NMN: A Stable, Reliable NAD+Activator and Anti-Aging Molecule (2020) | Hacker News Reader

NMN: A Stable, Reliable NAD+Activator and Anti-Aging Molecule (2020)

ncbi.nlm.nih.gov

This is an interesting topic. I've followed Dr. Sinclairs work for some time. For me specifically I personally did not experience any notable gains but I only used NMN for about 6 months and it was one of the more expensive supplements of the 50 or so that I take.

I've since switch back to just taking NAM daily since excess NMN is converted back to NAM for storage. I would like to learn how to improve the process of converting NAM -> NR -> NMN -> NAD+ but I have not found much literature on this process. Just flow diagrams. The literature explains that the bi-directional cycle of conversion slows with age but I can't find anything explaining what the specific mechanisms are that degrade with age and how to modify the root cause of the degradation.

>of the 50 or so that I take

I'm no doctor and have absolutely no idea what I'm talking about with respect to supplements, but my god that seems like just an absurd amount of supplements (especially if some of them are doing multiple things like a multivitamin or whatever). Do you take all 50 of these daily? Do you like... Blend them up so your not popping pills for 15 minutes straight every morning?

I cycle some molecules up and down. Some molecules I take at different times of the day or week. Some can only be taken a couple times a week as they can be toxic if not used correctly. Some are safe to take daily. I have researched all of them extensively. Some of them I take at levels that would make people cringe as the known literature around some of them is incomplete.

I am not a fan of multivitamins though I do keep one around and rarely touch it. Most of them contain very low quality components, most notably the vitamin E which is nearly almost always alpha-tocopherol and since I am male that is a major risk for prostate cancer if not taken with the right balance of gamma-tocopherol and selenium. Rather I prefer to take the tocotrienols. Multivitamins also contain a low quality form of vitamin C in the form of ascorbic acid and that is a topic in and of itself. I prefer to get the majority of my vitamin C from green leafy vegetables using a high powered blender that acts as a juicer.

I do at times carry with me a small metal canister that can hold about 10-15 pills when I know I will be eating food someone else made, but most of that is for different formulas of garlic extracts, digestive enzymes, TUDCA, oregano oil and other things that assist with digestion and neutralization of pathogens in food.

If you are interested in these topics a good starting point is nih.gov, just be highly skeptical of any studies you find. Their search is awful so I would use google and put in "site:nih.gov some topic"

Thanks for a great answer. I also feel that 50 pills/day seems really excessive, but at least you seem to be very knowledgeable about the subject, and to have done extensive research, with the right dose of skepticism.

I think it would be nice for you to write an article on your approach, and share it with the world - or at least the HN crowd :)

I don't think I'll ever try to emulate you, but I would happily read how you got to this point, and which supplements you decided to include in your list.

Also, your view on multivitamins, and how "poor" most supplements are, is equally intriguing. It seems that the world of supplements is full of garbage and get-rich-quick schemes, and even if you can theoretically nail the right type and amount of supplements for your health, it is very likely that you won't be able to source them properly.

I would be curious, if you are willing, to see a complete list of the items you take and why.

+1, I would love to get this!

I think the underlying question was "Why not eat food ?" or "Why do you use so much complements if you can eat normally ?"

That is a good question. I personally am compensating for the lack of nutrients in food and also over-compensating for damage that I have done to my organs from a lifetime of eating a "standard american diet" or what I prefer to call a "first world diet". A healthy food diet just wasn't cutting it for me, especially given that stomach acid and other aspects of digestion decrease with age. I can compensate with digestive enzymes, tudca, benfotiamine and chelated zinc but that has rapidly diminishing effects.

My goals go far beyond what a good diet and moderate exercise and decent sleep alone can accomplish but I would never even try to convince anyone to do what I am doing nor would I even suggest it unless one researches all of the molecules and their downstream effects ad-nauseam.

Move to Italy. I grew up here, lived abroad for ~13 years, 9 of which in San Francisco (before: Luxembourg and Singapore), working for AWS and other tech firms. I can assure you that the quality of produce I can find in Italy cannot be beaten. Comparable in some parts of the Mediterranean. Whole Foods? Give me a break, not even close.

I'm not too serious (I know it's not easy to "move to Italy", just like that), but I find it really interesting that the US is so rich, and yet the quality of food is so poor.

The tomatoes are a great example. Visit Italy, buy some tomatoes, eat them raw. You will not believe your senses.

I think there is something to be said for this, especially foods that are home grown and home prepared. In the town I grew up in there was an Italian family that owned a restaurant and would get most of their ingredients from Italy. My friends mom made everything from scratch. No highly processed foods. My friend her son was built like a tank. We used to arm wrestle all the time if for no other reason than his insane strength and my laughably futile attempts to win.

I should add that since then I have not once in my life enjoyed a calzone like his mom made. It was worth the 45+ minute wait.

Cringe of 'known literature' in an area where pharma companies buy their own safety studies is warranted.. in exactly the opposite way in which you cringe.

The burden of safety is on the consumer to navigate cherry picked and designed studies whose purpose is to minimize perceived risk, not to understate safety margins...

I also hope your research is in pharmacology school and not blogs and tiktok.

How much do you spend on supplements every month?

I honestly do not keep track of it. I consider this an alternative to other expensive hobbies that I have since given up such as off-roading and renting ultra-lights. I know that it does not come close to what I used to spend on repairing off-road vehicles.

can't imagine being this afraid of mortality

I have a different view on this topic. I can walk into any sports bar and ask any person who is going to win. They will not only have a fairly accurate answer but will also be able to tell me who will make how many touch-downs, intercepts, passes with a high degree of accuracy.

And yet...

If I ask that same person what percentage of their thymus has converted to fat I will get blank stares or receive ad-hominem attacks from them. Whereas they predicted touch-downs I can predict their risks of all cause mortality and health span by observing their behavior and physical characteristics. I would never point it out to them as that would be rude and counter-productive. Knowing advanced analytical statistics on football players might net them some money from gambling but will not extend their healthspan or lifespan.

I find this to be both fascinating and disturbing at the same time. To me, the priorities of people are topsy-turvy upside down and backwards. I do not expect many people to share my view.

But you're not taking all that stuff (plus the research) so you can be the one with the most knowledge about mortality in the bar, so what's the real reason? Obviously you mentioned it, to extend healthspan/lifespan.

Or maybe you do want to feel superior to others, heck I know that's a motivator for some of my actions.

> What's the real reason?

Not OP but their message resonates: the reason to do that regimen is to maximize the amount of healthy living. And to do so being comfortable spending money there that might not seem like a sure thing (but the payoff would be worth it).

> If I ask that same person what percentage of their thymus has converted to fat

I am curious, how could they know, measure it? (apart from inferred it from their age)

I generally feel that anyone not afraid of mortality has some extreme denial or depression going on (more often the former).

I am afraid on the decline before my death, death itself while not immediately desirable is not that frightening in comparison.

An uncle recently deceased in from cardiac arrest in his bed at his home during his sleep at 83. He was fishing the day before.... That's an ideal death IMHO. If you knew that you would have a similar death, would you be afraid ? I would not.

Even the idea of an "ideal death" just rings of denial to me. Yes, getting punched is getting better than stabbed, but I wouldn't exactly romanticize it.

The issue isn't the "dying", it's the endless trillions of years of experience we are deprived of in death.

"the endless trillions of years ..."

Noted in your uniquely written contract at birth is the ultimate outcome at somewhere around three score and ten. Get the most out of the experience you are given.

I can't think of a more reasonable thing to fear than death.

For most, the fear is more of old age problems, not death, I think.

For most levels of sick I've witnessed in people's old age, I'd far rather be sick than dead.

And people who claim to want to die before they're very sick in their old age seem usually to falsify the claim when they later reach that threshold.

NAM NR and NMN all use different absorption pathways and have different pitfalls.

There's good reason people stopped using NAM once there were alternatives available, topic well outside the scope of HN but not hard to google.

You cannot change the conversion process/rate, at least not with current knowledge, it is rate limited by multiple biological processes.

I strongly caution to use google scholar and not blogs/youtube for information.

Also everyone should be aware because of the high cost there is A LOT of counterfeit NMN out there, never buy unknown brands/sources.

> never buy unknown brands/sources

All NMN brands are unknown to me - how do I judge?

You cannot change the conversion process/rate, at least not with current knowledge

That is precisely the wall I have hit but I am a stubborn old bastard and will not give up.

There are PhDs with multi-million dollar grants who cannot do it.

I mean let's say they did somehow figure out an enzyme to speed it up, it would likely cost more than just supplementing more of the desired precursors.

There might be some obscure food or supplement that does what you want but it will cost more because it will be rare and then you've got the problem of huge consistency between batches because all manufacturing in China/India is the wild-west.

Easier to just take the precursors which are mass produced so prices slowly coming down, though covid/inflation/supply-chain threw it a curve.

Do you have a list published somewhere?

I do not. I used to list my methods on a website but I prefer to have people research this topic themselves and fully understand it as their physiology and pre-existing conditions will differ from mine. What works for me may have negative side effects on others and I would prefer they take responsibility for the trial-and-error process they will have to go through. I've even stopped using the scientific method as it is just too slow given the complexity of all the systems in a mammal and how they interact with one another and I could not in good conscience promote that for others.

Do you have a blog? If not, would you be interested in making one? You could post it on HN and as the replies surely are telling you already, people will enjoy reading it.

You may get some useful comments too with suggestions for different supplements and stuff.

yeah, i have just thought about making the Big List Of Supplements with what they are supposed to do, just adding papers for/against any to each

Been taking this for nearly 5 years. Shits the real deal. No pretending when you’re competing still against 20-something that barely washed out of their pro nhl career… but yeah not like being 55 and playing high level hockey is any sort of ‘proof’ around here (or my multiple sets of 20-25 pull-ups I do regularly and I could barely do 10 when I was 30).

Before taking this, please read https://www.foundmyfitness.com/topics/nicotinamide-mononucle... and the possible link between NMN and increased cancer prevalence. I believe the research is still too early and there is a risk with this compound.

Look up Dr. Standfield on YouTube he has a great health channel on all this stuff and digs into everything including NMN/nr and all the backing metadata / Cochrane research papers…

This Dr. Stanfield? /s

"Molecules I Used To Take But Have Now Stopped

NMN:

I focus on stopping my NAD from declining by using Apigenin, Quercetin, Fisetin, Niacin, regular exercise, a great diet, periods of safe fasting, and restful sleep.

Since I’m 30, there’s not a reason for me to take NMN in addition to the above strategies at the moment.

As I enter my mid-30s, if my NAD levels are going down I will start taking NR.

At this stage, there is far more published human data on NR compared with NMN. NR also has its Generally Recognized As Safe (GRAS) certification from the FDA. For those reasons, I would start NR, and not NMN."

https://drstanfield.com/my-supplements/

Brad had a fallout with Sinclair and Sinclair blocked him on twitter for asking a question about NMN and it's risks.

Since that Brad has stopped taking NMN and also requests people not to.

That’s not 100% true, he recommends NR because there are human trials and NMN is still being studded. Also he won’t be adding either until he’s around 45-50 (he’s only in his 30s)

I had a one-on-one phone call with him Sunday (Dr. Standfield) and we discussed my experience with NMN vs NR and which was ideal for my situation. Long / short his review of my stack was summed up as ‘you are doing everything right stick with NMN.’ The only change was to switch from l-serine to glycine.

It is true Sinclair blocked him after he asked for clarion some of his research (so rude!).

thats good to hear. His messaging on youtube was bit ambigous and i thought he was requesting people to be off NMN

Do you also supplement it with anything else, such as TMG or another methyl group donor, as Sinclair recommends?

Also, if you don't mind, what is your dose per unit of body weight, frequency and/or delivery method (oral/sublingual)?

I do. Along with Apigenin, and a few other new molecules.

Sublingual.

What’s your dose and brand? Why NMN vs NR?

I take 250mg / day of NMN from NOVOS Labs (https://novoslabs.com/product/novos-boost/). I can't definitively say I feel the effects.

The site offers a nice write up on NMN: https://novoslabs.com/nicotinamide-mononucleotide-nmn-and-lo....

Also, what about NMN versus Niagen (Tru)? Also as I understand these molecule may be fragile, do you keep them in the fridge?

Niagen is a trade name for NR. So you're asking the same question.

I do put all the more advanced stuff in the fridge including NMN, NR, rapamycin, heavy molecular weight Hyaluronic Acid

I’ve been taking NR too on and off as well, in my experience it doesn’t seem to have much effect on my athletic performance. So for me I’m sticking with an NMN even though there’s more clinical studies on nr at the moment

These are great questions, I'd also like to know dose frequency.

1gram every morning except my rest day when I take rapamycin.

alivebyscience.com (they recently changed their name and I can’t remember how to spell it sorry ha ha)

If I had to guess, when you started taking it at 50 you were also exceptionally fit and healthy for your age. Would you invest that money in a supplement if you were already over the hill ?

According to Dr.Sinclair (referenced in another comment), the NMN most people buy is probably worthless given it isn't stable. I buy it anyway because I have no better option and it doesn't burden my budget.

True, I played high-level hockey my whole life. And have actively worked out at a very high level most of my life… However I noticed everything dropping off around 50 and nothing seem to curb that. Especially my on ice speed which used to be always in the mid-20s and had dropped to the upper teens…

After starting NMN particular my VO two max and on ice speed went back up to my norm and have remained the same and actually gone back up and he’s always 22 to 25 miles an hour, at least when I’m playing against other high-end talent…. Sorry for the Poor grammar working out and using voice Rec

How are you taking it? And what does it cost?

The problem with NMN and NAD+ activators in general is that these don't[1] seem to increase (even) the mouse lifespan in ITP trials[2], which is more or less a benchmark for preclinical testing of longevity-modulating substances. On the other hand, there is a handful of substances that passed this trial with evidence of some positive influence over lifespan, at least in mice, and as such are interesting candidates for human trials: [3][4][5][6]. There is also a very interesting class of substances that seem not only to extend lifespan in mice but even to rejuvenate some aspects of their physiology upon a short course of treatment: senolytics[7][8].

1. https://www.fightaging.org/archives/2021/04/the-latest-data-...

2. https://www.nia.nih.gov/research/dab/interventions-testing-p...

3. https://www.nature.com/articles/s41573-020-0067-7

4. https://pubmed.ncbi.nlm.nih.gov/24245565/

5. https://www.nature.com/articles/nature08221

6. https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/faseb...

7. https://www.thelancet.com/journals/ebiom/article/PIIS2352-39...

8. https://www.nature.com/articles/s41591-022-01923-y

You can also take NAD+ intravenously. IV clinics in most major cities will be able to offer it and it's nothing short of incredible. The difference to energy levels and mental clarity after taking it are both immediate and undeniable.

In your experience, how long does the effect last for? At around $600/treatment (at least according to a quick Google), it better last awhile.

I do them once every two months. The benefits are most noticeable for the first couple weeks.

Why pay a bunch of money for that?

Anyone can buy bacteriostatic water from medical supply websites, along with syringes, themselves. I can personally recommend Hospira brand.

Just give yourself the IV.

DIY NAD+ IV will give an uncomfortable rush if you take too much too quickly. I presume you mean infusion which needs to be done slowly with a drip or an infusion pump.

What if the substance comes as a powder? How do you know if it dissolves completely? It just sounds too risky.

I afraid of needles and of opiate addiction so I never used injectable drugs but if I had to inject myself with an homemade solution, I would follow that manual¹ , use a syringe that include a filter² and usebacteriostatic water like gavinray said.

That should cover all the probable risks, with the exception of those caused by the substance itself.

1) https://harmreduction.org/issues/safer-drug-use/injection-sa...

2) https://www.exchangesupplies.org/shopdisp_filter_syringe.php

I think it is strange that the filter doesn't have a description of the pore size.

Can you IM it too? IM usually has a slight drop in bioavailability vs IV, but it's much easier.

NAD+ IM will hurt a fair bit at the injection site.

I've tried high dose NAD+ IV and the effect wears off too quickly for me for it to be worth it. The 750mg dose only giving a boost for less than 24hrs.

Since a lot of people are asking me different questions in this thread I figured I’d let people know if you wanna just email me look at my profile and reach out. Happy to share my entire stack with anybody that wants to see it…

Or if you happen to be a high-level hockey player in Denver we’re starting to look for a few guys to fill out our winter roster =)

been taking not exactly NMN, but NR (tru niagen) for a few months. my liver enzymes (alt/ast) first time in a very long time are back in proper range.

Do you drink a lot? Were you drinking a lot before you started taking them, and reduced drinking - or did you change anything other that adding NR/NMN to your intake?

Drinking same as before (1.5l-3l at any given day). Also got some different multivitamins, but I doubt that they changed anything.

There are some mouse studies that nmn/nr improve alt/ast level, but it not really clear is it just enzyme level normalization or does it actually repair anything. So i am not sure at this point of time is it improvement or "improvement"

Edit. in case by drinking it was implied alcohol and not water, no. just some wine here and there. no big changes

Not the GP, but I'm pretty sure they were asking if you drank a lot of alcohol, not water :)

Heh, saw 1.5/3L/day and I just thought, well, that's a lot of alcohol.

ooopsie...(there are also a lot of discussions about how much water you drink, etc...) in this case not more than usual. some wine here and there. nothing major and no alcoholism, if this is what was implied

I tried both NMN and NR. NMN did absolutely nothing for me. NR is noticeable - can sustain heavy exertion for much longer. Much faster recovery.

Taken NMN 500g pill in morning for the first time last week, for 4 days. I felt physically and mentally very energized. My sleep length reduced to only couple of hours at night, so I stopped completely. First night after stopping was completely sleepless. Second night was solid and back to normal sleep pattern and energy.

i am a bit wary of any doctor with a podcast

Reply on news.ycombinator.com