Our Kids Are in Ketosis

Some time ago, I published an article on Medium titled “Our Kids Are In Ketosis”. The article turned many heads and has been shared thousands of times on social media. It has also been cited by an MD in a YouTube video here. So what is the fuss about?

Various ways of eating are labelled as “diet fads” by many people, including many doctors, scientists, and nutritionists. A fad is defined as “an intense and widely shared enthusiasm for something, especially one that is short-lived and without basis in the object’s qualities; a craze” (Google dictionary). Some diets should be labelled fads because it is impossible to maintain them long term. Fruitarian, for example, is one such fad; it is impossible to maintain safely long-term by humans, primarily because one may die from starvation, pancreatic cancer, or as a result of insufficient nutrients in a diet that contains only fruits. In addition to the demand that is placed on the use of insulin to remove the glucose oversupply from the blood, fruitarian diets lack essential amino acids and essential fatty acids for survival.

Some may suggest that the Standard American Diet (SAD), also referred to as the Western Diet, is a fad. The majority of the US population consumes the SAD diet with dire outcome: heart disease, obesity, type 2 diabetes, non-alcoholic fatty liver disease, cancer, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, nearly all (if not all) autoimmune diseases, and a host of other non-communicable diseases are outcomes of the SAD diet. While on a human life scale we may think of the SAD diet as sustainable, it clearly is not. It has been on the menu for over 50 years, and it feels awkward calling it a fad, even though it most certainly meets “without basis in the object’s qualities”.

“Let food be thy medicine, and let medicine be thy food”

This wise sentence is attributed to Hippocrates. As ancient as this statement is, it still holds true today—if only we followed its wisdom. I am a follower of another Hippocrates saying with a slight modification: “You are not what you eat but how you metabolize what you have eaten!” You will find this sentence as my intro (mission statement) on my FB page. The distinction between what we eat and how we metabolize what we have eaten is essential; it defines who we are.

Understanding Diet and Nutrition

In order to understand how nutrition affects us and what we should be eating, much needs to be understood about the human digestive and metabolic systems. While there is a lot of discussion about the importance of carbohydrates in our diet today—particularly consuming many servings of complex carbohydrates, such as whole grains, starchy vegetables, and fruits daily—this was not always our understanding. For example, when I grew up, carbohydrates were understood to cause obesity(1). Most of my childhood was spent on a relatively low carbohydrate diet—and that was normal for Europe at that time. Cereals—whole grain or otherwise—didn’t exist, neither was I growing up drinking orange juice and eating pancakes with syrup in the morning. In those years, the role of carbohydrates in metabolic disease was clearly understood—and metabolic disease was very rare.

I grew up eating lots of animal meat: pork, bacon, beef, eggs, poultry—including duck and geese—and organ meats, including liver, kidneys, bone marrow, heart, gizzards, pork ears, snouts, hoof, chicken feet, even chicken blood, pork and beef blood in sausages, such as blood sausage—still sold in many places—cooked in pork lard, duck fat butter, or beef tallow, and lots of fatty fish. We also ate a lot of dairy, including milk and cheeses plus all other dairy forms. We had various dairy and cultured milks as well. Of course, we drank milk that could be placed in the window for a day and by next day it was kefir without any added culture and without rotting. Our staples were potatoes, beans, rice, onions, and apples that lasted through February in cold storage. Other fruits and vegetables were all only seasonal, lasting a very short time.

We didn’t have processed foods and processed oils of any kind. While some canned foods and sweetened drinks certainly existed, those were seldom consumed. There was no such as daily dessert. If I was a good girl, maybe once a month I was taken to special pastry places and I could pick one dessert. If you think my family was poor and hence I was eating this way, you are wrong. I was a privileged child. I spent several of my childhood summers in the South of France eating more seafood, but basically the same exact diet. The European diet, when I grew up, was a very cholesterol rich fat-heavy low carbohydrate diet.

It is important to note that while cholesterol levels have been consistently dropping over the past several decades(2)—as a result of the recommended SAD diet full of vegetable oils—the rates of cardiovascular and metabolic diseases have been increasing over the same period, indicating a possible inverse relationship. This is promptly ignored by medicine and there is a continual push toward the consumption of lower cholesterol foods, such as whole grains, fruits and vegetables, and vegetable oils. This, in spite of several studies showing the above mentioned inverse relationship, suggesting that higher cholesterol extends healthy lifespan(3,4). The reason I mention cholesterol is because a reduced carbohydrate diet, such as the one I grew up on, is necessarily a heavy saturated fat and cholesterol diet.

Yet, during those years in Europe, metabolic diseases (such as non-alcoholic fatty liver, cardiovascular disease (CVD), stroke, type 2 diabetes, etc.,) were rare. This article shows the confusion. In it, they discuss the rates of CVD, which was very low in France at the time, to be caused by a “lag”. The assumption being that the heavy saturated fat-filled foods will catch up with the French and they will eventually develop CVD. Interestingly, the French ate heavy saturated fat for centuries before this study, so the catching up is a silly theory aiming to explain the French Paradox. And the catching up is still going on without any success—though now that American junk food is available to the French, it may be only a matter of time.

Ketosis

When one consumes a low carbohydrate high fat diet, even with high protein and some beans time to time, the person will be in a state of ketosis. In ketosis, the body can use both glucose and fat (both consumed and stored fat) as its fuel. Fat is converted to ketones, or β-Hydroxybutyrate (BHB). This state is reached by diets rich in animal fats, medium amounts of protein, and little or no carbohydrates. Rather than hindering health, ketosis supports and protects it (5), as it can be seen in the treatment of epilepsy(6). Ketosis is the basic human metabolic process. This is further discussed later.

Carbohydrates Versus Fats

When some time ago I bumped into the book Metabolic regulation: A Human Perspective by Keith N. Frayn (3rd edition), in chapter 2.1 and 2.2 I came to two very unusual sections that made me jump up.

The chapter section states the following:

“…fatty acids are usually a preferred fuel (over glucose) for skeletal muscle… Fatty acid release is very effectively switched off by insulin, so muscles no longer have the option of using fatty acids… The characteristics of individual cells or tissues ‘set the scene’ for metabolic regulation. For instance, the metabolic characteristics of the liver mean that it will inevitably be able to take up excess glucose from plasma, whereas other tissues cannot adjust their rates of utilization so readily… The brain, in contrast, has a pathway for utilizing glucose at a rate that is relatively constant whatever the utilizing glucose concentration, a very reasonable adaptation since we would not want to be super-intelligent only after eating carbohydrate, and intellectually challenged between meals.”

I was surprised. In all literature that advises healthy nutrition, we are told to consume a ton of carbohydrates. The USDA Dietary Guidelines recommend My Plate (what used to be the food pyramid, see the history of the USDA guidelines here), which is mostly carbohydrates, with a little bit of meat or fish, eggs, dairy, and some oil on top. Basically most of the diet—over 60 percent—is supposed to come from carbohydrates, such as whole grains, fresh fruits, vegetables, nuts, and seeds. Those are all carbs. The paragraph from the book was intriguing to me, because it tells us that we don’t need to eat carbs, contrary to USDA dietary recommendations.

Skeletal muscles actually prefer to use fat rather than glucose! We have a very carbohydrate-centric view of nutrition today, much more so than when I grew up, yet our muscles and some other organs too, such as the heart(7,8), actually prefer fat as fuel and not glucose! Why are we eating so many carbohydrates?

The Fuels of Our Body

Few professionals, even within the field of nutrition, realize that glucose is not our primary fuel and ketones are not our backup fuel. The human body has no primary or backup fuel: it has three fuels. Some of these fuels are toxic if they stay in the blood too long in larger amounts than needed, and so the body must remove them fast. I presume that the urgency for glucose use—meaning the urgency for the removal of glucose from the blood—is misleading and makes people think that if the body switches to using glucose the moment it is provided, it must be its primary fuel; but this is incorrect assumption. This suggests that the first task that has to be done is the preferred task, but this is seldom the case. For example, assume you trip on your way to a dinner party, hit your head into the cement, and now see double. Although your urgent task now is to head to emergency to see if you received a concussion or other serious damage, the emergency visit is not your preferred task. It just suddenly became a priority you need to tend to immediately before you join the dinner party.

It is true that when we eat carbohydrates, the body must stop everything and remove the excess glucose from the blood. The maximum comfort level for glucose in the blood is 99 mg/dL (5.5 mmol/L) and if we eat carbohydrates in such amounts that this is exceeded, it is literally an emergency and the body must remove the excess glucose. For reference, 99 mg/dL is one teaspoon of glucose in the entire 5 liters of blood. Extra glucose in the blood is toxic. However, having to remove glucose immediately does not make it into the primary fuel.

The three fuels our body can use are: alcohol, providing 7 kcal per gram, glucose, providing 4 kcal per gram, and fat, providing 9 kcal per gram. While alcohol is a viable fuel for the human body, it creates many adverse effects, causing damage, so it is not recommended to be used as fuel, though alcoholics often use it as such. Given that alcohol is the most dangerous of all the fuels(9), if our body is provided the three fuels simultaneously, alcohol will be burned first. Yet we don’t ever assume that alcohol is our primary fuel.

How the Body Prioritizes Fuels

Priority can be assigned for many reasons. One can give priority to something preferred, but if this means that something harmful has to wait to be removed, there is a risk of disease. If this was the method our body chose for prioritization, we may not have remained alive long enough to become who we are today. One can prioritize by the amount of energy each fuel gives, using up first the one that gives the most energy, and saving the rest for later. But, again, if the rest causes damage while waiting to be used, then this has to be avoided. One can also prioritize based on the removal of toxic fuel first and save the least toxic fuel to be used last.

If our body prioritizes based on preventing damage by burning the fuel in order of toxicity, then the order would be:

Alcohol Glucose Fat

If priority would be given to those fuels that provide the most energy, the order would be:

Fat Alcohol Glucose

If the priority is based on the USDA dietary guidelines, then the order would be (alcohol as fuel is usually not mentioned anywhere):

Glucose Fat

What we actually see happening is that the body burns fuel in the order of which it causes the most damage in the blood. The most dangerous fuel in the blood is alcohol. Its side effects can even be fatal, so clearing that from the body is necessarily task #1.

The urgency with which we must respond to the situation is dependent upon its outcome.

Glucose is the second most dangerous fuel in the human body after alcohol. Fructose, a sugar that is part of table sugar, honey, and most fruits, turns into ethanol (an alcohol) causing damage, and glucose—referred to as blood sugar—is toxic to our nerves, may cause eye damage and type 2 diabetes, and cardiovascular disease (including stroke) as well.

By contrast, fat is a safe fuel to the point that it is usually stored in our body—something many of us wish to have less of. It is not a toxic substance and at 9 kcal per gram, it provides the most energy. Alcohol inhibits the burning of glucose and fats, making it the mandatory first fuel to burn. So the actual order of fuel priority is:

Alcohol Glucose Fat

So why was I so surprised reading that some organs prefer to use fat for fuel? We read and hear so much about carbohydrates as the most important fuel, the kinds of carbohydrates we should be eating, and how much. We can learn very little about the other important fuels: alcohol and fats. Yet, as the surprising paragraph suggests above, often the other fuels are more important. In particular, if we look at the human lifespan, other fuel needs become stunningly obvious. I think we have forgotten that babies are born in ketosis and their primary fuel is ketones.

Human Fuel from Conception

Indeed, babies are born in ketosis(10) and mother’s milk is low in carbohydrate and high in fat (LCHF), which keeps the newborn in ketosis all through nursing. Breast milk contains more glucose across time, as the child matures. At full maturation (about one month), its nutritional content per cup (8 oz) is 10.8 gr fat, 2.53 gr protein, 16.9 gr carbohydrates (in the form of lactose) and total energy of 174.92 kcal. It also contains 87.5 gr water. Subtracting the water and looking at the macronutrient ratios only, this glass of mature nursing milk is 55.57% fat, 5.79% protein, and 38.65% carbohydrates (in lactose, so not free sugar). In terms of fatty acid composition: 4.942 gr saturated fat, 4.079 gr monounsaturated fat, and 1.223 gr polyunsaturated fat, which in percentages: 48.24% saturated fat, 39.82% monounsaturated fat, and 11.94% polyunsaturated fat. One must agree that babies are not fed poison by their mothers and that Nature didn’t provide toxic nursing milk such. In fact, we can see that babies grow very rapidly while nursing milk and we know from studies that babies who are nursed, have a better chance for survival, grow healthier, faster, and their brain develops better (see here and here).

As babies grow, they retain metabolic flexibility, meaning they stay in ketosis for periods time, which changes by age and how often they are fed, and they do enter the carbohydrate metabolic process as they eat(10-12).

The below figure is very telling. On the vertical axis you find β-hydroxybutyrate [BHB], which is the level of ketones measured in blood, and on the horizontal axis, time passing in hours and days between feeding times. The graph inside contains people of all age groups and both genders. Officially, a fed person (with carbohydrate containing food) has zero amount of BHB in her/his blood. As time passes, and if the person fasts for a blood test or a medical procedure, slowly BHB increases in the blood. The clinically accepted level of BHB in the blood that is not considered ketosis is 0.3 mmol/L, which can easily be reached by healthy individuals as a result of such fasting. Anything above 0.3 mmol/L and chronically maintained 0.3 mmol/L means the person is in ketosis.

From Annu. Rev. Nutr. 2006. 26:1–22; doi: 10.1146/annurev.nutr.26.061505.111258

Figure 1. George F. Cahill Jr. showing time passing without food and ketosis level by age and gender

Note that babies are born with 0.5 mmol/L or higher level of BHB and remain in ketosis until they are fed, which immediately after birth cannot happen since the mother has no milk yet—this means the baby remains in ketosis until the time comes that milk is released by the breast of the mom. It is suggested that the baby is in ketosis because it is not being fed(10), meaning starvation, but this is questionable, since babies remain in ketosis even after being fed—more on this later. The human brain uses 20% of the energy the body generates. In the case of infants, the need for energy arises very quickly, as shown in Figure 1, approximately in 20 minutes. There are other factors as well, such as the brain is over 80% fat and cholesterol(13), with the cholesterol alone representing 20-25% of the total cholesterol of the body (here).

Thus ketosis, in one scenario, is a state into which our metabolism reverts to when food is not immediately available on demand (starvation). On the other hand, studies on the fetus in utero show that the fetus is in ketosis even though it is never under nutritional duress(14,15) and there are ketones in the placenta(16) as well. Therefore, it is very difficult to suggest that ketones are a backup fuel used only in starvation if the fetus is in ketosis time to time even without starvation. Clearly, being in ketosis provides some benefits that are not possible to achieve using the glucose metabolic process. I venture to suggest that the ketogenic and the glucogenic metabolic processes have distinct functions, each to benefit us on its own way.

Concluding Thoughts

To conclude the importance of ketosis, let me offer some anecdotal evidence. In the Facebook migraine groups I manage (see here and here), all migraineurs are asked to run a special blood glucose/blood ketone test that starts with fasting and premeal tests and continues for 5 hours postprandial. There are many children with migraines whose parents are in the groups—the children are from ages 2-18, so for them parental help is required. Thus, over time, I have had the opportunity to evaluate the 5-hour blood test results of children of all ages—I think the youngest was 5 years old and the oldest 16, so far. I have yet to see a blood ketone test of a child anywhere in this age group that is not showing ketosis both before and after a meal—even if the meal has fruits and dairy in it.

I suppose ignorance is bliss. Few doctors or researchers have the same opportunity I have in being able to measure the blood ketones of various ages of children for five hours postprandial plus fasting and premeal measures, therefore, most don’t realize just how much our kids are in ketosis.

Thus, while today in most countries around the world any type of food is just a short walk/drive away 24/7, and we need not experience hunger and starvation, our children are still in ketosis 24/7. Shouldn’t that tell us something about the importance of ketosis?

References

Dawkins, M. Carbohydrates and Adiposity. British medical journal 1, 719-720, doi:10.1136/bmj.1.5385.719 (1964). Farzadfar, F. et al. National, regional, and global trends in serum total cholesterol since 1980: systematic analysis of health examination surveys and epidemiological studies with 321 country-years and 3.0 million participants. The Lancet 377, 578-586, doi:10.1016/S0140-6736(10)62038-7 (2011). Ravnskov, U. High cholesterol may protect against infections and atherosclerosis. QJM: An International Journal of Medicine 96, 927-934, doi:10.1093/qjmed/hcg150 (2003). Kaysen, G. A. et al. Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results. Journal of lipid research 59, 1519-1528, doi:10.1194/jlr.P084277 (2018). DuBroff, R. & de Lorgeril, M. Fat or fiction: the diet-heart hypothesis. BMJ Evidence-Based Medicine, bmjebm-2019-111180, doi:10.1136/bmjebm-2019-111180 (2019). Berghoff, S. A. et al. Dietary cholesterol promotes repair of demyelinated lesions in the adult brain. Nature communications 8, 14241-14241, doi:10.1038/ncomms14241 (2017). Park, T.S., Yamashita, H., Blaner, W. S. & Goldberg, I. J. Lipids in the heart: a source of fuel and a source of toxins. Current Opinion in Lipidology 18, 277-282, doi:10.1097/MOL.0b013e32814a57db (2007). Noh, H.-L., Yamashita, H. & Goldberg, I. J. Cardiac Metabolism and Mechanics are Altered by Genetic Loss of Lipoprotein Triglyceride Lipolysis. Cardiovascular Drugs and Therapy 20, 441-444, doi:10.1007/s10557-006-0633-1 (2006). Van de Wiel, A. Diabetes mellitus and alcohol. Diabetes/Metabolism Research and Reviews 20, 263-267, doi:10.1002/dmrr.492 (2004). Cahill, G. F. Starvation in man. N Engl J Med 282, doi:10.1056/nejm197003052821026 (1970). Storlien, L., Oakes, N. D. & Kelley, D. E. Metabolic flexibility. Proceedings of the Nutrition Society 63, 363-368, doi:10.1079/PNS2004349 (2007). George F. Cahill, J. Fuel Metabolism in Starvation. Annual Review of Nutrition 26, 1-22, doi:10.1146/annurev.nutr.26.061505.111258 (2006). Chang, C. K., DS; Chen, JY;. Essential fatty acids and human brain. Acta Neurologica Taiwanica 18, 10 (2009). Herrera, E. & Amusquivar, E. Lipid metabolism in the fetus and the newborn. Diabetes/Metabolism Research and Reviews 16, 202-210, doi:doi:10.1002/1520-7560(200005/06)16:3<202::AID-DMRR116>3.0.CO;2-# (2000). Herrera, E. Lipid metabolism in pregnancy and its consequences in the fetus and newborn. Endocrine 19, 43-55, doi:10.1385/endo:19:1:43 (2002). Orczyk-Pawilowicz, M. et al. Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy. PloS one 11, e0152740-e0152740, doi:10.1371/journal.pone.0152740 (2016).

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