2255 replies to this topic

[Bryan_S]

Potential treatment for pregnant women who suffer from preeclampsia found in a vitamin

Vitamin B3 nicotinamide

https://www.scienced...61219100556.htm

 

 

Good find, you know NR will become NAM in the end so this is relevant and could be a secondary effect. We posted about "Nicotinamide Riboside Delivery Generates NAD+ Reserves to Protect Vascular Cells Against Oxidative Damage" So the study you found is consistent with others we've read.

[Bryan_S]

Correcting NAD+ depletion may improve muscular degeneration in Duchenne muscular dystrophy [PreClinical]

 

http://www.2minuteme...hy-preclinical/

 

1. Dietary supplementation with nicotinamide riboside (NR), a form of vitamin B3 that acts as a precursor to nicotinamide adenine dinucleotide (NAD+), increased levels of NAD+ and reduced deterioration of muscle structure in mouse models of Duchenne muscular dystrophy (DMD).

 

2. Concomitantly, NR treatment led to improved mitochondrial energetics and function of cardiac and skeletal muscle.

 

Evidence Rating Level: 2 (Good)

 

Study Rundown: Neuromuscular diseases like DMD are marked by severe muscle weakness and degeneration and often cause death by heart or respiratory failure. Though research has focused on correcting genetic mutations that cause the disease, there are currently no therapeutic treatments for DMD. In this work, researchers demonstrated the efficacy of a member of the vitamin B3 family, NR, in preventing the progression of DMD.

 

We posted this topic awhile ago and its making its rounds again and is worth mention.

http://www.longecity...-47#entry793039

http://stm.sciencema.../8/361/361ra139

Edited by Bryan_S, 22 December 2016 - 04:38 PM.

[Iporuru]

SELECTIVE SOLVENT FREE PHOSPHORYLATION

A synthetic process is provided for the preparation of phosphorylated analogs of nicotinamide riboside (“NR”) having the formula (I), or salts thereof, and reduced or modified derivatives thereof, having the formula (II), wherein X⁻, Y¹, Y², Z¹, Z², n, R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are as defined herein. The present disclosure also relates to the preparation of phosphorylated analogs of nicotinic acid riboside (“NAR”) having the formula (I), or salts thereof, and reduced or modified derivatives thereof, having the formula (II). Generally solvent-free conditions are employed using appropriate mechano-chemical techniques as described.

 

http://www.freepaten...16/0355539.html

[Bryan_S]

Happy holidays to everyone.

 

Bryan

[Supierce]

Happy holidays to everyone.
 
Bryan

And a wonderful 2017 to you, Bryan. Thank you so much for all you do here!

[markkhicks]

Was there a followup response on the thread on the possible cancer promotion?


Sent from my iPad using Tapatalk

[Bryan_S]

Role of CD38 in age-related NAD+ depletion: implication for age-related metabolic dysfunction and NAD+ replacement therapy.

 

http://www.sbbq.org....os/R08029-1.pdf

 

Juliana Camacho-Pereira 1,2 , Veronica Nin 2 , Claudia Chini2 , Mariana Tarrago 2 , Antonio Galina 1 , Eduardo Chini2

 

1Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil; 2Mayo Clinic College of Medicine, Kogod Aging Center and Anesthesiology Department, Rochester, MN, EUA

 

A decrease in intracellular levels of nicotinamide adenine dinucleotide (NAD+) has been shown to occur during the aging process. This decrease in NAD+ levels has a causal role on the development of age-related mitochondrial dysfunction and metabolic decline. To date, the mechanisms responsible for the age-related NAD+ decline have not been identified. It has been proposed that accumulation of DNA damage driven PARP activation may be involved. However, we identify that PARP levels and activity decline with aging. In contrast, we demonstrate for the first time that the expression and activity of the enzyme CD38 increases with aging and plays an active role in the age-related NAD+ decline in vivo and the subsequent development of age related mitochondrial dysfunction. In addition, we also identify CD38 as the main enzyme involved in the degradation of NAD+ precursors such as nicotinamide mononucleotide (NMN) in vivo and to have a role in the modulation of the response to NAD+ replacement therapy in aging. These data demonstrates the key role of CD38 in age-related NAD+ and metabolic decline, and highlights the potential role of CD38 inhibition for the development of an effective ìNAD+ replacement therapy" for aging and other metabolic diseases.

 

Keywords: Age-related metabolic diseases, mitochondrial dysfunction, NAD+ replacement therapy

 

Published (Fri, 23 Dec 2016) 

Synthesis and Evaluation of Thiazoloquinolinones with Linkers To Enable Targeting of CD38

http://pubs.acs.org/...hemlett.6b00409

 

 

Some of you will remember the " Why NAD+ Declines during Aging: It's Destroyed"

http://www.longecity...-47#entry793317

[Harkijn]

 

Role of CD38 in age-related NAD+ depletion: implication for age-related metabolic dysfunction and NAD+ replacement therapy.

 

http://www.sbbq.org....os/R08029-1.pdf

 

Juliana Camacho-Pereira 1,2 , Veronica Nin 2 , Claudia Chini2 , Mariana Tarrago 2 , Antonio Galina 1 , Eduardo Chini2

 

1Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil; 2Mayo Clinic College of Medicine, Kogod Aging Center and Anesthesiology Department, Rochester, MN, EUA

 

A decrease in intracellular levels of nicotinamide adenine dinucleotide (NAD+) has been shown to occur during the aging process. This decrease in NAD+ levels has a causal role on the development of age-related mitochondrial dysfunction and metabolic decline. To date, the mechanisms responsible for the age-related NAD+ decline have not been identified. It has been proposed that accumulation of DNA damage driven PARP activation may be involved. However, we identify that PARP levels and activity decline with aging. In contrast, we demonstrate for the first time that the expression and activity of the enzyme CD38 increases with aging and plays an active role in the age-related NAD+ decline in vivo and the subsequent development of age related mitochondrial dysfunction. In addition, we also identify CD38 as the main enzyme involved in the degradation of NAD+ precursors such as nicotinamide mononucleotide (NMN) in vivo and to have a role in the modulation of the response to NAD+ replacement therapy in aging. These data demonstrates the key role of CD38 in age-related NAD+ and metabolic decline, and highlights the potential role of CD38 inhibition for the development of an effective ìNAD+ replacement therapy" for aging and other metabolic diseases.

 

Keywords: Age-related metabolic diseases, mitochondrial dysfunction, NAD+ replacement therapy

 

Published (Fri, 23 Dec 2016) 

Synthesis and Evaluation of Thiazoloquinolinones with Linkers To Enable Targeting of CD38

http://pubs.acs.org/...hemlett.6b00409

 

 

Some of you will remember the " Why NAD+ Declines during Aging: It's Destroyed"

http://www.longecity...-47#entry793317

 

Reading through the  article I am mainly frustrated about how much I can't even begin to understand. On CD38 my takeaway is that the authors see it as a total 'bad guy' while previous researchers had a more balanced view of it's actions . Then again this new study is about cancerous cells and in cancer all norms are subverted. So I am still unsure about permanent anti CD38 supplementation in healthy people.

[Bryan_S]

 

 

Role of CD38 in age-related NAD+ depletion: implication for age-related metabolic dysfunction and NAD+ replacement therapy.

 

http://www.sbbq.org....os/R08029-1.pdf

 

Juliana Camacho-Pereira 1,2 , Veronica Nin 2 , Claudia Chini2 , Mariana Tarrago 2 , Antonio Galina 1 , Eduardo Chini2

 

1Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil; 2Mayo Clinic College of Medicine, Kogod Aging Center and Anesthesiology Department, Rochester, MN, EUA

 

A decrease in intracellular levels of nicotinamide adenine dinucleotide (NAD+) has been shown to occur during the aging process. This decrease in NAD+ levels has a causal role on the development of age-related mitochondrial dysfunction and metabolic decline. To date, the mechanisms responsible for the age-related NAD+ decline have not been identified. It has been proposed that accumulation of DNA damage driven PARP activation may be involved. However, we identify that PARP levels and activity decline with aging. In contrast, we demonstrate for the first time that the expression and activity of the enzyme CD38 increases with aging and plays an active role in the age-related NAD+ decline in vivo and the subsequent development of age related mitochondrial dysfunction. In addition, we also identify CD38 as the main enzyme involved in the degradation of NAD+ precursors such as nicotinamide mononucleotide (NMN) in vivo and to have a role in the modulation of the response to NAD+ replacement therapy in aging. These data demonstrates the key role of CD38 in age-related NAD+ and metabolic decline, and highlights the potential role of CD38 inhibition for the development of an effective ìNAD+ replacement therapy" for aging and other metabolic diseases.

 

Keywords: Age-related metabolic diseases, mitochondrial dysfunction, NAD+ replacement therapy

 

Published (Fri, 23 Dec 2016) 

Synthesis and Evaluation of Thiazoloquinolinones with Linkers To Enable Targeting of CD38

http://pubs.acs.org/...hemlett.6b00409

 

 

Some of you will remember the " Why NAD+ Declines during Aging: It's Destroyed"

http://www.longecity...-47#entry793317

 

Reading through the  article I am mainly frustrated about how much I can't even begin to understand. On CD38 my takeaway is that the authors see it as a total 'bad guy' while previous researchers had a more balanced view of it's actions . Then again this new study is about cancerous cells and in cancer all norms are subverted. So I am still unsure about permanent anti CD38 supplementation in healthy people.

 

 

My takeaway is now that they've learned how to target it maybe they can use that ability to selectively kill cells that have become bad apples is one thought. Maybe to help deliver drugs to specific sites.

 

"Our interests in targeted nanomedicines have led us to evaluate molecules that bind CD38 as potential targeting ligands to enhance the delivery of polymeric nanoparticles termed ACCURINS11,12 containing drug payloads to diseased tissues."

 

So lets say our target is senescent cells and these cells have a specific sensitivity to a specific compound. CD38 provides a selective marker that can attract the nanoparticles and they carry a substance that only senescent cells are sensitive too.

 

I think its fascinating, so here is an enzyme we know eats our NAD and eventually runs rampant in old age. Now a way has been developed to send medicine straight to the problem. What that medicine does is up to the imagination.

 

As always JMHO

[trakker]

Chromadex says filed complaint in U.S. court naming Elysium Health Inc as defendant - SEC filing

 

I find this quite curious.  Anyone have insight into this?

 

Seems like if it was simply a matter of Elysium not living up to their purchase quota, it wouldn't make it to level of lawsuit so quickly, which is likely to affect confidence in one or both companies.

Edited by trakker, 07 January 2017 - 07:46 PM.

[Michael]

Chromadex says filed complaint in U.S. court naming Elysium Health Inc as defendant - SEC filing
 
I find this quite curious.  Anyone have insight into this?
 
Seems like if it was simply a matter of Elysium not living up to their purchase quota, it wouldn't make it to level of lawsuit so quickly, which is likely to affect confidence in one or both companies.

 

See Chromadex's 01/06/17 SEC 8-K filing, Report of unscheduled material events or corporate event, whose Exhibit includes their court filing, and which contains a mixture of reputed facts and allegations (whose underlying factuality or legal probity I am in no way asserting or passing judgement of course):
 

4.    Beginning in 2015, Mark Morris, who was the Vice President of Business Development of ChromaDex at the time, but is now the Head of Scientific Technology at Elysium [my emphasis], was the primary manager of Elysium's account at ChromaDex.

5.    In all of 2015, Elysium ordered 900 kg of NIAGEN NR from ChromaDex. In the first quarter of 2016, Elysium ordered 1590 kg of NIAGEN NR  and  …. raised concerns about pricing under the NIAGEN Supply Agreement directly with Frank Jalcsch, co-founder and CEO of ChromaDex, and Will Black, ChromaDex's Vice President of Sales and Marketing. Mr. Jaksch reached out to Elysium in an effort to open a  dialogue about their concerns and ultimately resolve them. Elysium, however, refused  or ignored these offers to talk.  

On June 28. 2016, without any prior discussion or advance notification,  Elysium submitted extraordinarily large purchase orders for 6600 kg of NIAGEN NR  and 1260 kg of pTeroPure pterostilbene (the "June 28 Purchase Orders"). These amounts were approximately four times larger than any previous order from Elysium,  and more than double the sum of all Elysium's prior orders. The June 28 Purchase  Orders included a demand for pricing at $400/kg, far below the parties' agreed price of S1000/kg for NIAGEN NR, even though Elysium never discussed the proposed pricing changes with ChromaDex. Elysium knew or should have know that ChromaDex would not accept the June 28 Purchase Orders at that price.

Because the June 28 Purchase Orders were wildly inconsistent with the parties' Supply Agreements and past dealings, and in light of Elysium's subsequent failure to pay for NIAGEN NR and pTeroPure pterostilbene supplied by ChromaDex, ChromaDex alleges on information and belief that Elysium intended to induce ChromaDex to inadvertently supply large amounts of NIAGEN NR and pTeroPure pterostilbene to Elysium at grossly discounted prices .

 ChromaDex noticed the grossly discounted prices on the June 28 Purchase Orders and did not Mill them. Instead, ChromaDex reached out to Elysium to discuss [them] …   After Elysium again showed an unwillingness to engage with ChromaDex's senior management to discuss the June 28 Purchase Orders, Morris— who was the one person at ChromaDex whom Elysium would respond to in a  productive manner—helped schedule a call between ChromaDex and Elysium …

10.    On June 30, 2016, Mr. Jaksch and Mr. Black of ChromaDex, joined a call with Elysium's CEO, Eric Marcotulli, and COO, Dan Alminana (the "June 30 Call").

11.    On the June 30 Call, the parties discussed Elysium's concerns and the appropriate pricing of NIAGEN NR for the orders Elysium wished to place. Alminana and Marcotulli stated that Elysium intended to be a good business partner to ChromaDex and explained that Elysium was ramping up, which was the reason the June 28 Purchase Orders were far larger than their past orders. Though Elysium was not entirely satisfied with the price of $800 per kg of NIAGEN NR, which is what ChromaDex offered, Marcotulli represented that Elysium would accept that price now, place an order so that their supply was not interrupted, and work to resolve Elysium's remaining concerns another day.

12.    Later that day, June 30, 2016, Elysium submitted two purchase orders to ChromaDex for 580 kg of pTeroPure pterostilbene and 3000 kg of NIAGEN NR (the "June 30 Purchase Orders"). As agreed upon during the June 30 Call, the June 30 Purchase Orders superceded the (in retrospect, disingenuous) June 28 Purchase Orders. And although smaller than the June 28 Purchase Orders, the June 30 Purchase Orders were still two times the size of any of Elysium's previous fulfilled orders.

13.    Around the middle of July, Morris left ChromaDex to work for Elysium. …

14.    According to the terms of the Supply Agreements, and in reliance on the representations Alminana and Marcotulli made on the June 30 Call, ChromaDex filled the June 30 Purchase Orders  … [and]  provided Elysium with invoices for the shipments …

15.    The total amount Elysium owes ChromaDex for the Past Due Invoices is $2,983,350.

16.    At the time Marcotulli and Alminana spoke on the June 30 Call, Elysium had no intention of (1) ever working with ChromaDex to resolve Elysium's concerns about the NIAGEN Supply Agreement, (2) paying for the … June 30 Purchase Orders, or (3) ramping up their sales to the degree they represented.

17.    Instead, having failed to induce ChromaDex to supply NIAGEN NR and pTeroPure pterostilbene at grossly discounted prices … Marcotulli and Alminana made their false representations on the June 30 Call with the intent of inducing ChromaDex to provide it with large supplies of NIAGEN NR and pTeroPure pterostilbene and to exert financial pressure on ChromaDex by refusing to pay for the orders.

18.    Marcotulli and Alminana's false promises were further motivated by the fact that Elysium, which was seeking financing during the middle of 2016 and into November, has been able to improve its balance sheet by continuing to sell its product for millions of dollars in revenue without paying ChromaDex for its supply.

19.    On August 10, 2016—the day after ChromaDex shipped the last portion of pTeroPure pterostilbene—Alminana wrote an email to ChromaDex stating that Elysium would not pay the Past Due Invoices until the concerns raised on the June 30 Call were fixed according to terms set by Elysium. However, over the next several weeks, Alminana refused ChromaDex's sincere offers to meet and resolve his and Elysium's concerns, all the while maintaining that Elysium would not pay until its concerns were resolved.

20.    Elysium breached the Supply Agreements by failing to pay the Past Due Invoices  … [and] also breached the License Agreement by failing to deliver to ChromaDex (1) a report accounting for its net sales and royalties due (a "Royalty Report") for the quarter ended June 30. 2016 (l:)2 2016") and (2) payment

Edited by Michael, 07 January 2017 - 09:47 PM.

[Oakman]

Chromadex says filed complaint in U.S. court naming Elysium Health Inc as defendant - SEC filing

 

I find this quite curious.  Anyone have insight into this?

 

Seems like if it was simply a matter of Elysium not living up to their purchase quota, it wouldn't make it to level of lawsuit so quickly, which is likely to affect confidence in one or both companies.

 

If that is what happened >  A company soon to hire supplier's product purchasing agent, orders product (with pricing a controversy), and with said product delivered, withholds payment as leverage against pricing and payment. Also, we're talking >10% of suppliers' revenue. Not good.

[bluemoon]

 

 

If that is what happened >  A company soon to hire supplier's product purchasing agent, orders product (with pricing a controversy), and with said product delivered, withholds payment as leverage against pricing and payment. Also, we're talking >10% of suppliers' revenue. Not good.

 

 

There seems to be some very good news (for us) in this mess.

 

Notice that Elysium's larger than ever purchases were in June, which happened to be at the midway point of their two month study. It looks like they knew they had good results after the trial had been going on a month to where they also thought they could knock the cost down by more than half. Admittedly, they seem to be playing hard ball, and I'm not saying "right" -- we don't know Elysium's side at all here -- but this is a case where a company with the seven Nobel laureates can at least test pricing demands against a monopoly supplier.

 

Check out how much Elysium stands to make on each 250 mg dose of NR if they get the $400/kilo price. This looks to me like they are going large scale in 2017 and will start charging more like $30 per month (with pterostilbine) instead of $50 per month.

[midas]

 

 

 

If that is what happened >  A company soon to hire supplier's product purchasing agent, orders product (with pricing a controversy), and with said product delivered, withholds payment as leverage against pricing and payment. Also, we're talking >10% of suppliers' revenue. Not good.

 

 

There seems to be some very good news (for us) in this mess.

 

Notice that Elysium's larger than ever purchases were in June, which happened to be at the midway point of their two month study. It looks like they knew they had good results after the trial had been going on a month to where they also thought they could knock the cost down by more than half. Admittedly, they seem to be playing hard ball, and I'm not saying "right" -- we don't know Elysium's side at all here -- but this is a case where a company with the seven Nobel laureates can at least test pricing demands against a monopoly supplier.

 

Check out how much Elysium stands to make on each 250 mg dose of NR if they get the $400/kilo price. This looks to me like they are going large scale in 2017 and will start charging more like $30 per month (with pterostilbine) instead of $50 per month.

 

 

I like your thinking here, but I cant quite understand why a company that is "possibly" reacting to good study results would rock the boat with the ONE AND ONLY supplier of the raw product by not paying their bills.......!

Sort of sounds like you are poisoning your only water supply..

[stefan_001]

 

 

 

 

If that is what happened >  A company soon to hire supplier's product purchasing agent, orders product (with pricing a controversy), and with said product delivered, withholds payment as leverage against pricing and payment. Also, we're talking >10% of suppliers' revenue. Not good.

 

 

There seems to be some very good news (for us) in this mess.

 

Notice that Elysium's larger than ever purchases were in June, which happened to be at the midway point of their two month study. It looks like they knew they had good results after the trial had been going on a month to where they also thought they could knock the cost down by more than half. Admittedly, they seem to be playing hard ball, and I'm not saying "right" -- we don't know Elysium's side at all here -- but this is a case where a company with the seven Nobel laureates can at least test pricing demands against a monopoly supplier.

 

Check out how much Elysium stands to make on each 250 mg dose of NR if they get the $400/kilo price. This looks to me like they are going large scale in 2017 and will start charging more like $30 per month (with pterostilbine) instead of $50 per month.

 

 

I like your thinking here, but I cant quite understand why a company that is "possibly" reacting to good study results would rock the boat with the ONE AND ONLY supplier of the raw product by not paying their bills.......!

Sort of sounds like you are poisoning your only water supply..

 

 

its shocking how much money is "lost" in packing the NR into pills by companies like Elysium. Chromadex should open a direct supply to consumers:

- 1000USD / kg would translate into 7.5USD for a  month supply.

Elysium burns the consumer cash on marketing like paying for fancy names and themselves.
 

Edited by stefan_001, 08 January 2017 - 08:32 AM.

[bluemoon]

 

 

its shocking how much money is "lost" in packing the NR into pills by companies like Elysium. Chromadex should open a direct supply to consumers:

- 1000USD / kg would translate into 7.5USD for a  month supply.

Elysium burns the consumer cash on marketing like paying for fancy names and themselves.
 

 

 

 

But Elysium doesn't have a monopoly on NR at the retail level. Chromadex gets to set the wholesale price based on how much it can think it can sell and Elysium, HPN, etc can take it or leave it.  I wonder what Elysium's side of the story is. 

[stefan_001]

 

 

 

its shocking how much money is "lost" in packing the NR into pills by companies like Elysium. Chromadex should open a direct supply to consumers:

- 1000USD / kg would translate into 7.5USD for a  month supply.

Elysium burns the consumer cash on marketing like paying for fancy names and themselves.
 

 

 

 

But Elysium doesn't have a monopoly on NR at the retail level. Chromadex gets to set the wholesale price based on how much it can think it can sell and Elysium, HPN, etc can take it or leave it.  I wonder what Elysium's side of the story is. 

 

 

well at least it appears they play with fire. This article shows a snapshot stating the elisium contract with chromadex ends in February and will not be extended:

http://www.timelessl...t-paying-bills/

 

[Nate-2004]

 

 

 

 

its shocking how much money is "lost" in packing the NR into pills by companies like Elysium. Chromadex should open a direct supply to consumers:

- 1000USD / kg would translate into 7.5USD for a  month supply.

Elysium burns the consumer cash on marketing like paying for fancy names and themselves.
 

 

 

 

But Elysium doesn't have a monopoly on NR at the retail level. Chromadex gets to set the wholesale price based on how much it can think it can sell and Elysium, HPN, etc can take it or leave it.  I wonder what Elysium's side of the story is. 

 

 

well at least it appears they play with fire. This article shows a snapshot stating the elisium contract with chromadex ends in February and will not be extended:

http://www.timelessl...t-paying-bills/

 

 

 

That's totally messed up that they would do this, risking all the credibility they were espousing with their team of nobel scientists. Really odd.

[TaiChiKid]

But NR is a natural substance, and Chromadex only has an exclusive for producing NR by a particular method.  Could it be that a second, unique process to produce NR has surfaced?  The latter is another possibility.  I do not think that with all the positive research reviewed on this forum that Elysium would cut off their foot..

[bluemoon]

 

 

That's totally messed up that they would do this, risking all the credibility they were espousing with their team of nobel scientists. Really odd.

 

 

This looks odd because we don't know important pieces to the story. 

 

I think Elysium, which keeps expanding its advisory board with big names, brought an important Chromadex employee to its company,  recently raised $20 million and is holding onto potentially very good news about its summer trial, knows what it's doing. 

 

The first trial results showed that 500 mg of NR with 100 mg of pterostilbine raised NAD+ levels 90 percent as opposed to 45 percent at 250 mg NR and 50 mg of pterostilbine. It's possible that the trial results showed clear health benefits at the higher dose but knows most will be reluctant to pay $3.30 a day for this and so are trying to force down their costs.

 

Leonard Guarente said the trial results will be published in a peer reviewed journal, but Elysium can put them up on its homepage at any time as it said it would do three years ago. My guess is that they are waiting to do so until it can figure out its dose recommendation and possible change in pricing. 

 

Isn't it also possible Elysium could start to sell NMN if those production costs were lowered?

[stefan_001]

That's totally messed up that they would do this, risking all the credibility they were espousing with their team of nobel scientists. Really odd.

This looks odd because we don't know important pieces to the story.

I think Elysium, which keeps expanding its advisory board with big names, brought an important Chromadex employee to its company, recently raised $20 million and is holding onto potentially very good news about its summer trial, knows what it's doing.

The first trial results showed that 500 mg of NR with 100 mg of pterostilbine raised NAD+ levels 90 percent as opposed to 45 percent at 250 mg NR and 50 mg of pterostilbine. It's possible that the trial results showed clear health benefits at the higher dose but knows most will be reluctant to pay $3.30 a day for this and so are trying to force down their costs.

Leonard Guarente said the trial results will be published in a peer reviewed journal, but Elysium can put them up on its homepage at any time as it said it would do three years ago. My guess is that they are waiting to do so until it can figure out its dose recommendation and possible change in pricing.

Isn't it also possible Elysium could start to sell NMN if those production costs were lowered?

Or they have a cash management problem and simply cannot pay

[bluemoon]

 

Or they have a cash management problem and simply cannot pay

 

 

Unlikely. Elysium couldn't keep attracting top talent, even a guy from Chromadex, if its financial situation was that bad.  

[stefan_001]

Or they have a cash management problem and simply cannot pay

Unlikely. Elysium couldn't keep attracting top talent, even a guy from Chromadex, if its financial situation was that bad.

My guess is that they expected the recent financing deal to be done much earlier so they overspend. Probably the actual cash from the deal is still not in. That what companies do, first you screw your suppliers to conserve cash, then employees. Simply poor management, makes you wonder what they spend the income on.

[Bryan_S]

I don’t know If you guys see what a rare opportunity we have here.

 

This gives us a glimpse of the “preferred” vendor pricing and what kind of volume it takes to maintain it. So the $400/kilo price Elysium Health's been refused is telling, I believe it represents the best pricing currently being given to our biggest "volume" distributers and I know this price point has been claimed as a break even point in the past. So even if the $400/kilo price can be beat I know it hasn't been beat by much, if at all.

 

Elysium Health has been playing chicken in a head-on collision with Chromadex to force a deal reserved for only high-volume distributers and they've obviously not reached this plateau. If their contract plays out at the end of February 2017 they'll have no other source of NR to buy and I’d say Elysium Health is done. If there is another source I think we'd have found it by now.

 

So I doubt if we have any vendors below this $400/kilo price but if they exist they'd definitely have to massively exceed Elysium’s sales figures to move them unto the sub $4  per gram range. I do not believe Elysium Health has deservedly reached this sales plateau and I'm not holding my breath that they pull through, yet they’ve become a one of the top players, which most of us will agree. They want this volume pricing to compete against the 2 best established vendors and they are forcing a price point issue only "sales volume" can drive. I certainly wish them luck. This has put them in a precarious position of losing their contract but ChromaDex doesn't want the non-payment loss on their balance sheet either, so we will see.

 

The most optimistic situation would be Elysium Health wins and if they do we'll see another round of this with other vendors wanting a price break their previous numbers didn't support.

 

Now lets look at the bright side for us, this gives us a unique insight into the latest vendor price wars which serves our community.

 

Some of you already monitor "Nicotinamide Riboside (NR)/Niagen vendor vetting and discussion" Now with this fighting going on in the background, what's the likelihood that a vendor can distribute Niagen at $3.00 per gram and make a profit? Guys we’ve seen the pricing, we know there are vendors undercutting the 2 largest distributers and some of us have asked how. . . . I don’t have to point out names, but I can say these rogue vendors have put out the most highly suspect pricing. Remember any one under 4 dollars per gram wholesale is selling NR for less than the price Elysium was denied by ChromaDex. ($400/kilo works out to $4 per gram with Zero profit)

 

So this now helps us to post buyer beware notices because we can now see if a particular vendor is selling their product for less than ChromaDex's best volume pricing. I think with this Elysium price fight we now have access to a metric where we can now weed out credible offers from those that are suspect. I can point to 3 vendors right now who's pricing is saying we are the top volume distributers in the world and of those three, I only halfway believe one of them as credible.

 

So guys we have a rare glimpse into whether a vender is selling their product for a price too good to be true or not. Its rather easy to pass nicotinamide off as NR or combined the 2 to stretch ChromaDex's supplied NR to a price point under $400/kilo. I for one don't want my NR cut with anything and if I want nicotinamide on the side, I want it to be my decision.

 

So if you are offered NR at under the sub $400/kilo price, either they are giving away some free product and taking a loss or they are a bigger distributer than someone like HPN. Yes I'm going to use them as a bench mark as one of the first vendors to sign up as an early adopter and we know them well.

 

In pursuit of better Group Buy pricing I’ve approached the biggest distributers and have been flat-out told it can’t be sold for less than Blank, . . and make a profit.

 

This lawsuit appears to have confirmed what I’d suspected. At this moment Thorne Research and High Performance Nutrition appear to have the lowest legitimate pricing and beyond them I’d have to say buyers beware.

 

As always JMHO

 

Missed a decimal point disregard this post.

Edited by Bryan_S, 10 January 2017 - 01:32 AM.
wrong premiss

[Oakman]

A kilogram is 1000 grams > $400 divided by 1000 grams = $.40 a gram not $4. But Chromadex is not selling at that price, rather somewhere between $800-$1000/kg, i.e., between $.80/g and $1/g.

 

Plenty of room for $3 NR.

[stefan_001]

A kilogram is 1000 grams > $400 divided by 1000 grams = $.40 a gram not $4. But Chromadex is not selling at that price, rather somewhere between $800-$1000/kg, i.e., between $.80/g and $1/g.

 

Plenty of room for $3 NR.

 

agree, a 1 month supply can of 30 x 250mg = 7.5gram. Like I wrote earlier that's 7.5USD. Total product cost of the entire can probably 9USD. So yeah there is a lot of air in the pricing. With a sales price for a can of 40USD that means 40-9=31USD goes into the pockets of the distribution chain. Theoretically speaking that would mean if the NR price is zero and the capsules get filled with air the retail price would still be 32.5USD..............

Edited by stefan_001, 09 January 2017 - 08:43 AM.

[Mike C]

http://www.northbayb...vato?artslide=3

[Nate-2004]

http://www.northbayb...vato?artslide=3

 

I was looking to invest in Unity Biotechnology a couple of weeks ago but found they weren't public. One thing these companies could do is go public, I'm not sure what the downside of that for them is but it's one way to crowd fund. I have a some of my IRA in stem cell companies. The article comments on NR, which I assume is why it's relevant.

 

Another way SENS has been getting funding recently in a pretty successful way is through regular kickstarter style crowd funding. I would also be more willing to contribute to specific agendas like that.

Edited by Nate-2004, 09 January 2017 - 07:18 PM.

[Vastmandana]

 

A kilogram is 1000 grams > $400 divided by 1000 grams = $.40 a gram not $4. But Chromadex is not selling at that price, rather somewhere between $800-$1000/kg, i.e., between $.80/g and $1/g.

 

Plenty of room for $3 NR.

 

agree, a 1 month supply can of 30 x 250mg = 7.5gram. Like I wrote earlier that's 7.5USD. Total product cost of the entire can probably 9USD. So yeah there is a lot of air in the pricing. With a sales price for a can of 40USD that means 40-9=31USD goes into the pockets of the distribution chain. Theoretically speaking that would mean if the NR price is zero and the capsules get filled with air the retail price would still be 32.5USD..............

 

The bane of math... that decimal point!!!

Haven't chimed in for over a year, lurking as too much other chaos in my life!  But this disclosure of bulk prices makes me feel much better, as it now appears that there is plenty of room for Live Cell to be making a very hefty profit, even at their 50% sale last week... At 66 and with a very stressed and declining income, I've chosen to continue with them, buying whenever they were offering their 40% off deals, despite the controversy... as I couldn't afford to take 1G/day otherwise...and I routinely create great gardens for less than others by choosing not to be too greedy... On a purely accounting point, selling for less to sell more is often a good business practice if you're looking for market share and markups are big...

 

I do agree, Bryan that this is huge information to have... and what it DOES show is that the profit/markups are ridiculous...

 

And... wtf is Elysium doing?  They built their name on the credibility of the folks on their team... seems a very foolish move on soooo many levels... playing hardball is one thing but not paying what you agreed to for product received and using THIS as leverage... yuck!  Even if they now have insider info, from their recent hire, that Chromadex's production costs are way lower, this approach seems bad juju all around.  

 

Based on the info revealed, seems all vendors are sucking up our money and laughing all the way to the bank!

 

Note:  I am still very excited about all the scientific data that continues to flow on NR but pricing it out of the hands of most folks...by middlemen... is why "America" free enterprise sucks these days...rape, pillage, plunder till the last tree is gone.  Sad.

Edited by Vastmandana, 09 January 2017 - 08:42 PM.

[Vastmandana]

Needless to say, I just received an email linking me to the writeup below is I feel is full of questionable conclusions about NR but adds some info on this controversy (from seeking alpha)

 

Summary

Niagen's phenomenal growth is a myth. After all, NR looks just like a very expensive version of vitamin B3.

Elysium has pulled in its future Niagen/pTeroPure demand, thus drying up its future revenue contribution to ChromaDex.

Elysium also played a timing game with ChromaDex to induce huge price concession, likely taking advantage of ChromaDex's channel-stuffing-based sales culture.

Expect weak future quarterly performance, especially Q4 and 1Q17.

Deteriorating customer credit quality likely implies more widespread problem than just Elysium.

In a previous article, I sounded alarm on the stock of ChromaDex (NASDAQ: CDXC) due to its spiking DSO and deteriorating customer credit quality. I laid out a range of possibility on what this could have meant for the company, the stock and investors.

The most benign interpretation as I deduced was a weak Q3. The most severe implication as seen by me was channel stuffing (in article title and main body), or fictitious revenue (via intense discussion with my readers in the comments area).

The company's subsequent Q3 earnings release validated my concern. Q3 net sales collapsed totally, driven by the meltdown of its core ingredients revenue. Q3 net sales declined 43.3% QoQ and 20.4% YoY, respectively, to $5.0 million from Q2's $8.8 million and 3Q15's $6.3 million. Q3's ingredients net sales net sales collapsed to $2.7 million from Q2's $6.2 million (-57% QoQ) and 3Q15's $4.1 million (-36% YoY).

Just compare Q3's net sales performance to Q2's (45% YoY growth, driven by 83% YoY growth in ingredients net sales) and you should have understood why I characterize the Q3 performance as a collapse or meltdown.

Pricing Dispute With Largest Customer

The most shocking revelation from the company's 10-Q was the following:

"We currently have a disagreement with a significant customer, and a disruption in sales to or the ability to collect from this customer, or other significant customers in the future, could materially harm our financial results."

"We currently have a disagreement over the interpretation of certain terms of a supply agreement with a customer that we expect will represent greater than 10% of our net sales for the year ending December 31, 2016. Because of the disagreement, this customer has not paid us approximately $3.0 million for previous purchase orders."

This customer is none other than the company's largest customer, "Customer C", which had an outstanding trade receivable accounting for 48.8% of the total trade receivables, or about $3.2 million, at the end of Q3. And this customer ceased to be the company's largest customer in Q3. Its percentage contribution to net sales went down from Q2's 34.5% to less than 10%, though exact net sales were not disclosed in that filing.

I argued that Customer C was Elysium Health in my previous article. A recent 8-K filing has now confirmed this. This filing made it clear that Elysium's contribution to Q3 net sales amounted to only $180K, or less than 4% of total net sales. And this contribution was entirely attributable to a huge quarter-end purchase order placed in Q2. Elysium didn't place any purchase order in Q3 and Q4. ChromaDex is now suing Elysium for three counts of Breach of Contract as well as one count of Fraudulent Deceit.

So what can we learn from this supplier-customer high drama? Here are some of my thoughts.

1. Niagen's Sustained Growth Is A Myth

Any new products go through an initial phase of phenomenal growth, from zero sales to non-zero sales. Since Niagen was introduced in May 2013, it has gone through a honeymoon period of "phenomenal growth". But that phenomenal growth was due to the low-base-number effect. The challenge is to deliver sustained growth in the long run.

Elysium is supposed to be the key growth engine of Niagen, since this is a company that boasts 7 Nobel Laureates on its Scientific Advisory Board and its Basis product is the most successful among all Niagen supplements due to the company's exceptional marketing prowess.

Now we have learned that Niagen has hit a wall even in a niche that targets affluent consumers who are attracted to the halo (and marketing hype) of famous scientists. Elysium has misrepresented its growth to induce massive price discount from its supplier ChromaDex. Actual growth is far from what you have read in the press or ChromaDex's past quarterly earnings releases.

 

Then there's CVS, which rolled out a Niagen NR product ("Age Defense") only to withdraw it from the market within less than a year. SNG (Specialty Nutrition Group, Inc.) appears to have followed CVS' footstep. It rolled out the F1RST brand of Niagen in GNC stores a year ago. The product appears to have quietly disappeared from GNC website. As of today (1/8/2017), if you search for Niagen on GNC website, the only product that returns is Jarrow Formulas Nicotinamide Riboside.

CVS, and potentially SNG as well, likely have figured out that marketing an extremely expensive version of vitamin B3 is not exactly a profitable endeavor. And this brings me to my second point.

2. Niagen Is An Expensive Vitamin B3. Pricing Is The Devil.

There's no doubt that Niagen NR is capable of boosting NAD+. But the problem is that all three variations of vitamin B3 are capable of accomplishing the same (at differing efficacy). If you are just slightly familiar with the science of NAD+ precursor metabolism (Preiss-Handler Pathway, NAD+ Salvage Pathway, etc.), you should have known that all three variations of vitamin B3, NR, NAM (Nicotinamide), and NA (Nicotinic Acid) are precursors of NAD+. All three produce NAD+ in the human body.

NAM is quite close to NR in boosting NAD+ in terms of equimolar efficacy. In ChromaDex's own study (mouse gavage/first clinical study by U. Iowa/Queens U./ChromaDex), NR achieves higher NAD+ boosting efficacy than NAM, but the difference was not statistically significant.

For consumers like me, who are wary of NAM's potential sertuin-inhibition effect, they can still use NA to achieve the same effect. NA and NAM are much cheaper than NR. By my calculation, NA can achieve the same level of NAD+ boosting effect at 1/70 the cost of Niagen NR.

NA does cause the unpleasant flushing side effect on some consumers. However, the side effect diminishes after extended period of use. I have used NA for months now and have used to the flushing side effect that has diminished gradually.

 

Consumers who don't mind NAM's potential sertuin inhibition impact can achieve the same result at even greater savings than using NA. Like NR, NAM is a no-flush version of vitamin B3.

Given NR is so much more expensive compared to its siblings (NAM and NA), there's no wonder that pricing is the key battleground in Niagen's vendor-customer relationship. There will be increasing pricing pressure from customers as the sales stall out. Now that ChromaDex's pricing dispute with Elysium has gone public, other customers might have gained more weapons in their pricing negotiation with ChromaDex.

Investors should also be informed that exercise, fasting, or caloric restriction can also boost NAD+ at virtually zero monetary cost.

3. Elysium Is Playing Timing Game To Gain Price Concession

The Elysium drama is a classical case of timing game being played between a supplier and its customers. When a supplier is under pressure to deliver numbers toward of the end of a quarter or year, it is more willing to make concession to its price. Companies engaged in this period-end pricing concession strategy are basically engaged in the practice of channel stuffing. When customers found this out, they are more likely to hold on their purchase order to the end of a quarter or year to induce price concession from their suppliers.

Elysium placed a monster order on June 28th. Though that order was not delivered, it triggered an outsized order that was placed on June 30th and was fulfilled on July 1st, only one day before the end of ChromaDex's fiscal 2Q16. That was how ChromaDex managed to report ingredients net sales growth of 83% for that quarter.

Of course, Elysium's drama went beyond timing of purchase order. It also involved immense pulling-in of future demand into a single order to induce price concession. But there's no argument that timing tactic was also in play here.

4. Expect Weak Net Sales In Coming Quarters

Elysium has not placed any order in Q3 and Q4. It pulled in its future Niagen demand in 2016 and the supply should be able to last into early 2017. With the demand from this top customer having totally dried up, expect to see weak sales figure in Q4 and 1Q17.

 

5. Suspicion of Recognizing Disputed Revenue

From the 8-K filing, it's obvious that ChromaDex was willing to address Elysium's pricing concern. With pricing dispute going on, ChromaDex rushed to deliver the huge June 30th order right before the end of Q2. The order was subsequently recognized as Q2 revenue. From the time of delivery of the purchase order to the time 10-Q was filed, the pricing dispute was still going on. This raises the question of if the company has knowingly recognized revenue in dispute. If yes, this would be in violation of GAAP accounting rules.

Of course, if the court rules entirely to the company's favor, the blame could be squarely placed on Elysium's shoulder. But so far we have only heard ChromaDex's one-sided argument. Any counter-claim from Elysium or this court proceeding alone might reveal a lot more regarding what has actually occurred behind the curtain.

There's also the likelihood of a settlement. The company can settle for less than the nominal amount of receivables owed. That would also be a proof that management knowingly recognized revenue in dispute in 2Q16.

6. Deteriorating Credit Quality Implies More Widespread Customer Problem

As pointed out in my previous article, ChromaDex's customer credit quality has deteriorated since 4Q15. This can be seen from the chart below that plots the trend on AR (accounts receivable) and DA (doubtful accounts) allowances since 1Q13.

Chart 1. A/R and Doubtful Accounts Allowances trend 2013-16. (Source: author, based on public filings.)

Don't rush to assume that the DA allowances were due to the Elysium dispute. Recall that the Elysium dispute involved $2,983,350 in purchase order plus some royalty revenue as well. As revealed in the 8-K filing, the total amount in dispute has now amounted to no less than $3,983,350, or almost $4 million.

 

The $603K DA allowances amounted to nothing when compared to the disputed revenue with Elysium. So, most likely they were attributable to other customers. Some simple math would tell you that the DA allowances were a whopping 18.1% of the total AR balance less what was owed by Elysium, as of the end of Q3.

Such low customer credit quality should not be taken lightly because it is a warning that the quality of the revenue or net sales is questionable as well.

Final Remarks

Elysium Health reported positive clinical trial on its Basis supplement product, which cheered the investing community. But when you think through it, the clinical trial result is nothing unexpected. If you are just slightly familiar with the science of NAD+ precursor metabolism (Preiss-Handler Pathway, NAD+ Salvage Pathway, etc.), you should have been aware that all three variations of vitamin B3, NR, NAM, and NA, serve to produce/boost NAD+ in the human body.

Yes, NR is slightly more potent than NA and NAM in boosting NAD+ on an equimolar basis. But why should that matter much when it is orders of magnitude more expensive than NA and NAM?

The high drama between ChromaDex and its top customer Elysium Health should have taught investors a thing or two. Looking beneath the surface, a lot of red flags are lurking and call for a cautious approach when considering this company as a long-term investment candidate.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

 

 

Edited by Vastmandana, 09 January 2017 - 09:02 PM.