2284 replies to this topic

[Nate-2004]

Is anyone trying ice baths for biogenesis?

[sumguy90]

I apologize is this has been answered but I haven't foufd the answer in the thread. Has anyone tried apigenin yet?

I will report my extremely limited data that I tried 500mg niacinamide with 1500mg ribose and a strong cup of chamomile lavender tea before bed. The result was I woke up feeling completely wiped out and caught a bad cold, and as I'm still recovering from the cold haven't tried it again.

Edited by sumguy90, 05 October 2017 - 02:24 AM.

[Turnbuckle]

I apologize is this has been answered but I haven't foufd the answer in the thread. Has anyone tried apigenin yet?

I will report my extremely limited data that I tried 500mg niacinamide with 1500mg ribose and a strong cup of chamomile lavender tea before bed. The result was I woke up feeling completely wiped out and caught a bad cold, and as I'm still recovering from the cold haven't tried it again.

 

 

I've tried apigenin and didn't see any advantage to it, but I'd already been doing the fission/fusion protocol for some time. When starting this, I would go in gingerly and not include all the extras. I made that mistake myself by starting out with four days in a row of just nicotinamide, ribose (2g/5g) and light exercise. I did okay until the fourth day, then was wiped out for a week. Overwhelming the lysosomal system could potentially be a problem, as can heavy depletion of mitochondria.

 

In response to modest mitophagy, myocytes can utilize their mitochondrial reserve to maintain energy production without affecting contractility. However, excessive mitophagy in the absence of mitochondrial biogenesis will result in the depletion of the bioenergetic reserve in the remaining mitochondria and subsequent cell death.

 

https://www.ncbi.nlm...les/PMC3538875/

 

 

Once defective mitochondria are brought down to reasonable levels, this shouldn't be a problem. At least in my experience.

[Fafner55]

Once defective mitochondria are brought down to reasonable levels, this shouldn't be a problem. At least in my experience. 

 

 

 

I can confirm that experience.

[sumguy90]

Given that lactate promotes such drastic biogenesis I think I'll avoid it until I've gotten rid of more bad mitochondria.

Does anyone know how powerful pqq is for biogenesis?

Does anyone have an intuition for what kind of balance might be optimal between fission and pqq biogenesis to avoid inefficiencies from replicating bad mitochondria in a person with a lot?

Edited by sumguy90, 05 October 2017 - 02:50 PM.

[Nate-2004]

I don't think that's necessary to wait, and I agree with Turbuckle's most recent suggestion that fission should be well separated from fusion and 3 days of fission followed by 3 days of fusion followed by 1 day break sound like what would be ideal so long as you aren't on keto. I'm still not sure about vitamin C recycling on keto or if it's that dangerous to go 3 days without it or what. Not sure how much of a role insulin plays in that but vitamin C is apparently important especially between fission into fusion from what I gather.  I'm adopting his 3/3 protocol soon as I'm off keto in a week.

Edited by Nate-2004, 05 October 2017 - 07:19 PM.

[Turnbuckle]

More thoughts on how to taper off the protocol. 

 

Once defective mitochondria are completely eliminated*, then there is no point in continuing. In post 438 I advocated leaving the protocol with several days of fusion, thus leaving cells with a high mitochondrial mass. But that's not the only concern. Another is where the NAD+/NADH ratio is at that point. In my experience that ratio seems to be surprisingly persistent, and a state of fusion is not a good place to leave it. So tailing off with a final fission dose to raise the NAD+ level might be best. One dose is not going to do much to the mito mass, especially if they are all healthy. Then the question is what to do long term. If the decline of NAD+ with age is due to the decline of healthy mitochondria in a vicious feedback loop, then one could leave it there. But if there is some other source for the decline of NAD+, then topping off NAD+ with an occasional small dose of N+R might be required.

 

*The cellular load of defective mitochondria is likely to vary considerably from cell to cell in a stochastic fashion. Some may already be close to death due to a heavy load of them, and thus will require much longer to return to a healthy state. 

[Nate-2004]

I thought NAD decline was due to an increase in NAD dependent CD38 which in turn could be due to SASP.

[Turnbuckle]

I thought NAD decline was due to an increase in NAD dependent CD38 which in turn could be due to SASP.

 

This paper certainly makes a case for CD38 eating up NAD, in which case N+R supplementation should continue. And that suggests other supplements post protocol--

 

 We confirmed that quercetin is a CD38 inhibitor in vitro and in cells. Importantly, we demonstrate that apigenin is a novel inhibitor of CD38 in vitro and in vivo. Treatment of cells with apigenin or quercetin inhibits CD38 and promotes an increase in intracellular NAD+ levels. 

 

http://diabetes.diab...ntent/62/4/1084

 

 

Edited by Turnbuckle, 06 October 2017 - 01:27 PM.

[ambivalent]

Turnbuckle,

 

A couple of questions:

 

Is 5HTP likely to be fine instead of tryptophan? Have you ever used NR? 

 

I've tried high doses of both regimes although not an especially controlled way. In particular while consuming very high doses of NR I was taking a lot of Sulforaphane,  which perhaps expectedly let to some wildly inconsistent effects. Undoubtedly, though, part of the problem was raised histamine levels firing up a seasonal allergy (NR, NAM undoubtedly increased histamine, while NA seemed to reduce it). Even before then, though, at times when dosing high I would experience considerable brain fog and the next day remarkable clarity. With N+R there was brain fog/headaches without the  heightened clarity but I was very rough with doses. When I weighed it out as accurately as I could one evening before sleep, I awoke to the expressed muscle tone you'd described but also had failed to notice when changing the dose, so it is no surprise that the improved muscle tone was a one-off. 

 

I've just started taking the odd high doses of NR 2-3 grams and I've experienced some of those headache symptoms, I do believe I felt some improvement when taking ribose, but I will know with certainty in time if this is the case. But if it is true Ribose can relieve these intermittent but quite consistent (for me) symptoms of NR then this would add weight to your argument of NR -> N+R. However, I still feel that NR is doing something different to N+R especially as I've not noticed anyone report the mental acuity experienced with NR while taking N+R.

 

I was wondering if you would consider experimenting with high doses of NR to see if there is distinct experience. I realise it is a cost but would happily to contribute $100 to some crowd-sourced longecity fund.

 

Also it would be great to see an update of your experience a few months in. In particular you observed improvement in your skin. Has this continued and do you still put this down to lysine (ingestion or application) N+R or both? 

 

 

  

 

Edited by ambivalent, 06 October 2017 - 01:52 PM.

[Turnbuckle]

Turnbuckle,

 

A couple of questions:

 

 

 

Is 5HTP likely to be fine instead of tryptophan? Have you ever used NR? 

 

Why would it be fine? I wasn't aware that it converted to NAD+ (though it may participate in oxidizing NADH). And yes, I tried NR, but didn't notice much of anything. I gave NR to my wife, who also noticed nothing, but did from N+R, and continues to take it (even though she's adverse to taking anything).

 

I've tried high doses of both regimes although not an especially controlled way. In particular while consuming very high doses of NR I was taking a lot of Sulforaphane,  which perhaps expectedly let to some wildly inconsistent effects. Undoubtedly, though, part of the problem was raised histamine levels firing up a seasonal allergy (NR, NAM undoubtedly increased histamine, while NA seemed to reduce it). Even before then, though, at times when dosing high I would experience considerable brain fog and the next day remarkable clarity. With N+R there was brain fog/headaches without the  heightened clarity but I was very rough with doses. When I weighed it out as accurately as I could one evening before sleep, I awoke to the expressed muscle tone you'd described but also had failed to notice when changing the dose, so it is no surprise that the improved muscle tone was a one-off. 

 

NR + sulforaphane is pissing in the wind.

I can't say about the brain fog as I've never experienced it. However, fission will naturally reduce ATP production and could thus impact brain functioning, esp. if you have a lot of dysfunctional mitochondria.

 

I've just started taking the odd high doses of NR 2-3 grams and I've experienced some of those headache symptoms, I do believe I felt some improvement when taking ribose, but I will know with certainty in time if this is the case. But if it is true Ribose can relieve these intermittent but quite consistent (for me) symptoms of NR then this would add weight to your argument of NR -> N+R. However, I still feel that NR is doing something different to N+R especially as I've not noticed anyone report the mental acuity experienced with NR while taking N+R.

 

One of the biggest improvements I've gotten out of the Fission/Fusion protocol is in mental acuity. And it has all been N+R.

 

I was wondering if you would consider experimenting with high doses of NR to see if there is distinct experience. I realise it is a cost but would happy to contribute $100 to some crowd-sourced longecity fund.

 

Even if I wanted to, it's too late.

 

Also it would be great to see an update of your experience a few months in. In particular you observed improvement in your skin. Has this continued and do you still put this down to lysine (ingestion or application) N+R or both? 

 

I'd put skin improvement about equal to C60 when I first started it, and that was very good. It doesn't do anything for crosslinking, however, and for that I've found dermal rolling to be quite impressive when used with a water solution of lysine.

[ambivalent]

Thanks TB.

 

5htp: My mistake, I had some recollection 5htp was a precursor to tryptohan, not the otherway round.

 

NR + sulforaphane dosing I undertook certainly wasn't pissing in the wind, I experienced some quite dramatic effects in both physical endurance and mental agility. In addition (I felt) a more youthful look after a few days. Naturally, I can't compare the effects of high dose NR without the Sulforaphane - it may well be that I didn't dose sufficiently high enough to offset the amount of NR I was consuming.

 

Why would it be too late? If NR and N+R are operating similarly then there should be no discernible difference to you, which would be a very powerful result?

 

Nate: have you noticed enhanced cognitive effects with N+R too?

 

 

EDIT (unfinished!)

Edited by ambivalent, 06 October 2017 - 02:27 PM.

[Turnbuckle]

 

 

NR + sulforaphane dosing I undertook certainly wasn't pissing in the wind, I experienced some quite dramatic effects in both physical endurance and mental agility. In addition (I felt) a more youthful look after a few days. Naturally, I can't compare the effects of high dose NR without the Sulforaphane - it may well be that I didn't dose sufficiently high enough to offset the amount of NR I was consuming.

 

 

 

NR promotes fission while sulforaphane inhibits it. However, sulforaphane has a half life of around 2.5 hours while NR isn't absorbed until it is digested, so won't even begin to act for about 4 hours. So maybe the better analogy is to ships passing in the night.

[MikeDC]

Aging causes mitochandrial dynamics dysfunction and mitochandrial fragmentation. So aging most likely affects fusion more than fission. Exercise activate pgc-1a to counter mitochandrial fragmentation. So will calorie restriction and NR

https://www.ncbi.nlm...ubmed/28577890/

So NR supplementation restores mitochandrial dynamics. Not just favor fission. There is an dynamic equilibrium between fusion and fission that maintain healthy cells. So saying NR favors fission is not correct. Artificially manipulate mitochandrial dynamics is not healthy and beneficial for health or anti aging.

[ambivalent]

That might explain the effects, though I've had some quite quick responses to NR - particularly w.r.t histamine. There were certainly delayed effects, generally there was a build-up to the cognitive eutopia of days of high dosing. Equally though I did sometimes experience a buzz quite quickly from NR, though some of the more immediate effects could have been down to trans-ptero. The delayed effect was also born out by a friend of mine who dosed two consecutive days and noticed profound physical and mental effects of day 2 (around 700mg/day with TP). However, there was certainly a rapid NR response on histamine - I can't rule out Sulforaphane being involved but I'm pretty sure it was NR, I had the same effect with NAM (hayfever symptoms within the hour). There is evidence of Nicotinamide raising histamine which I posted on one of the NR threads. That said it may not have taken much as my 'histamine bucket' would have been full (I also believe I read and possibly posted that histamine can increase alertness).

 

 

 

[MikeDC]

The idea that you can control healthy mitochandria to only fusion or fission in the time frame of days is ridiculously. The dynamics in the phrase of "mitochandrial dynamics" has a meaning. It means fusion and fission are ocuring continuously in the time frame of minutes. It will definitely harm your health by stopping either fission or fussion on the scale of days. I don't even think it is possible. Your body will be in a disease state when that happens.

[Richard McGee]

The idea that you can control healthy mitochandria to only fusion or fission in the time frame of days is ridiculously. The dynamics in the phrase of "mitochandrial dynamics" has a meaning. It means fusion and fission are ocuring continuously in the time frame of minutes. It will definitely harm your health by stopping either fission or fussion on the scale of days. I don't even think it is possible. Your body will be in a disease state when that happens.

I've read through this thread completely at least three times. No one is making the claim you apparently believe they are making. "Manipulating mitochondrial dynamics" does not mean stopping anything.

Edited by Richard McGee, 06 October 2017 - 05:22 PM.

[Turnbuckle]

After half a year of fission/fusion I am now transitioning to a maintenance program. That will likely vary as much as the protocol did, but is presently 500 mg nicotinamide and 700 mg ribose. (For those who recognize that NR must be digested before absorption, this is equivalent to 1 gram of NR.) I am also continuing with AMPK activators. Previously they greatly decreased my appetite, but that effect faded a bit with time. Salicates are known to increase their effectiveness by binding to AMPK, but have drawbacks like tinnitus, so I'm looking around for alternatives.

 

 

[Nate-2004]

Turnbuckle, why transition now? What kinds of things have you noticed at this point as far as over all effects and improvements?

 

Also when I do the same, I may still take NR regularly but separate NR and broccomax into morning and late afternoon respectively. That should be enough separation I think.

[sumguy90]

The idea that you can control healthy mitochandria to only fusion or fission in the time frame of days is ridiculously. The dynamics in the phrase of "mitochandrial dynamics" has a meaning. It means fusion and fission are ocuring continuously in the time frame of minutes. It will definitely harm your health by stopping either fission or fussion on the scale of days. I don't even think it is possible. Your body will be in a disease state when that happens.

It's already been thoroughly discussed that what we think we're taking about is merely tipping the balance, increasing the rate of fission and possibly decreasing the rate of fusion to achieve an equilibrium of many smaller mitochondria, then after atleast hours to allow mitiphagy tipping the balance back to achieve an equilibrium with fewer larger mitochondria then promoting biogenesis.

[Turnbuckle]

Sumguy--Let's not get into debates with Cromadex trolls whose opinions are informed by their financial stake in the company. It's a waste of time and clogs up the thread. 

 

Nate--Six months is longer than I thought it would take to remove defective mitochondria. Are they all removed? I doubt it, but I've gotten to the point that further improvements are difficult to discern. Improvements are similar to those I got from C60 back in 2012, but C60 improvements tended to fade. Today I believe C60 ups mitochondrial function but does nothing for QC.

[sumguy90]

After half a year of fission/fusion I am now transitioning to a maintenance program. That will likely vary as much as the protocol did, but is presently 500 mg nicotinamide and 700 mg ribose.

Why the change in ratio of ribose to nicotinamide? I believe you've been using a ratio either 3:1, 2:1, or 5:2 until now.

[ambivalent]

Today I believe C60 ups mitochondrial function but does nothing for QC.

 

In fact the opposite, judged from your previous observations - c60oo would inhibit mitophagy though extending the lifespan of mitochondria which would otherwise be tagged for recycling. It would be interesting to see the effects of c60oo post-protocol - would there be a greater & extended effect due to the improved quality of the mitochondria, or were it the case the c60 boon was due to c60 ramping up the performance of defective mitochondria. I'm guessing the later is more likely. If there is little effect post-protocol then at least we can ease off c60 although would we not expect there still to be other gains from c60 acting as an ROS scavenger?   

[Turnbuckle]

 

After half a year of fission/fusion I am now transitioning to a maintenance program. That will likely vary as much as the protocol did, but is presently 500 mg nicotinamide and 700 mg ribose.

Why the change in ratio of ribose to nicotinamide? I believe you've been using a ratio either 3:1, 2:1, or 5:2 until now.

 

 

 

With time I reduced the ribose part as unnecessary, and although my latest fission protocol was 1.5g nicotinamide, 1g tryptophan and 2.8g ribose (4 caps of 700 mg ribose), I reported this as 3g ribose so people wouldn't think there was anything magical about it, which there isn't. Now I have 500 mg nicotinamide caps and 700 mg ribose caps, and that's what I'm using. That's it. It's a matter of convenience. To establish a best ratio (if there is one) would require a laboratory and multiple subjects.

Edited by Turnbuckle, 07 October 2017 - 05:43 PM.

[Nate-2004]

Use this pdf as a reference for fission days if you want to avoid stearic acid as much as possible, which is really quite difficult to avoid, especially with keto, but considering I try to fast on these days it works out.

 

Cheddar cheese may have spermadine but it also has stearic acid, so I'll have to drop that from my fission.

 

Turnbuckle I'm considering your MCT formulation of C60 in a few months when I'm done with this protocol.

Edited by Nate-2004, 07 October 2017 - 07:38 PM.

[Nate-2004]

I can't reply to the "Exercise like a girl" thread as it's locked. Probably the title given that it's a little offensive. 

 

However, I'm wondering more about the exercise portion of the protocol. Trying to refine that more today and I wanna know what to do exactly. 

 

I don't typically do weight lifting these days because it tends to hurt my lower back. I switched to bodyweight exercises instead. The question I have though is how to deplete ATP, is it just lower weight more sets and reps?

 

You posted about lactic acid and how it induces biogenesis but is there any way to avoid that? Exercise pretty much guarantees lactic acid on some level no?

 

Edited by Nate-2004, 08 October 2017 - 04:43 PM.

[Turnbuckle]

I can't reply to the "Exercise like a girl" thread as it's locked. Probably the title given that it's a little offensive. 

 

However, I'm wondering more about the exercise portion of the protocol. Trying to refine that more today and I wanna know what to do exactly. 

 

I don't typically do weight lifting these days because it tends to hurt my lower back. I switched to bodyweight exercises instead. The question I have though is how to deplete ATP, is it just lower weight more sets and reps?

 

You posted about lactic acid and how it induces biogenesis but is there any way to avoid that? Exercise pretty much guarantees lactic acid on some level no?

 

 

The thread was locked out when I first posted it, then someone unlocked it (thanks to whoever that was), and now it's locked again. Don't know what to make of it, but given the titles of some threads here I can't image that's the reason.

 

The basic idea is to do weights during heavy fission, where ATP production is at a minimum. Another point touched on briefly in that thread is the impact on lactate--

 

The [NAD+]/[NADH] ratio is reciprocally regulated by the [pyruvate]/[lactate] ratio...

https://www.ncbi.nlm...les/PMC3365962/

 

 

 

Or equivalently, lactate/pyruvate is high when NAD+/NADH is high. So it should be easier to achieve a burn during N+R fission, even though you are using less weight.

 

While the functions of lactate/lactic acid are still emerging science, it seems that this is how the effect of exercise impacts all tissues, including the brain--

 

Additionally, lactate function in the brain is far from being understood; however, apart from being an energy source, it is implicated in important functions such as norepinephrine release and brain plasticity. Lactate is one of many molecules that are increased during exercise, and it is highly transported between tissues, having many different roles. Despite its clear influence in many signaling pathways, it is not clear yet how lactate affects these pathways; therefore, further research must be done to clarify the mechanism by which lactate is mediating adaptations, particularly exercise-induced adaptations. Additionally, due to the apparently positive effects (exercise-like induced adaptations) of lactate in the organism, it would be interesting to consider it as a sports supplement.

https://www.ncbi.nlm...les/PMC5192418/

 

 

Edited by Turnbuckle, 08 October 2017 - 04:57 PM.

[Nate-2004]

So it seems with lactic acid we may have a lot of trouble trying to confine biogenesis to fusion but I suppose we can do our best.

 

I wonder what effect heat stress has had on this protocol, given that I do about 20 mins in the sauna 4x a week. I wonder if heat stress is better for fission while of course cold stress (ice baths) is best left for fusion.

 

There is a lot of learning and absorption to be done on this thread, I appreciate all your contributions.

 

We could try to Wiki all this info once we have a year or so of refinement and then try to teach it with a Youtube video and animations. Who's up for that?

Edited by Nate-2004, 08 October 2017 - 06:23 PM.

[Nate-2004]

Reporting back on the tremor, turns out I was wrong on two counts, it wasn't the keto or this protocol improving my tremor. It was the caprylic (octanoic) acid in the MCT oil I had begun using just prior to starting keto as a means of getting my body used to ketosis and staving off carb hunger. Turns out octanoic acid is a metabolite of 1-octanol which is what they have been spending the last 6 years researching with its effects on tremor. So while unfortunately it was not this protocol, I do still think this may be beneficial to continue for another year. Perhaps that would be more of a strike at the root cause.

 

The upside is that I have found an effective treatment that is at least three times as effective as propranolol or even ethanol. How I managed to miss this connection, I don't know.

 

I'm on my 6th cycle of fusion (I think) and I feel fantastic. I'm coming out of keto so we'll see what changes. I'll have to worry less about stearic acid on fission days.

Edited by Nate-2004, 10 October 2017 - 06:43 PM.

[mrkosh1]

Nate,

 

My mother's essential tremor is continuing to grow more worrisome and mine perhaps subsided for a short time due to fasting. I'm fascinated with MCT oil being a potential treatment. A 90% reduction in symptoms is phenomenal. If you could answer a few questions, I'd appreciate it.

 

1) My concern with MCT Oil is the laxative effect. A few years ago I was consuming coconut oil as part of a low carb diet but before I could boost my dosage I ended up having horrible diarrhea (although I think I was overdoing it physically at the time too which also enhanced the effect). What dose are you taking and have you noticed any laxative effect?

 

2) How do you mix MCT Oil with your coffee? Do you blend it like the folks who make bulletproof coffee with grass fed butter do? 

 

3) What is the name of the app you are using to measure your essential tremor? I have an older android phone. If the app is compatible with it, I'd be interested in testing both my mother and myself before and after MCT Oil. 

 

4) What is the mechanism that you think the caprylic acid is using to fight essential tremor? Is it the caprylic acid itself or is something happening like the caprylic acid being converted into keytones?