What Your Organs Burn
Here's a question for you - do all cells and organs in your body use the same fuels? Specifically; if your diet consists of 20% protein, 30% fat, and 50% carbs, do all cells throughout the body use this identical fuel mix? The answer, of course, is "no" (because if it were "yes", why would we be asking this question?)
Some cells prefer fats for fuel, others prefer glucose, and some are so specialized that they prefer just one particular amino acid. So no matter what you eat, it seems that some types of cells would feel deprived unless the body had a way to divvy up energy sources among organs and cells and also had alternatives when necessary. As a result, the inter-organ exchange of fuel is both complex and dynamic. Here are a few simple tastes of the complexity and elegance of this system.
Muscle: When we say muscle, we typically mean the things that move our arms and legs, technically called skeletal muscles (which differ in form and function from the cardiac muscle in our heart and also from the third type of muscle (smooth) that lines blood vessels and our gastrointestinal tract). At rest, skeletal muscles prefer fat for fuel, using glucose only when insulin levels are high and blood sugar needs some place to go. During sustained exercise, fat is still the preferred fuel at intensities up to 50-60% of that muscle's maximum continuous effort. Above 60% of maximum effort, glucose (or stored glycogen) progressively assumes a dominant role, although this dominance is attenuated when individuals are given a few weeks to adapt to a low carbohydrate diet[23, 271. Also at these higher intensities, some of this glucose is not completely metabolized but is partially broken down to lactate and released back into the bloodstream rather than being oxidized in muscle mitochondria all the way to CO, and water. By contrast, during resistance exercise (very high intensity, brief duration), most of the fuel use consists of glucose made into lactate.
But here's the interesting part. Lactate has a had reputation as a cause of muscle fatigue and pain. This is a classic case of guilt by association. During transition from rest to intense exercise, the increased production of lactic acid rapidly disassociates into lactate and hydrogen ion. It is the accumulation of hydrogen ion, not lactate per se, that contributes to fatigue due to acidosis. Lactate has a much more interesting and positive role to play in the human body. Much of the lactate released from muscle during exercise gets taken up by the liver and made back into glucose (a process called gluconeogenesis) and sent back to the muscles where it can be made into lactate again. And because the liver uses mostly fat to power gluconeogenesis, this shuttle of glucose out from the liver and lactate back (called the Cori cycle) actually ends up powering resistance exercise from energy released by fat oxidation in the liver.
Heart: The predominant fuel preferred by your heart when you are not exercising is fat. The heart rarely uses much glucose, with the only exception being during a heart attack when a vessel is plugged and the oxygen supply to that part of the muscle is cut off or severely reduced. In that case, the small amount of glycogen in heart muscle is used anaerobically to make lactate. And here's one more bit of heresy about lactate. During exercise, a healthy and well-perfused heart actually takes up lactate from the circulation and burns it to CO2 and water. Lactate is preferred by heart muscle cells over glucose, and during endurance exercise, lactate can provide as much as 50% of your heart's energy need [28].
Liver: The liver does a whole lot of important things for the rest of the body, such as making, storing, and releasing glucose when necessary,making ketones when carbohydrate intake is restricted for more than a few days, collecting and secreting fats and lipids as lipoproteins, and making and secreting a number of important blood proteins. As a result, the liver uses a lot of energy for an organ its size, and most of the energy it uses comes from fat. The liver can get the fat it needs from circulating fatty acids released from fat cells, from remnant lipoproteins it removes from the circulation, or by making fat from carbohydrates (lipogenesis).
Brain: The brain is the spoiled child of the organ family. It can burn glucose or ketones (or a combination of the two) and it can't burn fat. This is interesting because the brain itself contains a lot of fatty acids in all its membranes and myelin (although little or none as triglycerides), and the many types of brain cells all contain mitochondria that should be capable of oxidizing fatty acids. Another surprise about the brain is how much energy it consumes each day (600 kcal) despite weighing just 3 pounds. This is more than 10-times the average energy use per pound of the rest of the body, which explains why the brain has such a large blood supply (to provide fuel and oxygen and also to keep it cool).
The other important fact about the brain's fuel supply is that it contains no reserve supply of glycogen, and because it can't burn fat, it is absolutely dependent upon a minute-by-minute blood supply containing both fuel and oxygen to meet its needs. This is why even a transient drop in blood sugar causes an intense physiological response (increased heart rate, shaking, anxiety, and intense hunger/cravings). And if blood sugar suddenly drops to less than half of the lower limit of normal, it causes coma. The shaking, anxiety, and fast heart rate that occur when blood glucose levels fall are due to a dramatic increase in adrenergic nervous system activity (release of nor-adrenaline from nerve endings) and adrenaline from the adrenal glands. Among other effects, this acute response to hypoglycemia stimulates two processes in liver: the breakdown of any glycogen present and formation of glucose from anything available (lactate or amino acids from protein).
Understanding this combination of facts helps explain why rapid weight loss diets, especially those emphasizing carbohydrates, can be tough to follow. If for example you decide to eat 1200 kcal per day, composed of 25% protein (75 grams), 25 % fat, and 50% carbohydrate, your daily carb intake totals just 600 kcal. That's more than enough to prevent your liver from making ketones, but it's just barely enough to feed your brain. But, you say, your liver can also make glucose from some of the protein via gluconeogenesis, which is correct, but that totals less than 50 grams (200 kcal) per day. Still, this 1200 kcal diet should support your brain's fuel needs just fine.
But what happens if you decide to go jog 5 miles in 50 minutes (which consumes 100 kcal per mile). Even at this relatively slow pace of 6 miles per hour, about half of your muscle fuel use will come from glucose or glycogen, so you burn about 250 kcal of carbohydrate fuel. In this scenario, in the 24-hours that includes this exercise, the 600 + 250 kcal of glucose use exceed the 600 + 200 kcal available supply. Typically in this setting, people start to feel lousy (see "bonking" below). Your body can make up the difference by drawing down its limited glycogen reserves or by the net breakdown of some muscle to increase liver gluconeogenesis. But if you stick to the diet and continue the daily exercise, something's got to give. And what typically happens is that your instincts (only a masochist likes to feel bad day after day) get the upper hand over your best intentions, prompting you to either eat more or exercise less.
In this situation, it would be convenient if this fuel conundrum could be solved by your liver making some ketones from body fat to help fill the gap in the brain's fuel supply. However, this appears to be a flaw in human design because liver ketone production does not kick in until daily carbohydrate intake is consistently at or under 50 grams (200 kcal) per day for a number of days. Thus there appears to be a functional gap in the body's fuel homeostasis when dietary carbohydrate intake is consistently somewhere between 600 and 200 kcal per day.
So let's consider an alternative diet, say 1200 kcal consisting of 30% protein, 15% carbs (i.e., 180 kcal or 45 grams), and 55% fat. After a week or two of getting adapted (during which you may experience some of the fuel limitation symptoms discussed above), your serum ketones rise up in the range (1-2 millimolar) where they meet at least half of the brain's fuel supply. Now if you go for that 5 mile run, almost all of your body's muscle fuel comes from fat, leaving your dietary carb intake plus gluconeogenesis
from protein to meet the minor fraction of your brain's energy need not provided from ketones. And, oh yes, after your run while on the low carb diet, your ketone levels actually go up a bit (not dangerously so), further improving fuel flow to your brain.
So what does this mean for the rest of us who are not compulsive runners? Well, this illustrates that the keto-adapted state allows your body more flexibility in meeting its critical organ energy needs than a 'balanced' but energy-restricted diet. And in particular, this also means that your brain is a "carbohydrate dependent organ" (as claimed by the USDA Dietary Guidelines Advisory Committee as noted in Chapter 3) ONLY when you are eating a high carbohydrate diet. When carbohydrate is restricted as in the example above, your body's appropriate production of ketones frees the brain from this supposed state of 'carbohydrate dependency' And because exercise stimulates ketone production, your brain's fuel supply is better supported during and after intense exercise when on a low carbo-hydrate diet than when your carbohydrate intake is high