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Cycling Protocols for NAD+ Precursors

nad+ nmn cycling supplements sulforaphane sublingual bioavailability tolerance downregulation

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#31 Nate-2004

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Posted 02 October 2018 - 08:12 PM

I've changed my cycling of this a bit. I only take it on mornings of days when I plan to exercise, around 5 hours prior to a workout. This doesn't mean I always do it, because some weeks I'm trying the stem cell protocol with c60. However, at this point I may be done with that for a while so I'm back to only taking NR on the mornings I exercise, which is 4x per week, Mon,Tues,Weds,Fri.

 

I plan to swap out NR with the pure powder form of NMN from Alive By Nature next time around, but unlike NR, I don't know how long it takes before NMN is broken down and NAD+ is elevated in other cells.


Edited by Nate-2004, 02 October 2018 - 08:14 PM.


#32 Oakman

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Posted 02 October 2018 - 09:21 PM

I only take it on mornings of days when I plan to exercise, around 5 hours prior to a workout. This doesn't mean I always do it, because some weeks I'm trying the stem cell protocol with c60. However, at this point I may be done with that for a while so I'm back to only taking NR on the mornings I exercise, which is 4x per week, Mon,Tues,Weds,Fri.

 

I plan to swap out NR with the pure powder form of NMN from Alive By Nature next time around, but unlike NR, I don't know how long it takes before NMN is broken down and NAD+ is elevated in other cells.

 

The ABN website has a wealth of info and references. In mice they say there ~15 min or so to enter circulation to Cmax. People take longer supposedly, but for the powder or tabs sublingual, "We recommend taking 4-8 times per day, with at least 1 hour between dosages." and "We recommend taking 2-3 days off per week, ideally on days when you will be getting the least exercise."
 
I take a 250 mg capsule of NR every.single.day, regardless. I consider its use as a background NAD+ booster. When I know tomorrow will be an exercise day, I start with a small NMN bedtime dose (125 mg) sublingual, then the next morning I stage for my exercise 1 hr prior to leaving with 200mg powder sublingual, and take 2-4 tabs (125 mg each) during exercise about 1 every 1/2 hr....  or 300-400 mg in my hydration drink or... sometimes both for experimenting (like today). Then I take a break break until the evening before the next exercise day and start again, usually 1-3 days later depending on my HRV (Heart Rate Variability) readings.
 
Doing the extra dosing today (perhaps) was what helped me break my 17 mph average on a particular 4 mile cycling segment I regularly do and upping it to 17.1 mph. It's not much, but going faster is getting harder, so any help these supplements can provide is a minor miracle at this point.
 
I suggest experimenting as any amt of sublingual NMN seems side effect free to me, so have fun and see what works best for you.

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#33 Leon93

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Posted 05 October 2018 - 02:37 PM

I've been taking immediate release niacin up to 500mg every other day at age 25 forbabout half a year now... I like the warmth and slightl energy increases it gives me. I take sufficient leafy Greenspan as a methyl donor (which I've read some time ago is probably a decent remedy).
Anyone thinks this is a good way to go for me?

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#34 Nate-2004

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Posted 05 October 2018 - 04:39 PM

I've been taking immediate release niacin up to 500mg every other day at age 25 forbabout half a year now... I like the warmth and slightl energy increases it gives me. I take sufficient leafy Greenspan as a methyl donor (which I've read some time ago is probably a decent remedy).
Anyone thinks this is a good way to go for me?

 

I don't see the point at age 25, you're still at max NAD+ right now and have hardly begun any kind of decline. You may even be throwing off your salvage cycle. I would stick to good exercise, maybe sauna use for now. If I could go back in time to 25, I'd definitely change my diet and start exercising 4x per week. I would even start fasting. I would have stopped smoking weed so much too, mainly because of the smoking part. I'd also have saved my marriage LOL.

 

You can go supplement free for a long while man, at least the next 5 years, if you try to include fresh, never frozen raw broccoli in your diet, some turmeric (tsp a day) in your meals and stay as plant based as you can most of the time, you'll stave off aging for quite a while. Wear uvb/uva blocker and avoid too much sunlight and you'll look 30 at 40. But by then I imagine we'll be way ahead of the current state of the roadmap.


Edited by Nate-2004, 05 October 2018 - 04:42 PM.

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#35 Leon93

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Posted 05 October 2018 - 04:54 PM

Wow thanks Nate for your reply, you're the best!

Thing is I already do all those things you advise, except for the sauna. But then I always find myself back on this site trying to learn more, considering different supplements. I looked into regimens of other highly trusted users and notice they use supplements like glycine, glucosamine, coq10, andrographis etc.
Would you say even considering astragalus root, willow bark/aspirin and stuff like dasatinib, methylene blue, rapamycin, metformin, c60oo, apigenin, FOXO4, valerian root, pterostilbene, resveratrol etc. is useless for someone my age? I've read some of them are useful when started early, and useless when started late® in life.

I'm not too fond of expensive regimens however. I also wonder when senescense will become a problem. And as far as I know, k2mk7 is not needed when sufficient leafy greens are consumed

(And Jesus, next time I have to check my comments for erroneous auto-edits)

EDIT: important thing I forgot to mention; I took the niacin as I saw a graph on Longecity somewhere NAD+ levels were already in decline earlier in life, not just starting somewhere around 30 or so

Edited by Leon93, 05 October 2018 - 05:45 PM.


#36 Nate-2004

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Posted 10 October 2018 - 04:26 PM

All those things you mention are utterly useless at this point. Especially dasatinib, metformin, FOXO4, if you have ANY senescent cells they're easily being eliminated by your immune system. 

 

Just add 20 mins in the sauna 4x a week to your exercise routine, that would be the only thing helpful on many levels for anyone of any age, especially around mental health and exercise gains for someone your age but long term helps with keeping CRP and other inflammation low and improving protein fold integrity.


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#37 SearchHorizon

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Posted 13 October 2018 - 06:41 PM

At age 55, I have been taking nicotinamide (1.5 g) + ribose (5 g) once per day for about a year for exercise-performance improvement. There is no drop off.

 

Since starting on nicotinamide, I have experienced steady increases in strength while on a slight daily caloric deficit. People who understand anything about bodybuilding know how unusual this is - any experienced lifter knows that it is nearly impossible to make gains over significant period of time while losing body fat PROVIDED one's in a reasonably good shape.

 

It is an incredible supplement. Over the past 20+ years, I have used a lot of different supplements. Nothing I have ever used had nicotinamide like effects.

 

 

 


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#38 Leon93

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Posted 14 October 2018 - 10:37 AM

Thank you once again for your input Nate. Is there a specific reason to why sauna's are helpful? Instead I often hear longevity 'freaks' and health advocator talk all about cold showers. Wouldn't hot showers or hot baths work as a subsititute for sauna's?

On the immediate release niacin I have atm, would you recommend I discard them or keep them for later? I am confident I noticed a graph here on Longecity where a user showed NAD levels were in decline earlier in life than at age 25. Or perhaps (very) small doses instead will do?

I am extremely confident my diet, lifestyle and even added spices/herbs are already all in check.

Edited by Leon93, 14 October 2018 - 10:41 AM.


#39 Nate-2004

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Posted 16 October 2018 - 04:36 PM

I wouldn't risk wasting time on hot baths and cold showers. The larger studies on hyper/hypothermic therapies are in either 80+ degrees celsius or less than 4 degrees celsius in ice water, not cold showers.

 

The two main studies are large scale longitudinal studies on Finnish men and there is another study measuring C-Reactive Protein changes as a result of sauna use in the same temperature range. 

 

Anything else is completely anecdotal and while it may or may not work the same I wouldn't bother going outside the bounds of what's been shown in a clinical human study or trial.

 

You can find more on Rhonda Patrick's channel and you can easily Google or search PubMed for the details.

 

I've seen a lot of graphs on NAD+ decline and nothing till 35 is significant. I'd hold off because you don't want to get an excess of NAM and honestly, Niacin isn't really all that useful for NAD+ since it can go in any number of pathways. There's also some debate about whether NAM inhibits sirtuin activity.


Edited by Nate-2004, 16 October 2018 - 04:39 PM.

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#40 joesixpack

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Posted 30 November 2018 - 03:32 AM

Thank you once again for your input Nate. Is there a specific reason to why sauna's are helpful? Instead I often hear longevity 'freaks' and health advocator talk all about cold showers. Wouldn't hot showers or hot baths work as a subsititute for sauna's?

On the immediate release niacin I have atm, would you recommend I discard them or keep them for later? I am confident I noticed a graph here on Longecity where a user showed NAD levels were in decline earlier in life than at age 25. Or perhaps (very) small doses instead will do?

I am extremely confident my diet, lifestyle and even added spices/herbs are already all in check.

 

The sauna shocks the body, like exercise, and leads to the production of NAD+. At least that is what I have been told. Sort of a double hit when you exercise, and it feels good.


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#41 Blueflash

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Posted 01 December 2018 - 07:36 PM

At age 55, I have been taking nicotinamide (1.5 g) + ribose (5 g) once per day for about a year for exercise-performance improvement. There is no drop off.

 

Since starting on nicotinamide, I have experienced steady increases in strength while on a slight daily caloric deficit. People who understand anything about bodybuilding know how unusual this is - any experienced lifter knows that it is nearly impossible to make gains over significant period of time while losing body fat PROVIDED one's in a reasonably good shape.

 

It is an incredible supplement. Over the past 20+ years, I have used a lot of different supplements. Nothing I have ever used had nicotinamide like effects.

Do you take the nicotinamide all at once, or several doses?



#42 joesixpack

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Posted 31 December 2018 - 08:02 PM

The sauna shocks the body, like exercise, and leads to the production of NAD+. At least that is what I have been told. Sort of a double hit when you exercise, and it feels good.

Someone indicated that there should be a reference for this statement. Google is your friend. Here is a website that mentions saunas as a means to produce NAD+.

 

http://miosuperhealt...t-in-your-body/


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#43 RichardAlan

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Posted 02 January 2019 - 05:10 AM

I have used NR about 3.5 year continuously and have not noticed a drop off. I have experimented with dosing and method but never did a washout. Currently taking 250mg oral in the evening (liver health) and 250mg sublingual in the morning. The sublingual works, I have woken up now and then with a slight headache, its gone after sublingual administration.

 

What I do rotate are various ather supplements e.g. fisetin, milk thistle (should help NAD boosting), pterostilbene. Also for a few months using Taurine.

 

What I write now is pure speculation but I would believe Brenner who uses 2 x 250mg per day tests himself regularly. Afterall he is the "test subject" in the Trammel thesis and tested his blood. And as he doesnt talk about need for cycling.

 

You mention using NR sublingual.  Where do you get this from?  I thought the particle size was too big to be used sublingually.



#44 stefan_001

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Posted 02 January 2019 - 02:00 PM

You mention using NR sublingual.  Where do you get this from?  I thought the particle size was too big to be used sublingually.

 

The particle size is not too big. I simply empty the capsule under my tongue. Not the most effective but it will somewhat work.


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#45 able

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Posted 02 January 2019 - 04:58 PM

Unfortunately, the 125 or 150 mg of NR is packaged in a capsule that holds around 450 mg, so you get a lot of filler that doesn't dissolve as well as the NR.  Plus the fact that NR is actually NR + C (Chloride), so you have to put up with the salty taste.  

 

I did it for a month or so and it does work, but just get tired of the hassle and bad taste.

 

 


Edited by able, 02 January 2019 - 05:22 PM.

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#46 stefan_001

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Posted 13 January 2019 - 07:31 PM

Unfortunately, the 125 or 150 mg of NR is packaged in a capsule that holds around 450 mg, so you get a lot of filler that doesn't dissolve as well as the NR.  Plus the fact that NR is actually NR + C (Chloride), so you have to put up with the salty taste.  

 

I did it for a month or so and it does work, but just get tired of the hassle and bad taste.

 

Personally I got used to it fast. Both my parents also do it. They cut the capsule in half and put the powder on a teaspoon.
 


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#47 KBAnthis

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Posted 26 May 2019 - 01:14 AM

I have just recently started taking NMN sublingual several times a day and on day 3. I have gotten quite burnt out and may be overdoing it. I am going to lower my dosing tomorrow. I have noticed sublingual magtein and creapure have been helping with the burnt out feeling. Also plenty of d3 and k2 as I have been burning through it since starting NMN it seems. Plenty of B vitamins and OptiMSM has been added in case of methylation issues. I enjoy NMN powder much more than niacin powder and have had less side effects. Have any of you tried Moringa? I was going to try sulforaphane but decided not to since I already take moringa and from what I read it does a similar thing in the body. I did try some broccoli sprouts once and didn't notice much of a difference, well I did but it was not as much as I got from moringa powder. So I did notice over say baseline fasting or unsupplemented etc but no where near as good feeling do to the various other substance contained in Moringa. Sometimes in the last 3 days I have gotten rather burnt out feeling, perhaps lack of some type of minerals or building materials my body needs, and other times I have never felt better. So I am trying to see what people are doing to counteract the burnt out feeling. Creatine, Magtein, and magnesium (TRAACS) have been doing a great job. I am going to try a 72 hour snake juice fast with probably some coffee and green tea after tomorrow so I will cycle off for that, but have been thinking about going a full week on. But then again if I am over doing it may be best to try a cycle as I am taking a lot of stuff to try to balance it.  It seems I am just using to much And will have to report back after a fast. 


Edited by KBAnthis, 26 May 2019 - 01:17 AM.

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#48 MikeDC

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Posted 26 September 2019 - 11:24 PM

There is nothing wrong with increased NAD+ everyday. The issue is one specific supplement may have a negative feedback loop. Long term use without cycling will reduce the effectiveness of the supplement. Lifetime use of NAM in mice makes NAM useless since tissue NAD+ will no longer be elevated. NAM/NR/NMN all have the same issue because most of NR and NMN degrades into NAM. Niacin doesn’t use NAMPT. So one can recycle between NR/NMN and Niacin.
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#49 Smith

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Posted 10 November 2019 - 10:00 PM

There is nothing wrong with increased NAD+ everyday. The issue is one specific supplement may have a negative feedback loop. Long term use without cycling will reduce the effectiveness of the supplement. Lifetime use of NAM in mice makes NAM useless since tissue NAD+ will no longer be elevated. NAM/NR/NMN all have the same issue because most of NR and NMN degrades into NAM. Niacin doesn’t use NAMPT. So one can recycle between NR/NMN and Niacin.

 

According to a study authored by Dr. Sinclair and others, a noted increased in mice healthspan with NAM supplementation... so I wouldn't call NAM supplementation useless.

Also a recent German review of NAD+ precursors indicated clinically significant boost in NAD+ levels with NAM supplementation.  Also it seems Dr. Sinclair's study may have only looked at liver NAD+ levels with NAM supplementation:

 

 

Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Though neither hepatic NAD+ nor NADP+ were boosted by NAM...

 

Furthermore, a 2017 study indicates NAM supplementation may actually upregulate Sirt1 rather than downregulate it.  Much of the data seems to indicate NAM may be as effective as NR or NMN at boosting NAD+ levels.  Certainly, its safety is better studied than either NMN or NR.  If its as effective as NMN or NR as a NAD+ precursor, why would companies such as Tru Niagen be pushing the much more expensive NR/NMN?


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#50 able

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Posted 11 November 2019 - 01:28 AM

According to a study authored by Dr. Sinclair and others, a noted increased in mice healthspan with NAM supplementation... so I wouldn't call NAM supplementation useless.

Also a recent German review of NAD+ precursors indicated clinically significant boost in NAD+ levels with NAM supplementation.  Also it seems Dr. Sinclair's study may have only looked at liver NAD+ levels with NAM supplementation:

 

Furthermore, a 2017 study indicates NAM supplementation may actually upregulate Sirt1 rather than downregulate it.  Much of the data seems to indicate NAM may be as effective as NR or NMN at boosting NAD+ levels.  Certainly, its safety is better studied than either NMN or NR.  If its as effective as NMN or NR as a NAD+ precursor, why would companies such as Tru Niagen be pushing the much more expensive NR/NMN?

 

 

Because it is not as effective as NMN or NR.  NAM does boost NAD+ and has been effective for some conditions, but there have been numerous studies where NR, NMN, and even NAD+ supplementation has proven effective and NAM has not.


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#51 Smith

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Posted 11 November 2019 - 08:56 PM

Because it is not as effective as NMN or NR.  NAM does boost NAD+ and has been effective for some conditions, but there have been numerous studies where NR, NMN, and even NAD+ supplementation has proven effective and NAM has not.

 

OK, It's entirely possible that NAM is not as effective as the much more expensive NR/NMN; however, an April 2018 study published in Cell Metabolism found that NR and NMN are almost entirely converted to NAM in the liver.  Here is what the author's wrote: 

 

Nearly complete first-pass metabolism of oral NR and NMN [likely results] in these compounds having systemic effects similar to or indistinguishable from oral NAM.

 

If true, then that means the $4/bottle of NAM is as effective as the $65/bottle NR or NMN.  I am not asserting that this is true; however, I would be interested if you could provide some references to the studies you refer to that compare the effectiveness of NAM to NR/NMN wrt NAD+.  Also, I wonder why Tru Niagen did not look at NAM in their study?  One theory is because they couldn't make any money selling NAM which can be purchased inexpensively on Amazon, while their patented NR can be sold at a premium.  Another theory is, NAM just doesn't work as well as NR.  I'd really like to know if there are studies that can help with drawing a conclusion, or perhaps someone with more knowledge can provide some insight into this.


Edited by Smith, 11 November 2019 - 09:03 PM.

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#52 joesixpack

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Posted 21 November 2019 - 03:48 AM

One more thought on cycling is that an obvious objection to cycling off of NAD+ precursors or any supplement is that one might be missing out on the beneficial effects for those off-cycle days.  An idea I'd like to offer for those of you who might be reluctant to try cycling for this reason is to maintain your total weekly (or monthly) mg intake, but concentrate it into your on-cycle days.  So instead of 250 mg daily without cycling, you might try upping your dosage to 375 mg daily with cycling, for example.  You wouldn't save any money this way, but it never hurts to have another option!  ;)

Good idea. We are now at 300 mg of NR. I do it for 5 days a week, and then quit. It seems to work. But based on how I feel, I change from 5 to 6, and alternate days where I Take C60. It seems to be beneficial, you have to be fluid. After all this is an experiment. I think you can feel when you need to back off off theses doses and then get back on them.


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#53 MikeDC

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Posted 22 November 2019 - 09:33 PM

OK, It's entirely possible that NAM is not as effective as the much more expensive NR/NMN; however, an April 2018 study published in Cell Metabolism found that NR and NMN are almost entirely converted to NAM in the liver. Here is what the author's wrote:


If true, then that means the $4/bottle of NAM is as effective as the $65/bottle NR or NMN. I am not asserting that this is true; however, I would be interested if you could provide some references to the studies you refer to that compare the effectiveness of NAM to NR/NMN wrt NAD+. Also, I wonder why Tru Niagen did not look at NAM in their study? One theory is because they couldn't make any money selling NAM which can be purchased inexpensively on Amazon, while their patented NR can be sold at a premium. Another theory is, NAM just doesn't work as well as NR. I'd really like to know if there are studies that can help with drawing a conclusion, or perhaps someone with more knowledge can provide some insight into this.

I am copying what I posted in another thread below. The good effects of NR may not be due to how high it can raise the NAD+. It is due to the small amount of NR that can get into cells that can’t make NAD+ from NAM or NA.
“NR and NMN definitely provide more benefits than NAM and Niacin. A recent mice study shows that if you delete NRK1 which converts NR to NMN and NAD+, liver health deteriorates. Even supplementing NAM does not help. So NR is an important precursor even without supplementation. Even though NR bioavailability is low, it can still increase baseline NR by a few hundreds percent. This is why NR has more health advantages than NAM. NAM has been shown to improve aspects of mice health, but not lifespan. NR has been shown to increase lifespan even late in life.

Dr Carles Canto, scientist at Nestlé and corresponding author of the study said, “This is the first paper suggesting a functional uniqueness of NR that cannot be mimicked by other precursors. This research highlights the opportunity for the development of dietary supplements and medical food products better tailored to specific states of NAD+ deficiency.”

https://www.nestlehe...ng-liver-health

Edited by MikeDC, 22 November 2019 - 09:35 PM.

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#54 Linux

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Posted 23 November 2019 - 06:02 AM

It follows that NMN would share the same "functional uniqueness" then as NRK1 phosphorylates NR to NMN which converts into NAD.
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#55 MikeDC

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Posted 23 November 2019 - 11:47 AM

It follows that NMN would share the same "functional uniqueness" then as NRK1 phosphorylates NR to NMN which converts into NAD.


This study confirms that NMN needs to convert to NR before entering cells. If NMN can enter cells, NRK1 is no longer needed. NMN acts as NR precursor.
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#56 Linux

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Posted 23 November 2019 - 11:58 AM

This study confirms that NMN needs to convert to NR before entering cells. If NMN can enter cells, NRK1 is no longer needed. NMN acts as NR precursor.

 

NMN probably both acts as an NR precursor and may utilise the NMN-transporter in other cells than the small intestine. But this isn´t proven yet, just speculation.



#57 MikeDC

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Posted 23 November 2019 - 02:42 PM

NMN probably both acts as an NR precursor and may utilise the NMN-transporter in other cells than the small intestine. But this isn´t proven yet, just speculation.


The NMN transporter study is flawed. Mountains of data shows NMN can’t enter cells.
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#58 Linux

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Posted 23 November 2019 - 04:07 PM

The NMN transporter study is flawed. Mountains of data shows NMN can’t enter cells.

 

You do know that professor Shin-ichiro Imai, one of the leading NAD-researchers in the world, conducted that study? 

 

https://developmenta...in-ichiro-imai/

 

I know that a Chromadex employee wrote a rebuttal where he embarassingly mistook Slc12a8 for a "salt transporter".

 

Who is MikeDC and who are you to judge the merits of this research? What "mountains of data" are you referring to?

 

Much is till unknown about the metabolic fate of different forms of vitamin B3 and their intermediaries in humans. I don´t think your definite statement can be supported at this time.


Edited by Linux, 23 November 2019 - 04:40 PM.

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#59 Iporuru

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Posted 23 November 2019 - 05:30 PM


 

Who is MikeDC and who are you to judge the merits of this research? What "mountains of data" are you referring to?

 

 

 

MikeDC is known on these boards as a Chromadex shill so you can safely ignore anything he writes
 


Edited by Iporuru, 23 November 2019 - 05:47 PM.

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#60 MikeDC

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Posted 23 November 2019 - 08:27 PM

You do know that professor Shin-ichiro Imai, one of the leading NAD-researchers in the world, conducted that study?

https://developmenta...in-ichiro-imai/

I know that a Chromadex employee wrote a rebuttal where he embarassingly mistook Slc12a8 for a "salt transporter".

Who is MikeDC and who are you to judge the merits of this research? What "mountains of data" are you referring to?

Much is till unknown about the metabolic fate of different forms of vitamin B3 and their intermediaries in humans. I don´t think your definite statement can be supported at this time.


Dr. Brenner wrote a rebuttal paper saying the data were shifted and was background noise.
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Also tagged with one or more of these keywords: nad+, nmn, cycling, supplements, sulforaphane, sublingual, bioavailability, tolerance, downregulation

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