Is Ketosis Dangerous? (Science of Fasting & Low Carb Keto)

Recently, low carb diets, intermittent fasting
and even prolonged fasting have become very popular and they all have something in common. They move you towards entering the state of
ketosis. Ketosis is a state where your body is running
primarily on fat, fat from your diet or your body. Ketogenesis is when Fats are broken down into
something called ketones. These ketones (or ketone bodies) are usually
thought of as an alternate fuel source, because instead of glucose, ketones are used to power
most tissues as well as the brain. Sustaining ketosis means restricting protein
to less than 20% of your calories and carbs to less than 5% Unfortunately, there seems to be a lot of
confusion around ketones, most people have been taught that ketosis is a dangerous unnatural
state that appears only during starvation or in diabetics… So with this video I’d like to clear up
some misunderstandings and, I’ll present to you why entering this fat burning state
of ketosis can be perfectly natural, and might even even be the preferred state for humans,
compared to having our bodies always running off of carbohydrate. To see how there can be so much confusion
around a topic like ketosis, let’s first take a look at the story of the thymus gland.

Back around the 18th and 19th century, it
was hard to get cadavers for anatomical study. People didn’t really like having their recently
deceased loved ones cut up for examination. So people called resurrectionists were employed
by anatomists to exhume the bodies of the recently dead. Sometimes resurrectionists would even wait
near a funeral and snatch the body right then and there. Because of this, wealthy people would purchase
very well crafted lockable coffins and they would hire armed guards to protect the graves
of their loved ones. The 1832 Anatomy Act even said that if a person
died in a poor house, or their relatives could not pay for medical expenses, their body was
to be immediately turned over to the anatomist for study. This meant that anatomists were much more
likely to get their hands on the body of a poor person who couldn’t afford such measures.

So… what about the thymus? Well, people facing the hardships that come
from being poor, are of course going to be under a lot of stress. Chronic stress. Nowadays we’re very familiar with the fact
that chronic stress leads to all types of diseases, and that it can atrophy certain
organs. In the case of the thymus, stress can reduce
its size by as much as 75%. So what ended up being recorded into the anatomy
books as a normal thymus gland was actually a thymus that was severely reduced in size. Then, in the 1900’s a german anatomist called
Paltauf was trying to find the cause of Sudden Infant Death syndrome. Manny middle and upper class babies were abruptly
dying of this. So Paltauf examines the bodies of these higher
class babies and notices that their thymus glands appear to be abnormally large. So he concluded that if you wanted to be a
good parent you should irradiate the thymus gland of your child to make it smaller and
prevent sudden infant death syndrome. By the 1920’s all the the leading pediatric
textbooks were offering this advice.

Paltauf of course didn’t realize that he
was simply someone who had the rare chance to look at the bodies of children whose thymus
was not affected by the chronic stress of poverty. Unfortunately this misunderstanding persisted
well into the 1950’s, having several thousands of people die from irradiation induced cancer. So, what does any of this have to do with
ketosis? Well, ketones also have the misfortune of
being misunderstood due to how they were discovered. Physicians first noticed ketones in the latter
part of the 19th century, when they were noticed to be in abundance in the urine of patients
in a diabetic coma. It was understood that a vast overproduction
of ketones was responsible for the terrible symptoms of something called diabetic ketoacidosis.

So for half a century ketones were thought
to be the very negative product of impaired carbohydrate utilization. Only after technology and analytical techniques
improved did we understand that ketone bodies are perfectly normal components of the blood. Even if you’re not technically in ketosis,
Ketone bodies are always present in the blood of a healthy person and their levels increase
the longer you go without food. After an overnight fast, ketone bodies supply
2–6% of the body's energy requirements, while they supply 30–40% of the energy needs
after a 3-day fast. Before we continue, being in ketosis through
fasting or diet is nothing like diabetic ketoacidosis. Ketoacidosis involves exorbitant levels of
ketone production, far higher than what you could achieve even when fasting for weeks. Being worried about ketoacidosis through diet
or fasting is like worrying that eating at a sushi restaurant is going to put you in
brief coma just like that one kid who chugged a bottle of soy sauce on a dare.

So not only are ketones normally found in
healthy people, but it’s been found that certain tissues prefer to use ketone bodies. In fact, as is explained in the Biochemistry
textbook published by W.H. Freeman “Fatty acids are the heart's main source of fuel,
although ketone bodies as well as lactate can serve as fuel for heart muscle. In fact, heart muscle consumes acetoacetate
(a ketone body) in preference to glucose.” Some people actually purposely enter ketosis
through fasting in order to improve mental performance. A study at the University of Cambridge concluded
that a ketogenic diet “improved physical performance and cognitive function in rats,
and its energy-sparing properties suggest that it may help to treat a range of human
conditions with metabolic abnormalities.” I guess Plato figured this out for himself
when he said “I fast for greater physical and mental efficiency." Going without food for better cognitive function
may sound ridiculous considering it was for a long while thought that the brain can run
only on glucose ( carbohydrates).

George Cahill and his group at Harvard Medical
School demonstrated in 1967 that the brain can use ketone bodies as a source of energy. What he found was that during starvation,
ketones are the predominant fuel for the peripheral tissues and the brain, with the brain deriving
more than two thirds of its energy from ketone bodies. Despite this, the body still requires some
glucose, even when you aren’t eating anything. For example red blood cells can’t run off
of ketone bodies because they don’t have any mitochondria to metabolize them with. But all of the body’s glucose needs are
met by the fact that the body can make its own glucose, for example it can make glucose
from the glycerol backbone of fat.

For this reason, even during prolonged fasting,
people will keep a stable blood glucose level. This also illustrates that there is actually
no dietary requirement for carbohydrate. Of course vegetables and some fruit are very
important because they have all kinds of micronutrients and fiber, but your body doesn’t actually
require the carbohydrate inside those foods. I’m not necessarily saying a zero carbohydrate
diet is best, just that it’s very possible to live without dietary carbohydrate assuming
you get enough fat and protein. There are essential amino acids and there
are essential fatty acids – types of protein and fat you must get from the diet. However, there is no such thing as an essential
dietary carbohydrate – your body is perfectly capable of making as much glucose as it needs. In fact, in the absence of dietary carbohydrate,
the brain runs so efficiently off of ketone bodies that you can drastically deplete glucose
levels of people in deep ketosis and it won’t affect them.

A 1972 paper describes an ethically questionable
study where overweight patients fasted for 2 months, putting them in deep ketosis meaning
they were producing a very large amount of ketone bodies. Insulin was then infused into these patients
until their blood glucose went as low as low as 9mg per deciliter – a level that should
cause coma or death. However, the patients didn’t really react
to this. There was no particular change in cognition,
nor did their body react to the drastic drop in blood sugar. "The only people in the room who had palpations
and sweating and anxiety were the physicians. The people who had the blood sugar levels
that should be associated with coma or death were completely unphased. Had completely normal mentation. It is clear that the human brain is perfectly
happy with beta hydroxybutyrate as not just its majority fuel, but essentially its sole
fuel." Actually anyone watching this video would
have, at at least one point in their lives, been in a similar situation where blood glucose
is very low and ketone utilization is very high in their bodies. It’s estimated that a newborn’s brain
consumes on average between 60 and 71% of its body’s energy budget.

Compare that to the lowly 25% of the body’s
energy budget an adult brain uses. Despite this massive need for energy, a newborn’s
blood glucose level is incredibly low at around 35mg per deciliter. This is half of the lower end of a normal
adult’s blood glucose level. This means that the newborn’s brain would
have to be deriving more than half of its energy from ketone bodies.

In his book on the health potential of ketones,
Dr. Muneta Tetsuo, director of Muneta Maternity Clinic in Japan explains that pregnant women,
whether they are restricting carbohydrate or not are producing higher than normal levels
of ketones. By comparing the mother’s blood with the
newborn’s umbilical cord blood, he found that out of 416 cases, 70% of babies were
born with even higher levels of ketones than that of the mother. By analyzing the villi that provide contact
with the mother's blood to the fetal membrane, Muneta deduced that the fetus must be living
in an environment of elevated ketones from the start of pregnancy. And, even a month after birth, babies on average
had a blood ketone level 5 times higher than that of a normal person.

As Muneta wrote in his book: “Newborns are
living off of ketones!” Not only is ketosis helpful for supplying
the energy needs of the newborn baby, it may also be an important factor in the development
of the brain. It’s been understood that exercise is beneficial
for the brain because it increases the level of Brain Derived Neurotrophic Factor – BDNF,
which is a protein that promotes the growth of new brain cells. Because of this, Dr. John Ratey of Harvard
Medical School has given BDNF the nickname of “miracle gro for the brain.” However, the mechanism for how exercise triggers
BDNF was not clear for some time, until a paper came out last year that was headed by
Assistant Professor of Biochemistry Dr. Sama Sleiman. I think the title is quite straightforward:
“Exercise promotes the expression of brain derived neurotrophic factor through the action
of the ketone body beta hydroxybutyrate.” Growth of the brain is very important in a
more broad sense as well – growing a big brain is of course what allowed us to become human.

And When it comes to human evolution, efficiency
is the name of the game. That is our bodies had to develop methods
for more efficient extraction and utilization of energy, mainly to support our big energy
hungry brain. One tradeoff for a bigger brain was a smaller
gut- less energy spent on the gut meant more for the brain. As is stated in a Public Library of Science
article titled "Man the Fat Hunter," to adjust for the high metabolic cost of a large brain
“…shrinkage in gut size was a necessary accompaniment.

… A shorter human gut, had evolved to be
more dependent on nutrient and energy-dense foods than other primates. A smaller gut is less efficient at extracting
sufficient energy and nutrition from fibrous foods and considerably more dependent on higher-density,
higher bio-available foods that require less energy for their digestion per unit of energy
/ nutrition released.” This implicates fat as an important food source
because it is obviously very energy dense, providing 9 calories per gram. But the efficiency of using fat for fuel is
deeper than just calories. Also, our brains’ power and capacity for
intellect comes not just from the increase in size, but also from enhanced blood flow
and efficient use of oxygen.

Roger Seymour of the University of Adelaide
and his team found that bloodflow to the brain increased at an unexpectedly rapid pace over
a period of 3 million years. Seymour says: “While brain size was increasing
3.5 times, blood flow rate surprisingly increased six hundred percent, from about 1.2ml per
second to 7ml per second. …This indicates that our brains are six
times as hungry for oxygen as those of our ancestors, presumably because our cognitive
ability is greater and therefore more energy-intensive.” This would suggest that the most important
fuel for the brain is going to be one that uses oxygen more efficiently. And this is exactly what ketones do.

Dr. Richard L Veech found in 1994 that administering
ketone bodies to a rat heart led to a 25% increase in hydraulic work, but a decrease
in oxygen consumption. Theodore VanItallie explained this phenomenon
in a 2003 article by saying that the ketone body beta hydroxybutyrate increases the efficiency
of energy production in the cell’s mitochondria. If you were schooled in the states and attended
even a day of biology class, you would know that mitochondria are the “powerhouses of
the cell.” But is this improvement in efficiency happening
in the powerhouses of the brain cells? Well, Vanitallie says that “Studies of blood flow and oxygen consumption
in the brains of food-deprived obese human subjects revealed values that were well below
the normal levels for adult human brains… they suggest an increase in the metabolic
efficiency in human brains using ketoacids as their principal energy source in place
of glucose.” People who have done extended fasts will sometimes
report a euphoric or drastically enhanced state of mental clarity around day 6 or 7
– this is when ketone bodies have reached a particularly high concentration: somewhere
over 5 millimolars per liter depending on the person.

In essence ketone bodies may be a preferred
fuel source for the brain as they provide more cellular energy per unit of oxygen compared
to glucose. Getting more bang for your oxygen through
ketosis would be incredibly significant for the development and maintenance of big brains. Some of Dr. Dominic D’Agostino’s work
revolves around taking advantage of ketosis’s efficient usage of oxygen in the cells. His research touches on ketosis’s potential
for treating a variety of illnesses including Epilepsy, ALS, Alzheimer's , Parkinson's and
even some cancers. His initial research, funded by the Office
of Navy Research, was aimed at improving Navy Seal Divers diving capabilities. The most straightforward display of ketones
efficient use of oxygen is that simply by being in the state of ketosis, Dr. D’Agostino
was able to double his breath hold time from 2 minutes to 4 minutes without any prior training. To sum all this up, when fasting long enough,
or when protein and carbohydrate intake are restricted enough, our bodies switch over
to breaking down fat and making ketones – potentially the most efficient fuel that can be used by
humans. The brain is a massive blood flow, oxygen
and energy hog that needs to constantly be fueled – anything that could enhance energy
efficiency would be very important for the survival of big brained humans.

Despite the evidence that our bodies and brains
may actually prefer to run on ketones, ketosis is still frequently misunderstood as a potentially
dangerous state. Going back to the thymus story, surely children’s
thymuses wouldn’t have been irradiated if the anatomical data of healthy children had
been available at the time. And, maybe with ketones, the perception of
them would be totally different if the first pieces of data didn’t come from a diabetic,
but say a healthy pregnant mother, or a healthy newborn..

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