Metabolism and Ketosis, from Michael Eades, M.D.
Since posting the piece on ketone bodies and their causing breathalyzer problems I’ve had enough comments and emails to make me realize that there are probably many people unsure of what ketones really are, where they come from and why. Let’s take a look at the goals and priorities of our metabolic system to see what happens. Fear not, I’m going to try to keep the biochemistry to a minimum.
The primary goal of our metabolic system is to provide fuels in the amounts needed at the times needed to keep us alive and functioning. As long as we’ve got plenty of food, the metabolic systems busies itself with allocating it to the right places and storing what’s left over. In a society such as ours, there is usually too much food so the metabolic system has to deal with it in amounts and configurations that it wasn’t really designed to handle, leading to all kinds of problems. But that’s a story for another day.
If you read any medical school biochemistry textbook, you’ll find a section devoted to what happens metabolically during starvation. If you read these sections with a knowing eye, you’ll realize that everything discussed as happening during starvation happens during carbohydrate restriction as well. There have been a few papers published recently showing the same thing: the metabolism of carb restriction = the metabolism of starvation. I would maintain, however, based on my study of the Paleolithic diet, that starvation and carb restriction are simply the polar ends of a continuum, and that carb restriction was the norm for most of our existence as upright walking beings on this planet, making the metabolism of what biochemistry textbook authors call starvation the ‘normal’ metabolism.
So, bearing in mind that carb restriction and starvation are opposite ends of the same stick and that what applies to one applies to the other, let’s look at how it all works. I’ll explain it from a starvation perspective, but all the mechanisms work the same for a carb-restricted diet.
During starvation the primary goal of the metabolic system is to provide enough glucose to the brain and other tissues (the red blood cells, certain kidney cells, and others) that absolutely require glucose to function. Which makes sense if you think about it. You’re a Paleolithic man or woman, you’re starving, you’ve got to find food, you need a brain, red blood cells, etc. to do it. You’ve got to be alert, quick on your feet, and not focused on how hungry you are.
If you’re not eating or if you’re on a low-carbohydrate diet, where does this glucose come from?
If you’re starving, glucose comes mainly from one place, and that is from the body’s protein reservoir: muscle. A little can come from stored fat, but not from the fatty acids themselves. Although glucose can be converted to fat, the reaction can’t go the other way. Fat is stored as a triglyceride, which is three fatty acids hooked on to a glycerol molecule. The glycerol molecule is a three-carbon structure that, when freed from the attached fatty acids, can combine with another glycerol molecule to make glucose. Thus a starving person can get a little glucose from the fat that is released from the fat cells, but not nearly enough. The lion’s share has to come from muscle that breaks down into amino acids, several of which can be converted by the liver into glucose. (There are a few other minor sources of glucose conversion: the Cori cycle, for example, but these are not major sources, so we’ll leave them for another, more technical, discussion.)
But the breakdown of muscle creates another problem, namely, that (in Paleolithic times and before) survival was dependent upon our being able to hunt down other animals and/or forage for plant foods. It makes it tough to do this if a lot of muscle is being converted into glucose and your muscle mass is dwindling.
The metabolic system is then presented with two problems: 1) getting glucose for the glucose-dependent tissues; and 2) maintaining as much muscle mass as possible to allow hunting and foraging to continue.
Early on, the metabolic system doesn’t know that the starvation is going to go on for a day or for a week or two weeks. At first it plunders the muscle to get its sugar. And remember from a past post that a normal blood sugar represents only about a teaspoon of sugar dissolved in the entire blood volume, so keeping the blood sugar normal for a day or so doesn’t require a whole lot of muscular sacrifice. If we figure that an average person requires about 200 grams of sugar per day to meet all the needs of the glucose-dependent tissues, we’re looking at maybe a third of a pound of muscle per day, which isn’t all that big a deal over the first day. But we wouldn’t want it to continue at that rate. If we could reduce that amount and allow our muscle mass to last as long as possible, it would be a big help.
The metabolic system could solve its problem by a coming up with a way to reduce the glucose-dependent tissues’ need for glucose so that the protein could be spared as long as possible.
Ketones to the rescue.
The liver requires energy to convert the protein to glucose. The energy comes from fat. As the liver breaks down the fat to release its energy to power gluconeogenesis, the conversion of protein to sugar, it produces ketones as a byproduct. And what a byproduct they are.
Ketones are basically water soluble (meaning they dissolve in blood) fats that are a source of energy for many tissues including the muscles, brain and heart. In fact, ketones act as a stand in for sugar in the brain. Although ketones can’t totally replace all the sugar required by the brain, they can replace a pretty good chunk of it. By reducing the body’s need for sugar, less protein is required, allowing the muscle mass (the protein reservoir) to last a lot longer before it is depleted. And ketones are the preferred fuel for the heart, making that organ operate at about 28 percent greater efficiency.
Fat is the perfect fuel. Part of it provides energy to the liver so that the liver can convert protein to glucose. The unusable part of the fat then converts to ketones, which reduce the need for glucose and spare the muscle in the process.
If, instead of starving, you’re following a low-carb diet, it gets even better. The protein you eat is converted to glucose instead of the protein in your muscles. If you keep the carbs low enough so that the liver still has to make some sugar, then you will be in fat-burning mode while maintaining your muscle mass, the best of all worlds. How low is low enough? Well, when the ketosis process is humming along nicely and the brain and other tissues have converted to ketones for fuel, the requirement for glucose drops to about 120-130 gm per day. If you keep your carbs below that at, say, 60 grams per day, you’re liver will have to produce at least 60-70 grams of glucose to make up the deficit, so you will generate ketones that entire time.
So, on a low-carb diet you can feast and starve all at the same time. Is it any wonder it’s so effective for weight loss?