12 replies to this topic

[experimenting]

NMN, NR, NAM + Ribose have come up as interesting therapies for mitochondrial quality control and for chronic fatigue. I’ve been playing around with these and certainly noticed something...more investigation needed. But...

Is D-Ribose dangerous? I’ve read a few things regarding

1) Triggering long-lasting metabolic issues
2) lowering blood sugar
3) AGEs?
4) Neurotoxicity/Cytotoxicity

Anyone got anything? Obviously, I want to proceed with EXTREME caution.

[Turnbuckle]

The level of ribose in NMN, NR, or NAD+Ribose at the levels normally consumed should not be a concern. With aging or with certain pathologies, cellular ribose production can fall off, and individuals can then benefit from supplemental ribose, even without the nicotinamide component.

 

D-ribose has been used both orally and intravenously in patients for many different pathologic conditions such as chronic fatigue syndrome (41), fibromyalgia (42), and myocardial dysfunction (40). It is often used to improve athletic performance and reduce symptoms of cramping, pain, and stiffness following exercise (41). Under different pathologic conditions, ATP, ADP, and adenosine monophosphate are degraded and not available for energy production. Supplemental D-ribose has been shown to enhance recovery of ATP levels and reduce cellular injury in humans and animals (9,43). A study by Pliml et al. found that patients with severe coronary artery disease who consumed D-ribose for 3 days had improved myocardial tolerance to ischemia.

 

 

The levels in NMN, NR, or NAD+Ribose are actually fairly low --

 

Supplemental D-ribose can be purchased in a dry powder form, and the recommended dose ranges from 5 to 15 grams per day and not by body mass units (42). The powder is mixed in a non-carbonated drink and has a sweet taste. It is readily metabolized if consumed within 30 minutes after being mixed in fluid. The side effects are minimal, but patients have reported mild diarrhea, slight nausea, and stomach discomfort that was reduced by consuming the drink with food (45–47). There had been some concerns about the safety of ribose therapy related to the inhibitory effects of ribose on cell proliferation in vitro. However, Pliml et al. investigated possible side effects of ribose on human lymphocytes. They found no significant inhibition of human lymphocyte proliferation in vitro in mitogen-stimulated cells and no evidence that ribose therapy was harmful to human cells

 

 

Reference: https://www.ncbi.nlm...les/PMC5959283/

 

I would certainly not take more NMN, NR, or NAD+Ribose than necessary as ribose is more subject to cross-linking than other sugars, producing advanced glycation end products, nor would I use them every day as they will prevent mito fusion. Like with virtually everything, the dose makes the poison.

Edited by Turnbuckle, 04 July 2020 - 10:07 AM.

[experimenting]

The level of ribose in NMN, NR, or NAD+Ribose at the levels normally consumed should not be a concern. With aging or with certain pathologies, cellular ribose production can fall off, and individuals can then benefit from supplemental ribose, even without the nicotinamide component.


The levels in NMN, NR, or NAD+Ribose are actually fairly low --


Reference: https://www.ncbi.nlm...les/PMC5959283/

I would certainly not take more NMN, NR, or NAD+Ribose than necessary as ribose is more subject to cross-linking than other sugars, producing advanced glycation end products, nor would I use them every day as they will prevent mito fusion. Like with virtually everything, the dose makes the poison.

Thanks for the timely and thoughtful response.

Your mito protocol has had profound effects on me in the span of a few short weeks; however I’m having trouble isolating what’s going on and how to “lock in” the effects.

I’ve started only with the NMN/NR/NAM + Ribose components.

1) NR gives me at times a brutal kind of mania, ie mania +energy + cognition + libido, things I’ve never had due to unknown pathology. There’s some kind of steroid effect occurring as other users have also noted-I observed DHT like oily skin and harder muscles.

The feeling was wonderful but it doesn’t really last. If I could
lock this in and control the mania just a little, it would be amazing.

2) NMN on its own seemed to do better for resolving my chronic back pain. A few days last week I was totally
pain free and flexible, something I don’t think I ever have really been.

3) I added some Ribose in a few days ago and felt better, almost as if NR/NMN had drained it. However, too much ribose on its own and I feel a little tired (blood sugar)?

I also need to discuss the worst side effect of all, which is hard to describe. It’s almost as if, after a few hours, NMN/NR “bloat” my stomach. Stomach seems to stick out and I have to suck it back in. Add to this a weird psychological restlessness and a kind of body dysmorphia (am I ripped? How do I look? Those kinds of constant questions). Is this a B vitamin imbalance? A methylation imbalance? Feels like I’m missing a cofactor.

Needless to say, I’m excited/desperate, because for the first time in almost a decade I have woken up and just felt “good”. No pain, good mood, morning erection (sorry TMI), etc. This has not happened with anything else; I’ve largely gotten through life with a regimen of supplements that have acute effects only (eg D3, K2 and some other stuff). So it’s like I’m on the verge of actually fixing something. Either that or it’s the B-activity that’s solving this, however B complex vitamins have largely not done much for me except make me fat.

[Turnbuckle]

Your mito protocol has had profound effects on me in the span of a few short weeks; however I’m having trouble isolating what’s going on and how to “lock in” the effects.

 

 

The time it takes to restore mito health is dependent on the level of dysfunction. If you have only a few bad loops of mitochondrial DNA (mtDNA), one cycle might do it. If you have a high level, it could take the better part of a year. 

 

You can reduce the total population of mtDNA by 20% in a couple of days, and those eliminated will all be bad strands. However, when you then expand the population again, both good and bad strands are duplicated. So it's an iterative process.

 

For example--

 

Let's say a cell has a thousand strands of mtDNA and they are 90% dysfunctional -- 100 good and 900 bad. If one cycle of fission eliminates 20% of the bad strands and then the population is returned to a thousand with fusion and PQQ, the cell now has 122 good strands and 878 bad. The dysfunctional fraction has been reduced to just under 88%. Not that impressive, but the rate of improvement will steadily increase as you continue. Once you get the dysfunctional fraction down to 20%, the next cycle will get rid of all of them.

Edited by Turnbuckle, 04 July 2020 - 12:36 PM.

[experimenting]

The time it takes to restore mito health is dependent on the level of dysfunction. If you have only a few bad loops of mitochondrial DNA (mtDNA), one cycle might do it. If you have a high level, it could take the better part of a year.

You can reduce the total population of mtDNA by 20% in a couple of days, and those eliminated will all be bad strands. However, when you then expand the population again, both good and bad strands are duplicated. So it's an iterative process.

For example--

Let's say a cell has a thousand strands of mtDNA and they are 90% dysfunctional -- 100 good and 900 bad. If one cycle of fission eliminates 20% of the bad strands and then the population is returned to a thousand with fusion and PQQ, the cell now has 122 good strands and 878 bad. The dysfunctional fraction has been reduced to just under 88%. Not that impressive, but the rate of improvement will steadily increase as you continue. Once you get the dysfunctional fraction down to 20%, the next cycle will get rid of all of them.

Interesting thanks.

You have any clue about the side effects I mentioned?

[Turnbuckle]

Interesting thanks.

You have any clue about the side effects I mentioned?

 

 

No, I don't. The major side effect I noted from the mito protocol was a large drop in blood pressure. I stopped taking any BP medication for a time, and it was still low. Ultimately it returned to what it was before I began, while the statin damage I had lived with for years was gone. (My high BP had preceded the statin damage.)

Edited by Turnbuckle, 04 July 2020 - 01:08 PM.

[experimenting]

No, I don't. The major side effect I noted from the mito protocol was a large drop in blood pressure. I stopped taking any BP medication for a time, and it was still low. Ultimately it returned to what it was before I began, while the statin damage I had lived with for years was gone. (My high BP had preceded the statin damage.)

Shame. I and others have reported some kind of a hormonal effect as you’ll see in other threads. No idea what the root cause of this is but I don’t mind it-again it seems like DHT increases. For example:

https://www.longecit...inamide-ribose/


And then of course there is the weird mental flutter I note. Might be due to overuse?

What would a proper schedule look like?

Sorry to bother you, just a novice and getting great results, and trying to hack it all together. The results are at times, absolutely stunning, my mood/cognition are, in these very brief windows, what they were a decade ago before I went off the cliff.

[Taiidan]

Where can I find Turnbuckle's mito protocol? 

[Jesus Evola]

The induced hypoglycemia is marginal, but large oral doses >8-10g, will produce transient hypoglycemia as well as gastrointestinal discomfort. 

 

The glycation issue is present with all reducing sugars - including glucose.  Comparative studies show little to now difference in glycation between ribose and glucose. 

 

The studies demonstrating issues with protein folding and the generation of neurotoxicity typically use IP/IV administration, in large doses, well beyond the recommended use as an oral dietary supplement.   

 

Adding ribose to nicotinamide in a co-crystal vehicle reduces the 5-mNam production in hepatic tissue.  When we looked at a 5:1 ratio of ribose to Nam over the course of 2 weeks of high dose in rats, no 5-mNam was observed by NMR/mass spec.  

 

In the pre-clinical data an equimolar comparison of 5:1 ribose+nam and NR (equimolar with respect to nicotinamide content), the free form ribose+nam out performed NR by 28% in terms of NAD generation, about 15% in terms of measured oxidation of tissue (AMP+GSSH).  In other words, the N+R contained significantly more high energy phosphates species and more glutathione.

 

 

Edited by Jesus Evola, 31 March 2021 - 06:16 PM.

[zorba990]

The induced hypoglycemia is marginal, but large oral doses >8-10g, will produce transient hypoglycemia as well as gastrointestinal discomfort.

The glycation issue is present with all reducing sugars - including glucose. Comparative studies show little to now difference in glycation between ribose and glucose.

The studies demonstrating issues with protein folding and the generation of neurotoxicity typically use IP/IV administration, in large doses, well beyond the recommended use as an oral dietary supplement.

Adding ribose to nicotinamide in a co-crystal vehicle reduces the 5-mNam production in hepatic tissue. When we looked at a 5:1 ratio of ribose to Nam over the course of 2 weeks of high dose in rats, no 5-mNam was observed by NMR/mass spec.

In the pre-clinical data an equimolar comparison of 5:1 ribose+nam and NR (equimolar with respect to nicotinamide content), the free form ribose+nam out performed NR by 28% in terms of NAD generation, about 15% in terms of measured oxidation of tissue (AMP+GSSH). In other words, the N+R contained significantly more high energy phosphates species and more glutathione.

References please, though most of us know this already: ("the free form ribose+nam out performed NR by 28% in terms of NAD generation, about 15% in terms of measured oxidation of tissue (AMP+GSSH). In other words, the N+R contained significantly more high energy phosphates species and more glutathione.")

[Jesus Evola]

References please, though most of us know this already: ("the free form ribose+nam out performed NR by 28% in terms of NAD generation, about 15% in terms of measured oxidation of tissue (AMP+GSSH). In other words, the N+R contained significantly more high energy phosphates species and more glutathione.")

 

The data related to the project is proprietary and currently published in patent statements, the manuscripts are not yet published.  

[orion22]

The induced hypoglycemia is marginal, but large oral doses >8-10g, will produce transient hypoglycemia as well as gastrointestinal discomfort. 

 

The glycation issue is present with all reducing sugars - including glucose.  Comparative studies show little to now difference in glycation between ribose and glucose. 

 

The studies demonstrating issues with protein folding and the generation of neurotoxicity typically use IP/IV administration, in large doses, well beyond the recommended use as an oral dietary supplement.   

 

Adding ribose to nicotinamide in a co-crystal vehicle reduces the 5-mNam production in hepatic tissue.  When we looked at a 5:1 ratio of ribose to Nam over the course of 2 weeks of high dose in rats, no 5-mNam was observed by NMR/mass spec.  

 

In the pre-clinical data an equimolar comparison of 5:1 ribose+nam and NR (equimolar with respect to nicotinamide content), the free form ribose+nam out performed NR by 28% in terms of NAD generation, about 15% in terms of measured oxidation of tissue (AMP+GSSH).  In other words, the N+R contained significantly more high energy phosphates species and more glutathione.

what dose would you say its good for humans of  ribose+nam 

[Jesus Evola]

what dose would you say its good for humans of  ribose+nam 

 

It is much easier to discuss what dose of B3 is relevant.  Our dose response curve indicated a 4:1 ratio of DR+NAM required a minimum of 100mg of nicotinamide to increase NAD levels over the course of 8 weeks, whereas doses as high as 1000mg B3 BID along with 4g of DR failed to show any 5-Methyl-NAM production over the course of 3 weeks.  

 

Thus, for long term benefit without incurring any of the known potential issues with respect to methylation (tentatively), 600mg total of the combination is safe and effective.  For acute circumstances, 5g total produced 20% increases over baseline in about 5 days, while showing steady decreases in salivary cortisol, steady increases in total glutathione, and steady increases in the pyridine series (NAD, NADH, NADP, and NADPH), increased ATP, etc.   

  

 

In my opinion, depending on the circumstances, which is to say the degree to which the combination serves as a stress prophylactic, this is a safe range.