2284 replies to this topic

[Stanfoo]

You mentioned one of the effects you experienced with this protocol was reduced appetite.

 

Why is this? What's it doing to the body to cause that?

[naxleo]

I have a question: Is there any relationship between fusion/fission and body temperature?

 

If this is so, we might use individual variations in body temperature to roughly understand whether a certain protocol is successful in inducing fusion/fission.  

[Turnbuckle]

You mentioned one of the effects you experienced with this protocol was reduced appetite.

 

Why is this? What's it doing to the body to cause that?

 

It's just an observation, but certainly if you are producing ATP more efficiently, you should require less fuel, and thus will experience less hunger. Hunger is moderated by the hypothalamus, so increased ATP production with the same fuel availability may result in a reduced hunger signal.  See Increased ATP content/production in the hypothalamus may be a signal for energy-sensing of satiety.

 

I have a question: Is there any relationship between fusion/fission and body temperature?

 

If this is so, we might use individual variations in body temperature to roughly understand whether a certain protocol is successful in inducing fusion/fission.  

 

I've not seen anything on the effects of body temperature on mito morphology in humans, but it can make a considerable difference in hibernators vs non-hibernators in hypothermic situations. See this paper. 

 

Also, there seems to be some dispute about the operating temperature of mitochondria. Since most of the heat of endotherms is due to the activity of mitochondria, it is expected that they will run hotter than the rest of the cell. Due to their small size, however, it was expected that this would be a tiny fraction of one degree. However, the following paper suggests it might be very large -- on the order of 10 degrees C.

 

we found that the rise in mitochondrial temperature due to full activation of respiration is as high as about 10 °C (n = 10, range 7–12 °C, compared to 38 °C, the temperature of the cell suspension medium). We also showed that respiratory chain (RC) activities measured in intact mitochondria can be increased up to threefold when assayed at the inferred mitochondrial temperature of intact cells.

https://www.ncbi.nlm...les/PMC5784887/

 

 

The activity going up with temperature is not surprising, as the rule of thumb in chemical reactions is a doubling of the rate with each 10 °C rise in temperature. So what effect will this have on defective mitochondria in the fissioned state, say during exercise? Myocyte mitochondria should run even hotter with exercise, but as mito membrane potential drops, the heat production should also drop. Thus the ATP output between mitochondria with good and bad mtDNA should be accentuated. But will that make any difference to PINK1/Parkin, giving that labeling for mitophagy requires zero membrane potential?

 

As for knowing whether you are in fission or fusion, the bicep curls to failure technique should be a good indicator, as long as you have defective mitochondria.

Edited by Turnbuckle, 21 July 2021 - 06:40 PM.

[naxleo]

I've not seen anything on the effects of body temperature on mito morphology in humans, but it can make a considerable difference in hibernators vs non-hibernators in hypothermic situations. See this paper. 

 

Also, there seems to be some dispute about the operating temperature of mitochondria. Since most of the heat of endotherms is due to the activity of mitochondria, it is expected that they will run hotter than the rest of the cell. Due to their small size, however, it was expected that this would be a tiny fraction of one degree. However, the following paper suggests it might be very large -- on the order of 10 degrees C.

 

 

The activity going up with temperature is not surprising, as the rule of thumb in chemical reactions is a doubling of the rate with each 10 °C rise in temperature. So what effect will this have on defective mitochondria in the fissioned state, say during exercise? Myocyte mitochondria should run even hotter with exercise, but as mito membrane potential drops, the heat production should also drop. Thus the ATP output between mitochondria with good and bad mtDNA should be accentuated. But will that make any difference to PINK1/Parkin, giving that labeling for mitophagy requires zero membrane potential?

 

Thanks for the answer. I understand that, theoretically, the issue is not easy to solve.

 

Those following the fission/fusion protocol might record their body temperature in fission and fusion days. This would empirically suggest an answer. 

[Turnbuckle]

Thanks for the answer. I understand that, theoretically, the issue is not easy to solve.

 

Those following the fission/fusion protocol might record their body temperature in fission and fusion days. This would empirically suggest an answer. 

 

I doubt body temp would be a good indicator, as that is kept in close control, whereas curls to failure shows a big difference.

[stephen_b]

I started the mitochondrial protocol in July of last year at a weight of 161 lbs. I also experienced reduced appetite. Without doing much I lost 10 pounds at a regular weight.

[naxleo]

I doubt body temp would be a good indicator, as that is kept in close control, whereas curls to failure shows a big difference.

 

I hope not to bother you insisting on a similar point.

 

My initial guess was that body temperature and heart rate were positively correlated with fission, due to the reduced efficiency during fission which should trigger enhanced activity to compensate (and hence higher body temperature and heart rate).

 

I understand that Turnbuckle sees no compelling argument for an appreciable effect of mito morphology on body temperature.

 

My question now is: can we say anything on the relation between fission/fusion and heart rate?

[Empiricus]

There are many drugs that can damage mitochondria, but certainly the most pervasive is sodium fluoride. A paper published this year examined the effect of fluoride levels on child intelligence in China and found —

 

Ug. I have been guzzling San Pellegrino by the 1L bottle.  It has nearly 0.5 ppm of fluoride which approaches the "minimum recommended fluoridation level" for the US tap water which was lowered to 0.7 in 2015.  

[Empiricus]

The problem for us following a carnivore diet is that if it doesn't work we don't know whether it's because our mitochondria are optimized or because we eat so much stearic acid that the N+R combo does not kick us into Fission. 

 

For example, I followed the protocol doing the "push-ups to failure" bit and did not see the pattern at all. Control, Fusion and Fission days I did the same number of repetitions. And I don't believe that my mitochondria are already optimized.

 

Since I am doing Carnivore as an elimination diet it comes with a cost for me to substitute beef for something else to avoid nutritional Fusion. Nevertheless, I am planning on doing a chicken+fisk week and see if I can get in and out of Fission/Fusion. 

 

Will post if anything interesting happens.

 

Saludos,

 

S.

 

I follow a carnivore diet (mostly beef) and my tracked progress on the current mitochondria protocol seemed consistent with Turnbuckle's experience.  

[FlorianReicht]

I adjusted my weekly diet to enhance the effect of this great protocol, as stearic acid inhibits Fission and has a half-life of 17h

 

Thursday:  Fruits only

Friday:       Carb refeed (fasting till evening Fission dose)

Saturday:   Fish with carrots and celery (fasting till evening Fusion dose)

Sun-Wed:   Bulletproof Diet meals

 

Noticed reduced resting HR, better sleep, less hunger, faster recovery, better memory - all after 3cycles already.

 

Thank you for sharing this Protocol Turnbuckle

[Turnbuckle]

I adjusted my weekly diet to enhance the effect of this great protocol, as stearic acid inhibits Fission and has a half-life of 17h

 

 

How long fusion lasts will be greatly dependent on the source and dose. Ten grams of stearic acid triglyceride in a brownie will produce a much longer period of fusion than one gram of GMS. And there are alternatives for fusion, like sulforaphane, which has a half life of around two hours. The minimum cycle time will likely be dependent of the rate of mitophagy and biogenesis, and will vary with tissue type. Biogenesis is relatively fast while mitophagy (with the fission half cycle) is substantially slower. 

 

Damaged mitochondria were efficiently sequestered within autophagosomes, but lysosomal fusion or acidification was significantly delayed. Surprisingly, engulfed mitochondria persisted in non-acidified vesicular compartments for hours to days after initial damage.

https://www.ncbi.nlm...les/PMC7144876/

 

 

From the experiment I reported a while back, 24 hours seems both sufficient and convenient for a half-cycle, either fission or fusion.

Edited by Turnbuckle, 08 September 2021 - 02:05 PM.

[CTraylor]

Post 1619 of Turnbuckle's stem cell thread has a new fusion protocol. Is the time 0 portion of the protocol a better fusion for this mitochondrial protocol? I find the blood, brain barrier fusion to be an appealing addition.

[CTraylor]

After 9 cycles of the Feb 17, 2021 protocol, I did a Sufferfest bicycle power test. Here's how I now compare to myself prior to doing protocol.

[CTraylor]

Sorry, here's the latest curve.

 

[stephen_b]

Any thoughts on whether taking betaine (trimethylglycine TMG) will impact the mitochondrial protocol?

 

Even though I've done many cycles in the past, I did mito1 and mito2 days both with 1g betaine, this time doing the dumbbell test. I got 50 reps on the mito1 day and 76 on the mito2.

 

I'm wondering either if I need betaine to get the most out of this protocol (I'm heterozygous for MTHFR), or whether betaine benefits everyone regardless of status.

[EliotH]

I had a minor scare a couple of nights ago. I was putting the D-Ribose into my glass and managed to spill much more than 1 gram (maybe 5-10 grams) into the water. I figured what the heck it's only sugar so I mixed it in and drank it with the AKG and went to bed. About an hour later I woke up and my body was vibrating. It was like shivers from being cold but I was actually warm. This lasted maybe 10 minutes before I fell asleep again. When I got up in the morning I felt fine. Also, I use 1 gram of niacin (flushing) and not niacinamide for this protocol.

[aribadabar]

I had a minor scare a couple of nights ago. I was putting the D-Ribose into my glass and managed to spill much more than 1 gram (maybe 5-10 grams) into the water. I figured what the heck it's only sugar so I mixed it in and drank it with the AKG and went to bed. About an hour later I woke up and my body was vibrating. It was like shivers from being cold but I was actually warm. This lasted maybe 10 minutes before I fell asleep again. When I got up in the morning I felt fine. Also, I use 1 gram of niacin (flushing) and not niacinamide for this protocol.

 

10g of D-Ribose is A LOT all at once. It sounds like you had a hypoglycemic shock as D-ribose is known to reduce blood sugar levels.

[Repack Racing]

An updated Mito protocol

 

The previous protocol can be found at post #1366

 

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.

 

 

 

Hello to all the mito folks out there!

 

I am writing with a very important comment regarding the new protocol, as well as soliciting Turnbuckle and the community-at-large for a solution.

 

I first want to thank Turnbuckle for all his work on this topic and also on stem cell renewal. I learned a lot and benefited from both the knowledge and use of the protocols. Thanks to all of the other contributors as well.

 

My comment to everyone is to be very careful with AKG/AAKG if you have any type of depression or anxiety, or in my case low-level bipolar.

 

Background:

 

I began the new protocol a few weeks ago. During that time I started to feel very tired and out of it. Also very irritable, according to other. Of course, like usual, it took a while to put all the pieces of the puzzle together and didn't make the connection to AKG right away - and hence continued the protocol. It turns out that many (but not all) people who have depression or anxiety related conditions have very high levels of glutamate. The connection is well established, I have linked some articles below. More than that, once I stopped the AKG my own symptoms abated. Nothing like first-hand experience to validate.

 

It seems that at least one reason for elevated glutamate is that many people with depression/anxiety conditions have trouble converting glutamate to GABA, so glutamate builds up. There's probably more to it.

 

If you suffer from a condition and have noticed changes since starting this protocol - AKG may be why. 

 

So that's a cautionary tell for everyone. It leaves me (and others if they head this warning) with a problem - is there a good alternative that will have a similar effect to AKG in this protocol? Obviously there is no perfect replacement, but we if consider the action of AKG in the protocol there may be a "next best" that doesn't increase glutamate. It's my understanding that AKG is converted into GABA, is that right? Is that the mechanism that drives the benefit in this protocol?

 

Those are the questions I pose to the community. I'd like to find an alternative to AKG if that is at all possible.

 

Thanks!

 

Links to AKG and bipolar/depression/anxiety (there are endless articles):

 

https://www.frontier...021.640977/full

https://psychnews.ps...pi.pn.2014.7a17

https://www.karger.c...Fulltext/496294

https://grantome.com...R21-MH110850-02

https://www.nature.c...icles/tp2017141

https://www.medscape...ressive-illness

 

Glutamate --> GABA:

 

https://bebrainfit.c...urotransmitter/

https://www.geneticl...urotransmitter/

 

Glutamate - GABA problem, genetic?:

 

https://drkirshner.c...ety-be-genetic/

https://www.holistic...nxiety-genetic/

[Turnbuckle]

 

 

Those are the questions I pose to the community. I'd like to find an alternative to AKG if that is at all possible.

 

 

 

If you have a problem with AKG, you could eliminate it from the fusion part, and if you still have a problem, you could eliminate it from the fission side as well. Most of the work in removing defective and methylated mtDNA is done by combining fission and biogenesis. I expect it will take longer, but it doesn't take that long to begin with.

Edited by Turnbuckle, 28 September 2021 - 08:35 PM.

[EliotH]

10g of D-Ribose is A LOT all at once. It sounds like you had a hypoglycemic shock as D-ribose is known to reduce blood sugar levels.

 

Thanks, I was wondering what it could be. It seems D-Ribose stimulates an insulin release. I was afraid the combination with niacin might have nuked my mitos.

[albedo]

Just in case you will find something interesting here:

https://memento.epfl...mpk-targets-th/

[kurt9]

Just in case you will find something interesting here:

https://memento.epfl...mpk-targets-th/

 

AMPK activator is available from LEF. I found a reaction path diagram that showed that AMPK is essentially "exercise in a pill". So I ordered a bunch of it up during the lockdowns last year when I could not go to the gym. It worked for me.

[Repack Racing]

If you have a problem with AKG, you could eliminate it from the fusion part, and if you still have a problem, you could eliminate it from the fission side as well. Most of the work in removing defective and methylated mtDNA is done by combining fission and biogenesis. I expect it will take longer, but it doesn't take that long to begin with.

Turnbuckle - thanks for the quick response.

 

Yeah, there's no way it's worth messing with brain chemistry on this one. So, just to clarify, you think that by doing the rest of the protocol: D1 NAD+R, PPQ; D2 GMS, PPQ will still work just not as effectively?

 

Any sense in trying to add GABA?

 

Thanks!

[Turnbuckle]

Turnbuckle - thanks for the quick response.

 

Yeah, there's no way it's worth messing with brain chemistry on this one. So, just to clarify, you think that by doing the rest of the protocol: D1 NAD+R, PPQ; D2 GMS, PPQ will still work just not as effectively?

 

Any sense in trying to add GABA?

 

Thanks!

 

 

You could also space out the treatments, and you might look at adding theanine and/or taurine.

Edited by Turnbuckle, 02 October 2021 - 06:50 PM.

[Old grandpa]

Hello all. I'm no scientist but I'm educated (engineer), so I won't have much to add to the scientific discussion; only my experimental results. (How I landed here I don't recall, but I've read this entire thread along with the papers linked. Psheww! Heady stuff.)
You seem to believe that rather than prolonging the life of damaged mitochondria with various supplement regimens to extend life (and health), it is better to speed up the death and replacement of them. It would seem you will run out eventually unless every single mitochondria is functioning at 100% with no genetic errors. If the best you have is 95% efficiency you can't get back above that with this protocol, correct? It would seem there will be a time when switching over to prolonging the life of damaged mitochondria due to accumulated damage will be necessary. Of course, we have no gauge to signal low fuel to know when this will occur but this method would seem to greatly increase our mileage. It's a fascinating idea.
I plan to follow the protocol closely except for the minor addition of sulphoraphane during fusion (due to crossing the BBB).
I have a couple questions. The switch to GMS from Stearic acid-- is this due to the shorter half life and quicker turn around between cycles, or because the faster action leads to less chance for methylation during biogenesis, or a completely different reason? I have high blood pressure (controlled naturally with celery seed extract, olive leaf extract, and l-citrulline) so I'm a little worried about the GMS. Additionally, will any of these supplements negatively effect either fusion or fission? I also take 10 mg. time release Vitamin C and 7mg. Melatonin before bed. Yay or nay on keeping these on cycle days? Do I need GMS if using sulphoraphane and will it effect demethylation?
I've ordered needed supplements and will post progress. I guess I should add this-- I'm 57, 75 lbs. overweight, and have never exercised as an adult. Starting alternate day fasting to lose the pounds. Hoping this gives me the energy and motivation to exercise. I spent the decade of my 30s using cocaine and my 40s using heroin, so I'm guessing lots of damage. No medications and have sexual intercourse 2-3 times per week, which is how I gauge health, lol. When that quits working I'm clocking out!

[CTraylor]

Vit C will stop fission, so skip it on the fission day. I believe the same it true with the olive leaf extract. You can take both with fusion.

 

You may want to start fission off at half a dose. For many, the first few fission cycles give flu like symptoms. If that happens, you can give the body a few days to recover and/or cut it short with a dose of vitamin C.

[Old grandpa]

Thank you. I looked at the olive leaf and it contains hydroxytyrosol. I tried searching for that as I remember Turnbuckle using it in his protocol at one point but I couldn't find the post and I don't recall which portion he used it for. I'll keep searching.

[Old grandpa]

I found the post on hydroxytyrosol. It was indeed used during fusion, so I will drop it on those days. I have a home bp monitor. I plan to try a half dose of GMS by itself just to keep an eye on its effect on my bp. I have an old unused scrip of metaprolol that I could take if it started rising unless anyone knows of contraindications. I checked for those but GMS wasn't listed.

Edited by Old grandpa, 02 January 2022 - 04:06 AM.

[stephen_b]

I sometimes would take a gram of taurine with the GMS.

[Phoebus]

Do PQQ and CoQ10 promote mito fission or mito fusion? 

 

Same question about ALCAR - fission or fusion or neither? although I think there may not be enough data out there to make that determination. 

 

thanks 

Edited by Phoebus, 05 January 2022 - 05:35 PM.