87 replies to this topic

[John Schloendorn]

I'm currently looking at finding a source of GDF-11. I'm corresponding with a molecular biologist I know and would be interested in finding like minded individuals. We are currently talking about a eukaryotic cell cultures because GDF-11 is a glycoprotein and bacterial-expressed proteins would not be glycosylated, so there are initial issues that need some clarification. Then there is the necessary infrastructure to pull this off along with purification. 

 

Uh just one little detail here... You're probably referring to the inactive precursor.  For all these inhibitory TGFs, the glycosylation site is part of the pre-pro / sequence that gets removed.  The mature version is a non-glycosylated homodimer of 109. 

[Bryan_S]

 

I'm currently looking at finding a source of GDF-11. I'm corresponding with a molecular biologist I know and would be interested in finding like minded individuals. We are currently talking about a eukaryotic cell cultures because GDF-11 is a glycoprotein and bacterial-expressed proteins would not be glycosylated, so there are initial issues that need some clarification. Then there is the necessary infrastructure to pull this off along with purification. 

 

Uh just one little detail here... You're probably referring to the inactive precursor.  For all these inhibitory TGFs, the glycosylation site is part of the pre-pro / sequence that gets removed.  The mature version is a non-glycosylated homodimer of 109. 

 

 

Thanks that's why I put this out here. I could not discern from the publications and didn't know if it was important to be bioactive. I thought the sequence contained one potential N-linked glycosylation site at asparagine 94.

 

OK here is the background:

Growth Differentiation Factor 11 (GDF­11), also known as BMP­11, is a member of the TGF­β superfamily and is highly related to GDF­8. GDF­11 encodes a 407 amino acid (aa) prepropeptide which contains a signal sequence for secretion and an RXXR proteolytic processing site to yield a 109 aa residue carboxy­terminal mature protein (1). Mature GDF­11 contains the canonical 7­cysteine motif common to other TGF­β superfamily members; however, like the TGF­βs, Activins and GDF­8, GDF­11 also contains one extra pair of cysteine residues. At the amino acid sequence level, mature human, mouse, rat and chicken GDF­11 are 99 ­ 100% identical. GDF­11 and GDF­8 share 90% amino acid sequence identity within the mature protein. As detected by in situ hybridization, GDF­11 is expressed in diverse regions of the mouse embryo: tailbud, somitic precursors, limbs, mandibular and branchial arches, dorsal neural tube, odontoblasts, nasal epithelium, and particular regions of the brain (1, 2). Likewise, a targeted deletion of GDF­11 in mice results in a spectrum of abnormalities including palatal malformation, vertebral defects, elongated trunks with a reduced or absent tail, missing or malformed kidneys, and an increased number of neurons in the olfactory epithelium (2 ­ 5). An intriguing finding in the knockout mice was that the trunk elongation was due to an increase in the number of thoracic vertebrae (4). This implicates GDF­11 as the first secreted factor to influence the specification of segmental identity in vertebrates (3). In fact, GDF­11 does regulate expression of segmental transcription factors, the Hox genes (6). GDF­11 signals through the Activin type II receptors and induces phosphorylation of Smad2 to mediate axial patterning (7). Despite the strong expression in the limb throughout development, no limb abnormalities were found in the knockout mice. However, in vitro micromass studies indicate that GDF­11 inhibits myogenic and chondrogenic cell differentiation and may impact formation and development of the limb skeleton (6). R&D Systems recombinant GDF­11 preparations have been shown to act similarly to GDF­8 in both the Xenopus animal cap and the K562 assays.

 

Thanks John so this can be E. coli­ derived and remain bioactive?

[John Schloendorn]

Thanks John so this can be E. coli­ derived and remain bioactive?

 

 

All I can see is that there are some vendors out there, who make money from saying that this is the case, do indeed say that this is the case.  There are no known reasons that it wouldn't.  Just keep in mind that "bioactivity" is a multidimensional thing.  Your best bet is probably to make a small amount and then test the particular, specific activity that you care about directly. 

 

 

 

 

 

[ceridwen]

Can you get me some bexarotene please?

Can you get me some bexarotene please?

asap please

asap please

asap please

[Synchro]

Synchro
When you say don't drink alcohol are you referring to methanol?

 

I didn't say that, I just said that alcohol is one of those things that is always toxic, and you have to choose wisely when and how much to drink if you're going to be serious about antiaging. OTOH, hey, alcohol falls into that giant OTTCGY category; you can't avoid all risks, you pays yer munny and yer takes yer chances.

As for methanol, haven't drunk it since I stopped indulging in diet soda's lol.

[Synchro]

 

Thanks John so this can be E. coli­ derived and remain bioactive?

 

 

All I can see is that there are some vendors out there, who make money from saying that this is the case, do indeed say that this is the case.  There are no known reasons that it wouldn't.  Just keep in mind that "bioactivity" is a multidimensional thing.  Your best bet is probably to make a small amount and then test the particular, specific activity that you care about directly. 

 

 

Thanks, John, for the info, very much. I was thinking along the same lines. I jumped back into longecity because I could see with the research project I have coming up soon, I would be equipped to take on production of GDF11 and analogs - and it's a very important point here that the matter of analogs are just beginning to be explored, we're at the tip of the iceberg - heck, we're at the tip of the gnat's butt on the tail-feather of the penguin standing on top of the iceberg - so I wished to establish contact with those who would be interested in collaborating. This is all for personal use, or use within a very small club very carefully constructed, not at this time for a giant buyers' club although with proper legal structuring it could get there.

 

But, in any case, I'm a committed Berserker who will make it and use it and we'll find out what the hell happens to me.

 

I will post again more, but what I'm seeing right now is this potential synergy between NMN and things like GDF11; I could see, for example, putting myself on GDF11, establishing a baseline, watching for "oopsies!!" lol, then titrating NMN into the picture, and see what happens. There is no faster way; I like fast. I'm not any different from physicians in centuries past who experimented on themselves, and yes, I'm perfectly aware of the cautionary tales of the ones who did themselves in. Alexander Bogdonov is one of my favorites; for the grace of God have gone I more than a few times. Anyway, in eventual anticipation of various things like NMN, I am going to go ahead and have a port put in soon, but the immediate purpose of the port is 24 hour IV vit C, things like that, so, no, I'm not crazy jumping ahead to IV NMN, just taking groundwork steps one at a time; been contemplating the port thing to enable 24 hour IV's such as vitamin C for a while. Probably will start 500 mg / hour, go up to 1 gram per hour. This is not an antiaging strategy for now; it is a prevention of OTTCGY strategy, especially the diabetes, which is progressing and which I'll talk about later.

 

Very Best, Synchro

 

 

 

 

[Primal]

 but hurry cos I'm fading fast

 

if you're fading fast you should consider other factors driving you down, such as mold illness, chronic infections, etc

[IpolitBender]

Certainly not my area of expertise but I thought glycosylation was generally required to get the folding right?

 

Also isn't gene modification well guarded against by eukaryotic cells?

[ceridwen]

Could be mould,or Lymes

[Synchro]

Certainly not my area of expertise but I thought glycosylation was generally required to get the folding right?

 

Also isn't gene modification well guarded against by eukaryotic cells?

 

 

Yes, gene modification is well guarded against. This is why the NMN study was so important; upregulation of all 7 SIRT genes by the application of one agent? Wow. Ditto GDF11; another agent that appears to be able to globally or semi-globally modify gene expression. My theoretical concern with NMN is that, dramatic as the results were, perhaps it is along the lines of putting nitro into the gas tank of a VW - for a few miles, it sure acts like a Mazaratti...until it blows up. This is why for myself I am thinking along the lines of giving myself GDF11 (or another modulator) and then titrating in MNM. As for the folding for the GDF11, yeah, it's a detail to be worked out.

[Primal]

 My theoretical concern with NMN is that, dramatic as the results were, perhaps it is along the lines of putting nitro into the gas tank of a VW - for a few miles, it sure acts like a Mazaratti...until it blows up. This is why for myself I am thinking along the lines of giving myself GDF11 (or another modulator) and then titrating in MNM. As for the folding for the GDF11, yeah, it's a detail to be worked out.

 

 

this is definitely a concern, because if vitamin B3 availability is indeed not rate limiting then supplying high dose NR/NMN is artificially boosting the system, like nitro in a VW. It could be a good reset button for having eaten too many calories and causing no long term problems, but it could also be going against your hypothalamus/pituitary or whatever else that is deciding the rate of NAD biosynthesis in your cells. I really hope some researchers will dig deep into finding why the NAD concentrations go down overtime. Maybe lack of folates/methylation or other nutrients. 

[IpolitBender]

I included NR in my regime about four months back and no flames out the exhuast yet and up to 2g/day now.  Does anyone have a negative anecdotal report from a long term user of NR?  A couple years back there was two weeks on a respirator from cerebral swelling when neem reacted with something so more cautious now.

[Bryan_S]

I'm now very much into the NR path, its turned my health around. I take it sublingual but we've had some heated conversation currently going on over intestinal absorption. So I'm keen to see how all that all shakes out. I'd say after 4 months of personal experience if the engine parts were going to self destruct I'd have seen a crash in my metabolism. I'll keep you posted if that happens.

 

But back to the overall discussion. NAD+ boosting and GDF-11 are completely different approaches but I believe they'll prove to be complementary. Here's the basic logic.

 

Mitochondrial metabolism and NAD+ boosting:

As we age our NAD levels fall and at this point I haven't seen any research that has fingered the culprit. NR is converted to NAD+ in only two metabolic steps, so in taking oral NR we're bypassing a number of processes. For those following the threads NMN would be the most direct route but few of us could afford it or put up with the injections. So from this angle the strategy is to boost your available ATP and a whole host of other cellular processes benefit. (a huge topic for a different thread) 

 

I like the idea of this approach because it's making better use of your existing cells. (hardware) Now from what I've read you can only ramp up the cellular metabolism so much and at some point its self limiting. So the pinnacle of performance would likely be the cellular energy levels of a young man or woman. I'm also under the assumption from reading personal experience threads that older individuals see the benefits of NAD+ boosting more than younger individuals. In terms of what benefits we each see I think this is a bit more complicated as we age and our cellular hardware slowly self destructs due to life style and those diminishing NAD levels. So increasing NAD+ levels likely will not bring us back to 100% of our past performance due to cellular degradation. Still a far cry better than where we were. So in my opinion its a whole lot safer to boost your mitochondria than unleashing a bunch of old stem cells on a system weakened by age.

 

GDF-11

So this brings us to GDF-11 and possibly a number of currently unidentified growth factors. I believe this is a sound but cautious path. Once we begin waking up our old stems cells it might be prudent to make sure our existing cellular hardware is already preforming at "your" peak performance first. There is a lot going on in cell division and we wouldn't want any errors cropping in. Also as we all know the body's immune system destroys would-be cancer cells daily. So ideally we'd want to optimize our entire system before unleashing a legion of stem cell reserves.

 

Keep in mind also our stem cell reserves are a limited resource. So how much is too much? Unfortunately mammalian cell lines can only divide so many times before senescence. (Cancers being the immortal exception) So in the long hall a GDF-11 path may entail slowly prodding these reserves to maximize personal performance and your longevity. We wouldn't want to burn ourselves out in a spectacular peak, the collapse could be as sudden.

 

So the way I see it. In the next 1 or 2 years those of us who have taken the NR path will either prove or disprove its viability to those of us on the sidelines. Then as the growth factors are better understood we may have a population of people who are less prone to cancers before "slowly" unleashing our stem cell reserves with substances like GDF-11.

[IpolitBender]

I agree. My experience with NR has also been very positive.

[Synchro]

Thanks so much for info on NR; I am going to incorporate it soon. I really appreciate the info.

 

My additions recently have been or are about to be: 

    

     creatinine 5 grams four times a day (Yeah, I'm pushing a little past the 12 gram per day mark)

     going to start the C60. I'm presuming I do it IV; I'll check the C60 threads.

     NR as soon as I source it; again, I'll check the NR threads for info, and I'm also going to shoot an email to my source in China and see if she can source it for me bulk/pure

     astragaloside IV 100 mg daily - I need to find the thread that talks about it not working - what a drag if I chose the wrong stuff

     having the IV port put in so I can start 25 grams of intravenous vit C per 24 hours, and be able to do other things IV at the same time

 

and for the future, when I have the research contract and can look at making the GDF-11, as well as NMN, but it's very exciting to me that perhaps NR is going to partially fill that gap until I can get there.

 

right now I have capGC and can check for organic contaminants, but until I get the HPLC/MS verifying purity has to wait; I just have to trust my source and the COA's. She's in that industry and has an upper level position, so I have reasonable trust she gets the real stuff and trustworthy COA's.

 

and then the whole list of a zillion things that are supportive, including the fish oil very high dose along with omega-7, etc, etc

Edited by Synchro, 03 July 2014 - 02:52 AM.

[Primal]

 so I can start 25 grams of intravenous vit C per 24 hours

 

I have injected more than that, I dont think I got benefits from it

 

 

ncluding the fish oil very high dose 

 

I think that's a bad idea

[PWAIN]

Don't inject the C60, Mix it in high phenol extra virgin olive oil and drink about a tablespoon (thats what I do). Thats also how it was done in the experiment on rats that worked. It should turn the olive oil a reddish purple colour.

 

 

     going to start the C60. I'm presuming I do it IV; I'll check the C60 threads.

[Synchro]

Primal said: "I have injected more than that, I dont think I got benefits from it"

 

You're right, under normal circumstances, high dose vitamin IV C is not of any particular use, I totally agree. There are medicinal uses for high dose IVC; as Dr. Jenner, and several other pioneers, showed a long time ago, massive IVC's in patients seriously ill from viremia can stop the harm from the virus in its tracks. For example, he showed that polio victims would not sustain any more nerve damage once the IV V's were started. I am quite certain that all our new scary viruses could be rendered harmless by high dose IVC, such as dengue fever, etc, but the medical establishment (which I'm a very unhappy part of) is absolutely immovable. It doesn't matter what evidence you present, hospitals will NOT give high dose vit C, even though it WOULD save the patient's life. Un-friggin-believable. I am ashamed of the profession of medicine; it is so appallingly blind.

 

However, in my case, I have a special reason for doing IV C 24/7. I have battled diabetes for over 20 years now, and I'm definitely starting to lose the battle. the only reason I'm still reasonably healthy is I've been taking 3 to 9 grams a day oral C religiously. 

 

The way that vitamin C protects against diabetes is by inhibiting aldose reductase. Nerve damage in diabetes is mainly caused by the buildup of excess sorbitol in tissue/stroma adjacent to nerves. Aldose reductase is the enzyme that converts excess glucose into sorbitol. The sorbitol builds up in the tissues/stroma, but not in the nerves. Consequently, an osmotic differential happens whereby the sorbitol is under osmotic pressure to migrate into the nerves. However, sorbitol cannot migrate across nerve membranes - so, instead, as the osmotic pressure builds up, eventually the sorbitol actually punches through the membrane, damaging the nerve. This leads to neuropathy, and it leads to eventual organ damage all over the body due to the damage to the nerves supplying somatic, sympathetic and parasympathetic innervation to those organs.

 

Because vitamin C is nature's very effective aldose reductase inhibitor, vit C slows down the conversion of excess glucose to sorbitol, and this in turn relieves a lot of the osmotic differential of sorbitol between tissue and nerves, and prevents a lot of nerve damage.

 

9 grams a day orally is about all I find I can take; more causes diarrhea. Plus, I very much doubt that all of that 9 grams gets absorbed. 

 

Finally, sorbitol also plays a significant role in the glycation of proteins, one manner of which is reflected by the A1c; glycated hemoglobin.

 

so, the idea is simple: most animals on earth make the human equivalent of about 15 to 25 grams a day in their livers, circulated in the blood to all body compartments. Humans, the main primates, a few bats, guinea pigs, etc, are the few species who have lost the vitamin C gene. If they don't get C in their diet, they die. 

 

Linus Pauling argued that humans should have about 25 grams of C  per day - but doing that orally is impossible.

 

thus, my idea to put in a port and give myself 25 grams a day of IVC, and let's see what happens to my A1c over at least three months of non-stop high dose IVC - and any other measurement of glycation that is feasible.

 

What a wowser it would be if I could actually drive my A1c way down, despite my blood sugar being partially out of control.

 

You know, this thing of A1c being "normal" if it's less than 6 is misleading - the A1c should be zero - there is no such thing as "good glycation".

 

Besides, if I have a port, and I'm running a backpack IV bag every day anyway, just think of what else I could put in that bag, hmmmm???   

[Primal]

I agree with you on vitamin C injections, I think patients/patients' families should have the right to require 200g of vitamin C per day. I would ask for it for viral infections, bad burns, car accidents, any sort of major trauma. I also think huge doses of active B vitamins should be given, for example for your nerve damage etc  Unfortunately all IV compouding pharmacies in the US that I know of dont have active Bs. non-active Bs still work but I'm sure the active form would be better for high doses.  

 

With a port you have access to lots of good stuff. I have an extremist personnality so I have to watch out not to get too carried away. Sounds like you may also have a tendency toward that as well. 

 

I've made my own injections of sodium ascorbate, to test the NO/ONOO- theory of Prof Martin Pall. Much cheaper to make your own than to buy sterilized vials. I can take 5g orally of vitamin C every hours, so in 12 hours I can take 60g, without diarrhea. Above that I need to do fast push or infusions. But what concentration is needed to inhibit aldose reductase? Wouldnt it be better to take a gram every hour than a 25g infusion?

 

Regarding diabetes did you read http://www.ncbi.nlm....les/PMC3204926/ ? 

 

 

[gt35r]

"You know, this thing of A1c being "normal" if it's less than 6 is misleading - the A1c should be zero - there is no such thing as "good glycation"."

 

I agree but as a physician you should know why a less than 4 or 5  a1c is a concern.

 

Most people are not concerned  that there is too little glycation in general, but that the RBC are not living there full life and therefore having only a small amount o time to be glycated. 

 

Getting a1c below 4.5 is very rare and hard. If someone has an a1c of a 2 or 3 it is more likely that their RBC are dying and turning over unusually fast rather then their bodies glycation rate is low. Getting an a1c down to 0 is next to impossible considering that RBC are glycolysis dependent and can not run off of any other pathway due to the lack of mitochondria; they will always need some glucose.

[Synchro]

Hi, I need someone to help me figure out why I can't post a new topic. 

 

Yeah, I read the FAQ's, and yeah I tried emailing the administration of Longecity, and got nowhere.

 

My email was returned to me as unread. Yes, I used the contact form which then resulted in me being redirected to sending an email directly which then was returned to me as unread. WTF??????

 

Anyway, I posted a new topic asking for information from members on putting together a group buy for NR, and as far as I can tell my new posting got blocked. It's not accessible and it has a weird iris symbol on it that I sure didn't put there.

 

so, here's the info I TRIED to post as a new thread:

 

I have made progress on sourcing NR offshore in bulk. I am continuing to search, and I have my Chinese agent talking to several supplement factories asking them to consider becoming a manufacturer of NR. She is getting some interest.

 

So far, the first source I found offshore is far too expensive: greater than USD 80 per gram, in kg quantity.

 

What I need to know (since there are members here vastly more knowledgeable than me on this subject, I thought I'd just ask for help instead of trying to figure it out on my own, which is like reinventing the wheel) are the following:

1. for truly effective dosing of NR, where cost is not an issue, what would likely be the optimal daily dose total?

2. what price range would members consider investing in for a three month's or six month's supply at a time?

 

I am NOT doing this to make money. I AM doing this so I can get the price down to where I can have it too!

 

The cost of the group buy will be cost+   ....   that is, the actual cost from the factory, shipping (I have a way of getting it shipped direct to you from the factory in China), plus my agent's commission (very reasonable), plus a small percentage for overhead and administration, probably 10%, certainly not more, maybe less.

 

The feedback would be very helpful to me. I need you to be realistic about cost; 10 cents a day just isn't possible LOL...I am very hopeful I can get the cost down to around a buck a gram, but not making any promises.

 

Very Best, Synchro

[Bryan_S]

Synchro I'm setting up a group buy for NR in a little less than 2 weeks for 30% off and your welcome to tag on. In the beginning I tried working with several Chinese suppliers and I'd get the "Oh yes we can help you" but it was just a ploy to get me to send cash. One of the guys here on Longecity bought some and had it tested and it wasn't NR. So buyer beware and be sure to get it tested. So this group buy I mentioned is for Longecity members as team pricing and its ongoing every 2 months and it's the real thing. 

 

On the dosage question that clinical data isn't in yet but may get published soon. The study "Estimated Primary Completion Date August 2014"

 

Current NR Pharmacokinetics Study

A Study of the Pharmacokinetics of Three Dosages of Niagen in Healthy Subjects (14NBHC)

 

 

Group Buy

 

http://www.longecity...city-group-buy/

Edited by Bryan_S, 04 August 2014 - 12:49 AM.

[Synchro]

OK, well that explains part of it. I guess. I still don't know why my post in the other thread is blocked. Did you block it? Or did I just goof somehow and posted it in the wrong place or in the wrong manner? And why do I see your iris symbol on it when I go to try to access it? Goodness - all these mysteries for such a simple thing!!

 

In any case, the group buy you're offering works out to $4.48 a gram. Which would have been a good detail to include, don't you think? It's a lot better than USD 80/gram, I'll give you that, but it's still too much, I rather suspect, for truly effective dosing in aged humans.

 

I think I'll pass, until I'm a millionaire or can source NR for down around a buck a gram. My resources are pretty good, and you can damn betcha it will be tested before I pay for it and accept it. But I also have a couple of my colleagues working on figuring out our own industrial process for manufacturing it, so sooner or later I'll have the ability to make and take this stuff in quantity at an affordable price, and then maybe we can do a do-over on this group buy thing.

 

Thanks for the link, I'll check it out.

 

Very Best, Synchro

[Bryan_S]

Topic blocking I have no such powers.

 

As far as the NR is concerned we will have PK data soon and be able to take an intelligent approach to human dosing. The mouse to human translations are insane and I believe will be seriously revised after the human PK study is over.

 

Is anyone making any progress on securing GDF11?

[Synchro]

We're making progress on GDF-11, but far from sourcing it. Right now we're working on defining the process of making it so that it could be scaled up to industrial scale.

 

My intuition is that the effective dose range of NR for a human is well above a gram a day, but I was encouraged by the poster who talked about not noticing its effect until he stopped it, who was at 1 gram. I find the same with nanocurcumin; the effect is subtle, but real, and you don't necessarily notice until you stop taking it.

 

But with NR I would think the effect would be quite noticeable if the dose is high enough...which leads me to suspect that 1 gram a day is not near enough.

 

My blocked post remains a mystery. I'm glad to hear you're not involved. I still have not figured out how to successfully contact the administration here. I don't really give a crap, though; Longecity can go to hell, it's not the only rejuvenation forum out there.

 

Very Best, Synchro

[Bryan_S]

We're making progress on GDF-11, but far from sourcing it. Right now we're working on defining the process of making it so that it could be scaled up to industrial scale.

 

My intuition is that the effective dose range of NR for a human is well above a gram a day, but I was encouraged by the poster who talked about not noticing its effect until he stopped it, who was at 1 gram. I find the same with nanocurcumin; the effect is subtle, but real, and you don't necessarily notice until you stop taking it.

 

But with NR I would think the effect would be quite noticeable if the dose is high enough...which leads me to suspect that 1 gram a day is not near enough.

 

My blocked post remains a mystery. I'm glad to hear you're not involved. I still have not figured out how to successfully contact the administration here. I don't really give a crap, though; Longecity can go to hell, it's not the only rejuvenation forum out there.

 

Very Best, Synchro

 

 

Not sure who you're speaking about but I posted about stopping for a week and later resuming but I wasn't taking a gram per day.

 

The effects are subtle and its more like bringing you back to a state of past normal than anything profound or earth shattering as I expect GDF-11 will turn out to be.

 

Since I have a surplus from my last group purchase and I'm about to make another purchase I'm experimenting with over a gram per day now but I haven't shared that with anyone before today. 

 

I'd advise finding your own benchmark and seeing if NR will make a noticeable difference in your life before you invest your time in anything risky like investing in a Chinese lab to produce it. Keep in mind "Nicotinamide Riboside" is not a huge market, at least yet. The rest of the world is still watching to see if it will generate a beneficial human effect. So as far as competitors the initial cost of production coupled with the uncertainty of this market is still huge. It's going to take time for this market to grow and that volume will bring the price down and elicit competition.

 

Enough of us on Longecity have already been bamboozled with the fake Chinese offerings, who's going to trust them as a source. Also the commercial NR is stabilized as a salt and the Chinese if they can produce it at some point will have to overcome that IP hurdle as well. 

 

And people wonder why the rest of the World hates the Chinese so much, Stolen Intellectual property for one and Mislabeling products and selling fakes is number two.

 

Buyer beware!

[Synchro]

I agree with you, Bryan. The Chinese are very difficult to deal with. I have traveled and visited in Thailand and the Philippines, and have many professional friends in both places.

 

I can tell you that throughout Asia the Chinese are called "the cheaters". As one business friend of mine who lives in China half the time told me: "It's not a question of whether the Chinese will screw you, it's just a question of when they will screw you."

 

However, like all peoples in the world, not all Chinese are evil. I have an agent in China who has been absolutely trustworthy, with not a single instance of anything but perfect performance. Every bulk item I have gotten through her has tested absolutely pure and in complete accordance with the COA.

 

Now, I certainly understand the special situation of NR, and how tempting it would be to cheat on that item.

 

However, I reiterate that if I do enter into a manufacturing agreement for NR, it will be through my agent, there will be strict requirements, and I will be testing every single bulk shipment with HPLC/MS/MS/MS for purity, and capGC for organic contaminants.

 

I am surprised that there are so few interested at this time in megadosing NR. I wish I could piggy-back on your bulk order, but right now I'm between funding cycles and scraping bottom. As soon as I'm flush again I will certainly be doing my own experiment, and I'll certainly be going well above a gram a day, that's for damn sure.

 

Very Best, Synchro

[Primal]

As far as the NR is concerned we will have PK data soon and be able to take an intelligent approach to human dosing. The mouse to human translations are insane and I believe will be seriously revised after the human PK study is over.

 

 

 

What I need to know (since there are members here vastly more knowledgeable than me on this subject, I thought I'd just ask for help instead of trying to figure it out on my own, which is like reinventing the wheel) are the following:

1. for truly effective dosing of NR, where cost is not an issue, what would likely be the optimal daily dose total?

2. what price range would members consider investing in for a three month's or six month's supply at a time?

 

I dont think anybody knows at this point. I guess the mouse dosage is a good upper bound for a dose that should produce significant results. I'm eager to see the results of the upcoming human studies, but I also suspect that 1g/d might be too low for the kind of results you are after. 

 

I hope a product with no fillers at all will surface soon, about a dollar per gram as you suggest would be nice too but not sure if it's realistic for now

 

However, I reiterate that if I do enter into a manufacturing agreement for NR, it will be through my agent, there will be strict requirements, and I will be testing every single bulk shipment with HPLC/MS/MS/MS for purity, and capGC for organic contaminants.

 

Would you mind sharing, here or via private message, the testing lab that you have used for this?