2287 replies to this topic

[Ken Mark]

If I have not misunderstood who has defects in the respiratory chain, does greater fission prevail?

What kind of defect in respiratory chain? If there's defect in fusion, there will be more fission. If there's defect in fission, there will be more fusion.

[kurt9]

If the steric acid or some other component of this protocol gets rid of visceral fat, is it not likely that this protocol is the single best approach to minimize one's susceptibility to COVID-19?

 

It is true that one must careful self-isolate (quarantine) during the fission portion of this protocol, which is what I am doing.

 

Nevertheless, visceral fat is the strongest correlate and cause of diabetes (metabolic syndrome), CVD, and possibly cancer. All of these things correlate with increased death from COVID-19. Thus, a reduction of visceral fat,in and of itself, may be the single best effort one can do to reduce their chances of suffering and/or dying from COVID-19.

 

Even if this is not the case, reduction of visceral fat is nevertheless the best approach to increasing one's chances to making it to LEV.

[Turnbuckle]

If the steric acid or some other component of this protocol gets rid of visceral fat, is it not likely that this protocol is the single best approach to minimize one's susceptibility to COVID-19?

 

It is true that one must careful self-isolate (quarantine) during the fission portion of this protocol, which is what I am doing.

 

Nevertheless, visceral fat is the strongest correlate and cause of diabetes (metabolic syndrome), CVD, and possibly cancer. All of these things correlate with increased death from COVID-19. Thus, a reduction of visceral fat,in and of itself, may be the single best effort one can do to reduce their chances of suffering and/or dying from COVID-19.

 

Even if this is not the case, reduction of visceral fat is nevertheless the best approach to increasing one's chances to making it to LEV.

 

 

It's possible that mito fusion may offer some resistance to the disease, giving your immune system extra time to deal with it. This is in addition to the points you made. See my thread, Can mito fusion stop Covid-19?

[Unclebob]

Came across this today. 

 

Edward Omron MD, MPH who took Niacinamide and Metformin for two years. The presentation discusses his results and underlying processes.  

 

Why is this relevant to the visceral fat loss discussion? 

 

Well over the two years he lost 50lbs with little dietary change and no exercise.  Just the suplementation.

 

Worth the watch if you have not seen it before.  https://www.youtube....h?v=nq-s7rDuLnc

 

Interesting he experience the same weight loss at the same rate as myself although I am not taking metaformin.

 

Hope this adds to the discussion

 

Cheers

 

Edited by Unclebob, 08 April 2020 - 07:32 AM.

[kurt9]

Days 4 and 5 of the protocol are fusion days. One takes the fusion ingredients both the morning and evening of days 4 and 5. How long does the steric acid stay in the body from the time one eats a brownie? For example, I eat a brownies on mornings of days 4 and 5, then take the other stuff 3 hours later. Should I have a brownie 3 hours before I take the evening round as well? This is what I have been doing (a brownie 3 hours before, both morning and evening for a total of 4 per week). Perhaps the steric acid remains in the body long enough that I can get away with eating the brownie only in the morning for 2 per week.

 

Any thoughts?

[Nate-2004]

COVID is making PQQ access a bit limited, but realizing that maybe extreme cold exposure like a 4 min ice bath and perhaps lactic acid from HIIT style exercise and yogurt consumption (squat jumps, sprints, fast or explosive pushups, other extreme anaerobic style exercises) is the better approach to biogenesis anyway. All the evidence for inducing biogenesis is in mice, nothing for humans that I can find, no idea why.

[ambivalent]

Is is okay to calibrate the fission-state for as long and as intense enough as can be endured - so would say 5 days of restful fission be viable? In addition, N+R in juice ok? 

[Biotochandron]

Another potential way to intensifiy the protocol and boost the QC process would be hypoxic breathing while in fission-state (with a hypoxic generator for 400-500$ from alibaba). Maybe a hypoxic breathing method like "Wim Hof Breathing" would help also. However this could be dangerous for people with a lot of defective mtDNA loops and should probably only be done by people who don't get effects from two days 2g N+R anymore.

 

[Turnbuckle]

Another potential way to intensifiy the protocol and boost the QC process would be hypoxic breathing while in fission-state (with a hypoxic generator for 400-500$ from alibaba). Maybe a hypoxic breathing method like "Wim Hof Breathing" would help also. However this could be dangerous for people with a lot of defective mtDNA loops and should probably only be done by people who don't get effects from two days 2g N+R anymore.

 

 

Nothing like this is needed.

[sub7]

The mitochondrial metabolic checkpoint in stem cell aging and rejuvenation [2020]

doi for sci-hub: 10.1016/j.mad.2020.111254

Abstract:

Stem cell aging contributes to aging-associated tissue degeneration and dysfunction. Recent studies reveal a mitochondrial metabolic checkpoint that regulates stem cell quiescence and maintenance, and dysregulation of the checkpoint leads to functional deterioration of aged stem cells. Here, we present the evidence supporting the mitochondrial metabolic checkpoint regulating stem cell aging and demonstrating the feasibility to target this checkpoint to reverse stem cell aging.
We discuss the mechanisms by which mitochondrial stress leads to stem cell deterioration. We speculate the therapeutic potential of targeting the mitochondrial metabolic checkpoint for rejuvenating aged stem cells and improving aging tissue functions.

 

 

 

Turnbuckle,

To what extent does your protocol address mitochondria in the stem cells? Would they benefit too?

[Turnbuckle]

 

The mitochondrial metabolic checkpoint in stem cell aging and rejuvenation [2020]

doi for sci-hub: 10.1016/j.mad.2020.111254

Abstract:

Stem cell aging contributes to aging-associated tissue degeneration and dysfunction. Recent studies reveal a mitochondrial metabolic checkpoint that regulates stem cell quiescence and maintenance, and dysregulation of the checkpoint leads to functional deterioration of aged stem cells. Here, we present the evidence supporting the mitochondrial metabolic checkpoint regulating stem cell aging and demonstrating the feasibility to target this checkpoint to reverse stem cell aging.
We discuss the mechanisms by which mitochondrial stress leads to stem cell deterioration. We speculate the therapeutic potential of targeting the mitochondrial metabolic checkpoint for rejuvenating aged stem cells and improving aging tissue functions.

 

 

 

Turnbuckle,

To what extent does your protocol address mitochondria in the stem cells? Would they benefit too?

 

 

 

When a stem cell divides asymmetrically into a somatic cell and new stem cell, mitochondria are segregated according to quality, with the lower quality mitochondria going to the somatic cell where QA processes are most active. Thus mito aging in SCs doesn't seem like a big deal.

 

As for the above paper, it doesn't even mention telomeres as a source of stem cell senescence, nor is senescence of adult stem cells necessarily a bad thing. After all, they are subject to epigenetic aging as they are partially methylated. Thus wouldn't it be better if old adult stem cells were cleared out and replaced by VSELs? These are pluripotent cells that circulate in the blood and have minimal methylation. See more on this in my post here.* 

 

The subject of VSELs is contentious, with some researchers claiming they can't find them and others swearing by them. I find the pro-VSEL researchers more convincing.

 

---------------------

*Note that my comment about threonine is likely incorrect, as humans have a deficiency in the ability to use threonine compared to other species.

Edited by Turnbuckle, 04 May 2020 - 08:50 PM.

[mitomutant]

Maybe relevant to this thread and for sure relevant to my specific condition.

 

This is targeting people with a primary mitochondria dysfunction due to a genetic condition. Specifically, patients with single mtDNA deletion (this is what I have) or multiple mtDNA deletions. In this context, a percentage (30-35% in my case) of mitochondria are defective and unable to produce any ATP and, what is worse, those defective mitochondria have a replication advantage (clonal expansion) and end up shifting the ratio of wild-type vs mutant mitochondria in the wrong direction, making this disease progressive.

 

Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy

 

 

 

NAD + is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD + depletion occurs in patients with degenerative disorders and whether NAD + repletion improves their symptoms has remained open. Here, we report systemic NAD + deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD +-booster niacin, a vitamin B3 form (to 750–1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD + increased in all subjects, up to 8-fold, and muscle NAD + of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD + deficiency and points niacin to be an efficient NAD + booster for treating mitochondrial myopathy.

 

We have exact dosage at the clinical trial page

 

 

 

Dietary Supplement: Niacin

The dose for a slow-released form of niacin will be 750-1000 mg/day. The daily niacin dose, 250 mg/day, is gradually escalated by 250 mg/month so that the full dose is reached after 3 months. The intervention time with the full niacin dose is 1 and 7 months for controls and patients, respectively, and subsequently total intervention time 4 and 10 months, respectively. At the end of the study, the daily dose will be decreased by 250 mg/month rate.

Other Name: Nicotinic acid

 

[turtlelonglife]

first week of turnbuckle's mito dynamics protocol. 33 year old male.

 

deviations:

used 800mg of longvida curcumin until my apigenin arrives.

using a 5mg version of HT(from olive leaf/fruit blend) until my 20mg arrives.

using NADH sublingual lozenges on fusion days to lower the NAD+ ratio.

using cacao butter until my GMS arrives.

 

started slow with 1g of N+R on the first day then 1.5g on the second day and loose with the antioxidants that may have been interfering with fission. 

felt a little flu like the second day but after a day of fusion(cocoa butter AND 100mg crucera sulforaphane ) things returned to normal.

 

went to 2g of N+R the second cycle.

On the 1st day, I felt tired by the end of the day. I slept an additional 2 hrs, at least, as I woke up tired and a bit achy.

2nd day I was pretty much in a state of stupor having difficulty turning on the right stove burner.

 

immediately went to a fusion day after the 2nd day of fission and felt better by the end of the day, but not 3 hours after consuming cocoa butter in oatmeal so I am looking forward to seeing how I react to GMS.

after the first day of fusion, I still slept in a bit longer than usual but felt normal.

 

I will try fission with apigenin next. Does anyone know if curcumin(longvida) is ok for this protocol? I see it's used as a senescent in turnbuckle's stemcell protocol so I would assume it can be used in this protocol's fission part without issue...

Edited by turtlelonglife, 09 May 2020 - 03:18 PM.

[turtlelonglife]

Update:

I did a cycle of fission with apigenin, feeling noticeable weaker on the 2nd day of it but seemingly less so than the previous cycle.

For the next cycle I will use apigenin with curcumin.

 

For the fusion cycle I actually felt equally as bad or even more so. I believe it has to do with the introduction of hydroxytyrosol. Seems to be giving me a herxheimer reaction, as I was a bit feverish especially on the second day when I combined the olive fruit supplement(hydroxytyrosol 20mg) with the remaining olive leaf supplement I had(5mg hydroxytyrosol, 100mg oleuropein)

 

As for the cocoa butter vs GMS, I can't say I noticed a significant difference. the above reaction may be interfering with a discernible fusion effect, but since i don't have a blood pressure monitor I plan to use about 2g of GMS with 10g of cocoa butter(~4g of stearic acid) moving forward.

 

 

Needless to say, this week has been a bit rough. I am optimistic this protocol will improve my health based off the strong response I am having from the first few cycles.

 

Edited by turtlelonglife, 14 May 2020 - 11:46 PM.

[kurt9]

You definitely want to self-quarantine while doing fission. I learned this the hard way back in January. Fission causes apoptosis, which can spread certain viruses around if you have them. I got sick again (after another trip) in February and suspended this protocol for a couple of weeks until I got better.

[turtlelonglife]

After taking kurt9's advice, I suspended fission for a week and focused on recovering with fusion. It seems hydroxytyrosol was indeed causing a herx reaction, as symptoms of joint pain, fatigue, GI issues, brain fog persisted for a week without fission.

I seemed to have mostly recovered now but will give myself a couple of days before restarting the fission protocol.

[longcity90]

If I wanted to obtain 125 mg of NMR, is the ratio of 60mg of Niacinamide and 125mg of ribose right?

 

Thanks

[Nate-2004]

Relevant article published Monday on mito qc:

 

https://www.frontier...2020.00515/full

 

 

Mitochondrial Quality Control and Cellular Proteostasis: Two Sides of the Same Coin

Mitochondrial dysfunction is a hallmark of cardiac pathophysiology. Defects in mitochondrial performance disrupt contractile function, overwhelm myocytes with reactive oxygen species (ROS), and transform these cellular powerhouses into pro-death organelles. Thus, quality control (QC) pathways aimed at identifying and removing damaged mitochondrial proteins, components, or entire mitochondria are crucial processes in post-mitotic cells such as cardiac myocytes. Almost all of the mitochondrial proteins are encoded by the nuclear genome and the trafficking of these nuclear-encoded proteins necessitates significant cross-talk with the cytosolic protein QC machinery to ensure that only functional proteins are delivered to the mitochondria. Within the organelle, mitochondria contain their own protein QC system consisting of chaperones and proteases. This system represents another level of QC to promote mitochondrial protein folding and prevent aggregation. If this system is overwhelmed, a conserved transcriptional response known as the mitochondrial unfolded protein response is activated to increase the expression of proteins involved in restoring mitochondrial proteostasis. If the mitochondrion is beyond repair, the entire organelle must be removed before it becomes cytotoxic and causes cellular damage. Recent evidence has also uncovered mitochondria as participants in cytosolic protein QC where misfolded cytosolic proteins can be imported and degraded inside mitochondria. However, this process also places increased pressure on mitochondrial QC pathways to ensure that the imported proteins do not cause mitochondrial dysfunction. This review is focused on discussing the pathways involved in regulating mitochondrial QC and their relationship to cellular proteostasis and mitochondrial health in the heart.

Edited by Nate-2004, 17 June 2020 - 05:41 PM.

[mitomutant]

One month in using the simplified protocol described in this post. Lots of interesting effects:

 

My only gauge is perceived vitality for my everyday tasks and performance when doing exercise.

 

As a reminder, I have a primary mitochondrial dysfunction due to a genetic condition.

 

• No difference between fission and fusion days
• On average, vitality is a little lower. Not that I feel tired, but it is a strange feeling, like some kind of "dumbness". Could be also defined as "calmness". No brain frog though.
• Vitality swings are non-existent, which is extremely good, given that I would crash some days for no apparent reason.

 

Exercise: I am in good shape. Doing classic boxing 2-3 times per week, 1 hour. Classic boxing means doing rope, shadow boxing, heavy bag, padding and occasional sparring. Using standard boxing round times, that is, 3 mins exercise, 1 min rest. Average around 155 beats per minute. So, we can say I am doing HIIT.

 

• Peak performance (p.e. end of heavy bag round) at about the same level, maybe slightly better.
• Total performance, that is, the ability to keep performance at a high level during the whole training: noticeable improvement
• Recovery between rounds: Pretty amazing improvement.
• Recovery between workouts: Big improvement as well. Here, it is strange that I wake up feeling exhausted, but after an hour or so, I feel just fine. Before starting this protocol, the reverse was the norm: I would wake up refreshed and then, I would feel exhausted. 
• No aches or tiredness, which were usual before starting this protocol.

 

Taking only 500 mg Nicotinamide + 500 mg d-ribose for fission days. If I take more, I get a terrible stomach upset.

 

Will continue this protocol a couple of additional months, trying to increase the Nicotinamide/D-Ribose dosage. Overall, pretty happy with it.

 

Thanks Turnbuckle !

 

 

 

[Starjumper7]

Sorry if this question has already come up, but I just got my supplies delivered via shipping courier and want to start on the first fission tomorrow.  The question is about Niacin vs. Niacinamide.  My concern is that Niacinamide is said to be liver toxic, and my liver has already been 'wounded' by some toxic medicine I took some years ago.  I would prefer to take Niacin instead if it will do the same job as Niacinamide.  Please advise on that.  Thanks. 

[aribadabar]

The question is about Niacin vs. Niacinamide. My concern is that Niacinamide is said to be liver toxic, and my liver has already been 'wounded' by some toxic medicine I took some years ago. I would prefer to take Niacin instead if it will do the same job as Niacinamide. Please advise on that. Thanks.

I think you are mixing up nicotinamide/niacinamide with inositol hexanicotinate (extended release niacin) which is found to be slightly liver toxic. You will be fine with nicotinamide at sane doses. Also, without gradual ramping up, 500mg or more of (instant release) Niacin (nicotinic acid) will cause intense flushing that some people dislike - no such thing will occur with Niacinamide.

Edited by aribadabar, 03 July 2020 - 10:32 AM.

[Starjumper7]

I think you are mixing up nicotinamide/niacinamide with inositol hexanicotinate (extended release niacin) which is found to be slightly liver toxic. You will be fine with nicotinamide at sane doses. Also, without gradual ramping up, 500mg or more of (instant release) Niacin (nicotinic acid) will cause intense flushing that some people dislike - no such thing will occur with Niacinamide.

 

It's true, i did think nicotinamide was the extended release version, but still, it is said to potentially cause liver problems at high doses.  There appears to be no information on what is considered to be a normal amount or a high dose.

 

https://en.wikipedia...ki/Nicotinamide

Side effects are minimal.^[6][7] At high doses liver problems may occur.^[6] Normal amounts are safe for use during pregnancy.

 

I've been practicing with my niacin, and taken up to 1500mg and found the flushing to be mild and not a problem.  I discovered that I build up tolerance to flushing very fast these days, when before, when I lived in the land of poison, it seemed I did not build up tolerance at all.  I'm guessing it's due to the pure living and high nutrition diet these last years.  Besides, I'm a tough old fart.

 

So I'll take the 2G of niacin and can report back on that.

Edited by Starjumper7, 03 July 2020 - 11:53 AM.

[Starjumper7]

Another question.  I recently started taking resveratrol with Niacin, but during this fission/fussion regime would it be better to take the resveratrol during the fission or the fusion part?

[Turnbuckle]

It's true, i did think nicotinamide was the extended release version, but still, it is said to potentially cause liver problems at high doses.  There appears to be no information on what is considered to be a normal amount or a high dose.

 

https://en.wikipedia...ki/Nicotinamide

 

I've been practicing with my niacin, and taken up to 1500mg and found the flushing to be mild and not a problem.  I discovered that I build up tolerance to flushing very fast these days, when before, when I lived in the land of poison, it seemed I did not build up tolerance at all.  I'm guessing it's due to the pure living and high nutrition diet these last years.  Besides, I'm a tough old fart.

 

So I'll take the 2G of niacin and can report back on that.

 

 

Either niacin or nicotinamide will get you there. They will both produce NAD+, and it is the elevation of the NAD+/NADH ratio that produces fission. Nicotinamide produces more NAD+ over a longer period than niacin as its half life is longer. Nicotinamide is not extended release niacin, however. It is chemically different, and it's extended release niacin that is associated with liver problems. In any case, this protocol does not involve continued, long term use, thus such problems are highly unlikely to occur with either.

 

I don't recommend resveratrol as it causes joint damage in some people (including me). It is known to stimulate mito biogenesis and thus would work better with fusion, but then so does PQQ, and without the potential problems.

Edited by Turnbuckle, 03 July 2020 - 01:05 PM.

[theobromananda]

I am still young and this is not really urgent - but I'd be interested:

 

 

I drink about 10-30g of raw cacao and take 100mg of jiaogulan extract every day; also there are 50mg of B3 in my B-complex.

 

Would I still benefit from using sulphoraphane and higher doses of N+R on alternating days, or are the confounding factors mentioned above so strong so that they disrupt effective fusion and fission? Which ones would need to be stopped?

 

 

Also, thank you again for your Alzheimers protocol. My mother is significantly better now.

[Starjumper7]

Either niacin or nicotinamide will get you there. They will both produce NAD+, and it is the elevation of the NAD+/NADH ratio that produces fission. Nicotinamide produces more NAD+ over a longer period than niacin as its half life is longer. Nicotinamide is not extended release niacin, however. It is chemically different, and it's extended release niacin that is associated with liver problems. In any case, this protocol does not involve continued, long term use, thus such problems are highly unlikely to occur with either.

 

I don't recommend resveratrol as it causes joint damage in some people (including me). It is known to stimulate mito biogenesis and thus would work better with fusion, but then so does PQQ, and without the potential problems.

 

Thanks for the info.  The first day of fission with niacin I felt kind of tired and weak so I decided to not take nicotinamide for the second day since you said it would be stronger.  The second day of fission I didn't feel that tired or weak, so I think for the next cycle I'll take just the nicotinamide or start with 50/50.  I noticed I was a bit light headed and felt a little 'high' the first day.  Not a problem.

 

The first day of 2g of niacin the flush was moderate and not bad, the second day of 2g of niacin I hardly felt the flush at all.  I decided to only do two days of fission and today I started the fusion, since I have to get blood tests tomorrow for an upcoming hand surgery.  I added 1g of resveratrol to the fusion, since for me it doesn't seem to cause joint problems, but I'll be watching for that.

[stephen_b]

For example, I eat a brownies on mornings of days 4 and 5, then take the other stuff 3 hours later.

 

Just FYI, the protocol calls for stearic acid just on day 4.

 

kurt9, you have done a lot of cycles. I would be interested in hearing how your experience of it has varied since you started. Do you still feel the fission day effects?

 

By the way, I've started my 2nd cycle today.

Edited by stephen_b, 09 July 2020 - 08:19 PM.

[kurt9]

I did 12 cycles. I felt a little out of it during fission. But that feeling passed after about the 7th or 8th cycle. Fusion definitely perked me up during these cycles.

 

I've noticed my abs are tight. This could be due to the fission/fusion thing. It could also be due to ALA (alpha lipoic acid) chelation I did for all of 2019. It may also be due to me taking LEF's AMPK activator. I started taking this when the gyms shutdown due to the COVID-19 business and I could not work out. It might be all three. My plan is to stop taking the AMPK activator once the gyms, along with the pools (I swim in addition to bodybuilding) are completely open and everything is back to normal.

 

The shutdown of the gyms really pissed me off. My employer shutting down two weeks ago was even worse. However, I am getting lots of interviews and have set up my LLC in order to go out on my own as well. I am an automation and control system engineer (design and program PLC-based control systems).

[stephen_b]

Thanks kurt9. I'm a  mid-fifties distance runner, so I will be paying attention to how the protocol affects running, particularly the relationship between average heart rate  and average pace.

[Starjumper7]

I have a question about the Leucine.  In the protocol it suggest cooking it into food, but the taste is bad and I prefer ketogenic foods rather than oatmeal, so I'm wondering if it is OK to just mix it in a cup of cold water and toss it down?  In other words, not cooking it.

 

Another question. I got the glycerol monostearate to use, and have cooked it into oatmeal (once a week isn't so bad).  I accidentally put in twice the amount, using a rounded tablespoon instead of a rounded half table spoon.  It seems to have not been a problem.  I was concerned about the possible blood pressure rise, and I don't have any blood pressure lowering medicines here, except for a twenty year old bottle of Cardiotone, of which the main ingredient is Rawolvia, which has a powerful blood presure lowering effect.  In fact it's so powerful it can reduce a person's blood pressure to zero.

 

So the question here is, what is the danger of taking 10G of glycerol monstearate rather than 5G?  Also, since it is labeled as causing fusion, is it OK to take it on both the first and second days of fusion?

Edited by Starjumper7, 11 July 2020 - 01:51 PM.