The basics of ketogenic diet: works of Shaffer and Wilder & Winter

Glucose,Ketogenic diet,Ketone bodies,Ketosis, ketogenesis,Methodology — Tags: , — 6:16 am

It is interesting that while the ketogenic diet becomes well researched as a method for improving energy metabolism during quite a few medical conditions and the number of original research articles as well as reviews grow currently approaching 15,000, only 19 out of all of them cite the original work, which in fact is the basis of the diet. >>> Read more

The ketogenic diet is no longer considered a strictly anti-epileptic diet: its suggested and tested applications includes a broad spectrum of disorders of energy metabolism. The ketogenic ratio formula used in clinics for calculating the ketogenic diet composition was offered by Wilder and Winter in 1922 (1). They argued that the levels of ketogenic substances depend on the ratio between fatty acids and glucose of the metabolizing foods. The ratio when ketogenesis is initiated they called the threshold of ketogenesis: “When the proportion of acetoacetic acid to glucose in such mixtures was that of 1 (or possibly 2) molecules of acetoacetic acid to 1 of glucose, the former substance was completely oxidized. When the proportion of glucose was less, a considerable fraction of acetoacetic acid escaped oxidation.”

Shaffer (2, 3) calculated the number of molecules of ketogenic substrates corresponding to the number of molecules of glucose and concluded that the maximal ratio compatible with the oxidation of the ketogeniec compounds was reached when a ratio of of ketogenic molecules to the number of glucose molecules was 1: 1. He subsequently considered that each glucose molecule is ketolytic for 2 molecules of acetoacetic acid, a 2:l ratio.

Wilder and Winter, 1922 included in their formula the following measurements obtained in clinical settings:

1) basal metabolism for 24 hour periods plus 10 per cent for the specific dynamic action of food and 10 per cent for movements;

2) the calories from the protein metabolism assessed by nitrogen excretion;

3) the calories from fat metabolism taken as the sum of the calories of protein and carbohydrate combined subtracted from the total calories of the day.

The values for carbohydrate and fat are used in the calculation of the ratio between the ketogenic molecules and the glucose molecules (2, 3).

“Under the conditions of these experiments, provided these assumptions are tenable, the ratio between the ketogenic and the glucose molecules at which a clinically significant ketosis appears has a value of at least 2: 1. A ratio of this value implies that every molecule of glucose is ketolytic for 2 molecules of acetoacetic acid.”

References

  1. Wilder R., Winter M. Thew threshold of ketogenesis. J. Biol. Chem. 1922 52: 393-401.
  2. Shaffer, P. A., Antiketogenesis. I. An in vitro analogy, J. Biol.Chem., 1921, xlvii, 433.
  3. Shaffer, P. A., Antiketogenesis. II. The ketogenic antiketogenic balance in man, J. Biol. Chem., 1921, xlvii, 449.

 

 

 

On the mechanisms of brain protection by ketones

Dementia,Excitatory GABA,Ketogenic diet,Ketone bodies,Neuroprotectors — Tags: , , , , , , , , — 8:17 am

Neuronal activity in immature neocortical neurons depends on the availability of ketone bodies in ACSF

The provoking findings of Rheims et al. suggest that an important caveat of previous electrophysiological experiments is that they were carried out with artificial cerebrospinal fluid (ACSF) added with energy sources that can only be metabolized through glycolytic pathways (e.g. glucose).

The provoking findings of Rheims et al. suggest that an important caveat of previous electrophysiological experiments is that they were carried out with artificial cerebrospinal fluid (ACSF) added with energy sources that can only be metabolized through glycolytic pathways (e.g. glucose).

Researchers studied how naturally occurring ketones influenced activity of brain cells during development. They showed that a shortage of ketones caused pathological changes in brain cells resulting in abnormal behavior of GABA, the principal brain chemical helping to resist hyperactivity. It was repeatedly reported earlier that, normally working as a “break pedal”, GABA did not do the job in the immature brain and acted as a “gas pedal” instead. To imagine the devastating consequences, picture a car having two gas pedals and no brakes.

To make things worse, the energy deficit during hyperactivity is usually combined with increased energy demands thus starting a vicious circle — demands/deficit/demands — a well known feature of many neurodegenerative diseases including Alzheimer’s, Parkinson’s, epilepsy, encephalopathies, dementia, or multiple sclerosis. For many of them, the ketogenic diet was shown to be of a significant help. In the new article, the French and UK researchers offered an explanation. When there was enough of ketone bodies, GABA displayed its natural “break” properties and parameters of brain cells were also normal — as it happens in real life, in real animals and babies.

Researchers suggest that sufficient supply of appropriate brain fuels can break the vicious circle and prevent brain’s hyper-excitation. They now look into other natural energy substrates possibly having greater potential as a “diet in a bottle” than the costly ketones while being as efficient as the overly-stringent ketogenic diet.

Source: J Neurochem. 2009 Aug;110(4):1330-8. Epub 2009 Jun 22. GABA action in immature neocortical neurons directly depends on the availability of ketone bodies. Rheims S, Holmgren CD, Chazal G, Mulder J, Harkany T, Zilberter T, Zilberter Y.

To make things worse, the energy deficit during hyperactivity is usually combined with increased energy demands thus starting a vicious circle — demands/deficit/demands — a well known feature of many neurodegenerative diseases including Alzheimer’s, Parkinson’s, epilepsy, encephalopathies, dementia, or multiple sclerosis. For many of them, the ketogenic diet was shown to be of a significant help. In the new article, the French and UK researchers offered an explanation. When there was enough of ketone bodies, GABA displayed its natural “break” properties and parameters of brain cells were also normal — as it happens in real life, in real animals and babies.

Researchers suggest that sufficient supply of appropriate brain fuels can break the vicious circle and prevent brain’s hyper-excitation. They now look into other natural energy substrates possibly having greater potential as a “diet in a bottle” than the costly ketones while being as efficient as the overly-stringent ketogenic diet.Source: J Neurochem. 2009 Aug;110(4):1330-8. Epub 2009 Jun 22.

GABA action in immature neocortical neurons directly depends on the availability of ketone bodies. Rheims S, Holmgren CD, Chazal G, Mulder J, Harkany T, Zilberter T, Zilberter Y.

http://starturl.com/GAGA-ketones

Physiological effects of ketone bodies

Applications,Ketogenic diet,Ketone bodies — Tags: , , , , , , — 8:33 am

See References in this post

Anticonvulsant action of the ketogenig diet

Ketogenic diet,Ketone bodies,Theories — Tags: , , , , — 8:31 am

Anticonvulsant action of the ketogenig diet

HYPOTHESES:

Ketogenic diet reduces seizures by:

a) promoting inhibitory action of GABA

b) reducing cellular consequences of energy deficiency by supplying an alternative and 40 % more efficient fuel

c) eliminating damaging consequences of excessive glycolysis

Question: what does work in this case — ketone bodies or glycolysis exclusion?


Is ketosis natural?

Ketogenic diet,Ketone bodies,Ketosis, ketogenesis,Methodology — Tags: , , , — 8:29 am

“Repeat after me three times, ketones are not evil, ketones are not evil, ketones are not evil… OK, now that we have gotten that out of the way…”

– Jeffrey Paul Krabb, MD

In general medical literature, ketosis is often defined as abnormally high levels of ketone bodies in the blood.

Meanwhile, ketosis — but not ketoacidosis! — naturally occurs:

  • Every morning after the night fast
  • During fasting and calorie restriction
  • After intensive prolonged exercise
  • As a result of a diet significantly higher in fat comparing tha in carbohydrates
  • Early in ontogenesis

Effects of ketone bodies: references

Applications,Ketogenic diet — 8:50 am

Energy substrates availability in milk

Energy Substrates,Ketogenic diet — Tags: — 8:44 am

 

We calculated the ketogenic potential of different kinds of milk using the standard formula suggested by (Wilder, Winter, 1922) – see also The basics of the ketogenic diet

Ketogenic to Anti-Ketogenic Macronutrient Ratio


K:A=(0.9 fat +0.46 protein) : (1.0 carb +0.1 fat+0.54 protein)

This formula essentially reflects the rate of utilization of either carbohydrate or lipid substrates depending of their availability

The numbers in front of nutrient names are coefficients that are calculated based on nutrient ability to cause or resist ketosis.

1) Carbohydrate is assigned the coefficient 1.0 because it is an absolutely anti-ketogenic nutrient. The more carbohydrate grams contained in a diet, the less KB the body can produce

2) Fat is a 90-percent ketogenic nutrient

3)Protein can participate in the process of gluconeogenesis.



Here are K:A ratios of milk of some species.


Human milk – 0,568

Cow milk – 0,663

Goat milk – 0,779

Rat milk – 1,628

Mouse milk – 2,846


(Clinical data: out of 21,000 human neonates, 47 were in ketosis)

 

Source: Wilder R., Winter M. Thew threshold of ketogenesis. J. Biol. Chem. 1922 52: 393-401.

 

 

Ketogenic diet compared to antiepilepsy drugs

Ketogenic diet,Ketone bodies,Methodology — Tags: — 7:46 am


    The ketogenic diet’s success rate greatly exceeds that of the medications.
    Its side effects, both cognitive and allergic, appear fewer than most available medications.
    Understand why changing from a glucose energy to a ketone energy is anticonvulsant can
    help in developing a pharmacological approach simulating the biochemical effects of
    the ketogenic diet.
      The ketogenic diet’s success rate greatly exceeds that of the medications.
      Its side effects, both cognitive and allergic, appear fewer than most available medications.
      Understand why changing from a glucose energy to a ketone energy is anticonvulsant can
      help in developing a pharmacological approach simulating the biochemical effects of
      the ketogenic diet.

    Source : The Ketogenic diet. Advances in Pediatrics, 1997.

Ketogenic diet efficiency in experiments and clinical trials

Epilepsy,Glucose,Ketogenic diet,Ketone bodies — Tags: , , , , , — 8:48 am

 

See References in this post

 
Ketogenic diet efficiency has been studied for different age groups, species, types of diet including LCT and MCT triglycerides or types of fatty acids, calorie restriction, glycolysis limitation, etc.

Ketogenic diet efficiency in experiments and clinical trials

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