2287 replies to this topic

[Nate-2004]

 

Interesting how it works during ketosis. Does it work as NAD/fission or  NAD/fusion?

 

 

 

It probably works with either, as both are unregulated by a ketogenic diet (KD)--

 

Existing research supports the notion that fission gene expression is upregulated with nutrient availability (Holmström et al., 2012; Jheng et al., 2012) and fusion genes are upregulated with nutrient deficiency (Rambold et al., 2011). Contrary to this, the present liver and brain data suggest a global upregulation of fission and fusion genes when fed the KD.

https://www.ncbi.nlm...les/PMC5186794/

 

 

 

Both fission and fusion simultaneously?

[Turnbuckle]

Doesn't seem that great, does it? Still, it should be easy enough to push them in one direction or another, just as stearic acid trumps NAD+/NADH--or seems to, in my experience.

[Nate-2004]

I'd love to know why it has such a significant impact on my essential tremor after a couple of weeks of KD. If it's related to mitochondrial mutation or what. It's a sort of lasting effect that doesn't just go away after I cycle off the diet.

[lost69]

i check BP, pulse, HRV, Rmssd and reaction time everyday at wake up (same time) to be sure gdf11 dose is not too much.

 

on the first fission day HRV and rmssd got to the lowest value, pulse a little higher to 64, reaction time good.on fusion they improved but lower than baseline

 

second day of fission jan 19th at 1800, lowest value of HRV and rmssd, pulse 60 and reaction time good.

after fission hrv and rmssd kept going further down despite taking the fusion supplements

 

energy levels are very good even the day of fission jan 19th

 

 

 

 

can this be a everyday protocol with few days fission per months when most defective mitos are cleared?

i also use AMPK from LEF but what do you mean by 1g?many pills so that gynostemma+rose hip reaches 1g so 2 pills?

 

i forgot to mention in my previous feedback that while my BP lowered a little (125-130/85-90 to 115-120/80-85) my pulse increased from 55-60 to 65-70 at the same time HRV worsen a lot:

HRV from 57-47 to 49-45 and rmssd from 50-30 to 14-20.i take HRV to see cardio improvement from gdf11 use but rmssd (many studies corralate this to cardio health) has worsen a lot on the protocol for now (it could also be from gdf11, when it reaches a point beyond what is needed it lowers HRV/rmssd instead of increasing it, my doses are very very very low on gdf so this should be unlikly)

 

 

 

 

 

2 500mg pills.

 

As for HRV, was this during (or after) fission or fusion? It appears that HRV is sensitive to the condition of mitochondria, so if you are deleting them during fission, it's possible that it will lower HRV. HRV is used by at least one group to assess mito health--http://www.mitochondrialtherapy.com/

 

 

[zorba990]

High energy protocol — NAD/fusion (experimental)


Rationale: While high NAD+/NADH typically drives mitochondria into fission, stearic acid overrides that and drives them into fusion, producing a high ATP state.

(morning, 3 days)
Nicotinamide (NAD) — 2g
Ribose (NAD) — 2g
Stearic acid (fusion) — 5g
AMPK activators (Life Extension or jiaogulan leaf) — 1g

Warning: While NAD/fission drops my BP, NAD/fusion raises it. I had to triple my anti-hypertension dosage on the first day.

Results: After three days this feels similar to my first experience with C60 in 2012. That is, more energy, flexibility, and more youthful looking skin. With C60 the effects faded, at least in part as it did nothing to eliminate defective mitochondria.

Can you add the lysine tmg combo to lower the bp effect?

[BieraK]

So, has anyone done the (N+R)+AMPK protocol while doing a Ketogenic Diet?
In my experience the N+R gets me off ketosis, it feels like I loose the increased energy, low inflammatioj and clarity of mind, and then puts me in a fatigued state with a bit of brain fog.

I wonder if this is particular to me or if the D-Ribose/Nicotinamide has something to do, in the past AMPK activators, specially Gynostemma with or without Grape Seed haven't shown dimished effect on my ketogenic state, on the contrary these seem increase it. 

[PAMPAGUY]

High energy protocol — NAD/fusion (experimental)


Rationale: While high NAD+/NADH typically drives mitochondria into fission, stearic acid overrides that and drives them into fusion, producing a high ATP state.

(morning, 3 days)
Nicotinamide (NAD) — 2g
Ribose (NAD) — 2g
Stearic acid (fusion) — 5g
AMPK activators (Life Extension or jiaogulan leaf) — 1g

Warning: While NAD/fission drops my BP, NAD/fusion raises it. I had to triple my anti-hypertension dosage on the first day.

Results: After three days this feels similar to my first experience with C60 in 2012. That is, more energy, flexibility, and more youthful looking skin. With C60 the effects faded, at least in part as it did nothing to eliminate defective mitochondria.

[PAMPAGUY]

Turnbuckle, Icannot handle 2 gm dosages at this time. Will try with 1 gm each. Should I take half dosage of Stearic Acid also? It might be possible to handle higher dose with the Stearic acid added to mitigate the fission. Will wait and see.

Thanks

[Andey]

So, has anyone done the (N+R)+AMPK protocol while doing a Ketogenic Diet?
In my experience the N+R gets me off ketosis, it feels like I loose the increased energy, low inflammatioj and clarity of mind, and then puts me in a fatigued state with a bit of brain fog.

I wonder if this is particular to me or if the D-Ribose/Nicotinamide has something to do, in the past AMPK activators, specially Gynostemma with or without Grape Seed haven't shown dimished effect on my ketogenic state, on the contrary these seem increase it. 

 

  As far as I am aware of I don't get out of ketosis, but I haven't measured it extensively. At least on a night protocol, I am well within ketosis at waking up. An hour after N+R+delayed exercise I have ketones at 0.6-1.2 and blood sugar up to 6. But I am quite sure it's about the same with exercise only. My usual ketone levels are pretty high though, so anything below 1.2 is a sign of a overstretch for me. 

[Andey]

Doesn't seem that great, does it? Still, it should be easy enough to push them in one direction or another, just as stearic acid trumps NAD+/NADH--or seems to, in my experience.

 

  Seems like no proper data exists at this moment but at least in vitro ketones show a beneficial effect on MQC.

https://www.ncbi.nlm...pubmed/15389892

Impairment of mitochondrial energy metabolism has been associated with a wide range of human disorders. Large-scale partial deletions of mitochondrial DNA (mtDNA) cause sporadic Kearns-Sayre syndrome, a fatal multisystem disorder, in which the majority of mtDNAs in affected tissues have deletions (Delta-mtDNAs). Since most mtDNA-related diseases, including Kearns-Sayre syndrome, are recessive, only a few wild-type mtDNAs can compensate for the deleterious effects of many Delta-mtDNAs. We have developed a pharmacological approach to reduce the proportion of Delta-mtDNAs in vitro, in which we grow cells in medium containing ketone bodies, replacing glucose as the carbon source. Cells containing 100% Delta-mtDNA died after 5 days of treatment, whereas those containing 100% wild-type mtDNA survived. Furthermore, in a cloned heteroplasmic cell line, the proportion of wild-type mtDNA increased from 13% initially to approximately 22% after 5 days in ketogenic medium and was accompanied by a dramatic improvement in mitochondrial protein synthesis. We also present evidence that treatment with ketone bodies caused "heteroplasmic shifting" not only among cells (ie, intercellular selection) but also within cells (ie, intracellular selection). The demonstration that ketone bodies can distinguish between normal and respiratorily compromised cells points to the potential use of a ketogenic diet to treat patients with heteroplasmic mtDNA disorders.

 

Unfortunately, only abstract is available.

[Turnbuckle]

 

 

Seems like no proper data exists at this moment but at least in vitro ketones show a beneficial effect on MQC.

https://www.ncbi.nlm...pubmed/15389892

 

Unfortunately, only abstract is available.

 

 

 

 

This, like millions of papers can be found on that Russian site-- http://sci-hub.tw/

 

It's an old paper, however, and doesn't mention fission or fusion or mitophagy. In any case, it says--

 

 

We have found that ketone bodies can be used to distinguish between respiratory-competent and respiratory incompetent cells. We have also shown that ketogenic medium can shift the heteroplasmy of cells harboring a mixture of wild-type and partially deleted mtDNAs. This heteroplasmic shift was probably due to an intracellular selection for wild-type mitochondria, with a concomitant rescue of mitochondrial protein synthesis that occurred largely within 2–3 days of this treatment, and was complete by day 5. The nearly complete restoration of protein synthesis in cells harboring more than 20% wt-mtDNAs is consistent with the threshold values for function seen previously by others.

 

 

That sounds good in general, but not always. In one mice study, KD increased the population of swollen and defective mitochondria, what another paper called zombies--

 

Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABAA) receptor subunits α1. However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial in mitochondrial disorders.

https://www.ncbi.nlm...les/PMC5629920/

 

[Turnbuckle]

Turnbuckle, Icannot handle 2 gm dosages at this time. Will try with 1 gm each. Should I take half dosage of Stearic Acid also? It might be possible to handle higher dose with the Stearic acid added to mitigate the fission. Will wait and see.

Thanks

 

 

I wouldn't cut the stearic acid. It's already minimal for this purpose and most people get quite a bit in their diet. The long term problem with taking a fusion promoter, of course, is reducing fission and thus quality control, while in the short term it can show benefits, as in this 4 week trial--

 

CONCLUSION: Results from this study indicate that stearic acid (19g/day) in the diet has beneficial effects on thrombogenic and atherogenic risk factors in males. The food industry might wish to consider the enrichment of foods with stearic acid in place of palmitic acid and trans fatty acids.

https://www.ncbi.nlm...pubmed/11305631

 

 

That's a rather irresponsible recommendation based on such a short trial, when long term it could have negative effects on the mitochondrial population.

 

For protocols alternating between fusion and fission I minimized it only because of its long half life--17 hours. Works for me, but others may need more. And I should repeat, I've only tried these things on myself. Results may vary.

Edited by Turnbuckle, 26 January 2018 - 11:10 AM.

[Andey]

 

 

 

 

  Looks like it's not a one size fits all approach and KD could inhibit or promote different types of mtDNA mutations. Like everything in life thought )

In vivo, even with glucose sparing, there would be still some glucose available inside cells and first, beneficial, study would not translate so well to real life.

[PAMPAGUY]

Here is the latest paper on NAD precussors. Excellent. Thanks to Turnbuckle for unlock website

http://www.cell.com/...4131(17)30670-8

[Andey]

Here is the latest paper on NAD precussors. Excellent. Thanks to Turnbuckle for unlock website

http://www.cell.com/...4131(17)30670-8

 

  I've looked through some of the references and overall picture still looks very uncertain. Is it that NMN converts first to NR, is it that NR converts first to NAM (except for the small amount that got through by Nrk1) etc.

Maybe its as simple as d-ribose is a limiting factor. CFS sufferers on phoenixrising reports boost in energy after small d-ribose supplementation(doctors even prescribe it)  that cannot be explained via small carbohydrate intake.

http://forums.phoeni...lly-works.4309/

 

It could make sense as we have some NAM levels available that salvage pathway could not process. Adding ribose on itself would be an equivalent to taking some NR.

I will try to modify protocol and take ribose, not in one chunk but in a few separate dosages separated by hour intervals.

[Heisok]

I have a sugestion for a test. Take a dose of D-Ribose on it's own. Maybe 2 plus grams. Test yout blood sugar before and 15 to 20 minutes after. My results show a short term spike in blood glucose from low 100 range to around 130, before going down within an hour or so, but not lower than it started. If you are using the Stearic acid, chew on some a little bit before washing it down with water. Use the same test as above. I am not challenging the protocol, as the reports of those who are Ketogenic seem to be excellent. I test B.G. but not Ketoes. Recently my Dr. added a Ketone urine and blood test to some other labwork my Beta hydroxybutyrate was 3.8, and my Urine Ketones were around 80 mg

 

For some reason, maybe very low carb diet related, I am intolerant to D-Ribose. Multiple tests with 2 different manufacturer's months apart. I used to take it in 5 to 10 gram doses years ago with no known issues, but I do not recall those specifics except I was never low carb. It is many years ago, and the posters did not follow up to report on any resolution to their issues, but 2 individuals who were very low carb, had bad reactions to D-Ribose.

 

Since I am posting, I will report an observation. (It is not with N but is with N.R.) I quit taking it for a long time. I am taking an 820 mg dose once or twice per day of Gynostemma extract. Every time I tried to restart N.R., I was very tired. It was frustrating, and I tried many times. When I thought about Turnbuckles work, I guess that the 2 combined simply create too much fission for me. When I take the N.R. or Gynostemma separately, I am fine.

 

So, has anyone done the (N+R)+AMPK protocol while doing a Ketogenic Diet?
In my experience the N+R gets me off ketosis, it feels like I loose the increased energy, low inflammatioj and clarity of mind, and then puts me in a fatigued state with a bit of brain fog.

I wonder if this is particular to me or if the D-Ribose/Nicotinamide has something to do, in the past AMPK activators, specially Gynostemma with or without Grape Seed haven't shown dimished effect on my ketogenic state, on the contrary these seem increase it. 

 

[Andey]

 

Here is the latest paper on NAD precussors. Excellent. Thanks to Turnbuckle for unlock website

http://www.cell.com/...4131(17)30670-8

 

  I've looked through some of the references and overall picture still looks very uncertain. Is it that NMN converts first to NR, is it that NR converts first to NAM (except for the small amount that got through by Nrk1) etc.

Maybe its as simple as d-ribose is a limiting factor. CFS sufferers on phoenixrising reports boost in energy after small d-ribose supplementation(doctors even prescribe it)  that cannot be explained via small carbohydrate intake.

http://forums.phoeni...lly-works.4309/

 

It could make sense as we have some NAM levels available that salvage pathway could not process. Adding ribose on itself would be an equivalent to taking some NR.

I will try to modify protocol and take ribose, not in one chunk but in a few separate dosages separated by hour intervals.

 

 

I've tried it today actually. I took 2gr NAM + 3 1gr doses of ribose separated by an hour, the last one was before exercise.  Felt a bit dizzy, my exercise capacity drops a bit and I got more fatigued after the workout.

My BG went up to 7(140 mg/dL)but I am still in ketosis as ketone level is 1.2. (never thought its even possible to reach diabetic level of BG  while staying in ketosis)

Overall it looks like I fissioned deeper this time. The only caveat, I took LEF AMPK for the first time too as I got it delivered yesterday.

 

P.S. Thanks, Turnbuckle, that Russian site is a real treat ) 

Edited by Andey, 27 January 2018 - 11:08 AM.

[zorba990]

Here is the latest paper on NAD precussors. Excellent. Thanks to Turnbuckle for unlock website

http://www.cell.com/...4131(17)30670-8

I've looked through some of the references and overall picture still looks very uncertain. Is it that NMN converts first to NR, is it that NR converts first to NAM (except for the small amount that got through by Nrk1) etc.
Maybe its as simple as d-ribose is a limiting factor. CFS sufferers on phoenixrising reports boost in energy after small d-ribose supplementation(doctors even prescribe it) that cannot be explained via small carbohydrate intake.
http://forums.phoeni...lly-works.4309/

It could make sense as we have some NAM levels available that salvage pathway could not process. Adding ribose on itself would be an equivalent to taking some NR.
I will try to modify protocol and take ribose, not in one chunk but in a few separate dosages separated by hour intervals.

I've tried it today actually. I took 2gr NAM + 3 1gr doses of ribose separated by an hour, the last one was before exercise. Felt a bit dizzy, my exercise capacity drops a bit and I got more fatigued after the workout.
My BG went up to 7(140 mg/dL)but I am still in ketosis as ketone level is 1.2. (never thought its even possible to reach diabetic level of BG while staying in ketosis)
Overall it looks like I fissioned deeper this time. The only caveat, I took LEF AMPK for the first time too as I got it delivered yesterday.

P.S. Thanks, Turnbuckle, that Russian site is a real treat )

Is it possible one or more things you are taking are interfering with the BG test?
I know vitamin c is reported to do that.

[Nate-2004]

I don't use nearly that much ribose in my mix. I put 1g NAM for every 750mg Ribose. I don't know if even that much ribose is necessary. I think the NAM is more important. I still take NR though.  When I'm on keto and maintaining around 2.5 to 3.5 blood ketone levels I don't get kicked out of it by taking ribose, but then again I'm not taking nearly as much.

Edited by Nate-2004, 27 January 2018 - 04:26 PM.

[PAMPAGUY]

Nate

Read the cell.com article above. Ribose enabled Nicotinamide to enter cell. No Riboside no NAD

[Turnbuckle]

Nate

Read the cell.com article above. Ribose enabled Nicotinamide to enter cell. No Riboside no NAD

 

 

I can't find where it says that. It does hit on the importance of NAMPT.

Edited by Turnbuckle, 27 January 2018 - 07:15 PM.

[Nate-2004]

Nate

Read the cell.com article above. Ribose enabled Nicotinamide to enter cell. No Riboside no NAD

 

Interesting. Yeah I'm still including ribose just not nearly as much as you guys.

[BieraK]

Well the next time while on Keto I will try just N+R without ginostemma.

Maybe Keto Diet + Fission protocol is the best way to eliminate damaged mitochondria. I have not seen any study that shows the effects of ketogenic diet in conjunction with interventions that stimulate mitophagy

 

So at this time, we can say that standard doses Nicotinamide Riboside consumption produces its effects on health through increasing mitochondrial fission?

[lost69]

it took 9days of fusion but today HRV registered the highest pick i ve ever had (hrv 62, rmssd 55.8), if these values hold in time i really upgraded my cardio system.thank you for pointing out the correlation between hrv and mito

 

shall i give fission protocol a break for this week?i felt nothing at this second round of fission although it lowered hrv as ever

 

 

 

can this be a everyday protocol with few days fission per months when most defective mitos are cleared?

i also use AMPK from LEF but what do you mean by 1g?many pills so that gynostemma+rose hip reaches 1g so 2 pills?

 

i forgot to mention in my previous feedback that while my BP lowered a little (125-130/85-90 to 115-120/80-85) my pulse increased from 55-60 to 65-70 at the same time HRV worsen a lot:

HRV from 57-47 to 49-45 and rmssd from 50-30 to 14-20.i take HRV to see cardio improvement from gdf11 use but rmssd (many studies corralate this to cardio health) has worsen a lot on the protocol for now (it could also be from gdf11, when it reaches a point beyond what is needed it lowers HRV/rmssd instead of increasing it, my doses are very very very low on gdf so this should be unlikly)

 

 

 

 

 

2 500mg pills.

 

As for HRV, was this during (or after) fission or fusion? It appears that HRV is sensitive to the condition of mitochondria, so if you are deleting them during fission, it's possible that it will lower HRV. HRV is used by at least one group to assess mito health--http://www.mitochondrialtherapy.com/

 

 

Edited by lost69, 28 January 2018 - 09:15 AM.

[Turnbuckle]

 

it took 9days of fusion but today HRV registered the highest pick i ve ever had (hrv 62, rmssd 55.8), if these values hold in time i really upgraded my cardio system.thank you for pointing out the correlation between hrv and mito

 

shall i give fission protocol a break for this week?i felt nothing at this second round of fission although it lowered hrv as ever

 

 

 

 

 

 

Perhaps you might stop both and watch the hrv. I'd expect it to drift down as the stearic acid is metabolized, and hopefully it will stabilize at a higher baseline.

[lost69]

i used broccomax only and some raw cocoa in oat milk, i couldn t find stearic acid in europe.if it's really needed i ll buy it from US

 

 

 

it took 9days of fusion but today HRV registered the highest pick i ve ever had (hrv 62, rmssd 55.8), if these values hold in time i really upgraded my cardio system.thank you for pointing out the correlation between hrv and mito

 

shall i give fission protocol a break for this week?i felt nothing at this second round of fission although it lowered hrv as ever

 

 

 

 

 

 

Perhaps you might stop both and watch the hrv. I'd expect it to drift down as the stearic acid is metabolized, and hopefully it will stabilize at a higher baseline.

 

 

[PAMPAGUY]

 

i used broccomax only and some raw cocoa in oat milk, i couldn t find stearic acid in europe.if it's really needed i ll buy it from US

 

 

 

it took 9days of fusion but today HRV registered the highest pick i ve ever had (hrv 62, rmssd 55.8), if these values hold in time i really upgraded my cardio system.thank you for pointing out the correlation between hrv and mito

 

shall i give fission protocol a break for this week?i felt nothing at this second round of fission although it lowered hrv as ever

 

 

 

 

 

 

Perhaps you might stop both and watch the hrv. I'd expect it to drift down as the stearic acid is metabolized, and hopefully it will stabilize at a higher baseline.

 

 

 

[PAMPAGUY]

lost69,

Bee Beautiful Stearic Acid (1kg)

I live in europe also.  Got my Stearic Acid from Amazon.uk.  

 

Kerry

I would like to apoligize to the board and Nate for my comment on using Ribose with Nicotinamide.  I mis-spoked without rereading the article.  I completely blew it.  Sorry again.

 

 

[lost69]

thanks but that item doesn t look foodgrade.

 

another member just suggested i can get it from compounding pharmacies, i ll get it there easier

 

lost69,

Bee Beautiful Stearic Acid (1kg)

I live in europe also.  Got my Stearic Acid from Amazon.uk.  

 

Kerry

I would like to apoligize to the board and Nate for my comment on using Ribose with Nicotinamide.  I mis-spoked without rereading the article.  I completely blew it.  Sorry again.

 

[mag1]

  Here's a recent mito story that I hope will be of interest to the thread.

  Mitochondria are heat generators of the cell; implication for reaction rates.

 

"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."

 

PMID:29370167

Edited by mag1, 28 January 2018 - 07:47 PM.