Ketosis

Ketosis

November 5, 2019 0 By William Morgan


Ketosis
Ketosis /kɨˈtoʊsɨs/ is a state of elevated levels of ketone bodies in the body. It is
almost always generalized throughout the body, with hyperketonemia, that is, an elevated
level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when liver
glycogen stores are depleted. The ketone bodies acetoacetate and β-hydroxybutyrate are used
for energy. Ketosis may result from fasting or switching to a low-carbohydrate diet from
a high-carbohydrate one. Deliberately induced ketosis serves as a medical intervention for
intractable epilepsy. Metabolic pathways
When glycogen stores are not available in the cells, fat (triacylglycerol) is cleaved
to provide 3 fatty acid chains and 1 glycerol molecule in a process known as lipolysis.
Most of the body is able to use fatty acids as an alternative source of energy in a process
called beta-oxidation. One of the products of beta-oxidation is acetyl-CoA, which can
be further used in the citric acid cycle. During prolonged fasting or starvation, or
as the intentional result of a ketogenic diet, acetyl-CoA in the liver is used to produce
ketone bodies instead, leading to a state of ketosis.
During starvation or a long physical training session, the body starts using fatty acids
instead of glucose. The brain cannot use long-chain fatty acids for energy because they are completely
albumin-bound and cannot cross the blood–brain barrier. Not all medium-chain fatty acids
are bound to albumin. The unbound medium-chain fatty acids are soluble in the blood and can
cross the blood–brain barrier. The ketone bodies produced in the liver can also cross
the blood–brain barrier. In the brain, these ketone bodies are then incorporated into acetyl-CoA
and used in the citric acid cycle. The ketone body acetoacetate will slowly decarboxylate
into acetone, a volatile compound that is both metabolized as an energy source and lost
in the breath and urine. Ketoacidosis
Ketone bodies are acidic, but acid-base homeostasis in the blood is normally maintained through
bicarbonate buffering, respiratory compensation to vary the amount of CO2 in the bloodstream,
hydrogen ion absorption by tissue proteins and bone, and renal compensation through increased
excretion of dihydrogen phosphate and ammonium ions. Prolonged excess of ketone bodies can
overwhelm normal compensatory mechanisms, leading to acidosis if blood pH falls below
7.35. There are two major causes of ketoacidosis:
Most commonly, ketoacidosis is diabetic ketoacidosis (DKA), resulting from increased fat metabolism
due to a shortage of insulin. It is associated primarily with type I diabetes, and may result
in a diabetic coma if left untreated. Alcoholic ketoacidosis (AKA) presents infrequently,
but can occur with acute alcohol intoxication, most often following a binge in alcoholics
with acute or chronic liver or pancreatic disorders. Alcoholic ketoacidosis occurs more
frequently following methanol or ethylene glycol intoxication than following intoxication
with uncontaminated ethanol. A mild acidosis may result from prolonged
fasting or when following a ketogenic diet or a very low calorie diet.
Diet If the diet is changed from one that is high
in carbohydrates to one that does not provide sufficient carbohydrate to replenish glycogen
stores, the body goes through a set of stages to enter ketosis. During the initial stages
of this process, blood glucose levels are maintained through gluconeogenesis, and the
adult brain does not burn ketones. However, the brain makes immediate use of ketones for
lipid synthesis in the brain. After about 48 hours of this process, the brain starts
burning ketones in order to more directly use the energy from the fat stores that are
being depended upon, and to reserve the glucose only for its absolute needs, thus avoiding
the depletion of the body’s protein store in the muscles.
Ketosis is deliberately induced by use of a ketogenic diet as a medical intervention
in cases of intractable epilepsy. Other uses of low-carbohydrate diets remain controversial.
Induced ketosis or low-carbohydrate diet terms have very wide interpretation. Therefore Stephen
S. Phinney and Jeff S. Volek coined the term nutritional ketosis to avoid the confusion.
Diagnosis Whether ketosis is taking place can be checked
by using special urine test strips such as Ketostix. The strips have a small pad on the
end which is dipped in a fresh specimen of urine. Within a matter of seconds, the strip
changes color indicating the level of ketone bodies detected, which reflects the degree
of ketonuria, which, in turn, can be used to give a rough estimation of the level of
hyperketonemia in the body (see table below). Alternatively, some products targeted to diabetics
such as the Abbott Precision Xtra or the Nova Max can be used to take a blood sample and
measure the ketone levels directly. Normal serum reference ranges for ketone bodies are
0.5–3.0 mg/dL, equivalent to 0.05–0.29 mmol/L. Also, when the body is in ketosis, one’s breath
may smell of acetone. This is due to the breakdown of acetoacetic acid into acetone and carbon
dioxide which is exhaled through the lungs. Acetone is the chemical responsible for the
smell of nail polish remover and some paint thinners.
Controversy Some clinicians regard restricting a diet
from all carbohydrates as unhealthy and dangerous. However, it is not necessary to completely
eliminate all carbohydrates from the diet in order to achieve a state of ketosis. Other
clinicians regard ketosis as a safe biochemical process that occurs during the fat-burning
state. Ketogenesis can occur solely from the byproduct of fat degradation: acetyl-CoA.
Ketosis, which is accompanied by gluconeogenesis (the creation of glucose de novo from pyruvate),
is the specific state with which some clinicians are concerned. However, it is unlikely for
a normal functioning person to reach life-threatening levels of ketosis, defined as serum beta-hydroxybutyrate
(B-OHB) levels above 15 millimolar (mM) compared to ketogenic diets among non diabetics which
“rarely run serum B-OHB levels above 3 mM.” This is avoided with proper basal secretion
of pancreatic insulin. People who are unable to secrete basal insulin, such as type 1 diabetics
and long-term type II diabetics, are liable to enter an unsafe level of ketosis, causing
an eventual comatose state that requires emergency medical treatment.
The anti-ketosis conclusions have been challenged by a number of doctors and advocates of low-carbohydrate
diets, who dispute assertions that the body has a preference for glucose and that there
are dangers associated with ketosis. The Inuit are often cited an example of a culture that
has lived for thousands of years on a low-carbohydrate diet. However, in multiple studies the Inuit
diet has not been shown to be a ketogenic diet, as the Inuit consumed as much as 15-20%
of their calories from carbohydrates, largely from the glycogen found in the raw meats.
Whether a no-carbohydrate diet would be safe for non-Inuit is also disputed: Nick Lane
speculates that the Inuit may have a genetic predisposition allowing them to eat a ketogenic
diet and remain healthy. According to this view, such an evolutionary adaptation would
have been caused by environmental stresses. This speculation is unsupported, however,
in light of the many arctic explorers, including John Rae, Fridtjof Nansen, and Frederick Schwatka,
who adapted to Inuit diets with no adverse effects. Schwatka specifically commented that
after a 2- to 3-week period of adaptation to the Inuit diet he could manage “prolonged
sledge journeys,” including the longest sledge journey on record, relying solely on the Inuit
diet without difficulty. Furthermore, in a comprehensive review of the anthropological
and nutritional evidence collected on 229 hunter-gatherer societies it was found that,
“Most (73%) of the worldwide hunter-gatherer societies derived greater than 50% (≥56–65%
of energy) of their subsistence from animal foods, whereas only 14% of these societies
derived greater than 50% (≥56–65% of energy) of their subsistence from gathered plant foods,”
suggesting that the ability to thrive on low carbohydrate diets is widespread and not limited
to any particular genetic predisposition. While it is believed that carbohydrate intake
after exercise is the most effective way of replacing depleted glycogen stores, studies
have shown that, after a period of 2–4 weeks of adaptation, physical endurance (as opposed
to physical intensity) is unaffected by ketosis, as long as the diet contains high amounts
of fat. It seems appropriate that some clinicians refer to this period of keto-adaptation as
the “Schwatka Imperative” after the explorer who first identified the transition period
from glucose-adaptation to keto-adaptation. Veterinary medicine
In dairy cattle, ketosis is a common ailment that usually occurs during the first weeks
after giving birth to a calf. Ketosis is in these cases sometimes referred to as acetonemia.
A study from 2011 revealed that whether ketosis is developed or not depends on the lipids
a cow uses to create butterfat. Animals prone to ketosis mobilize fatty acids from adipose
tissue, while robust animals create fatty acids from blood phosphatidylcholine (lecithin).
Healthy animals can be recognized by high levels of milk glycerophosphocholine and low
levels of milk phosphocholine. In sheep, ketosis, evidenced by hyperketonemia
with beta-hydroxybutyrate in blood over 0.7 mmol/L, occurs in pregnancy toxemia. This may develop
in late pregnancy in ewes bearing multiple fetuses, and is associated with the considerable
glucose demands of the conceptuses. In ruminants, because most glucose in the digestive tract
is metabolized by rumen organisms, glucose must be supplied by gluconeogenesis, for which
propionate (produced by rumen bacteria and absorbed across the rumen wall) is normally
the principal substrate in sheep, with other gluconeogenic substrates increasing in importance
when glucose demand is high or propionate is limited. Pregnancy toxemia is most likely
to occur in late pregnancy because most fetal growth (and hence most glucose demand) occurs
in the final weeks of gestation; it may be triggered by insufficient feed energy intake
(anorexia due to weather conditions, stress or other causes), necessitating reliance on
hydrolysis of stored triglyceride, with the glycerol moiety being used in gluconeogenesis
and the fatty acid moieties being subject to oxidation, producing ketone bodies. Among
ewes with pregnancy toxemia, beta-hydroxybutyrate in blood tends to be higher in those that
die than in survivors. Prompt recovery may occur with natural parturition, Caesarean
section or induced abortion. Prevention (through appropriate feeding and other management)
is more effective than treatment of advanced stages of ovine ketosis.