Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis

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[https://www.nature.com/articles/s41392-020-00411-4](https://www.nature.com/articles/s41392-020-00411-4)

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What does this all mean?

In: Biology
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This is a refereed scientific paper that found there were heart side-effects to long-term keto diets, in lab mice.

That means you should not choose a mouse food with low carb and high fat if you want to maximize their life expectancy.

Studies in people are much more difficult, because human lifespan is much longer than mouse lifespan, but this is an indication that people on keto diets might benefit from considering the effect observed in these mice:

> Mechanistically, increased levels of the ketone body β-hydroxybutyrate (β-OHB), an HDAC2 inhibitor, promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription.

This could lead to β-OHB monitoring, through blood tests, in people who are on these diets to see that levels remain normal.

>decreased mitochondrial biogenesis

Mitochondria are the powerhouse of the cell as you may have heard – shove calories into them and they turn it into usable energy like coal into a coal powerplant. Biogenesis is a fancy word for “organically making more of something”. So mitochondrial biogenesis is cells making more mitochondria. Decreased mitochondrial biogenesis is the cells building fewer power plants and therefore not having as much available energy as they would prefer to have.

> reduced cell respiration

Respiration is, in simple terms, the name for the process of mitochondria generating energy. This should make sense: fewer powerplants, less energy generation.

> increased cardiomyocyte apoptosis

Cardiomyocyte is a fancy word for “heart cell”, apoptosis is a fancy word for “committing suicide”. So what this is saying is increased rate of heart cells killing themselves.

> [increased] cardiac fibrosis

Cardiac means “concerning the heart”, eg “Cardiac arrest” means “heart arrests (stops working)”. Fibrosis is, in simple terms, scarring. So basically what this is saying is as heart cells are dying off, the body is replacing them with scar tissue (which doesn’t do anything but fill holes), instead of new heart cells.

>Mechanistically, increased levels of the ketone body β-hydroxybutyrate (β-OHB), an HDAC2 inhibitor, promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription. This in turn inhibited the transcription of mitochondrial ribosome-encoding genes and mitochondrial biogenesis, leading to cardiomyocyte apoptosis and cardiac fibrosis.

This is basically telling a story: A chemical that increases on a ketone diet breaks the system that heart cells use to create functional mitochondria. This leads to the death of heart cells, which are then replaced by scar tissue, lowering the function of the heart in a way that looks similar to the cellular damage found in a condition called atrial fibrillation (which is where the heart can’t get it’s shit together and just flutters pointlessly. This is what a defibrillator is designed to solve, hence the name de-fibrillator).

So, essentially, if you’re a mouse and you go on a ketone diet you fuck your heart up.