Clarified in patents and papers on the ketogenic diet

The main physiological functions of ketone bodies are as follows.

 

(1) Decrease in blood sugar level
(2)     Suppression of oxidative stress
(3)     anticancer effect
(4)     Protective effect on nerve cells (inhibition of epileptic seizures, etc.)
(5)     Reduction of blood fatty acids
(6)     suppression of inflammatory response

(7)     improvement of kidney function

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"Blood sugar level spike suppression effect"

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Diabetes is chronically high blood glucose levels caused by excessive glucose in the blood. If left untreated, arteriosclerosis progresses and blood vessels become more susceptible to damage. My blood sugar fluctuates all the time and I was diagnosed with diabetes.It is not uncommon for postprandial blood glucose levels to be 140 mg/dL or higher, even in people who do not. This rise in blood sugar level for about 1 to 2 hours after eating before falling into a state of constant high blood sugar level is called "blood sugar level spike". Controlling "blood sugar level spikes," in which blood sugar levels rise sharply in a short period of time after meals, is the basis of dietary habits to prevent diabetes. Ketone bodies areIt is known to strongly suppress blood sugar level spikes. That is, ketone bodies are known to activate their receptor HCAR2 and promote the uptake of glucose into tissues (eg, skeletal muscles of the arms and legs).

 

 

“Acquisition of resistance to oxidative stress (active oxygen)”

 

Cell survival depends on mitochondrial energy metabolism, but at the same time, it is thought that it is endangered by reactive oxygen species generated from this. Almost all cells have enzymes that remove active oxygen by themselves. Their expression is regulated at the gene level. One such regulation that occurs at the gene level is histone acetylation. When histones are acetylated, enzymes that scavenge active oxygen are produced more and more, and resistance to oxidative stress can be acquired. The presence of ketone bodies at this time promotes acetylation and can further enhance resistance to active oxygen.

A group from the University of Tokyo School of Medicine clarified the mechanism (published in 2013 / US scientific journal Science), and found that ketone bodies bind to histone deacetylase and inhibit it (release the inhibition of histone acetylation). rice field.

 

"Protection of nerve cells"

Direct administration of ketone bodies to cultured rat hippocampal cells reduced cell death caused by addition of amyloid-β, and similarly, in cultured midbrain cells, it prevented cell destruction by free radicals produced by Parkinson's disease (PK) causative agents. understood. Ketone bodies have the effect of activating gene expression by inhibiting histone deacetylase, a nuclear protein that binds to DNA and regulates gene expression. Ketone bodies act as regulators of gene expression and induce a group of enzymes that remove active oxygen. Ketone bodies thus protect nerve cells. The ketogenic diet may be one of the mechanisms by which neurodegenerative diseases associated with oxidative stress such as Parkinson's disease and Alzheimer's disease are effective.
 

“Neural cell membrane stabilization effect”

Ketone bodies have the effect of stabilizing the membrane potential of nerve cells and suppressing abnormal excitation. Ketone bodies activate ATP-dependent potassium channels, lower membrane potential, and suppress neuronal abnormal excitation. This is the molecular mechanism by which the ketogenic diet suppresses epileptic seizures. However, the membrane potential stabilizing effect of ketone bodies on nerve cells requires an increase in concentration to at least the mM order, and a thorough ketogenic diet is required. It has been known for more than 100 years that the ketogenic diet is highly effective against intractable epilepsy, but the reason why it is not widely used in clinical practice is that this thorough ketogenic diet is necessary. There is a cause. However, since ketone bodies have the function of maintaining a wide variety of brain functions normally, a ketogenic diet that can increase ketone bodies to the mM order is effective in preventing or treating various neurodegenerative diseases. It is believed that there is.

"Cancer suppression effect"

Ketone bodies suppress the growth of cancer cells and have the effect of regressing cancer. Cancer cells use only glycolysis to proliferate (Warburg effect). In other words, even if mitochondria exist in cancer cells, they are hardly utilized, and most of the energy substrates they need use glycolysis. mitochondCancer cells are known to undergo apoptosis or stop growing under conditions where ketone bodies and other organic acids, which can act directly on the rear, predominate. In addition to acting as an energy substrate for ketone bodies, it has been suggested that ketone bodies may inhibit cancer cell growth through activation of the HCAR2 receptor, inhibiting the growth of many types of cancer cells. reported to do.
 

"Adjuvant action"

Of particular interest in the cancer-suppressing action of ketone bodies are gliomas. Gliomas are characterized by the following two characteristics. One is that radiotherapy is possible due to its low invasiveness. The other is that most anticancer drugs cannot pass through the blood-brain barrier, so they have little effect on gliomas. On the other hand, ketone bodies are highly transmissible to the brain, and 20-30% of ketone bodies are translocated to the brain. In this sense, the combination of radiotherapy and ketone bodies is a combination with high clinical expectations. Against this background, cancer adjuvant action has attracted attention as a prominent action of the ketogenic diet. We found that irradiation of mouse gliomas significantly improved mouse survival, but radiation plus a ketogenic diet improved mouse survival even more. The effect of ketone bodies on inhibiting the growth of cancer cells is not limited to gliomas, but is observed in many cancer cells, so this report is noteworthy in terms of the effective use of ketone bodies as food in the medical science field. It can be said that the ketogenic diet is effective as a means for significantly enhancing the therapeutic effects of 1) chemotherapy, 2) radiation therapy and 3) surgical therapy, which are the most basic therapies for cancer. Focusing on this adjuvant action, clinical trials for cancer treatment are being conducted in various countries.

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​​ " Neutral fat lowering effect"

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When a healthy person follows a ketogenic diet, the concentration of ketone bodies in the blood increases. It activates mitochondrial metabolism throughout the body (especially in skeletal muscle).

Therefore, in skeletal muscle, the function shifts in the direction of producing energy (by decomposing fat). The amount of triglycerides taken up from the blood by skeletal muscles is increased, and blood glycerol (triglycerides) is significantly reduced. metabolism like thisThe shift in is an energy shift to permanently eliminate obesity.Conceivable.

 

 

"Anti-inflammatory action"

Ketone bodies suppress chronic inflammation. That is, ketone bodiesIt suppresses the function of the protein NLRP3, which is a component of the protein complex necessary to continuously promote sexual inflammation, and suppresses chronic inflammation. In addition, ketone bodies have the ability to activate HCAR2, a receptor for some organic acids, suppress various inflammatory reactions, and consequently suppress cancer. From these basic studies, it can be easily inferred that ketone bodies have inhibitory effects on pathological conditions involving inflammatory reactions such as ulcerative colitis, colon cancer, rheumatism, arteriosclerosis, and obesity.

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“Renal function improving effect”

 

A group at Shiga University of Medical Science has revealed that ketone bodies activate autophagy and suppress diabetic nephropathy.

(Published in July 2020 / American scientific journal   Cell Metabolism) ​

In experiments with mice, administration of a ketone body precursor (1,3-butanediol: 1,3-BD) ameliorated the increase in serum cystatin C and tissue damage, which indicate increased renal dysfunction in a diabetes model. Feeding a substance (butanediol  *1) that converts to ketone bodies in the liver decreases the protein cystatin C in the blood, which indicates a decline in renal function.

Therefore, it can be expected to improve the symptoms of diabetic nephropathy in humans as well.

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*For citation sources, please refer to the references below.