20 replies to this topic

[aribadabar]

Hello,

 

Can some of the more knowledgeable and experienced members explain the differences (if any) in action between these different mitochondrial enhancers?

My biochemical knowledge is pretty limited to put them in perspective so any insight would be greatly appreciated.

 

My layman understanding is that CoQ10 helps with the ATP production, PQQ creates new mitochondria, C60oo acting as an electron buffer thus keeping ETC in good shape....and MitoQ sharing properties of both C60 and CoQ10.

Is this accurate or I am way off the mark?

 

I think it would be interesting to many.

 

Thank you!

Edited by aribadabar, 28 July 2014 - 08:29 PM.

[The Ripper]

This is a good question so I'll chime in to say I'd also appreciate anyone taking the time to explain this. 

[gt35r]

Yes. CoQ10 is part of an electron carrier in the electron transport chain reaction; as age goes down formation of CoQ10 seems to go down. C60oo, though not fully understood, is believed to work by preventing the mitochondria from overly injury itself by oxidation. 

[niner]

These compounds overlap in various ways.  All are capable of acting as antioxidants, particularly toward radical species like superoxide.  MitoQ is specifically targeted to the mitochondria, and c60oo probably also ends up in the mitochondria, though it is not a 'designed' compound like MitoQ.  OTOH, fullerenes are more potent anti-superoxide agents than quinones. 

[The Ripper]

Would a sensible approach be to use PQQ for its gene activation properties then something like C60oo for the rest of its mitochondria-targetted antioxidant and other properties?

[zorba990]

What about butyrate?

 

http://diabetes.diab.../58/7/1509.long

RESULTS On the high-fat diet, supplementation of butyrate prevented development of insulin resistance and obesity in C57BL/6 mice. Fasting blood glucose, fasting insulin, and insulin tolerance were all preserved in the treated mice. Body fat content was maintained at 10% without a reduction in food intake. Adaptive thermogenesis and fatty acid oxidation were enhanced. An increase in mitochondrial function and biogenesis was observed in skeletal muscle and brown fat. The type I fiber was enriched in skeletal muscle. Peroxisome proliferator–activated receptor-γ coactivator-1α expression was elevated at mRNA and protein levels. AMP kinase and p38 activities were elevated. In the obese mice, supplementation of butyrate led to an increase in insulin sensitivity and a reduction in adiposity.

[Turnbuckle]

These compounds probably go to different places in the mitochondria due to their solubility. C60 and CoQ10 are hydrophobic while MitoQ and PQQ are hydrophilic, thus the combination should be synergistic. I've tried EVOO with C60 (.8 mg/ml) on my face, but found the effects not much better than EVOO alone, possibly because the C60 molecule is too large to readily penetrate. When I added CoQ10 (3.4 mg/ml) to the mix, however, I found a much more dramatic and longer lasting effect. PQQ esters are oil soluble and would make an interesting addition--

 

The monoester of PQQ with a methoxycarbonyl group at C-2 of PQQ is a most effective compound because of its NGF inducing activity, limited toxicity, safety and chemical stability.

http://www.ncbi.nlm..../pubmed/8922270

 

 

[pone11]

 

These compounds probably go to different places in the mitochondria due to their solubility. C60 and CoQ10 are hydrophobic while MitoQ and PQQ are hydrophilic, thus the combination should be synergistic. I've tried EVOO with C60 (.8 mg/ml) on my face, but found the effects not much better than EVOO alone, possibly because the C60 molecule is too large to readily penetrate. When I added CoQ10 (3.4 mg/ml) to the mix, however, I found a much more dramatic and longer lasting effect. PQQ esters are oil soluble and would make an interesting addition--

 

 

CoQ10 is sold as ubiquinone or ubiquinol.   Ubiquinol contains two hydroxyl groups that enable it to be more hydrophilic than ubiquinone.   But as I understand it - once CoQ10 is embedded into the mitochondrial inner membrane - it switches back and forth between these two forms.     So I don't think your point should be about different forms of CoQ10 going to different places, because ultimately they would become the same thing.  The point should be about which form of CoQ10 is better absorbed in the first place.   That's a contentious point from what I have seen, with some saying that both forms absorb about the same, and others claiming one form absorbs better than the other.     MitoQ has the advantage of having charge characteristics that make it absorb much more readily.

Edited by pone11, 25 February 2015 - 09:03 PM.

[niner]

 

These compounds probably go to different places in the mitochondria due to their solubility. C60 and CoQ10 are hydrophobic while MitoQ and PQQ are hydrophilic, thus the combination should be synergistic. I've tried EVOO with C60 (.8 mg/ml) on my face, but found the effects not much better than EVOO alone, possibly because the C60 molecule is too large to readily penetrate. When I added CoQ10 (3.4 mg/ml) to the mix, however, I found a much more dramatic and longer lasting effect. PQQ esters are oil soluble and would make an interesting addition--

 

PQQ is hydrophilic, and C60oo is hydrophobic, but CoQ10 and MitoQ are hydrophobic as hell.  Ubiquinone has a computed logP of 17, which makes it substantially more hydrophobic than pristine c60.  This may seem odd, but it has to do with the difference between the behavior of aromatics and floppy aliphatics in water.  In addition to possessing the ubiquinone moiety, MitoQ has a triphenylphosphine group, which is also quite a greaseball.  The key thing with MitoQ is the cationic TPP group, which specifically attracts it to the mitochondrial inner membrane.  Because the fatty acid adduct of c60 is anionic, it will probably find its way into most membranes, including the MIM.  With the fatty acid functionality, it holds out the possibility of engaging in phospholipid synthesis as well.

[niner]

CoQ10 is sold as ubiquinone or ubiquinol.   Ubiquinol contains two hydroxyl groups that enable it to be more hydrophilic than ubiquinone.   But as I understand it - once CoQ10 is embedded into the mitochondrial inner membrane - it switches back and forth between these two forms.     So I don't think your point should be about different forms of CoQ10 going to different places, because ultimately they would become the same thing.  The point should be about which form of CoQ10 is better absorbed in the first place.   That's a contentious point from what I have seen, with some saying that both forms absorb about the same, and others claiming one form absorbs better than the other.     MitoQ has the advantage of not only being hydrophilic (a form of ubiquinol) but having charge characteristics that make it absorb much more readily.

 

I don't think it's contentious unless someone has a vested interest in the sale of one or the other.  The bioavailability of ubiquinol is better than unformulated ubiquinone.  The PK data is available.  The problem is that it's not better enough to justify the higher cost of ubiquinol.  It's cheaper to just take a larger dose of ubiquinone.  There are also various formulations of ubiquinone that have better bioavailability than unformulated ubiquinone, but again, the cost is probably not worth it.

 

MitoQ is not hydrophilic, although it is at least cationic.  Sometimes hydrophobes have better bioavailability than you might think, strictly based on their logP.  They are probably hitching a ride in chylomicrons as part of normal lipid digestion. 

[pone11]

 

 

These compounds probably go to different places in the mitochondria due to their solubility. C60 and CoQ10 are hydrophobic while MitoQ and PQQ are hydrophilic, thus the combination should be synergistic. I've tried EVOO with C60 (.8 mg/ml) on my face, but found the effects not much better than EVOO alone, possibly because the C60 molecule is too large to readily penetrate. When I added CoQ10 (3.4 mg/ml) to the mix, however, I found a much more dramatic and longer lasting effect. PQQ esters are oil soluble and would make an interesting addition--

 

PQQ is hydrophilic, and C60oo is hydrophobic, but CoQ10 and MitoQ are hydrophobic as hell.  Ubiquinone has a computed logP of 17, which makes it substantially more hydrophobic than pristine c60.  This may seem odd, but it has to do with the difference between the behavior of aromatics and floppy aliphatics in water.  In addition to possessing the ubiquinone moiety, MitoQ has a triphenylphosphine group, which is also quite a greaseball.  The key thing with MitoQ is the cationic TPP group, which specifically attracts it to the mitochondrial inner membrane.  Because the fatty acid adduct of c60 is anionic, it will probably find its way into most membranes, including the MIM.  With the fatty acid functionality, it holds out the possibility of engaging in phospholipid synthesis as well.

 

 

And the point worth adding here is that experimental evidence shows very little CoQ10 of either form gets absorbed to mitochondrial membranes.  I've seen numbers around 1% to 2%:

http://informahealth...544.2014.993747

 

The above study contains the line "Onoue et al. (2012) prepared s-SEDDS of CoQ10 using medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose and tested it in rats. The absolute bioavailability was extremely low in case of the crystalline CoQ10 (0.44%) but it was improved to 2.2% by the oral administration of s-SEDDS...."

 

MitoQ has research showing absorption levels that are orders of magnitude better.    So, apparently, that cationic TPP group is critical to incorporation into mitochondrial membranes.

 

One thing I still do not understand is when would it make sense to take both MitoQ and a traditional form of CoQ10?

[Turnbuckle]

 

 

These compounds probably go to different places in the mitochondria due to their solubility. C60 and CoQ10 are hydrophobic while MitoQ and PQQ are hydrophilic, thus the combination should be synergistic. I've tried EVOO with C60 (.8 mg/ml) on my face, but found the effects not much better than EVOO alone, possibly because the C60 molecule is too large to readily penetrate. When I added CoQ10 (3.4 mg/ml) to the mix, however, I found a much more dramatic and longer lasting effect. PQQ esters are oil soluble and would make an interesting addition--

 

 

CoQ10 is sold as ubiquinone or ubiquinol.   Ubiquinol contains two hydroxyl groups that enable it to be more hydrophilic than ubiquinone.   But as I understand it - once CoQ10 is embedded into the mitochondrial inner membrane - it switches back and forth between these two forms.     So I don't think your point should be about different forms of CoQ10 going to different places, because ultimately they would become the same thing.  The point should be about which form of CoQ10 is better absorbed in the first place.   That's a contentious point from what I have seen, with some saying that both forms absorb about the same, and others claiming one form absorbs better than the other.     MitoQ has the advantage of having charge characteristics that make it absorb much more readily.

 

 

 

My point was not about different forms of CoQ10 going to different places. In any case, I'm using ubiquinone dissolved in olive oil, which is known to have much better absorption. The entire body content of CoQ10 is estimated to be .5 to 1.5 grams. 

 

The whole body content of CoQ10 is only about 500-1500 mg and decreases with age.

http://www.ncbi.nlm....les/PMC3178961/

 

 

While a one week treatment with 100 mg/day of CoQ10 in oil more than doubled the plasma content of CoQ10, suggesting that absorption was high--

 

 

Oral bioavailability of the model emulsified CoQ10 product was

investigated and compared with that of a standard commercial

CoQ10 product. The total content of CoQ10 (TQ) and the ratio of total

CoQ10 content to total content of cholesterol (TQ/TC) in plasma

samples from the five study participants at each stage are shown in

Figs. 3 and 4, respectively. When the standard commercial CoQ10

product was administered to the study participants for 1 week, TQ

and TQ/TC increased up to 2.2-fold and 2.4-fold, respectively. Three

weeks after the administration was stopped, TQ and TQ/TC had

returned to their initial values.

 

http://www.thaiscien...od industry.pdf

 

 

 

[pone11]

 

The whole body content of CoQ10 is only about 500-1500 mg and decreases with age.

http://www.ncbi.nlm....les/PMC3178961/

 

 

While a one week treatment with 100 mg/day of CoQ10 in oil more than doubled the plasma content of CoQ10, suggesting that absorption was high--

 

 

 

CoQ10 is used to shuttle between Complex 1 and 3 of the electron transport chain, inside the mitochondrial membrane.   Indirect measurements of plasma content is probably very misleading.  What you care about is how much of that plasma content gets absorbed into the mitochondrial inner membrane.

[Turnbuckle]

 

 

 

These compounds probably go to different places in the mitochondria due to their solubility. C60 and CoQ10 are hydrophobic while MitoQ and PQQ are hydrophilic, thus the combination should be synergistic. I've tried EVOO with C60 (.8 mg/ml) on my face, but found the effects not much better than EVOO alone, possibly because the C60 molecule is too large to readily penetrate. When I added CoQ10 (3.4 mg/ml) to the mix, however, I found a much more dramatic and longer lasting effect. PQQ esters are oil soluble and would make an interesting addition--

 

PQQ is hydrophilic, and C60oo is hydrophobic, but CoQ10 and MitoQ are hydrophobic as hell.  Ubiquinone has a computed logP of 17, which makes it substantially more hydrophobic than pristine c60.  This may seem odd, but it has to do with the difference between the behavior of aromatics and floppy aliphatics in water.  In addition to possessing the ubiquinone moiety, MitoQ has a triphenylphosphine group, which is also quite a greaseball.  The key thing with MitoQ is the cationic TPP group, which specifically attracts it to the mitochondrial inner membrane.  Because the fatty acid adduct of c60 is anionic, it will probably find its way into most membranes, including the MIM.  With the fatty acid functionality, it holds out the possibility of engaging in phospholipid synthesis as well.

 

 

And the point worth adding here is that experimental evidence shows very little CoQ10 of either form gets absorbed to mitochondrial membranes.  I've seen numbers around 1% to 2%:

http://informahealth...544.2014.993747

 

The above study contains the line "Onoue et al. (2012) prepared s-SEDDS of CoQ10 using medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose and tested it in rats. The absolute bioavailability was extremely low in case of the crystalline CoQ10 (0.44%) but it was improved to 2.2% by the oral administration of s-SEDDS...."

 

MitoQ has research showing absorption levels that are orders of magnitude better.    So, apparently, that cationic TPP group is critical to incorporation into mitochondrial membranes.

 

One thing I still do not understand is when would it make sense to take both MitoQ and a traditional form of CoQ10?

 

 

If dissolving C60 in EVOO delivers C60 to mitochondria with high efficiency, why wouldn't the same be true for CoQ10?

[niner]

 

One thing I still do not understand is when would it make sense to take both MitoQ and a traditional form of CoQ10?

 

If dissolving C60 in EVOO delivers C60 to mitochondria with high efficiency, why wouldn't the same be true for CoQ10?

 

We'd probably need a lab that was capable of sensitive bioenergetic measurements to tell if there was a benefit to supplementing both ubiquinone and MitoQ.  They're both quinones with long hydrocarbon chains to serve as membrane anchors.  The anchors are structurally different, which will probably influence positioning and mobility.  If you are young and wouldn't expect to need CoQ10, then you probably wouldn't need to supplement it.  If you're older, I suppose you might as well use it; doesn't seem like it would hurt much.

 

I think that if we dissolved CoQ10 in the same mix as c60, we'd have a problem, because the c60 would probably react with the unsaturated hydrocarbon tail of CoQ10.  If we dissolve CoQ10 in plain olive oil, I think it would just dissolve, but not react.  That should, as you pointed out, improved its bioavailability over dry CoQ10, but I don't see a mechanism for mitochondrial targeting.  Even with C60oo, I don't see why it would be particularly targeted to mitochondria.  I think that the adduct would be happy in any membrane, including the MIM, but also others.   I suppose it's possible that the membrane potential would polarize the c60, given its highly mobile electrons, and you'd see some electrostatic attraction.  That might work to concentrate fullerenes in general in mitochondria.

[pone11]

 

 

One thing I still do not understand is when would it make sense to take both MitoQ and a traditional form of CoQ10?

 

If dissolving C60 in EVOO delivers C60 to mitochondria with high efficiency, why wouldn't the same be true for CoQ10?

 

We'd probably need a lab that was capable of sensitive bioenergetic measurements to tell if there was a benefit to supplementing both ubiquinone and MitoQ.  They're both quinones with long hydrocarbon chains to serve as membrane anchors.  The anchors are structurally different, which will probably influence positioning and mobility.  If you are young and wouldn't expect to need CoQ10, then you probably wouldn't need to supplement it.  If you're older, I suppose you might as well use it; doesn't seem like it would hurt much.

 

I think that if we dissolved CoQ10 in the same mix as c60, we'd have a problem, because the c60 would probably react with the unsaturated hydrocarbon tail of CoQ10.  If we dissolve CoQ10 in plain olive oil, I think it would just dissolve, but not react.  That should, as you pointed out, improved its bioavailability over dry CoQ10, but I don't see a mechanism for mitochondrial targeting.  Even with C60oo, I don't see why it would be particularly targeted to mitochondria.  I think that the adduct would be happy in any membrane, including the MIM, but also others.   I suppose it's possible that the membrane potential would polarize the c60, given its highly mobile electrons, and you'd see some electrostatic attraction.  That might work to concentrate fullerenes in general in mitochondria.

 

 

Here is a summary of early development of MitoQ and some comparisons of absorbability against regular CoQ10:

http://www.science20...heard_of-136215

 

From the article " By adding a phosphonium group to the Coenzyme Q quinone group they introduced a positive charge and discovered that the antioxidant could still be quickly reduced to active quinol form by cells - but at levels 800-1200 times greater than CoQ10. "

 

Here is the original research that article is based on:

http://www.annualrev...7.120505.105110

 

@Niner, look at Figure 6.  Maybe you could help us understand how each of the mitochondrial antioxidants in that diagram are working, as they seem to be saying there is a different mechanism for each.   Also, see the section in this paper "Uptake and Distribution of MitoQ10 and MitoE2 Within Cells"

 

I couldn't help but notice the MitoQ study references a hydrogen peroxide antioxidant named Mitoperoxidase, which is based on a more generic supplement Ebselen (I see it available but not sure if it is being sold only for research...is it available for human use?).   I'll look to see what others are saying about these and I may start a new thread to discuss that.   As discussed in other threads, many of the newer SOD mimics (MitoQ, MitoTempo, and C60) may convert superoxide radical to hydrogen peroxide.   It's normally the job of catalase to convert H2O2 to harmless metabolites.   It might be very desirable to find another antioxidant that does not downregulate catalase to help fight the extra H2O2 created by these antioxidants.   That's why this topic does tie to C60.

Edited by pone11, 26 February 2015 - 01:40 AM.

[Invicta Immortalem]

Please be aware of this recent study entitled:

 

The targeted anti‐oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

 

https://www.ncbi.nlm...les/PMC5880956/

 

Any comments?

[osris]

Here is what ChatGPT says:

 

Mitochondria are critical cellular organelles responsible for generating energy in the form of adenosine triphosphate (ATP). Maintaining mitochondrial health is essential for overall cellular function and overall well-being. Coenzyme Q10 (CoQ10), MitoQ, Pyrroloquinoline quinone (PQQ), and C60oo (Carbon 60) have all been studied for their potential benefits on mitochondrial health. Here's an overview of the mitochondrial health benefits of each:

 

Coenzyme Q10 (CoQ10):

 

CoQ10 is a naturally occurring compound in the body that plays a key role in the electron transport chain, which is essential for ATP production.

It acts as an antioxidant, protecting mitochondria from oxidative damage. CoQ10 supplementation may help improve mitochondrial function, particularly in individuals with CoQ10 deficiency or certain medical conditions. Benefits may include increased energy production, improved exercise performance, and potential support for conditions like heart disease and neurodegenerative disorders.

 

MitoQ:

 

MitoQ is a specialized form of CoQ10 that is designed to target mitochondria specifically. It is believed to enhance the delivery of CoQ10 to mitochondria, potentially increasing its effectiveness. MitoQ's antioxidant properties may help reduce oxidative stress within mitochondria and support their function. Some studies suggest that MitoQ supplementation may improve mitochondrial health and overall cellular function.

 

Pyrroloquinoline quinone (PQQ):

 

PQQ is a compound with antioxidant properties that can support mitochondrial function and biogenesis (the process of creating new mitochondria).

It may stimulate the growth of new mitochondria (mitochondrial biogenesis), which is important for overall mitochondrial health. PQQ may also help protect mitochondria from oxidative damage and enhance energy production. Research on PQQ is ongoing, but it shows promise as a potential supplement for mitochondrial support.

 

Carbon 60 (C60oo):

 

Carbon 60 (C60), when dissolved in olive oil (C60oo), has gained attention for its potential antioxidant properties. Some studies suggest that C60oo may help reduce oxidative stress, which can indirectly support mitochondrial health by protecting mitochondria from damage. However, more research is needed to fully understand the mechanisms and long-term effects of C60oo on mitochondrial health.

 

 

 

[Mind]

 

Please be aware of this recent study entitled:

 

The targeted anti‐oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

 

https://www.ncbi.nlm...les/PMC5880956/

 

Any comments?

 

 

Looks like an In Vitro study. If so, I am not too concerned. To date, MitoQ has a ton of positive research behind it - including clinical trials in real humans.

[adamh]

Since we are talking about mitochondrial health, its surprising no one has mentioned NMN which is very good for that. Dr david sinclair, a noted longevity scientist, has recommended it and uses it himself. I also use it and it is one of the few supplements I can really feel. Even after months its effects are noticeable. 

[ta5]

 

Please be aware of this recent study entitled:

 

The targeted anti‐oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

 

https://www.ncbi.nlm...les/PMC5880956/

 

Any comments?

 

 

Looks like an In Vitro study. If so, I am not too concerned. To date, MitoQ has a ton of positive research behind it - including clinical trials in real humans.

 

It was also discussed here, here, and here by Greg Macpherson the CEO of MitoQ.