Free Fatty Acids (FFA) and ketones
Most tissues of the body can use FFA for fuel if it is available. This includes skeletal
muscle, the heart, and most organs. However, there are other tissues such as the brain, red
blood cells, the renal medulla, bone marrow and Type II muscle fibers which cannot use FFA and
require glucose (2).
The fact that the brain is incapable of using FFA for fuel has led to one of the biggest
misconceptions about human physiology: that the brain can only use glucose for fuel. While it is
true that the brain normally runs on glucose, the brain will readily use ketones for fuel if they are
available (4-6).
Arguably the most important tissue in terms of ketone utilization is the brain which can
derive up to 75% of its total energy requirements from ketones after adaptation (4-6). In all
likelihood, ketones exist primarily to provide a fat-derived fuel for the brain during periods when
carbohydrates are unavailable (2,7).
As with glucose and FFA, the utilization of ketones is related to their availability (7).
Under normal dietary conditions, ketone concentrations are so low that ketones provide a
negligible amount of energy to the tissues of the body (5,8). If ketone concentrations increase,
most tissues in the body will begin to derive some portion of their energy requirements from
ketones (9). Some research also suggests that ketones are the preferred fuel of many tissues (9).
One exception is the liver which does not use ketones for fuel, relying instead on FFA (7,10,11).
By the third day of ketosis, all of the non-protein fuel is derived from the oxidation of FFA
and ketones (12,13). As ketosis develops, most tissues which can use ketones for fuel will stop
using them to a significant degree by the third week (7,9). This decrease in ketone utilization
occurs due to a down regulation of the enzymes responsible for ketone use and occurs in all
tissues except the brain (7). After three weeks, most tissues will meet their energy requirements
almost exclusively through the breakdown of FFA (9). This is thought to be an adaptation to
ensure adequate ketone levels for the brain.
Except in the case of Type I diabetes, ketones will only be present in the bloodstream
under conditions where FFA use by the body has increased. For all practical purposes we can
assume that a large increase in FFA use is accompanied by an increase in ketone utilization and
these two fuels can be considered together.

Hormone levels
There are a host of regulatory hormones which determine fuel use in the human body. The
primary hormone is insulin and its levels, to a great degree, determine the levels of other
hormones and the overall metabolism of the body (2,16,23). A brief examination of the major
hormones involved in fuel use appears below.
Insulin is a peptide (protein based) hormone released from the pancreas, primarily in
response to increases in blood glucose. When blood glucose increases, insulin levels increase as
well, causing glucose in the bloodstream to be stored as glycogen in the muscle or liver. Excess
glucose can be pushed into fat cells for storage (as alpha-glycerophosphate). Protein synthesis is
stimulated and free amino acids (the building blocks of proteins) are be moved into muscle cells
and incorporated into larger proteins. Fat synthesis (called lipogenesis) and fat storage are both
stimulated. FFA release from fat cells is inhibited by even small amounts of insulin.
The primary role of insulin is to keep blood glucose in the fairly narrow range of roughly 80-
120 mg/dl. When blood glucose increases outside of this range, insulin is released to lower blood
glucose back to normal. The greatest increase in blood glucose levels (and the greatest increase
in insulin) occurs from the consumption of dietary carbohydrates. Protein causes a smaller
increase in insulin output because some individual amino acids can be converted to glucose. FFA
can stimulate insulin release as can high concentrations of ketone bodies although to a much
lesser degree than carbohydrate or protein. This is discussed in chapter 4.
23When blood glucose drops (during exercise or with carbohydrate restriction), insulin levels
generally drop as well. When insulin drops and other hormones such as glucagon increase, the
body will break down stored fuels. Triglyceride stored in fat cells is broken down into FFA and
glycerol and released into the bloodstream. Proteins may be broken down into individual amino
acids and used to produce glucose. Glycogen stored in the liver is broken down into glucose and
released into the bloodstream (2). These substances can then be used for fuel in the body.
An inability to produce insulin indicates a pathological state called Type I diabetes (or
Insulin Dependent Diabetes Mellitus, IDDM). Type I diabetics suffer from a defect in the
pancreas leaving them completely without the ability to make or release insulin. IDDM diabetics
must inject themselves with insulin to maintain blood glucose within normal levels. This will
become important when the distinction between diabetic ketoacidosis and dietary induced ketosis
is made in the next chapter.
Glucagon is essentially insulin’s mirror hormone and has essentially opposite effects. Like
insulin, glucagon is also a peptide hormone released from the pancreas and its primary role is also
to maintain blood glucose levels. However, glucagon acts by raising blood glucose when it drops
below normal.
Glucagon’s main action is in the liver, stimulating the breakdown of liver glycogen which is
then released into the bloodstream. Glucagon release is stimulated by a variety of stimuli
including a drop in blood glucose/insulin, exercise, and the consumption of a protein meal (24).
High levels of insulin inhibit the pancreas from releasing glucagon.
Under normal conditions, glucagon has very little effect in tissues other than the liver (i.e.
fat and muscle cells). However, when insulin is very low, as occurs with carbohydrate restriction
and exercise, glucagon plays a minor role in muscle glycogen breakdown as well as fat
mobilization. In addition to its primary role in maintaining blood glucose under conditions of low
blood sugar, glucagon also plays a pivotal role in ketone body formation in the liver, discussed in
detail in the next chapter.
From the above descriptions, it should be clear that insulin and glucagon play antagonistic
roles to one another. Whereas insulin is primarily a storage hormone, increasing storage of
glucose, protein and fat in the body ; glucagon’s primary role is to mobilize those same fuel stores
for use by the body.
As a general rule, when insulin is high, glucagon levels are low. By the same token, if
insulin levels decrease, glucagon will increase. The majority of the literature (especially as it
pertains to ketone body formation) emphasizes the ratio of insulin to glucagon, called the
insulin/glucagon ratio (I/G ratio), rather than absolute levels of either hormone. This ratio is an
important factor in the discussion of ketogenesis in the next chapter. While insulin and glucagon
play the major roles in determining the anabolic or catabolic state of the body, there are several
other hormones which play additional roles. They are briefly discussed here.
Growth hormone (GH) is another peptide hormone which has numerous effects on the
body, both on tissue growth as well as fuel mobilization. GH is released in response to a variety of
stressors the most important of which for our purposes are exercise, a decrease in blood glucose,
and carbohydrate restriction or fasting. As its name suggests, GH is a growth promoting
hormone, increasing protein synthesis in the muscle and liver. GH also tends to mobilize FFA
from fat cells for energy.
24In all likelihood, most of the anabolic actions of GH are mediated through a class of
hormones called somatomedins, also called insulin-like growth factors (IGFs). The primary IGF
in the human body is insulin like growth factor-1 (IGF-1) which has anabolic effects on most
tissues of the body. GH stimulates the liver to produce IGF-1 but only in the presence of insulin.
High GH levels along with high insulin levels (as would be seen with a protein and
carbohydrate containing meal) will raise IGF-1 levels as well as increasing anabolic reactions in
the body. To the contrary, high GH levels with low levels of insulin, as seen in fasting or
carbohydrate restriction, will not cause an increase in IGF-1 levels. This is one of the reasons
that ketogenic diets are not ideal for situations requiring tissue synthesis, such as muscle growth
or recovery from certain injuries: the lack of insulin may compromise IGF-1 levels as well as
affecting protein synthesis.
There are two thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Both are
released from the thyroid gland in the ratio of about 80% T4 and 20% T3. In the human body, T4
is primarily a storage form of T3 and plays few physiological roles itself. The majority of T3 is not
released from the thyroid gland but rather is converted from T4 in other tissues, primarily the
liver. Although thyroid hormones affect all tissues of the body, we are primarily concerned with
the effects of thyroid on metabolic rate and protein synthesis. The effects of low-carbohydrate
diets on levels of thyroid hormones as well as their actions are discussed in chapter 5.
Cortisol is a catabolic hormone released from the adrenal cortex and is involved in many
reactions in the body, most related to fuel utilization. Cortisol is involved in the breakdown of
protein to glucose as well as being involved in fat breakdown.
Although cortisol is absolutely required for life, an excess of cortisol (caused by stress and
other factors) is detrimental in the long term, causing a continuous drain on body proteins
including muscle, bone, connective tissue and skin. Cortisol tends to play a permissive effect in
its actions, allowing other hormones to work more effectively.
Adrenaline and noradrenaline (also called epinephrine and norepinephrine) are frequently
referred to as ‘fight or flight’ hormones. They are generally released in response to stress such as
exercise, cold, or fasting. Epinephrine is released primarily from the adrenal medulla, traveling in
the bloodstream to exert its effects on most tissues in the body. Norepinephrine is released
primarily from the nerve terminals, exerting its effects only on specific tissues of the body.
The interactions of the catecholamines on the various tissues of the body are quite
complex and beyond the scope of this book. The primary role that the catecholamines have in
terms of the ketogenic diet is to stimulate free fatty acid release from fat cells.
When insulin levels are low, epinephrine and norepinephrine are both involved in fat
mobilization. In humans, only insulin and the catecholamines have any real effect on fat
mobilization with insulin inhibiting fat breakdown and the catecholamines stimulating fat
breakdown.

What are ketone bodies?
The three ketone bodies are acetoacetate (AcAc), beta-hydroxybutyrate (BHB) and
acetone. AcAc and BHB are produced from the condensation of acetyl-CoA, a product of
incomplete breakdown of free fatty acids (FFA) in the liver. While ketones can technically be
made from certain amino acids, this is not thought to contribute significantly to ketosis (1).
Roughly one-third of AcAc is converted to acetone, which is excreted in the breath and urine.
This gives some individuals on a ketogenic diet a ‘fruity’ smelling breath.
As a side note, urinary and breath excretion of acetone is negligible in terms of caloric loss,
amounting to a maximum of 100 calories per day (2). The fact that ketones are excreted through
this pathway has led some authors to argue that fat loss is being accomplished through urination
and breathing. While this may be very loosely true, in that ketones are produced from the
breakdown of fat and energy is being lost through these routes, the number of calories lost per
day will have a minimal effect on fat loss.

What is ketosis?
Ketosis is the end result of a shift in the insulin/glucagon ratio and indicates an overall shift
from a glucose based metabolism to a fat based metabolism. Ketosis occurs in a number of
physiological states including fasting (called starvation ketosis), the consumption of a high fat
diet (called dietary ketosis), and immediately after exercise (called post-exercise ketosis). Two
pathological and potentially fatal metabolic states during which ketosis occurs are diabetic
ketoacidosis and alcoholic ketoacidosis.
The major difference between starvation, dietary and diabetic/alcoholic ketoacidosis is in
the level of ketone concentrations seen in the blood. Starvation and dietary ketosis will normally
not progress to dangerous levels, due to various feedback loops which are present in the body
(12). Diabetic and alcoholic ketoacidosis are both potentially fatal conditions (12).
All ketotic states ultimately occur for the same reasons. The first is a reduction of the
hormone insulin and an increase in the hormone glucagon both of which are dependent on the
depletion of liver glycogen. The second is an increase in FFA availability to the liver, either from
dietary fat or the release of stored bodyfat.
Under normal conditions, ketone bodies are present in the bloodstream in minute amounts,
approximately 0.1 mmol/dl (1,6). When ketone body formation increases in the liver, ketones
begin to accumulate in the bloodstream. Ketosis is defined clinically as a ketone concentration
above 0.2 mmol/dl (6). Mild ketosis, around 2 mmol, also occurs following aerobic exercise. (4).
The impact of exercise on ketosis is discussed in chapter 21.
32Ketoacidosis is defined as any ketone concentration above 7 mmol/dl. Diabetic and
alcoholic ketoacidosis result in ketone concentrations up to 25 mmol (6). This level of ketosis will
never occur in non-diabetic or alcoholic individuals (12)

Ketonemia and ketonuria
The general metabolic state of ketosis can be further subdivided into two categories. The
first is ketonemia which describes the buildup of ketone bodies in the bloodstream. Technically
ketonemia is the true indicator that ketosis has been induced. However the only way to measure
the level of ketonemia is with a blood test which is not practical for ketogenic dieters.
The second subdivision is ketonuria which describes the buildup and excretion of ketone
bodies in the urine, which occurs due to the accumulation of ketones in the kidney. The excretion
of ketones into the urine may represent 10-20% of the total ketones made in the liver (4).
However, this may only amount to 10-20 grams of total ketones excreted per day (17). Since
ketones have a caloric value of 4.5 calories/gram, (17) the loss of calories through the urine is only
45-90 calories per day.
The degree of ketonuria, which is an indirect indicator of ketonemia, can be measured by
the use of Ketostix (tm), small paper strips which react with urinary ketones and change color.
Ketonemia will always occur before ketonuria. Ketone concentrations tend to vary throughout
the day and are generally lower in the morning, reaching a peak around midnight (6). This may
occur from changes in hormone levels throughout the day (18). Additionally, women appear to
show deeper ketone levels than men (19,20) and children develop deeper ketosis than do adults
(5). Finally, certain supplements, such as N-acetyl-cysteine, a popular anti-oxidant, can falsely
indicate ketosis (4).
The distinction between ketonuria and ketonemia is important from a practical
33The distinction between ketonuria and ketonemia is important from a practical
standpoint. Some individuals, who have followed all of the guidelines for establishing ketosis will
not show urinary ketones. However this does not mean that they are not technically in ketosis.
Ketonuria is only an indirect measure of ketone concentrations in the bloodstream and Ketostix
(tm) measurements can be inaccurate

спасибо за тему, интересно будет почитать.

Я читаю научные книги

),ребята приводят другие доводы(из ЖФ и каких-то других источников).

многие на ЖФ также перечитали книги Лайла..

на ЖФ всё разжовывают не научным,а обычным человеческим языком...поэтому разница лишь в передачи информации=))

Changes in hormones and fuel availability
Although some mention is made in the discussions below of the adaptations seen during
this time period, most of the major adaptations to ketosis start to occur by the third day,
continuing for at least 3 weeks (4-6). During the first 3 days of fasting, blood glucose drops from
normal levels of 80-120 mg/dl to roughly 65-75 mg/dl. Insulin drops from 40-50 µU/ml to 7-10
µU/ml (5,7,8). Both remain constant for the duration of the fast. One thing to note is that the
body strives to maintain near-normal blood glucose levels even under conditions of total fasting
(5). The popularly held belief that ketosis will not occur until blood glucose falls to 50 mg/dl is
incorrect. Additionally, the popular belief that there is no insulin present on a ketogenic diet is
incorrect (7).
One difference between fasting and a ketogenic diet is that the slight insulin response to
dietary protein will cause blood glucose to be maintained at a slightly higher level, approximately
80-85 mg/dl (1). This most likely occurs due to the conversion of dietary protein to glucose in the
liver.
39At the same time that insulin and glucose are decreasing from carbohydrate restriction,
other hormones such as glucagon and growth hormone are increasing, as are the levels of
adrenaline and noradrenaline (7,10-12). Cortisol may actually decrease (13). This increases the
rate of fat breakdown and blood levels of FFA and ketones increase (6,8,10,14,15).
Although the liver is producing ketones at its maximum rate by day three (14), blood
ketone levels will continue to increase finally reaching a plateau by three weeks (6). The decrease
in blood glucose and subsequent increase in FFA and ketones appear to be the signal for the
adaptations which are seen, and which are discussed below (16).
In addition to increases in FFA and ketones, there are changes in blood levels of some
amino acids (AAs). Increases are seen in the the branch chain amino acids, indicating increased
protein breakdown (1, 17-19). As well, there are decreases in other AAs, especially alanine (1,
10,17-19) This most likely represents increased removal by the liver but may also be caused by
decreased release of alanine from the muscles (16). This is discussed in further detail in section 3.
Changes in levels of the other amino acids also occur and interested readers should examine the
references cited. Blood levels of urea, a breakdown product of protein also increase (1). All of this
data points to increased protein breakdown during the initial stages of starvation.
By the third day of carbohydrate restriction, the body is no longer using an appreciable
amount of glucose for fuel. At this time essentially all of the non-protein energy is being derived
from the oxidation of fat, both directly from FFA and indirectly via ketone bodies (20).

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
41nervous 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.

Decreasing the body’s glucose requirements
This is arguably the primary mechanism through which ketosis spares nitrogen losses.
This adaptation is discussed in detail in the previous sections and is well established in the
45literature. To briefly recap, by shifting the body’s overall metabolism to fat and ketones
(especially in the brain), less protein is converted to glucose and protein is spared (6,27). This
mechanism is not discussed in further detail here.
It should be noted that preventing the development of ketosis, either with drugs or with the
provision of too much dietary carbohydrate, maintains the nitrogen losses during starvation (31).
That is, the development of ketosis is a critical aspect of preventing excessive nitrogen
losses during periods of caloric insufficiency. This suggests that non-ketogenic low-carbohydrate
diets (frequently used by bodybuilders) may actually cause greater protein losses by preventing
the body from maximizing the use of fat for fuel, which is addressed in chapter 6 .
Decreased nitrogen excretion via the kidney
The kidney is a major site of ketone uptake and the buildup of ketones in the kidney has at
least two metabolic effects (32). The first is an increase in urinary excretion of ketones, which
can be detected with Ketostix (tm). The second is an impairment of uric acid uptake, which is
discussed in chapter 7.
The excretion of ketones through the kidneys has an important implication for nitrogen
sparing. The kidney produces ammonia, which requires nitrogen, as a base to balance out the
acidic nature of ketones and prevent the urine from becoming acidic. This is at least one possible
site for an increase in protein losses during ketosis (32). In all likelihood, the increased excretion of
ammonia may be the basis of the idea (long held in bodybuilding) that ketone excretion is
indicative of protein loss.
As ketosis develops, however, there is an adaptation in the kidney to prevent excessive
ammonia loss. As blood ketone concentrations increase, the kidney increases its absorption of
ketones. If this increased absorption was accompanied by increased ketone excretion, there
would be further nitrogen loss through ammonia production.
However urinary excretion of ketones does not increase, staying extremely constant from
the first few days of ketosis on. Therefore, most of the ketones being absorbed by the kidney are
not being excreted. The resorption of ketones appears to be an adaptation to prevent further
nitrogen losses, which would occur from increasing ammonia synthesis (16,32). This adaptation
has the potential to spare 7 grams of nitrogen (roughly 42 grams of body protein) per day from
being lost (32).
Directly affecting protein synthesis and breakdown.
As stated, it is well established that protein breakdown decreases during the adaptation to
total starvation and one of the mechanisms for this decrease is a lessening of the brain’s glucose
requirements. It has also been suggested that protein sparing is directly related to ketosis (5,26).
As well, many popular authors have suggested that ketones are directly anti-catabolic but this
has not been found in all studies.
As described previously, muscles will derive up to 50% of their energy requirements from
ketones during the first few days of ketosis. However this drops rapidly and by the third week of
46ketosis, muscles derive less only 4-6% of their energy from ketone bodies (22). This becomes
important when considering the time course for nitrogen sparing during ketosis.
Infusion studies
Several studies have examined the effects on protein breakdown during the infusion of
ketone bodies at levels that would be seen in fasting or a ketogenic diet. Of these studies, three
have shown a decrease in protein breakdown (33-35) while two others have not (36,37). One
study suggested that ketones were directly anabolic (38). One oddity of these studies is that the
infusion of ketones (usually as a ketone salt such as sodium-acetoacetate) causes an increase in
blood pH (36,38), contrary to the slight drop in blood pH which normally occurs during a ketogenic
diet.
At least one study suggests that the rise in pH is responsible for the decrease in protein
breakdown rather than the ketones themselves (36); and sodium bicarbonate ingestion can
reduce protein breakdown during a ketogenic diet (39). However, since blood pH is normalized
within a few days of initiating ketosis, while maximal protein sparing does not occur until the third
week, it seems unlikely that changes in blood pH can explain the protein sparing effects of
ketosis.
It should be noted that these studies are different than the normal physiological state of
ketosis for several reasons. First and foremost, the mixture of ketone salts used is not
chemically identical to the ketones that appear in the bloodstream. Additionally, the increase in
pH seen with ketone salt infusion is in direct contrast to the drop in pH seen on a ketogenic diet
suggesting a difference in effect. Therefore, ketones produced during metabolic ketosis may still
have a direct anti-catabolic effect.
Possibly the biggest argument against the idea that ketones are directly anti-catabolic is
the time course for changes in nitrogen balance. Most of the infusion studies were done on
individuals who had been fasting for short periods of time, overnight or a few days. The major
decrease in nitrogen sparing does not occur until approximately the third week of ketosis, at
which time muscles are no longer using ketones to any significant degree (22,40). All of the
above data makes it difficult to postulate a mechanism by which ketones directly affect muscle
protein breakdown. In all likelihood, contrary to popular belief, ketones are not directly anticatabolic.
Affecting thyroid levels
A fourth possible mechanism by which ketosis may reduce protein breakdown involves
the thyroid hormones, primarily triiodothyronine (T3). T3 is arguably one of the most active
hormones in the human body (42-44). While most think of T3 simply as a controller of metabolic
rate, it affects just about every tissue of the body including protein synthesis. A decrease in T3
will slow protein synthesis and vice versa. As a side note, this is one reason why low
carbohydrate diets are not ideal for individuals wishing to gain muscle tissue: the decrease in T3
will negatively affect protein synthesis.
47The body has two types of thyroid hormones (42). The primary active thyroid hormone is
T3, called triiodothyronine. T3 is responsible most of the metabolic effects in the body. The other
thyroid hormone is T4, called thyroxine. Thyroxine is approximately one-fifth as metabolically
active as T3 and is considered to be a storage form of T3 in that it can be converted to T3 in the
liver.
T3 levels in the body are primarily related to the carbohydrate content of the diet (44-46)
although calories also play a role (47-49). When calories are above 800 per day, the
carbohydrate content of the diet is the critical factor in regulating T3 levels and a minimum of 50
grams per day of carbohydrate is necessary to prevent the drop in T3 (44,48,49). To the
contrary, one study found that a 1500 calorie diet of 50% carbohydrate and 50% fat still caused a
drop in T3, suggesting that fat intake may also affect thyroid hormone metabolism (50).
Below 800 calories per day, even if 100% of those calories come from carbohydrate, T3
levels drop (47). Within days of starting a ketogenic diet, T3 drops quickly. This is part of the
adaptation to prevent protein losses and the addition of synthetic T3 increases nitrogen losses
during a ketogenic diet (1). In fact the ability to rapidly decrease T3 levels may be one
determinant of how much protein is spared while dieting (51).
Hypothyroidism and euthyroid stress syndrome (ESS)
There are two common syndromes associated with low levels of T3 which need to be
differentiated from one another. Hypothyroidism is a disease characterized by higher than
normal thyroid stimulating hormone (TSH) and lower levels of T3 and T4. The symptoms of this
disease include fatigue and a low metabolic rate.
The decrease in T3 due to hypothyroidism must be contrasted to the decrease seen during
dieting or carbohydrate restriction. Low levels of T3 with normal levels of T4 and TSH (as seen in
ketogenic dieting) is known clinically as euthyroid stress syndrome (ESS) and is not associated
with the metabolic derangements seen in hypothyroidism (1). The drop in T3 does not appear to
be linked to a drop in metabolic rate during a ketogenic diet (17,52).
As with other hormones in the body (for example insulin), the decrease in circulating T3
levels may be compensated for by an increase in receptor activity and/or number (1). This has
been shown to occur in mononuclear blood cells but has not been studied in human muscle or fat
cells (53). So while T3 does go down on a ketogenic diet, this does not appear to be the reason for a
decrease in metabolic rate.

How much dietary protein is necessary to prevent nitrogen losses?
Without going into the details of protein requirements, which are affected by activity and
are discussed in the next chapter, we can determine the minimum amount of protein which is
necessary to prevent body protein losses by looking at two factors: the amount of glucose
required by the brain, and the amount of glucose produced from the ingestion of a given amount of
dietary protein.
Both of these factors are discussed in previous chapters and a few brief calculations will
tell us how much protein is necessary. In the next section, these values are compared to a
number of diet studies to see if they are accurate.
To briefly recap, during the first weeks of ketosis, approximately 75 grams of glucose must
be produced (the other 18 grams of glucose coming from the conversion of glycerol to glucose) to
satisfy the brain’s requirements of ~100 grams of glucose per day. After approximately 3 weeks
of ketosis, the brain’s glucose requirements drop to approximately 40 grams of glucose. Of this,
18 grams are derived from the conversion of glycerol, leaving 25 grams of glucose to be made
from protein.
Since 58% of all dietary protein will appear in the bloodstream as glucose (3)Assuming zero carbohydrate intake, during the first 3 weeks of a ketogenic diet a protein
intake of ~150 grams per day should be sufficient to achieve nitrogen balance. Therefore,
regardless of bodyweight, the minimum amount of protein which should be consumed during the
initial three weeks of a ketogenic diet is 150 grams per day.
After 3 weeks of ketosis, as little as 50 grams of protein per day should provide enough
glucose to achieve nitrogen balance. The inclusion of exercise will increase protein requirements
and is discussed in chapter 9.