A long time ago, when I went to medical school, the concept of glucose production from ketones was considered very small and very rare. It was like a myth, because glucose level in blood was controlling hormones related to metabolism minute to minute in normal people, and nobody wanted to investigate ketones which were present in patients with diabetes. It was considered irrelevant to study ketone bodies to win a Nobel prize. Severo Ochoa worked on glycolysis (breakdown of glucose for fuel) and fermentation since 1936 and won the Nobel Prize in 1959 (https://en.wikipedia.org/wiki/Severo_Ochoa). The Krebs cycle was studied from the point of view of glycolysis, I was told that glucose was needed in order to burn fat. George Cahill lost the political battle in science and his research on ketone bodies was not the one to follow. Marketing carbohydrates changed our lives and put us in this obesity crisis worldwide, as one of Cahill’s students put it:
This story begins in the early 1960s when the
general level of knowledge about whole‐body
metabolism during human starvation was grossly deficient. This was partly
caused by a lack of accurate and specific methods for measuring hormones and
fuels in biological fluids, which became available about 1965.1 Rigidly
designed protocols for studying human volunteers or obese patients, who
underwent semi‐ or total
starvation for prolonged periods of time, were not widely employed, and much of
the published data regarding metabolic events during starvation were not
readily accessible. To complicate matters further, a great deal of the
available data was confusing because much of the supposition regarding
mechanisms used by the body to survive prolonged periods of starvation was
based upon information that was obtained from nonstandardized and often
erroneous procedures for studying metabolism… The pathway to knowledge on the nature
and regulation of human fuel metabolism has taken a long and circuitous route.
It is easy to understand how physician‐scientists
initially formulated erroneous concepts regarding the requirements of the brain
and other tissues for fuels such as glucose. Ironically, studies of diabetics
and patients with insulin‐induced
hypoglycemia complicated (rather than clarified) the understanding of the
normal metabolism of the brain. The treatment for diabetes became available
with the discovery of insulin at the University of Toronto in 1921–22. This
scientific breakthrough was one of the most dramatic events for the management
of any disease. By lowering the level of blood glucose, insulin's impact on a
diabetic patient was sensational and seemingly miraculous.2 However,
initial research of brain metabolism was hindered by the widespread yet
erroneous hypothesis that developed as a consequence of treating diabetic
patients with insulin.3
https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/bmb.2005.49403304246
Gluconeogenesis was
considered small because we were already eating great quantities of sugar
(glucose), and the need to produce our own glucose was not there according to
doctors. Ketones as fuel for the brain
was considered just in extreme cases. Over the years I learned the following:
16.3.5. The Generation of Free Glucose Is an Important Control Point
The fructose 6-phosphate
generated by fructose 1,6-bisphosphatase is readily converted into glucose
6-phosphate. In most tissues, gluconeogenesis ends here. Free glucose is not
generated; rather, the glucose 6-phosphate is processed in some other fashion,
notably to form glycogen. One advantage to ending gluconeogenesis at glucose
6-phosphate is that, unlike free glucose, the molecule cannot diffuse out of
the cell. To keep glucose inside the cell, the generation of free glucose is
controlled in two ways. First, the enzyme responsible for the conversion of
glucose 6-phosphate into glucose, glucose
6-phosphatase, is regulated. Second, the enzyme is present only in
tissues whose metabolic duty is to maintain blood-glucose homeostasis—tissues
that release glucose into the blood. These tissues are the liver and to a
lesser extent the kidney.
This final step in the
generation of glucose does not take place in the cytosol. Rather, glucose
6-phosphate is transported into the lumen of the endoplasmic reticulum, where
it is hydrolyzed to glucose by glucose 6-phosphatase, which is bound to the
membrane (Figure 16.29). An associated Ca2+-binding stabilizing protein is essential for
phosphatase activity. Glucose and Pi are then shuttled back to the cytosol by a
pair of transporters. The glucose transporter in the endoplasmic reticulum
membrane is like those found in the plasma membrane (Section
16.2.4). It is striking that five proteins are needed
to transform cytosolic glucose 6-phosphate into glucose.
But let’s continue with Dr.
Oliver Owen narrative:
Early insulin therapy was not perfect; insulin
saved the lives of experimental animals and subsequently humans, but
researchers initially had no way of knowing how much to administer or how to
best administer it. They recognized that in the absence of insulin the
concentration of blood glucose rose to high levels and death occurred. Also,
injecting too much insulin lowered the blood glucose to a point where a
“peculiar” behavior occurred; animals and humans began frothing at the mouth,
became unconscious, developed convulsions, and died. Eating carbohydrate‐rich foods (i.e. orange juice or candy) or receiving intravenous
glucose reversed these adverse effects. Glucose was clearly the key fuel
metabolized by the brain; the possibility that other fuels, such as ketone
bodies, were also metabolized by this organ was completely ignored. The
presence of ketone bodies in the blood and urine of insulin‐deficient diabetic patients was recognized in
the 1880s and was associated with severe disease states. In the 1920s, it
became evident that insulin lowered the content of glucose in the blood and
urine of diabetic humans, and it also removed ketone bodies. Nonetheless, the
idea that insulin controlled only glucose metabolism and that too little
glucose in the blood led to brain dysfunction led to the widely held concept
that glucose was the only fuel used by the brain. In the 1950–60s, researchers
learned that insulin lowered not only the concentration of glucose and ketone
bodies in the blood and urine but also a host of other fuels, including free
fatty acids and amino acids. Unfortunately, these isolated discoveries did not
correct the widely held misconception that ketone bodies were unhealthy and
that glucose was the only source of fuel for the brain.
¿Are we over the
persecution? Tim Noakes lost his job when he mentioned what it is here (2014),
and blamed the high carb diet marketed for the obesity epidemic. He even was accused in court, in a trial that
looked like the Greek trial of Socrates.
No wonder Noam Chomsky says that our civilization is “involuding:”
The trial of Socrates (399 BC)[1] was
held to determine the philosopher’s guilt of two charges: asebeia (impiety)
against the pantheon of
Athens, and corruption of the youth of the city-state; the accusers cited two
impious acts by Socrates: "failing to acknowledge the gods that the city
acknowledges" and "introducing new deities".
https://www.youtube.com/watch?v=rtmK8ZBsUJg
I let you with this video
from GCN which is well done and illustrates what we should do. The induction time for the diet should be
longer, three weeks at least.
https://www.youtube.com/watch?v=_NdyZ-wIhcU
