179 replies to this topic

[Fafner55]

Yes I read that, I also looked at the ALT changes there were some reasonable large outliers at 1000mg. Vehicle 85+/-26, 1000mg 106+/-45. For a weeks experiment probably not a big worry but typically ALT up indicates potentially some liver damage.

 

 

You make a good point about the ALT changes.  I plan to back the dose down on my next experiment.  It should be possible to get the same effect with a lower dose.

[Fafner55]

For completeness, the changes stefan referred to are shown in the attached table.

 

 hematological changes from feeding rats large doses of NR for 90 days.jpg   151.34KB   9 downloads

 

 

[niner]

 

Yes I read that, I also looked at the ALT changes there were some reasonable large outliers at 1000mg. Vehicle 85+/-26, 1000mg 106+/-45. For a weeks experiment probably not a big worry but typically ALT up indicates potentially some liver damage.

 

You make a good point about the ALT changes.  I plan to back the dose down on my next experiment.  It should be possible to get the same effect with a lower dose.

 

I don't see anything to worry about in the ALT results.  First of all, these are dosed per kilogram of body weight, so they are massive doses.  Second, ALT is very easy to move around.  You can do it with a couple drinks.  Also note that at the 300 mg/kg dose, ALT went DOWN compared to vehicle rather than up.  While I wouldn't take that to mean anything, a naive person might claim that the lower (but still gigantic) dose was hepatoprotective(!)  It would be interesting to get a standard panel of blood tests after the protocol to see what it's doing in practice.

Edited by niner, 06 November 2016 - 01:13 AM.

[stefan_001]

Yes I read that, I also looked at the ALT changes there were some reasonable large outliers at 1000mg. Vehicle 85+/-26, 1000mg 106+/-45. For a weeks experiment probably not a big worry but typically ALT up indicates potentially some liver damage.

You make a good point about the ALT changes. I plan to back the dose down on my next experiment. It should be possible to get the same effect with a lower dose.

I don't see anything to worry about in the ALT results. First of all, these are dosed per kilogram of body weight, so they are massive doses. Second, ALT is very easy to move around. You can do it with a couple drinks. Also note that at the 300 mg/kg dose, ALT went DOWN compared to vehicle rather than up. While I wouldn't take that to mean anything, a naive person might claim that the lower (but still gigantic) dose was hepatoprotective(!) It would be interesting to get a standard panel of blood tests after the protocol to see what it's doing in practice.

Could well be but ALT is further up at 3000mg/kg so it seems somewhat reasonable to keep an eye on that and not go extreme high in dosing in the mito experiments unless really needed, at least that is what I will do if I try it. JMHO

[richard hnry]

Give the fact that the ALT is up, what would be the recommended dosage of NR for the treatment?  The 10 capsules a day would perhaps be too high?  What in your opinion would be the optimum amount of NR?

[Nate-2004]

A post related to Essential Tremor and mitochondrial DNA. I don't quite understand this fully but it was posted in the Essential Tremor Reddit, was hoping someone might be able to shed some light on this for someone like me with ET.

 

https://www.research...ssential_tremor

 

Abstract

Essential tremor (ET) is one of the most common of the movement disorders. However, there has been little agreement in the neurological literature regarding diagnostic criteria for ET. It is not clear to what extent ET is associated with defects of mitochondrial DNA. In this study, we analyzed mitochondrial DNA (mtDNA) from the blood cells of the normal and ET patients using the long and accurate polymerase chain reaction (LA-PCR) and PCR. The large deletions were detected within several regions of mtDNA, but were not detected in the D-loop or CO I regions in ET patients. From our study, it is suggested that ET is a disorder showing a deficiency of mtDNA multicomplexes, and it also appears that mitochondrial dysfunction could be one of the causative factors of ET.

[richard hnry]

When you say "induction time" what do you mean by it exactly?

[richard hnry]

 

Fafner55, thanks for the pomegranate extract report.  Although I'm not certain that a Human Equivalent Dose calculation is called for in this particular case, it probably is.  If that's the case, then the HED for a mouse getting 4mg/kg/d in a 70kg human is 280/12 = 23 mg UA.  Using the same assumptions as you have above, that would translate to about one half to one gram per day, which is a lot easier to stomach.   I think it's unlikely that the pomegranate extract caused your diverticulitis.  I think it's more likely that it was coincidental, although you did take a lot of extract, so it's not like we can rule it in or out as a cause. 

 

If you did have a higher level of mitophagy, how would you know?  A sudden change in apparent cardiovascular fitness?  What sort of time course would one expect in such an improvement?

 

ps:  Just saw the NR post.  Very interesting!  We need better ways to quantify the effects.

 

Niner, I mistyped in post #58 when I stated "4 mg/kg/day in mice". The authors of Urolithin-A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents wrote "Notably, the in vivo results were obtained after administration of UA at a dose of 50 mg/kg/d in mice, which is equivalent to 4 mg/kg/d in humans ..."  (not 4 mg/kg/day in mice as I wrote).  

 

At 4 mg/kg/day, the dose for a 70 kg individual is 280 gm.  It follows that the amount of pomegranate extract needed to get the equivalent dose of UA (if the right gut bacteria is present) is likely in the range of 5.6  to 11.2 gm.

 

Regarding the diverticulitis, it was most likely caused by the large amounts of pomegranate extract I was taking.  Consider, if you were to empty a capsule of Jarrow Formulas PomeGuard brand extract into a cup of water and stir it with a spoon, you would find that small pieces of ground pomegranate would glue to the spoon.  They are quite difficult to get off.  I can guess that in the same way particles of pomegranate adhered to my colon and led to an infection.

 

I think you mean 280 mg per day not 280 grams.  I was able to find a supplier for Urolithin A on Alibaba and it looks like it costs about $10 per gram.  That would translate to a cost of about $2.80 per dose.  I do not know how many doses you would need to jump start our mitophagy.  Maybe we only need to take it for a few weeks?

[Hip]

Mitochondrial problems can come from the immune system attacking them. There are several autoantibodies that the immune system sometimes produces, and which can attack and disrupt mitochondria. These anti-mitochondrial antibodies are sometimes triggered by infection. 

 

More info:  Anti-mitochondrial antibody - Wikipedia

[Fafner55]

I think you mean 280 mg per day not 280 grams.  I was able to find a supplier for Urolithin A on Alibaba and it looks like it costs about $10 per gram.  That would translate to a cost of about $2.80 per dose.  I do not know how many doses you would need to jump start our mitophagy.  Maybe we only need to take it for a few weeks?

 

 

Yes, mg not gm.

 

The authors of the study treated mice for 6 weeks.  Since mitochondria only live a few days continuous treatment for 6 weeks seems long, but that is the only data point I am aware of for the induction of mitophagy with Urolithin A.

 

Are you planning a group buy?

[richard hnry]

 

I think you mean 280 mg per day not 280 grams.  I was able to find a supplier for Urolithin A on Alibaba and it looks like it costs about $10 per gram.  That would translate to a cost of about $2.80 per dose.  I do not know how many doses you would need to jump start our mitophagy.  Maybe we only need to take it for a few weeks?

 

 

Yes, mg not gm.

 

The authors of the study treated mice for 6 weeks.  Since mitochondria only live a few days continuous treatment for 6 weeks seems long, but that is the only data point I am aware of for the induction of mitophagy with Urolithin A.

 

Are you planning a group buy?

 

 

If I were not so ill I would most definitely do a group buy.  I have too much weakness and my day to day activities are about all I can handle right now.  Thanks for all of the really interesting information though.
 

[Turnbuckle]

 

The authors of the study treated mice for 6 weeks.  Since mitochondria only live a few days continuous treatment for 6 weeks seems long, but that is the only data point I am aware of for the induction of mitophagy with Urolithin A.

 

 

 

It's difficult to say how long mitochondria live, as they are constantly fusing with other mitochondria and then fissioning again. They can do this 5 times an hour. So it would be better to ask about the half life of mtDNA, which ranges considerably depending on tissue type. 

 

Mitochondrial DNA has a half-life of 6.7 days in heart, 9.4 days in liver, 10.4 days in kidney, and about 31 days in brain.

 

http://www.jbc.org/content/244/6/1552

 

 

So 6 weeks is not out of line.

[richard hnry]

I contacted several companies on Alibaba and the best price per gram of Urolithin A is about $23 a gram.  I thought it would be about $10 a gram as it said in the description.  This $23/gram price is only available if you buy 500 grams or more.  This would be a pretty high price for sure.  What do you think about group buy for this?

 

I think you mean 280 mg per day not 280 grams.  I was able to find a supplier for Urolithin A on Alibaba and it looks like it costs about $10 per gram.  That would translate to a cost of about $2.80 per dose.  I do not know how many doses you would need to jump start our mitophagy.  Maybe we only need to take it for a few weeks?

 

 

Yes, mg not gm.

 

The authors of the study treated mice for 6 weeks.  Since mitochondria only live a few days continuous treatment for 6 weeks seems long, but that is the only data point I am aware of for the induction of mitophagy with Urolithin A.

 

Are you planning a group buy?

 

 

 

[Fafner55]

 

I contacted several companies on Alibaba and the best price per gram of Urolithin A is about $23 a gram.  I thought it would be about $10 a gram as it said in the description.  This $23/gram price is only available if you buy 500 grams or more.  This would be a pretty high price for sure.  What do you think about group buy for this?

 

 

No other mitophagy treatment has shown the benefits of Urolithin A.  If you put together a group buy, I'm in.

[Turnbuckle]

 

 

No other mitophagy treatment has shown the benefits of Urolithin A...

 

 

You previously posted figures for nicotinamide that look extremely good (Post #59). Do you have comparative data for Urolithin A?

 

BTW, I've found that nicotinamide at the gram+ level gives me a slightly unpleasant feeling, however NR does not. But adding ribose (at a dose of 2X +) to nicotinamide eliminates the unpleasing feeling. So it is possible that NR is just an expensive method of getting the necessary ribose.

[Nate-2004]

 

 

 

No other mitophagy treatment has shown the benefits of Urolithin A...

 

 

You previously posted figures for nicotinamide that look extremely good (Post #59). Do you have comparative data for Urolithin A?

 

BTW, I've found that nicotinamide at the gram+ level gives me a slightly unpleasant feeling, however NR does not. But adding ribose (at a dose of 2X +) to nicotinamide eliminates the unpleasing feeling. So it is possible that NR is just an expensive method of getting the necessary ribose.

 

 

I don't think the posted figures regarding high dose NR has any actual proof in terms of study associated with it. It's just theoretical/anecdotal. The Urolithin A treatment at least has a single (and as far as I know) uncontrolled study associated with it. I'd be interested in purchasing Urolithin A in a group buy especially given the study I posted regarding Essential Tremor a few posts back.  One thread on this forum claims that baking soda enables mitochondrial biogenesis, yet offers no real proof. I can't seem to find any proof of the claim anywhere but that too would be interesting.

Edited by Nate-2004, 08 December 2016 - 06:04 PM.

[Fafner55]

 

 

 

No other mitophagy treatment has shown the benefits of Urolithin A...

 

 

You previously posted figures for nicotinamide that look extremely good (Post #59). Do you have comparative data for Urolithin A?

 

BTW, I've found that nicotinamide at the gram+ level gives me a slightly unpleasant feeling, however NR does not. But adding ribose (at a dose of 2X +) to nicotinamide eliminates the unpleasing feeling. So it is possible that NR is just an expensive method of getting the necessary ribose.

 

 

Raising NAM is proven to induce mitophagy, as indicated in Post #59, as does Urolithin A.  However, by at least one measure it appears that Urolithin A gives benefits that NR and possibly nicotinamide might not - lifespan of C. elegans.

 

"Urolithin-A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents" reports

1. 45% increase in lifespan in C. elegans
2. 42% increase in running endurance in aged rats

 

In contrast, NR is shown to give 16% increase in mean lifespan in C. elegans.   “The NAD+/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling” (2013) http://www.cell.com/...674(13)00755-1 

 

I don't have comparative results for rat running endurance or grip strength with age with either NR or nicotinamide treatment, or C. elegans lifespan changes from nicotinamide treatment.

 

As for nicotinamide + ribose, you might be right that this is as effective as NR but I don't have enough in the way of supporting data.

Edited by Fafner55, 08 December 2016 - 06:36 PM.

[Turnbuckle]

 

 

 

 

No other mitophagy treatment has shown the benefits of Urolithin A...

 

 

You previously posted figures for nicotinamide that look extremely good (Post #59). Do you have comparative data for Urolithin A?

 

BTW, I've found that nicotinamide at the gram+ level gives me a slightly unpleasant feeling, however NR does not. But adding ribose (at a dose of 2X +) to nicotinamide eliminates the unpleasing feeling. So it is possible that NR is just an expensive method of getting the necessary ribose.

 

 

I don't think the posted figures regarding high dose NR has any actual proof in terms of study associated with it. It's just theoretical/anecdotal. The Urolithin A treatment at least has a single (and as far as I know) uncontrolled study associated with it. I'd be interested in purchasing Urolithin A in a group buy especially given the study I posted regarding Essential Tremor a few posts back.  One thread on this forum claims that baking soda enables mitochondrial biogenesis, yet offers no real proof. I can't seem to find any proof of the claim anywhere but that too would be interesting.

 

 

These are real results with NAM. You are right that the NR researcher presented his own results (an n=1), and that has been used for marketing.

 

As for baking soda, here is one source--

 

 

This suggests that both mitochondrial mass and mitochondrial function were significantly greater in BIC. [BIC is the rat group receiving baking soda before exercise.]

http://ajpendo.physi...299/2/E225.long

 

 

Edited by Turnbuckle, 08 December 2016 - 07:41 PM.

[lost69]

 

 

I contacted several companies on Alibaba and the best price per gram of Urolithin A is about $23 a gram.  I thought it would be about $10 a gram as it said in the description.  This $23/gram price is only available if you buy 500 grams or more.  This would be a pretty high price for sure.  What do you think about group buy for this?

 

 

No other mitophagy treatment has shown the benefits of Urolithin A.  If you put together a group buy, I'm in.

 

 

i am interested too in group buy

[richard hnry]

Let me know how much you are in for as we need to get up to 500 grams before we can get this price break.

 

 

 

I contacted several companies on Alibaba and the best price per gram of Urolithin A is about $23 a gram.  I thought it would be about $10 a gram as it said in the description.  This $23/gram price is only available if you buy 500 grams or more.  This would be a pretty high price for sure.  What do you think about group buy for this?

 

 

No other mitophagy treatment has shown the benefits of Urolithin A.  If you put together a group buy, I'm in.

 

 

i am interested too in group buy

 

 

[Fred_CALICO]

I am interested too in group buy (Urolithin A.)

[tunt01]

I would be interested in Urolithin A.  25 grams @ $23/g.

[lost69]

interested in 15gr

[richard hnry]

interested in 15gr

 

I found another vendor who offered a lower price at $19.50/gram.

[Nate-2004]

If 33 days is long enough at around 300mg per day for an 80kg human I could go for 10 grams as well so put me in.

[richard hnry]

So far in a group buy scenario I have:

 

Nate-2004    10 grams

Prophets        25 grams

Lost69             15 grams

Richard hnry   15 grams

[lost69]

So far in a group buy scenario I have:

 

Nate-2004    10 grams

Prophets        25 grams

Lost69             15 grams

Richard hnry   15 grams

 

i think we need a separate post with the studies on Urolithin A, safety, doses and what benefits we can expect, so maybe more readers can be interested

[Turnbuckle]

 

 

Richard hnry   15 grams

i think we need a separate post with the studies on Urolithin A, safety, doses and what benefits we can expect, so maybe more readers can be interested

 

 

A separate Urolithin group buy thread is warranted, so as not to bury it pages back in this thread. 

[Fafner55]

Experiment #3: Inducing Mitophagy with NR

Following personal Experiment #1 and Experiment #2, this experiment is an attempt to determine if a lower dose of NR (2625 mg / day) might induce mitophagy.

 

2016-12-04  Day 1. Begin taking 7 capsules (875 mg) of NR three times per day for a total of 2625 mg / day. I have not taken C60-OO or any supplements or medications for a two weeks.

2016-12-07  Day 4. I have noticed any symptoms or side effects since beginning this treatment other than an occasional sensation of flushing a few minutes after ingesting NR.

2016-12-08  Day 5. There are no noticeable symptoms.  

2016-12-09  Day 6. Last day of this trial.  

2016-12-12  Day 9. Unlike Experiments #1 and #2, during this trial my normally regular, quiet lifestyle was interrupted due to unexpected business travel followed on days 6 and 7 by physically demanding, days-long home repair.  During days 6-9, I experienced an unusual level of muscle ache and stiffness.  I can’t determine the extent which this treatment or the home repair might have contributed to these muscle ache symptoms, or even if this this dose was sufficient to induce mitophagy at all.  A follow up experiment #4 at the earlier higher dose of NR (3750 mg/day) with my normal lifestyle will help clarify this situation.  If NR has been effective in inducing mitophagy, I would expect that there would be fewer symptoms of muscle ache in an experiment #4 even at the higher dose.

 

[Nate-2004]

I'm pretty skeptical about NR inducing mitophagy or biogenesis and even if the NAD ratio is relevant, NR doses beyond 300mg have a diminishing returns on NAD+. Taking that much NR is likely a waste of money if this is what you're trying to achieve. Plus you get a 50% boost in NAD+ from 300mg alone that lasts most of the day, peaking at specific times. 

 

PQQ has some preliminary evidence for humans. There is so little research on PQQ, no controlled or double blind tests to be sure because preliminary evidence showed little promise for a lot of specific conditions being treated. There are several diseases theorized to be related to mitochondrial dysfunction including the one I have, Essential Tremor, but this theory is relatively recent. 

 

I'm considering taking some but worried it's just throwing my money down the drain yet again.