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Manipulating mitochondrial dynamics

nad nad+ c60 mito fission fusion stearic acid mtdna methylene blue

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#1471 Turnbuckle

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Posted 20 January 2020 - 09:35 AM

This question is for Turnbuckle.  Noticed that you blamed Statins for messing up your mitochondria.  I take 5 mg Crestor.  Would you recommend I stop taking this.  Know your not a Doctor, but just asking for your personal opinion.  Not asking for medical advise.  I like to keep my LDL as low as possible is the reason for it.  I'm 73 yo male in good health.

 

I found Crestor to be a mito poison. All statins are poisons, and in my opinion the pharmaceutical industry is running the biggest medical scam in history. Fig. 1 of this massive study will indicate your CV mortality risk  for your age group, BP, sex, and smoking status. The study found that for women, higher cholesterol is protective overall, and for men there is a sweet spot, with low cholesterol worse than high cholesterol.


Edited by Turnbuckle, 20 January 2020 - 09:37 AM.

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#1472 mitomutant

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Posted 20 January 2020 - 09:54 AM

 

Today is the first day of fission and I started with 50mg of B3 (NIACINA) and 500mg of RIbose, therefore a ratio of 1:10.
 
 

 

AFAIK, niacine is not the same as nicotinamide; different therapeutics effects. Not sure if using Niacin is valid for this protocol

 



#1473 Turnbuckle

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Posted 20 January 2020 - 10:13 AM

AFAIK, niacine is not the same as nicotinamide; different therapeutics effects. Not sure if using Niacin is valid for this protocol

 

Niacin plus ribose will also raise NAD+ and create fission.  I have experimented with both together (1g each of niacin and nicotinamide and 2g of ribose), but haven't decided if there's any advantage to it. See Fig. 5B of the Brenner paper. Here they compared the NAD+ produced by NR vs nicotinamide or niacin. They did not use ribose with the nicotinamide or niacin, and they used twice as much NR as nicotinamide or niacin by weight. So not exactly a fair test. Note that both niacin and nicotinamide produce NAD+ quickly, with niacin faster than nicotinamide. Nicotinamide produces a longer term effect as its half-life is longer. NR takes about 4 hours to get going, apparently because it has to be broken down first, thus I don't recommended it for this protocol. The higher NAD+ peak reached by NR is likely due to NR supplying ribose, as ribose is a scarce commodity in cells. Thus it makes more sense to take N+R to begin with and not wait for digestion of NR to N+R.


Edited by Turnbuckle, 20 January 2020 - 10:35 AM.

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#1474 JPY

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Posted 20 January 2020 - 10:37 AM

Do you take ribose and niacinamide on an empty stomach together in the morning?

 

Yes. Sometimes I also took 1g/1g in the morning (empty stomach) and 1g/1g in the mid-afternoon, which also seemed to work but the effect was less intense. 


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#1475 mitomutant

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Posted 20 January 2020 - 12:22 PM

Niacin plus ribose will also raise NAD+ and create fission.  I have experimented with both together (1g each of niacin and nicotinamide and 2g of ribose), but haven't decided if there's any advantage to it. See Fig. 5B of the Brenner paper. Here they compared the NAD+ produced by NR vs nicotinamide or niacin. They did not use ribose with the nicotinamide or niacin, and they used twice as much NR as nicotinamide or niacin by weight. So not exactly a fair test. Note that both niacin and nicotinamide produce NAD+ quickly, with niacin faster than nicotinamide. Nicotinamide produces a longer term effect as its half-life is longer. NR takes about 4 hours to get going, apparently because it has to be broken down first, thus I don't recommended it for this protocol. The higher NAD+ peak reached by NR is likely due to NR supplying ribose, as ribose is a scarce commodity in cells. Thus it makes more sense to take N+R to begin with and not wait for digestion of NR to N+R.

 

Thanks. Crystal clear now.



#1476 Kentavr

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Posted 20 January 2020 - 07:25 PM

Niacin plus ribose will also raise NAD+ and create fission. I have experimented with both together (1g each of niacin and nicotinamide and 2g of ribose), but haven't decided if there's any advantage to it. See Fig. 5B of the Brenner paper. Here they compared the NAD+ produced by NR vs nicotinamide or niacin. They did not use ribose with the nicotinamide or niacin, and they used twice as much NR as nicotinamide or niacin by weight. So not exactly a fair test. Note that both niacin and nicotinamide produce NAD+ quickly, with niacin faster than nicotinamide. Nicotinamide produces a longer term effect as its half-life is longer. NR takes about 4 hours to get going, apparently because it has to be broken down first, thus I don't recommended it for this protocol. The higher NAD+ peak reached by NR is likely due to NR supplying ribose, as ribose is a scarce commodity in cells. Thus it makes more sense to take N+R to begin with and not wait for digestion of NR to N+R.


Turnbuckle, why aren't you using NMN in your protocols?

#1477 Turnbuckle

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Posted 20 January 2020 - 07:38 PM

Turnbuckle, why aren't you using NMN in your protocols?

 

I always look for the least expensive and most available ingredients. I know that N+R works, and 4g of N+R costs under fifty cents while while 4g of NMN costs about $25 -- 50 times more. So it's an easy decision. 

 

Of course, people can use whatever expensive substitute they want. I'm just reporting what I use.


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#1478 PAMPAGUY

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Posted 27 January 2020 - 06:35 AM

I found Crestor to be a mito poison. All statins are poisons, and in my opinion the pharmaceutical industry is running the biggest medical scam in history. Fig. 1 of this massive study will indicate your CV mortality risk  for your age group, BP, sex, and smoking status. The study found that for women, higher cholesterol is protective overall, and for men there is a sweet spot, with low cholesterol worse than high cholesterol.

Turnbuckle, thank you for responding to my question on statins.  Paper very informative.



#1479 kurt9

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Posted 27 January 2020 - 06:53 PM

I also think Statins are poison as well. Statins shutdown production of Coenzyme Q, which is an essential compound used in the electron transport chain in mitochondria. To interfere with such a fundamental process (metabolism is probably the most fundamental process in animal life) in order to prevent cholesterol accumulation in blood vessels does not make bio-engineering sense. Yet this is what passes for modern medicine.

 

BTW, I'm on my third week of the mito fission/fusion protocol (I plan to do 10 rounds of this) and notice that I feel somewhat crappy during day 2 and 3 of fission. Is this normal? 



#1480 Turnbuckle

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Posted 27 January 2020 - 08:58 PM

 

BTW, I'm on my third week of the mito fission/fusion protocol (I plan to do 10 rounds of this) and notice that I feel somewhat crappy during day 2 and 3 of fission. Is this normal? 

 

 

No reason to kill yourself with it. If it's too much you could try alternating days, using N+R on day 1, sulforaphane and PQQ on day 2, then repeating that sequence as necessary. (Using no apigenin or stearic acid, which have long half lives.) I haven't tried that myself, but I don't see why it wouldn't work. If you have been poisoned by statins, it could take quite a few cycles to get rid of the damage.

 


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#1481 kurt9

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Posted 28 January 2020 - 04:47 AM

No, I've never used Statins. I've never had any reason to. One can't avoid hearing about them. So, I decided to look them up and see how they work. That reaction chain graphic that you see everywhere on the net makes clear they are generally bad for you. I suspect I have a cold. I was traveling last week and did not get much sleep. I expect to feel better tomorrow or the next day.



#1482 Turnbuckle

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Posted 28 January 2020 - 08:56 AM

No, I've never used Statins. I've never had any reason to. One can't avoid hearing about them. So, I decided to look them up and see how they work. That reaction chain graphic that you see everywhere on the net makes clear they are generally bad for you. I suspect I have a cold. I was traveling last week and did not get much sleep. I expect to feel better tomorrow or the next day.

 

 

You definitely don't want to do mito fission if you have any sort of virus. For colds and the flu, cells are filled up with viral particles, which are then released by cell death and rupture. Mito fission can potentially enhance both processes hijacked by viruses and make the disease worse--

 

 

Autophagy and apoptosis are two major interconnected host cell responses to viral infection, including influenza A virus (IAV)...Taken together, our data indicate that PR8 infection simultaneously induces autophagy and Bax/caspase-dependent apoptosis, with autophagy playing a role to support PR8 replication, in part, by modulating virus-induced apoptosis.

https://www.ncbi.nlm...pubmed/29108912

 


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#1483 longcity90

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Posted 28 January 2020 - 12:59 PM

If during the day we practice a controlled fasting with a consequent increase in NAD + AMPK compared to NADH, and we use niacinamide, ribose to induce fission ... what do you think if in the evening we make a single meal in a narrow period of time of about 1-2 hours with components used in fusion? the two phases would be obtained within 24 hours. Does this make sense ?



#1484 Nate-2004

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Posted 29 January 2020 - 09:03 PM

1. You can also boost NAD+ with T's recommended amount of niacinamide and a bioavailability enhanced apigenin ( basically just add black pepper extract, fish oil and a small amount of vitamin c on an empty stomach with 50mg apigenin). This is the active part of a NAD+ supplement that Nuchido is selling. I do not know if it would help to add D Ribose but I may start trying that. 

 

2. I think dark chocolate (the more cocoa solids the better probably) has a good amount of stearic acid in it, and less so palmitic. Mango butter definitely has the better ratio. C16:0 is terrible while C18:0 is good. I doubt there's any real way to separate palmitic and stearic without a real lab.  As mentioned earlier sulforaphane will also do the trick but I don't think the same in vivo study has been done on humans yet. Also I can't have too much saturated fat as my FTO polymorphism won't allow for it. I also don't know, based on the in vivo human study, if the normal triglyceride form of saturated fat that you would get in a natural butter like cocoa or mango is the same as the pure form they studied. Sulforaphane bypasses Nrf2 to induce fusion but not sure about stearic, I googled it and can't find any mention. Not even sure this matters.

 


Edited by Nate-2004, 29 January 2020 - 09:06 PM.


#1485 Blu

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Posted 29 January 2020 - 09:17 PM

Further options are glycerol monostearate and shea butter.

BTW, the former is very appreciated in bodybuilding as a pre-WO because it enhances strength and energy. Which could suggest fusion, at this point.



#1486 QuestforLife

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Posted 29 January 2020 - 09:25 PM

2. I think dark chocolate (the more cocoa solids the better probably) has a good amount of stearic acid in it, and less so palmitic. Mango butter definitely has the better ratio. C16:0 is terrible while C18:0 is good. I doubt there's any real way to separate palmitic and stearic without a real lab. As mentioned earlier sulforaphane will also do the trick but I don't think the same in vivo study has been done on humans yet. Also I can't have too much saturated fat as my FTO polymorphism won't allow for it. I also don't know, based on the in vivo human study, if the normal triglyceride form of saturated fat that you would get in a natural butter like cocoa or mango is the same as the pure form they studied. Sulforaphane bypasses Nrf2 to induce fusion but not sure about stearic, I googled it and can't find any mention. Not even sure this matters.


The in vitro study with sulforaphane used 50uM concentration, which seems to me to be a totally unobtainable dose in Vivo. See http://dx.doi.org/10...dox.2016.11.007

At least the stearic acid study was in people. Having said that, they stirred pure stearic acid into a banana milk shake and somehow ingested it (and in the supplementary info stirred it into heated water and drank that to eliminate any contribution to fusion from the milkshake!) How could you possibly digest that? See DOI:10.1038/s41467-018-05614-6

Stick to Turnbuckle's brownies or use glycerol monostearate in water I think.
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#1487 Nate-2004

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Posted 29 January 2020 - 11:30 PM

The in vitro study with sulforaphane used 50uM concentration, which seems to me to be a totally unobtainable dose in Vivo. See http://dx.doi.org/10...dox.2016.11.007

At least the stearic acid study was in people. Having said that, they stirred pure stearic acid into a banana milk shake and somehow ingested it (and in the supplementary info stirred it into heated water and drank that to eliminate any contribution to fusion from the milkshake!) How could you possibly digest that? See DOI:10.1038/s41467-018-05614-6

Stick to Turnbuckle's brownies or use glycerol monostearate in water I think.

 

I think it's hard to judge any effective human dose from an in vitro study. Glycerol monostearate in water? How is that the same thing as stearic acid? Regardless of where you get stearic acid, there is always going to be a strong mix of palmitic unless you can get it from the lab source others on this board got it from. I missed out on that.


Edited by Nate-2004, 29 January 2020 - 11:32 PM.


#1488 mitomutant

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Posted 03 February 2020 - 12:29 PM

One week into the simplified protocol (pqq/NAM+Ribose on alternate days).

 

Noting better endurance at the gym (HIIT) and improved vitality, but at higher doses (NAM (2g) + Ribose (2g)) I feel light headed and slightly nauseated.

 

Should I persist some more days or lower the dosage a bit ?

 

Thanks.



#1489 Graviton

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Posted 03 February 2020 - 04:24 PM

The in vitro study with sulforaphane used 50uM concentration, which seems to me to be a totally unobtainable dose in Vivo. See http://dx.doi.org/10...dox.2016.11.007

At least the stearic acid study was in people. Having said that, they stirred pure stearic acid into a banana milk shake and somehow ingested it (and in the supplementary info stirred it into heated water and drank that to eliminate any contribution to fusion from the milkshake!) How could you possibly digest that? See DOI:10.1038/s41467-018-05614-6

Stick to Turnbuckle's brownies or use glycerol monostearate in water I think.

 

Sulforaphane at 50uM seems to be toxic. 

 

https://www.ncbi.nlm...pubmed/28142224

 

 

 

NSCs were exposed to SFN at the concentrations ranging from 0.25 to 10 µM.

 

 

 

The expression of key proteins in the Wnt signaling pathway, including β-catenin and cyclin D1, in response to SFN treatment or the Wnt inhibitor, DKK-1, was determined by Western blotting. No significant cytotoxicity was seen for SFN on NSCs with SFN at concentrations of less than 10 µM. On the contrary, SFN of low concentrations stimulated cell proliferation and prominently increased neurosphere formation and NSC differentiation to neurons. SFN treatment upregulated Wnt signaling in the NSCs, whereas DKK-1 attenuated the effects of SFN. SFN is a drug to promote NSC proliferation and neuronal differentiation when used at low concentrations.

 

It seems that sulforaphane can be used in other senses at the decently low concentration.


Edited by Graviton, 03 February 2020 - 04:28 PM.


#1490 Graviton

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Posted 03 February 2020 - 05:37 PM

1. You can also boost NAD+ with T's recommended amount of niacinamide and a bioavailability enhanced apigenin ( basically just add black pepper extract, fish oil and a small amount of vitamin c on an empty stomach with 50mg apigenin). This is the active part of a NAD+ supplement that Nuchido is selling. I do not know if it would help to add D Ribose but I may start trying that. 

 

2. I think dark chocolate (the more cocoa solids the better probably) has a good amount of stearic acid in it, and less so palmitic. Mango butter definitely has the better ratio. C16:0 is terrible while C18:0 is good. I doubt there's any real way to separate palmitic and stearic without a real lab.  As mentioned earlier sulforaphane will also do the trick but I don't think the same in vivo study has been done on humans yet. Also I can't have too much saturated fat as my FTO polymorphism won't allow for it. I also don't know, based on the in vivo human study, if the normal triglyceride form of saturated fat that you would get in a natural butter like cocoa or mango is the same as the pure form they studied. Sulforaphane bypasses Nrf2 to induce fusion but not sure about stearic, I googled it and can't find any mention. Not even sure this matters.

I am not aware if there is commercial food grade mango butter. There is a concern regarding to chemicals during the refining process such as deodorants.



#1491 Turnbuckle

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Posted 04 February 2020 - 12:37 AM

The in vitro study with sulforaphane used 50uM concentration, which seems to me to be a totally unobtainable dose in Vivo. See http://dx.doi.org/10...dox.2016.11.007

At least the stearic acid study was in people. Having said that, they stirred pure stearic acid into a banana milk shake and somehow ingested it (and in the supplementary info stirred it into heated water and drank that to eliminate any contribution to fusion from the milkshake!) How could you possibly digest that? See DOI:10.1038/s41467-018-05614-6

Stick to Turnbuckle's brownies or use glycerol monostearate in water I think.

 

Sulforaphane has a MW of 177 g/M. At the stated concentration of μM, that would require 50 μM x 177 = 8.85 mg/kg.

The human body is about 60% water, so a 80 kg subject would have 48 kg (or liters).

Total required sulforaphane is then 48 kg x 8.85 mg/kg = 425 mg.

Thorne's 50 mg Sulforaphane glucosinolate (MW 438) caps contain 50 x 177/438 = 20.2 mg sulforaphane.

So you would need 425/20.2 = 21 caps.

A little expensive, but not totally unobtainable.

And I doubt you would actually need the concentration stated in the paper.


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#1492 Turnbuckle

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Posted 04 February 2020 - 10:11 AM

One week into the simplified protocol (pqq/NAM+Ribose on alternate days).

 

Noting better endurance at the gym (HIIT) and improved vitality, but at higher doses (NAM (2g) + Ribose (2g)) I feel light headed and slightly nauseated.

 

Should I persist some more days or lower the dosage a bit ?

 

Thanks.

 

 

Don't beat yourself up. Use a level you're comfortable with.


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#1493 longcity90

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Posted 08 February 2020 - 01:56 PM

Has anyone experienced a lowering of cortisol and adrenaline with Niacinamide? I seem to accuse this in the following hours ... even a slight depression.
 
I don't think it's a methylation problem even though I haven't tried an equal dose of TMG as suggested in another post.
 
I am still using very low dosages of Niaciniamide 50-100mg and Ribose 500mg ... (PS: I have confirmed the deficiency of complex one which is dependent on NAD / NADH).
 
Beyond this I am experiencing excellent benefits! for those who are at the beginning I recommend starting slowly

 

Edited by longcity90, 08 February 2020 - 01:59 PM.


#1494 Nate-2004

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Posted 10 February 2020 - 06:19 PM

I get the sense that my bp, adrenaline and cortisol actually rise during NAD+ boosting. I can really only measure BP but I can tell if adrenaline is up by the tremor in my hands. It's always worse. 

 

On another topic, I'm still hunting down a way to determine what foods are high in stearic acid but low in palmitic acid. It's only just now coming into public awareness that stearic has positive effects on mitochondrial function and cardiovascular health (or at least its neutral effect on CVh). I've been doing all I can to lower my bp by dropping saturated fat but I don't want to drop stearic if I can help it. 

 

One solid way is to eat 85% or higher dark chocolate. The stearic to palmitic is 2 to 1 respectively. It's about the same with mango butter, but obviously chocolate is more enjoyable and a source of caffeine in the mornings.

 

There's a site that lists foods high in stearic acid and the same site lists foods high in palmitic acid, maybe I can do some kind of inverse comparison on the two lists that singles out any that are high in the former and low in the latter. Unless I'm reinventing the wheel here. I could write the script in python. I'll post the results here if successful.

 

 



#1495 BigLabRat

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Posted 10 February 2020 - 06:52 PM

I've been doing all I can to lower my bp by dropping saturated fat...

 

You're living in the 70s if you believe that will work, but good luck!


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#1496 Nate-2004

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Posted 10 February 2020 - 08:02 PM

You're living in the 70s if you believe that will work, but good luck!

 

Actually, not exactly true for everyone, because so far it's working, also I have 3 FTO gene polymorphisms that say otherwise, making me particularly vulnerable to saturated fat. I think genes are important in nutrition and this may be why there is so much conflicting data out there and why some diets work for some people while others do not.


Edited by Nate-2004, 10 February 2020 - 08:19 PM.

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#1497 Turnbuckle

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Posted 10 February 2020 - 09:40 PM

I get the sense that my bp, adrenaline and cortisol actually rise during NAD+ boosting. I can really only measure BP but I can tell if adrenaline is up by the tremor in my hands. It's always worse. 

 

On another topic, I'm still hunting down a way to determine what foods are high in stearic acid but low in palmitic acid. It's only just now coming into public awareness that stearic has positive effects on mitochondrial function and cardiovascular health (or at least its neutral effect on CVh). I've been doing all I can to lower my bp by dropping saturated fat but I don't want to drop stearic if I can help it. 

 

One solid way is to eat 85% or higher dark chocolate. The stearic to palmitic is 2 to 1 respectively. It's about the same with mango butter, but obviously chocolate is more enjoyable and a source of caffeine in the mornings.

 

There's a site that lists foods high in stearic acid and the same site lists foods high in palmitic acid, maybe I can do some kind of inverse comparison on the two lists that singles out any that are high in the former and low in the latter. Unless I'm reinventing the wheel here. I could write the script in python. I'll post the results here if successful.

 

 

I recommend you use the brownie method, either with food grade stearic acid, which is a triglyceride with approximately half stearic acid by weight, or with stearic acid as a FFA. You can obtain the former from Amazon and other places, and the latter from Carolina Biological.


Edited by Turnbuckle, 10 February 2020 - 09:47 PM.

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#1498 Graviton

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Posted 11 February 2020 - 07:14 PM

I recommend you use the brownie method, either with food grade stearic acid, which is a triglyceride with approximately half stearic acid by weight, or with stearic acid as a FFA. You can obtain the former from Amazon and other places, and the latter from Carolina Biological.

As you said before, the commercial stearic acid claimed by manufacturers is usually half stearic acid and half palmitic acid, which is worse than dark chocolate. The latter one you mentioned doesn't seem to say it is food grade, and also it does not provide CoA.

 

Earlier, there was the discussion that GMS can be decomposed to glycerin and stearic acid. How much portion of GMS can be broken down to active form of stearic acid, which can rise the mitochondrial fusion. Considering that it also contains glycerin component, the smaller portion of stearic acid would be yielded.

 

Ice cream and bakery industry uses the GMS for their production. Would there be safe upper limit for human consumption of GMS mixed in water?


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#1499 Turnbuckle

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Posted 11 February 2020 - 07:53 PM

As you said before, the commercial stearic acid claimed by manufacturers is usually half stearic acid and half palmitic acid, which is worse than dark chocolate. The latter one you mentioned doesn't seem to say it is food grade, and also it does not provide CoA.

 

 

 

It's laboratory grade. I don't know any source of stearic FFA that's food grade. But like the people using C60, you have to ignore the FDA sometimes.


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#1500 Nate-2004

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Posted 14 February 2020 - 03:57 AM

I recommend you use the brownie method, either with food grade stearic acid, which is a triglyceride with approximately half stearic acid by weight, or with stearic acid as a FFA. You can obtain the former from Amazon and other places, and the latter from Carolina Biological.

 

Is there anything wrong with getting it from straight dark chocolate or mango butter? Because I think a lot of us are super worried about palmitic acid.

 

Another group buy of that USP grade stuff from sigma would be ideal obviously.


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