At the same time that FFA and ketone use is increasing, the body’s use of glucose and protein are going down. This is a critical adaptation for two reasons. First and foremost, there are tissues in the body which can not use FFA for fuel, requiring glucose. By decreasing their use of glucose, those tissues which do not require glucose for energy spare what little is available for the tissue which do require it. Thus, there is always a small requirement for glucose under any condition. As we shall see, this small glucose requirement can easily be met without the consumption of carbohydrates.
The second reason is that a reduction in protein losses is critical to survival during total starvation. The loss of too much muscle tissue will eventually cause death (6). From a fat loss standpoint, the ‘protein sparing’ effect of ketosis is also important to prevent lean body mass losses.
To examine the adaptations to ketosis in terms of glucose and protein, we first need to discuss which tissues do and do not require glucose. Then the adaptations which occur during starvation, in terms of the conservation of glucose, can be examined.
Which tissues use glucose?
All tissues in the body have the capacity to use glucose. With the exception of the brain and a few other tissues (leukocytes, bone marrow, erythrocytes), all tissues in the body can use FFA or ketones for fuel when carbohydrate is not available (5,23).
Under normal dietary conditions, glucose is the standard fuel for the brain and central nervous system (CNS) (24,25). The CNS and brain are the largest consumers of glucose on a daily basis, requiring roughly 104 grams of glucose per day (5,25).
This peculiarity of brain metabolism has led to probably the most important misconception regarding the ketogenic diet. A commonly heard statement is that the brain can only use glucose for fuel but this is only conditionally true. It has been known for over 30 years that, once ketosis has been established for a few days, the brain will derive more and more of its fuel requirements from ketones, finally deriving over half of its energy needs from ketones with the remainder coming from glucose (6,26,27).
As a few tissues do continue to use glucose for fuel, and since the brain’s glucose requirement never drops to zero, there will still be a small glucose requirement on a ketogenic diet.
This raises the question of how much glucose is required by the body and whether or not this amount can be provided on a diet completely devoid of carbohydrate.
How much carbohydrate per day is needed to sustain the body?
When carbohydrate is removed from the diet, the body undergoes at least three major adaptations to conserve what little glucose and protein it does have (5). The primary adaptation is an overall shift in fuel utilization from glucose to FFA in most tissues, as discussed in the previous section (5,6). This shift spares what little glucose is available to fuel the brain.
The second adaptation occurs in the leukocytes, erythrocytes and bone marrow which continue to use glucose (6). To prevent a depletion of available glucose stores, these tissues break down glucose partially to lactate and pyruvate which go to the liver and are recycled back to glucose again (5,6). Thus there is no net loss of glucose in the body from these tissues and they can be ignored in terms of the body’s carbohydrate requirements.
The third, and probably the most important, adaptation, occurs in the brain, which shifts from using solely carbohydrate for fuel to deriving up to 75% of its energy requirements from ketones by the third week of sustained ketosis. (5,6,26) As the brain is the only tissue that continues to deplete glucose in the body, it is all we need concern ourselves with in terms of daily carbohydrate requirements.
The brain’s glucose requirements
In a non-ketotic state, the brain utilizes roughly 100 grams of glucose per day (5,25). This means that any diet which contains less than 100 grams of carbohydrate per day will induce ketosis, the depth of which will depend on how many carbohydrates are consumed (i.e. less carbohydrates will mean deeper ketosis). During the initial stages of ketosis, any carbohydrate intake below 100 grams will induce ketosis (28). As the brain adapts to using ketones for fuel and the body’s glucose requirements decrease, less carbohydrate must be consumed if ketosis is to be maintained.
The question which requires an answer is this: What sources of glucose does the body have other than the ingestion of dietary carbohydrate? Put differently, assuming zero dietary carbohydrate intake, can the body produce enough glucose to sustain itself?
Please note that the following discussion is only truly relevant to individuals on a Standard Ketogenic Diet (SKD) who are not exercising. However the same information also applies to individuals using a TKD or CKD as some period is spent in ketosis. The impact and implications of exercise on carbohydrate requirements is discussed in other posts in the website.
Sources of glucose in the body during short term ketosis
The easiest way to examine the body’s requirements for glucose is to look at the effects of complete fasting in both the short term (a few hours to 3 weeks) and the long term (3 weeks and up). The few differences between complete fasting and a ketogenic diet are discussed afterwards.
Liver glycogen and gluconeogenesis
The initial storage depot of carbohydrate in the body is the liver, which contains enough glycogen to sustain the brain’s glucose needs for approximately 12-16 hours (4). We will assume for the following discussion that liver glycogen has been depleted, ketosis established, and that the only source of glucose is from endogenous fuel stores (i.e. stored bodyfat and protein). The effects of food intake on ketosis is discussed in other posts in this website.
After its glycogen has been depleted, the liver is one of the major sources for the production of glucose (gluconeogenesis) and it produces glucose from glycerol, lactate/pyruvate and the amino acids alanine and glutamine (5,6,25) The kidney also produces glucose as starvation proceeds (8).
Glycerol comes from the breakdown of adipose tissue triglyceride, lactate and pyruvate from the breakdown of glycogen and glucose, and alanine and glutamine are released from muscle.
Since we are ultimately concerned with the loss of muscle tissue during ketosis, gluconeogenesis from alanine and glutamine are discussed further.
With the induction of starvation, blood alanine/glutamine levels both increase significantly, indicating an increase in muscle protein breakdown (6,19). Alanine is absorbed by the liver, converted to glucose and released back into the bloodstream. Glutamine is converted to glucose in the kidney (8). There are also increases in blood levels of the branch-chain amino acids, indicating the breakdown of skeletal muscle (18).
During the initial weeks of starvation, there is an excretion of 12 grams of nitrogen per day. Since approximately 16% of protein is nitrogen, this represents the breakdown of roughly grams of body protein to produce 75 grams of glucose (6). If this rate of protein breakdown were to continued unchecked, the body’s protein stores would be depleted in a matter of weeks, causing death.
After even 1 week of starvation, blood alanine levels begin to drop and uptake by the kidneys decreases, indicating that the body is already trying to spare protein losses (19). During longer periods of starvation, blood levels of alanine and glutamine continue to decrease, as does glucose production by the liver (6,21). As glucose production in the liver is decreasing, there is increased glucose production in the kidney (21).
Because of these adaptations, nitrogen losses decrease to 3-4 grams per day by the third week of starvation, indicating the breakdown of approximately 20 grams of body protein (6).
With extremely long term starvation, nitrogen losses may drop to 1 gram per day (7), indicating the breakdown of only 6 grams of body protein. However at no time does protein breakdown decrease to zero, as there is always a small requirement for glucose (10). As we shall see in a later section, the development of ketosis during starvation is critical for protein sparing.
The glycerol portion of triglycerides (TG) is converted to glucose in the liver with roughly ten percent of the total grams of TG broken down (whether from bodyfat or dietary fat) appearing as glucose (25,29). An average sized individual (150 lbs) may catabolize 160-180 grams of fat per day which will yield 16-18 grams of glucose (10). Obviously a larger individual would oxidize more fat, producing more glucose. The amount of glycerol converted to glucose is fairly constant on a day to day basis and will depend primarily on metabolic rate.
Protein and fat
Excluding the glucose made by recycling lactate and pyruvate, the body will produce the 100 grams of glucose which it needs from the breakdown of approximately 180 grams of TG and 75 grams of muscle protein (see Table 1) (6).
Table 1: Sources of glucose during the initial stages of starvation Source
Glucose produced (grams)
Amount of carbohydrate required by brain
Breakdown of 180 grams of TG
Breakdown of 75 grams of protein
Total carbohydrate produced per day
in the liver
Production of glucose during long term starvation
As long term adaptation to ketosis continues, there are a number of adaptations which occur to further spare glucose. From the third day of ketosis to three weeks of fasting, the brain gradually increases its use of ketones for fuel, ultimately deriving up to 75% of its total energy from ketones (6,26). This shift to using ketones by the brain means that only 40 grams of glucose per day is required, the remaining 60-75 grams of energy being provided by ketones (26).
This means that less protein must be broken down to produce glucose. Since TG breakdown will still provide 18 grams of glucose per day, protein breakdown will only be 20 grams per day still provide 18 grams of glucose per day, protein breakdown will only be 20 grams per day (see table 2 on the next page) (6). As stated previously, is appears the primary purpose of ketones in humans is to provide the brain with a non-glucose, fat-derived fuel for the brain (27,30).
The implication of the adaptations discussed above is that the body does not require dietary carbohydrates for survival (exercise and muscle growth are a separate issue). That is, there is no such thing as an essential dietary carbohydrate as the body can produce what little glucose it needs from other sources.
Of course, the price paid is the loss of body protein, which will ultimately cause death if continued for long periods of time. This loss of body protein during total starvation is unacceptable but the above discussion only serves to show that the body goes through a series of adaptations to conserve its protein. The addition of dietary protein will maintain ketosis, while preventing the breakdown of bodily protein. In brief, rather than break down bodily protein to produce glucose, the body will use some of the incoming dietary protein for glucose production. This should allow maximal fat utilization while sparing protein losses.
Table 2: Sources of glucose during long term starvation
Glucose produced (grams)
Amount of carbohydrate required by brain
Breakdown of 180 grams of fat
Breakdown of 20 grams of protein
Total carbohydrate produced per day
in the liver and kidney
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