2287 replies to this topic

[Andey]

Turnbuckle or anyone who can help,

 

I have ordered all the supplements for my Fission/Fusion experiment.  I will be using NR and Stearic Acid.(only 1 day a week)  Seems the stearic acid is a waxy substance, and that will be different ingesting it.  2 days Fission then 2 days Fusion with 3 days off at first.  Working my way up to a weekly 3+3 with 1 day off in time.  I found broccoli sprout extract, 500 mg (per capsule) with 5% sulforaphane taking 2 capsules.  Do I skip the broccoli on the 1st. day when taking the Stearic Acid?

 

I have been taking 500 mg NR twice a week until I get started.  I would like to say that the 500 mg kicks my ass for that day.  Afraid of what 2-3 gm will do.  I feel really tired and out of it when I take the NR for most of the day.  Clearing out those Zombies is hard work.

 

Is there anything I can do to help with the feeling of being wiped out??  All I do is lay around and over eat.

 

Will post this on NR experiences forum as well.

 

  Try to do fission cycle during fast.

 I've noticed that if I fast during this day NAM+R are hardly noticeable, just little buzz.

 If I eat I became a little bit groggy if I add baking chocolate with coffee I end up wiped out. 

Having said that 500mg NR is nothing compared to NAM+R doses that are used here (I hardly notice usual doses of NR at all).

I would suggest buildup your mito machinery slowly and supplement with cofactors esp methyl group donors like betaine, PScholine, maybe preload with creatine as the majority of methyl groups usually used to create it, so you will decrease demand on methyl groups simultaneously with increase uptake from betaine and/or PS choline (few poached egg yolks would tick that box).

[Nate-2004]

So I was considering honokiol during the fission cycle as it has an effect on mitochondrial membrane potential (though the title of this seems misleading). 

 

https://www.nature.c...cles/ncomms7656

 

http://journals.plos...al.pone.0184003

 

Still searching around but let me know what you think.

[Turnbuckle]

So I was considering honokiol during the fission cycle as it has an effect on mitochondrial membrane potential (though the title of this seems misleading). 

 

https://www.nature.c...cles/ncomms7656

 

http://journals.plos...al.pone.0184003

 

Still searching around but let me know what you think.

 

Why would you want to damage your mitochondrial DNA?

[Nate-2004]

The idea isn't to damage it, I don't think honokiol damages it (that title was misleading), but the reduced membrane potential in the fission phase would enable better targeting for quality control would it not? Honokiol is a SIRT3 activator (see above links) and I just figure it's another QC approach, also it has anti-inflammatory effects and is a good anxiolytic.

Edited by Nate-2004, 30 October 2017 - 02:52 PM.

[Turnbuckle]

The idea isn't to damage it, I don't think honokiol damages it (that title was misleading), but the reduced membrane potential in the fission phase would enable better targeting for quality control would it not? Honokiol is a SIRT3 activator (see above links) and I just figure it's another QC approach, also it has anti-inflammatory effects and is a good anxiolytic.

 

From your second reference--

 

...we observed increased transcription of mitochondrial genes (ATP6 and COX2) after honokiol exposure (Fig 5). It is possible that cells after honokiol exposure attempts to overcome the ROS-induced mtDNA damage by increased mtDNA genes expression, which reflects a compensatory mechanism...

 

Honokiol targets on the mitochondrial respiratory electron transport chain C I inducing ROS production (mainly O2·−) and mitochondria dysfunction. ROS induces mtDNA damage, mtΔψ decrease, oxidation of proteins and lipids.

 

Honokiol treatment caused mitochondrial dysfunction and then damaged the cell wall integrity, thus, increased sensitivity to cell wall perturbing agents.

 

This work not only provides insights on the mechanism by which honokiol interferes with fungal cell, demonstrating previously unknown effects on mitochondrial physiology, but also raises a note of caution on the use of M. officinalis as a Chinese medicine due to the toxic for mitochondria and suggests the possibility of using honokiol as chemosensitizer.

 

I'm also wondering if you've even tried N+R fission yet, and why you'd want to add stuff like this before you've tried it.

Edited by Turnbuckle, 30 October 2017 - 03:07 PM.

[Nate-2004]

 

The idea isn't to damage it, I don't think honokiol damages it (that title was misleading), but the reduced membrane potential in the fission phase would enable better targeting for quality control would it not? Honokiol is a SIRT3 activator (see above links) and I just figure it's another QC approach, also it has anti-inflammatory effects and is a good anxiolytic.

 

From your second reference--

 

...we observed increased transcription of mitochondrial genes (ATP6 and COX2) after honokiol exposure (Fig 5). It is possible that cells after honokiol exposure attempts to overcome the ROS-induced mtDNA damage by increased mtDNA genes expression, which reflects a compensatory mechanism...

 

Honokiol targets on the mitochondrial respiratory electron transport chain C I inducing ROS production (mainly O2·−) and mitochondria dysfunction. ROS induces mtDNA damage, mtΔψ decrease, oxidation of proteins and lipids.

 

Honokiol treatment caused mitochondrial dysfunction and then damaged the cell wall integrity, thus, increased sensitivity to cell wall perturbing agents.

 

This work not only provides insights on the mechanism by which honokiol interferes with fungal cell, demonstrating previously unknown effects on mitochondrial physiology, but also raises a note of caution on the use of M. officinalis as a Chinese medicine due to the toxic for mitochondria and suggests the possibility of using honokiol as chemosensitizer.

 

I'm also wondering if you've even tried N+R fission yet, and why you'd want to add stuff like this before you've tried it.

 

 

Yes I've tried it just the other day. I actually ended up with insomnia that night though not sure if it was related. I plan to combine it with NR over the three day period but will do the N+R part a couple of hours before workout.  I'll be trying it again with just N+R tomorrow or Weds.

 

I'll leave out the honokiol for now, good points.

Edited by Nate-2004, 30 October 2017 - 03:58 PM.

[Turnbuckle]

 

 

 

Yes I've tried it just the other day. I actually ended up with insomnia that night though not sure if it was related.

 

 

 

 

This is one advantage of adding a gram of tryptophan to an evening dose.

[Nate-2004]

 

 

 

 

Yes I've tried it just the other day. I actually ended up with insomnia that night though not sure if it was related.

 

 

 

 

This is one advantage of adding a gram of tryptophan to an evening dose.

 

 

Actually weirdly enough, tryptophan can also trigger my insomnia as well, assuming because of its effect on serotonin. I'll try again though.

[smithx]

Sorry if this has been asked and answered before in this thread or elsewhere, but:

Is there evidence showing that nicatinomide by itself plus ribose by itself, when taken together actually do increase intra-celular NAD+?

I'm looking for any papers which have shown this to be true, not logical arguments for why it might happen.

[Turnbuckle]

Sorry if this has been asked and answered before in this thread or elsewhere, but:

Is there evidence showing that nicatinomide by itself plus ribose by itself, when taken together actually do increase intra-celular NAD+?

I'm looking for any papers which have shown this to be true, not logical arguments for why it might happen.

 

 

You will find that the same paper that claims NR is orally available (falsely, in my opinion), also shows that NAM at about half the dose by weight of NR produces about 90% of the NAD+ as NR over time. You can find the discussion on this thread, where it should be discussed.

[smithx]

OK, So NAM may increase NAD+, but no studies showing that nicatinomide + riboside taken together actually do increase it?

Sorry if this has been asked and answered before in this thread or elsewhere, but:

Is there evidence showing that nicatinomide by itself plus ribose by itself, when taken together actually do increase intra-celular NAD+?

I'm looking for any papers which have shown this to be true, not logical arguments for why it might happen.

 
 
You will find that the same paper that claims NR is orally available (falsely, in my opinion), also shows that NAM at about half the dose by weight of NR produces about 90% of the NAD+ as NR over time. You can find the discussion on this thread, where it should be discussed.

[Turnbuckle]

OK, So NAM may increase NAD+, but no studies showing that nicatinomide + riboside taken together actually do increase it?

 

 

 

 

Exactly. The NR researchers compared NR to a lot of things, but somehow failed to compare it to N+R.

[PAMPAGUY]

 

 

 

 

 

Yes I've tried it just the other day. I actually ended up with insomnia that night though not sure if it was related.

 

 

 

 

This is one advantage of adding a gram of tryptophan to an evening dose.

I'm going to start taking L-Tryptophan 1 gm on NR days and see how I feel  Will report back

 

Actually weirdly enough, tryptophan can also trigger my insomnia as well, assuming because of its effect on serotonin. I'll try again though.

 

 

I'm going to start taking L-Tryptophan 1 gm on NR days and see how I feel  Will report back

[smithx]

So you are confirming that your hypothesis that N + R increases NAD+ is just a hypothesis. There's no actual data showing that it works.

But there is evidence that high doses of nicotinamide can be harmful: http://journals.sage...915810500434183

And reports that d-ribose also causes problems for some people: http://www.longecity...nd-proteinuria/

So suggesting that people should avoid nicotinamide riboside and instead take nicotinamide and d-ribose seems at best speculative and at worst bad advice which potentially may harm people.


 

OK, So NAM may increase NAD+, but no studies showing that nicotinamide + riboside taken together actually do increase it?

 
Exactly. The NR researchers compared NR to a lot of things, but somehow failed to compare it to N+R.

Edited by smithx, 31 October 2017 - 05:54 PM.

[Turnbuckle]

So you are confirming that your hypothesis that N + R increases NAD+ is just a hypothesis. There's no actual data showing that it works.

 

So I take it you are a Cromadex stockholder. We have enough of those already at Longecity, and plenty of threads about NR. This thread is for those who want to experiment with fission/fusion, and with N+R. I'm not telling anyone to do anything, only laying out my own experiments with it. Those telling people to take NR, and especially those who advocate taking it every day, are merely pushing a product for profit. There is no data for humans taking it for long periods, and taking it every day could be harmful if it results in a permanent state of fission.

Edited by Turnbuckle, 31 October 2017 - 06:41 PM.

[BigLabRat]

So you are confirming that your hypothesis that N + R increases NAD+ is just a hypothesis. There's no actual data showing that it works.

But there is evidence that high doses of nicotinamide can be harmful: http://journals.sage...915810500434183

And reports that d-ribose also causes problems for some people: http://www.longecity...nd-proteinuria/

So suggesting that people should avoid nicotinamide riboside and instead take nicotinamide and d-ribose seems at best speculative and at worst bad advice which potentially may harm people.

 

Wow, that's really confused.

 

There is no evidence than NAM + R increases NAD+ more than NAM alone. But there is ample evidence that NAM increases NAD+. As does Niacin. Indeed, depending on what time index you use and how you adjust for molecular weight, any of these three (including NR) might be "more effective." But they all clearly work to raise NAD+.

 

Does ribose increase the effect? Not clear. But ribose is involved in many places--and not just in the NAD cycles. It is critical to ATP generation, and an essential component of DNA. And it is often administered by doctors after heart failure.

 

As to your "reports" that ribose causes "problems for some people," you are quoting a very short thread from 2012 that is citing scattered anecdotes from the internet and then turns to the topic of acupuncture.

 

The report that you cite on the dangers of NAM instead concludes the exact opposite of what you claim. It specifically says: "While Niacinamide is more toxic than Niacin in acute toxicity studies, both are relatively non-toxic."

 

NAM and Niacin have been extensively studied for decades. NR has not. So it's you who is giving bad advice.

[Heisok]

Thanks smithx. I have seen that Low Carb and D-Ribose before in a couple threads here, and there did not seem to be long-term follow-up by the posters. I hope all their issues resolved, although the tie to D-Ribose might not be true. Who knows. (P.S. I have never gotten an inclination that you are a shill for stockholders.)

 

I am still curious if there are any Ketogenic or Low Carb members trying the protocol? Checking blood glucose?

 

I trust Turnbuckles opinion, and result reports. His theory, and personal experience are plenty. Past experience says that, he will report as contrary data or experience come to him. High integrity member.There have been plenty who are taking shots at this thread, maybe some should watch for awhile.

Edited by Heisok, 31 October 2017 - 10:15 PM.

[smithx]

Anyone who questions you does not necessarily have an agenda Turnbuckle.
I've been on these forums for many years and no, I don't own stock in any supplements company.

I am always looking for the truth, and for what could benefit me and others. In this case, you admittedly have been making assumptions about something and basing lots of actions on your assumptions, and it appears that a number of people are following your example. I want everyone to be clear about what is and is not supported by evidence.

With regard to nicotinamide raising NAD+ substantially, is there any study data to back that up? If so, it might be possible to at least have a baseline comparison that could be made between that and NR.

 

So you are confirming that your hypothesis that N + R increases NAD+ is just a hypothesis. There's no actual data showing that it works.

 
So I take it you are a Cromadex stockholder. We have enough of those already at Longecity, and plenty of threads about NR. This thread is for those who want to experiment with fission/fusion, and with N+R. I'm not telling anyone to do anything, only laying out my own experiments with it. Those telling people to take NR, and especially those who advocate taking it every day, are merely pushing a product for profit. There is no data for humans taking it for long periods, and taking it every day could be harmful if it results in a permanent state of fission.

Edited by smithx, 31 October 2017 - 10:30 PM.

[smithx]

There is no evidence than NAM + R increases NAD+ more than NAM alone.

That's my point really. I don't see any evidence of this presented, and it seems rather like magical thinking.

The study I quoted was for skin, so not that germane. Apologies.

This discussion notes at least transient heptotoxicity: https://livertox.nlm....gov/Niacin.htm

My point is that nicotinamide is not completely benign and people should be somewhat careful with it. And that the idea that if you take two components of a compound together it somehow has the same effect as the compound, in the absence of any data supporting that, is not particularly likely to be correct.

[smithx]

... taking it every day could be harmful if it results in a permanent state of fission.

Another point I'm curious about:

- What studies support your idea that fusion and fission of mitochondria can be controlled through the diet?
- What studies support your idea that a "permanent state of fission" could arise?
- What studies support your idea that such a state, if it did occur, would be harmful?

[BigLabRat]

I'm low-carb. Haven't noticed any unusual effects from the protocol.

 

I don't currently check blood glucose. I'm not sure what I'd do with the information if I did. Does a blood glucose test register ribose as glucose? Does glycation when you're taking excess ribose mean the same thing it does when you're eating "normally"?

 

As an example, a number of people have been breathalyzed as drunk because of ketones from low-carbing. The problem is that the meaning of the measurement includes a lot of unstated assumptions.

 

For another example, according to his BMI, Arnold Schwartzeneggar at his peak Mr Olympia shape was "Clinically Obese"...at about 5% body fat.

[Heisok]

BigLabRat, those are good questions. All I can say is my experience. Taking D-Ribose now given everything individual about me, I get a spike in B.G. after taking D-Ribose. It goes down after a few hours. Being Low Carb/Ketogenic might have a role, pre-diabetes might, activity level etc......

 

Many years ago, I took from 5 gm to 10 gms per day. I did not personally test B.G. at that time, but periodic lab tests did not indicate any fasting test issues. Just my experience, and honestly I do not have a judgement whether or not my current results are a problem.

Edited by Heisok, 31 October 2017 - 10:45 PM.

[pamojja]

I am still curious if there are any Ketogenic or Low Carb members trying the protocol? Checking blood glucose?

 

I reported my experience with low carb, Niacin, Ribbose and Hb1Ac for 9 years a page before:

 

http://www.longecity...ndpost&p=831164
 

[BigLabRat]

 

There is no evidence than NAM + R increases NAD+ more than NAM alone.

That's my point really. I don't see any evidence of this presented, and it seems rather like magical thinking.

The study I quoted was for skin, so not that germane. Apologies.

This discussion notes at least transient heptotoxicity: https://livertox.nlm....gov/Niacin.htm

My point is that nicotinamide is not completely benign and people should be somewhat careful with it. And that the idea that if you take two components of a compound together it somehow has the same effect as the compound, in the absence of any data supporting that, is not particularly likely to be correct.

 

 

1) "That's my point really. I don't see any evidence of this presented, and it seems rather like magical thinking." Ah, but that's not what you asked. You said that NAM + Ribose increasing NAD was just a hypothesis. It isn't. It definitely increases NAD, and arguably does so as well as NR.

 

Does that mean that the ribose increases NAD even more than NAM alone? Not necessarily. Is it bad to include it? Probably not. It's a relatively small dose of ribose.

 

Is it riskier than NR? Definitely not. NAM and ribose are supplements that have been used for decades.

 

NR supplementation is new. The number of reports from members of connective tissue problems with NR is a little concerning. The long-term issues are not well-understood. If NR were not a (rather uncommon) natural substance, it wouldn't be for sale; its long-term safety isn't demonstrated.

 

2) "This discussion notes at least transient heptotoxicity: https://livertox.nlm...ov/Niacin.htm" I'm afraid I can't find any reference to NAM in your link, just to Niacin, which is processed through a completely separate set of pathways.

 

All evidence of niacin toxicity is from sustained-release formulations. No one completely understands the story with niacin (no money in it), but it appears that the transient elevations in liver enzymes is a part of the beneficial effects on cholesterol levels and composition (ie LDL vs HDL). It appears the the elevations in liver enzymes is a part of the clearance process rather than 'damage.' It's a not a good idea to keep high levels of blood niacin round-the-clock.

 

It also may not be smart to keep high levels of NR in the body round the clock.

 

Very high levels of NAM--especially round the clock--might not be a good idea, either. (But your reference doesn't mention NAM. For someone who lectures everyone that two components aren't the same as a compound of the two components, that's odd.) 

 

These are all very potent vitamins. Super-high levels of Vitamin D also aren't smart. Super-high levels of most things aren't smart.

 

I thought everybody knew this already. When the drug companies tested Niacin against Statins, they made sure to use sustained-release Niacin for just this reason--to increase liver enzymes.

 

3) "And that the idea that if you take two components of a compound together it somehow has the same effect as the compound, in the absence of any data supporting that, is not particularly likely to be correct."

 

Sometimes yes, sometimes no. Welcome to biochemistry.

 

There is some evidence that NR is a loosely associated compound that is split into NAM and Ribose during absorption. (And, like most loosely complexed compounds, likely actually exists in an equilibrium state.)This is a poorly understood area, as it is all new. There are also quite likely a number of conversion pathways that haven't been discovered (there's some evidence for this).

 

We don't know. But the evidence for NR being somehow unique and especially bio-friendly is quite weak.

 

4) NAM is the main 'salvage' pathway from NAD+. So taking in NR, or Niacin, or even NMN, will result in more NAM being produced.

 

So, if NAM is a problem, we're in trouble with NR, Niacin, and even Tryptophan.

 

-----------------------

 

I'm not an N+R advocate, but I'm messing around with the protocol(s). So far, I've got more out of it that I did from NR. I'm not sure what that means.

 

-----------------------

 

That said, the real thrust of this thread is Turnbuckle's idea that you can favor fission over fusion, and cycle between the two.

 

To me, whether this needs NAM + R, or only NAM, or even NR, is beside the point.

[BigLabRat]

 

There is no evidence than NAM + R increases NAD+ more than NAM alone.

That's my point really. I don't see any evidence of this presented, and it seems rather like magical thinking.

The study I quoted was for skin, so not that germane. Apologies.

This discussion notes at least transient heptotoxicity: https://livertox.nlm....gov/Niacin.htm

My point is that nicotinamide is not completely benign and people should be somewhat careful with it. And that the idea that if you take two components of a compound together it somehow has the same effect as the compound, in the absence of any data supporting that, is not particularly likely to be correct.

 

 

1) "That's my point really. I don't see any evidence of this presented, and it seems rather like magical thinking." Ah, but that's not what you asked. You said that NAM + Ribose increasing NAD was just a hypothesis. It isn't. It definitely increases NAD, and arguably does so as well as NR.

 

Does that mean that the ribose increases NAD even more than NAM alone? Not necessarily. Is it bad to include it? Probably not. It's a relatively small dose of ribose.

 

Is it riskier than NR? Definitely not. NAM and ribose are supplements that have been used for decades.

 

NR supplementation is new. The number of reports from members of connective tissue problems with NR is a little concerning. The long-term issues are not well-understood. If NR were not a (rather uncommon) natural substance, it wouldn't be for sale; its long-term safety isn't demonstrated.

 

2) "This discussion notes at least transient heptotoxicity: https://livertox.nlm...ov/Niacin.htm" I'm afraid I can't find any reference to NAM in your link, just to Niacin, which is processed through a completely separate set of pathways.

 

All evidence of niacin toxicity is from sustained-release formulations. No one completely understands the story with niacin (no money in it), but it appears that the transient elevations in liver enzymes is a part of the beneficial effects on cholesterol levels and composition (ie LDL vs HDL). It appears the the elevations in liver enzymes is a part of the clearance process rather than 'damage.' It's a not a good idea to keep high levels of blood niacin round-the-clock.

 

It also may not be smart to keep high levels of NR in the body round the clock.

 

Very high levels of NAM--especially round the clock--might not be a good idea, either. (But your reference doesn't mention NAM. For someone who lectures everyone that two components aren't the same as a compound of the two components, that's odd.) 

 

These are all very potent vitamins. Super-high levels of Vitamin D also aren't smart. Super-high levels of most things aren't smart.

 

I thought everybody knew this already. When the drug companies tested Niacin against Statins, they made sure to use sustained-release Niacin for just this reason--to increase liver enzymes.

 

3) "And that the idea that if you take two components of a compound together it somehow has the same effect as the compound, in the absence of any data supporting that, is not particularly likely to be correct."

 

Sometimes yes, sometimes no. Welcome to biochemistry.

 

There is some evidence that NR is a loosely associated compound that is split into NAM and Ribose during absorption. (And, like most loosely complexed compounds, likely actually exists in an equilibrium state.)This is a poorly understood area, as it is all new. There are also quite likely a number of conversion pathways that haven't been discovered (there's some evidence for this).

 

We don't know. But the evidence for NR being somehow unique and especially bio-friendly is quite weak.

 

4) NAM is the main 'salvage' pathway from NAD+. So taking in NR, or Niacin, or even NMN, will result in more NAM being produced.

 

So, if NAM is a problem, we're in trouble with NR, Niacin, and even Tryptophan.

 

-----------------------

 

I'm not an N+R advocate, but I'm messing around with the protocol(s). So far, I've got more out of it that I did from NR. I'm not sure what that means.

 

-----------------------

 

That said, the real thrust of this thread is Turnbuckle's idea that you can favor fission over fusion, and cycle between the two.

 

To me, whether this needs NAM + R, or only NAM, or even NR, is beside the point.

[smithx]

OK, so I was missing something basic, and didn't realize that NAM is a short name for nicotinamide. I thought it was a distinct compound.

So now that I know they are the same, whats the evidence that NAM does increase NAD+ and by what amount compared to NR and NMN? Are there studies?

I'm trying to understand something very simple here:

What is based on actual research data, and what is based on speculation or hypothesizing?

- That levels of NAD+ are raised by nicotinamide?
- That they are raised by a certain percentage of NR's measured increase (assuming those studies are not inaccurate)?
- That diet can influence mitochondrial fission and fusion?
- That there would be a benefit from influencing this?
- That taking d-ribose plus nicotinamide is beneficial or at all similar to taking NR?

Which of these is backed up by actual convincing research, which is sort of reasonable maybe, and which is wild speculation, if anything falls into any of those categories?

Also, what reports of connective tissue issues?

Edited by smithx, 01 November 2017 - 01:25 AM.

[sumguy90]

What is based on actual research data, and what is based on speculation or hypothesizing?

Have you skimmed the thread for links? A number of your questions have been answered with citations already.

That said I do think it would be a good idea to have a post summarizing the research findings the protocol is based on and putting all the links in one place similar to Turnbuckle's wonderful summary posts of the whole protocol. I'm thinking especially of the paper on NAM improving mitophagy, the sterolation paper, and the one with the many charts of NAD level over time. This might be better done by one of the people actually posting research, but if no one beats me to it I might attempt that in the next day or two.

[ambivalent]

I would certainly advise caution on both NR and N+R. As reported I have some undiagnosed kidney pain almost certainly brought on by (N+R and NR) - I believe it is blood glucose related as the problem is manageable if I watch my diet. The warning signs were there, extremity pain, pains around eye-socket, fingers and especially the feet with some patchy dizziness. I've noticed both these symptoms while taking just NR as well as NR with N+R (& in my younger days while my BG would have undoubtedly been very high). Ironically, extremity pain aside, I was feeling fabulous leading up to the sudden acute kidney pain. I'm hoping this is just related to glycated haemoglobin which I will cycle out over the next few months with hopefully no lasting kidney damage.

 

(Last week after a few pain free days I decided to try 300mg of NR, 18  hours later I had a deal of kidney pain lasting around 18 hours). Fabulous for a few days after, then within 20 minutes of eating a piece of fudge handed to me in a coffee shop, pain for another 12 hours, though my diet had been less than perfect that day, so perhaps it took me over a threshold).

 

Certainly, though, my advice would be to abort or take blood tests if you notice these extremity pains & take it slowly.

 

My plan is to fast and see and trial take c60oo in a couple of weeks and see if there is improvement. 

 

 

[Nate-2004]

I would hesitate to blame NR or the fudge on kidney problems, the post hoc ergo propter hoc fallacy is a common mistake in self-experimentation. You might want to just see a doctor to be sure rather than wait, if at all possible.

 

There is another thread linked earlier for the N+R vs NR discussion, this isn't the thread for that. This thread is about manipulating mitochondrial dynamics and there are plenty of links and plenty of discussion as to the literature backing the hypothesis. I'm somewhat convinced now that this works not just because of the logic, but given my ever increasing energy levels over the period of time since I began this experiment (with today as an exception as a halloween party left me hungover).

 

 

Edited by Nate-2004, 01 November 2017 - 01:25 PM.

[Turnbuckle]

 

 

 The number of reports from members of connective tissue problems with NR is a little concerning. 

 

 

 

I doubt that has anything to do with NR per se, as NR doesn't get past the digestive system and/or liver in anything but trace amounts. So any such problems should also apply to N+R, and I have seen this myself. When I first started fission/fusion early this year, I did 4 days of fission + exercise in a row (see the OP, Exercise like a girl), and not only felt beat-up for a week, but developed a knee injury that lasted much longer. This in spite of doing rather light workouts. The problem lies at least partly in the numbers of mitochondria. Heart cells have some ten thousand, skeletal muscle cells around a thousand, while cartilage cells have many fewer. And chondrocytes depend more on glycolisis for ATP--

 

Cartilage is a hypoxic tissue—while most human cells’ mitochondria use an oxidant-rich process of phosphorylation to produce ATP, chondrocytes’ mitochondria produce ATP through glycolisis, which requires small amounts of oxygen.

https://www.ncbi.nlm...les/PMC5516774/

 

 

There are fewer and use glycolisis, so a high level of fission might have an outsized effect on such cells. The answer is to ease into the protocol and eliminate defective mitochondria slowly, not combining fission with exercise right off the bat, and not forgetting fusion (and biogenesis), as that is when cells are functioning at their highest level and where healing occurs. It's known, for instance, that fusion helps liver cells avoid damage-- 

 

Using a transgenic mouse model inducibly expressing a dominant-negative fission mutant specifically in the liver, we demonstrated that decreasing mitochondrial fission substantially diminished ROS levels, liver injury, and fibrosis under cholestatic conditions. Taken together, our results provide new evidence that controlling mitochondrial fission is an effective strategy for ameliorating cholestatic liver injury.

https://www.science....ial injury.html