LONGECITY

So the question is, at what point does taking supplements that enhance the mitochondria, either through energy usage or mitochondrial biogenesis, become redundant or even counter-productive?

I ask because right now I'm taking at least four - PQQ 20 mg non-training days, 40 mg training days, CoQ-10 100 mg, ALCAR 500-1000 mg, and C-60oo, 1.5 mg. This is not an extreme stack, at least by Longecity standards, and I'm only going to be taking these four daily until I run a half-marathon on Oct. 18th, at which point I will cut back and likely cycle them. As a reference point I normally only take 10 mg PQQ and 100 mg CoQ-10 but consider this a fun experiment to see how it affects my endurance.

I'm 25 and in good shape but was curious as to if this is redundant or if this combo, as a stack, is something that I should keep cycling indefinitely.

At 25, you probably aren't going to get a big bang out of these, although they will probably make a difference in athletic performance.  It might be hard to see if you started out in not so good shape, because there will be a training effect.  The best way to detect a difference is to start in a trained state, and get accurate measurements of your performance on fixed tasks over several days before and after using the drugs.  You probably don't need the CoQ10 at your age.  You could definitely cut the c60 dosage back, to a half or a third of your current dose, and you could bunch those doses at weekly, biweekly, or even monthly intervals.   If you want to cycle c60, the off periods will need to be months rather than weeks or days, due to its extremely long half life.

Thanks for the input niner. I started out in quite good shape, though I don't train for endurance, more strength training, HIIT and shorter trail runs, so I won't be able to judge whether I've seen any statistical improvements. 

Re the CoQ10, I'm sure I don't "need" it per se at my age, but looking at all of it's benefits I'll likely continue using it at a much lower dosage, maybe 50 mg every other day. This is also how I feel about the PQQ - will prob use 10 mg every other day. Having seen how much it (CoQ) helps cardiac patients, combined with all the stories of marathon runners dropping dead from heart failure, I'll definitely be using it while training - not that I'm worried about dropping dead at all, but just to practice damage control.

As per the c60, you're saying a half or a third my current dosage, and even once a month? So possibly as low as .4 mg once a month, or am I missing something?

 I'm with Niner, but I think the C60oo is a good idea and have seen first hand what it can do for endurance. As for the rest of your stack, save the money, your too young to need them, yet.

Mike

PS,

on C60 you can do real tendon/ligament damage if you push too hard or too long.

Err on the side of caution.

Thanks mpe. And I remember reading through a bunch of posts on c60, hearing about how people push too far and get injured. On my runs I've been going a lot farther in a short amount of time than I normally do and am making myself stop, despite having the energy for more. I have to admit, using just a few adaptogens and mitochondrial enhancers, my endurance has shot up remarkably in just a few weeks.

I'll probably use the c60 at a low dose, maybe a pipette (1.5 mg) once a week or every other week, until the bottle runs out. Despite reading mostly good things about it I'm still going to err on the side of caution. As for the PQQ and CoQ10, I'll likely do 10 mg and 50 mg respectively, every other day. I've just read too many exciting things about these compounds.

Thanks for the input niner. I started out in quite good shape, though I don't train for endurance, more strength training, HIIT and shorter trail runs, so I won't be able to judge whether I've seen any statistical improvements. 

 

Re the CoQ10, I'm sure I don't "need" it per se at my age, but looking at all of it's benefits I'll likely continue using it at a much lower dosage, maybe 50 mg every other day. This is also how I feel about the PQQ - will prob use 10 mg every other day. Having seen how much it (CoQ) helps cardiac patients, combined with all the stories of marathon runners dropping dead from heart failure, I'll definitely be using it while training - not that I'm worried about dropping dead at all, but just to practice damage control.

 

As per the c60, you're saying a half or a third my current dosage, and even once a month? So possibly as low as .4 mg once a month, or am I missing something?

That's the dose per day, although you don't have to take it every day.  If you took it weekly, it would 7*0.4 = 2.8mg, and monthly would be 12 mg.    That might be a little on the low side; you could bump it up some, although considering your age and fitness it would probably be fine.

I'll probably use the c60 at a low dose, maybe a pipette (1.5 mg) once a week or every other week, until the bottle runs out. Despite reading mostly good things about it I'm still going to err on the side of caution. As for the PQQ and CoQ10, I'll likely do 10 mg and 50 mg respectively, every other day. I've just read too many exciting things about these compounds.

These compounds are wonder drugs in the elderly.  Ubiquinol made a huge difference for my 91 year old father in law.  I'm in my fifties, and I don't use Q10.  I've tried it a few times, but can't tell any difference.  I definitely felt c60 though.  Never tried PQQ.

I'm 58 and have tried quite a few things. Q10 was a waste of money as was PQQ (perhaps I am still too young).

C60 is a winner I take 12.5 to 15 mg once a week.

I've had mixed results with N/R, its effects appear to be very dose and cofactor dependent.

Mito-Q appears to be a winner and seems to synergise very nicely with N/R and c60.

But as I said I'm 58, apart from the C60 the other supplements only appear to be replacing or covering up age related deficiencies, deficiencies you shouldn't have yet.

By all means take them, they certainly wont hurt you, but I don't think they'll work for you either.

Good luck with the half marathon.

Mike

Great, thanks for the replies guys. Good to know about c60's dose and long half-life.

c60 does wonder for endurance but pqq and coq10 didn't do much for me. Unless you take statins for cholesterol, you probably don't need those.

I run tracks and play soccer at a good level and train 6-12 times a week and the only thing that really helped my performances so far are C60oo (I am absolutely not kidding: it cured my shin splints in 24 hours and I've had those since I was 18!), TB500 (amazing to repair nagging injuries) and ITTP (major boost in endurance similar to hyperbaric chamber but a bit on the experimental side).

When I first started C60oo, I could run 1 mile an hour faster on my 20k and made a 15-20% improvement on intervals and I was not a believer at all until I saw it.

Interesting experiences cani!, I have not heard of TB500 or ITTP. 

I realize I'm young and in good health. As regards to PQQ and CoQ10, I'm doing a small dose of each every other day. There's so many benefits from each that I don't see why I wouldn't want to include them in my routine, even if I may not "need" them. As for c60, it's definitely an interesting compound with noticeable improvements in endurance. Very cool to hear about it helping your shin splints.

I find it interesting that I've never seen mentioned that mitochondrial hormetic agents (e.g. berberine, schizandra etc) acutely have the exact opposite effects of agents that optimize oxidative phosphorylation (e.g. carnitine, CoQ10, PQQ, methylene blue, etc) and that combining the two types of supplements could in theory potentially defeat the benefits of the other supplement. Berberine and CoQ10 are prime examples where berberine inhibits complex 1 in the electron transport chain while CoQ10 optimizes it. (Side Note: Id chose berberine over CoQ10 every day of the week)

At the age of 25 I can all but guarantee that mitochondrial hormetics will have a better effect on you than optimizers of oxidative phosphorylation, which are generally considered to only have significant effects in the elderly who lose efficiency at oxidative phosphorylation as aging progresses and those with metabolic syndrome, either way Id still generally have more faith in hormetics like berberine to have more real-life effects.

Unless you have metabolic syndrome, are vegetarian or get tangible effects from the ALCAR, both the Coq10 and ALCAR could be dropped from your regimen since they are essentially pointless at your age with an omnivorous diet. Any rate-limitations in the electron transport chain have already met their saturation point, the one exception being cytochrome C (the natural rate limiter in oxidative phosphorylation) which could be further optimized in healthy individuals with things like methylene blue and LLLT, both of which are too understudied to seriously suggest chronic use.

Thanks for the input Bateau. I do use schizandra regularly but haven't read anywhere about it's effects on mitochondria. I'll have to do some reading up on it, as well as berberine. This is exactly the info I was hoping to find as I know there's not going to be much of an effect at my age with things like CoQ10 or ALCAR.

I find it interesting that I've never seen mentioned that mitochondrial hormetic agents (e.g. berberine, schizandra etc) acutely have the exact opposite effects of agents that optimize oxidative phosphorylation (e.g. carnitine, CoQ10, PQQ, methylene blue, etc) and that combining the two types of supplements could in theory potentially defeat the benefits of the other supplement. Berberine and CoQ10 are prime examples where berberine inhibits complex 1 in the electron transport chain while CoQ10 optimizes it. (Side Note: Id chose berberine over CoQ10 every day of the week)

 

At the age of 25 I can all but guarantee that mitochondrial hormetics will have a better effect on you than optimizers of oxidative phosphorylation, which are generally considered to only have significant effects in the elderly who lose efficiency at oxidative phosphorylation as aging progresses and those with metabolic syndrome, either way Id still generally have more faith in hormetics like berberine to have more real-life effects.

I had a similiar theory to this, but a conversation I had with Greg Macpherson set my mind mostly at ease.

Here is the relevant excerpt:

"I was also wondering how these mitochondrial antioxidants might affect the relationship between hormesis and oxidative stress. Since damage from free radicals/oxidative stress is necessary for the beneficial, hormetic effects of exercise to take place, would a mitochondrial antioxidant possibly mop up these free radicals too quickly for any hormetic effects to occur?

This is a great question.  Most antioxidants on the market today appear to have a negative effect on hormesis.  CoQ10 in the mitochondria selectively ignores certain free radical messengers and allows free radical signalling associated with the hormetic process. MitoQ does the same. "

 

I find it interesting that I've never seen mentioned that mitochondrial hormetic agents (e.g. berberine, schizandra etc) acutely have the exact opposite effects of agents that optimize oxidative phosphorylation (e.g. carnitine, CoQ10, PQQ, methylene blue, etc) and that combining the two types of supplements could in theory potentially defeat the benefits of the other supplement. Berberine and CoQ10 are prime examples where berberine inhibits complex 1 in the electron transport chain while CoQ10 optimizes it. (Side Note: Id chose berberine over CoQ10 every day of the week)

 

At the age of 25 I can all but guarantee that mitochondrial hormetics will have a better effect on you than optimizers of oxidative phosphorylation, which are generally considered to only have significant effects in the elderly who lose efficiency at oxidative phosphorylation as aging progresses and those with metabolic syndrome, either way Id still generally have more faith in hormetics like berberine to have more real-life effects.

 

I had a similiar theory to this, but a conversation I had with Greg Macpherson set my mind mostly at ease.

Here is the relevant excerpt:

"I was also wondering how these mitochondrial antioxidants might affect the relationship between hormesis and oxidative stress. Since damage from free radicals/oxidative stress is necessary for the beneficial, hormetic effects of exercise to take place, would a mitochondrial antioxidant possibly mop up these free radicals too quickly for any hormetic effects to occur?

 

This is a great question.  Most antioxidants on the market today appear to have a negative effect on hormesis.  CoQ10 in the mitochondria selectively ignores certain free radical messengers and allows free radical signalling associated with the hormetic process. MitoQ does the same. "

 

That's somewhat relieving, but the problem with berberine is that were not totally sure how it activates AMPK. At low doses it seems to activate it indirectly through NAMPT> NAD+>SIRT>LKB1>AMPK, while at medium doses it activates AMPK directly though Redox (Oxidation), and at higher doses seems to directly inhibition Complex 1 in the electron transport chain.

So these basic mitochondrial optimizers (CoQ10, ALCAR etc.) should be fine with berberine if berberine is acting through the first two mechanisms at the lower and medium dose. but if berberine is inhibiting the transport chain, like at the higher dose, again it would made taking the two types of supplements together potentially wasteful. Same goes for taking these supplements with Metformin or TZD's.