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Manipulating mitochondrial dynamics

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

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#1441 longcity90

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Posted 19 November 2019 - 07:38 AM

Goodmorning everyone! I hope to get help writing in this thread.
 
I contacted "Turnbuckle" privately but I wouldn't want to bother him too much ... so if anyone feels able to help me I would be really grateful.
 
I am 29 years old and I live in Italy ... country that unfortunately in front of mitochondrial pathologies and energy metabolism is not helping me as I thought.
 
Since childhood I developed neurological and physical disorders to which no doctor could give me an answer.
 
I have continuous drops and unexplained weight gains (in the last period I am only gaining weight) regardless of how much food I introduce and what is done, energy "crashes", language compromised speech difficulties, sudden and inexplicable changes of personality / mood, every day is different and I accuse strong mental fogginess accompanied by large drops in physical energy, ability to work and logic compromises, loss of motivation, loss of empathy and emotions, edema and loss of muscle tone, reduced field of vision, increase in eye pressure. ... I lose the sense of reality and enter a psychotic state.
 
My blood tests are apparently all regular and in the range of the laboratory ... even the hormones (Testosterone, Estrogens, Vitamin D, Cortisol, Insulin, Thyroid) but B12 and folates are high. Homocysteine 11.7.
 
Only a year ago thanks to the internet I discovered the possibility of having something at the level of the energy transport chain in mitochondria.
 
Someone could tell me: did you make a diagnosis yourself without tests that confirm your theory? it's true, I don't have a diagnosis but the experience of 20 years of symptoms is enough.
 
In the last 5 years I have had a great cognitive and neuromuscular decline.
 
In the last 3 months I am benefiting from Vitamin E, Melatonin, ALCAR, Retinol, Ubiquinol and Bitter Cocoa (probably for Stearic Acid and Antioxidant?), B1 Thiamine HCL, B3 Niacin but only in the first month.
 
Is it possible to know which substances stimulate the various respiratory complexes? I maintain that there may be some flaws in the first and second complexes.
 
What would you do in my case? I really feel with little hope.
 
Thanks, see you soon!

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#1442 Turnbuckle

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Posted 19 November 2019 - 11:10 AM

To get advice on your difficulty, longcity90, please start a new thread.


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#1443 longcity90

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Posted 20 November 2019 - 10:09 AM

To get advice on your difficulty, longcity90, please start a new thread.

 

I opened a new thread in the "genetics" section. Can't delete the message above? I apologize for the error.
 
That said ... I was wondering if it is physiologically possible through mitochondrial fusion / fission / regeneration to increase muscle mass and decrease fat at the same time? in the fitness industry, almost everyone says this is not possible.
 
Based on your direct experience, what can you tell me about it?
 
How much index really Cal IN vs Cal out?


#1444 dlewis1453

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Posted 20 November 2019 - 04:19 PM

 

I opened a new thread in the "genetics" section. Can't delete the message above? I apologize for the error.
 
That said ... I was wondering if it is physiologically possible through mitochondrial fusion / fission / regeneration to increase muscle mass and decrease fat at the same time? in the fitness industry, almost everyone says this is not possible.
 
Based on your direct experience, what can you tell me about it?
 
How much index really Cal IN vs Cal out?

 

 

 

Hi Longcity90, I just responded to you in your new thread. Here is the link for anyone who would like to join: 

 

https://www.longecit...olism/?p=881884


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#1445 longcity90

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Posted 23 November 2019 - 09:06 AM

Can anyone confirm or deny that fructose increases brain lactate as well as fermented foods?


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#1446 orion22

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Posted 23 November 2019 - 01:52 PM

Can anyone confirm or deny that fructose increases brain lactate as well as fermented foods?

25% of fructose in converted to lactic acid rest is converted to fat in the liver


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#1447 Richard McGee

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Posted 17 December 2019 - 02:15 AM

This is speculative (not to mention anecdotal) but I'm going to throw it out here anyway. I am now 70 years old. I had a heart attack in 2009, with intervention and placement of stents. My ejection fraction has been measured in the intervening decade at 35 - 40 % range, reflective of significant damage to the heart muscle. My latest echocardiogram unexpectedly gave me an estmated 50 - 55% EF measurement - close to the normal range. Needless to say, I was stunned but very pleased. I will look forward to future measurements to see if this is an outlier, or truly indicative of substantial improvement.

 

I can't really account for this due to any change in diet or exercise routine. My prescription drug regime has been stable for years now.

 

The one intervention I can readily point to is following Turnbuckle's MMD protocols at the beginning of 2018, on and off for 6 months. Even from my limited understanding of heart disease, it's obvious that metachondrial function plays a significant role in cardiac function. I have read a number of scientific articles reporting on mitochondrial therapy as a treatment for heart disease, including https://www.nature.c...cardio.2016.203

 

41569_2017_Article_BFnrcardio2016203_Fig


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#1448 coreyaus

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Posted 29 December 2019 - 12:03 PM

This is a great read. I will go over it all and try a protocol myself. Dermal ageing and neurogenesis/TBI recovery/brain function as focus. One quick question,

Im currently using sr9009 and have read about the mitochondrial growth benefits of it. Is that something you have looked into and should it be cycled accordingly with fission/fusion phases? 



#1449 Turnbuckle

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Posted 29 December 2019 - 12:56 PM

This is a great read. I will go over it all and try a protocol myself. Dermal ageing and neurogenesis/TBI recovery/brain function as focus. One quick question,

Im currently using sr9009 and have read about the mitochondrial growth benefits of it. Is that something you have looked into and should it be cycled accordingly with fission/fusion phases? 

 

That question was previously asked and discussed here

 

This protocol is directed to eliminating and replacing defective mitochondrial DNA (mtDNA) in an iterative process. If you are young and healthy, you probably won't benefit much from it, as it only serves to amplify the natural cellular mechanisms of quality control. With age and with certain drugs (such as statins), mtDNA damage can get so severe that QC can't keep up. That's where this protocol can help. Will sr9009 do anything PQQ can't do re biogenesis? I don't know as I have no personal experience, but I doubt it. However, it apparently has shorter term effects beyond biogenesis, and I can't say how that would interact with this protocol. It would more likely fit with the fusion phase, or separately, after defective mtDNA have been eliminated.


Edited by Turnbuckle, 29 December 2019 - 01:11 PM.

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#1450 Soalian

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Posted 01 January 2020 - 11:51 AM

This is a great read. I will go over it all and try a protocol myself. Dermal ageing and neurogenesis/TBI recovery/brain function as focus. One quick question,
Im currently using sr9009 and have read about the mitochondrial growth benefits of it. Is that something you have looked into and should it be cycled accordingly with fission/fusion phases?


I've been meaning to try Sr-9009 for it's purported effects on circadian rythms, research on mitochondrial enhancing properties of SR-9009 is scarce, I wouldn't take it only for that purpose, but granted I don't suffer from mitochondrial diseases. As for it's integration into the fission/fusion protocol, I'm afraid you will have to be the Guinea pig here, as it is uncharted territory for most of us.

What effects do you get from SR-9009 (sleep,endurance,...)?

Edited by Soalian, 01 January 2020 - 11:56 AM.


#1451 kurt9

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Posted 07 January 2020 - 04:32 PM

A question about the protocol regarding the Steric Acid. 

 

Should the Steric Acid be taken both morning and evening of days 4 and 5 (fusion days) or should it be taken only on the morning of day 4, as implied by the way the protocol is written?

 

Thanks.



#1452 longcity90

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Posted 08 January 2020 - 08:01 AM

I was wondering if the use of a thyroid drug (combination of T3 + T4) can be useful in fission or fusion? referring to this image I think they have a lot of correlation.

 

 

https://imgur.com/hzR0fum



#1453 coreyaus

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Posted 09 January 2020 - 03:08 AM

What effects do you get from SR-9009 (sleep,endurance,...)?

 

I'm big into the gym hence initial finding of this. I'm not 100% sure but it seems to be great for fat loss and effort in the gym. i don't notice anything sleep wise but i have trouble with that due to brain injury anyway. also iv being told of its great effect on cholesterol levels and cyto-toxic to cancers ect.. its a very overlooked product i think. one of my favorites for sure. i take it sublingual as there are some things iv read saying orally isn't good (apparently topically is though).



#1454 Soalian

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Posted 09 January 2020 - 01:08 PM

Thank you for the detailed reply.

Do you feel it may help with recovery from exercise(what I'm mainly interested in)?
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#1455 mitomutant

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Posted 13 January 2020 - 06:22 PM

Planning to start this protocol. Would love to hear your opinions about this (I am looking at you, Turnbuckle).

 

As I do have a primary mitochondrial dysfunction, the number of damaged mitochondria is high (tissue dependant, but 80% in my eye muscles and around 30%-35% in skeletal muscle, as seen in a muscle biopsy of my biceps some years ago).

 

Given this, I have a couple of doubts:

 

  • I understand that it is better to start slow, specially the fission cycle. Should I decrease amounts, remove some of the supps, limit days, a combination of some ?
  • What symptoms would be an indication to stop ?  (for example, profound fatigue is a symptom of my disease. It's different from "normal" fatigue. I get it every 2-3 months, lasting 3-4 days. Nowadays I can see it coming and stop it with extra sleep, enada NADH supplement and an extra dose of reduced glutathione).

 

I would really appreciate any suggestion

 

Thanks

 


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#1456 Turnbuckle

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Posted 13 January 2020 - 07:48 PM

Planning to start this protocol. Would love to hear your opinions about this (I am looking at you, Turnbuckle).

 

As I do have a primary mitochondrial dysfunction, the number of damaged mitochondria is high (tissue dependant, but 80% in my eye muscles and around 30%-35% in skeletal muscle, as seen in a muscle biopsy of my biceps some years ago).

 

Given this, I have a couple of doubts:

 

  • I understand that it is better to start slow, specially the fission cycle. Should I decrease amounts, remove some of the supps, limit days, a combination of some ?
  • What symptoms would be an indication to stop ?  (for example, profound fatigue is a symptom of my disease. It's different from "normal" fatigue. I get it every 2-3 months, lasting 3-4 days. Nowadays I can see it coming and stop it with extra sleep, enada NADH supplement and an extra dose of reduced glutathione).

 

I would really appreciate any suggestion

 

Thanks

 

This is all shooting in the dark, for while I had a very high level of damage, it was acquired from statins. Nevertheless, if it were me I'd go with a much simplified protocol, starting with PQQ, then N+R, then PQQ, and so on, using them on alternate days, building up the N+R from a starting dose I knew I could handle. Later I might add some of the other things. For fusion, I'd either leave it off or use 50 mg sulforaphane. This has a much shorter half life compared to stearic acid, and can get through the BBB. 


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#1457 mitomutant

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Posted 14 January 2020 - 09:32 AM

This is all shooting in the dark, for while I had a very high level of damage, it was acquired from statins. Nevertheless, if it were me I'd go with a much simplified protocol, starting with PQQ, then N+R, then PQQ, and so on, using them on alternate days, building up the N+R from a starting dose I knew I could handle. Later I might add some of the other things. For fusion, I'd either leave it off or use 50 mg sulforaphane. This has a much shorter half life compared to stearic acid, and can get through the BBB. 

 

Thanks for your suggestions. Good to know you started this because of statin damage. The molecular features of an acquired mitochondrial myopathy from statin use are pretty similar to my disease, so I guess this should work for me as well.

 

If I am understanding your suggestion correctly, this would be my plan:

 

Day 1: Fusion/biogenesis
PQQ - 20mg
Sulforaphane - 50mg
 
Day 2: Fission/mitophagy
Nicotinamide (NAD+) - start with 500mg and increase up to 2g
Ribose (NAD+) - start with 500mg and increase up to 2g
 
 
Day 3: Same as 1
Day 4: Same as 2
 
And so on ...
 
 
I would keep on doing this until I noticed some effect. If I do not notice anything in 3-4 weeks (*), is it wise to add the rest of the supps ?
 
Thanks again.
 
(*) Using this period from previous experiences (CoQ10 has helped me a lot; it takes this time to kick-in)

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#1458 longcity90

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Posted 14 January 2020 - 10:02 AM

About the Thiamine ...

 

https://synergyhw.bl...l-function.html

 

could it be used in Fusion instead of Nicotinamide and see what happens? other thing ... during the fusion it is good not to consume fats in particular rich in stearic acid?

 

Thanks



#1459 Turnbuckle

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Posted 14 January 2020 - 11:28 AM

 

I would keep on doing this until I noticed some effect. If I do not notice anything in 3-4 weeks (*), is it wise to add the rest of the supps ?

 

 

 

mitomutant: I will be surprised if you don't notice anything, but yeah.

 

longcity90: Nicotinamide (plus ribose) is used for fission, not for fusion. Stearic acid and/or sulforaphane are used for fusion. Supplements for fusion, in my experience, appear to override supplements for fission.


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#1460 longcity90

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Posted 14 January 2020 - 11:43 AM

mitomutant: I will be surprised if you don't notice anything, but yeah.

 

longcity90: Nicotinamide (plus ribose) is used for fission, not for fusion. Stearic acid and/or sulforaphane are used for fusion. Supplements for fusion, in my experience, appear to override supplements for fission.

You're right, forgive my wording error.



#1461 mitomutant

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Posted 14 January 2020 - 11:57 AM

mitomutant: I will be surprised if you don't notice anything, but yeah.

 

 

 

Great. Supps ordered.

 

I will report updates in this thread.

 

Thanks.



#1462 longcity90

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Posted 14 January 2020 - 12:24 PM

Would using the Fusion with a caloric deficit be counterproductive since fasting / calorie restriction would also increase the nad / nadh ratio?


Edited by longcity90, 14 January 2020 - 12:25 PM.


#1463 JPY

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Posted 15 January 2020 - 10:28 AM

I just wanted to add an experience report to this thread. 

 

In July 2016 I had an EBV/mono reactivation that left me sick for many months, and the symptoms persisted long after the virus had cleared in blood tests (including PCR). Eventually I reached the conclusion that the virus had probably damaged my mitochondria, something others above have also reported in post-viral situations. 

 

I used things like PQQ and C60 with some success initially but the results faded. I then came across Turnbuckle's protocol and began it in June 2019. 

 

Almost immediately I started to see an improvement and now, around half a year later, I would say that I am 90-95% better and expect a full recovery. Most importantly, the results appear to be sustained.

 

I did not change anything else in that time, and before beginning the protocol my rate of recovery was painfully slow. So I can only conclude that this protocol is powerful and effective, including in post-viral cases.

 

 


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#1464 longcity90

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Posted 19 January 2020 - 10:28 AM

Today I decided to start the protocol in a very "soft" way as regards the dosages because I PROBABLY have one or more defects in the mitochondrial transport chain (in addition to other probable deficiencies such as Q10, carnitine, mutations in Krebs) especially in the first complex .
 
I think I have two days of fission and two days of fusion.
 
Today is the first day of fission and I started with 50mg of B3 (NIACINA) and 500mg of RIbose, therefore a ratio of 1:10.
 
I know well that they are decidedly lower dosages than those proposed.
 
My past experience with Niacin was positive at the beginning but negative in the following days ... I think I was only increasing serotonin and I assure you that it is not nice to be with high serotonin! Bad experience.
 
Today after months ... decidedly positive sensations ... taken on an empty stomach with ribose. I'm not sure if I stimulated the first complex more ... or what else but the morning was excellent ... I also did some bodyweight exercises because I felt I could do them ... I didn't experience post-stress symptoms.
 
Breakfast was fat free ... only skim milk, yogurt, fruit and coffee.
 
Is it advisable on FISSION days to keep the calories lower to activate AMPK?
 
Should stearic acid contained in dietary fats be avoided? and avoid antioxidants?
 
I can say with certainty that I have never seen the light after such a long time of suffering as today! I think it's the right way!

Edited by longcity90, 19 January 2020 - 10:36 AM.


#1465 Kentavr

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Posted 19 January 2020 - 01:12 PM

I just wanted to add an experience report to this thread.

In July 2016 I had an EBV/mono reactivation that left me sick for many months, and the symptoms persisted long after the virus had cleared in blood tests (including PCR). Eventually I reached the conclusion that the virus had probably damaged my mitochondria, something others above have also reported in post-viral situations.

I used things like PQQ and C60 with some success initially but the results faded. I then came across Turnbuckle's protocol and began it in June 2019.

Almost immediately I started to see an improvement and now, around half a year later, I would say that I am 90-95% better and expect a full recovery. Most importantly, the results appear to be sustained.

I did not change anything else in that time, and before beginning the protocol my rate of recovery was painfully slow. So I can only conclude that this protocol is powerful and effective, including in post-viral cases.


Please describe what you did and which protocol you used.

#1466 JPY

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Posted 19 January 2020 - 05:07 PM

Initially I followed the protocol on Turnbuckle's profile page almost exactly, except for using glycerol monostearate in place of the stearic acid brownies. Over time I adapted it a bit based on how I was responding to different things, e.g. cutting out the evening doses due to sleeping problems, using sulforaphane in place of GMS as it made me feel a bit weird. The protocol I settled on was as follows, which I did back-to-back:

 

Fission: 2 days

Niacinamide 2g

D-Ribose 2g

Fisetin 200mg

AMPK Metabolic Activator from LE 2 caps = 900mg jiaogulan extract

 

Fusion: 2 days

Sulforaphane (Broccomax 2 caps)

PQQ+Ubiquinol 20mg/200mg

Hydroxytyrosol 200mg (from olive leaf extract)

 

I also tried, from time to time, adding NADH 15mg on the fusion days, thinking that if a higher NAD+/NADH ratio encouraged fission, then perhaps increasing the NADH side would help fusion. Anecdotally it seemed to help, but I'm not a biochemist so I don't know if this makes sense in terms of the various pathways. 

 

I have not yet tried the stearic acid brownies as I was unsure where I could source good/pure stearic acid where I live (in Germany) and was seeing good results anyway. But I intend to try them now to see if it can strengthen the effects of the protocol further.

 


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#1467 Blu

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Posted 19 January 2020 - 06:08 PM

I have thoroughly read this thread and saw no mention of shea butter for triggering fusion.

To my knowledge, shea butter has the higher quantity of stearic acid among natural sources (around 35%) and a negligible amount of palmitic acid. It should be highly bioavailable on its own.


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#1468 PAMPAGUY

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Posted 20 January 2020 - 06:31 AM

Initially I followed the protocol on Turnbuckle's profile page almost exactly, except for using glycerol monostearate in place of the stearic acid brownies. Over time I adapted it a bit based on how I was responding to different things, e.g. cutting out the evening doses due to sleeping problems, using sulforaphane in place of GMS as it made me feel a bit weird. The protocol I settled on was as follows, which I did back-to-back:

 

Fission: 2 days

Niacinamide 2g

D-Ribose 2g

Fisetin 200mg

AMPK Metabolic Activator from LE 2 caps = 900mg jiaogulan extract

 

Fusion: 2 days

Sulforaphane (Broccomax 2 caps)

PQQ+Ubiquinol 20mg/200mg

Hydroxytyrosol 200mg (from olive leaf extract)

 

I also tried, from time to time, adding NADH 15mg on the fusion days, thinking that if a higher NAD+/NADH ratio encouraged fission, then perhaps increasing the NADH side would help fusion. Anecdotally it seemed to help, but I'm not a biochemist so I don't know if this makes sense in terms of the various pathways. 

 

I have not yet tried the stearic acid brownies as I was unsure where I could source good/pure stearic acid where I live (in Germany) and was seeing good results anyway. But I intend to try them now to see if it can strengthen the effects of the protocol further.

I also live in Europe, Spain to be exact and have had no luck finding food grade Stearic Acid, so I have substituted 5 grams of glycerol monosterate.  Have used it in brownies and oatmeal.  As Turnbuckle recommended.    "Alternatively you can substitute 5 grams of glycerol monosterate (mixing it into hot chocolate or a hot food like oatmeal) and take it at the same time as the other ingredients. It is far more rapidly digested and thus may rapidly push up blood pressure. This can be controlled with BP medications and/or 5-10g taurine and a gram or two of oleopein."



#1469 PAMPAGUY

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Posted 20 January 2020 - 06:42 AM

This question is for Turnbuckle.  Noticed that you blamed Statins for messing up your mitochondria.  I take 5 mg Crestor.  Would you recommend I stop taking this.  Know your not a Doctor, but just asking for your personal opinion.  Not asking for medical advise.  I like to keep my LDL as low as possible is the reason for it.  I'm 73 yo male in good health.



#1470 longcity90

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Posted 20 January 2020 - 07:10 AM

Initially I followed the protocol on Turnbuckle's profile page almost exactly, except for using glycerol monostearate in place of the stearic acid brownies. Over time I adapted it a bit based on how I was responding to different things, e.g. cutting out the evening doses due to sleeping problems, using sulforaphane in place of GMS as it made me feel a bit weird. The protocol I settled on was as follows, which I did back-to-back:

 

Fission: 2 days

Niacinamide 2g

D-Ribose 2g

Fisetin 200mg

AMPK Metabolic Activator from LE 2 caps = 900mg jiaogulan extract

 

Fusion: 2 days

Sulforaphane (Broccomax 2 caps)

PQQ+Ubiquinol 20mg/200mg

Hydroxytyrosol 200mg (from olive leaf extract)

 

I also tried, from time to time, adding NADH 15mg on the fusion days, thinking that if a higher NAD+/NADH ratio encouraged fission, then perhaps increasing the NADH side would help fusion. Anecdotally it seemed to help, but I'm not a biochemist so I don't know if this makes sense in terms of the various pathways. 

 

I have not yet tried the stearic acid brownies as I was unsure where I could source good/pure stearic acid where I live (in Germany) and was seeing good results anyway. But I intend to try them now to see if it can strengthen the effects of the protocol further.

 

Do you take ribose and niacinamide on an empty stomach together in the morning?







Also tagged with one or more of these keywords: nad, nad+, c60, mito, fission, fusion, stearic acid, mtdna, methylene blue

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