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Manipulating mitochondrial dynamics

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

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#1051 stephen_b

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Posted 09 August 2018 - 03:43 AM

In the study Mitochondrial Fusion Is Essential for Steroid Biosynthesis, if I have understood correctly, fusion is needed for the conversion of cholesterol to pregnenolone.

 

 

 

Our results indicate that fusion per se is obligatory for steroid biosynthesis

 

That seems to imply that pregnenolone production is reduced when in fission, like after taking N+R.

 

I get a great energy boost from pregnenolone at 50 mg, lots of mental energy all day and a noticeable increase in endurance exercise capacity. I get just the opposite with higher doses of fission promoters, making me wonder if the fission blahs might be partly due to low pregnenolone.

 

If that's the case, then supplementing with pregnenolone might make taking fission promoters easier.


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#1052 tunt01

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Posted 11 August 2018 - 12:44 PM

In vivo data with controls & T2D for mitofusion dynamics caused by stearic acid intake.  

 

Dietary stearic acid regulates mitochondria in vivo in humans

 

 

Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. We previously showed that the fatty acid stearic acid (C18:0) signals via a dedicated pathway to regulate mitofusin activity and thereby mitochondrial morphology and function in cell culture. Whether this pathway is poised to sense changes in dietary intake of C18:0 in humans is not known. We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.

 

 

 
 
 
 
Senyilmaz-Tiebe, D., Pfaff, D., Virtue, S., Schwarz, K., Fleming, T., & Altamura, S. et al. (2018). Dietary stearic acid regulates mitochondria in vivo in humans. Nature Communications9(1). doi:10.1038/s41467-018-05614-6

 

 

 

 


Edited by tunt01, 11 August 2018 - 12:44 PM.

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#1053 biggyrat

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Posted 11 August 2018 - 09:49 PM

Hi Turnbuckle and all, 

 

So I am about to begin gathering the ingredients and then trying the protocol discussed in this thread.  I don't have a scientific background at all, just an interest so I am trying to understand as best as I can.  I'm 65 years, female, nothing dramatic going on in terms of my health. I do notice loss of muscle, am trying to exercise more consistently.    Also, have various aches and pains, knee, back mainly.  Also suffer from depression often, but maybe that's not relevant for this protocol.  At any rate,  I thought I would go with the protocol Turnbuckle mentions in post 977 ( Turnbuckle- unless you think I should do otherwise). The thing is, that for the most part, I am don't have an understanding of what nutrients/ lifestyle interventions, etc , contribute to fusion or fission, outside of the protocol.  I'm not sure if I need to concern myself with these issues, but I do take other supplements generally and then there is diet / eating/ not eating , to consider.  I'm wondering how much I need to be concerned with these issues when implementing this protocol. In other words, do I wait to eat when taking the supplements for fission or fusion? Do I stop my other supplements while doing this protocol? Although sounds like it could go on for a number of years possibly, but I don't want to do anything that might interfere with its effectiveness.  Hope I'm being clear enough. 

 

Thanks in advance for any pointers. 

 

 


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#1054 Andey

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Posted 12 August 2018 - 01:56 PM

Hi Turnbuckle and all, 

 

So I am about to begin gathering the ingredients and then trying the protocol discussed in this thread.  I don't have a scientific background at all, just an interest so I am trying to understand as best as I can.  I'm 65 years, female, nothing dramatic going on in terms of my health. I do notice loss of muscle, am trying to exercise more consistently.    Also, have various aches and pains, knee, back mainly.  Also suffer from depression often, but maybe that's not relevant for this protocol.  At any rate,  I thought I would go with the protocol Turnbuckle mentions in post 977 ( Turnbuckle- unless you think I should do otherwise). The thing is, that for the most part, I am don't have an understanding of what nutrients/ lifestyle interventions, etc , contribute to fusion or fission, outside of the protocol.  I'm not sure if I need to concern myself with these issues, but I do take other supplements generally and then there is diet / eating/ not eating , to consider.  I'm wondering how much I need to be concerned with these issues when implementing this protocol. In other words, do I wait to eat when taking the supplements for fission or fusion? Do I stop my other supplements while doing this protocol? Although sounds like it could go on for a number of years possibly, but I don't want to do anything that might interfere with its effectiveness.  Hope I'm being clear enough. 

 

Thanks in advance for any pointers. 

 

  Probably I am not the most qualified person to answer, as I simply don't know how each one supplement would influence the protocol.

As far as I understand fusion part is compatible with fasting, fission with a fed state.

I would advice go slower and build up the tolerance with a fission part as it could be unpleasant. Fusion, on the other hand, at least for me, doesn't differ much from a baseline state.



#1055 biggyrat

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Posted 12 August 2018 - 10:41 PM

  Probably I am not the most qualified person to answer, as I simply don't know how each one supplement would influence the protocol.

As far as I understand fusion part is compatible with fasting, fission with a fed state.

I would advice go slower and build up the tolerance with a fission part as it could be unpleasant. Fusion, on the other hand, at least for me, doesn't differ much from a baseline state.

Thank you Andey- 

 

So I'm not the best a fasting... in fact the most I have done so far is to try to have 15 or so hours between evening meal and morning/ mid- day meal.  I guess my question would be, do I need to be in a fasted state, or at least take before food,  for the fusion part of this then.  I'm assuming its not a concern for the fission part.   

 

And I'll heed your advise regarding taking fission slowly.   I guess I'll just one day and see how I feel. 

 

Cheers...



#1056 Turnbuckle

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Posted 12 August 2018 - 11:09 PM

Thank you Andey- 

 

So I'm not the best a fasting... in fact the most I have done so far is to try to have 15 or so hours between evening meal and morning/ mid- day meal.  I guess my question would be, do I need to be in a fasted state, or at least take before food,  for the fusion part of this then.  I'm assuming its not a concern for the fission part.   

 

And I'll heed your advise regarding taking fission slowly.   I guess I'll just one day and see how I feel. 

 

Cheers...

 

You may not need to do this at all. If you try the fission step and get little response or none at all, you may not have many defective mitochondria. If you have a lot it could take months of cycling to clear them out. But not years. No fasting is required. I typically did these things in the morning before eating, but after that I didn't worry about it. Just do it away from meals at first, then you can see how it goes. And once you're satisfied you've cleared out the bad actors, then you can move on to my stem cell protocol.


Edited by Turnbuckle, 12 August 2018 - 11:09 PM.

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#1057 biggyrat

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Posted 13 August 2018 - 03:31 AM

You may not need to do this at all. If you try the fission step and get little response or none at all, you may not have many defective mitochondria. If you have a lot it could take months of cycling to clear them out. But not years. No fasting is required. I typically did these things in the morning before eating, but after that I didn't worry about it. Just do it away from meals at first, then you can see how it goes. And once you're satisfied you've cleared out the bad actors, then you can move on to my stem cell protocol.

Thanks mucho, Turnbuckle.    Assuming I do the fusion portion,  for Hydroxytyrosol -  I found this one. 

 

20% Hydroxytyrosol Complex Olive Fruit Extract - Super Strength from Real European Olive Trees. 100 mg, 90 Capsules. from Island Nutrition

 

 

And for Jiaogulan leaf -

 

Gynostemma Capsules – Jiaogulan Veggie Capsules an AMPK Activator Weight Loss Supplement - Potent Antioxidant & Adaptogen Pills - Caffeine-Free Immortality Herb, All Natural, No Chemicals or Extracts - 100 x 500mg  ( this one says 7.5- 7.77% gynostemma , 75 mg per 2 caps of 1000 mg Jiaogulan)> 

 

 

or 

 

Jiaogulan, Paradise Herbs, 12:1, each cap has 250 mg of the herb. 

 

Do all these seem adequate? 

 

Thanks..

 

 

 

 
 
 
 
 
 


#1058 Barfly

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Posted 15 August 2018 - 06:18 PM

Really interesting thread.

 

I have a fatigue fighting stack which saved me that consists of PQQ (biggest improvement for me by far), CoQ10, ALCAR, Nicotinamide+ riboside, creatine and LLLT which I take daily (except LLLT) and I noticed from your thread  that I have lumped fussion/fission supplements together and I was wondering if that is a bad idea longterm, do these supplements mixed on same day work against each other somehow?

 

Sorry if it is a silly question but whole thread is a bit too advanced for me and thank you for your help

 

 

 

 



#1059 Climactic

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Posted 17 August 2018 - 04:53 PM

SAFETY ALERT

Duda Energy stearic acid is 47% pure.

 

This is warn you guys that after a painstaking investigation, I have discovered that the Duda Energy food grade stearic acid product on Amazon is only 47% C18 (stearic acid). This is per the latest Dec 2017 CoA (alt link) that was sent to me in Aug 2018 by Duda Energy. Going by the product title of "stear1f Stearic Acid Food Grade NF USP Pure White Flakes Hystrene 5016", I was grossly misled into thinking that it should be just stearic acid. The seller apparently purchased the NF-FG product from PMC Biogenix whereas he should've purchased NF-EXT instead. The seller is so typo-ridden that the product description states it is "Hysteron 5106"; no such PMC product exists.

 

The product is believed to have 52% palmitic acid which according to numerous studies will have a harmful effect, and definitely not the effect that is intended from a stearic acid product. I have made a complain to Amazon and the FDA, but most people these days are grossly incompetent, and I don't expect any action to be taken. I also complained to PMC but they probably wouldn't be concerned of what resellers do.

 

If you consumed this product, I encourage you to get the CoA on your own, and then sue for damages in court, considering that the seller knowingly misrepresented the product description. I also then encourage you to complain to Amzn, write an appropriate Amzn review, and file an FDA report too if you're a US resident. Last but not least, think twice about what you buy and eat.


Edited by Climactic, 17 August 2018 - 04:56 PM.

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#1060 Andey

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Posted 17 August 2018 - 05:56 PM

 

 

This is warn you guys that after a painstaking investigation, I have discovered that the Duda Energy food grade stearic acid product on Amazon is only 47% C18 (stearic acid).

 

I am sitting now with freshly received 5lb of Dudas Energy 'product' )

I don't think though that palmitic acid is harmful, it's just a most common saturated fatty acid in food and probably neutral for all intended purposes of this protocol.

 

Hopefully, Turnbuckle will clarify what product he used. If its Duda Energy than probably half dosage of stearic acid is enough too.


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#1061 Turnbuckle

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Posted 17 August 2018 - 06:24 PM

I am sitting now with freshly received 5lb of Dudas Energy 'product' )

I don't think though that palmitic acid is harmful, it's just a most common saturated fatty acid in food and probably neutral for all intended purposes of this protocol.

 

Hopefully, Turnbuckle will clarify what product he used. If its Duda Energy than probably half dosage of stearic acid is enough too.

 

My first experiments were with stearic acid from a chem supply house. I never used Duda and palmitic acid isn't neural here--

 

Further to this hypothesis, Jheng et al. (20) recently reported that in C2C12 cells [an immortalized mouse myoblast cell line] preincubation with palmitic acid induced Drp1-mediated mitochondrial fragmentation, higher levels of oxidative stress, reduced ATP production, and reduced insulin-mediated glucose uptake.

https://www.ncbi.nlm...PMC4122691/#B20

 


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#1062 Climactic

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Posted 17 August 2018 - 08:34 PM

According to these articles, palmitic acid is pretty bad:

 

Dietary stearic acid regulates mitochondria in vivo in humans. (2018)

> C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.

 

Associations of Plasma Phospholipid SFAs with Total and Cause-Specific Mortality in Older Adults Differ According to SFA Chain Length. (2016)

> Higher concentrations of the plasma phospholipid SFAs 18:0, 22:0, and 24:0 were associated with a lower risk of total mortality [multivariable-adjusted HRs (95% CIs)] for the top compared with the bottom quintile: 0.85 (0.75, 0.95) for 18:0; 0.85 (0.75, 0.95) for 22:0; and 0.80 (0.71, 0.90) for 24:0. In contrast, plasma 16:0 concentrations in the highest quintile were associated with a higher risk of total mortality compared with concentrations in the lowest quintile [1.25 (1.11, 1.41)]. We also found no association of plasma phospholipid 20:0 with total mortality.

 

> 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.


Edited by Climactic, 17 August 2018 - 08:37 PM.

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#1063 ementic

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Posted 18 August 2018 - 01:16 AM

Okay last potentially silly question on my part. I'm looking to do a five day fast once a month for the next few months in a row. From what I understand theres a lot of autophagy, and mitophagy that happens during it. Would these fasts be enough to take care of the fission half of the protocol on their own?



#1064 Andey

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Posted 18 August 2018 - 06:01 AM

Where can we buy a pure stearic acid then?

 

From my search yesterday it looks like its a common practice to label C16+C18 mix as a stearic acid. At least all food grade sources I 've seen are like this.

We don't know what is in the SAAQIN stearic acid that sold on Amazon but I suspect it could be the same.

 

BTW Hystrene 5016 NF-EXT is the same mix, only for external use

Looks like we need something like Panreac 162590.1210


Edited by Andey, 18 August 2018 - 06:58 AM.


#1065 Turnbuckle

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Posted 18 August 2018 - 07:03 AM

 

From my search yesterday it looks like its a common practice to label C16+C18 mix as a stearic acid. At least all food grade sources I 've seen are like this.

 

 

I haven't seen that even once.


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#1066 Andey

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Posted 18 August 2018 - 08:09 AM

I haven't seen that even once.

 

Just going down on google search page on "Stearic acid food grade"

http://shop.chemical...l.asp?id=ST035V (same Hystrene product)

http://www.foodchema...ts/stearic-acid (C18 content 40-45%)

https://www.sciencel...R/23027/SLS3742 (looking at the price it could be the pure version but "A mixture of solid organic acids obtained from fats" makes me wonder)

http://www.chempri.c...oductgroep_id=6

 

As far as I understand C16 and C18 acids go hand in hand in nature, so there are no pure sources. Separating palmitic and stearic acid is not a trivial process, and everything that is just 'triple pressed' is a mix by definition. 

There is also not a lot of incentive for the food industry to get a pure stearic acid. For all their intended purposes mix is as good and doesn't need additional processes and in the end, it will be named E570 regardless.

 

Even lab oriented products are [Octadecanoic Acid] A mixture of stearic acid (C18H36O2) and palmitic acid (C16H32O2). CAS#: 57-11-4

https://www.amazon.c...34581901&sr=8-5

 

I think best bet is to buy stearic acid for synthesis. 

 

 


Edited by Andey, 18 August 2018 - 08:41 AM.

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#1067 Turnbuckle

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Posted 18 August 2018 - 10:30 AM

Just going down on google search page on "Stearic acid food grade"

http://shop.chemical...l.asp?id=ST035V (same Hystrene product)

http://www.foodchema...ts/stearic-acid (C18 content 40-45%)

https://www.sciencel...R/23027/SLS3742 (looking at the price it could be the pure version but "A mixture of solid organic acids obtained from fats" makes me wonder)

http://www.chempri.c...oductgroep_id=6

 

As far as I understand C16 and C18 acids go hand in hand in nature, so there are no pure sources. Separating palmitic and stearic acid is not a trivial process, and everything that is just 'triple pressed' is a mix by definition. 

There is also not a lot of incentive for the food industry to get a pure stearic acid. For all their intended purposes mix is as good and doesn't need additional processes and in the end, it will be named E570 regardless.

 

Even lab oriented products are [Octadecanoic Acid] A mixture of stearic acid (C18H36O2) and palmitic acid (C16H32O2). CAS#: 57-11-4

https://www.amazon.c...34581901&sr=8-5

 

I think best bet is to buy stearic acid for synthesis. 

 

 

That's a bitch. So how about this one: https://www.amazon.c...L70_&dpSrc=srch

 

One bottle would be convenient for a batch of 12 brownies.


Edited by Turnbuckle, 18 August 2018 - 10:55 AM.

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#1068 Andey

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Posted 18 August 2018 - 12:04 PM

That's a bitch. So how about this one: https://www.amazon.c...L70_&dpSrc=srch

 

One bottle would be convenient for a batch of 12 brownies.

Looks good but in the light of the recent news...

I wrote them a message to info@eisengolden.com asking to share some information about it.


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#1069 RWhigham

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Posted 18 August 2018 - 02:54 PM

Reagent quality  CAS 57-11-4  97% Stearic Acid from Acros Organics is sold by  Fisher Scientific for $33.10/kg  [$51.19 with shipping and Colorado state tax]

 

 

[Edit: Was a Canadian link and price. Now US link and price]


Edited by RWhigham, 18 August 2018 - 03:10 PM.

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#1070 Nate-2004

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Posted 18 August 2018 - 03:08 PM

Wow and I just bought more of the Duda stuff. Let me know what the turnout is on that Eisen-Golden labs brand. Definitely way more expensive. Guess I'll have to throw out the stuff I just bought from Duda. Ugh. Frustrating. You think you have good stuff and then it turns out you don't. Maybe just stick with broccomax and broccoli for now.

 

Unfortunately I don't think anyone can buy from Fisher-Scientific without a business lab address.


Edited by Nate-2004, 18 August 2018 - 03:09 PM.


#1071 RWhigham

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Posted 18 August 2018 - 03:26 PM

Unfortunately I don't think anyone can buy from Fisher-Scientific without a business lab address.

 

I just placed an order using "Guest" checkout and my home address


Edited by RWhigham, 18 August 2018 - 03:39 PM.


#1072 Nate-2004

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Posted 18 August 2018 - 03:31 PM

I just placed an order using "Guest" checkout and my home address

 

Usually they come back saying sorry must be lab address and cancel your order. I've tried before but maybe it's fine for this product.



#1073 RWhigham

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Posted 18 August 2018 - 03:43 PM

Usually they come back saying sorry must be lab address and cancel your order. I've tried before but maybe it's fine for this product.

They sent me an order confirmation via email.  I will keep you informed.


Edited by RWhigham, 18 August 2018 - 03:45 PM.


#1074 Phoebus

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Posted 18 August 2018 - 03:57 PM

Usually they come back saying sorry must be lab address and cancel your order. I've tried before but maybe it's fine for this product.

 

 

depends on the product 

 

some are marked for lab only, others can be bought by any shlub off the street. 


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#1075 stephen_b

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Posted 18 August 2018 - 09:40 PM

That's a bitch. So how about this one: https://www.amazon.c...L70_&dpSrc=srch

 

One bottle would be convenient for a batch of 12 brownies.

 

The MSDS from Eisen-Golden says C18 only. So far so good.



#1076 cmpercell

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Posted 18 August 2018 - 09:57 PM

I have been using the saaqin brand mentioned earlier in this thread.

 

Using a candy thermometer, I heated water on the stove to a consistent 150F, placed an amount of the claimed stearic acid in a ziplock bag and placed it into the water.  60-70% of it melted. Stearic Acid shouldn't melt until around 156F.

 

This isn't very scientific, but am very excited about my early results using a variant of Turnbuckle's protocol.

 

I have reclaimed the solid portions from the oil with the assumption it is Stearic acid and will continue to use it.


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#1077 RWhigham

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Posted 18 August 2018 - 10:21 PM

Reagent quality  CAS 57-11-4  97% Stearic Acid from Acros Organics is sold by  Fisher Scientific for $33.10/kg  [$51.19 with shipping and Colorado state tax]

 

Fisher Scientific 97% Stearic Acid Not for Human Consumption

I requested a cancellation and refund from Fisher Scientific. On further checking, the Fisher Scientific product is specified "not for human consumption" and is not tested to USP standards.

 

USP-NF Stearic Acid - 50, 70, & 95

The NF standard is now combined with the USP (United States Pharmacopeia) standard. The USP Stearic Acid specifies 3 Food grades of Stearic Acid: Stearic Acid 50, Stearic Acid 70, and Stearic Acid 95. If the seller specifies just "USP" with no further qualification, then I would always assume it is the lowest cost "Stearic Acid 50" grade, and that may contain as little as 40% stearic acid (40-65%). I have been unable to find a convenient source for the USP-NF Stearic Acid 95

 

Eisen-Golden 99%

This looks promising. I hope someone tries the temperature melt test,

Palmitic Acid Melting Point:  145.2  F

Stearic Acid Melting Point:   156,7  F


Edited by RWhigham, 18 August 2018 - 10:59 PM.

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#1078 zorba990

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Posted 19 August 2018 - 03:35 AM

I guess chances of my "halaleveryday" brand stearic acid being pure are slim.
Not sure I much blame the sellers as they aren't probably used to people consuming it.
Magnesium stearate is used as a flow agent for many supplements for encapsulation I wonder if it would do since it must be fairly inexpensive.

Edited by zorba990, 19 August 2018 - 03:38 AM.


#1079 onz

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Posted 19 August 2018 - 06:19 AM

This is quite discouraging, any ideas for alternatives to stearic acid? Or perhaps a reliable way to purify what we've already bought? Can anyone provide some insight into cmpercell's method?

#1080 Andey

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Posted 19 August 2018 - 06:43 AM

I 've also ordered and then requested cancellation from Fischer. Though will reorder again from them if other options fail

 

IMO best source is to buy it from Sigma-Aldrich. 95% Food Grade. Its the source of stearic acid for the recent study in Nature https://www.nature.c...467-018-05614-6

https://www.sigmaald...ng=en&region=US

Not very economical on small volume though, but 25 kg is about the same price as Duda

 

I 've ordered 1kg, waiting for an order review, they would probably reject it.







Also tagged with one or more of these keywords: nad, nad+, c60, mito, fission, fusion, stearic acid, mtdna, methylene blue

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