Oral administration of NMN is safe and efficiently increases blood NAD levels | Hacker News Reader

Oral administration of NMN is safe and efficiently increases blood NAD levels

ncbi.nlm.nih.gov

70 pointsevo_946 comments

Note that this study shows that supplements increase _blood serum_ levels of NAD, not concentrations inside the cell and mitochondria where it counts. So I'd say that without further qualification, this study shows safety more than efficacy. The role (if any) of exogenous NAD precursor supplementation is still a topic of debate, and there's a lot of money in selling these formulations. FWIW, I personally take NAD precursors because they likely do no damage (other than to the wallet), and they possibly do some small amount of good. There are plenty of other supplements I'd spend my money before NAD precursors. (And of course diet and exercise outweigh them all for most...)

Is it generally available to buy?

You can get NMN at most supplement places. NootropicsDepot sells it for example.

Sure - you can find many NR and NMN supplements on AMZN for example. NMN has gained popularity over NR, I believe mostly due to longer shelf life. Elysium and TruNiagen are two famous brands, that IIR were sueing each other at some point? I take another/cheaper NMN supplement. Caveat emptor - there's really no way to tell what you're getting from many of these - and even if you're getting pure ingredients, the jury is still out.

For the past couple of years I’ve been taking Nicotinamide Riboside I buy on Amazon and it has basically eliminated inflammation and pain I used to get in my hands, wrists, and sometimes elbows. FWIW, I’m going to be 52 this year.

Yes, but you've got to be careful as there's plenty of fake NMN out there, and it's also not shelf stable according to David Sinclair (in a tweet).

The stuff I got was from Alive By Science, now Renue, and they claim theirs is shelf stable. https://renuebyscience.com/how-long-does-our-nmn-retain-its-...

proHealth NMN is good: https://www.reddit.com/r/NMN/comments/rsbne9/fake_nmn_produc...

I get NMN from https://youngle.com/ . Their NMN purity is verified by a German laboratory: https://youngle.com/

NAD precursors can vastly accelerate the development of any pre-existing cancer you might have, but not know about: https://www.reddit.com/r/NicotinamideRiboside/comments/mvr6x...

What are your “before nad” supplements?

250 mg/day is 4.4 mg/kg. In the mouse study published in Cell they used 400 mg/kg/day.

I believe safety at these levels is irrevelant, so I prefer just working out every day and limiting my sugar and alcohol intake, all of which have proven life extension effects.

Just a heads up about NAD, its not recommended to take NAD if you or your family has a known history of cancer (primarily at younger ages <50).

While it does not itself cause cancer, it accelerates cancer growth and thus can make catching it early less likely.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315198/

That sounds like a plausible reason for evolution to have given us lower NAD levels when we're older.

For the vast majority of our species' existence, we overwhelmingly died of causes other than cancer, so if there is any evolutionary pressure in this regard, it should be weak. Cancer as a significant cause of death is a Modern Age phenomenon.

Also, the mechanism may be more complicated. What if NAD+ levels influence the immune system somehow? (Our first line defence against cancer.) Metabolism isn't a straightforward (A -> B) system at all.

I have to disagree with you on that. There are a great many mechanisms we evolved, most long before we were human, that appear to be anticancer mechanisms. Off the top of my head senescence, apoptosis, and telomeres. The fact we don't all die of cancer earlier is a result of this.

This reminds me of Weinstein’s theory that cellular regeneration and cancer are two sides of the same coin. Senescence acts as a last resort against uncontrolled mitosis, ie cancer. This is why for example a mole that grows round and stops isn’t worrisome, but one that starts growing again from an arbitrary point and is thus asymmetric is very worrisome. In the former case the would-be tumor has burned out its telomeres and can’t grow anymore. In the latter case it indicates that the telomeric failsafe has failed and that tumor will grow without bound.

Do note conflict of interest:

>YU, YF, TaS, and ToS were employees of Mitsubishi Corporation Life Sciences Limited and prepared NMN and the placebo

Nice. More NMN studies are a good thing. I've been taking 250mg every morning and I feel like I have more energy, but I'm not convinced it's not a placebo effect.

Interesting. 15 test and 15 control subjects for 3 months seems like a pretty small-scale study to definitively declare something safe, but maybe that's normal procedure for them?

I assume the FDA is the final arbiter of what's safe and what isn't, but do they have a position? Or is this in the nebulous world of vitamin and mineral supplements that they don't regulate?

If other commenters are correct that NMN accelerates preexisting cancers, then 15 test subjects would only have caught that effect if at least one happened to have cancer at the time.

The FDA does not really police supplements.

I’ve been taking flush niacin, which I believe has the same effect at a much lower cost. Flush is really only annoying the first day.

Flush niacin has been the only thing which has reliably improved my "long covid" symptoms.

You should consider doing a cycle of magnesium lthreonate for its potent synaptothrophic properties

Try L Citruline. It easily passes the gut and readily converts to arginine which is a strong vasoprotector. Covid damages the lining of blood vessels. My belief is long covid is a redirection of free arginine to extensive vascular system damage and inflammation. At the minimum, it worked like a miracle for my long covid, YMMV. (Placebo possible of course, but citruline is used for body building as an energy and performance enhancer so the improvement in energy and thought clarity isn’t unexpected and has been shown to be beneficial in sickle cell which causes low free arginine due to the shape of the red cell irritating the lining of the blood vessels https://pubmed.ncbi.nlm.nih.gov/11688916/)

Were you taking 0.1 g/kg? How long was your treatment?

Yes. A few months but I felt results immediately, like within 30 minutes. I checked with my doctor first and she had no anxiety about trying it - she said any excess beyond what my body can manage would be immediately urinated out and citrulline is plentiful in the body.

Thanks!

source on niacin flush having an action on mitochondria? Last time I checked the only study for its pro mood effect was from 1950 and the phenomenon was unexplained.

You mean niacin, specifically? There's also the niacinamide (or nicotinamide) which doesn't cause flush. Both are Vitamin B3.

The pathway that trigger the release of prostaglandin is responsible for the dramatic effects niacin has on the lipid profile.[1] If you can't stand the sensation, you can block it by taking 200mg of ibuprofen 30min before taking niacin [2], but personally I love the feeling.

I started taking niacin before doing push-ups when I read that it cause a 3 to 6 fold increase in growth hormone during exercise.[3]

1- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779993/

2- same article page 14 to 15

3‐ https://pubmed.ncbi.nlm.nih.gov/7564973/

edit: formatting

Is an elevation of NAD levels desirable? (Why?)

It seems it is an anti aging treatment and may help reduce aging related diseases.

Your NAD levels decrease as you age. Returning NAD+ levels to a more youthful state is one of the things researchers are experimenting with to reduce the effects of aging.

Quoted from https://www.nmn.com/precursors/what-is-nad

"NAD+ works as a shuttle bus, transferring electrons from one molecule to another within cells to carry out all sorts of reactions and processes. With its molecular counterpart, NADH, this vital molecule participates in various metabolic reactions that generate our cell’s energy."

What is the effect of NMN on the lipid/glucose mitochondria consumption ratio?

Can you help elucidate us on why this matters?

Basically the ratio can be altered and it is very unclear if preferentially consuming lipids vs glucose is healthier than the converse. ALCAR shift said ratio towards pro lipids consumptions, which increase beta-oxidation. Thus it increase a kind of oxidative stress however in most studies it seems to both improve mitochondria bioenergetics and to reduce oxidative stress. ALCAR improve many aspects of health and conditions in a potent way while having no acute nefast side effects. You should see on reddit (e.g. sirsadalot), ALCAR is a very popular supplement and I was hyped like others because of the scientific evidence.

Very few people know it but there exist a ~direct opposite to ALCAR: https://en.wikipedia.org/wiki/Meldonium#Physio-pharmacology This drug decrease beta-oxidation and increase the ratio of glucose consumption. As you can see e.g. on the wikipedia page, the rethoric behind mildronate sounds too very positive except many of the statements pro ALCAR/Mildronate are contradictory, in direct opposition. So either there is an explanatory factor that resolve the contradictions, either one or the other do actually significant harm, despite both having backing scientific evidence of improving health. This topic is major since those are the most potent mechanics toward mitochondria bioenergetics regulation, which is a major way to improve your lifespan/healthspan and even cognition.

The issue is that the quality of the dicussion/research needed to elucidate those issues is above the level found on online forums and no paper directly address the question, so I am stuck in uncertainty.

Nmn is generally said w b fast-mimicking. In me it leads to collagen generation, soft skin, much faster than fasting or hyper-green drinks. ...if that helps your question...

I wish I knew someone that had a lot of knowledge of ALCAR. As someone that takes many different supplements, consumes no sugar, does IF, remains mostly keto+, the one supplement I can't seem to take is ALCAR. It makes me feel "ill" for about 24 hours. It's hard to even describe the feeling. Just an overwhelming feeling that something is very wrong and generally just "feel like crap" for a day. I feel relief after a good full nights sleep which suggests to me that my brain is clearing the compound or a byproduct of it but that is just a theory.

Hmm that seems like a pretty rare side effects, at least I've never seen it reported on reddit. (Although some people have insomnia/palpitations which can be explained by e.g. TMAO) Maybe ALCAR makes your body consume not enough sugar but that seems unlikely. > that is just a theory well if you try to not sleep or only have a short night duration I think the result would be similar. The half life of ALCAR is ~17h so after 24h you no longer have a pharmacologically relevant dose, assuming you take as low as 500mg.

BTW I recently discovered the organelle https://en.wikipedia.org/wiki/Peroxisome which is actually important in lipid (and therefore glucose) and oxidative metabolism

The glucose theory may be a good one to test out. I consume almost no glucose in my diet and I take several supplements that effectively also reduce gluconeogenesis. I also use Berberine. I will try a few different methods to boost either glucose or ketones in the brain prior to experimenting with ALCAR again.

> several supplements that effectively also reduce gluconeogenesis: names? Also did you know that Berberine is the only drug (along with another exception) that significantly slow myopia progression?

effect of ALCAR on brain-glucose: https://pubmed.ncbi.nlm.nih.gov/22549035/

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