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Manipulating mitochondrial dynamics

nad nad+ c60 mito fission fusion stearic acid mtdna methylene blue

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#871 Krell

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Posted 21 March 2018 - 08:43 PM

Thanks for the comments from Turnbuckle and QuestforLife.

 

Today I reduced the fission protocol quantities to

  0.5g nicotinamide (1 tab biophix),

  0.5g D-Ribose (1 tab BoostCeuticals), 

  450mg LE AMPK (1 tab LE),

  100mg Fisetin (1 tab DrBest)

 

and had no problems with heart rate irregularity

during my stardard M/T/W workout:

  7am coffee and tablets

  8am tennis

  9am weight lifting

 10am HIIT on stair-stepper with heart rate monitor.

I got my heart rate up to 150, near to my age rated max of

about 156 without any HR irregularities.

 

I will do the standard fusion protocol the next 3 days.

 

Since it is inconvient for me to change my exercise schedule

to separate aerobic and anerobic exercise as suggested,

I will try building up my tolerance to the fission dosage over

the next few weeks.

 



#872 PAMPAGUY

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Posted 22 March 2018 - 07:58 AM

Here is an excellent paper out of Harvard  with Dr. David Sinclair on NAD precussors including Niacin.  Have included the unlocking website so everyone can read entire article.

 

You can access it on http://sci-hub.tw

 

Search for the PMID # (29514064) not the title.


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#873 Nate-2004

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Posted 24 March 2018 - 12:50 AM

So this article was linked on another thread and I'm realizing that the glucosamine sulfate I take needs to probably be taken only during fission, whereas the SkQ1 I've been taken should be taken only during fusion. 


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#874 Empiricus

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Posted 25 March 2018 - 05:12 AM

Well, having finally received stearic acid, I started the protocol where you combine the stearic with the other stuff.

 

This is my day 1, I took following before weights workout:

 

Nicotinamide - 500 mg

Nicotinamide - 500 mg as NR

Ribose - 500 mg as NR

Stearic - 2 g

AMPK - 500 mg

Broccomax - 500 mg

 

Results:  Felt remarkably energized all day.  

 

I'm now on day 2.  I just completed weights, prior to which I took

 

Nicotinamide - 1000 mg

Nicotinamide - 500 mg as NR

Ribose - 500 mg as NR

Stearic - 3-7 g (I'm not sure)

AMPK - 500 mg

Broccomax - 1000 mg

Pomegranate juice (fresh) - 18 ounces

 

Results:  I felt unusually energetic during workout.  But after the workout, about 2.5 hours after taking the supplements, I noticed I was getting a bit jittery (beyond what 1 cup of coffee could account for). I was about to buy some coffee and felt a bit shaky. Waitress seemed to have noticed and asked if I was OK.   I noticed from a heart monitor that my heart rate was rocketing upwards very fast all of a sudden. I got blood pressure taken by a pharmacist. I was told my bp was normal, and to relax and not drink any coffee and have my heart rate checked in a half hour.  Anyway, heart rate seems to be moving down into a more normal range.   

 

I'm not sure about relationship between heart rate and blood pressure.  Anyway, a suddenly rapid heart rate several hours after supplement ingestion seems to be an effect of the above protocol for me anyway.

 

Another thing: I've taken all the ingredients of the protocol many times in the past except pure stearic.  The use of pure stearic acid -- as opposed to stearic consumed in a food like cocoa, moreover stearic not taken with any other food except coffee -- seems to make a big difference to the effect of the protocol.

 


Edited by Empiricus, 25 March 2018 - 05:53 AM.


#875 Turnbuckle

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Posted 25 March 2018 - 12:54 PM

 

Another thing: I've taken all the ingredients of the protocol many times in the past except pure stearic.  The use of pure stearic acid -- as opposed to stearic consumed in a food like cocoa, moreover stearic not taken with any other food except coffee -- seems to make a big difference to the effect of the protocol.

 

 

Sounds like the NR began working about the time you began feeling jittery. NR should not even register for several hours, so I wouldn't use it with a reverse protocol (or any protocol). And I would use 5-10g stearic acid to force fusion, if that's what you want, as high NAD+ drives mitochondria to fission. 


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#876 MikeDC

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Posted 25 March 2018 - 01:42 PM


Another thing: I've taken all the ingredients of the protocol many times in the past except pure stearic. The use of pure stearic acid -- as opposed to stearic consumed in a food like cocoa, moreover stearic not taken with any other food except coffee -- seems to make a big difference to the effect of the protocol.



Sounds like the NR began working about the time you began feeling jittery. NR should not even register for several hours, so I wouldn't use it with a reverse protocol (or any protocol). And I would use 5-10g stearic acid to force fusion, if that's what you want, as high NAD+ drives mitochondria to fission.

There is no NR in his protocol. it is not a fact that N+R = NR. NAD+ doesn’t drive mitochandria to fission. NAD+ helps to drive mitochandria to reach optimum fusion and fission equilibrium.
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#877 aribadabar

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Posted 25 March 2018 - 03:33 PM

Well, having finally received stearic acid, I started the protocol where you combine the stearic with the other stuff.

 

This is my day 1, I took following before weights workout:

 

Nicotinamide - 500 mg

Nicotinamide - 500 mg as NR

Ribose - 500 mg as NR

Stearic - 2 g

AMPK - 500 mg

Broccomax - 500 mg

 

Results:  Felt remarkably energized all day.  

 

I'm now on day 2.  I just completed weights, prior to which I took

 

Nicotinamide - 1000 mg

Nicotinamide - 500 mg as NR

Ribose - 500 mg as NR

Stearic - 3-7 g (I'm not sure)

AMPK - 500 mg

Broccomax - 1000 mg

Pomegranate juice (fresh) - 18 ounces

 

N+R , a fission combination, is taken concurrently with stearic acid  and Broccomax, supps used during fusion ?

What is your rationale for that?



#878 Turnbuckle

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Posted 25 March 2018 - 04:17 PM

 

Well, having finally received stearic acid, I started the protocol where you combine the stearic with the other stuff.

 

This is my day 1, I took following before weights workout:

 

Nicotinamide - 500 mg

Nicotinamide - 500 mg as NR

Ribose - 500 mg as NR

Stearic - 2 g

AMPK - 500 mg

Broccomax - 500 mg

 

Results:  Felt remarkably energized all day.  

 

I'm now on day 2.  I just completed weights, prior to which I took

 

Nicotinamide - 1000 mg

Nicotinamide - 500 mg as NR

Ribose - 500 mg as NR

Stearic - 3-7 g (I'm not sure)

AMPK - 500 mg

Broccomax - 1000 mg

Pomegranate juice (fresh) - 18 ounces

 

N+R , a fission combination, is taken concurrently with stearic acid  and Broccomax, supps used during fusion ?

What is your rationale for that?

 

 

 

This is likely from my post #746, which is intended to boost cellular function after the regular protocol is used to get rid of defective mitochondria, though I didn't make that clear. I never recommended NR, however. NR should not be used with these protocols because of the time delay before it is digested back to N+R.


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#879 Empiricus

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Posted 26 March 2018 - 02:15 AM

Yes, I adopted it from your post #746 (boost cellular function) protocol.  Thank you for your feedback.  I will try without the NR sourced N and R.  

 

My stearic acid is like wax. It doesn't dissolve into hot water, but floats on the top.  It's amazing to think it's even digestible.  I'm surprised there hasn't been more discussion about how to take it.   I wonder if it gets absorbed faster or slower than the N and R.  By the way, would a teaspoon of stearic flakes be about 4 grams?  

 

It sounds like the idea is to wait a full 2 hours before "exercising like a girl." Last time I waited only 1.5 hours. I wonder if my timing was off with respect to the N and R and stearic components as well as the NR.  Another question I have is whether stearic can be taken earlier or later than the N and R or if it has to be consumed at same time to still be doing a 746 (obviously much later and it's fission followed by fusion protocol).

 


Edited by Empiricus, 26 March 2018 - 02:30 AM.


#880 Turnbuckle

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Posted 26 March 2018 - 03:05 AM

Yes, I adopted it from your post #746 (boost cellular function) protocol.  Thank you for your feedback.  I will try without the NR sourced N and R.  

 

My stearic acid is like wax. It doesn't dissolve into hot water, but floats on the top.  It's amazing to think it's even digestible.  I'm surprised there hasn't been more discussion about how to take it.   I wonder if it gets absorbed faster or slower than the N and R.  By the way, would a teaspoon of stearic flakes be about 4 grams?  

 

It sounds like the idea is to wait a full 2 hours before "exercising like a girl." Last time I waited only 1.5 hours. I wonder if my timing was off with respect to the N and R and stearic components as well as the NR.  Another question I have is whether stearic can be taken earlier or later than the N and R or if it has to be consumed at same time to still be doing a 746 (obviously much later and it's fission followed by fusion protocol).

 

You can use stearic acid in hot chocolate if you add roughly the same amount of lecithin. I do it in the microwave that way. You can also add it into fudge or cookies with or without lecithin. As for timing, it would be possible to add stearic acid after N+R and exercise, and thus get fission/mitophagy followed by fusion (which I would only do if you've already gotten rid of most of the bad mitochondria). But I don't think taking it before N+R makes sense, as the cellular response to stearic acid is faster than for N+R. The latter takes chemical processing to get to NAD.


Edited by Turnbuckle, 26 March 2018 - 03:11 AM.

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#881 PAMPAGUY

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Posted 26 March 2018 - 09:32 AM

https://www.fightagi...ratrol-in-mice/

 

 

A new article on NAD precussors.


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#882 PAMPAGUY

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Posted 26 March 2018 - 05:31 PM

Dr. Sinclair has a new molecule that has a synergistic effect on NMN that increases NAD+ levels.  Never heard of H2S?

Lead author Dr Abhirup Das, from UNSW's School of Medical Sciences and a visiting scientist at Harvard Medical School, emphasised the significant effect NMN and H2S could have on frailty, circulation and the capacity to run.

"H2S alone has some anti-aging properties but the two combined have a synergistic relationship that helped mice to run at least 50-60% further," says Dr Das.

https://www.news-med...der-people.aspx


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#883 MikeDC

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Posted 26 March 2018 - 05:40 PM



Dr. Sinclair has a new molecule that has a synergistic effect on NMN that increases NAD+ levels. Never heard of H2S?


Lead author Dr Abhirup Das, from UNSW's School of Medical Sciences and a visiting scientist at Harvard Medical School, emphasised the significant effect NMN and H2S could have on frailty, circulation and the capacity to run.

"H2S alone has some anti-aging properties but the two combined have a synergistic relationship that helped mice to run at least 50-60% further," says Dr Das.

https://www.news-med...der-people.aspx

It is really h2s and NAD+. They both contribute to endothelial health in its own ways. NAD+ increase mitochandria functions and energy, H2S increases blood flow to tissues. But how many people want to try H2S?

“Hydrogen sulfide is a broad-spectrum poison, meaning that it can poison several different systems in the body, although the nervous system is most affected. The toxicity of H
2S is comparable with that of carbon monoxide.[26] It binds with iron in the mitochondrial cytochrome enzymes, thus preventing cellular respiration.”

Edited by MikeDC, 26 March 2018 - 05:56 PM.

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#884 William Sterog

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Posted 27 March 2018 - 09:00 AM

After treatment for 12 weeks, the plasma taurine and H2S levels were significantly higher in the prehypertensive individuals treated with taurine (plasma H2S level: 43.8±20.82 µmol/L at baseline to 87.0±24.51 µmol/L after treatment; P<0.001 and plasma taurine level: 108.3±55.27 µmol/L at baseline to 142.3±62.14 µmol/L after treatment; P<0.05)

http://hyper.ahajour...115.06624/-/DC1
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#885 William Sterog

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Posted 27 March 2018 - 09:06 AM



Dr. Sinclair has a new molecule that has a synergistic effect on NMN that increases NAD+ levels. Never heard of H2S?


Lead author Dr Abhirup Das, from UNSW's School of Medical Sciences and a visiting scientist at Harvard Medical School, emphasised the significant effect NMN and H2S could have on frailty, circulation and the capacity to run.

"H2S alone has some anti-aging properties but the two combined have a synergistic relationship that helped mice to run at least 50-60% further," says Dr Das.

https://www.news-med...der-people.aspx

It is really h2s and NAD+. They both contribute to endothelial health in its own ways. NAD+ increase mitochandria functions and energy, H2S increases blood flow to tissues. But how many people want to try H2S?

“Hydrogen sulfide is a broad-spectrum poison, meaning that it can poison several different systems in the body, although the nervous system is most affected. The toxicity of H
2S is comparable with that of carbon monoxide.[26] It binds with iron in the mitochondrial cytochrome enzymes, thus preventing cellular respiration.”

According to the research, it is the Sirt1 activation and the H2S. Sirt1 can be activated with PQQ, Epimedium, DHA or anything that stimulates cAMP, not only with NAD+.

Taurine + DHA or Taurine + Epimedium (which is on its own a good supplement in regards of endothelial function), may be good alternatives, way cheaper than NR or NMN.

https://www.ncbi.nlm...pubmed/26275361
https://www.ncbi.nlm...pubmed/20381504
https://www.ncbi.nlm...pubmed/23806688
https://www.ncbi.nlm...pubmed/22195961

#886 MikeDC

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Posted 27 March 2018 - 10:48 AM



Dr. Sinclair has a new molecule that has a synergistic effect on NMN that increases NAD+ levels. Never heard of H2S?


Lead author Dr Abhirup Das, from UNSW's School of Medical Sciences and a visiting scientist at Harvard Medical School, emphasised the significant effect NMN and H2S could have on frailty, circulation and the capacity to run.

"H2S alone has some anti-aging properties but the two combined have a synergistic relationship that helped mice to run at least 50-60% further," says Dr Das.

https://www.news-med...der-people.aspx

It is really h2s and NAD+. They both contribute to endothelial health in its own ways. NAD+ increase mitochandria functions and energy, H2S increases blood flow to tissues. But how many people want to try H2S?

“Hydrogen sulfide is a broad-spectrum poison, meaning that it can poison several different systems in the body, although the nervous system is most affected. The toxicity of H
2S is comparable with that of carbon monoxide.[26] It binds with iron in the mitochondrial cytochrome enzymes, thus preventing cellular respiration.”
According to the research, it is the Sirt1 activation and the H2S. Sirt1 can be activated with PQQ, Epimedium, DHA or anything that stimulates cAMP, not only with NAD+.

Taurine + DHA or Taurine + Epimedium (which is on its own a good supplement in regards of endothelial function), may be good alternatives, way cheaper than NR or NMN.

https://www.ncbi.nlm...pubmed/26275361
https://www.ncbi.nlm...pubmed/20381504
https://www.ncbi.nlm...pubmed/23806688
https://www.ncbi.nlm...pubmed/22195961

NAD+ is native sirtuins activator. Other activators are just gimmicks like Resveratrol.
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#887 William Sterog

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Posted 27 March 2018 - 02:35 PM

Garlic and Sulforaphane may also be useful in increasing H2S:

2.1. H2S
Hydrogen sulfide is one of three major gasotransmitters in the human body (transmitting molecules which happen to be gasses) alongside nitric oxide and carbon monoxide, and is the major underlying factor in garlic supplementation. Cruciferous vegetables are known to confer a smell of H2S when cooked, and since garlic has its cardioprotective effects mediated by sulfur[12] and sulforaphane has similar protective effects[13] it was investigated if there was a connection and it was found that, in prostatic cancer cells and mouse liver homogenate at 10µM, sulforaphane releases H2S.[14] It is thought that any molecule with an isothiocyanate group (-N=C=S) can act as a sulfur donating molecule for the production of H2S.

https://examine.com/...s/sulforaphane/
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#888 Nate-2004

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Posted 27 March 2018 - 03:47 PM

I take a lot of garlic, two twice a day with food for a couple years now. I tend to cycle the sulforaphane in on fusion days, 60mg worth (6x). Good to know this helps and this was mentioned I think in the other thread on NR w/Sulforaphane. 

 

 



#889 Turnbuckle

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Posted 27 March 2018 - 08:20 PM

H2S does look interesting in combination with fusion/biogenesis--

 

Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK.

CONCLUSIONS:
Together, these results suggest that hydrogen sulfide is an important regulator of cardiac mitochondrial content and establishes that exogenous hydrogen sulfide can induce mitochondrial biogenesis via an AMPK-PGC1α signaling cascade.

 

 
 
This research used SG-1002, which releases H2S and NO, but they found that the biogenesis was due to the H2S and not the NO. Thus garlic should be sufficient to get the benefit--

Diallyl disulfide ameliorates isoproterenol induced cardiac hypertrophy activating mitochondrial biogenesis via eNOS-Nrf2-Tfam pathway in rats
 
In conclusion, garlic and DADS induces mitochondrial biogenesis and ameliorates cardiac hypertrophy via activation of eNOS-Nrf2-Tfam pathway in rats.

 

 

 


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#890 Nate-2004

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Posted 27 March 2018 - 09:44 PM

Maybe I should cycle the garlic in and out with the glucosamine sulfate, keep garlic on the fusion side and GS on the fission side. My fusion cycles are getting longer tho, a whole week at this point, I'm thinking of just doing fission for 5 days of the month perhaps, then fusion or that other combination the rest of the time.


Edited by Nate-2004, 27 March 2018 - 09:46 PM.


#891 Turnbuckle

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Posted 27 March 2018 - 09:51 PM

Maybe I should cycle the garlic in and out with the glucosamine sulfate, keep garlic on the fusion side and GS on the fission side. My fusion cycles are getting longer tho, a whole week at this point, I'm thinking of just doing fission for 5 days of the month perhaps, then fusion or that other combination the rest of the time.

 

 

Glucosamine also increases biogenesis. 

 

d-Glucosamine (GlcN) is a freely available and commonly used dietary supplement potentially promoting cartilage health in humans, which also acts as an inhibitor of glycolysis. Here we show that GlcN, independent of the hexosamine pathway, extends Caenorhabditis elegans life span by impairing glucose metabolism that activates AMP-activated protein kinase (AMPK/AAK-2) and increases mitochondrial biogenesis.

https://www.ncbi.nlm...les/PMC3988823/

 


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#892 Nate-2004

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Posted 28 March 2018 - 03:09 AM

If AMPK activation results in biogenesis then why take AMPK activators during fission? Also I wonder to what degree it induces biogenesis considering that it also assists with ROS enabled mitophagy and QC through inhibiting glycolysis, as the article I linked earlier stated.


Edited by Nate-2004, 28 March 2018 - 03:10 AM.


#893 Turnbuckle

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Posted 28 March 2018 - 06:37 AM

If AMPK activation results in biogenesis then why take AMPK activators during fission? Also I wonder to what degree it induces biogenesis considering that it also assists with ROS enabled mitophagy and QC through inhibiting glycolysis, as the article I linked earlier stated.

 

 

It appears to do both, though it is more critical for fission/mitophagy--

 

AMPK is rapidly activated by mitochondrial stress and acutely triggers mitochondrial fission, at least in part via phosphorylation of MFF. This rapid AMPK-dependent induction of mitochondrial fission may serve as one way for the cell to prepare to initiate mitophagy of those mitochondrial fragments that have extensive damage (38). Though AMPK is a highly conserved sensor of mitochondrial damage across eukaryotes, MFF is one of the first AMPK substrates to have been discovered to directly control mitochondrial biology. AMPK is also known to induce mitochondrial biogenesis in various tissues (13), and AMPK directly phosphorylates and activates the first component of the autophagy cascade, the kinase ULK1 (15). Thus, AMPK emerges as a master regulator of mitochondrial homeostasis, coupling fission to mitophagy and, after prolonged energy stress, signaling the nucleus to initiate biogenesis of new mitochondria to replace the damaged ones.

https://www.ncbi.nlm...les/PMC4852862/

 


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#894 Turnbuckle

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Posted 29 March 2018 - 06:38 PM

In the OP I wrote about the use of stearic acid with C60, but I didn't follow up with it at the time. Now I've found research suggesting that mito morphology dictates the likely path of dividing stem cells--whether they divide asymmetrically (as usual) or symmetrically. With symmetrical division you can increase your stem cell pool. I've broken this out into a new thread, otherwise it would be quickly buried here on page 30.

 

See Stem cell self-renewal with C60.


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#895 Andey

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Posted 30 March 2018 - 08:35 AM

Ive noticed that fission, particularly with exercise, substantially increase inflammation for me and with few consecutive fission days, it gains a momentum and became a problem in itself. Ive decided to ease up a bit and do cycles less frequently and shorter.


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#896 Turnbuckle

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Posted 30 March 2018 - 10:37 AM

Ive noticed that fission, particularly with exercise, substantially increase inflammation for me and with few consecutive fission days, it gains a momentum and became a problem in itself. Ive decided to ease up a bit and do cycles less frequently and shorter.

 

I can't speak to inflammation in general, but too much fission can be a problem for cartilaginous tissue, probably due to the low numbers of mitochondria. Whatever the reason, I developed a swollen/painful knee by doing fission/exercise 4 days in a row when I first tried my "exercise like a girl" idea. This was an old injury I'd re-injured doing this. Backing off the fission and a gram a day of Minerva cucurmin took care of it. Ordinary cucurmin did nothing. 


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#897 Nate-2004

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Posted 30 March 2018 - 05:38 PM

The last two times I've done full on fission, from Tuesday through today and in the previous week another 3 days, both utilizing Apigenin and in the first period NAM+R, this time NR and NAM+R at different points, timed to my workouts and 2 NR at night before bed, I have felt incredibly energetic. Towards the end of each fission cycle the last two times I have noticed a significant reduction in tremor. It tends to come back over several days of fusion though. I have yet to add stearic acid back into the mix though since I am waiting on delivery. I was using both broccomax and broccoli in my smoothies instead (the broccoli was blended in water first and allowed to sit 20 minutes).

 

So why do I have such a huge amount of boundless energy despite the otherwise expected loss of mitochondria? I mean, energy that is sustained even through eating carby foods, which normally result in brain drain and a loss of energy.

 

I'm going to try to keep the fission going through the weekend I think.

 

Here's my fission protocol:

 

07:00

EGCG

 

07:30

4x NR (500mg)

1x 50mg Apigenin

1x 600mg Trans Resveratrol

2x 600mg Glucosamine Sulfate

 

08:00

Coffee, black, w/1.5g Ceylon Cinnamon

 

10:30

1x 600mg Trans Resveratrol

2g NAM + 1.8g R

2x 600mg Glucosamine Sulfate

 

12:00

Exercise:

 

3x 10 Deadlifts w/100lbs

3x 20 Pushups

3x 10 pullups

3x 100 yard sled push (125 lbs)

3x 10 leg curls (55lbs)

 

01:00

2x NR (250mg)

1x Lithium Orotate w/food

 

05:00 (with food)

 

Vitamin D 4000 IU

Glucosamine Sulfate 1200mg

600 mg trans Resveratrol

1.5g Ceylon Cinnamon

 

23:00

 

NR 250mg

100mg Apigenin

4g glycine

250mg magnesium (chelated)

L-theanine

 

 

Diet mostly normal, no broccoli or cruciferous, no fish oil or anything that might induce fusion.

 

Remember the resveratrol is apparently synergistic with apigenin, in terms of bioavailability.


Edited by Nate-2004, 30 March 2018 - 06:35 PM.

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#898 Turnbuckle

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Posted 31 March 2018 - 03:30 AM

Previously you reported exhaustion from NR, but now you report the opposite, so possibly you are getting more NAD+ due to the clearing out of defective mitochondria in the previous 6 months. Hard to say with your complex protocol. As for tremors, they can be associated with mito dysfunction, either with nuclear or mito genes--

 

Movement disorders in mitochondrial disease.

 
Other movement disorders associated with mitochondrial disease include choreoathetosis, spasticity, tremor and restless leg syndrome...Tremor is a less frequent movement disorder associated with mitochondrial disease but has been described in LHON [83, 109] and in cytochrome c oxidase defciency, due to COX20 mutations. 

 

 

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#899 PAMPAGUY

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Posted 31 March 2018 - 08:38 AM

New trial results from ChromaDex on Niagen 500 mg twice a day.  Now they can sell twice as much on an inflated markup.

 

https://www.nature.c...467-018-03421-7


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#900 Turnbuckle

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Posted 31 March 2018 - 09:49 AM

Can we keep the ChromaDex stuff to the NR threads?


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