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Manipulating mitochondrial dynamics

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

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#1801 mike20g

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Posted 26 February 2021 - 03:10 PM

 

 

 The reality is that boosting endurance with any sort of intervention -except of course specific exercise regimens- is extremely hard. If only you guys saw how little benefit such famous doping substances as EPO or cortisol provide, you'd be shocked (strength output BTW is a little different and can be elevated relatively more easily in the short term -albeit the results will likely not be long-lasting).

 

A healthy criticism is good and since the post by sub7 is addressed specifically to Turnbuckle I will limit my post to the quoted sentence. When I first tried NMN without any other changes to my regular activities, absolutely no exercise regimens for me, I saw a significant difference in boosting endurance and many other factors. This boost stayed permanent so far for a couple of years already. This was replicated with my older relatives too. 


Edited by mike20g, 26 February 2021 - 03:21 PM.


#1802 yz69

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Posted 26 February 2021 - 03:34 PM

Boosting endurance for athletes is totally different from boosting endurance for a regular, sub-healthy guy. I have tried Turnbuckle's protocol last year and saw my best swimming results in 10 years: >3 minute reduction in 1000yards.


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#1803 mike20g

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Posted 26 February 2021 - 03:37 PM

Boosting endurance for athletes is totally different from boosting endurance for a regular, sub-healthy guy. I have tried Turnbuckle's protocol last year and saw my best swimming results in 10 years: >3 minute reduction in 1000yards.

 

Who says regular guy is sub-healthy? Who says professional athletes are healthy and generally enjoy longer life span? And how is your sentence relevant to sub7's argument or my comment? 


Edited by mike20g, 26 February 2021 - 03:49 PM.


#1804 sub7

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Posted 26 February 2021 - 06:07 PM

A healthy criticism is good and since the post by sub7 is addressed specifically to Turnbuckle I will limit my post to the quoted sentence. When I first tried NMN without any other changes to my regular activities, absolutely no exercise regimens for me, I saw a significant difference in boosting endurance and many other factors. This boost stayed permanent so far for a couple of years already. This was replicated with my older relatives too. 

 

Thanks a lot for the kind words and for sharing your personal results Mike. 
I am not going to let this thread get derailed by belaboring this point, but your comment makes for a perfect example for why I am skeptical. Allow me to make one last post on this (and retain the option to maybe respond to what will come after this as my final commentary on this sub-topic) and move on.

This boost stayed permanent so far for a couple of years already. 

 

I am absolutely not saying you are making this up; very hard to think of a realistic motivation for making up something like this. But you all please understand where I am coming from. I am unaware of a single substance on earth which is capable of such a feat. Can you or anyone else point to a single substance on earth -natural or synthetic, legal or illegal- that has been documented to do something like this; a substance that will boost endurance such that the said improvement will last for "couple of years" after cessation of treatment with the said substance?

 

Maybe there are other substances that can accomplish something like this, but as someone who is very well-read in the field of performance enhancing substances, I have never come across or even heard or of something like this. 


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#1805 userCK

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Posted 26 February 2021 - 07:28 PM

@sub7 my understanding of the results is not that it enhanced performance or gives you some superhuman boost. It simply returns part of your mitochondrial population to a more youthful state. So, overall, you re-gain some of your original levels of energy; you don't gain any more than what you were originally born with. This is not some magic serum from Marvel or DC movies.

 



#1806 mike20g

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Posted 26 February 2021 - 08:57 PM

I agree with userCK.

 

sub7 - I agree with you, don't want to derail this thread, which seems to be successful in making people feel better. I am actually going to try new protocol soon, albeit at very slow pace. As for published results I saw original study on mice (not humans) using NMN. From my memory within 2 weeks old mice was as energetic as young mice and then after 2 weeks mice were "opened" by anatomic pathologists who could not tell a difference between old and young mice. This would suggest fast acting booster that is "permanent", a published study although not on humans. Curious to see human studies without "opening" part of course :)

 

I respect your point of view and myself wonder what exactly helped people who tried mito protocol if it is not what Turnbuckle thinks, but so far I cannot find another explanation.. 



#1807 userCK

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Posted 26 February 2021 - 09:09 PM

@Mike20g - when you say NMN, Did you mean just taking NMN or NR daily or did you mean one of the previous versions of this protocol? What dose/duration?

 


Edited by userCK, 26 February 2021 - 09:11 PM.


#1808 stephen_b

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Posted 26 February 2021 - 10:53 PM

This a a very large number of cycles. Have you noticed any significant anti-aging / rejuvenation effects that you believe will be relatively long lasting -ı.e. effects that appear likely to continue at least for a while, even if you were to do no more cycles from here on?

 

 

There are confounding factors in my case. I'm a year into picking up running again and 2 years post hip resurfacing (I'm 57). After the surgery I had to take a year off, and fitness suffered.

 

I also may have had covid last year, and my baseline running performance went way down. At times during a 3-6 mile run I had to take walking breaks. I felt that I made a lot of improvements then when I started with the original mitochondrial protocol on 2020-07-02. I finished round 15 around 2020-10-18. I was able to go on runs without walk breaks, and my pace improved. I did not get back to my post-surgery fitness level (3:36 marathoner), but that was the work of years of training.

 

I did 8 stem cell rounds after that starting 2020-10-13 and ending on 2021-01-14 before restarting with the new mitochondria protocol on 2021-02-21.

 

I'm trying to keep a good supplement diary the entire time, but is still hard to draw firm conclusions. I just did finished cycle 4 of the new protocol, doing fusion last night before bed. I had a relaxed 11.2 mile run this afternoon, So I feel I'm seeing progress.


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#1809 Kimer Med

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Posted 27 February 2021 - 12:07 AM

I decided to work my way up to the new protocol, and thought others might be interested in a few early results. I don't actually have all of the supplements needed yet, so I'm doing a slight variant, but still seeing measurable changes.

 

I'm doing the suggested Mito 1: PQQ, AKG, D-Ribose, NAM. I've also been including Jiaogulan, since I have some and don't want it to go to waste.

For Mito 2: PQQ, AKG, Sulforaphane, liposomal Melatonin, and 20 gr dark chocolate for a little stearic acid and epicatechin.

Dosing for both has been right before sleep, with strength measurement shortly after waking.

 

I've only done 4 cycles so far. I wasn't able to include AKG until the 3rd cycle. Glycerol Monostearate is on order.

 

So far, the main result I can report is that when measured in terms of weight lifting reps to failure, I have about a 40% decrease in strength on Mito 1 / fission days compared to Mito 2 / fusion days. The trend in both modes has been pretty flat; I haven't seen any significant changes yet in either mode. However, the difference in strength is substantial and repeatable.

 

I included a Methyl-B12 injection on two of the fusion days. I was concerned at first that the added methyl group availability might interfere, but at least in terms of reps, it hasn't.

 

I also added red + NIR light therapy on one fusion day. No measurable difference, but I plan on regularly including it anyway, for other reasons.

 


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#1810 userCK

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Posted 27 February 2021 - 11:09 AM

Thanks @ Kimer Med. I've also started the protocol but slightly modified it.

 

Mito 1 (Fission day):

Time 00:00 -

  • AAKG 4800 mg (1200mgx4 caps). This would yield about 1 gram of AKG.

Time: 01:00

  • 1.5 grams of Thorne Nicianmide (500mg x 3 caps)
  • 1.5 grams of  Jarrow D-Ribose ( 1 tablet and other half tablet, Berry flavor)

Time: 01:10:

  • Jarrow BioPQQ 30mg (10mg x 3)

I took this last night before going to bed. Woke-up and did 20 push-ups (which is what I normally do).

 

Tonight, I'll do Fusion and my plan is:

 

Mito 2 (Fusion Day):

 

Time 00:00 -

  • AAKG 4800 mg (1200mgx4 caps). This should yield about 1 gram of AKG.

Time: 01:00

  • 1 teaspoon of GMS powder (Bulk Powders Glycerol MonoStearate). This should be 2-3 grams

Time: 01:10:

  • Jarrow BioPQQ 30mg (10mg x 3)

 

 



#1811 PAMPAGUY

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Posted 27 February 2021 - 03:40 PM

 

Thanks @ Kimer Med. I've also started the protocol but slightly modified it.

 

Mito 1 (Fission day):

Time 00:00 -

  • AAKG 4800 mg (1200mgx4 caps). This would yield about 1 gram of AKG.

Time: 01:00

  • 1.5 grams of Thorne Nicianmide (500mg x 3 caps)
  • 1.5 grams of  Jarrow D-Ribose ( 1 tablet and other half tablet, Berry flavor)

Time: 01:10:

  • Jarrow BioPQQ 30mg (10mg x 3)

I took this last night before going to bed. Woke-up and did 20 push-ups (which is what I normally do).

 

Tonight, I'll do Fusion and my plan is:

 

Mito 2 (Fusion Day):

 

Time 00:00 -

  • AAKG 4800 mg (1200mgx4 caps). This should yield about 1 gram of AKG.

Time: 01:00

  • 1 teaspoon of GMS powder (Bulk Powders Glycerol MonoStearate). This should be 2-3 grams

Time: 01:10:

  • Jarrow BioPQQ 30mg (10mg x 3)

 

How did you determine that 5 gms AAKG = 1 gms AKG?  Also, why do 30mg PQQ instead of 20mg as recommended?  Thanks



#1812 Ken Mark

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Posted 27 February 2021 - 03:53 PM

I just though I would note interesting changes that may be associated with the protocol.

I'm 55 and I came across this protocol last year and did 25 cycles then and after a break another 15 cycles this year. I had to start the protocol on low dosages otherwise I felt wiped out and have only been able to reach the full dosages of N + M for the last 10 cycles.

Over the last month I've noticed a number of the grey hairs on my head and chest are brown near the root and grey at the tip. The brown sections are 3-5cms long and the remainder of the hair is grey.

I haven't changed my diet significantly in the last few years. For exercise, I mainly do short runs a few times a week and two HIT on bike or rebounder plus some static holds/planks. Over the last year I have lost abdomen mass, 82 kg -> 78kg, but while I am in good shape i don't necessarily associate that with the protocol.


Has the grey hair turning black trend continuing for you? This is true rejuvenation IMO. Not many things can do that, except perhaps niacin (the one that causes flush). I think Turnbuckle once said he hasn't come across anything that can turn grey hair black. His protocol is going beyond his expectations.

Were you taking Niacin or Niacinamide as N in your N + R?

What about other health markers if you're keeping track?

Josh Mitteldorf in his "ageing matters" blog's latest post has mentioned something like : most epigenetic markers of aging (methylation) are related to mitochondria.

#1813 userCK

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Posted 27 February 2021 - 05:00 PM

How did you determine that 5 gms AAKG = 1 gms AKG?  Also, why do 30mg PQQ instead of 20mg as recommended?  Thanks

Turnbuckle mentioned it at some point that you'd have to take 4x because of higher molecular weight. But also on the bottle of AAKG capsules, it says about 845 mg of AKG in 3600mg of AAKG. Rest is Arginine

 

PQQ 30mg just in case PQQ is under-dosed. I took extra of every ingredient (1.5 grams of Niacinmide, 1.5g of D-Ribose too) because these supplements are not FDA tested/regulated so they can be under or over dosed. So, to account for under-dosing, I took some extra.


Edited by userCK, 27 February 2021 - 05:02 PM.


#1814 mike20g

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Posted 27 February 2021 - 05:40 PM

@Mike20g - when you say NMN, Did you mean just taking NMN or NR daily or did you mean one of the previous versions of this protocol? What dose/duration?

 

Not related to the protocol, which I have never done before. In the past I was looking for cure of hypothyroidism for my relative and chose several herbs from traditional chinese medicine - official western medicine considers hypothyroidism uncurable as of now. Hypothyroidism is likely relevant to problems with mitochondria. The process of healing is usually long with TCM, but when NMN was added the process went faster. I was impressed with the results so I tried this myself omitting some of the herbs. I took it slow and used low NMN dosage first two weeks 125 mg , then doubling it to 250mg. I generally try not to take supplements longer than 1 month. As I shared the results for me were visible within 1-2 weeks and they stayed for over 2 years now. I am going to try mito protocol, the latest one and will report how it went. I am very optimistic as it includes AKG, which I believe would have been useful for me anyway.


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#1815 aribadabar

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Posted 27 February 2021 - 11:02 PM

Mito1 (fission)

● NAM+R, 1 g of each

● AKG, 1 g

● PQQ, 20 mg

 

I have a few questions:

 

What was the rationale for having PQQ on fission days?

 

Isn't having PQQ saving somewhat defective mitochondria that would otherwise be tagged for removal during fission?

 

Shouldn't mito biogenesis boosters be reserved for predominantly fusion periods i.e. Mito 2 days? If not, why not?

 

Thanks!


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#1816 Phoebus

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Posted 28 February 2021 - 12:31 AM

I am surprised there is no mention of carnitine in this protocol at all. 

 

Carnitine ushers vital nutrients into the mitochondria. Usually long chain fatty acids, in this case the stearic acid. 

 

 

 

 Fatty acids are transported via carnitine into mitochondria for their subsequent oxidation to generate ATP. Carnitines also remove the acyl groups from the mitochondria as acylcarnitines. Increase in free fatty acid levels can induce mitochondrial dysfunction resulting in cell death and/or enhanced secondary generation of reactive oxygen species. These effects can be attenuated with L-carnitine treatment [22]. In addition, L-carnitine can suppress the palmitoyl-CoA induced dysfunction, membrane permeability transition (MPT), and cytochrome c release of isolated mitochondria as well as reduce the mitochondrial swelling and depolarization induced by long chain fatty acids (LCFAs) and palmitoyl-CoA through a protective mechanism thought to occur in and around the mitochondrial membrane [23]. L-carnitine also suppresses oleic acid-mediated MPT by accelerating β-oxidation [24]. Studies have also shown that carnitine has a protective effect both on mitochondria and in whole cells by inhibiting free fatty acid-induced mitochondrial membrane damage and/or its secondary effects [23,25]. The protective effects of carnitine and related metabolites have been postulated to be due to improved energy metabolism and the inhibition of electron leakage from mitochondrial electron transport systems [26]. Administration of carnitine has also been shown to decrease free fatty acids in serum and tissues and prevent tissue injury in juvenile visceral steatosis (JVS) mice that lack a carnitine transporter [27]. 

 

:text=Fatty%20acids%20are%20transported%20via,subsequent%20oxidation%20to%20generate%20ATP.&text=Studies%20have%20also%20shown%20that,effects%20%5B23%2C25%5D' class='bbc_url' title='External link' rel='nofollow external'>https://www.ncbi.nlm...effects [23,25].

 

If you do take carnitine, be sure to take at least 2 grams or more at a time. And it MUST be taken with 30 - 40 grams carbs, simple carbs work better in fact. This is due to insulin being the mechanism that suffuses the carnitine into the muscle and nerve cells. Without an insulin spike, taking carnitine is nearly pointless. 

 

ACL is a good version of carnitine, but  propionyl carnitine (glycine free version) may actually be the best and most absorbable form. 


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#1817 Turnbuckle

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Posted 28 February 2021 - 09:38 AM

I am surprised there is no mention of carnitine in this protocol at all. 

 

There are many things that help mitochondrial function, but are not useful here. The object of this protocol is not to coddle mitochondria, but to expose mutated and methylated mtDNA and get rid of them by a combination of mitophagy and demethylation. It's a boot camp for mitochondria, not a nursing home. See post 1739 for details.


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#1818 mike20g

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Posted 28 February 2021 - 12:36 PM

I see new protocol was used in the evening before bedtime. What is the rational? This may help with high blood pressure if this is a concern, anything else beyond that?

#1819 sub7

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Posted 28 February 2021 - 01:26 PM

As far as I can see there is not a single and generally acknowledged method of observing mitochondrial rejuvenation. People are trying to assess the state of their mitochondria -and if the mitochondria quality has improved- through such things as exercise performance or cognitive acuity. These are all good, but this research is interesting and can be extremely relevant. 

 

It could be that by measuring Color Contrast Sensitivity, we could get a fairly good idea about how well the protocol is working.

 

The research can be found here
https://www.ajmc.com...mprove-eyesight

 

Basically, the reduction in eyesight that accompanies aging is, according to the authors of this paper, largely attributed to reduced mitochondrial output. Simply increasing mitochondrial energy production resulted in easily observable changes.

 

I am therefore speculating that doing Color Contrast Sensitivity tests on oneself before and after applying the Turnbuckle Protocol can give a good idea about how well the protocol is working (just to clarify, I am not suggesting the use of red light therapy as an added dimension to Turnbuckle's Protocol.... I am merely suggesting using the same test technique as was used in this study). A short quote from the link above.

 

To assess CCS, the researchers measured color contrast thresholds across the protan (red visual axis) and tritan (blue visual axis) axes both prior to and after 670-nm exposure. To test rod thresholds, subjects had their pupils dilated and dark adapted for 40 minutes. Investigators used the Medmont dark-adapted chromatic perimeter to measure retinal sensitivities.
 
At baseline, individuals older than 40 exhibited signs of visual function decline. Specifically, “in the tritan axis, baseline color contrast sensitivity increased significantly over about 40 years compared to younger subjects by [a] maximum of 47% and an average of around 20% (P ≤.0001).”

 


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#1820 PAMPAGUY

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Posted 28 February 2021 - 01:42 PM

I see new protocol was used in the evening before bedtime. What is the rational? This may help with high blood pressure if this is a concern, anything else beyond that?

I cannot speak for others, but doing it 1 hour before bed has really helped me.  Fission always knocked me for a loop.  I felt tired and washed out for the rest of day when taking it in morning.  I sleep better at night and feel better next day.  Just started new protocol, but so far it is working great at night.


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#1821 userCK

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Posted 28 February 2021 - 05:00 PM

@Turnbuckle, I'm probably being paranoid but I saw in a study they analyzed composition of fatty acids in a Chicken. 

"The current study aims to determine the composition in fatty acids of 5 native chicken ecotypes of Benin reared under organic or conventional system. It appears that the predominant Fatty Acids (FA) in chicken meat of all treatments were palmitic and stearic (18:0) acids as Saturated Fatty Acid (SFA), oleic acid as Monounsaturated Fatty Acids (MUFA), Conjugated Linoleic Acid"

 

- Does this mean eating chicken or meat in general has been interfering with the protocol (fission days)?

 

 



#1822 Turnbuckle

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Posted 28 February 2021 - 09:40 PM

@Turnbuckle, I'm probably being paranoid but I saw in a study they analyzed composition of fatty acids in a Chicken. 

"The current study aims to determine the composition in fatty acids of 5 native chicken ecotypes of Benin reared under organic or conventional system. It appears that the predominant Fatty Acids (FA) in chicken meat of all treatments were palmitic and stearic (18:0) acids as Saturated Fatty Acid (SFA), oleic acid as Monounsaturated Fatty Acids (MUFA), Conjugated Linoleic Acid"

 

- Does this mean eating chicken or meat in general has been interfering with the protocol (fission days)?

 

 

Meats don't have that much unless you really pig out. Items like cheese, milk chocolate and sweet chocolate have far more. See Table 2 of this article.


Edited by Turnbuckle, 28 February 2021 - 09:42 PM.

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#1823 userCK

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Posted 01 March 2021 - 01:39 PM

Meats don't have that much unless you really pig out. Items like cheese, milk chocolate and sweet chocolate have far more. See Table 2 of this article.

Thanks! Yeah, I'm on Keto diet and so I've easily been eating 500 gram of fatty cut of meats (chicken, beef) for dinner.  Looks like 500g of chicken has 1.5gram of stearic acid, and 500gram of beef has 5grams of stearic acid. Enough to override fission, it seems! Going forward, I'm just gonna fast on fission days! Plus a tablespoon of coconut oil seems to be adding another 0.2 grams of stearic acid.



#1824 Turnbuckle

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Posted 01 March 2021 - 01:47 PM

Thanks! Yeah, I'm on Keto diet and so I've easily been eating 500 gram of fatty cut of meats (chicken, beef) for dinner.  Looks like 500g of chicken has 1.5gram of stearic acid, and 500gram of beef has 5grams of stearic acid. Enough to override fission, it seems! Going forward, I'm just gonna fast on fission days! Plus a tablespoon of coconut oil seems to be adding another 0.2 grams of stearic acid.

 

 

That is an unrecognized downside of keto diets, that a constant high intake of stearic acid will suppress fission and mito QC.


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#1825 pamojja

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Posted 01 March 2021 - 02:54 PM

Mito1 (fission)
● NAM+R, 1 g of each
● AKG, 1 g
● PQQ, 20 mg

Mito2 (fusion)
● GMS, 1 g
● AKG, 1 g
● PQQ, 20 mg

NAM+R (nicotinamide plus ribose) is a fission promoter, GMS (glycerol monostearate) is a fusion promoter, AKG (alpha-ketoglutarate) is a demethylase promoter, and PQQ is a biogenesis promoter. All of these are fast acting.

That is an unrecognized downside of keto diets, that a constant high intake of stearic acid will suppress fission and mito QC.

So what that means to those of us not intent on doing this protocol? - But following a low-carb diet for prediabetes control, take high dose niacin against Lp(a), additional to Ribbose for energy, AKG from AAKG and OAKK, and PQQ?

Would the high NA+R promoting fission just cancel out the high stearic acid's fussion? Or would the body not self-regulate for allowing both to happen to a certain extent?


edit: only a theoretical question to me, since my comprehensive supplementation and life-style changes already gave me remission from a walking-disability (from a 80% stenosis at my abdominal aorta), COPD1 and ME/CFS symptoms.

Edited by pamojja, 01 March 2021 - 03:01 PM.


#1826 Andey

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Posted 02 March 2021 - 07:29 AM

That is an unrecognized downside of keto diets, that a constant high intake of stearic acid will suppress fission and mito QC.

 

I recall you cited a paper that both fission and fusion are upregulated during keto.

I think about it as highly physiologic state as stearic acid only signals that mitochondria should be primed for fatty oxidation.

If one is skipping morning meals or exercise fasted than it will be triggered even without external stearic acid supply because majority of energy will come from fatty oxidation(unless somebody is completely metabolically deranged and burn trough glycogen during such conditions).

I personally use sulforaphane for fusion as it supposedly provides supraphysiologic levels of fusion,

and for fission I often add some honey(without any other food) so I am  burning carbohydrates for at least 2 hours while NAM works. But TBH I feel the same when I take NAM alone, NAM+R, NAM+R+honey. If I were to guess I think NAM is working regardless as its a quite a distinct feeling when I take it.



#1827 Turnbuckle

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Posted 02 March 2021 - 10:32 AM

I recall you cited a paper that both fission and fusion are upregulated during keto.

 

 

I might have, but I don't recall it.  A cursory search shows papers going every which way, and I expect the results will depend on what animals are used and the actual diet. One paper, for instance, says --

 

The ketogenic diet prevented mitochondrial fission and improved mitochondrial function in the myocardium of db/db mice.

http://www.agingandd...6011531-1.shtml

 

 

Db/db mice are a type II diabetes model, and the triglycerides in the diet weren't specified.

 

A few have found stearic acid a benefit as it promotes fusion and lowers ROS. But I haven't found one that worries about the long term effect on mito QC, which depends on fission. Bottom line, the build up of defective mitochondria isn't much concern for us -- given that we're getting rid of it -- except for the point userCK raised, that a diet high in stearic acid might interfere with the fission half of the protocol.


Edited by Turnbuckle, 02 March 2021 - 10:42 AM.

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#1828 mike20g

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Posted 03 March 2021 - 07:37 PM

I did new protocol day1+day2. This is my first experience. Day 1 - I took dosage in am, used liquid akg, powder n+r (tastes terrible), pqq caps. I took roughly half dosage specified in protocol. I did symbolocal workouts, should not really use word workout. Day 1 T+0 hours, immediately felt something, not pleasant and not bad feeling. Just felt something started happening. T+6-7 hours I started feeling somewhat bad, likely blood pressure although I don't typically have problems with this. It felt like my heart was squeezed and every breath made it squeeze more. I did lose some energy. I felt better on day 2. However heart squeeze feeling continued until I finally decided to use valerian root. Within 30 minutes or so I felt much better, heart squeeze was almost gone. Interestingly I did not experience desire to sleep after valerian root, which is typical for it. Instead I realized that my mind started working very clearly without efforts, generally I felt I had energy and desire to do a lot of things... I plan to wait until my heart squeeze feeling is completely gone before repeating cycle. For the future I would like to get aakg in capsule form instead of liquid akg and capsule forms of all the other ingredients.
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#1829 Advocatus Diaboli

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Posted 03 March 2021 - 07:45 PM

re: post #1828

 

mike20g, what brand of liquid akg did you use?



#1830 mike20g

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Posted 03 March 2021 - 07:49 PM

Same as Turnbuckle. Simpleasa or something





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

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