Why would you mix fission promoters with a fusion promoter?
Oops, mis-remembered when to add BroccoMax in your protocol, with Stearic acid, not with NAM + ribose.
Edited by RWhigham, 25 June 2017 - 10:03 PM.
Posted 25 June 2017 - 09:43 PM
Why would you mix fission promoters with a fusion promoter?
Oops, mis-remembered when to add BroccoMax in your protocol, with Stearic acid, not with NAM + ribose.
Edited by RWhigham, 25 June 2017 - 10:03 PM.
Posted 25 June 2017 - 10:23 PM
In had a similar experience (heawdache and some postural hypotension) doing the atomic protocol Friday (arms and shoulder at 75-80%) and Saturday (mobility work plus some amusment park running with my l.o.), in my case it's obviously sodium depletion and increasing electrolytes fixed it (I use packets from the WHO protocol but it's close to pedialyte). Nothing dramatic as the first time two day-ing the regular protocol. No flu like symptoms just a bit fatigued which resolved by evening. I went nearly 18 hours without eating since Friday night to Saturday's protocol as I just didn't feel like eating until Saturday afternoon. (Electrolyte drink has 14g carbs but I don't count it)I did the Atomic Protocol this morning again and I am now sure it's causing an annoying drop in my BP. My typical uncorrected BP is 135/85 and by evening it was 105/65. The annoying part is that the drop in BP causes a headache in the back of my head. BP should be normal again in the morning like the last time I did the protocol. I recall Turnbuckle mentioned this drop in BP before so it must be a common occurance. I am just curious as to what is causing it and if everyone's experience is similar.
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Edited by zorba990, 25 June 2017 - 10:43 PM.
Posted 27 June 2017 - 04:20 AM
I also did the atomic protocol this morning 8AM-to-10AM. My BP before the protocol was 104/70. My BP 3-hrs after the protocol was 102/64. In between I felt normal so I didn't check it. This contrasts sharply with post #114 (11 days ago) when my BP took a nose dive.
This time I took:
T=0 2 g NAM + 5 g ribose + 2 caps BroccoMax
In the fission protocol we take nicotinamide + ribose + exercise to raise the NAD+/NADH ratio
which causes an increase in mitochondrial fragmentation ref
A well known property of BroccoMax (sulforaphane) is increasing Nrf2. ref
Nrf2 increases NQO1 (unless blocked by BET as sometimes happens in old age).
NQO1 oxidizes NADH to NAD+ quickly increasing the NAD+/NADH ratio. ref
A less well known property of BroccoMax (sulforaphane) is that it inhibits Drp1 in mitochondria. ref
Drp1 forms loops around the mitochondria to split them apart.
No Drp1 = no fission. So my "fission protocol" did not work due to the misguided addition of BroccoMax.
List of natural Nrf2 activators in order of effectiveness
(shows the fold increase in Nrf2 attainable compared to milk thistle) ref
Edited by RWhigham, 27 June 2017 - 04:30 AM.
Posted 27 June 2017 - 05:10 AM
Edited by Female Scientist, 27 June 2017 - 05:12 AM.
Posted 27 June 2017 - 08:44 AM
A note on the lysine/TMG I'd originally included with fission in the atomic protocol--
Moving this to an off day and combining it with fusion (by adding stearic acid) gave me the same hypotensive/drowsy/drugged feeling I experienced taking it the first time. Each of these ingredients is mitochondrially active, but how this is lowering BP so effectively is mysterious. It is certainly worth exploring as a treatment for hypertension
Edited by Turnbuckle, 27 June 2017 - 08:45 AM.
Posted 27 June 2017 - 09:06 AM
Can we presume that the drop in BP is triggered by the TMG/Lysine combination and not the N+R?A note on the lysine/TMG I'd originally included with fission in the atomic protocol--
Moving this to an off day and combining it with fusion (by adding stearic acid) gave me the same hypotensive/drowsy/drugged feeling I experienced taking it the first time. Each of these ingredients is mitochondrially active, but how this is lowering BP so effectively is mysterious. It is certainly worth exploring as a treatment for hypertension
Posted 27 June 2017 - 01:33 PM
The other major mechanism is that betaine is as an osmolyte, or a molecule that is shuttled in and out of a cell to affect its hydration status. Similar to Creatine, increased intracellular concentrations of betaine promote cell hydration ref
Perhaps 1-2 g of TMG sends enough water into muscles to lower BP. The more muscle you have, the bigger the effect.
Edited by RWhigham, 27 June 2017 - 01:36 PM.
Posted 27 June 2017 - 01:37 PM
Thanks for the update. Even though I'm 49, my BP has always been low -- so low that postural hypotension is occasionally an issue. Definitely looking to try an atomic-type profile, but hoping not to pass out in the processA note on the lysine/TMG I'd originally included with fission in the atomic protocol--
Moving this to an off day and combining it with fusion (by adding stearic acid) gave me the same hypotensive/drowsy/drugged feeling I experienced taking it the first time. Each of these ingredients is mitochondrially active, but how this is lowering BP so effectively is mysterious. It is certainly worth exploring as a treatment for hypertension
Posted 27 June 2017 - 01:46 PM
Thanks for the update. Even though I'm 49, my BP has always been low -- so low that postural hypotension is occasionally an issue. Definitely looking to try an atomic-type profile, but hoping not to pass out in the processA note on the lysine/TMG I'd originally included with fission in the atomic protocol--
Moving this to an off day and combining it with fusion (by adding stearic acid) gave me the same hypotensive/drowsy/drugged feeling I experienced taking it the first time. Each of these ingredients is mitochondrially active, but how this is lowering BP so effectively is mysterious. It is certainly worth exploring as a treatment for hypertension
If you have low BP, definitely leave off the TMG/lysine. All the protocols I've posted are experimental and only for information purposes.
Posted 27 June 2017 - 06:43 PM
So stearic acid is a bit like shaved candle wax and floats in water, right?
Any thoughts on the merits of a fusion stack of broccomax/meriva curcumin in place of stearic acid?
The fission/fusion stack so far is working very well for me. I did broccomax/meriva curcumin fusion for a day before of my morning long run of 8 miles (13 km), and had a great run with a nice low heart rate for the pace. I started a new round of fission right after the run (nicotinamide, d-ribose, astaxanthin, TMG).
Posted 27 June 2017 - 08:51 PM
Any thoughts on the merits of a fusion stack of broccomax/meriva curcumin in place of stearic acid?
Thanks for mentioning meriva curcumin. The non extended release version looks like an interesting addition to the mito-manipulation toolbox. So now we have--
Fission
N+R (2g+5g)--better with exercise
Fusion
The HT treatment resulted in an enhancement of mitochondrial function, including an increase in activity and protein expression of Mitochondrial Complexes I, II, III and V; increased oxygen consumption; and a decrease in free fatty acid contents in the adipocytes. The mechanistic study of the PPARGC1α activation signaling pathway demonstrated that HT is an activator of 5′AMP-activated protein kinase and also up-regulates gene expression of PPARα, CPT-1 and PPARγ. These data suggest that HT is able to promote mitochondrial function by stimulating mitochondrial biogenesis
Recent evidence points to a strong relationship between increased mitochondrial biogenesis and increased survival in eukaryotes. Branched-chain amino acids (BCAAs) have been shown to extend chronological life span in yeast. However, the role of these amino acids in mitochondrial biogenesis and longevity in mammals is unknown. Here, we show that a BCAA-enriched mixture (BCAAem) increased the average life span of mice. BCAAem supplementation increased mitochondrial biogenesis and sirtuin 1 expression in primary cardiac and skeletal myocytes and in cardiac and skeletal muscle, but not in adipose tissue and liver of middle-aged mice, and this was accompanied by enhanced physical endurance. Moreover, the reactive oxygen species (ROS) defense system genes were upregulated, and ROS production was reduced by BCAAem supplementation.
Edited by Turnbuckle, 27 June 2017 - 09:05 PM.
Posted 27 June 2017 - 10:44 PM
Thanks for this grocery list, Turnbuckle. I'd been thinking about asking for one.
I'm a little confused on 2 non-supplement topics.
Exercise: I gather that the fusion days are supposed to be the mitogenesis days. So fusion days should be for HIIT and anerobic activity, right?
Food: I've heard both sides on this one, but it seems to be leaning towards fasting = increased autophagy and mitophagy. So fasting on fission days would be good, right? (And if this is true, it sounds like AMPK activators would be useful additions to the fission-day stacks.)
Posted 27 June 2017 - 11:22 PM
Posted 27 June 2017 - 11:32 PM
Thanks for this grocery list, Turnbuckle. I'd been thinking about asking for one.
I'm a little confused on 2 non-supplement topics.
Exercise: I gather that the fusion days are supposed to be the mitogenesis days. So fusion days should be for HIIT and anerobic activity, right?
Food: I've heard both sides on this one, but it seems to be leaning towards fasting = increased autophagy and mitophagy. So fasting on fission days would be good, right? (And if this is true, it sounds like AMPK activators would be useful additions to the fission-day stacks.)
My feeling is that fission is good for weights (see exercise like a girl) and fusion is good for aerobics and if you're looking for performance. For both fission and fusion I typically take these supplements first thing in the morning on an empty stomach. For fission I don't eat much and I don't take any antioxidants before working out. Fusion doesn't have these restrictions. This is just what works best for me, don't take it as gospel.
Posted 28 June 2017 - 12:13 AM
My feeling is that fission is good for weights (see exercise like a girl) and fusion is good for aerobics and if you're looking for performance. For both fission and fusion I typically take these supplements first thing in the morning on an empty stomach. For fission I don't eat much and I don't take any antioxidants before working out. Fusion doesn't have these restrictions. This is just what works best for me, don't take it as gospel.
I don't even take the gospel as gospel
What I have discerned so far is that mitogenesis is encouraged by activities intense enough to be anaerobic--i.e. leaves you in heavy oxygen debt. As I understand it, none of the exercise you're describing seems to fall into that category.
If I do activities that leave me gasping for breath--which promotes mitogenesis--would it be better to reserve it for fusion days? Or can mitogenesis be stimulated in both fission and fusion states?
(Or, is the answer, "Nobody knows"?)
Posted 28 June 2017 - 12:19 AM
BTW, here's an example of AMPK ---> fission ---> mitophagy
http://www.cell.com/...4131(16)30066-3
So maybe AMPK inducers would be useful on fission days...
Posted 28 June 2017 - 10:51 AM
If I do activities that leave me gasping for breath--which promotes mitogenesis--would it be better to reserve it for fusion days? Or can mitogenesis be stimulated in both fission and fusion states?
Try it both ways and report back. I've been leery of mitogenesis during fission simply because a mitochondrion containing a single loop undergoing replication (which can take a couple of hours as noted in the quoted material below) would be more likely to be labeled as dysfunctional by the QC machinery, even if it wasn't. This would be even more true when stressed.
------------------------
In regard to the toolbox of supplements I listed in post 191, not all of these go well together. For instance, taking broccoli extract with rhodiola rosea produced a rather unpleasant feeling until I added stearic acid. This is not the first time I've noticed something off with broccoli, and I will be sticking to stearic acid in the future. In any case, the advantage of broccoli was mostly in its short half life when attempting multiple episodes of biogenesis for demethylation. This is dependent on mito biogenesis (mtDNA replication, actually) being fast compared to methylation by methyltransferase. In fact, biogenesis is reasonably fast, but much slower than it is in bacteria--which can replicate their much larger genomes and divide in as little as 20 minutes:
The synthesis of full-length daughter strands [of mtDNA] requires approximately 1 hr, and the entire cycle is completed in approximately 2 hr. This means that the overall rate of polymerization is only -270 nucleotides per minute per strand, one of the slowest in vivo DNA-replication rates reported to date. In contrast, Escherichia coli DNA is replicated at ~200 times this rate.
http://bionumbers.hm...id=104930&ver=8
While I've not found it anywhere, the methylation rate of mtDNA will likely be slow, as it is not critical, and a slow rate allows its epigenetics to evolve in response to the environment.
-------------------------
As for AMPK, exercise is the main activator, but there are supplements as well, such as one sold by Life Extension that contains rose hips and gynostemma.
Edited by Turnbuckle, 28 June 2017 - 11:39 AM.
Posted 29 June 2017 - 09:46 AM
I'm thinking about adding cinnamon to the standard protocol, and I'm debating whether it belongs with fission or fusion.
Back in the early days of your protocol, Turnbuckle, you used cinnamon to augment fission. Your reasoning back then was "Supplements that enhance the genes PINK1 and Parkin, which direct fission and clearance. Such supplements would be include cinnamon and sodium benzoate. Cinnamon alone should be sufficient, as it is metabolized to sodium benzoate." I'm curious why you dropped it from later protocols.
It appears that cinnamon has effects that could be protective of mitochondria.
Of course, it's also an antioxidant. Incidentally, it's an antioxidant that has been found to be synergistic with epicatechin.
Would it be a mistake to include cinnamon on the fusion day(s)? Or is there a better case to be made for using it on a fission day -- as per the original Turnbuckle mitochondria upgrade protocol?
Edited by Empiricus, 29 June 2017 - 09:55 AM.
Posted 29 June 2017 - 11:03 AM
I'm thinking about adding cinnamon to the standard protocol, and I'm debating whether it belongs with fission or fusion.
Back in the early days of your protocol, Turnbuckle, you used cinnamon to augment fission. Your reasoning back then was "Supplements that enhance the genes PINK1 and Parkin, which direct fission and clearance. Such supplements would be include cinnamon and sodium benzoate. Cinnamon alone should be sufficient, as it is metabolized to sodium benzoate." I'm curious why you dropped it from later protocols.
It appears that cinnamon has effects that could be protective of mitochondria.
Of course, it's also an antioxidant. Incidentally, it's an antioxidant that has been found to be synergistic with epicatechin.
Would it be a mistake to include cinnamon on the fusion day(s)? Or is there a better case to be made for using it on a fission day -- as per the original Turnbuckle mitochondria upgrade protocol?
These things evolve and nothing is nailed down. I considered adding sodium benzoate to the fission toolbox but ultimately didn't. Partially because of the safety controversy around benzoate, and because increasing NAD+/NADH seems sufficient--
Active autophagy coupled with rapid mitochondrial fusion and fission constitutes an important mitochondrial quality control mechanism and is critical to cellular health. In our previous studies, we found that exposure of cells to nicotinamide causes a decrease in mitochondrial content and an increase in mitochondrial membrane potential (MMP) by activating autophagy and inducing mitochondrial fragmentation. Here, we present evidence to show that the effect of nicotinamide is mediated through an increase of the [NAD+]/[NADH] ratio and the activation of SIRT1, an NAD+-dependent deacetylase that plays a role in autophagy flux. The [NAD+]/[NADH] ratio was inversely correlated with the mitochondrial content, and an increase in the ratio by the mobilization of the malate-aspartate shuttle resulted in autophagy activation and mitochondrial transformation from lengthy filaments to short dots. Furthermore, treatment of cells with SIRT1 activators, fisetin or SRT1720, induced similar changes in the mitochondrial content.
https://www.ncbi.nlm...pubmed/22493485
I've tried sodium benzoate in gram quantities along with N+R, and didn't see any particular advantage for fission. As for adding it during fusion, I don't see any reason to do that from the last paper you linked to. The object is fusion, not quenching free radicals, and even there the advantage fell with increasing concentration--The interaction was less synergetic when cinnamon extract was added in higher proportion.
Edited by Turnbuckle, 29 June 2017 - 11:23 AM.
Posted 01 July 2017 - 05:43 AM
I've basically been doing fission days several times a week for 3 months. In my case that has consisted of Niacinamide + NR or Ribose + weights. (If my approach seems crude, it's partly because I hadn't been keeping up to date with reports in this thread).
On my non-fission days, I didn't take anything to stimulate fusion. Most days, I have taken at least 125-250 NR regardless. So arguably, I guess I was doing fission constantly (even if I told myself I wasn't). Also, I have been eating 100 grams of 99% dark chocolate every day regardless.
I have not noticed much in the way of positive results and have generally been feeling rather haggard. Also, I am told I look tired a lot of the time. I believe I may be paying a price for having neglected the fusion part of the protocol and contaminating the fission days with stearic acid rich dark chocolate. Basically, I don't think my approach is working.
Therefore, as of this week I am taking fusion days seriously. I am confining my chocolate consumption to the fission days, avoiding all NR on fusion days, and adding high doses of vitamin C to the fusion days.
Also, I will be taking cinnamon on fission days. Thanks, Turnbuckle, for your feedback on cinnamon.
Edited by Empiricus, 01 July 2017 - 06:05 AM.
Posted 01 July 2017 - 07:18 AM
When I perform the fission protocol religiously with weights and with calorie restriction, it takes its toll on my body. MY BP drops significantly by the evening and my muscles are sore for a good 3-4 days. I am comfortable doing fission once a week for now and will look at going to twice a week at some point. I basically don't look forward to the drop in BP (comes with a headache) and would like for muscle soreness to be over before doing fission again.I've basically been doing fission days several times a week for 3 months. In my case that has consisted of Niacinamide + NR or Ribose + weights. (If my approach seems crude, it's partly because I hadn't been keeping up to date with reports in this thread).
Edited by hsibai, 01 July 2017 - 08:10 AM.
Posted 01 July 2017 - 07:29 AM
Edited by hsibai, 01 July 2017 - 07:44 AM.
Posted 01 July 2017 - 09:21 AM
On my non-fission days, I didn't take anything to stimulate fusion. Most days, I have taken at least 125-250 NR regardless. So arguably, I guess I was doing fission constantly (even if I told myself I wasn't). Also, I have been eating 100 grams of 99% dark chocolate every day regardless.
I have not noticed much in the way of positive results and have generally been feeling rather haggard. Also, I am told I look tired a lot of the time. I believe I may be paying a price for having neglected the fusion part of the protocol and contaminating the fission days with stearic acid rich dark chocolate. Basically, I don't think my approach is working.
The point of this experimental protocol is to eliminate defective mitochondria and then create new ones, so just doing one side of this equation is not going to work. And certainly fission all the time is going to make you feel terrible, while mixing fission and fusion supplements is like accelerating a car with the brakes on. In any case, I wouldn't continue any protocol if it makes you feel terrible.
Posted 01 July 2017 - 11:26 AM
When I perform the fission protocol religiously with weights and with calorie restriction, it takes its toll on my body. MY BP drops significantly by the evening and my muscles are sore for a good 3-4 days. I am comfortable doing fission once a week for now and will look at going to twice a week at some point. I basically don't look forward to the drop in BP (comes with a headache) and would like for muscle soreness to be over before doing fission again.I've basically been doing fission days several times a week for 3 months. In my case that has consisted of Niacinamide + NR or Ribose + weights. (If my approach seems crude, it's partly because I hadn't been keeping up to date with reports in this thread).
You are doing far too much if you are sore for 3-4 days. This is not a one size fits all protocol and is not meant to beat you up, so perhaps you should cut down on the exercise and/or the nicotinamide--either to 1 gram or even half a gram. I've been having the opposite problem--the weights have been creeping up even as it became more difficult to develop a burn. And afterwards I wasn't sore at all. So I added ampk activators and pyruvate as a lactic acid source, and I was back to getting a burn very easily with less weight (though I can't say which is more responsible as I added these supplements at the same time).
Edited by Turnbuckle, 01 July 2017 - 11:36 AM.
Posted 01 July 2017 - 11:37 AM
You are doing far too much if you are sore for 3-4 days.
Edited by hsibai, 01 July 2017 - 11:54 AM.
Posted 01 July 2017 - 04:15 PM
The BP drop mechanism remains a mystery and this could very well point to a method for controlling hypertension without the side effects of big pharma hypertension drugs.
Hypertension in rats has been shown to be due to mito damage in the brain stem, so one might expect that fission/fusion would slowly normalize BP. However, at least one paper says that while nicotinamide crosses the BBB, it doesn't contribute to increased NAD. However, the ampk supplements gypenosides and rose hips also cross the BBB, and both are known to reduce BP, perhaps by cleaning up defective mitochondria. The effect is significant but not dramatic, but would likely be greatly improved by incorporation into a fission/fusion protocol.
Niacinamide transport through the blood-brain barrier.
niacinamide is transported rapidly and bidirectionally through the blood-brain barrier by a high capacity transport system. Although involved in the transfer of niacinamide between blood and brain, this transport system does not play an important regulatory role in the synthesis of NMN, NAD, and NADP from niacinamide in brain.
https://www.ncbi.nlm.../pubmed/2952896
Edited by Turnbuckle, 01 July 2017 - 04:16 PM.
Posted 01 July 2017 - 04:48 PM
On my non-fission days, I didn't take anything to stimulate fusion. Most days, I have taken at least 125-250 NR regardless. So arguably, I guess I was doing fission constantly (even if I told myself I wasn't). Also, I have been eating 100 grams of 99% dark chocolate every day regardless.
I have not noticed much in the way of positive results and have generally been feeling rather haggard. Also, I am told I look tired a lot of the time. I believe I may be paying a price for having neglected the fusion part of the protocol and contaminating the fission days with stearic acid rich dark chocolate. Basically, I don't think my approach is working.
The point of this experimental protocol is to eliminate defective mitochondria and then create new ones, so just doing one side of this equation is not going to work. And certainly fission all the time is going to make you feel terrible, while mixing fission and fusion supplements is like accelerating a car with the brakes on. In any case, I wouldn't continue any protocol if it makes you feel terrible.
"Doing fission all the time" describes the way many, if not most people are taking NR. And "accelerating the car with the breaks on" must happen a lot too.
Edited by Empiricus, 01 July 2017 - 04:50 PM.
Posted 01 July 2017 - 05:59 PM
I'm not sure that just taking NR (fission) "accelerates the car with the brakes on" as fusion happens fast. When I started taking NR several years ago, dark hair started growing in a munber of places. It was sparce and grew slowly but it grew. It stopped awhile back which may have been because my body "accomadated" my change (bodies do that). I believe it's helping me in other areas which are much more important to me than hair. I only take a few supplements with my Stearic on "non" supplement days versus the 80 I take on supplement days. I have started to take Stearic along with BroccoMax on a couple of non supplement days like yesterday.
I usually only go to the gym on fission days but went yesterday on a fussion day and broke my old record on the eliptical machine for calories burned (and till near the end, I don't look at calories burned). I also take very little protein in the morning as I want my body (mitochondria) to work harder (maybe clean out the cells a bit more [even though I practice autophagy] - it ain't scientific people, just logical to me). Also do this because of the IGF1 pathway shortening lifespan.
Posted 02 July 2017 - 03:12 AM
Posted 02 July 2017 - 09:55 AM
Any reason not to heat stearic acid? E.g. add it to green tea?
No reason not to, but I expect you will be drinking tea with a layer of oil on top. This may solidify and turn gritty in your mouth, and is thus not the most pleasant tea drinking experience. It disperses well in hot cereals such as oatmeal, changing the flavor slightly.
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