2284 replies to this topic

[Turnbuckle]

Thanks for the quick respons. Maybe i should reconsider taking NR and NMN... they are quite expensive...

after you cleaned all your mitochondria did you stop with all of these type of supplements?

 

 

No. I still use N+R after each SC/fusion cycle. See this post. The purpose, however, is to encourage apoptosis of senescent cells and subsequent replacement. Fission is necessary for apoptosis.

[Helios]

Found a podcast episode of guy that have "created" training approach that could be based on this thread or just the same research.

 

 

Craig Marker: Fission & Fusion Training

 

 

 

 

Could maybe alternating fission and fusion be good for better athleticism or maybe Fission/fusion target training could further boost the effects of this protocol.

 

This study that supports the notion that exercise can effect mitochondrial dynamics.

 

https://pubmed.ncbi....h.gov/30408342/

 

Exercise training remodels human skeletal muscle mitochondrial fission and fusion machinery towards a pro-elongation phenotype

 

[smithx]

Is this still current thinking?

 

Supplements for fission: These are NAD+ precursors, and appear to be effective in this sequence: niacin < nicotinamide < NR < (nicotinamide + ribose)

Supplement for fusion: C18:0 — stearic acid.

 

In other words, one day with NMN supplements and the next 2 with a couple bars of 100% chocolate (which is mainy stearic acid) would do it?

 

Alternate every 3 days?

 

What is the minimal protocol that would work if not that one?

 

 

 

 

[Turnbuckle]

Is this still current thinking?

 

 

 

 

No. The current thinking is here.

[stephen_b]

No. The current thinking is here.

 

One thing I'm wondering about is that runners, as I've noticed in my own case, have gains over long timeframes. For example, marathon times fall and plateau for a person starting out with the event over 5 years or so. I wonder what is happening at the mitochondrial level there.

[smithx]

Thanks Turnbuckle. So current thinking is:

 

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

 

But what's your estimation of the effectiveness of this as an alternative, using things I already take?

 

Day 1

• NMN sublingual - 1g
• calcium-AKG - 1g
• PQQ - 20mg

 

Day 2

• 30gm 100% chocolate containing about 16gm 18:0 stearic acid (or could do 60gm if that's better)
• calcium-AKG - 1g
• PQQ - 20mg

 

 

 

Edited by smithx, 15 April 2022 - 11:16 PM.

[smithx]

By the way, some good things about dietary stearic acid (and by extension, probably good things about chocolate):

https://www.ncbi.nlm...les/PMC4164353/

 

Stearic acid (C18:0) is a long chain dietary saturated fatty acid that has been shown to reduce metastatic tumor burden. Based on preliminary observations and the growing evidence that visceral fat is related to metastasis and decreased survival, we hypothesized that dietary stearic acid may reduce visceral fat. Athymic nude mice, which are used in models of human breast cancer metastasis, were fed a stearic acid, linoleic acid (safflower oil), or oleic acid (corn oil) enriched diet or a low fat diet ad libitum. Total body weight did not differ significantly between dietary groups over the course of the experiment. However visceral fat was reduced by ∼70% in the stearic acid fed group compared to other diets. In contrast total body fat was only slightly reduced in the stearic acid diet fed mice when measured by dual-energy x-ray absorptiometry and quantitative magnetic resonance. Lean body mass was increased in the stearic acid fed group compared to all other groups by dual-energy x-ray absorptiometry. Dietary stearic acid significantly reduced serum glucose compared to all other diets and increased monocyte chemotactic protein-1 (MCP-1) compared to the low fat control. The low fat control diet had increased serum leptin compared to all other diets. To investigate possible mechanisms whereby stearic acid reduced visceral fat we used 3T3L1 fibroblasts/preadipocytes. Stearic acid had no direct effects on the process of differentiation or on the viability of mature adipocytes. However, unlike oleic acid and linoleic acid, stearic acid caused increased apoptosis (programmed cell death) and cytotoxicity in preadipocytes. The apoptosis was, at least in part, due to increased caspase-3 activity and was associated with decreased cellular inhibitor of apoptosis protein-2 (cIAP2) and increased Bax gene expression. In conclusion, dietary stearic acid leads to dramatically reduced visceral fat likely by causing the apoptosis of preadipocytes.

 

 

[anon2099]

 

Thanks Turnbuckle. So current thinking is:

 

 

But what's your estimation of the effectiveness of this as an alternative, using things I already take?

 

Day 1

• NMN sublingual - 1g
• calcium-AKG - 1g
• PQQ - 20mg

 

Day 2

• 30gm 100% chocolate containing about 16gm 18:0 stearic acid (or could do 60gm if that's better)
• calcium-AKG - 1g
• PQQ - 20mg

 

 

NMN, CAKG and chocolate are slower acting compared to N+R, AKG and GMS so you may need to adjust timing.

[PAMPAGUY]

I have been on the protocol for 30 days now and have more energy which I am very happy for at almost 76 yo of age. My bicep curls are still increasing.  Will start C60 stem cell renewal after this.   I have 2 questions for Turnbuckle or anyone else.

 

1.  I was sent 80 mg capsules of PQQ by accident from a supplier instead of 20 mg which I ordered.  I was told to keep the 80 mg., and was credited back on my CC.  How will taking 80 mg PQQ vs 20 mg affect my protocol?

 

2.  Does NAM and Riboside have a specific shelf life?

 

Thanks for a wonderful and helpful blog this is.

[Turnbuckle]

I have been on the protocol for 30 days now and have more energy which I am very happy for at almost 76 yo of age. My bicep curls are still increasing.  Will start C60 stem cell renewal after this.   I have 2 questions for Turnbuckle or anyone else.

 

1.  I was sent 80 mg capsules of PQQ by accident from a supplier instead of 20 mg which I ordered.  I was told to keep the 80 mg., and was credited back on my CC.  How will taking 80 mg PQQ vs 20 mg affect my protocol?

 

2.  Does NAM and Riboside have a specific shelf life?

 

Thanks for a wonderful and helpful blog this is.

 

1. I expect it won't make any difference. But if you see a difference, let us know.

 

2. NAM and ribose are very stable if you keep them dry. I expect them to last many years. If you are referring to nicotinamide riboside, I don't recommend it because of the delay. It requires digestion before it can be absorbed.

Edited by Turnbuckle, 27 May 2022 - 10:37 AM.

[PAMPAGUY]

1. I expect it won't make any difference. But if you see a difference, let us know.

 

2. NAM and ribose are very stable if you keep them dry. I expect them to last many years. If you are referring to nicotinamide riboside, I don't recommend it because of the delay. It requires digestion before it can be absorbed.

No, I have NAM and riboside not NR. Thanks for the response.  Will keep you informed on the 80 mg. PQQ.

 

Thanks

[teniffog]

Thanks for the updated information, Turnbuckle. You are a wealth of knowledge. Any sourcing suggestions for the powder? I want to make sure I get it from a reputable supplier. Also, do you still take C60?

 

Thanks

An updated Mito protocol

 

The previous protocol can be found at post #1366

 

 

Background:

 

Previously I posted methods of cycling mitochondrial morphology to clean up defective mtDNA, which eliminated mutations via the PINK1/Parkin QC process. The normal QC process can detect mutated mtDNA genes during fission as all mito genes are critical and thus the mito membrane potential goes to zero if just one is defective. Greatly magnifying fission and fusion with supplements will aid that process. But there is another source of mitochondrial damage that isn’t so easily eliminated — epigenetic damage. Like nDNA, mtDNA also picks up aberrant methylation with age. This methylation degrades ATP production, but the QC process doesn’t catch it unless the problem is addressed at a critical time, like during biogenesis. If a mitochondrion with one loop of methylated mtDNA runs out of enzymes while involved with replication, then membrane potential may dip to zero and it will get labeled for recycling. Thanks to methylation, it won’t have as much enzyme reserves as other mitochondria, so it will be preferentially targeted. Also, biogenesis is the best time to demethylate mtDNA as methyltransferase can’t operate while there is only one strand.

 

Until recently, mtDNA wasn’t even known to have methylation, and researchers are still confused as to why it is there. Some speak of mtDNA hypermethylation like it is bad while normal methylation has some purpose.

 

See, for instance: Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility

 

I don’t agree. I say all mtDNA methylation is bad. Methylated mtDNA mooches enzymes off other mtDNA, and because they don’t produce as much ATP they don’t produce as much ROS, and thus have a survival advantage as they are less prone to mutation. Eventually the cell will become full of moochers and result in fatigue and many other problems of aging.

 

So I say get rid of them all, mutations and methylation alike.

 

The new protocol:

 

This new procedure is much simplified. It requires only two doses, Mito1 and Mito2, which are alternated on a daily basis.

 

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.

 

A two week experiment using reps to failure:

 

Warm water was sufficient to dissolve everything, but the PQQ was taken in a capsule to insure that the other ingredients got a slight head start (probably unnecessary).

 

Mito1 and Mito2 were taken on alternating days. Each dose was taken in the evening and reps of dumbbell curls to failure counted first thing in the morning — five or six hours after dosing — using the same arm.

 

My hypothesis was that the number of reps would reflect mito damage. With mito fusion, enzymes are shared, thus ATP production and reps would be maximum. With fission, methylated (or otherwise damaged) mtDNA produce less ATP and reps would be minimum. The difference would reflect average damage, and if the treatment worked, the difference should decline. If all damage was removed, then the difference should go to zero.

 

Which in fact it did. See the plot below. The y-axis shows the reps and % difference, while the x-axis shows days. The curve labeled baseline is without any treatment, and likely reflects the normal intermediate situation with mito morphology in a dynamic state. It is stable at 16 reps. The upper fusion curve is relatively flat and higher than baseline as expected, while the lower fission curve is lower than baseline, but rises to meet the fusion curve after about two weeks, and stays there. Thus the percent difference goes to zero.

 

Results:

 

Improvement in running endurance, reduced hunger, and reduced need for hypertension medication.

 

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[stephen_b]

I had been taking 250 mg niacinamide + 250 mg ribose with either cocoa butter pancakes or 250mg GMS. My thought was that it was helping with my cholesterol numbers.

 

I decided to revisit the mitochondrial protocol after having had some success with the stem cell protocol. I had hoped also to see some improvement with my running, which was dragging lately (trouble going more than 4-5 miles and running at about a 10:45 min/mi pace).

 

I decided to do pushups to track progress, but only 24 hours after fusion and right before taking the fission supplements (so every other day).

 

From my diary:

 

2022-06-05: fission day 1, baseline of 33 pushups.

2022-06-07: fission, 36 pushups

2022-06-08: fusion day and an excellent track workout (4x1 mile progressive). Nice incremental improvements so far. Tomorrow another pushup trial before fission.

2022-06-09: 40 pushups this morning, and after that fission.

2022-06-11:Nice recent improvements in fitness and pace. 7.59 mi @ 9:26 min/mi followed by 42 pushups.

 

I'm very happy with the progress, and the endurance increases have been remarkable.

Edited by stephen_b, 11 June 2022 - 02:41 PM.

[rastilin]

I had been taking 250 mg niacinamide + 250 mg ribose with either cocoa butter pancakes or 250mg GMS. My thought was that it was helping with my cholesterol numbers.

 

I decided to revisit the mitochondrial protocol after having had some success with the stem cell protocol. I had hoped also to see some improvement with my running, which was dragging lately (trouble going more than 4-5 miles and running at about a 10:45 min/mi pace).

 

I decided to do pushups to track progress, but only 24 hours after fusion and right before taking the fission supplements (so every other day).

 

From my diary:

 

2022-06-05: fission day 1, baseline of 33 pushups.

2022-06-07: fission, 36 pushups

2022-06-08: fusion day and an excellent track workout (4x1 mile progressive). Nice incremental improvements so far. Tomorrow another pushup trial before fission.

2022-06-09: 40 pushups this morning, and after that fission.

2022-06-11:Nice recent improvements in fitness and pace. 7.59 mi @ 9:26 min/mi followed by 42 pushups.

 

I'm very happy with the progress, and the endurance increases have been remarkable.

 

Those are very impressive improvements. Are you still trying it, are there any further changes? Even a 30% benefit to pushup maximum is significant, so I'm curious if there are improvements beyond that.
 

[stephen_b]

Those are very impressive improvements. Are you still trying it, are there any further changes? Even a 30% benefit to pushup maximum is significant, so I'm curious if there are improvements beyond that.
 

 

Yes. 

 

2022-06-14: 44 pushups then fission in morning. As an experiment, tried fusion before bed

2022-06-15: no supps

2022-06-16: 43 pushups then fission

2022-06-17: fusion

2022-06-18: no mito supps. 10.5 mile run at just over 10 min/mi. After run, did 45 pushups.

 

I'm finding that I get better aerobic performance the day after a fusion day (no supps that day) than I do on the fusion day itself (take fusion in the morning then exercise late afternoon).

Edited by stephen_b, 18 June 2022 - 04:49 PM.

[rastilin]

Yes. 

 

2022-06-14: 44 pushups then fission in morning. As an experiment, tried fusion before bed

2022-06-15: no supps

2022-06-16: 43 pushups then fission

2022-06-17: fusion

2022-06-18: no mito supps. 10.5 mile run at just over 10 min/mi. After run, did 45 pushups.

 

I'm finding that I get better aerobic performance the day after a fusion day (no supps that day) than I do on the fusion day itself (take fusion in the morning then exercise late afternoon).

 

Thanks for the update. That's very impressive, a 39% improvement to pushups in two weeks and a doubling of running endurance.

 

I'm trying it myself, but I'm still waiting for some things to arrive.

 

It will be interesting to find out if this also helps build muscle more effectively going forward, and if it works in combination with creatine supplementation; which is supposed to only improve endurance by 10% or so, but massively improve the rate of strength gain from exercise.

[Wookie]

So I guess mornings are fine for this protocol from what Ive read. 

 

1) How long do I have to wait before I eat after taking mito 1 and 2?

 

2) Can I take an argine supplement like pro argi 9 while on this protocol and how long should I wait to take other supplements after mito 1 or 2?

 

Thanks!

[Wookie]

This question is for anyone who may know. Should the supplements below be avoided entirely on mito days? Or perhaps just taken several hours later? Thank you in advance

 

There is no cure for mitochondrial disease. Certain supplements—thiamine (B1), riboflavin (B12), vitamin C, vitamin E, Lipoic acid, and coenzyme Q10—​may help treat certain aspects of the disease.

[Turnbuckle]

 

There is no cure for mitochondrial disease. Certain supplements—thiamine (B1), riboflavin (B12), vitamin C, vitamin E, Lipoic acid, and coenzyme Q10—​may help treat certain aspects of the disease.

 

Not necessarily true. If every mitochondria is defective since birth, then this will not help. But for cells that have at least one good mitochondrion, then this protocol can magnify the good over the bad. Even if all mitochondria were bad, it might still be possible to fix it by first supplying a mitochondrial transplant. 

 

Mitochondrial transplantation, an innovative therapeutic solution for mitochondria-associated disorders, has been validated by clinical trials and animal studies to be effective in treating IRI6–9. Through replacing the damaged mitochondria with exogenous healthy mitochondria, this method supplements the compromised cells with mtDNA, ATP and antioxidants and promotes their self-repair6–9.

https://journals.sag...636897211024210

 

 

Since these transplants would be greatly in the minority, they could then be amplified by the present technique.

[Wookie]

Not necessarily true. If every mitochondria is defective since birth, then this will not help. But for cells that have at least one good mitochondrion, then this protocol can magnify the good over the bad. Even if all mitochondria were bad, it might still be possible to fix it by first supplying a mitochondrial transplant. 

 

 

Since these transplants would be greatly in the minority, they could then be amplified by the present technique.

Thank you very much for the reply. 

 

I am certain your protocol works and Google is wrong about no cure. I was just curious weather it messed up the protocol to take those supplements in your opinion or if Im overthinking it.. I would hate to do anything counter productive.

[resveratrol_guy]

Long time no post. Having not read all 69 pages in this thread, forgive me if this is a repeat, but for what it's worth it seems to me that white chocolate is a great way to dissolve GMS. I tried hot water, but I guess it wasn't hot enough. I also don't want to use chocolate or chocolate brownies because the last thing I want to do with a substance that raises BP is mix it with a source of caffeine, however modest. And if you can't tolerate the sugar, there are plenty of alternatives made with maltodextrin or stevia.

 

 

I would also think that stacking with pterostilbene would help, as it supposedly reverses some epigenetic drift due to inappropriate methylation. Or perhaps not because we would then convert bad mitochondria into merely inefficient ones, when we actually just want to fission them out of existence? Turnbuckle?

 

Also, I do wonder how long we can do this before it becomes counterproductive. I mean, can I just alternate the latest 2-day protocol indefinitely? Or does the effect invert and accelerate aging if we cross some critical threshold, as opposed to just becoming a waste of money? And finally, I've been slamming everything simultaneously on an empty stomach in the morning (with no other supplements until at least 30 minutes later). If that's stupid or even suboptimal, kindly let me know.

Edited by resveratrol_guy, 02 July 2022 - 12:43 AM.

[Wookie]

I had been taking 250 mg niacinamide + 250 mg ribose with either cocoa butter pancakes or 250mg GMS. My thought was that it was helping with my cholesterol numbers.

 

I decided to revisit the mitochondrial protocol after having had some success with the stem cell protocol. I had hoped also to see some improvement with my running, which was dragging lately (trouble going more than 4-5 miles and running at about a 10:45 min/mi pace).

 

I decided to do pushups to track progress, but only 24 hours after fusion and right before taking the fission supplements (so every other day).

 

From my diary:

 

2022-06-05: fission day 1, baseline of 33 pushups.

2022-06-07: fission, 36 pushups

2022-06-08: fusion day and an excellent track workout (4x1 mile progressive). Nice incremental improvements so far. Tomorrow another pushup trial before fission.

2022-06-09: 40 pushups this morning, and after that fission.

2022-06-11:Nice recent improvements in fitness and pace. 7.59 mi @ 9:26 min/mi followed by 42 pushups.

 

I'm very happy with the progress, and the endurance increases have been remarkable.

Impressive indeed. I was wondering if you (or anyone else) had seen any physical/superficial signs of de aging like less wrinkles or less grey hairs etc.

[stephen_b]

Impressive indeed. I was wondering if you (or anyone else) had seen any physical/superficial signs of de aging like less wrinkles or less grey hairs etc.

 

I'd say softer skin. Graying of hair is not progressing noticeably.

[CTraylor]

Impressive indeed. I was wondering if you (or anyone else) had seen any physical/superficial signs of de aging like less wrinkles or less grey hairs etc.

 

Greater sustained energy when I ride a stationary bike on Zwift is my #1 benefit. In terms of appearance, my skin did plump up reducing wrinkles and my balding top regained about 10-20% of my hair. LOL, that just means that there's about 30-40% coverage...

[johnhemming]

Impressive indeed. I was wondering if you (or anyone else) had seen any physical/superficial signs of de aging like less wrinkles or less grey hairs etc.

 

I have been doing a number of things over some time to improve my health and more recently have been coaching a few other people into how to follow my protocol (which includes aspects to deal with the mitochondria, but goes further than that).  Quite a few people have mentioned that they have noticed my skin improve (that's why my sister and a family friend have taken up the protocol).  My doctor looked at my skin on Thursday and he thought it was of a younger appearance than his (he is 49 I am 62) More recently I have obtained some new hair growth and the process of getting new hair is likely to continue, the hair tends to be quite fine and varies between dark and white.   I have found building muscle easier using a chin ups frame.  I can now do a couple of chin ups - which I could not do previously although I may have been able to do this in my teens  (I weigh 85kg) and expect to build on that.  I don't exercise a lot although when on my own I walk briskly (its too fast for most people).  My target is to beat my 29 year old son at arm wrestling at least with the left arm (his right is dominant, my left is dominant).  He, however, continues to work on building his strength so that is likely to be a continuing challenge.  We last had a contest last Sunday and I am getting close, however.  Another friend of mine (also on the protocol) has also been told he seems to look healthier and his hair is growing more quickly.

Edited by johnhemming, 03 July 2022 - 06:31 AM.

[Turnbuckle]

This thread has gotten very long, but thankfully someone at reddit has summarized it for us. See:  https://www.reddit.c..._fissionfusion/

 

Edited by Turnbuckle, 07 July 2022 - 09:52 PM.

[lamnongtnvn]

This thread has gotten very long, but thankfully someone at reddit has summarized it for us. See: https://www.reddit.c..._fissionfusion/

Hi Mr.Turnbuckle,
I have few questions. I hope you don't mind to answer it.

1. Is this protocol doable for a person who is below 30?
2. And could you give me the brand name of the supplements you are using for this protocol. I want to follow you 100% including supplement's brand just to be safe.

Thanks in advance!

[Kelvin]

Hi Mr.Turnbuckle,
I have few questions. I hope you don't mind to answer it.

1. Is this protocol doable for a person who is below 30?
2. And could you give me the brand name of the supplements you are using for this protocol. I want to follow you 100% including supplement's brand just to be safe.

Thanks in advance!

1) You probably won’t notice much difference after a few cycles because at your age your mitochondria are probably operating at optimal levels.

2) The brands for these supplements will be about equally good as long as you choose one that has a good reputation,

. There are a number of good brands to choose from. Some of them are Jarrow, DoubleWood, and Swanson vitamins.

[Kelvin]

I believe Turnbuckle said earlier in the thread that his source of AKG is the liquid form of Simplesa.

I also take Simplesa for my AKG brand but I use the capsules.

For PQQ I use caps from Double Wood, but just about any decent brand have the same quality of PQQ.

I also take sulforaphane and dihydromyricetin instead of GMS as my fusion promoters, and have had great results from them.

Edited by Kelvin, 18 July 2022 - 11:17 PM.

[Richard McGee]

I'm taking up this new version of the mitochondrial fission/fusion protocol, after having done the original in 2017 (can't believe this thread is 5 years old). One thing I didn't do before was any sort of baseline measurement to track my progress. Are reps-to-failure with dumbbells a sufficient metric? Also would a $110 investment in a TruMe biological age test be relevant with this protocol? I don't have a lot of cash to spare, but I could probably swing a before and after test.

 

So this is what I'm thinking:

 

Preliminary TruMe Epigenetic age test before starting protocol.

 

Day 1 Baseline reps test.

Day 2 Mito 1

Day 3 Mito 2

Day 4 Mito 1

Day 5 Mito 2

Day 6 Mito 1

Day 7 Mito 2

Day 8-14 Rest

 

Repeat 14 day cycle for 8 weeks.

Evaluate baseline tests.

 

Possible comparison TrueMe test.

 

I want to insert the week of rest into the cycle out of a superabundance of caution, given my age (72) and medical issues.