184 replies to this topic

[gregmacpherson]

Yes, still here! Just been a little quiet of late because of my work load.  Its been a very busy time. 

 

Lots happening in terms of human research across fibromyalgia, cardiovascular health, MS, kidney health, metabolic function and lung health.   I will post as an when the research is published.  There will be some this year and some next.  

 

If you take a look at pubmed.com and search MitoQ you will see some of the other research that has recently been published.  

 

And our big news from 2015 was that we were selected for the NIA's Intervention Testing Program - an independent anti-aging research programme. 

 

Re discounts ... we have a discount of 15% available to paid members of Longecity. 

 

Thanks, Greg

[Daniel Cooper]

 

Re discounts ... we have a discount of 15% available to paid members of Longecity. 

 

Thanks, Greg

 

Greg,

 

How does a paid member get access to the discount code?

[gregmacpherson]

 

 

Re discounts ... we have a discount of 15% available to paid members of Longecity. 

 

Thanks, Greg

 

Greg,

 

How does a paid member get access to the discount code?

 

 

Hi Daniel, please contact the LongeCity admin team and they will be able to give it to you. 

 

thanks

 

Greg

[bosharpe]

Did anyone ever see Vladimir Skulachev's comment on MitoQ on this longevity blog:

 http://joshmitteldor...coq10/#comments

 

Greg, have you any response to the Dr's comments regarding his first paragraph? 

[gregmacpherson]

Hi, yes a few comments on Skulachev's notes.  Skulachev is a smart chap who knows his way around MitoQ well so I was a little disappointed with his response as it was a touch misleading. We think Skulachev has an interesting compound in SKQ1 and follow his work. 

 

However, to clarify;

 

1. MitoQ is CoQ10 with a positive charged added causing it to target the negatively charged mitochondria

2. CoQ10 has two functions - it is an integral part of the electron transport chain (ETC) and it is an antioxidant that mops up the free radicals generated by the ETC in the process of generating ATP

3. MitoQ, because of the addition of the positive charge is not active in the ETC. Its effect primarily comes down to its effectiveness as an antioxidant and its ability to embed itself into and stabilise the inner mitochondrial membrane.  In so doing MitoQ supports all of the activity that is carried out within this membrane which includes supporting the multi complex ETC. So, albeit indirectly, MitoQ supports the generation of ATP with the side benefit of positively enhancing membrane function and all the activity that goes with it.  

4. MitoQ is effectively a highly bio-available form of CoQ10 and there is absolutely no issue with respect to pro-oxidant risk which makes sense given it is the same antioxidant moiety as CoQ10. 

5. You cannot compare plant cells with mammalian cells. 

 

All of the above has been evaluated and confirmed across a number of independent researchers over the years. 

 

For those of you who enjoy a deep dive into the research please visit pubmed and search for MitoQ.  It will give you a view on the potential of the compound and the latest research.

 

In terms of anti-aging, MitoQ was selected into the Interventions Testing Programme 2015 cohort.  Unfortunately we need to wait a few years for the results but the bar is relatively high to get into this programme and only compounds with significant anti-aging potential are accepted. 

 

We have a bunch of human research happening in the wings.  Most of it is independent of us other than we supplied the capsules and placebo. 

 

Interesting times here as more and more knowledge is generated with respect to the link between mitochondrial function and healthy aging. More to come as I am able to share. 

 

Essentially if we can "tune up" the mitochondria we are replicating the higher energy environment that is seen in younger cells. Cells are self repairing machines - giving them the energy they need to operate at that level can only be a good thing. 

 

Thanks and with regards

 

Greg

[bosharpe]

Thanks Greg.

[Kalliste]

Well I found a bottle from last summer with one 5mg pill left. I come of as a commercial now but that pill alone was enough to make me swallow the $60 cost of a bottle + Swe shipping. It really gets me going, followed a 20km local half marathon on bike with my son on the back and then hit the gym for an hour with a lot of energy.

 

I've been drinking beetroot juice and eating sodium bicarbonate aswell but those things alone didn't give that buzz.

Going to try this combo again, the effect seemed to stay with me for two or almost three days. Hrmm that was a nice experience. Def one of my most intense workout days in a long time.

[bosharpe]

Bought a bottle of Mitoq. Will report back here after dosing.

[bosharpe]

I received the Mitoq. Initially I took 1 cap per day for 5 days. YEsterday I took two and noticed a dramatic boost in energy levels and mental clarity for several hours. I was buzzing! I've taken another 2 today and not so much of an effect, in fact I can't be certain I feel much of a buzz at all. 

[Graviton]

greg,

how can you be sure that Mitoq skin serum can be absorbed into skin through its barriers, and then it can reach to its mitochondria?

[gregmacpherson]

greg,

how can you be sure that Mitoq skin serum can be absorbed into skin through its barriers, and then it can reach to its mitochondria?

 

Hi Graviton, 

 

We have done testing called Franz diffusion cell testing which measures the delivery of MitoQ across the layers of the skin and this shows that it reaches the dermis in levels high enough to be active. From there it migrates directly to the mitochondria per our mitochondria-targeting technology i.e. the positive charge on MitoQ is attracted to the negative charge within the mitochondria.  

 

Thanks. 

[Graviton]

 

greg,

how can you be sure that Mitoq skin serum can be absorbed into skin through its barriers, and then it can reach to its mitochondria?

 

Hi Graviton, 

 

We have done testing called Franz diffusion cell testing which measures the delivery of MitoQ across the layers of the skin and this shows that it reaches the dermis in levels high enough to be active. From there it migrates directly to the mitochondria per our mitochondria-targeting technology i.e. the positive charge on MitoQ is attracted to the negative charge within the mitochondria.  

 

Thanks. 

 

 

1. What about the stability and bioavailability of MitoQ? Is each capsule enteric coated? I am concerned about degradation of Mitoq by stomach acid, and I would like to know if I have to encapsulate separate MitoQ capsules with stomach acid protected capsules again.

2. Should I take MitoQ with food or in an empty stomach?

3. Can I take general advantages of MitoQ as described in MitoQ web-site if I am in early 20s? i.e. I wonder if Mitoq can fully act for young individuals who have sufficient amount of CoQ10, as it usually do to elderly people.

4. Any known UPDATED interactions with other supplements including C60, NR, pqq? (it has been asked before in this thread, but just to check any updates)

5. If taken sublingually, any toxicity or harms? (for example, from absorption of excipient materials etc) 

Edited by Graviton, 29 June 2016 - 06:50 AM.

[Kalliste]

 

 

greg,

how can you be sure that Mitoq skin serum can be absorbed into skin through its barriers, and then it can reach to its mitochondria?

 

Hi Graviton, 

 

We have done testing called Franz diffusion cell testing which measures the delivery of MitoQ across the layers of the skin and this shows that it reaches the dermis in levels high enough to be active. From there it migrates directly to the mitochondria per our mitochondria-targeting technology i.e. the positive charge on MitoQ is attracted to the negative charge within the mitochondria.  

 

Thanks. 

 

 

1. What about the stability and bioavailability of MitoQ? Is each capsule enteric coated? I am concerned about degradation of Mitoq by stomach acid, and I would like to know if I have to encapsulate separate MitoQ capsules with stomach acid protected capsules again.

2. Should I take MitoQ with food or in an empty stomach?

3. Can I take general advantages of MitoQ as described in MitoQ web-site if I am in early 20s? i.e. I wonder if Mitoq can fully act for young individuals who have sufficient amount of CoQ10, as it usually do to elderly people.

4. Any known UPDATED interactions with other supplements including C60, NR, pqq? (it has been asked before in this thread, but just to check any updates)

5. If taken sublingually, any toxicity or harms? (for example, from absorption of excipient materials etc) 

 

 

1. I think it has good stability, I've eaten it on empty stomach, eaten it with dairy and coffee (both of which can disturb some polyphenols and vitamin absorption). You do not need to modify the pill.

 

2. I've mostly taken it with food so why not do that.

 

3. I took it the first time last year, took 10mg in the morning, when I was 32. I was riding bike 100km/week when I started taking it and had been doing that for a year + eating lots of health stuff so I was in good condition.

Yet MitoQ had a pronounced effect, right away a few hours after the first dose.

That effect can very much be described as "more energy for stuff". Training in the gym, riding my bike, playing with my son, and some weird stuff like brushing my teeth really really hyper carefully.

I've taken a lot of supplements throughout the years expecting good results, but never experienced this effect as remarkably. Not even with 5ml C60oo every day for a while (tried VW and C60oliveoil.com), nor did CoQ10 at dosages of up to 200mg/day do anything noticeable.

 

4. What tox-concerns I know of:

- Could disturb MitoROS normally used to direct stem cell activity.

- Could disturb hormetic effects of exercise mediated by increased mtROS production.

 

5. I never tried taking it sublingually because oral administration worked wonders.

 

The only negative for me is that cost+shipping is $60. If it was cheaper I would like to take more.

 

One weird effect (not so weird if you plow through Lostfalcos Nootropic thread) is that MitoQ has a clearly noticeable psychological effect: It makes me markedly more outgoing and talkative. Falco has more on that, mitos play a central function in our brains so if you change them it follows that should literally change your mindstate.

[Graviton]

 

 

 

greg,

how can you be sure that Mitoq skin serum can be absorbed into skin through its barriers, and then it can reach to its mitochondria?

 

Hi Graviton, 

 

We have done testing called Franz diffusion cell testing which measures the delivery of MitoQ across the layers of the skin and this shows that it reaches the dermis in levels high enough to be active. From there it migrates directly to the mitochondria per our mitochondria-targeting technology i.e. the positive charge on MitoQ is attracted to the negative charge within the mitochondria.  

 

Thanks. 

 

 

1. What about the stability and bioavailability of MitoQ? Is each capsule enteric coated? I am concerned about degradation of Mitoq by stomach acid, and I would like to know if I have to encapsulate separate MitoQ capsules with stomach acid protected capsules again.

2. Should I take MitoQ with food or in an empty stomach?

3. Can I take general advantages of MitoQ as described in MitoQ web-site if I am in early 20s? i.e. I wonder if Mitoq can fully act for young individuals who have sufficient amount of CoQ10, as it usually do to elderly people.

4. Any known UPDATED interactions with other supplements including C60, NR, pqq? (it has been asked before in this thread, but just to check any updates)

5. If taken sublingually, any toxicity or harms? (for example, from absorption of excipient materials etc) 

 

 

1. I think it has good stability, I've eaten it on empty stomach, eaten it with dairy and coffee (both of which can disturb some polyphenols and vitamin absorption). You do not need to modify the pill.

 

2. I've mostly taken it with food so why not do that.

 

3. I took it the first time last year, took 10mg in the morning, when I was 32. I was riding bike 100km/week when I started taking it and had been doing that for a year + eating lots of health stuff so I was in good condition.

Yet MitoQ had a pronounced effect, right away a few hours after the first dose.

That effect can very much be described as "more energy for stuff". Training in the gym, riding my bike, playing with my son, and some weird stuff like brushing my teeth really really hyper carefully.

I've taken a lot of supplements throughout the years expecting good results, but never experienced this effect as remarkably. Not even with 5ml C60oo every day for a while (tried VW and C60oliveoil.com), nor did CoQ10 at dosages of up to 200mg/day do anything noticeable.

 

4. What tox-concerns I know of:

- Could disturb MitoROS normally used to direct stem cell activity.

- Could disturb hormetic effects of exercise mediated by increased mtROS production.

 

5. I never tried taking it sublingually because oral administration worked wonders.

 

The only negative for me is that cost+shipping is $60. If it was cheaper I would like to take more.

 

One weird effect (not so weird if you plow through Lostfalcos Nootropic thread) is that MitoQ has a clearly noticeable psychological effect: It makes me markedly more outgoing and talkative. Falco has more on that, mitos play a central function in our brains so if you change them it follows that should literally change your mindstate.

 

 

If MitoQ "Could disturb MitoROS normally used to direct stem cell activity,

  Could disturb hormetic effects of exercise mediated by increased mtROS production", it mgiht be a concern.

C60 seems to work as a hormetic pathway, and PQQ is known to upregulate some hormetic gene expressions. Not only that, other supplements such as curcumin, silymarin are generally known as a nrf2, sirt1 activator. This pathway is usually realized by imposing a little harm, then taking benefits from repair responses. If MitoQ merely acts as a direct ROS scavenging agent, there would be some concerns regarding to those gene expression in the mitochondria level.

Although the claim that taking commercial hormetic supplements can lead to a longevity in mammals is still unclear, I wonder the impacts of MitoQ on various longevity related gene expression in regard to how it regulate them.

Also, how can MitoQ affect on glycolysis, Krebs cycle, and electron transport chain? What about the change on their feedback loops?

 

Mixed herb extracts or single extract from botanical compounds failed to extend the lifespan of mouses in the study (http://www.ncbi.nlm....les/PMC4039264/, http://www.ncbi.nlm....ubmed/22451473) while some mixture of nrf2 activating herbal extracts seems to work for male mice to increase a bit of longevity (http://www.ncbi.nlm.nih.gov/pubmed/27312235).

As I guess, there is a study MitoQ supplemented mice(don't know if it is healthy mice or genetically issued) has about 6% increased (either maximum or mean) lifespan. And, MitoQ supplemented mice has better endogenous antioxidants' status(glutathione, SOD ...). I need to study a little more before taking them and get some more information.

 

Edited by Graviton, 29 June 2016 - 06:22 PM.

[sthira]

greg,
how can you be sure that Mitoq skin serum can be absorbed into skin through its barriers, and then it can reach to its mitochondria?

Hi Graviton,

We have done testing called Franz diffusion cell testing which measures the delivery of MitoQ across the layers of the skin and this shows that it reaches the dermis in levels high enough to be active. From there it migrates directly to the mitochondria per our mitochondria-targeting technology i.e. the positive charge on MitoQ is attracted to the negative charge within the mitochondria.

Thanks.

Ingredients: Aqua, Cetearyl Alcohol, Behentrimonium Methosulfate, Dicapryl Carbonate, Glycerin, Mitoquinol Mesylate, Potassium Sorbate, Phenoxyethanol 



For skin, doesn't plain ole normal ubiquinone find its way easily into mitochondria? It would not be good if MitoQ serum's "Mitoquinol Mesylate" caused the body to recognize our own ubiquinone as an invader. Has anyone developed allergies from this serum yet?

Are there any safety studies regarding regular use of this? It's been on retail for several years.

[gregmacpherson]

 

 

1. What about the stability and bioavailability of MitoQ? Is each capsule enteric coated? I am concerned about degradation of Mitoq by stomach acid, and I would like to know if I have to encapsulate separate MitoQ capsules with stomach acid protected capsules again.

 

MitoQ has been extensively studied through to Phase II clinical level.  There are no issues with stability/bioavailability nor with degradation by stomach acid. 

 

2. Should I take MitoQ with food or in an empty stomach?

 

For better results take on an empty stomach. 

 

3. Can I take general advantages of MitoQ as described in MitoQ web-site if I am in early 20s? i.e. I wonder if Mitoq can fully act for young individuals who have sufficient amount of CoQ10, as it usually do to elderly people.

 

A good question; as long as you don't have any conditions associated with mitochondrial dysfunction you are unlikely to get much benefit from MitoQ in your 20s because you have adequate mitochondrial function and CoQ10 levels.  We recommend it from your 30s.  That said, if you are going through a period of high stress, illness or over indulgence then MitoQ can help in your 20s.

 

4. Any known UPDATED interactions with other supplements including C60, NR, pqq? (it has been asked before in this thread, but just to check any updates)

 

No known interactions.   

 

5. If taken sublingually, any toxicity or harms? (for example, from absorption of excipient materials etc) 

 

Not that we are aware of. 

[gregmacpherson]

 

Ingredients: Aqua, Cetearyl Alcohol, Behentrimonium Methosulfate, Dicapryl Carbonate, Glycerin, Mitoquinol Mesylate, Potassium Sorbate, Phenoxyethanol 



For skin, doesn't plain ole normal ubiquinone find its way easily into mitochondria? It would not be good if MitoQ serum's "Mitoquinol Mesylate" caused the body to recognize our own ubiquinone as an invader. Has anyone developed allergies from this serum yet?

Are there any safety studies regarding regular use of this? It's been on retail for several years.

 

 

Ubiquinol is synthesised inside the mitochondria and does not cross membranes easily.  Ubiquinone taken as a supplement has very low penetration in to the mitochondria.   This is why MitoQ is such a breakthrough as it is able to cross membranes and accumulates in the mitochondria improving their antioxidant capacity and stabilising the mitochondrial membrane.

 

No issues regarding sensitisation over the past 4 years.   We have over 100,000 patient months in market. 

 

Thanks

[Daniel Cooper]

Greg,

 

I'm wondering if there exists any studies were MitoQ was administered and blood parameters were monitored (say CBC labs)? 

 

Thanks,

 

 

[gregmacpherson]

Hi Daniel,

 

There hasn’t been a study where something like a full blood panel or CBC has been done but blood measurements of certain parameters such as ALT, AST, OxLDL have been conducted in clinical trials.

 

Thanks.

[Daniel Cooper]

Hi Daniel,

 

There hasn’t been a study where something like a full blood panel or CBC has been done but blood measurements of certain parameters such as ALT, AST, OxLDL have been conducted in clinical trials.

 

Thanks.

 

 

Has anyone ever noticed an impact on hemoglobin/hematocrit?

Edited by Daniel Cooper, 25 May 2018 - 04:14 PM.

[John250]

Has anyone ever noticed an impact on hemoglobin/hematocrit?

I’ve been using 10mg/day MitoQ with 200mg Ubiquinol for about a month. I always check my hemoglobin as I have secondary erythrocytosis from HRT. No noticeable changes.

Edited by John250, 17 July 2018 - 01:03 AM.

[Kalliste]

Back on daily MitoQ 10mg/day. Been a 6 month break because finances did not allow this luxury.

 

The delivery was very fast, I had to wait 1 month the first time. Down 1 week this time, that was nice.

 

The effect is subtle and very robust. No other supplement* ever gives really this effect of increased energy and clarity.

 

Fasting properly or C60oo has a similar effect but the oil is probably dangerous and fasting is something I cannot undertake too often.

 

It does seem to make me a bit angrier in some cases, but that is not a certainty.

 

*(coffee, green tea, glucosamine, curcumin, bacopa, ashwangada, tart-cherry, acacia catechu, melatonin, astaxanthin, CoQ10, c-vitamin, myo-inositol)

[resting]

Is there still a members discount for this product(s)?

[Advocatus Diaboli]

"Invicta Immortalem" posted the following in the "Verdict on MitoQ" thread (post #2) :

 

"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?"

Edited by Advocatus Diaboli, 01 August 2018 - 08:54 PM.

[gregmacpherson]

 

"Invicta Immortalem" posted the following in the "Verdict on MitoQ" thread (post #2) :

 

"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?"

 

 

Definitely a few comments!

 

We were very surprised when we saw this study but it turns out that they literally flooded the cells with MitoQ and any compound at a high enough concentration will mess with cell function.   This is a low-quality study which just shows that high concentrations of hydrophobic TPP cations in vitro are accumulated and can cause swelling. In vitro experiments were done with high volume of buffer - neglecting  accumulation. We know that MitoQ is protective against the kidney in several studies in vivo and also during organ storage. If you incubated the cells with 500 mM sucrose they'd die as well but that doesn't mean anything.

 

We are almost at the end of a clinical trial for Chronic Kidney Disease being run out of Delaware U and from what I understand it has gone well - more to follow on that soon.  See study #9 https://clinicaltria...te=&city=&dist=

 

I have listed our previous kidney research below. 

 

Mitochondria-targeted antioxidant MitoQ reduced renal damage caused by ischemia-reperfusion injury in rodent kidneys: Longitudinal observations of T2 -weighted imaging and dynamic contrast-enhanced MRI.

Liu X et al. Magn Reson Med. 2018 Mar;79(3):1559-1567. DOI: 10.1002/mrm.26772

 

Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ROS-TXNIP-NLRP3 biological axis.

Han Y et al. Redox Biol. 2018 Feb 15;16: 32-46. DOI: 10.1016/j.redox.2018.02.013

 

Mitochondrial abnormality facilitates cyst formation in autosomal dominant polycystic kidney disease.

Ishimoto Y et al. Mol. Cell. Biol. 2017 Dec. 37: 24 e00337-17. DOI: 10.1128/MCB.00337-1

 

The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1.

Xiao L et al. Redox Biol. 2017 Apr; 11: 297–311. DOI: 10.1016/j.redox.2016.12.022

 

Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes.

Ward MS et al. Scientific Reports 2017. 7: 15190. DOI: 10.1038/s41598-017-15589-x

 

The swan-neck lesion: proximal tubular adaptation to oxidative stress in nephropathic cystinosis.

Galaretta CI et al. Am J Physiol Renal Physiol. 2015 May 15;308(10): F1155-66. DOI: 10.1152/ajprenal.00591.2014

 

Protection against renal ischemia–reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ.

Dare AJ et al. Redox Biol. 2015 Aug; 5: 163–168. DOI:  10.1016/j.redox.2015.04.008

 

Contribution of mitochondrial function to exercise-induced attenuation of renal dysfunction in spontaneously hypertensive rats.

Gu Q et al. Mol Cell Biochem. 2015 Aug;406(1-2):217-25. DOI: 10.1007/s11010-015-2439-6

 

Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK) cells.

Marine A et al. Redox Biol. 2014; 2: 348–357. DOI: 10.1016/j.redox.2014.01.014

 

Preclinical evaluation of the mitochondria-targeted antioxidant mitoquinone to treat sepsis-induced acute kidney injury.

Patil NK et al. FASEB J. 2013 27:1_supplement, 889.8-889.8 (LINK)

 

Prevention of diabetic nephropathy in Ins2^+/−AkitaJ mice by the mitochondria-targeted therapy MitoQ.

Chacko BK et al. Biochem J. 2010 Nov 15; 432(Pt 1): 9–19. DOI: 10.1042/BJ20100308

 

I hope that clarifies the situation satisfactorily. 

This is a low-quality study which just shows that high concentrations of hydrophobic TPP cations in vitro are accumulated and can cause swelling. In vitro experiments were done with high volume of buffer - neglecting  accumulation. No serum or BSA was used in the incubation medium (!). We know that MitoQ is protective against the kidney in several studies in vivo and also during organ storage. If you incubated the cells with 500 mM sucrose they'd die as well but that doesn't mean anything.

Is there still a members discount for this product(s)?

 

There should be. Please contact Longecity admin and if not please let me know and I will check in. Thanks. 

[Advocatus Diaboli]

Greg, just to be clear, the "Any comments?" question is part of the quote of "Invicta Immortalem" in the "Verdict on MitoQ" thread. "Invicta Immortalem" may not be aware of this thread, so posting your reply there, too (if you haven't already), probably would be helpful.

Edited by Advocatus Diaboli, 01 August 2018 - 10:23 PM.

[gregmacpherson]

Greg, just to be clear, the "Any comments?" question is part of the quote of "Invicta Immortalem" in the "Verdict on MitoQ" thread. "Invicta Immortalem" may not be aware of this thread, so posting your reply there, too (if you haven't already), probably would be helpful.

Thanks - have just cross posted!

[QuestforLife]

Hi Greg,

 

 

 

I hope that clarifies the situation satisfactorily. 

This is a low-quality study which just shows that high concentrations of hydrophobic TPP cations in vitro are accumulated and can cause swelling. In vitro experiments were done with high volume of buffer - neglecting  accumulation. No serum or BSA was used in the incubation medium (!). We know that MitoQ is protective against the kidney in several studies in vivo and also during organ storage. If you incubated the cells with 500 mM sucrose they'd die as well but that doesn't mean anything.

 

There should be. Please contact Longecity admin and if not please let me know and I will check in. Thanks. 

 

Please explain the bolded text further.

 

From my admittedly speedy reading of the paper, cells were incubated in 500nM not 500mM, hardly a high concentration and one easily achieved by taking your tablets, I'd expect.

 

 

[gregmacpherson]

Hello Questforlife, 

 

Explanations below. Thanks!

 

In vitro experiments were done with high volume of buffer - neglecting  accumulation.

The issue here is that the volume of the extracellular medium is high compared to the volume of the cells ( factors of 10,000- 1,000,000). Hence, compounds like MitoQ will be accumulated into the cells/mitochondria without effectively  lowering the external concentration hence the amounts in the mitochondria at equilibrium will depend on the extracellular volume. This isn't the case in vivo where the extracellular volume and the reservoir of compound outside cells are both v small.

No serum or BSA was used in the incubation medium

This is a major difference between in vivo and in vitro, and also between experiments with cells using serum. MitoQ binds more than 99% to serum albumin in plasma. Hence the free concentration is 1% of that in incubation without serum albumin, hence the uptake driven by the membrane potentials, which is described by the Nernst equation which only responds to free compound, means that the uptake in to cells - and hence the non-specific damage,  will be huge. 

In vivo we don't see kidney damage. Also, in vitro it is essential to do control experiments with a biologically inactive control compound to correct for these non-specific uptake artifacts.



If you incubated the cells with 500 mM sucrose they'd die as well but that doesn't mean anything.

The point here is that without the above controls the uptake of 500 nM MitoQ will be tens to hundreds of mM within mitochondria, so you will get nonspecific effects just as if you added a very high concentration of a compound that was not accumulated due to non-specific effects.
 

[QuestforLife]

Thanks for your response Greg.

 

Now if only MitoQ wasn't so expensive, I might buy it!