From Jeff Volek PhD and Dr Stephen Phinney MD’s book, The Art and Science of Low Carbohydrate Living, we read,
“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 noradrenaline 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.
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) 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 carbohydrate diet than when your carbohydrate intake is high.”