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Manipulating mitochondrial dynamics

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

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#1411 Rocket

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Posted 17 July 2019 - 01:08 AM

Any opinions on methelyne blue?
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#1412 mikey

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Posted 25 July 2019 - 02:14 PM

My experience is only with my C60 mix taken with five grams of pure stearic acid on an empty stomach. I can't say if that is the optimum dose, and I will try larger doses in future trials. Stearic acid is a free fatty acid while the stearic acid in coca butter is in the form of mixed triglycerides. What difference that would make for this purpose I can't say.  

 

Food grade stearic acid is ridiculously cheap--around $5/lb at Amazon. 

 

People attempt to elicit a response from C60 by mixing it with something that is oily.

 

It is the polyphenols in olive oil that bond with C60 to produce beneficial results. Stearic acid contains no polyphenols. We see companies vending C60 with various oils, such as coconut and avocado, which sound hip, and even corn oil.

 

But all of these other oils are lacking in polyphenols, either contains none or significantly less than extra virgin olive oil.(EVOO), which was used in the Baati study that all of this interest in C60 initiated.

 

The reason that Turnbuckle makes his C60 with hydroxytyrosol is that it is the most abundant polyphenol in high quality EVOO.


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#1413 bladedmind

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Posted 27 July 2019 - 10:42 PM

Please excuse my error, I posted this at the end of the old mitochondria thread, am reposting it here in the newer thread.  Thanks for your patience. 

 

I’ve done the Turnbuckle Alzheimer’s protocol 32 times, the stem cell renewal seven times (which in 2018 ended exercise intolerance I’d suffered since 2013), the senescence protocol once, and the mitochondrial twice.  I’ll stay on topic, and raise an item of interest relevant to the mitochondria protocol.  I’ve had chronic paresthesia in the extremities for three years and have tried various remedies (it’s about 50% better than peak worst).  I just checked and there are multiple recent references about a possible relationship between peripheral neuropathy and mitochondrial damage.   For example:

 

https://www.scienced...10303184111.htm

Neuropathies tend to hit the feet first, then travel up the legs. As they reach the knees, they often start affecting the hands. This painful condition tends to affect people who are older or taller more often than younger, shorter people. Though these patterns are typical of almost all cases of neuropathy, scientists have been stumped to explain why…. the reason might lie within mitochondria, the parts of cells that generate energy. While mitochondria for most cells in the body have a relatively quick turnover -- replacing themselves every month or so -- those in nerve cells often live much longer to accommodate the sometimes long journey from where a cell starts growing to where it ends. The nerve cells that supply the feet are about 3 to 4 feet long in a person of average height, Hoke explains. Consequently, the mitochondria in these nerve cells take about two to three years to travel from where the nerve originates near the spine to where it ends in the foot….

The researchers report in the January Annals of Neurology that in patients with neuropathy, DNA from mitochondria in the nerve endings at the ankle had about a 30-fold increase in a type of mutation that deleted a piece of this DNA compared to mitochondrial DNA from near the spine. The difference in the same deletion mutation between the matched samples in people without neuropathy was about threefold…..as mitochondria make the trek from near the spine to the feet, their DNA accumulates mutations with age. These older mitochondria might be more vulnerable to the assaults that come with disease than younger mitochondria near the spine, leading older mitochondria to become dysfunctional first. The finding also explains why people who are older or taller are more susceptible to neuropathies….if this discovery is confirmed for other types of neuropathy, it could lead to mitochondria-specific ways to treat this condition. For example, he says, doctors may eventually be able to give patients drugs that improve the function of older mitochondria, in turn improving the function of nerve cells and relieving pain.

 

 

 

https://medicine.uiowa.edu/diabetes/targeting-mitochondrial-fission-neuroprotection-diabetic-neuropathy

August 2018​

…grant from the National Institutes of Health and the National Institutes of Diabetes Digestive and Kidney Disease (NIDDK) entitled “Targeting mitochondrial fission for neuroprotection in diabetic neuropathy” for a total award of $1,702,888 over four years. The grant will support studies that will examine a new approach for treating Diabetic Nerve damage, also known as diabetic neuropathy. Presenting with chronic pain or loss of sensation, peripheral diabetic neuropathy (PDN) is a debilitating comorbidity of diabetes that affects at least half the diabetic patient population. Since only palliative treatments are available, there is an urgent need for therapies that prevent or reverse the “dying back” degeneration of sensory fibers innervating the skin. Recent evidence suggests that diabetes compromises mitochondria, the cellular powerhouse, in sensory neurons. However, the underlying mechanisms are unknown….Mitochondrial shape is controlled by opposing fission and fusion events….

The research team further proposes to investigate how diabetes causes mitochondrial fragmentation in sensory neurons and how inhibiting mitochondrial fragmentation protects peripheral axons in diabetes. Using new mouse models and innovative in vivo imaging approaches, they will test the hypothesis that dysregulation of the mitochondrial fission/fusion equilibrium contributes to the pathogenesis of diabetic neuropathy…

 

 

 

I raise this this issue for two reasons.  First, there may be readers who suffer from peripheral neuropathy and are looking for things to try.   Second, although educated, I am not trained in biochemistry, and would be glad to hear comments from more informed people about the proposed relationship between mitochondria and neuropathy. 

 

It’s interesting that it takes 2-3 years for mitochondria to migrate to the feet from nerve origin at the spine.  Implications for protocol? 

 

 

 


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#1414 Turnbuckle

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Posted 28 July 2019 - 11:48 AM

 

It’s interesting that it takes 2-3 years for mitochondria to migrate to the feet from nerve origin at the spine.  Implications for protocol? 

 

 

I expect the problem lies not with the migration of mitochondria* but with the long distance nuclear-encoded mitochondrial proteins must travel from the soma to the distal end of an axon. Those at the distal end have to make do with a reduced supply and thus are more sensitive to environmental toxins. But no matter where they are, they should be going through the cycle of fission and fusion whereby the cell's QC detects defective mtDNA and gets rid of them. If that process is not doing its job appropriately, then the distal ends of axons will show symptoms first as they become starved of ATP. Mitochondrial DNA has 37 genes and all are needed to make ATP. Since most mitochondria have more than one copy, they can cover for each other. All could have damage to a random gene and yet between them provide a full complement of enzymes within the mitochondrion to keep things going. Thus a cell can accumulate high levels of damage before you know it. I'd reached that point due to a few months of statin use, and it only got a little better over a period of years. Even after I developed this clearance protocol it took me the better part of a year to correct it. Probably around 40-50 cycles. Most people won't have that level of damage and will be able to clear them out with just a few, but peripheral nerve damage suggests a very high level.

 

*This bi-directional migration is likely to even things out over short distances, not to supply mitochondria from the soma.


Edited by Turnbuckle, 28 July 2019 - 12:32 PM.

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#1415 Aman

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Posted 29 July 2019 - 02:17 PM

Hi Turnbuckle,

 

I had a quick question for you. Does Nicotinamide in this protocol refer to NMN or plain old Nicotinamide/niacinamide?

 

Thanks.


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#1416 aribadabar

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Posted 30 July 2019 - 02:02 AM

 

Hi Turnbuckle,

 

I had a quick question for you. Does Nicotinamide in this protocol refer to NMN or plain old Nicotinamide/niacinamide?

 

Thanks.

 

 The latter.


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#1417 eigenber

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Posted 04 September 2019 - 07:07 AM

This is more of a theory-based question, generally related to aging and how mitochondrial/stem cell interventions might influence age progression.

 

So basically, considering the ‘accumulated damage’ theory of aging, it might be accurate to say the replacement parts are inferior to the original, and this use of ever-degrading parts and tools is repeated after every tissue repair. Such repairs or part-replacements happens just because of the ‘daily grind’ of food acquisition and digestion, as well as more traumatic injuries.  Damage accumulates because generally, the repairs are short of being complete; because the body is a closed energy system, more or less, such that when it repairs cells and tissues, it has access to only the tools and materials provided by the body at around the time of birth - tools and materials that become less effective over time. 

 

Theoretically then, if you could increase the quality of repairs to cells and tissues, you would correspondingly increase the length of time between a new cell and senescence, and thereby reduce at least those specific limitations on human longevity - that is, those imposed by use and damage - wear and tear. 

 

Assuming the soundness of the ‘accumulated damage’ hypothesis then, should we be asking of any proposed aging intervention, “in what way does it effect tissue repair and cell replacement?” The question then, for this thread is, “how might the mitochondria and stem cell protocols be effecting the processes of repair and replacement?”  

 

Caloric restriction works at least in part, because it reduces the workload pressed upon the metabolic engine. There is an expense for running the metabolic engine. The higher the caloric/tissue-digestive load, the longer and hotter the engine will run to keep a systemic balance. The longer and hotter the engine runs, the more frequently it needs its parts replaced. And the process of being replaced with evermore inferior parts, is manifested as accelerated aging. 

 

Besides running a cooler engine by eating less and better food, it may be possible to use exogenous chemistries to improve on repair and maintenance operations of the body. So, what might some of those chemistries be? 



#1418 Kentavr

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Posted 04 September 2019 - 08:54 AM

This is more of a theory-based question, generally related to aging and how mitochondrial/stem cell interventions might influence age progression.

So basically, considering the ‘accumulated damage’ theory of aging, it might be accurate to say the replacement parts are inferior to the original, and this use of ever-degrading parts and tools is repeated after every tissue repair. Such repairs or part-replacements happens just because of the ‘daily grind’ of food acquisition and digestion, as well as more traumatic injuries. Damage accumulates because generally, the repairs are short of being complete; because the body is a closed energy system, more or less, such that when it repairs cells and tissues, it has access to only the tools and materials provided by the body at around the time of birth - tools and materials that become less effective over time.

Theoretically then, if you could increase the quality of repairs to cells and tissues, you would correspondingly increase the length of time between a new cell and senescence, and thereby reduce at least those specific limitations on human longevity - that is, those imposed by use and damage - wear and tear.

Assuming the soundness of the ‘accumulated damage’ hypothesis then, should we be asking of any proposed aging intervention, “in what way does it effect tissue repair and cell replacement?” The question then, for this thread is, “how might the mitochondria and stem cell protocols be effecting the processes of repair and replacement?”

Caloric restriction works at least in part, because it reduces the workload pressed upon the metabolic engine. There is an expense for running the metabolic engine. The higher the caloric/tissue-digestive load, the longer and hotter the engine will run to keep a systemic balance. The longer and hotter the engine runs, the more frequently it needs its parts replaced. And the process of being replaced with evermore inferior parts, is manifested as accelerated aging.

Besides running a cooler engine by eating less and better food, it may be possible to use exogenous chemistries to improve on repair and maintenance operations of the body. So, what might some of those chemistries be?

MicroRNA.

They represent an analogue of executive files in a computer.

MicroRNA is involved in the expression of 60% of all genes.

Read about them.

Aging is basically a program.

This is proved by the fact that species live on the same locality, whose life span differs by 10–100 times, although they have a similar nutritional structure.

Edited by Kentavr, 04 September 2019 - 09:01 AM.


#1419 eigenber

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Posted 09 September 2019 - 11:32 PM

A quick question: On fission and fusion days should I be leaving off all other supplements?  I ask because I often take leucine before exercise, but leucine is for fusion. Is taking that on fission days likely to be detrimental to the fission process? 



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#1420 Turnbuckle

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Posted 10 September 2019 - 10:49 AM

A quick question: On fission and fusion days should I be leaving off all other supplements?  I ask because I often take leucine before exercise, but leucine is for fusion. Is taking that on fission days likely to be detrimental to the fission process? 

 

 

In this protocol, leucine isn't "for fusion," it's for biogenesis. I've avoided biogenesis during fission/mitophagy as I was concerned that mitochondria with only one mtDNA loop undergoing replication might get labeled as defective and recycled. The goal of the fission part of this protocol is to isolate mtDNA to only one loop per mitochondrion. If that loop is damaged, surface potential (ΔΨm) will drop and its mitochondrion will be labeled for recycling, eliminating that bad actor. And while I expect ΔΨm to drop during biogenesis of a healthy mtDNA in a fission state, I haven't seen any research on that. But the potential to eliminate some of the good along with the bad is likely increased.


Edited by Turnbuckle, 10 September 2019 - 10:50 AM.


#1421 PAMPAGUY

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Posted 11 September 2019 - 05:39 AM

This is a new podcast between Dr. Peter Attia and Dr. David Sinclair.  What is most important for this forum is the NAD/NR/NMN discussion.  There was a radioactive tracer trial that concluded that very little NR got out of the liver when taken orally.  This threw a wrench into all the people taking NR/NMN orally including SInclair.  You need precussors through out your body in other cells, muscle, etc.   Many have gone to sublingual adminstration.  In this Podcast they point out that NR is degraded in the mouth by the bacteria, and microbial action.  There was another trial that showed NR beyond the liver, and in this discussion they concluded that high doses of NR/NMN (1000 mg+) is necessary to get past the liver. (Which is what we do in this forum)

 

Believe that most in this forum including Turnbuckle will appreciate all the info in this Podcast.    https://peterattiamd...davidsinclair2/


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#1422 Turnbuckle

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Posted 11 September 2019 - 07:23 AM

NR is not recommended for this protocol. I don't recommend it at all as I consider it a borderline fraud. Also, there are forums for NR discussions. This is not one of them.



#1423 PAMPAGUY

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Posted 11 September 2019 - 10:22 AM

NR is not recommended for this protocol. I don't recommend it at all as I consider it a borderline fraud. Also, there are forums for NR discussions. This is not one of them.

 

I can understand your feelings.  But some people had wondered how oral N+R got through the liver into the cells and this trial proved that higher doses of NR (1000 mg) can overwhelm the liver and be transporte it to the rest of body.   So it would be common sense that N+R would do it even better at 1000-2000 mg.  Remember that the radioisotope study showed that NR was mostly taken up in the liver, but then they did not use a high dose.  Posting this had nothing to do with NR, it is the mechanism that the body uses to make NAD.  I happen to agree with you that the NR industry is a rip off.


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#1424 Turnbuckle

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Posted 11 September 2019 - 10:46 AM

  So it would be common sense that N+R would do it even better at 1000-2000 mg.  

 

 

There is a limit. The dose recommended here is 2 grams of N + 2 grams of R. I've tried higher levels but found no advantage. Once total fission is achieved, adding more has no apparent effect. 


Edited by Turnbuckle, 11 September 2019 - 10:47 AM.

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#1425 Nate-2004

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Posted 13 September 2019 - 07:24 PM

 

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.

 

 

I'm happy to see glycerol monosterate as an alternative to stearic acid in the protocol. Thanks for sharing.

 

 

What evidence is there for glycerol monostearate inducing fusion similar to stearic acid?

 

Is it because it's just stearic acid reacted with glycerine? Google says monostearate is the same thing.

 

https://www.vintaget... fats and oils.

 

Glyceryl stearate is made by reacting glycerin with stearic acid, a fatty acid obtained from animal and vegetable fats and oils.

 

 


Edited by Nate-2004, 13 September 2019 - 07:36 PM.


#1426 resting

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Posted 16 September 2019 - 12:22 PM

Does the 2000mg (2g)  of  Nicotinamide taken cause a potential over dose situation?

Are there any specific cautions in regard to this relating to blood pressure etc?



#1427 Turnbuckle

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Posted 16 September 2019 - 12:44 PM

Does the 2000mg (2g)  of  Nicotinamide taken cause a potential over dose situation?

Are there any specific cautions in regard to this relating to blood pressure etc?

 

 

No one has noted any negative side effects, and the potential effect on BP is to lower it. However, anyone worried about taking this much can take lower doses to assure themselves of its safety.



#1428 ambivalent

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Posted 19 September 2019 - 05:01 PM

No one has noted any negative side effects, and the potential effect on BP is to lower it. However, anyone worried about taking this much can take lower doses to assure themselves of its safety.

 

I certainly reported problems with histamine at higher doses of NR and with Nicotinamide and I wasn't the only person to record that problem. There is evidence to support it:

 

https://www.research...istamine_levels



#1429 Turnbuckle

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Posted 19 September 2019 - 05:22 PM

I certainly reported problems with histamine at higher doses of NR and with Nicotinamide and I wasn't the only person to record that problem. There is evidence to support it:

 

https://www.research...istamine_levels

 

 

I don't recall your post. How much nicotinamide did you take, and for how long?



#1430 ambivalent

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Posted 19 September 2019 - 05:51 PM

I certainly reported problems with histamine at higher doses of NR and with Nicotinamide and I wasn't the only person to record that problem. There is evidence to support it:

 

https://www.research...istamine_levels

 

 

I also experinced problems with uric acid too, from the Riboside, which you hypothesized, I believe there are issues with Riboside and Hba1c too. 

 

I dosed several grams a day of NR (up to 7 grams for a few weeks) - surfed some impressive highs as well as lows. There was definitely a high dosing effect, which I insisted upon, which contradicted the then present school of thought of a gram being the saturation dose. 

At around that time I went coastal walking in the spring and the seasonal allergies were very bad - any dose of NR or N made things bad and U became extremely sensitive to any dose. That's why I haven't got back on to this protocol yet, but I will as I'm sure I'm ok and now and appear to have addressed the allergy problems. 

 

I experienced remarkable endurance and fatigue, incredible clarity and complementary brain fog (the fog not the clarity with N+R too, though that might have been due to incorrect ratios). I was pretty sure too that I was attaining a more youthful appearance with the high does of NR, until I became ill with the histamine. 

 

The signals were neuropathy and foot pain iifc, which were reported by others, which was likely the uric acid. So yes, you can definitely dose too much - there are quite a lot of claims for Niagen testimonials on amazon of allergic reactions.

 

I wonder if the clarity experienced by others in taking NR is directly due to raised NAD or the increased serotonin reported from the Nicotinamide in the blood.

 

If you want links I'll try another time to dig up posts but it was from spring to fall of 2017 spread across a few threads.



#1431 Turnbuckle

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Posted 19 September 2019 - 07:40 PM

 

 

I dosed several grams a day of NR (up to 7 grams for a few weeks) 

 

 

This is far beyond what I recommend. See the latest protocol where I suggest 2 g/day for 2 days.


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#1432 ambivalent

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Posted 20 September 2019 - 03:06 PM

True, though I experienced problems with much lower doses using your protocol, but that was sensitivity resulting from the excessive NR dosing. But certainly others have experienced problems with lower doses of NR and N. Histamine, uric acid and Hb1AC would be markers to keep an eye on. This was posted a couple of years ago:

 

https://www.ncbi.nlm...pubmed/29033370

 

Thanks for the suggestion, I will get back on this protocol, I am probably planning a heavy fisetin dose at some point, then after that I'll resume. I wonder out of all of this if you have in mind a from scratch treatment for the 70+, one that would be gentler, as most ordinary folk don't hold the experimental-stoicism we all have. I am still pretty cautious, though, of recommending much to anyone at the moment. I'm going with senolytics but even then there is blood-clotting concerns, which I have experienced. Boosting NAD is still well within my parameters, but outside recommending to others, which I assume your protocol would achieve too. It may well be that if you're 75 now, you just need to get to 85 so just coast in rather than take any measures, which increases risk along with as well as probable life-extension. It is certainly a dilemma.

 

 

 

 


Edited by ambivalent, 20 September 2019 - 03:07 PM.


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#1433 zorba990

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Posted 21 September 2019 - 04:31 PM

Hi Turnbuckle, can you please write in more details about this dermaroller with lysine procedure and your results with it?

As for mito protocol, I've got mild results with 1g NAM + 1g Ribose (very very mild I would say). Will try 2g next week. And if 2g will not work will try atomic protocol.


Did you do two days in a row? I recently restarted this 1g of each and that seems to be more effective than a single day. I may try once in the evening and again in the morning as week-ends are the best nap opportunity for me.
I restarted this after experiencing fairly severe post viral fatigue and it seems to be working. I'd say one two-day fission preceeded by an antioxidant holiday has knocked out 50% of it. But it took almost 5 days to recover.
I didn't tune the fusion very well though as I needed to use more stearic acid I think. It was the first time trying Glycerol Stearate so I way under-dosed it (like 500mg 2 x ).

Maybe I will try Mango butter if there is a reliable clean source.

#1434 Turnbuckle

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Posted 21 September 2019 - 09:22 PM

I restarted this after experiencing fairly severe post viral fatigue 

 

If you are suffering from a virus, I suggest you don't use fission. Viruses typically spread by apoptosis, and apoptosis requires fission.

 

https://www.ncbi.nlm...pubmed/10547702

https://www.ncbi.nlm...pubmed/16025099


Edited by Turnbuckle, 21 September 2019 - 09:23 PM.

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#1435 zorba990

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Posted 22 September 2019 - 01:42 AM

If you are suffering from a virus, I suggest you don't use fission. Viruses typically spread by apoptosis, and apoptosis requires fission.

https://www.ncbi.nlm...pubmed/10547702
https://www.ncbi.nlm...pubmed/16025099


Thanks. I don't believe the virus is active anymore as this was many months ago. However after having flu like symptoms for approx a month I never seems to fully recover my energy.
Cough and other immediate symptoms abated but I've been dragging for a while.
So my thought was this is post viral fatigue and studies like this made me decide to try and see if I can cleanup any bad mitochondria damaged by the virus.
https://www.ncbi.nlm.../pubmed/1792865
https://journals.plo...al.pone.0186802

I suppose that I may be reactivating the virus, but I do see that niacinamide has anti viral activity:
https://www.ncbi.nlm...pubmed/19382275
so perhaps that covers that angle

#1436 BRIGHT

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Posted 22 September 2019 - 08:01 AM

Did you do two days in a row? I recently restarted this 1g of each and that seems to be more effective than a single day. I may try once in the evening and again in the morning as week-ends are the best nap opportunity for me.
I restarted this after experiencing fairly severe post viral fatigue and it seems to be working. I'd say one two-day fission preceeded by an antioxidant holiday has knocked out 50% of it. But it took almost 5 days to recover.
I didn't tune the fusion very well though as I needed to use more stearic acid I think. It was the first time trying Glycerol Stearate so I way under-dosed it (like 500mg 2 x ).

Maybe I will try Mango butter if there is a reliable clean source.

 

Yep, 1g 2 days in a row, just like the protocol suggested. After that I've tried 2g and got severe fever. I tend to think it was just an unlucky sequence of events. I was already infected before I started to weaken my immune system even more with 2g Niacinimide. So be cautious!


Edited by BRIGHT, 22 September 2019 - 08:03 AM.


#1437 Kentavr

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Posted 22 September 2019 - 08:18 AM

Thanks. I don't believe the virus is active anymore as this was many months ago. However after having flu like symptoms for approx a month I never seems to fully recover my energy.
Cough and other immediate symptoms abated but I've been dragging for a while.
So my thought was this is post viral fatigue and studies like this made me decide to try and see if I can cleanup any bad mitochondria damaged by the virus.
https://www.ncbi.nlm.../pubmed/1792865
https://journals.plo...al.pone.0186802

I suppose that I may be reactivating the virus, but I do see that niacinamide has anti viral activity:
https://www.ncbi.nlm...pubmed/19382275
so perhaps that covers that angle


If the virus is already in the cells, then fungi can help (shiitake, maitaki, etc.). It is necessary to take a mixture of mushrooms. Treatment for at least 3-6 months, while there is a very strong cleansing of the body from various viruses.

It is very important: you need to finish the treatment smoothly, gradually reducing the dose over 1-2 weeks. It is important at this time to simultaneously raise their own immunity. Otherwise, the immune system, accustomed to the fact that many princesses perform substances in mushrooms for it, will be seriously attacked by any harmless virus, and you can get sick from any infection for another six months.
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#1438 QuestforLife

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Posted 27 September 2019 - 03:40 PM

At around that time I went coastal walking in the spring and the seasonal allergies were very bad - any dose of NR or N made things bad and U became extremely sensitive to any dose.


You know this is a under methylation issue due to your body detoxifying all the nicotinamide, right?
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#1439 Turnbuckle

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Posted 27 September 2019 - 05:07 PM

You know this is a under methylation issue due to your body detoxifying all the nicotinamide, right?

 

 

This is an interesting point, and it begs the question about the addition and timing of methyl donors. If one is seeking fission, then boosting NAD+ should be the goal, but for energy, ATP would the goal, or you could do both sequentially by taking a methylation promoter some hours after N+R --

 

Nicotinamide methylation and its relation to NAD synthesis in rat liver tissue culture. Biochemical basis for the physiological activities of 1-methylnicotinamide.
 
The mode of [14C]nicotinamide conversion to NAD and 1-methylnicotinamide and the effects of exogenous 1-methylnicotinamide on this metabolic conversion were studied using rat liver slices incubated in a chemically defined culture medium. It was shown that at the physiological nicotinamide concentrations tested (11-500 microM), 1-methylnicotinamide is preferentially produced, rather than NAD. Upon increasing nicotinamide concentration to the levels that cause cytotoxicity (1-10 mM and higher), the rate of NAD synthesis dramatically increased and reached a level 6-fold higher than that of 1-methylnicotinamide. A dose-dependent inhibition (up to 60%) of NAD synthesis was seen by the exogenous addition of 1-methylnicotinamide; the degree of inhibition is affected also by the concentration of nicotinamide present as a precursor. A large depletion of intracellular ATP, associated with a marked accumulation of NAD, occurred in slices in response to the addition of high amounts of nicotinamide. However, the loss of ATP was overcome, when nicotinamide was given together with 1-methylnicotinamide. Finally, 1-methylnicotinamide per se was proven active in regulating cell growth by comparing the cytosolic activity of 1-methylnicotinamide oxidation of cultured RLC cells with that of rat liver. Thus, the previously observed growth stimulation of hepatic cells by 1-methylnicotinamide can reasonably been explained by its ATP-sparing effect due to the inhibition of NAD synthesis, a reaction which requires ATP.

 


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#1440 ambivalent

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Posted 02 October 2019 - 01:00 PM

@Quest Sorry for not replying earlier. I had read of methylation issues when taking NR, perhaps a year ago. I had suspected I was under methylated, nicotinamide certainly increased brain fog, severely at times, which in retrospect was probably due to methylation. I hadn't known of the connection to methylation and allergic reactions as you suggest; seasonal allergies were long standing, though dispelled during the fasting years, but returned while taking NR.

 

 







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

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