2266 replies to this topic

[Harkijn]

Nate, you really should have a look there: http://www.longecity...ce/#entry797366

 

I do not believe precursor are the best way to boost our NAD+. I tend to share more and more the view of the anti aging firewall

IOW Tom is peddling his own ware. That is not necessarily bad or fraudulous, it's just ...ehm...different from individual people giving each other advice and research info.

[Tom Andre F. (ex shinobi)]

Nope, since all my statement are based on data and analysis. I work with facts only. I gave in the link the study published that show the results: http://www.nature.co...icles/srep24977

 

 

[Nate-2004]

 

Nate, you really should have a look there: http://www.longecity...ce/#entry797366

 

I do not believe precursor are the best way to boost our NAD+. I tend to share more and more the view of the anti aging firewall

IOW Tom is peddling his own ware. That is not necessarily bad or fraudulous, it's just ...ehm...different from individual people giving each other advice and research info.

 

 

I also don't see how precursors are bad. My health is better than ever and my injury is recovering ridiculously fast. I don't see how grape seed extract, something my rapidly aging father has taken for decades, is going to boost NAD in humans. There's just not enough study or evidence compared to the amount of study and evidence NR has gotten over just the past year alone. A single study on mice is really not enough to go by. There have already been plenty of studies of NR on humans so far and it does a fine job of boosting NAD.

Edited by Nate-2004, 05 December 2016 - 06:46 PM.

[Tom Andre F. (ex shinobi)]

I never said precursor are bad, I said they are probably not the best way to boost NAD+ especially if we look at raw results and pathway involved. Thats all. And not all grape seed are same, i tried to explain it as best i can, as we studied this topic for months but the fact I sell it make me not... independent from these statement I understand, thats why people have to make their own choice based on data. And the mechanism explained in this study is very likely to be similar in human as confirmed by the tons of studies showing benefits in human

Edited by Tom Andre F. (ex shinobi), 05 December 2016 - 06:50 PM.

[Oakman]

Tom, it's certainly too early to say that (in humans), that this particular grape seed extract is better than NR for raising NAD+. No human trials, for example.

 

But it looks promising, as many things do. Still, if it were true, that would be a game changer, no doubt.

 

My question is more general, though. Let us say we now have a couple great methods of producing NAD+ and SIRT1, NR + your extract

 

Can one simply add NAD+ increases/ SIRT1 increases from consuming two substances such as this ....?

 

...as in 1+1=2 (twice as much) or is 1+1=1 (some limit) or 1+1=1.x (some loss, but more than either alone)

[Tom Andre F. (ex shinobi)]

I dont know Oakman, but mice shares same root of synthesis for NAD+: salvage pathway, de novo pathway and probably one different of these two: oxidation from nadh to nad+ (nqo1).

 

As far as I know NR got only one human study for now ? and NAD+ returned back fast to normal level

 

NR used kinases in some tissue only to provide NAD+ and this I debated into the proper thread. It uses then the salvage pathway.

 

Our very specific grape seed extract, according to the study, seems to increase the de novo pathway, wich is sexy. It also decreased CD38 an NAD+ consumer.

 

The two can then definitely be used in the same time. Would be interesting to see a study associating the two for sure or niacin (but niacin was increased unlike NR naturally by the extract)

 

 

Edited by Tom Andre F. (ex shinobi), 05 December 2016 - 08:44 PM.

[Nate-2004]

As far as I know NR got only one human study for now ? and NAD+ returned back fast to normal level

 

As I recall there have been multiple human studies at this point so far as nad boosting is concerned. 

[Tom Andre F. (ex shinobi)]

I stoped follow nicotinamide riboside topics at one point so possible. Please share these studies here I want to have a look too

[Oakman]

NR used kinases in some tissue only to provide NAD+ and this I debated into the proper thread. It uses then the salvage pathway.

 

Our very specific grape seed extract, according to the study, seems to increase the de novo pathway, wich is sexy. It also decreased CD38 an NAD+ consumer.

 

The two can then definitely be used in the same time. Would be interesting to see a study associating the two for sure or niacin (but niacin was increased unlike NR naturally by the extract)

 

This^ is interesting. As your extract increases NAD+ production de novo from trp, that is different...and if it downregulates CD38 & parp1 simultaneously, more the better.

 

Do we know, relative to NR, how much of an increase are we talking? Equal/more and at what dose. That would be something to understand.

 

One question..the study shows most effect at the 25/50mg dose (HED 284/560mg/day), why are your capsule size 100mg?

[Tom Andre F. (ex shinobi)]

here you go for exemple: https://www.ncbi.nlm...les/PMC3616313/

 

this study show after one week supplementation at 400mg / kg / day in mice, a 25/ 30% increase in NAD+ in the liver while the grape seed show a 50% increase at low dose (5mg/kg), more than  2 fold increase at average dose (25mg/kg) and a 4 fold increase at high dose (50mg/kg).

 

Note that we get result at low dose.

 

100mg per day is considered the standard dose in most grape seed and is shown effective already. However, some of my customer take 5 pills a day due to Lyme disease

Edited by Tom Andre F. (ex shinobi), 06 December 2016 - 09:05 AM.

[lost69]

 

The following was originally posted by Fafner55, on Turnbuckle's thread "A protocol to upgrade mitochondria":  http://www.longecity...e-2#entry791908

 

I thought it relevant and appropriate for the personal experience thread.

 

 

 

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Posted 11 October 2016 - 11:22 PM

Estimated Dose of NR Needed to Induce Mitophagy

• "Nicotinamide enhances mitochondria quality through autophagy activation in human cells" (2009)http://onlinelibrary...09.00487.x/full
• �Novel NAD+ metabolomic technologies and their applications to Nicotinamide Riboside interventions� (2016)  http://ir.uiowa.edu/etd/3203/  (Ph.D. thesis)
• �GENERALLY RECOGNIZED AS SAFE (GRAS) DETERMINATION FOR NIAGEN � (NICOTINAMIDE RIBOSIDE CHLORIDE)� (2015-12)http://www.fda.gov/d...y/ucm505226.pdf

  Decrease of mitochondrial mass in the NAM-treated human fibroblasts.jpg   36.56KB   3 downloads

 

The following data points and facts are known.

• Keeping NAD+ elevated by 50% for 5 to 7 days significantly decreases mtDNA mass by 50% (in vitro)  "Nicotinamide enhances mitochondria quality through autophagy activation in human cells" (2009) http://onlinelibrary...09.00487.x/full
• 1000 mg/day (15 mg/kg) in a 52 year old (n=1) increased (peak, after 8 hours) plasma concentrations of
  • NAD+ by 317%
  • NAM by 75% (from 0.8 to 1.4 �M) 
• Dose responses of NR chloride (in vivo, n=12) increased
  • NAM by 62% for 300 mg NR
  • NAM by 140% for 1000 mg NR
• Predose plasma concentration of NAM in the n=12 experiments ranged from 0.2 to 0.55 �M, and from 0.7 to 0.8 �M  in the 52 year old, indicating a wide range.
• NAM levels rose to a range of 0.6 to 0.85 �M for 1000 mg NR in the n=12 experiment.
• NR increases NAD+ in a dose-dependent manner.
• NR has a serum half life of about 4 hours.

 

From these data points and other facts I can surmise that

• My normal dose of NR at 250 mg twice per day with 50 mg pterostilbene should be sufficient to maintain a generally healthy population of mitochondria.
• While NR induces mitophagy, it has not shown in vivo results as impressive as Urolithin-A, which implies that additional mitophagy might be possible beyond those shown with 300 to 1000 mg doses of NR.
• 500 mg every 6 hours for 5 days (2 gm/day) might further increase mitophagy and cause a substantial clearance of defective mitochondria.

 

Experiment #1

Hypothesis: 500 mg (about 7.5 mg/kg) every 6 hours (2 gm/day) for 6 days might induce mitophagy and cause substantial clearance of defective mitochondria.

 

Test: NR is well tolerated at 1 gm/day (clinical trial), and at 2.5 gm/day (anecdotal) and showed no adverse conditions in mice at 400 mg/kg/day ( 32 gm/day HED, FDA submission).  Since it appears safe, and since there are no in vivo experiments on inducing mitophagy with NR, taking about 4 gm/day should give clear results if this treatment works.

 

NR is packaged in 125 mg capsules.  Taking 10 capsules (1250 mg) three times per day is a total daily dose of 3750 mg.  This amount is nearly twice the 2000 mg/day does I estimate from in vitro data that is needed to induce mitophagy.  In the absence of in vivo data, along with general safety of NR, this higher dose appears warranted, particularly since treatment with Urolithin A showed a significant 42% increase in running endurance in aged rats, which is a better performance increase than I have seen reported for NR and suggests that greater levels of mitophagy are possible.

 

2016-09-28  Day 1. Begin taking 10 capsules (1250 mg) three times per day. I have not taken C60-OO for a month or, for 10 days, any supplements or medications .

2016-09-29  Day 2 AM: My skin is definitely smoother and I have more energy, the kind of energy and sense of health and well being one feels in youth.  Otherwise there are no apparent side effects.  Smoother skin is not something I anticipated, but it is consistent with research showing cells returning to normal shape when (aged or dysfunctional) mitochondria is removed. 

�Mitochondria shown to trigger cell ageing� (2016) http://www.ncl.ac.uk...ggercellageing/,http://emboj.embopre...ontent/35/7/724

Late afternoon - my face has the feeling of being slightly flushed, as if I were taking a niacin.

2016-09-30   Day 3. Woke up with a headache, otherwise OK.  The headache could have been caused by dehydration.  It went away after drinking water and a cup of coffee. My muscles feel firmer and stronger: I am slouching less when sitting.  This sensation is probably related to increased ATP production and other benefits of NR, and not related to mitophagy.

2016-10-01  Day 4. The ambient temperature is 76� and I feel slightly cold.  Less body heat generation is consistent with reduced mitochondrial mass.  I feel no other symptoms.

2016-10-02  Day 5. Today is the fifth of this treatment.  I am unusually clear minded.  As for other symptoms, there is a slight feeling of niacin-like flushing when I take NR, otherwise nothing.  Since in vitro experiments should additional decrease in mitochondrial mass through 7 days of treatment, I plan to continue taking NR for one or two more days. 

�Nicotinamide enhances mitochondria quality through autophagy activation in human cells" (2009)http://onlinelibrary...09.00487.x/full 

2016-10-03  Day 6 and final day of this treatment.  My muscles feel small, inadequate and ache, which is consistent with significant decrease in mitochondria.  Otherwise I feel OK. General autophagy does not seem to be affected, as lipofuscin deposits on my hands remain the same.  Another observation is that my sense of smell has been unusually acute for the last several days.  My mitochondrial mass should be reduced by about 30% by the end of today if in vitro measurement results are an accurate indication.

2016-10-04  Day 7.  Took 10 mg PQQ about 7 AM, which should stimulate mitogenesis and restore my mass of mitochondria back to normal within hours.  Noontime: Other than muscle aches, I feel good, energetic and healthy.

2016-10-04  Day 8.  I feel  completely normal.

2016-10-05  Day 9.  I feel energetic.

2016-10-06  Day 10.   I feel even more energetic and my skin is noticeably smoother on my arms and face.  This treatment is unequivocally beneficial. 

 

 

Other thoughts

1. mtDNA 4977 bp deletion has been shown to increase at and average rate (in years) t 0.0002 exp(0.042 t)   �Mitochondrial DNA 4977 bp deletion is a common phenomenon in hair and increases with age� (2012)  http://www.ncbi.nlm....les/PMC4362429/
2. Measurements of averaged accumulation of dysfunctional mitochondria bely much higher concentrations in aged and postmitotic cells.
3. If in vitro tests are any indication, the experiment I described above should have reduced my mitochondria mass by an estimated 30%
4. Since dysfunctional mitochondria are preferentially recycled, as 30% reduction in mass might correspond to a 60% reduction in the mass of dysfunctional mitochondria (just a guess, assuming twice rate).
5. Then 3 treatments should reduced dysfunctional mitochondria by 65%, or by about 20 years average accumulation.  6 treatments would reduce dysfunctional mitochondria by about 89%, equal to about 50 years average accumulation. 

I am 61 years old.

•  Well Written x 1
•  Informative x 1
•  like x 1 

 

 

i wanted to try your protocol to clear defective mitochondria....i stopped c60 for about a week but not all other supplements (among them mitoq,PCC and so on)

took 1000mg of NR first day, the following day i m feeling very bad:

 

could not wake up  and woke up very very late

 

i feel very very cold despite room temp at 27°.i have subclinical hypothyroidism non-autoimmune.so i think thyroid function has worsen and the usual dose of t4 i take is not enough 

 

some muscles aches

 

very very bad nausea and light headache after breakfast.i never have headaches so even a very light one makes me bad nausea.i ll try a hot shower to see if it helps

 

not feeling energetic as i am usually while on c60 and NR

 

skin face very bad looking, bad color and some nasolabial folds visible.i dont drink alchool but i think i look like after the first night of a bad flu/swet or after being drunk and not sleeping for 24hrs 

 

i ll definitely stop this for now.any clues?so strange such bad effect after just 1 day of 1g NR, i actually had some stomach problems yesterday, very bloated (stomach full of hair) while increasing NR dose or maybe this is PQQ

 

can it be i have a lot of defective mitochondria?

 

i ll take PQQ today and only 200mg of NR and see if i feel better.tempted to take C60 immediately

[jjnz]

I've taken 1000mg 4 in morning 4 in afternoon , didn't notice much from my regular dose of 2morning/1afternoon. I'd be surprised if it was that. Only 1 way to tell, do it again next week.
Hope you get better.
If I get some pqq I might try this out

[Nate-2004]

Compared to NR at least so far, PQQ is not well studied.  I would just go with the recommended dosage in the dosing pdf that HPN sends. There appears to be a diminishing level of returns after 300mg.  I kind of wish they'd do 150 per cap instead of 125.

[to age or not to age]

Here is a link to aging firewalls and Jim Watson's analysis of NQo1 vis a vis increasing the NAD ratio.http://www.anti-agin...-interventions/ In the final section

he argues that beta lapachone affects NQo1. Here is a link to my new webpage for beta lapachone. On that page are links to literally a hundred recent studies on bata lapachone.http://toageornottoa...beta-lapachone/

[hoonto8]

Hi everyone, I'm new here but have been following the NR threads for a few months.

 

I wanted to mention, I've heard of people using NR via nasal inhalation (insufflation). Given that I am not aware of a way for consumers to purchase pure NR without excipients (if anyone knows, I would be curious where), I assume that these folks are breaking open gelcaps and using the contents in this fashion. This morning I broke a few open from a couple of different vendors (HPN and Prohealthspan), dissolved each in dH2O (reported NR solubility in water is 446.5 mg/ml, about 125% more soluble than table salt, fortunately) and filtered to leave (in both cases) a water insoluble white retentate that is possibly SiO2 (though I haven't confirmed). So for anyone doing this or considering this route of administration, be advised that SiO2 is not likely something you want in your lungs.

 

Anecdotally, NR at the recommended dosage has been an excellent mood booster for me (2x125mg each morning), my energy seems to be higher through the day, fasting is a bit more difficult (I try to do 8/16 IF on weekdays), and I didn't get sore after snowboarding for our first time last weekend in quite a few years whereas my wife was very sore (and she does not take NR).

Edited by hoonto, 14 December 2016 - 03:27 PM.

[hoonto8]

Hi everyone, I'm new here but have been following the NR threads for a few months.

 

I wanted to mention, I've heard of people using NR via nasal inhalation (insufflation). Given that I am not aware of a way for consumers to purchase pure NR without excipients (if anyone knows, I would be curious where), I assume that these folks are breaking open gelcaps and using the contents in this fashion. This morning I broke a few open from a couple of different vendors (HPN and Prohealthspan), dissolved each in dH2O (reported NR solubility in water is 446.5 mg/ml, about 125% more soluble than table salt, fortunately) and filtered to leave (in both cases) a water insoluble white retentate that is possibly SiO2 (though I haven't confirmed). So for anyone doing this or considering this route of administration, be advised that SiO2 is not likely something you want in your lungs.

 

Anecdotally, NR at the recommended dosage has been an excellent mood booster for me (2x125mg each morning), my energy seems to be higher through the day, fasting is a bit more difficult (I try to do 8/16 IF on weekdays), and I didn't get sore after snowboarding for our first time last weekend in quite a few years whereas my wife was very sore (and she does not take NR).

 

I just spoke with HPN customer service, they stated the following:

 

On Wed, Dec 14, 2016 at 5:27 PM, Customer Care <customercare@hpnsupplements.com> wrote:

 

Hi Matt,

 

 our capsule contain no artificial excipients. Its a plant based capsule no gelatin or animal product. We also have Niagen powder which is pure nicotinamide riboside. Each container contains 7.5g. (60 scoops of 125mgs per scoop). Unlike other companies we do not use any fillers or arificial ingredients during our manufacturing process. 

 

Which is most certainly at odds with my test this morning as all (or any, if there was any) NR in these capsules would have dissolved. My rotovap is out of commission at the moment so I'm manually drying the filtrate. If there is nothing there, well... my next email will be to Chromadex, asking them if they have recently tested the HPN product. I've also reached out to Prohealthspan, we'll see what they come back with. It was a nearly equivalent amount of excipient in both brands (within margin of error).

 

Nonetheless, the product absolutely does contain excipients.

 

This weekend, whether or not I can fix the rotovap I'll provide some measurements here, so we can all be aware of what % is soluble vs. insoluble. That would at least tell us the limit of how much of the powder in these gelcaps could be NR.

 

 

EDIT: Ok, spoke on the phone with HPN customer service, they said that it was a natural fiber of some kind, definitely not SiO2.

 

I'll still run some tests this weekend and see if I can verify but I could see this filtrand being a fiber of some kind.

Edited by hoonto, 14 December 2016 - 11:41 PM.

[Oakman]

^ I don't understand your surprise. All they told you was it contained not ARTIFICIAL excipients. Their bottle clearly states it DOES contain this NATURAL material:

 

Microcrystalline cellulose is a term for refined wood pulp and is used as a texturizer, an anti-caking agent, a fat substitute, an emulsifier, an extender, and a bulking agent in food production. The most common form is used in vitamin supplements or tablets.

[boylan]

I can say that vision in my right eye has improved. I've noticed this over the last year that my right eye was not as good as my left. Now they are almost equal. This is for distance only. I still need my cheaters to see the laptop screen. :-)

 

Age - 61

NR dose - 250 mg per day for about 2 months

Vision in my 20's was 20/15.

[hoonto8]

@Oakman, yeah you're right - I probably should have figured so. Well I was kind of dreading testing this (hate HF, don't like NaOH melts). Explanation fits the description of what I'm seeing here. I'm not terribly familiar with microcrystalline cellose, don't know its density etc, but I'll dig in this wknd and probably weigh in any case. Not a skeptic, just an engaged citizen here.

[Guardian4981]

I am still researching this whole Nad and NADH thing.

 

The reason I am posting here is I have been taking NADH at 20mg under the tongue in the morning.  I have found it has "worked" incredibly well for me.  The main benefits I find are mental and actually some physical.  Appears to reduce inflammation/soreness in joints and provides a boost of well being. 

 

So how does NADH relate to NAD?  If I do well with NADH would that potentially mean I would do worse taking NAD?  The "ratio" of them plays a role doesn't it?

 

I plan on trying NAD at some point.

[Kirito]

I am still researching this whole Nad and NADH thing.

 

The reason I am posting here is I have been taking NADH at 20mg under the tongue in the morning.  I have found it has "worked" incredibly well for me.  The main benefits I find are mental and actually some physical.  Appears to reduce inflammation/soreness in joints and provides a boost of well being. 

 

So how does NADH relate to NAD?  If I do well with NADH would that potentially mean I would do worse taking NAD?  The "ratio" of them plays a role doesn't it?

 

I plan on trying NAD at some point.

 

The issue with taking NAD or NADH is that we don't know if (or how much) will reach the cells membrane. Along with the high price point per mg. We know that NR does reach the cell membrane and does increase cellular NAD levels. We want a higher NAD+/NADH ratio, not the other way around.

[hoonto8]

Update on the whole excipient thing, got the rotovap working. The dried filtrate was a very sticky, clear goo thinly distributed around the edges of the flask. It measured under the amount expect when dried but definitely within mechanical losses (my lab technique was for crap). I also don't know how fast NR dissolves in a mix of microcrystalline cellulose, though its solubility is high. Re-dissolved into water and made kind of a nasal spray which I used Saturday, Sunday, and today - way more than my usual 250mg, good tolerance, no observable negative side-effects.

 

Update on personal experience: upped my dose significantly (no sense wasting the isolated putative NR). I went snowboarding yesterday again, drank two IPA's at lunch and got a little carried away on icy moguls in the latter half of the day, had some falls that would have probably caused mild concussion, each of them. Didn't need any advil, headache went away for the most part within an hour (before I even got in the car to go home), slept well, woke up, no stiffness or soreness at all today - feel amazing! By the way, I'd heard it reported that hangovers were nonexistent for someone, this seems to be true for me too.

Edited by hoonto, 19 December 2016 - 08:11 PM.

[ironfistx]

Now someone was like I stopped taking the nicotinamide and the tendonitis didn't go away therefore it wasn't the nicotinamide. Seriously? Tnedonitis takes a while to go away anyway. Just my comment. a strange thing to say.

[Journey2016]

Hi , my girlfirend recovered from hodgkin's lymphoma, shes 29

I use NR At 500mg a day to help me with addiction issues..

We have been looking at ways to improve her health and wanted her to try NR as ive had such good results on it.

Main question is can it do her any harm conssidering shes had cancer once

Shes did 3month cemo via IV to help cure it.

Thanks in advance

[stefan_001]

Hi , my girlfirend recovered from hodgkin's lymphoma, shes 29

I use NR At 500mg a day to help me with addiction issues..

We have been looking at ways to improve her health and wanted her to try NR as ive had such good results on it.

Main question is can it do her any harm conssidering shes had cancer once

Shes did 3month cemo via IV to help cure it.

Thanks in advance

Not as such a cancer expert but here my 2 cents. While I am not a believer that NR will accelerate cancer growth because there are likely other rate limiters I at least would not take NR when under chemo and other therapy. It seems obvious that NR will rescue cancer cells in case the chemo targets the NAMPT path. Also NR will increase sirt activity that will help cancer cells survive during chemo.

Before doing anything I would try to understand first whether at 29 years old after chemo NAD+ is at lower levels and supplementation would have any effects.. In healthy people NAD+ should be okay.

Edited by stefan_001, 27 December 2016 - 11:34 AM.

[hoonto8]

For some reason, it seems less is more with this stuff. For about a week I tried >2g/day (2 basis in the morning, 8-12 or so Tru Niagen (ProHealthspan), and quite a few heaping tablespoons of the niagen powder preparation from HPN at varied times through the day. I noticed that I didn't seem to be getting the same boost of energy as I used to. Then I cut it back to my regular 250mg/day and boom, it was back - not quite as nice as previously but back to the nice energy level and positive mood that I had prior to that level of dosing. Oh and yes, I did get a hangover (beer-induced) pre-Christmas when I was doing the massive dosing.

 

So from this point forward, I'm going to go back to 250mg/day (cost is not really a factor for me - so this is purely because I subjectively feel like a lower dose feels better, if anyone is wondering).

Edited by hoonto, 27 December 2016 - 09:58 PM.

[tintinet]

I've never felt any effect from taking NR at any dose.

[hoonto8]

Who knows then, maybe it's placebo - one thing I noticed too - incredible diarrhea that went away after going back to 250mg, it seems to be from taking massive amounts of the HPN Niagen in powder form (it has quite a bit of fructooligosaccharide's in it).

[midas]

I've never felt any effect from taking NR at any dose.

 

Probably because you have sufficient levels of NAD....

How many different doses have you tried?....

How old are you?...

What is your state of health?...

[tintinet]

I've never felt any effect from taking NR at any dose.

Probably because you have sufficient levels of NAD....
How many different doses have you tried?....
How old are you?...
What is your state of health?...

125 mg to 1 gram/day


Middle age

Decent health AFAIK!;