Both Dr. Sinclair & Attia say in a recent podcast that NR+ doesn't get passed the liver, therefore very little efficacy. Has anyone here seen any benefits to this protocol thus far?
This protocol doesn't use NR. It uses N+R.
Posted 24 January 2019 - 04:55 PM
Both Dr. Sinclair & Attia say in a recent podcast that NR+ doesn't get passed the liver, therefore very little efficacy. Has anyone here seen any benefits to this protocol thus far?
This protocol doesn't use NR. It uses N+R.
Posted 25 January 2019 - 03:20 AM
Both Dr. Sinclair & Attia say in a recent podcast that NR+ doesn't get passed the liver, therefore very little efficacy. Has anyone here seen any benefits to this protocol thus far?
Can you link the podcast? I would like to listen to it.
The answer to your question probably doesn't relate very directly to this thread, but maybe everyone will forgive a brief side conversation.
It depends on how you define effective.
NR paper from Nature: https://www.nature.c...les/ncomms12948
From that article: "We report that human blood NAD+ can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual..."
So, in at least 1 study of 1 individual, it increased NAD+ levels.
Here is another study:
https://www.nature.c...1514-017-0016-9
"NAD+ levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as compared to placebo and baseline."
If increased NAD+ levels is how you are defining effectiveness, it looks like it works based on the 2 studies quoted.
Edited by jgkyker, 25 January 2019 - 03:21 AM.
Posted 25 January 2019 - 10:09 AM
The liver can be overwhelmed by a few grams of nicotinamide, allowing serum levels to remain high and for the substance to travel to other parts of the body.
https://www.ncbi.nlm.../pubmed/7859933
Perhaps Sinclair is talking about only milligram dosages.
Posted 25 January 2019 - 11:36 AM
NR is not used here because most of it is broken down in the intestines and that takes several hours. N+R can be thought of as predigested NR, and thus is faster acting, not to mention far cheaper. If anyone wants to pursue it, there are plenty of NR threads on Longecity where one can do endless battle with those having financial interests in the product. But let's not do it here.
Posted 27 January 2019 - 02:19 PM
Posted 27 January 2019 - 02:59 PM
Thank you Turnbuckle and other contributors for this very useful topic.
Would Curcumin phytosome be a better fit with Mitophagy or Biogenesis?
I am inclined to think Mitophagy but not sure.
Thanks.
It might have some peripheral utility in mitophagy/biogenesis, but is more useful in apoptosis.
See Curcumin, mitochondrial biogenesis, and mitophagy: Exploring recent data and indicating future needs. This paper (see Fig. A) shows fisetin, luteolin and curcumin to be good agents for use against senescent cells.
Posted 28 January 2019 - 09:06 AM
My friend (42 yo male) tried last 2g N+R protocol and got severely SICK on 4th day.
He was sick for 3 weeks (had severe flu-like symptoms). He haven't got a flu for last 5 or 6 years and when he got it before he managed to become better in 2-3 days, not 3 weeks.
His HR went up to 100 on 4th day (normal 70), BP was normal all the time.
Seems like during fission days and few days after you immune system gets significantly weaker, so the protocol is dangerous and must be used with cautious. At least one other forum member got sick as well (Pampaguy).
He tried 1g N+R protocol (all ingredients were half-dozed) before, and had no effect at all. The same for me. I'm now scared to try 2g N+R.
@Turnbuckle, please share your thoughts on this, maybe there is a way to decrease a danger.
Posted 28 January 2019 - 10:12 AM
My friend (42 yo male) tried last 2g N+R protocol and got severely SICK on 4th day.
...
Seems like during fission days and few days after you immune system gets significantly weaker, so the protocol is dangerous and must be used with cautious. At least one other forum member got sick as well (Pampaguy).
Posted 28 January 2019 - 11:54 AM
I am 28, have chronic fatigue syndrome
Hi sumguy90, thanks for your response. How many times have you tried this protocol? Do you have any long lasting results?
Posted 28 January 2019 - 02:20 PM
My friend (42 yo male) tried last 2g N+R protocol and got severely SICK on 4th day.
He was sick for 3 weeks (had severe flu-like symptoms). He haven't got a flu for last 5 or 6 years and when he got it before he managed to become better in 2-3 days, not 3 weeks.
His HR went up to 100 on 4th day (normal 70), BP was normal all the time.
Seems like during fission days and few days after you immune system gets significantly weaker, so the protocol is dangerous and must be used with cautious. At least one other forum member got sick as well (Pampaguy).
He tried 1g N+R protocol (all ingredients were half-dozed) before, and had no effect at all. The same for me. I'm now scared to try 2g N+R.
@Turnbuckle, please share your thoughts on this, maybe there is a way to decrease a danger.
Thanks for that valuable input, as all the experiments were done with myself. This protocol has stopped evolving as it no longer has any effect on me, presumably as I've eliminated the defective mtDNA that had been seriously damaged by statin use.
My latest experimental protocol is here, and a link can be found on my profile page. I didn't recommend the fission part for more than 3 days as reducing your mito number when you already have a lot of defective mitochondrial DNA can have dramatic effects. It will lower your ATP production, of course, and that could certainly make you open to whatever bug is going around, though I never experienced that myself.
To minimize this, you might try reversing the protocol, starting off with fusion/biogenesis, and stopping the fission part after 2 days instead of 3, then finishing with more fusion/biogenesis.
Note that with fission, every mtDNA loop has to operate on its own. All of its 37 genes are critical, so even one defect will likely result in zero ATP production. In fusion, each mitochondrion has many loops, and since they are unlikely to be all damaged in the same spot, they can cover for each other. This is so effective that a cell could have all its mtDNA damaged and still operate in reasonable fashion (which also allows drug induced damage to creep up to very high levels unnoticed). So if you begin to get sick, I'd suggest you immediately discontinue fission and take stearic acid to return your mitochondria to fusion. In fact, stearic acid might prove useful for any acute illness.
Edited by Turnbuckle, 28 January 2019 - 02:42 PM.
Posted 28 January 2019 - 02:39 PM
Posted 28 January 2019 - 03:29 PM
So if you begin to get sick, I'd suggest you immediately discontinue fission and take stearic acid to return your mitochondria to fusion. In fact, stearic acid might prove useful for any acute illness.
We were using mango butter instead of stearic acid. So if one begins to get sick, he should stop fission immediately and take 20g mango butter, 5g leucine and 20mg PQQ (1 hour later), right? Or should he take more mango butter that day? Or maybe he should extend fusion days from 2 to 3 or 4? Or even 5... What is the best route to go with, from your knowledge?
Posted 28 January 2019 - 03:36 PM
Are most posters really old here? I dont think Nicotinamide should be used except to try and ward off skin cancer. Im not providing links, please look this up yourself. I feel all this work to try and increase NAD+ in the body without seriously strong evidence based information spanning at least a decade may be reckless.
Posted 28 January 2019 - 03:44 PM
We were using mango butter instead of stearic acid. So if one begins to get sick, he should stop fission immediately and take 20g mango butter, 5g leucine and 20mg PQQ (1 hour later), right? Or should he take more mango butter that day? Or maybe he should extend fusion days from 2 to 3 or 4? Or even 5... What is the best route to go with, from your knowledge?
I've never used mango butter and can't say how good it might be or what negative effects might come from using this much. Presently I am experimenting with five grams of glycerol monostearate (with my stem cell protocol). This appears to work much faster than triglycerides containing mixed stearic and palmitic acids -- a few minutes when taken on an empty stomach.
As I said, I haven't tried this, but if you begin to get sick, ending fission with fusion supplements seems the right way to go. Adding biogenesis should be okay.
Posted 28 January 2019 - 07:38 PM
As for glycerol monostearate, is this one (amazon link) good enough?
Edited by BRIGHT, 28 January 2019 - 07:38 PM.
Posted 28 January 2019 - 08:37 PM
As for glycerol monostearate, is this one (amazon link) good enough?
Should be. Be aware that mito fusion can raise blood pressure in some people, and for me this raised it very rapidly.
Posted 28 January 2019 - 11:33 PM
Hi sumguy90, thanks for your response. How many times have you tried this protocol? Do you have any long lasting results?
Posted 29 January 2019 - 12:21 AM
Should be. Be aware that mito fusion can raise blood pressure in some people, and for me this raised it very rapidly.
Posted 29 January 2019 - 09:40 AM
Posted 30 January 2019 - 12:56 AM
I've never used mango butter and can't say how good it might be or what negative effects might come from using this much. Presently I am experimenting with five grams of glycerol monostearate (with my stem cell protocol). This appears to work much faster than triglycerides containing mixed stearic and palmitic acids -- a few minutes when taken on an empty stomach.
As I said, I haven't tried this, but if you begin to get sick, ending fission with fusion supplements seems the right way to go. Adding biogenesis should be okay.
How do you know if GMS has a similar effect of stearic acid?
How is GMS metabolized in the body? Is GMS decomposed to glycerol and stearic acid when it is administrated?
Edited by Graviton, 30 January 2019 - 12:57 AM.
Posted 30 January 2019 - 01:44 AM
How do you know if GMS has a similar effect of stearic acid?
How is GMS metabolized in the body? Is GMS decomposed to glycerol and stearic acid when it is administrated?
Triglycerides are broken down during digestion into free fatty acids and monoglycerides such as glycerol monostearate. Thus GMS is effectively a predigested stearic acid triglyceride, and absorption can occur far more quickly.
Posted 30 January 2019 - 08:01 AM
Triglycerides are broken down during digestion into free fatty acids and monoglycerides such as glycerol monostearate. Thus GMS is effectively a predigested stearic acid triglyceride, and absorption can occur far more quickly.
Not sure about its absorption and if the ester is broken down to two smaller components. Are you saying based on the prediction that lipase will break down fatty acids? Or, do you have references in pharmacology?
Posted 30 January 2019 - 10:16 AM
Not sure about its absorption and if the ester is broken down to two smaller components. Are you saying based on the prediction that lipase will break down fatty acids? Or, do you have references in pharmacology?
Yes. That's how it works. By ingesting highly soluble monoglycerides, you bypass the need to break down triglycerides first physically into micelles, and then chemically into free fatty acids and monoglycerides, skipping two steps. From Britannica--
After ingested triglycerides pass through the stomach and into the small intestine, detergents called bile salts are secreted by the liver via the gall bladder and disperse the fat as micelles. Pancreatic enzymes called lipases then hydrolyze the dispersed fats to give monoglycerides and free fatty acids.
https://www.britanni...ary-fatty-acids
Edited by Turnbuckle, 30 January 2019 - 10:17 AM.
Posted 30 January 2019 - 06:00 PM
Just wanted to briefly report on my experience with this cycle... I have been on it about 1-1.5 weeks.
About 2 months ago, I began an intense sport (Brazilian jiu jitsu), and I sprained my left wrist and also pulled my groin. I really did not feel like I was making progress healing on my wrist until this week. It seems like my mobility has substantially improved. I think it may almost be healed. Now, just 1 week ago, I was receiving INTENSE pain if I moved the wrist anywhere near its extremes. It seems like it is healing substantially faster since beginning this protocol. One thing to note, however, is that I have been particularly stubborn about wearing my wrist guard. It seems like it is beyond that though...
The pulled groin however seems about the same (it was much farther along than the wrist, healing-wise, before the protocol... I think). Lastly, just 3 days ago, I had some dental work done around the gums. That seems to be healing very quickly as well. I cannot recall typically how long I would deal with dental pain like that, but it seems like generally it would take weeks. I barely feel anything as I type this.
Some additional things I am taking that may be helping: Bromelain and BCAAs (among many other things that probably aren't)
The BCAAs seem to make a substantial difference in everything, and I take them before bed, when I remember (trying to make this a habit when in a state of healing). These may make a difference particularly with me because I have not eaten meat in almost 1 year. I also eat very little dairy lately. I was taking the Bromelain before this protocol when I felt like I was not healing. Therefore, it may actually be doing very little.
Update on Injury Healing
It has been about 2 weeks since my last update. I now have about 95%+ mobility in my left wrist. So, to summarize, it seemed like I was making little to no progress healing my wrist sprain until I began to experiment with this fission/fusion cycle. Prior to this, I seemed to consistently re-injure my sprain either while sleeping or just doing various activities. Even when I stopped jiu jitsu for 2 weeks, I did not seem to make much progress in my wrist injury. I was occasionally wearing a wrist guard.
I have to emphasize that I became very serious about wearing the wrist guard, almost every moment, when I began this experimentation. So, that alone has to be a factor. Whatever the case, I felt healed enough 3-4 days ago that I no longer wear the guard.
Unfortunately, the groin pull is about the same. So, there may be other issues going on there. It does seem to be healing though, somewhat slower... it is hard to say still there. Maybe I can report further in 2 more weeks.
My goal is to get back to jiu jitsu and see if the protocol allows me to bounce back faster than what I was experiencing sans protocol. One session of jiu jitsu can leave me intensely sore for at least 24 hours sans protocol.
Reminder of Protocol
- Fission (NR) and Senescence Clearance (Quercetin) Day
- Fusion Day (NMN, Sulforaphane, C60, Stearic Acid in the form of cocoa butter, curcumin, cinnamon+) - higher exercise activity on this day
+ Just started adding cinnamon today, as I forgot about it.
Notes: I am also taking amino acids at night before bed through all of this. Some people are doing multiple days of fission. I am not doing that. I am doing 1 day of fission promotion and then 1 day of fusion promotion. I have now been doing this for about 2.5 weeks. Before that, I was just mixing all my supplements without regards to how they affect mitochondria.
N+R grams vs. NR mg:
I am not using the recommended N+R. I am using just regular Niagen NR, 300 mg x2 on fission days. I suppose my reasoning is that there are plenty of studies showing the effects of NR, and I am comfortable using it at the moment. Even though N+R probably does the same thing, I am fine with just using NR, especially due to the side effects some seem to be mentioning.
Thoughts on Amino Acids
A few days ago, I decided to steer away from BCAAs at night toward hydrolyzed collagen. I am very happy with this change in terms of how it seems to effect my sleep, but taking it in the morning seems to make me drowsy. Therefore, I plan to only take it at night before bed starting today. I firmly believe that amino acid supplementation has been incredibly important to my healing, but that could be because I have not eaten any meat in almost 1 year. People that eat meat may not need amino acid supplementation.
Curcumin
There was a question about curcumin. I treat this more like a fusion supplement because of this study:
"In contrast, curcumin enhanced mitochondrial fusion activity and reduced fission machinery, and increased biogenesis and synaptic proteins." https://www.ncbi.nlm...les/PMC5256118/
Perhaps, I am misguided there, but I will continue to use it as a fusion supplement for now while trying to understand Turnbuckle's thoughts he posted.
Posted 30 January 2019 - 06:10 PM
Update on Injury Healing
It has been about 2 weeks since my last update. I now have about 95%+ mobility in my left wrist. So, to summarize, it seemed like I was making little to no progress healing my wrist sprain until I began to experiment with this fission/fusion cycle. Prior to this, I seemed to consistently re-injure my sprain either while sleeping or just doing various activities. Even when I stopped jiu jitsu for 2 weeks, I did not seem to make much progress in my wrist injury. I was occasionally wearing a wrist guard.
I have to emphasize that I became very serious about wearing the wrist guard, almost every moment, when I began this experimentation. So, that alone has to be a factor. Whatever the case, I felt healed enough 3-4 days ago that I no longer wear the guard.
Unfortunately, the groin pull is about the same. So, there may be other issues going on there. It does seem to be healing though, somewhat slower... it is hard to say still there. Maybe I can report further in 2 more weeks.
My goal is to get back to jiu jitsu and see if the protocol allows me to bounce back faster than what I was experiencing sans protocol. One session of jiu jitsu can leave me intensely sore for at least 24 hours sans protocol.
Reminder of Protocol
- Fission (NR) and Senescence Clearance (Quercetin) Day
- Fusion Day (NMN, Sulforaphane, C60, Stearic Acid in the form of cocoa butter, curcumin, cinnamon+) - higher exercise activity on this day
+ Just started adding cinnamon today, as I forgot about it.
Notes: I am also taking amino acids at night before bed through all of this. Some people are doing multiple days of fission. I am not doing that. I am doing 1 day of fission promotion and then 1 day of fusion promotion. I have now been doing this for about 2.5 weeks. Before that, I was just mixing all my supplements without regards to how they affect mitochondria.
N+R grams vs. NR mg:
I am not using the recommended N+R. I am using just regular Niagen NR, 300 mg x2 on fission days. I suppose my reasoning is that there are plenty of studies showing the effects of NR, and I am comfortable using it at the moment. Even though N+R probably does the same thing, I am fine with just using NR, especially due to the side effects some seem to be mentioning.
Thoughts on Amino Acids
A few days ago, I decided to steer away from BCAAs at night toward hydrolyzed collagen. I am very happy with this change in terms of how it seems to effect my sleep, but taking it in the morning seems to make me drowsy. Therefore, I plan to only take it at night before bed starting today. I firmly believe that amino acid supplementation has been incredibly important to my healing, but that could be because I have not eaten any meat in almost 1 year. People that eat meat may not need amino acid supplementation.
Curcumin
There was a question about curcumin. I treat this more like a fusion supplement because of this study:
"In contrast, curcumin enhanced mitochondrial fusion activity and reduced fission machinery, and increased biogenesis and synaptic proteins." https://www.ncbi.nlm...les/PMC5256118/
Perhaps, I am misguided there, but I will continue to use it as a fusion supplement for now while trying to understand Turnbuckle's thoughts he posted.
Oh yeah, I forgot to comment on the dental work. I definitely think it healed faster than usual. I had the work done on the 15th. I was pain free without chewing about 3-4 days ago. I seem to recall having pain for up to 2-3 weeks after similar dental work, in the past. So, it seems like it healed to "pain-free" sans chewing in about 10-12 days vs. what maybe generally took 15-21 days for me in the past. I'm happy with it, anyway. Constant mouth pain is awful. I'm biting down right now, and there is 0 pain.
Edited by jgkyker, 30 January 2019 - 06:10 PM.
Posted 31 January 2019 - 10:16 AM
Reminder of Protocol
- Fission (NR) and Senescence Clearance (Quercetin) Day
- Fusion Day (NMN, Sulforaphane, C60, Stearic Acid in the form of cocoa butter, curcumin, cinnamon+) - higher exercise activity on this day
NMN for fusion? Surely it raises NAD+ therefore mitophagy and is therefore a fission stimulator?
Posted 31 January 2019 - 11:05 AM
Thanks for that valuable input, as all the experiments were done with myself. This protocol has stopped evolving as it no longer has any effect on me, presumably as I've eliminated the defective mtDNA that had been seriously damaged by statin use.
If this is indeed the case, are you also feeling dramatically younger than before the protocols?
Posted 31 January 2019 - 11:16 AM
If this is indeed the case, are you also feeling dramatically younger than before the protocols?
This reversed the statin damage and returned my energy level to about where I was 15 years before. But it is not the primary cause of aging, and to reverse that I began my stem cell protocol.
Posted 31 January 2019 - 05:42 PM
NMN for fusion? Surely it raises NAD+ therefore mitophagy and is therefore a fission stimulator?
Based on the following study, it doesn't seem like NAD+ is a direct cause of fusion or fission stimulation. Rather, somehow, NR and NMN are doing different things... Let me know your thoughts.
Check out this study:
"Furthermore, we found a shift in dynamics from fission to fusion proteins in the NMN-treated mice."
This is why I suspect we see an endurance/exercise performance increase on NMN, whereas we see a decrease with NR (promoter of fission).
If NR promotes fission and NMN promotes fusion, they are doing different things. If they both increase NAD+, NAD+ must not be the fission/fusion regulating mechanism. Of course, it probably isn't that simple... My guess is it has something to do with the differences in the way the body processes them, meaning, from my understanding NMN is processed more-so in the kidney and NR in the liver.
Edited by jgkyker, 31 January 2019 - 05:46 PM.
Posted 31 January 2019 - 07:19 PM
Based on the following study, it doesn't seem like NAD+ is a direct cause of fusion or fission stimulation. Rather, somehow, NR and NMN are doing different things... Let me know your thoughts.
Check out this study:
Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model
"Furthermore, we found a shift in dynamics from fission to fusion proteins in the NMN-treated mice."
This is why I suspect we see an endurance/exercise performance increase on NMN, whereas we see a decrease with NR (promoter of fission).
If NR promotes fission and NMN promotes fusion, they are doing different things. If they both increase NAD+, NAD+ must not be the fission/fusion regulating mechanism. Of course, it probably isn't that simple... My guess is it has something to do with the differences in the way the body processes them, meaning, from my understanding NMN is processed more-so in the kidney and NR in the liver.
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