Mitochondria may contribute to neurological and psychiatric disorders: research

I was in a lab meeting maybe 4 years ago or so and my PI had just come back from a conference on Alzheimer's. He reported back that groups had started investigating the role of mitochondrial dysfunction in the disease and had been able to find that lineages with variants in genes related to mitochondria and energy homoeostasis were far more likely to have or develop Alzheimer's. I haven't kept an eye on progress in that line of research, but it is in line with what is being reported/speculated here.

Finally, a couple of years ago I ran into the father of someone I went to middle school with and I learned that he was a biochemist. Somehow the conversation wound around to the challenge of understanding neurodegenerative diseases. I asked him for his take on a disease that only presents after 60ish years. His immediate answer was DNA damage during mitosis. But neuron's don't divide. And then it hit me. There IS something that is still dividing inside the neurons! It is the mitochondria! The other possibility is the astrocytes, the microglia, or some other mitotic cell population in the brain, but the mitochondria really stand out as fitting both the fact the neurons don't divide and the instinct from a veteran biochemist that something that takes so long to appear must be related to DNA damage.

- Delete backup mtDNA

- Cause oxidative damage to mitochondria, impairing their function

- Impair mitochondrial replication

It makes because fluoroquinolones are designed to block bacterial DNA replication by plugging up the enzyme that glues DNA back together after it's separated during cell division. mtDNA replication is very similar to bacterial replication. They damage eukaryotic cells too, likely through a different mechanism.

I've been interested in her ideas ever since close family contracted an autoimmune disease.

Brain fog is something I’ve suffered the last several years. Eventually got a diagnosis of autoimmune Sjogrens. Similar to Lupus.

A link between mitochondria and autoimmune has been of great interest to me as I battle to keep my wits.

If the contribution was significant, wouldn't we have seen folk tales about "if your mum goes mad, you'll go mad too!". Yet, as far as I know, no such tale exists.

I have struggled my entire life with various disorders. ADHD, many symptoms of autism, depression, extreme loss of energy and lethargy. For a long time I thought that I had chronic fatigue syndrome after I grew very sick from a viral infection.

Everything everyone is saying here resounds very strongly with a mitochondrial energy problem.

Diet helps me a lot. I have tried many diet approaches, recently a high protein diet has really been working well. I dont know what is wrong with me, but something isnt right.

Here is my 2 cents based on some experience with the topic. Autoimmune manifestations may be just a normal reaction of the organism to dysfunctional cells on their way to apoptosis. Apoptosis occurs when the percentage of broken mitochondria reaches a certain threshold. So you get the inflammation. It may look like the organism attacks its own tissues by mistake - but actually there is a reason.

When the inflammation kicks in, it also affects surrounding healthy cells adding insult to the damage. You get some kind of progressing encephalopathy that eventually leads to neurodegenerative disorders.

A plausible treatment for such condition: inhibit inflammation while trying to restore the normal mitochondrial function.

A gentle way to inhibit the inflammation is to use nonsteroidal anti-inflammatory drugs such as Acetylsalicylic Acid (Aspirin).

Restoring normal mitochondrial function is considered impossible if you have an inherited mutation in mitochondrial DNA (1 in 50000 of population). However this is a pretty rare condition while the most of mitochondrial manifestations (1 in 5000 of population) are acquired from environmental factors such as poisons, drugs, infections, nutritional imbalances.

The treatment for such an acquired mitochondrial dysfunction is two-fold: 1) eliminate the initial vector (poison, infection etc. 2) reverse the damage that occurred in mitochondria.

Infections, drugs and poisons are self-explanatory. The nutritional deficit is more intricate. But in case of mitochondria, it is basically covered by the Thiamine (B1 vitamin). The only gotcha is that you won't feel the effect with supportive B1 doses like the usual 2 mg per day. You would need therapeutic doses and a more bioavailable form for that to work, like 300 mg of Benfotiamine per day.

Now once that is covered, you would just stop the progression of mitochondrial dysfunction. But that may be not enough if it went too far. You might still have the apoptosis, the associated constant inflammation and the resulting degeneration.

What you can do to rejuvenate mitochondrial function is to use substances like Nicotinamide Riboside (100 mg per day). This is an efficient B3 vitamin precursor without the typical side effects of Niacin. It restores cell respiration by playing the role of an electronic transport in aerobic glycolysis pathway (Glucose + Oxygen -> ATP) which occurs in a healthy mitochondria. Nicotinamide Riboside is the preferred form of B3 because it also plays the role of a mitochondrial growth factor which is a big win in case of mitochondrial deficit.

Now once you combine all these methods, you may be onto something. By modulating the inflammatory response you win the time to restore the mitochondria thus avoiding massive cellular apoptosis.

By gradually restoring the mitochondrial aerobic glycolysis pathway, you are gradually reducing the associated lactic acidosis which also plays a huge negative role in neurological diseases. You break the viscous cycle of anaerobic glycolysis swapping it with a normal, healthy aerobic pathway.

If the damage to the tissues and nervous system is not too substantial, it may be a full recovery given some months of therapy.

Take it from someone who’s whole life has revolved around this topic for years: this is a huge deal, it’s real. There is a medical revolution in the pipes having to do with metabolism and inflammation. This article isn’t a scam.

This is the 21st century. There's no one weird trick to being healthy, successful, having a high quality anything.

Biological systems are complex and don't have a single variable which needs optimizing, they have many, need many, and every variable with leverage needs to be thought as a part of a whole.