but you would not be in ketosis. However, eating that many carbs would defeat one of the primary purposes and many goals cannot be achieved with that much carbohydrate consumption.

It is my opinion that 100 to 150 grams of carbs per day is too much for most people and that most of us are much better off staying between 60 and 70 grams per day (total not net), and many conditions respond best to somewhere between 20 and 50 grams (total) per day.

For conditions like anxiety, chronic stress, sympathetic dominance, sugar and carb addiction, lowering glutamate and increasing Gaba, adrenal fatigue, candida, high histamine, and SIBO, I think it is best not to strive for true ketosis, by keeping animal protein as the number one component of the diet instead of fat, but keeping the carb intake under 50 grams per day. Rich in animal protein, a moderate amount of fat, low carb – in that order. This way we are running mostly on ketones and fat and a little glucose, but we aren’t too high in fat which can be problematic for these conditions. But, each person can experiment with the fat, protein, and carb ratio and see what level works best for them. Some people do best by being in true ketosis.

References

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Dr. Amy Yasko, Autism: Pathways to Recovery. Neurological Research Institute, LLC 2004, 2007, 2009

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