Some time ago, I was reading the book Metabolic regulation: A Human Perspective by Keith N. Frayn (3rd edition) and in chapter 2.1 and 2.2 I came to a very unusual section that made me jump. It 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 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.”
This was revolutionary to me. Skeletal muscles actually prefer to use fat rather than glucose? We have a very carbohydrate-centric view of nutrition, yet our muscles and some other organs too, may prefer fat to glucose as fuel, and also the brain has no problems switching to ketones.
Ketones are not Backup & Glucose is not Primary
Few professionals, even within the field of nutrition, realize that ketones are not our backup fuel. Ketones are not any more backup than glucose is the primary fuel. The human body has no primary or backup fuel: it has two fuels. I presume that the urgency for glucose use — meaning the urgent 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 a mistaken argument, which assumes that the first task that has to be done is the preferred task. It is true that when we add glucose to our blood by, for example, eating carbohydrates, the body must immediately switch to remove that 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 such that this is exceeded, it is literally an emergency and the body must remove it from there. Too much glucose in the blood for extended time is toxic. However, having to remove glucose immediately does not make it into the primary fuel, it just makes it into an urgent task.
As an example, assume you need to go to the dentist because you have a huge toothache. While you most certainly would much rather go to a dinner with family and friends or some party or a game, than to the dentist, you must go to the dentist first. This doesn’t mean that you prefer the dentist. It merely means the urgency with which we must respond to the situation is dependent upon its outcome. The same is true with blood glucose. Glucose is not the preferred fuel, but it must urgently be removed, else it can have dire consequences.
Working to get Into Ketosis?
We can see that glucose is not the primary fuel because babies are born in ketosis(1) and mother’s milk is low carbs high fat (LCHF), which keeps the newborn in ketosis all through nursing. Milk gets more glucose as it matures, and at full maturation, its nutritional content per cup (8 oz) is 10.77 gr fat, 2.53 gr protein, 16.95 gr carbohydrates (in the form of lactose) and total energy of 172 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 55.5% fat, 5.57% protein, and 38.71% 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(2). One must agree that babies are not fed poison by their mothers and that Nature didn’t provide nursing milk such that it is toxic. In fact, we can see that babies grow very rapidly by 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.
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 may temporarily enter the carbohydrate metabolic process when they eat(1,3,4).
Figure 1. George F. Cahill Jr. showing time passing without food and ketosis level by age and gender
The above 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 is passing in hours and days between feeding times. The graph contains people of all age groups and both genders. Officially, a fed person (with carbohydrate containing food) has 0 amount of BHB in her/his blood. As time passes, say the person fasts for a blood test or a medical procedure, BHB starts showing up in the blood. The clinically accepted level of BHB in the blood that is not considered to be ketosis is up to 0.3 mmol/L, which can easily be reached by healthy individuals as a result of such fasting. Anything above 0.3 mmol/L, or 0.3 mmol/L continuously, is considered to be ketosis.
Note that babies are born with 0.5 mmol/L or higher level of BHB and remain in ketosis until they are fed. In the case of infants, the needs for energy arises very quickly, as shown in Figure 1, and in approximately 20 minutes after feeding the baby is back in ketosis.
Thus ketosis, in one scenario, is a state into which our metabolism reverts to when food is not immediately available on demand — this is labeled “starvation”. However, studies on the fetus in utero show that the fetus, which is never under nutritional duress, is also in ketosis time to time(5,6) and there are ketones in the placenta(7). Therefore, it is very difficult to suggest that ketones are a backup fuel of any kind if even the fetus is in ketosis time to time in the womb. Clearly, being in ketosis provides some benefits that are not possible to achieve using the glucose metabolic process. The ketogenic and the glucogenic metabolic processes have distinct functions, each specialized to benefit us in some way.
Concluding with an Example
To conclude the importance of ketosis, an anecdotal evidence suffices. In my Facebook migraine group migraineurs all are asked to run a special blood glucose and blood ketone test that lasts for 5 hours postprandial. There are many children with migraines whose parents are in the group — the children from 2–18 years of age, so parental help is required. In addition, children of migraineur moms that may or may not have migraines are also often tested by the mothers. Thus, over time, I have had the opportunity to evaluate the 5-hour test results of children of all ages. I have yet to see a blood ketone test of a child that doesn’t show ketosis both before and after a meal — even if the meal had fruits and dairy in it. I suppose few people have the same opportunity as I have in being able to measure the blood ketones of various ages of children for five hours postprandial plus fasting and pre-meal measures. And so ignorance is bliss…
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?
1 Cahill, G. F. Starvation in man. N Engl J Med 282, doi:10.1056/nejm197003052821026 (1970).
2 USDA. National Nutrient Database for Standard Reference Release 26. ( https://fdc.nal.usda.gov/fdc-app.html#/food-details/171279/nutrients).
3 Storlien, L., Oakes, N. D. & Kelley, D. E. Metabolic flexibility. Proceedings of the Nutrition Society 63, 363–368, doi:10.1079/PNS2004349 (2007).
4 George F. Cahill, J. Fuel Metabolism in Starvation. Annual Review of Nutrition 26, 1–22, doi:10.1146/annurev.nutr.26.061505.111258 (2006).
5 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).
6 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).
7 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).