326 replies to this topic

[able]

Lawrence,

 

There are several Chromadex stockholders on this forum that are eager to find problems with your results.

[stefan_001]

Your BUN level shows a remarkable drop after you started NMN. Could be eating or liver related or changed urea dialyses. Still in normal range though.
https://www.ncbi.nlm...05/#!po=75.0000


Able I think your comment on Chromadex shareholders is off base. 7.5Gram NMN per day for 8 months is unprecedented. Untill somebody does that with NR there is nothing to compare. Even more its is interesting to understand what would be the lasting impact of this high dosing, I dont think we should expect a different result with NR. Positive or negative. As for the stockholdings, its going great and I dont think this forum has any influence on it whatsoever.

Edited by stefan_001, 11 November 2017 - 10:44 PM.

[LawrenceW]

Aha, that explains a lot.  I have been lurking on this forum for several years and it appeared to me that most of the participants are genuinely interested in anti-aging and therefore I felt that it was time for me to share my own anti-aging experience.

 

I caught the anti-aging bug after reading Kurzweil's books. I also clearly remember reading Sinclair's December 19, 2013 article about the Harvard mice study and book marking it.  Several months later I was chatting with my microbiologist buddy Joel and he mentioned NMN and my ears perked up. He said that this was the same stuff from the Harvard study and I drove down the next day and had a very interesting lunch where he described to me in terms that I could understand what Sinclair's discovery was.  As I recollect, he described it as NMN is a naturally occurring substance in the human body that is produced constantly with 2 daily peaks and distributed by the blood to every cell in the body. Once entering the cell it converts into NAD+. The NAD+ in turn then acts as a switch to turn on the 7 sirtuins that perform the housekeeping (DNA repair, metabolism control, etc.) functions of the body.  He further described that from birth until puberty, biology's main concern is keeping the body as healthy as possible. It does this by running the sirtuins at maximum activity. Once the body hits puberty, energy is diverted to procreation and the house keeping function falls to the way side and daily production of NMN begins to drop.  By the time we are our age, NMN production is roughly 50% of what we produced when we were children. Sinclair's discovery was that by simply supplementing NMN back to the levels we received when we were children that the housekeeping functions of the sirtuins would be returned to maximum levels.

 

The conversation eventually progressed to my saying, that sounds great how do we get some of this NMN? Joel replied that Sinclair is supposed to be putting together a human trial in a year or so for another year so he might publish in 3 to 5 years.  I said that we were going to be old men by then.  How do we get some now? Joel replied that SIgma Aldrich makes it for $1,700 per gram.  I said how far does a gram get me? He asked my weight, did some calculations and then told me that I would need 7.5 grams a day for 8 months.  I said, Joel I love you like a brother but there is no way that I am paying $3,000,000 for this.  I added that this sounded like pharmaceutical pricing to me and added that you're a molecular biologist and should be able to figure out a way of getting some at a more reasonable price.  About 3 weeks later Joel called and said that he could get some for around $35 per gram but it would be a 10 KG minimum order.  I called up a couple of my buddies, told them about SInclair and NMN and we all chipped in for a group buy of NMN with Joel and his medical partners overseeing our anti-aging adventure.

[Heisok]

"Able I think your comment on Chromadex shareholders is off base. 7.5Gram NMN per day for 8 months is unprecedented. Untill somebody does that with NR there is nothing to compare. Even more its is interesting to understand what would be the lasting impact of this high dosing, I dont think we should expect a different result with NR. Positive or negative. "

 

I agree Stephan. I think that the comment by Able is unwarranted. I am definitely questioning, and taking seriously the blood work. I pointed out the PSA which, although showing a trend higher, is still low. There are other things that are interesting, but I already decided to not dissect any more of those.

 

I think the study is awesome, and that the sharing by LawrenceW is unprecedented, and very generous!!!! I think that looking at the results as what they are, and not as any "fair" comparison, or that the doses of NMN are not economical is doing us a disservice. They are what they are.

Edited by Heisok, 11 November 2017 - 11:03 PM.

[LawrenceW]

Your BUN level shows a remarkable drop after you started NMN. Could be eating or liver related or changed urea dialyses. Still in normal range though.
https://www.ncbi.nlm...05/#!po=75.0000


 

 

My doctor explained to me that she felt that the drop in my BUN number indicated an improvement in my kidney function. I look at it as having a younger, and healthier kidney.

[Advocatus Diaboli]

@Lawrence, thanks for providing the data.

 

In your spreadsheet the last 3 entries for the BUN/Creatine ratio should be flagged in red, as those entries are below the lower limit of the "9-20" normal range-- 8, 7.6, 7.4

 

Under Subfractionation, Average particle size, the "263.1" shouldn't be in red, if that number is correct, and the "269.7" should be in red, if it's true that the flag range is ">267.9" (You might want to check if the ">" value of "269.7" is correct. Also check the "267.9" -- seems strange to have these numbers so close in a Hamming-distance sense).

 

Under Testosterone the "2.76", if correct, should be in red, as it's slightly outside of the "1-2.70" range.

 

The entire row of "Basos" should be in red.if the "0-0.7" range is correct and the numbers you've entered are correct. You have red-flagged only the last entry (0.8).

 

 

[LawrenceW]

@Lawrence, thanks for providing the data.

 

In your spreadsheet the last 3 entries for the BUN/Creatine ratio should be flagged in red, as those entries are below the lower limit of the "9-20" normal range-- 8, 7.6, 7.4

 

Under Subfractionation, Average particle size, the "263.1" shouldn't be in red, if that number is correct, and the "269.7" should be in red, if it's true that the flag range is ">267.9" (You might want to check if the ">" value of "269.7" is correct. Also check the "267.9" -- seems strange to have these numbers so close in a Hamming-distance sense).

 

Under Testosterone the "2.76", if correct, should be in red, as it's slightly outside of the "1-2.70" range.

 

The entire row of "Basos" should be in red.if the "0-0.7" range is correct and the numbers you've entered are correct. You have red-flagged only the last entry (0.8).

 

Thanks for pointing those out.  Over the years I noticed that while I was entering the numbers that the "normal range" would vary slightly depending on which lab was doing the testing. Some values would be red from one lab and not another.  I would update the normal range and not update previous results.

Edited by LawrenceW, 11 November 2017 - 11:56 PM.

[LawrenceW]

All the comments seem to be focused on the last 2 columns of pre and post NR.  Any comments on the pre and 6 month into NMN columns?

[ryukenden]

http://www.longecity...attach_id=14587

Does the above mean Revgenetics NMN is genuine?

It would be interesting to know how the synt is done. My guess it uses NR as building block. This could be a method to hide that a company breaks the Chromadex patents.

Thank you. Where do you recommend me to buy NMN?

[stefan_001]

@heisok you are probably right that it may not make sense to analyze as its too far out of the feasible.

Lawrence sorry for the focus on the after period.

Personally I have similar positive experiences with NR at lower levels (I take 500mg - split morning, late night) as you have with the NMN experiment. I tried 750-1000mg range for a while but felt it was negatively impacting at least appearance, even got commented by others that I looked tired. But that can be all subjective and I decided I just go back to old dosing without experimenting more or do blood panels. There are human clinical studies soon to be released and then more will be known.There is also the belief that there is a ceiling in NAD+ boosting with precursers like NR and I think similar NMN. The toxity studies recommend a NR level clearly lower than what you take, NMN may have different levels though. Therefore I have been mainly looking at the after results, what happens when you do such mega dosing, does it hold up after you stop.It looks that aging picks up again after stopping, as somewhat expected, so NAD+ boosting requires lifelong supplementation. That means finding the right minimum dose is important in my view.

The NR period is interesting from the perspective it didnt influence. That could be because it needs more time, too low dosing in your case or it just doesnt work.

In any case great you posted this.

Edited by stefan_001, 12 November 2017 - 11:10 AM.

[LawrenceW]

Where do you recommend me to buy NMN?

Hello Stefan.
 
In my mind all of the commercially available NMN is way too expensive.
 
I would offer to let you join in our group buy but you live in the UK.  The NMN that we buy needs to be stored at -20C while in powder form. Once a month we have the next month's supply of liquid concentrate prepared.  This liquid concentrate needs to be refrigerated and has a shelf life of 2 months.

Edited by Michael, 13 November 2017 - 12:04 AM.
trim quotes

[ambivalent]

I'm not surprised by the effects at high doses of NMN only the consistency and lack of side-effects. I dosed high doses of NR for several weeks up to 7.5 grams a day earlier this year (and reported it in the experiences thread). There was no doubt there is an awful lot more going on at the higher dose of NR than at 1 gram and less. The clarity of mind was remarkable some days, but other days I would experience fatigue and brain fog. I was developing a growing sense of youthening face (more facial mass); however, unfortunately, though, I then went away on a walking holiday, initially, experienced some sensational stamina but then a seasonal allergy kicked in hard and NR undoubtedly significantly worsened it. So unfortunately the experiment was halted. The experience of fatigue may well have been as a result of too much fission.

 

Down the line I have run into problems with most likely uric acid and possibly elevated blood glucose when restarting with NR and N+R, which would equate to pretty high doses. At some point I will be looking to do some blood work.

 

The accepted view that dosing above 1g of NR is redundant is most certainly not my experience - there was undoubted benefit; however, I'd say there is unfortunate trade-off/risk at these levels.

[able]

In Lawrence blood tests,I  notice BUN, Cholesterol and Triglycerides all improved with NMN and remained low or showed a bit more improvement with NR.

 

Some numbers after NMN seem to show more improvements, but could be that homeostasis or feedback loop kicks in and the NMN would quit working as well. 

 

Most definately shows promise though. If those improvements can be maintained at a safe dosage, Pharmaceutical companies stand to lose $billions in sales of statins and such (assuming it was all due to supplementation, and no diet/lifestyle change influence).

 

@Lawrence  - Hope you can post the results from your December checkup.

 

You mention adding the other 2 products to the NMN you took in the trial.    Are you also taking those now, or just the NMN?  Are those  taking 500 mg NMN  alone, or with the other products?

 

Also, are ALL of the experiments using NMN in the liquid form - no capsules?  That must be to increase bioavailability?

 

Edited by able, 12 November 2017 - 06:23 PM.

[LawrenceW]

Hello Able.

 

My Dec. 7 followup will not be a full blood panel as the doctor is looking at just a couple of things.  I will ask that she includes the testosterone and other markers that were pointed out earlier in this thread.  I will  post the results as soon as I receive them.

 

At the higher dose of NMN it is an absolute must to take the triple compound or I will simply have very expensive urine and limited benefits.

 

The fellows that will be starting the 500mg will be taking NMN only. We believe that dose will be below the biological feedback loop threshold and not require the other compounds. Dr. Sinclair, having taken the 500mg dose for a long time, makes us believe this to be the case. Our hope is that a significant or meaningful percentage of the benefits and blood improvements from the higher dose will be realized with the lower dose. If that is the case, then we will have a quantifiable value proposition. Do I want to spend $x and achieve these results or do I want to spend a much larger $y and receive these results. 

[recon]

At the higher dose of NMN it is an absolute must to take the triple compound or I will simply have very expensive urine and limited benefits.

 

May I know what is this “triple compound”?

Edited by Michael, 13 November 2017 - 12:02 AM.
trim quote

[LawrenceW]

 

Hello Able.

My Dec. 7 followup will not be a full blood panel as the doctor is looking at just a couple of things. I will ask that she includes the testosterone and other markers that were pointed out earlier in this thread. I will post the results as soon as I receive them.

At the higher dose of NMN it is an absolute must to take the triple compound or I will simply have very expensive urine and limited benefits.

The fellows that will be starting the 500mg will be taking NMN only. We believe that dose will be below the biological feedback loop threshold and not require the other compounds. Dr. Sinclair, having taken the 500mg dose for a long time, makes us believe this to be the case. Our hope is that a significant or meaningful percentage of the benefits and blood improvements from the higher dose will be realized with the lower dose. If that is the case, then we will have a quantifiable value proposition. Do I want to spend $x and achieve these results or do I want to spend a much larger $y and receive these results.

May I know what is this “triple compound”?

 

Hello Able.

 

You will have to glean that out of this patent application for yourself.

 

https://www.egaceuti...application.pdf

[LawrenceW]

Please excuse me if this question is ignorant.

 

My understanding is that NMN is produced in the body, distributed by the bloodstream and once inside the cell the NMN converts into NAD+. If that is the case, why do they look for elevated levels of NAD+ in the blood to determine the efficacy of NMN or NR supplementation?

[Michael]

My understanding is that NMN is produced in the body, distributed by the bloodstream and once inside the cell the NMN converts into NAD+. If that is the case, why do they look for elevated levels of NAD+ in the blood to determine the efficacy of NMN or NR supplementation?

You wouldn't look for it in plasma — but there are, of course, cells in the blood, too. Whether it's preferable (in terms of scientific understanding or ease and expense) to test whole blood, PBMC, RBC, etc. is a question for individual scientists and/or "the field."

[Advocatus Diaboli]

Re: post #106:

 

xEva, in the thread "Egaceutical Corporation Demonstrates Human Age Reversal, Patent is Pending" post #5, points out an error in the Egaceutical patent application, and suggests that there may be others. Her example is that in the patent application "C. elegans" is identified as a "flatworm" (page 3 of the application), when, in fact, it's a roundworm (nematode).

Edited by Advocatus Diaboli, 13 November 2017 - 05:48 AM.

[ryukenden]

Have any of you tried a few days NR & a few days NMN a week?

[LawrenceW]

 

My understanding is that NMN is produced in the body, distributed by the bloodstream and once inside the cell the NMN converts into NAD+. If that is the case, why do they look for elevated levels of NAD+ in the blood to determine the efficacy of NMN or NR supplementation?

You wouldn't look for it in plasma — but there are, of course, cells in the blood, too. Whether it's preferable (in terms of scientific understanding or ease and expense) to test whole blood, PBMC, RBC, etc. is a question for individual scientists and/or "the field."

 

 

The reason that I asked the question is because of the 2nd sentence of the 2nd paragraph of Chromadex's press release.

 

The Study Establishes an Effective Dose Range and Validates Safety for NIAGEN^®Nicotinamide Riboside Chloride in 140 Humans Over an 8-week Period -

 

IRVINE, Calif., Sept. 26, 2017 (GLOBE NEWSWIRE) -- ChromaDex Corp. (NASDAQ:CDXC), an innovator of science-based, proprietary health and wellness consumer products and ingredient technologies that promote health longevity, announced today that the initial results of its second human clinical study of NIAGEN^® nicotinamide riboside chloride (NR) have confirmed NR significantly and sustainably raises the co-enzyme nicotinamide adenine dinucleotide (NAD+) in 140 healthy human volunteers over 8-weeks.

 

In this study, participants in the active group received 100, 300, or 1000mg per day.  Results from the randomized, double-blind, placebo controlled, parallel-arm trial demonstrated that NR produced statistically significant increases in blood NAD+ compared to placebo that were related to the dose of NR consumed, demonstrating a dose response.  Levels remained elevated throughout the duration of the study, thereby establishing an efficacious range for daily consumption.  The study confirms not only efficacy in raising NAD+, but also definitively documents the safety of daily use of NR.  

[Michael]

 

 

My understanding is that NMN is produced in the body, distributed by the bloodstream and once inside the cell the NMN converts into NAD+. If that is the case, why do they look for elevated levels of NAD+ in the blood to determine the efficacy of NMN or NR supplementation?

You wouldn't look for it in plasma — but there are, of course, cells in the blood, too. Whether it's preferable (in terms of scientific understanding or ease and expense) to test whole blood, PBMC, RBC, etc. is a question for individual scientists and/or "the field."

 

The reason that I asked the question is because of the 2nd sentence of the 2nd paragraph of Chromadex's press release.

 

The Study Establishes an Effective Dose Range and Validates Safety for NIAGEN^®Nicotinamide Riboside Chloride in 140 Humans Over an 8-week Period -

[...]

 

Results from the randomized, double-blind, placebo controlled, parallel-arm trial demonstrated that NR produced statistically significant increases in blood NAD+ compared to placebo that were related to the dose of NR consumed

 

 

Well, now you know the answer . In fact, that's simplifying language for the general public: they actually tested in PBMC. And there's an additional reason to look in blood in human studies: it's harder to recruit human volunteers, and harder to convince IRBs that the risk to healthy patients is justified, and much more expensive to do studies involving (say) a liver or muscle biopsy than those that involve a simple blood draw. At minimum, you'd want to get some preliminary evidence from blood tests that would justify such further testing.

Edited by Michael, 14 November 2017 - 03:27 AM.

[warner]

Lawrence's results with high dose NMN look largely like what you would expect to see with increased exercise/fitness and some glycemic carb reduction (lower wt, lower DBP, lower BG, higher GFR, lower A1C, lower TG, higher T, higher PSA, lower inflammatory markers, etc.).  And it's probably the case that many of us have achieved similar results with diet changes alone.  And what we also know is that such improvements may extend the life of the individual, but probably have no effect on potential/maximum lifespan.  (Also, one surprise was his big drop in HDL, which was probably not a healthy development, and counter to what normally happens with increased fitness and/or glycemic carb reduction.)

 

The rise in T was likely a response by his body to reduced fat mass and E2 levels, and the corresponding rise in PSA is often seen under these conditions, and is not far from what is a normal level for his age.  If it stabilizes near current values that would not be a concern.

 

Given the extraordinary dosing, I don't think this tells us anything about the relative merits of NMN vs. NR (as others have noted).

 

At this point, my main concern with both NMN and NR are reports that high concentrations of NMN are associated with axon degeneration, such as that seen with glaucoma.  In fact, in the research showing NAM to slow glaucoma progression in mice (from last year), the researchers purposely avoided treatment that promoted Nampt-driven production of NMN, since that had been shown to accelerate neuron degeneration, likely due to accumulation of NMN.  Instead, their approach was either to add NAM (an NAD precursor) or promote Nmnat (which converts NMN to NAD), and with the combined approach producing the greatest slowing of glaucoma progression.  iow, even when NMN increases NAD levels, it can simultaneously be toxic to stressed neurons (i.e., in some localized area of the body you may not even be aware of).  (I'll start a new thread with references to explore this question.)

Edited by warner, 14 November 2017 - 08:25 PM.

[LawrenceW]

Hello Warner.

 

Thanks for taking the time to assess my blood work. 

 

The nice thing about it is that I got these results without changing my exercise routine and while still being able to enjoy my twice a week indulgences of cheeseburgers, pizza or my favorite fettuccine alfredo.

 

Thanks again.

[warner]

The nice thing about it is that I got these results without changing my exercise routine and while still being able to enjoy my twice a week indulgences of cheeseburgers, pizza or my favorite fettuccine alfredo.

Yup, although those food items are not necessarily unhealthy, depending on how they are constructed (myself being an advocate of high-fat diets).

 

It will be interesting to see if high-dose NR or NMN supplementation generally has this effect on metabolism that is similar to increased fitness, what the side effects or drawbacks may be, and whether maximum lifespan is affected.

 

fyi, I added my discussion and references to high NMN levels being toxic to neurons [here]

Edited by Michael, 16 November 2017 - 01:08 AM.
Link to NMN & Wallerian Degeneration post

[able]

An n=1 study isn't proof of anything, but it is intriguing.

 

As for the extreme dosage -   7.5 grams is useful as a stronger indicator of safety than 1 gram, but somewhat unfortunate they used so high a dosage as people seem to think that is the reason for the excellent results.

 

If you recall, the Trammel study shows that there is little benefit from 1g of NR vs lower dosages.  After a certain dosage, any extra is either converted to NAAD, or excreted.  

 

I haven't seen any indication that extreme dosages of NR yield any benefit.   Why would NMN may be different in that respect?

 

Regardless of whether you  believe Lawrences' results are due to NMN, or some other change in diet, nutrition, or exercise - I don't see any reason to believe they are due to the extreme dosage.

[LawrenceW]

There are a couple guys starting up next week on the 500mg of NMN only dosage twice per day.  They have never taken either NR or NMN so we should get some clean blood work from them.

Edited by LawrenceW, 15 November 2017 - 02:52 AM.

[able]

Will be interesting to hear.  I suspect 1,000 mg will yield same result as higher dosages for most people, else we'd see Dr Sinclair taking higher dosages himself.

 

 

[LawrenceW]

Early on we found that a biological feedback loop set in after 3 or 4 weeks at the higher dose.  By adding 2 other supplements we found that the higher dose was once again effective.  We believe that the cutoff to trigger the bio feedback may be as low as 1.5 to 2 grams per day.  Sinclair has already demonstrated that it not as low as 1 gram per day and probably ran into the same bio feedback loop if he tried higher doses.

[2Sunny]

It is put together by a long term Longecity member. Please back up your statement.

 

That I know of, the contents or their products have been shown to be what they claim they are .  They show COA's.

 

natasjlp, If I were looking at NMN, I would try the product which you show.

 

 

 

Found this at RevGenetics (not bad considering other suppliers pricing):

Advanced NMN: Nicotinamide Mononucleotide 50 Mg Per Serving - 30 Servings - 60 Capsules Price: $37.95
https://www.revgenet...nucleotide.aspx

It is most likely junk.

 

 

 

COA http://www.longecity...attach_id=14587

 

 

People on this forum are so smart I do not understand how they let egregious misinformation pass.  The HPLC test of NMN being sold in the link above was found to be niacinamide USP39.  That is not NMN.  As far as I can tell true NMN is still not commercially available.  Obviously with the right connections one can get access to the stuff, but I'm not sure I see the point especially when one considers the instability of NMN.  NR is available and cheap and to date animal model research shows the results of NR supplementation to be almost identical to NMN supplementation.

 

https://www.ncbi.nlm...63/pdf/main.pdf

Attached Files

•  NMN.jpeg   21.2KB   1 downloads

Edited by 2Sunny, 15 November 2017 - 02:26 PM.