74 replies to this topic

[Turnbuckle]

Today when I tried the protocol, and made sure to note actually how the pumped-up appearance progressed. On bodybuilding sites, it seems that this is achieved during exercise, and for some in a matter of seconds. But it didn't work that way for me with N+R. Going to the gym 2 hours after beginning the protocol, I didn't note any hyperemia while exercising, and not until an hour later did it begin to appear, maxed out at two hours, and then faded away after another six hours. So that is suggestive of an initial decrease of ATP due to fission, and then a subsequent increase in ATP. I certainly did seem to have more muscle capacity during this time.

 

Allowing 4 hours to pass between beginning the protocol and the gym might give very different results.

[aconita]

Pumping might be GH related since pumping is known to become evident at high reps with short pauses between sets and we know that leads to GH peaks, we know the pumping doesn't really last long and we know exercise induced GH doesn't last long as well.

 

While on MK677 (a strong oral GH secretagogue) the pumping is 24-24.

 

MK677 leads to sweaty nights (typical of high GH), N+R leads me to the same (or very similar anyway), I am getting no noticeable pumping from N+R...nor during, after or later on exercising.

 

N+R seems somehow effecting my hoariness in a very similar way MK677 does, I don't know if it is due by sensitization of receptors, increased testosterone or DHT conversion, while on MK677 my tested testosterone was average.

 

I am finding certain aspects of N+R similar to MK677 (high GH), not all of them and certainly each one has its own peculiarity but I can't help to find some similarities which is totally unexpected (hardly a placebo here).

 

Because of the above considerations, which I have an hard time to consider just as coincidences, I think there is some anecdotal evidence pointing to an influence of N+R to the hormonal equilibrium, GH and related IGF-1 in particular.

 

No data to support the above, of course, but nevertheless i wouldn't be too quick to dismiss the hypothesis. 

[recon]

Where does resveratrol fit into these?
Stilbenoids are said to activate NAMPT which is required to convert niacinamide so resveratrol will be a fine addition to the nicianiamide.

However it is also, aside from being an antioxidant, said to blunt benefits from exercises.

[BieraK]

Turnbuckle what do you think about using BCCAs or Leucine as pre-workout shake with this protoctol?

Trained in a fasted state is a very common practice nowadays, and works well for reducing body fat and increasing muscle mass, however some aminoacids specially Leucine are used preveting muscle loss and enhancing fat use as a fuel, I've read that luecine is considered anti-catabolic in this way. So I wonder if the effects of Luecine or BCCAs could prevent or reduce the catabolic nature of mitopaghy. The same I wonder about eating protein meal or breakfeast before excercise 

[Turnbuckle]

Turnbuckle what do you think about using BCCAs or Leucine as pre-workout shake with this protoctol?

Trained in a fasted state is a very common practice nowadays, and works well for reducing body fat and increasing muscle mass, however some aminoacids specially Leucine are used preveting muscle loss and enhancing fat use as a fuel, I've read that luecine is considered anti-catabolic in this way. So I wonder if the effects of Luecine or BCCAs could prevent or reduce the catabolic nature of mitopaghy. The same I wonder about eating protein meal or breakfeast before excercise 

 

I'm using leucine with stearic acid and PQQ for mito fusion/biogenesis. Leucine is a strong promoter of biogenesis and I've avoided doing that during fission, as I fear that mitochondria with a single DNA loop undergoing replication could be mistaken as defective by the QC machinery. See this figure. As for protein, I take that afterward, and I've found MK-677 to be useful.

Where does resveratrol fit into these?
Stilbenoids are said to activate NAMPT which is required to convert niacinamide so resveratrol will be a fine addition to the nicianiamide.

However it is also, aside from being an antioxidant, said to blunt benefits from exercises.

 

I've used resveratrol with fission and it works well. However, it gives me joint problems, thus I avoid it.

Edited by Turnbuckle, 05 November 2017 - 09:15 PM.

[BieraK]

Thank you for such a quick response.

Apparently you have experience and knowledge about body building and related things.


1) What do you recommend for a fasted training (Like the Leangains protocol 16/8) while using N+R? The problem with doing resistance training in a total fasted state is muscle breakdown, fat is used also as a fuel, but if there is not some BCCAs or Leucine, muscle will be used for fuel also :/. However using Leucine with N+R could be counterproductie. Do you know a possible solution to this "pseudo-dilema"? or what do you think about this. My goal is to use this N+R protocol for building muscle also, however there is some stubborn fat that with age becomes harder to "burn". In the past I was doing a fasted training but without any BBCAs, just water first thing in the morning and then exercise, it worked well for gaining muscle and loosing fat, however I was younger at that time and stubborn fat was burning easy compared to my 29.

2) How many hours do you recommend between the end of the workout and a meal/protein shake?. Intuitively I tend to think that the more hours go between the end of the workout and the consumption of protein or fusion supplements, the greater the mitophagy. Basically I wan't to know if could be ok to take a protein shot (or a meal) for repairing muscle breakdown after the N+R workout and not hindering or decrease the protocol effectiveness.


 

Edited by BieraK, 05 November 2017 - 09:14 PM.

[recon]

BCAAs can be used by the muscle as fuel.
If the goal is to reduce energy production to expenditure ratio to the point that the body sees a need for more mitochondria (biogenesis) or the need to remove dysfunctional ones for efficiency (mitophagy), then shouldn’t BCAAs and proteins be avoided during the exercise?

Edited by recon, 05 November 2017 - 09:39 PM.

[Turnbuckle]

Thank you for such a quick response.

Apparently you have experience and knowledge about body building and related things.


1) What do you recommend for a fasted training (Like the Leangains protocol 16/8) while using N+R? The problem with doing resistance training in a total fasted state is muscle breakdown, fat is used also as a fuel, but if there is not some BCCAs or Leucine, muscle will be used for fuel also :/. However using Leucine with N+R could be counterproductie. Do you know a possible solution to this "pseudo-dilema"? or what do you think about this. My goal is to use this N+R protocol for building muscle also, however there is some stubborn fat that with age becomes harder to "burn". In the past I was doing a fasted training but without any BBCAs, just water first thing in the morning and then exercise, it worked well for gaining muscle and loosing fat, however I was younger at that time and stubborn fat was burning easy compared to my 29.

2) How many hours do you recommend between the end of the workout and a meal/protein shake?. Intuitively I tend to think that the more hours go between the end of the workout and the consumption of protein or fusion supplements, the greater the mitophagy. Basically I wan't to know if could be ok to take a protein shot (or a meal) for repairing muscle breakdown after the N+R workout and not hindering or decrease the protocol effectiveness.


 

 

I'm no body building expert. I just stumbled onto the N+R/exercise combination and loved it as I got a far better workout with considerably less effort, and (presumably) got rid of defective mitochondria at the same time. I cannot give advice to real body builders because I'm simply not doing that level of workout. I can say that I'm approaching the results I got 20 years ago when I went gym-crazy for six months and was working out 2 hours a day, drenched in sweat and using all the weights on most of the machines. Now I see those people as annoying, as now I'm doing half an hour every other day, not sweating at all, and using girly weights. Fat is slowly turning into muscle, and MK-677 (which I added recently) appears to have accelerated it.

 

You raise an excellent question about how long to wait after a workout before eating. I can only tell you that I have a glass muscle milk in fruit juice when I get home from the gym, and that seems to work fine. It appears that once a mitochondrion loses membrane potential, it can no longer fuse with other mitochondria, and is doomed--

 

Fragmented mitochondria can fuse together if they have normal membrane potential, but loss of membrane potential prevents fusion and leads to mitochondria segregation and subsequent degradation by mitophagy. In contrast, excessive fusion of mitochondria has been shown to inhibit the mitophagy process.

http://www.sciencedi...213231714001189

 

 

See this post for my fission/fusion protocol. To use it for exercise, delete the tryptophan, increase the nicotinamide to 2g, and use it 2 hours before the gym. I'd also leave 24 hours between fission and fusion.

 

I suggest 2-3 days of fission then 3 days of fusion (using stearic acid only on the first day of fusion, due to its 17 hour half-life).  For best fusion/biogenesis, NAD+/NADH should be lowered and the lactate/pyruvate ratio raised (these are inversely linked), and the best lactate-raising exercise is high intensity for short periods. Thus running should go well with fusion, weights with fission.

Edited by Turnbuckle, 05 November 2017 - 11:03 PM.

[whileitravel]

Brenner noted that “Neither NMN, niacin, nor nicotinamide are more efficient than NR at boosting NAD+,” and that “Mega-doses of nicotinamide and ribose are not equivalent to NR because high doses of nicotinamide inhibit sirtuin activities.”

[Turnbuckle]

Brenner noted that “Neither NMN, niacin, nor nicotinamide are more efficient than NR at boosting NAD+,” and that “Mega-doses of nicotinamide and ribose are not equivalent to NR because high doses of nicotinamide inhibit sirtuin activities.”

 

 

Both NR and NMN are substantially broken down into nicotinamide (N) when taken orally--this in spite of researcher/marketers' attempts to confuse the situation. This has been shown in rats (where NMN goes to NR and then to N in the intestines), and the double labeled NR studies blow a lot of smoke, but do not stand up to scrutiny. Most of the NR is digested, and anything that isn't is broken down in the liver. These researchers also compare apples with oranges, comparing NR with N instead of N+R, and marketing NR by saying the peak NAD+ for NR was twice as high as with N, when in fact the peak was transitory and the time-weighted increase obtained by NR vs N was substantially less impressive. So the situation for N+R and NR appears to be substantially the same, except NR has a delay of several hours as it must be digested first into N+R.  This was debated extensively in one of the NR threads, and I have no interest in debating it again here. 

Edited by Turnbuckle, 23 January 2018 - 09:43 AM.

[whileitravel]

 

Brenner noted that “Neither NMN, niacin, nor nicotinamide are more efficient than NR at boosting NAD+,” and that “Mega-doses of nicotinamide and ribose are not equivalent to NR because high doses of nicotinamide inhibit sirtuin activities.”

 

 

Both NR and NMN are substantially broken down into nicotinamide (N) when taken orally--this in spite of researcher/marketers' attempts to confuse the situation. This has been shown in rats (where NMN goes to NR and then to N in the intestines), and the double labeled NR studies blow a lot of smoke, but do not stand up to scrutiny. Most of the NR is digested, and anything that isn't is broken down in the liver. These researchers also compare apples with oranges, comparing NR with N instead of N+R, and marketing NR by saying the peak NAD+ for NR was twice as high as with N, when in fact the peak was transitory and the time-weighted increase obtained by NR vs N was substantially less impressive. So the situation for N+R and NR appears to be substantially the same, except NR has a delay of several hours as it must be digested first into N+R.  This was debated extensively in one of the NR threads, and I have no interest in debating it again here. 

 

I wasn't here to debate you Turnbuckle, I simply saw this late at night and arbitrarily posted it here not knowing this was previously debated! I do have a horse in this though. I'm taking nicotinamide and ribose per your posts.

 

Thanks.

 

 

[CWF1986]

BCAAs can be used by the muscle as fuel.
If the goal is to reduce energy production to expenditure ratio to the point that the body sees a need for more mitochondria (biogenesis) or the need to remove dysfunctional ones for efficiency (mitophagy), then shouldn’t BCAAs and proteins be avoided during the exercise?

 

I'm just speculating, but I'm thinking that unless you're in a fasted state or you're doing a ketogenic diet that wouldn't be an issue.  Muscles preferentially use carbohydrates for fuel.  

 

Typically in regard to muscle, amino acids/protein is best thought as 'building bricks' whereas carbohydrates are the 'workers' and fats affect the signaling through the endrocrine system in potentially 'good' and 'bad' ways.  

[Nate-2004]

Yes, I think earlier in this thread Turnbuckle explains his hypothesis on protein and BCAAs in terms of avoiding ATP production. I'm not sure I still understand it all well. I'm also still mildly offended for women regarding the title of this thread lol. He's an older guy so I give him a pass.

Edited by Nate-2004, 02 February 2018 - 02:48 PM.

[Turnbuckle]

 You are offended for women but you're giving me a pass because I'm old? That's funny, Nate, in an overly politically correct sort of way, but I'll give you a pass because you're young. As for BCAAs, you would not want to include them in any case, as BCAAs (and leucine in particular) promote mitochondrial biogenesis, and I've been leery of doing that during fission as it could result in perfectly good mitochondria being recycled. Better to use BCAAs during fusion.

Edited by Turnbuckle, 02 February 2018 - 03:10 PM.

[Advocatus Diaboli]

Turnbuckle wrote: "...but I'll give you a pass because you're young."

 

lol, a touche for Turnbuckle! (+1 for nuanced mordancy)

 

Also note that, in post 72 of Manipulating Mitochondrial Dynamics, Turnbuckle wrote, in part:

 

"As a side note, I was carded in a restaurant the other day, and the waitress was shocked when she looked at my birth date and realized I was old enough to be her grandfather."

 

That quote might suggest a youngish appearance, amongst other possibilities.

 

So, readers, when was the last time you were carded at a restaurant, etc.? (And I don't mean being told a joke by a wag. har har) 

 

 

 

[whileitravel]

I was 38 and was asked 3 times for id one weekend in Vegas. My buddy was like wth?!

 

That was long ago.

 

My profile picture was 2 years ago. Now 51.

Edited by whileitravel, 03 February 2018 - 04:59 PM.

[Nate-2004]

Haha touche. There's no winning with political correctness.

 

I had no idea that was why you should avoid biogenesis during fission, I didn't realize biogenesis involved recycling. I've been avoiding it all I can, opting for what amounts to a fast around fission points, the only calories being fats (coconut or heavy whipping cream) in my coffee.

Edited by Nate-2004, 03 February 2018 - 05:47 PM.

[HaplogroupW]

 As for BCAAs, you would not want to include them in any case, as BCAAs (and leucine in particular) promote mitochondrial biogenesis, and I've been leery of doing that during fission as it could result in perfectly good mitochondria being recycled. Better to use BCAAs during fusion.

 

Hrmm, I guess my mental model for all this needs updating.  I'd have thought:

 

AA (leucine & cetera) => mTOR activation => increased biogenesis and downregulated mitophagy

 

-vs-

 

nutrient starvation => mTOR inhibition => upregulated mitophagy

 

So taking BCAAs under this (simple-minded?) model would inhibit mitophagy, not cause it. Any chance you could point out what the mechanism is whereby BCAAs would lead to "mitochondria being recycled"? Not trying to be argumentative, merely understand. Thanks.

 

 

[Turnbuckle]

 

 As for BCAAs, you would not want to include them in any case, as BCAAs (and leucine in particular) promote mitochondrial biogenesis, and I've been leery of doing that during fission as it could result in perfectly good mitochondria being recycled. Better to use BCAAs during fusion.

 

Hrmm, I guess my mental model for all this needs updating.  I'd have thought:

 

AA (leucine & cetera) => mTOR activation => increased biogenesis and downregulated mitophagy

 

-vs-

 

nutrient starvation => mTOR inhibition => upregulated mitophagy

 

So taking BCAAs under this (simple-minded?) model would inhibit mitophagy, not cause it. Any chance you could point out what the mechanism is whereby BCAAs would lead to "mitochondria being recycled"? Not trying to be argumentative, merely understand. Thanks.

 

 

 

I haven't found any research directly on point, so it remains speculative. But if mitochondria are fissioned so that they contain a single mtDNA loop and that loop undergoes replication (which is slow compared to bacteria, taking over an hour) one would presume that the proteins required for ATP synthesis would decline. Normally this would not be a problem as mitochondria typically contain several loops of mtDNA, and as long as all are not undergoing replication simultaneously sufficient protein should be available and the membrane potential maintained. Therefore it is safer to stimulate biogenesis during fusion rather than fission. This is employed in my later thread, Manipulating mitochondrial dynamics, where mitochondria are fissioned and mitphagy encouraged for several days, and then the reverse where mitochondria are fused and biogenesis encouraged. 

 

And if mitophagy is down-regulated, then the problem of deleting good mitochondria is lessened, as is the advantage of eliminating bad ones during exercise. So there is no good reason for adding BCAAs.

Edited by Turnbuckle, 04 February 2018 - 11:11 AM.

[matrix83]

n=1. Took N+R on two mornings and was unusually wiped out by the evening. The morning of the third day (while still fasted), had a very big PR in the gym by my standard. Will try again later this week. Great threads BTW.  

[QuestforLife]

Turnbuckle, do you still get the same initial fatigue using your fission protocol?

 

I can certainly attest to the effects of N+R the first couple of times I took it, but I almost don't feel it now if I do it once a week. I'm thinking my mitochondria are in good condition now and I probably only need to do this once a month or so. I'm 39 and in good shape.

[Turnbuckle]

Turnbuckle, do you still get the same initial fatigue using your fission protocol?

 

I can certainly attest to the effects of N+R the first couple of times I took it, but I almost don't feel it now if I do it once a week. I'm thinking my mitochondria are in good condition now and I probably only need to do this once a month or so. I'm 39 and in good shape.

 

This effect will decline as you get rid of defective mitochondria. At that point it can be useful to reverse the protocol and use N+R with fusion. While N+R promotes fission, it appears that stearic acid will override that and drive mitochondria into fusion anyway, and if you add in supplements that promote ATP output, you can create a temporary state of super-health that promotes age regression. Of course you don't want to do that all the time as mito QC is suspended, but a few days makes a noticeable difference.

 

Supplements to promote ATP include CoQ10, L-Carnitine, and B vitamins and minerals used by mitochondria. C60 might be useful, but I haven't tried it yet with this reversed protocol.

Edited by Turnbuckle, 06 February 2018 - 12:13 PM.

[Nate-2004]

While N+R promotes fission, it appears that stearic acid will override that and drive mitochondria into fusion anyway, 

 

 

The thing is almost everything you eat has stearic acid in it to one degree or another, meat, dairy, avocado, flaxseed, nuts, etc. Were you avoiding all those things? I find it hard to avoid stearic acid so I've likely never really had a full fission experience. Only way I can think of to do it is to fast for more than 24 hrs and if the half life is 17 hrs for stearic acid then even that really isn't long enough to matter.

[Turnbuckle]

That's a good point, Nate. The average intake of stearic acid in the Western diet is very high, and is likely keeping many in a state of mito fusion most of the time. And this could result in disease and premature aging. On the other hand, low stearic acid is associated with obesity. So best if stearic acid is consumed in an intermittent fashion, or mitochondria driven into fission from time to time, overriding the diet. Apigenin with N+R seems to produce greater muscle weakening, and this is likely due to deeper level of mito fission. 

[Nate-2004]

That's a good point, Nate. The average intake of stearic acid in the Western diet is very high, and is likely keeping many in a state of mito fusion most of the time. And this could result in disease and premature aging. On the other hand, low stearic acid is associated with obesity. So best if stearic acid is consumed in an intermittent fashion, or mitochondria driven into fission from time to time, overriding the diet. Apigenin with N+R seems to produce greater muscle weakening, and this is likely due to deeper level of mito fission. 

 

Here is a very long list of foods with stearic acid, I'd probably conclude that all food has it to a small degree. Celery, Parsley, these have 1mg.

 

https://wholefoodcat...d/foods/high/1/

[QuestforLife]

This effect will decline as you get rid of defective mitochondria. At that point it can be useful to reverse the protocol and use N+R with fusion.

Supplements to promote ATP include CoQ10, L-Carnitine, and B vitamins and minerals used by mitochondria. C60 might be useful, but I haven't tried it yet with this reversed protocol.

Thanks for that Turnbuckle. I wonder about C60. I read you noted some time ago that when you used C60 with N+R it wiped you out for a good while and you concluded they were not a good combination. But operating on the assumption that atleast part of the mechanism of C60's action is its localisation to the mitochondria, via acquiring a charge first in the cyctoplasm, you'd expect that to cause a drop in membrane potential. So maybe the C60 and N+R is a 'good' combination in that it causes an almighty cull of fissioned mitochondria. But it would be a brave man to test this hypothesis!

[Turnbuckle]

 

This effect will decline as you get rid of defective mitochondria. At that point it can be useful to reverse the protocol and use N+R with fusion.

Supplements to promote ATP include CoQ10, L-Carnitine, and B vitamins and minerals used by mitochondria. C60 might be useful, but I haven't tried it yet with this reversed protocol.

Thanks for that Turnbuckle. I wonder about C60. I read you noted some time ago that when you used C60 with N+R it wiped you out for a good while and you concluded they were not a good combination. But operating on the assumption that atleast part of the mechanism of C60's action is its localisation to the mitochondria, via acquiring a charge first in the cyctoplasm, you'd expect that to cause a drop in membrane potential. So maybe the C60 and N+R is a 'good' combination in that it causes an almighty cull of fissioned mitochondria. But it would be a brave man to test this hypothesis!

 

 

 

Actually, it was niacin and not N+R. The combination of a gram of niacin and C60 was most unpleasant. And it may have been the flush that caused it. Still, I wouldn't advise combining C60 with N+R in a fission state, but I expect C60/N+R in a fusion state (using stearic acid) will be different.

[Nate-2004]

So what I'll probably do to avoid stearic acid is start with a fast for up to 24h, then go with my usual spinach or kale smoothies minus the avocado, then stick to eating a classic very low fat high carb diet for those three days. I'll ramp up the NAM+R and NR starting on day 1 and do my light resistance exercises each day, mostly bodyweight calisthenics. That should do the trick. Will report back.

[Randynaz]

Anybody got any brand recommendations or does it matter. I’m just trying to do the basic fission fusion starting out light. Just got off of C60 was on it got about 3 month straight. I can notice a big difference in my energy. I was diagnosed with narcolepsy at 17, whole still more sleepy than the average person on c60 I didn’t take any of my wakey meds. So I’m hoping to replicate those effects to a degree...

[capob]

Interestingly, in waiting 3 hours before exercise, with the following variation on protocol, I find my output capacity is nearly doubled.

 

- 0h

- - 3g niacinimide

- - 5g ribose

- - 2g pyruvate

- - 3g lactate

- - 2g TMG (account for niacinimte metabolism)

- - AMPK activators (mitophagy)

- - - jiaogulan/gynostemma 1g

- - SIRT1 activators (mitophagy)

- - - Fisetin 100mg

- 1.5 hr

- - apigenin (said to have faster metabolism (1hr)) (AMPK activators (mitophagy)) 100mg

- 3hr

- - exercise

 

Apart from the potential balancing component of lactate to pyruvate decreasing NAD/NADH ratio, I'm inclined to think this is a result of having hyper fused or fission-deficient mitochondria (my NAD levels were previously nearly always low)

 

https://www.ncbi.nlm...59/#!po=64.2857

"Here we observed further clustering of nucleoids in mitochondrial fission-deficient cells via mitochondrial hyperfusion. "

"It was recently reported that mitochondrial hyperfusion with highly developed cristae occurs during nutrient starvation to protect mitochondria from autophagic degradation and sustained cell viability "

"However, even though mito-bulbs have highly stacked cristae with abundant mtDNA, they do not enhance respiration, and the physiological roles of mito-bulbs in vivo and in healthy cells remain to be conclusively analyzed."

 

Interestingly, also from that paper:

"In contrast, live imaging of mitochondrial nucleoids in mammals, higher plants, and yeast has revealed that mitochondrial fission occurs independently of nucleoid fission "

 

A few of notes and questions.

 

1. Fission doesn't necessarily decrease ATP production - (hyperfused mitochondria is inefficient)

2. How long does fission take.  Could the reduction in output capacity you see be a result of working out during the process of fission, in which there would indeed be an ATP production diminishment?

3. Wouldn't it be more sensible to work out after fission occurs instead of during?  IE, isn't the idea to destroy faulty mitochondria, not to make them by inducing stress during fission?