Over the last few months, I've been noticing some trends, and as I spent another nearly sleepless night reading and watching videos, some of the pieces seem to be fitting together. In short, it seems that more and more theories and studies are focusing on mitochondria. In particular, a "biochemical defect" of Complex 1. "What's that?" you ask.
"Complex 1 is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex 1 is the first of five mitochondrial complexes that carry out a multi-step process called oxidative phosphorylation, through which cells derive much of their energy." *
"... These results indicated a specific defect of Complex 1 activity in the substantia nigra of patients with Parkinson’s disease. This biochemical defect is the same as that produced in animal models of parkinsonism by 1-methyl-4-phenyl- I ,2,3,6-tetrahydropyridine (MPTP) and adds further support to the proposition that [some cases of] Parkinson’s disease may be due to an environmental toxin with actions similar to those of MPTP." **
It's not just nerve cells in the substantial nigra that have this defect; there are neurons in the "gut brain" that do, too. This may explain how something from the outside environment could affect our substantia nigra: when we eat, drink, or breathe in MPTP (I'll just use MPTP as a stand-in for many possible attackers), it infects the "gut brain" and from there it is carried up the vegas nerve, which attaches to our main brain close to the substantia nigra.
So what happens to a neuron that becomes infected? The brain's immune system should be triggered to fight the infection. I won't get into this in detail, but the end result is PD; dead or badly damaged neurons that are not repaired, recycled, or replaced. Why? Remember; everything takes energy, and without functioning mitochondria, these cells have none. They can't even "self eat" (autophagy) because even that takes energy. So they become senescent cells if they survive at all. The MPTP (attacker) is evidently not gone, or at least its damage continues to spread. Could this be because the senescent cells spew something? Can we trigger autophagy to recycle and replace them?
Now we are finally ready to ask: "What can be done about this?" I was surprised to learn of a study in 2018 that might be pointing to a partial answer. They reported fairly substantial and consistent improvements in PD symptoms for PWP who switched to a very high-fat, low-carb keto diet. It hasn't been widely adopted yet, because a long-term keto diet would be very difficult to sustain by PWP. There was also an unnerving side effect; many of the PWP who switched to the keto diet experienced a significant worsening of their tremors. They faded after a few weeks.
This study also doesn't report on what happened when the subjects switched back to their pre-study diets. Did the subjects revert back to pre-study PD symptoms? If so, did it take time or did they just come rushing back? (I'll look into this more to see if they ever did a follow-up report on that.)
Keto worked (at least to some degree) probably because a keto diet doesn't require a mitochondria's Complex 1 in order to make energy (ketones). However, this (probably) didn't repair the damaged mitochondria. I've asked around a bit, and the few I've found who have tried this have reported that, yes it has lessened their PD symptoms, but their PD continues to progress. Why, and can we do something to repair or replace these mitochondria or the cells they're in? Does anyone know of ways to do this? Fisetin? Time+ (from Nuchido), NMN? Serrapeptase? Rapamycin? 30-day water fast? All of this and more?
This study's results are very interesting, though, because it suggests that we now *might* know what to fix in order to find real answers. They seem to have legitimately had improvements, short-lived or not. That has to give us some clues!
_______________ References
* => medlineplus.gov/genetics/co....
** => d1wqtxts1xzle7.cloudfront.n...
*** => youtu.be/O2yJAqRP0Y8
