Co Q10 vs Idebenone. Mitochondrial function, ROS, Anti oxidant activity; The science.

[keenly]

The last month Idebenone has stopped working for me.

I had no idea why and have been searching for answers. Prior to this month of hell, it helped immensely with energy levels and muscle function

I have been looking on pubmed for info

Border between natural product and drug: Comparison of the related benzoquinones idebenone and coenzyme Q10

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803797/

Idebenone as complex I inhibitor

In fact, more than just being an inefficient substrate, multiple studies consistently detected inhibition of complex I by idebenone, in contrast to the function of CoQ10 [10], [11], [12], [13], [14], [15], [16], [17], [19], [20]. Recent data confirm this inhibitory activity of idebenone using the sophisticated electrochemical detection of proton translocating activity of isolated mitochondrial membranes [16]. This inhibition of complex I by idebenone is thought to be based on the slow release of reduced idebenone from the CoQ10binding site within complex I, which therefore interferes with the physiological reduction of CoQ10 [15]. One possible explanation for this inhibitory activity is based on the size of the quinone binding pocket of complex I. The long lipophilic tail of CoQ10 safely secures the molecule in the mitochondrial membrane, while still allowing the quinone moiety to enter into the quinone binding pocket of complex I. Idebenone on the other hand can be expected by its much shorter tail to completely enter the binding pocket, which likely results in a much longer time within the pocket [15]. This difference in tail size and the arising difference in its interaction with complex I make idebenone, quite contrary to CoQ10, a competitive inhibitor of complex I.

Can idebenone substitute for CoQ10?

Most studies on the activities of idebenone have been carried out in cells and tissues that contained physiological levels of CoQ10...

.

https://www.ncbi.nlm.nih.gov/pubmed/21483849/

Idebenone and Neuroprotection: Antioxidant, Pro-oxidant, or Electron Carrier?

Although early work demonstrated that idebenone can restore complete succinate oxidation in CoQ-depleted brain mitochondria, NADH oxidation in the presence of idebenone was independent of downstream components of the ETC [37]. These findings suggest that idebenone is effective at transferring electrons from complex II (succinate dehydrogenase) but not from complex I (NADH dehydrogenase) to complex III. Experiments using intact cells, which oxidize primarily NADH-linked substrates, confirmed that idebenone cannot substitute for the electron transfer function of CoQ in CoQ-deficient fibroblasts [38]. However, several studies support the ability of idebenone to act as an effective electron carrier from complex II or glycerol-3-phosphate dehydrogenase to complex III

'At apparent odds with its presumptive neuroprotective potential, multiple groups reported that idebenone can inhibit complex I and promote superoxide production'

'it was also demonstrated that idebenone inhibits ADP-stimulated and uncoupled respiration by intact rat brain mitochondria in the presence of complex I-linked substrates'

Reduction of Hydrophilic Ubiquinones by the Flavin in Mitochondrial NADH:Ubiquinone Oxidoreductase (Complex I) and Production of Reactive Oxygen Species†

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651670/

'The antioxidant function of idebenone is critically dependent on two-electron reduction to idebenol without the creation of unstable intermediates. Recently, cytoplasmic
NAD(P)H:
quinone oxidoreductase 1 (NQO1) was identified as a major enzyme catalyzing idebenone reduction. While reduction allows idebenone to act as an antioxidant, evidence also suggests that NQO1 enables idebenone to shuttle reducing equivalents from cytoplasmic NAD(P)H to mitochondrial complex III, bypassing any upstream damage to the electron transport chain'

So I guess now Idebenone is causing more superoxide
why?

For 18 months it worked tremendously, to the point I went to the gym. Then did too much crashed, a few days later lots of B12 caused apparent B2 deficiency; the results Idebenone does not work for me at all.

How do I rectify this? Adding Coq10?

Can somebody who understands this better than me speak on it? I would greatly appreciate.

 

[Little Bluestem]

a few days later lots of B12 caused apparent B2 deficiency; the results Idebenone does not work for me at all.

Have you rectified the apparent B2 deficiency?

 

[keenly]

Have you rectified the apparent B2 deficiency?

I am trying, but I have no idea.

Sequence of events
Gym on Saturday, did too much, breathing problems.
B12, mixed B vitamin oils arrive a week later, immediately I use high dose, 3, 4 sprays.
3 days later, weak, shaky, irritable, fatigued, tingling

Now Idebenone does not work for me. I never had any fatigue in the house using it prior to this. I have tried stuff for 12 years and nothing worked like it.

 

[Little Bluestem]

@keenly - like many things, you need to start low and go slow with B2. It also needs a bunch of supporting nutrients. The is information in the threads on hair mineral testing and using B2.

 

[keenly]

@keenly - like many things, you need to start low and go slow with B2. It also needs a bunch of supporting nutrients. The is information in the threads on hair mineral testing and using B2.

I recently had a HMT, I am excreting high amounts of Selenium and tin!! Lithium and zirconium were almost non existent.