Does NMN improve metabolic health in humans? | Hacker News Reader

Does NMN improve metabolic health in humans?

peterattiamd.com

87 pointsnradov57 comments

Anecdote:

Started supplementing with NMN and NAD+ after coming across David Sinclair’s research and book.

I injured my knee in a motorcycle high side, and seemed to develop chronic osteoarthritis in the joint.

For 2 years I had dealt with this chronic pain and weakness that was only mitigated by leg/rehab exercises. However, the dull pain would come back if I stopped.

After taking NMN/NAD+ orally (1 pill every few days) I noticed that for the rest of the day inflammation was very much reduced for me - especially in my knee. A few months later now my knee is a lot better and I haven’t been taking the supplements.

I like Sinclair’s research a lot, and my anecdote aligns with many of the results anecdotes he has shared. Maybe my knee just healed naturally, but I think there is something here.

What age group are you in?

What brand supplements do you take and what dose? I did a cursory look online and was nervous about not finding any brands that I was familiar with, and I am concerned about quality given lack of regulations in the supplement market.

> nervous about not finding any brands that I was familiar with

Every "amazing" supplement I hear about encounters this problem. It has become laughable just how scammy/scummy some of the packages look.

Here's one of the more recent https://www.amazon.com/Thermal-Non-Stimulant-Thermogenic-Bur...

It's recommended by a seemingly serious and reputable doctor. I'm not buying it though.

The problem is that the supplement market has the incentive to maximize short-term marketing since their isn't any defensibility without a "proprietary" formula, which is a red flag in itself.

You didn’t even answer the op question… is it too much to ask what brand / supplement you took, and how much?

not the same person

I am dumb, and deserve these downvotes.

You are not dumb, you were just too interested in the answer... ;)

I've taken NOW brand for other things like Vitamin D and they seem pretty legitimate.

Though the reviews here seem like the side effects are horrible & counter the the purpose.

https://www.amazon.com/NOW-Supplements-Nicotinamide-Dinucleo...

Another anecdote.

42 y.o. male. My eyesight has improved since I started experimenting with NMN; over 1 dioptrie in one eye, actually. The effect was very quick, in a week or so. I definitely did not expect it.

Also, my left thumb joint cracks less.

My irony detector doesn't give me a clear signal on this

Maybe because it's actually your sarcasm detector that's broken...

Out of curiosity, if you think it worked, why did you stop taking it? Also, how old are you (in decades) :)?

Hey, we make can NAD+ ourselves, you just have to get the Quinolinic pathway flowing:

https://www.researchgate.net/figure/Overview-of-the-kynureni...

This is most important when you have any kind of inflammation since inflammation stimulates the IDO enzymes.

How do you do that? Probably with some of the cofactors of the enzymes in the pathway liken:

B6 for KYNU: https://www.uniprot.org/uniprot/Q16719

Riboflavin for KMO: https://www.uniprot.org/uniprot/O15229

I really wish the researchers would start testing people for these deficiencies more regularly.

Or even general blood screenings. I once went to the doctor for depression that was severe enough to affect work and marriage. I was fortunate that the doctor tested for B12 deficiency, a week of methylated b12 supplementation fully fixed my depression which hasn't returned in years.

Turns out there is a genetic component to B12 deficiency, and other family members have been turning up with the same kind of thing.

I wonder how many people get driven into expensive medication and treatment programs for relatively simple to treat vitamin/metabolic disorders.

All true. I can’t tell you how many women I know we’re suffering from “depression” and then they found out they were severely iron deficient.

In my opinion, all mood disorders are metabolic disorders so that’s what frustrates me about it all.

I've been supplementing with NR for the past couple of years and I've experienced a lot less inflammation-related problems in that time. For example, I used to wake up occasionally with sore joints (especially hands, wrists, and knees) and swelling in my hands to the point where the thumb on one hand could only bend about half as much as the thumb on my other hand.

I haven't had that problem at all since I added more vitamin D and NR to my usual multivitamin. I don't know if the NR or the additional D is responsible, but it coincides 100%. Nothing else has really changed.

What is NR?

NMN - nicotinamide mononucleotide

NR - Nicotinamide Riboside

NAD - Nicotinamide adenine dinucleotide

People should remember that all kinds of stimulants do not deliver energy by themselves. Instead, they push the organism to produce\overwork on what it already has.

How can one learn more about which stimulants have the “right” impacts?

None really. All they do is "borrow" with interest.

Take a look at Modafinil. Not a traditional stimulant. I've been taking it routinely at the start of the workday for focus with great success. No "come down".

Are you worried about building up tolerance? Although not 100% clear, it looks like it might potentially be an issue:

https://www.gwern.net/Modafinil#tolerance

My son is young and is dabbling with various things, mostly at raves and such. One thing I said about this which he said has stuck with him: stimulants aren't giving you energy -- they are borrowing tomorrow's energy.

Sure, but a lot of people would be perfectly happy eating 15% more calories to support a more energetic and healthy lifestyle.

Our biological limits evolved in a calorie-scarce environment; evolution made tradeoffs about what we should be capable of doing based on whether we would starve to death.

Those tradeoffs sometimes are maladapted to the 21st century, and the metabolic hack of "eating a bit more" is not a hardship.

Running your metabolism 15% faster might give you more energy in the short term, but I expect the additional oxidative stress would damage long term health. There's no free lunch.

This is pretty speculative. Jogging and doing hard word puzzles both use extra calories, and both help people live long and healthy lives.

Yes but the increased metabolic effect is mostly just during the activity. Resting metabolic rate doesn't change much. I am speculating that the extra oxidation would damage cells.

By contrast, GLP-1 is known to improve glucose uptake in skeletal muscle, among other benefits. Not an OTC drug or supplement however.

Web Abstract: https://diabetes.diabetesjournals.org/content/51/suppl_3/S43...

PDF: https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.48...

There’s some miracle chemical every few years that’s supposed to generally be healthy. So far none of them turned out to be generally recommended.

I’ll try to stick to a healthy lifestyle instead, without any supplements.

You're right, CBD, turmeric, Raspberry lactone, chlorophylls, resveratrol, colloidal silver...

I think that last one is in a class of its own.

tl;dr NMN = nicotinamide mononucleotide

The author explains a published paper and says though the reported results may be statistically significant, there is not convincing evidence that they are clinically significant. So, more study needed.

I find the chase for the "magic fix" drug fascinating. By that I mean not so much the research into it and developing the products (I understand the economic incentives), but more the number of often very smart people who experiment with all sorts of supplementation.

Someone in the thread said they are doing it to maintain their health when getting older, but we already know a proven and effective way of improving health and slowing ageing, exercise. It has many other beneficial side effects (decreasing risk of depression, heart disease etc), but instead of exercising people experiment with "wonder drugs", which might have significant detrimental side effects (look up the history of vitamin C supplements for example). I guess part of it is that our community has a strong predisposition to technological fixes. The other part is likely that exercise requires effort.

Everyone I know who uses these also exercises significantly, both weight training and cardiovascular fitness.

What are the negative side effects of vitamin C supplements?

Speaking as someone who I guess fits with smart person who has tried NMN it wasn't a case of thinking it was a "magic fix" - just that there is some evidence this stuff works so why not try it. It's not a case of NMN or exercise - you can do both and the NMN may help allow the exercise without your joints going. I actually didn't notice any difference to speak of but don't regret giving it a go.

You can probably assume that the very smart people researching supplements to maintain their health as they age are getting lots of exercise. Exercise, sleep, and diet are table stakes. The interesting questions are around what to do after that.

you could try this https://www.ncbi.nlm.nih.gov/books/NBK92758/

Why the downvote? This can be bought via biotechnological produced stock in any dietary supplement store and is pretty relevant to the post

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847515/

"Pharmacological studies on Yang and Yin tonifying herbs suggest that Yang tonifying herbs stimulate mitochondrial adenosine triphosphate (ATP) generation, "

Dr Brad Stanfield has done quite a few videos over the last few months on NMN and they have been quite informative. Lots of fantastic info on current research, etc.

Great channel and I really like that he use Cochrane Reports.

https://www.youtube.com/watch?v=f46mHDvdHcE

As someone that's already drank the NMN koolaid, I'm quite turned off by this channel. The number of times things are described as "epic" reminds me of an infomercial. Maybe his recommendations are still good but I wish there was more nuance. Results also seem to be given the most optimistic possible interpretation.

As someone that's already drunk the NMN koolaid, would you share your experience with two sentences? For example, have you noticed any results and if yes, how long after starting taking NMN?

The three big changes for me are feeling like I have more energy, sleeping better, and knowing I have ~$100 less in my bank account each month.

Honestly, it might just be placebo, but I'm going to keep doing it. My goal isn't to improve my current health but to maintain it (I'm about to enter my 40s, so maintaining my health has been on my mind a lot).

Part of me worries it's not doing anything - maybe it only helps people later in life with an NAD deficiency. Part of me worries I've been scammed - picking an NMN supplier is difficult because it's costly and there are no suppliers I'd consider a brand name. Part of me worries I'm lacking some other key ingredient - resveratrol is often mentioned, but I had an allergic reaction to it and stopped; you can see Dr Stanfield's list of supplements in his doc, and it's hard to know which ones matter: https://docs.google.com/document/d/1f4qoRL1sxVXiiOBaMJeJqxQr...

So, I'm not convinced it's doing anything. The chance it might do something later down the line is, for me, worth the price. I buy into Dr. Sinclair's research which is why I choose NMN over other alternatives.

In the same boat, (unlikely) worst case scenario seems to be if I already have cancer cells I could be causing them to grow.

Why don't you just stop for a bit and observe?

I've watched a few videos on that channel and there something that's been bugging me in the look of Dr Stanfield. I can't describe exactly what though ¯\_(ツ)_/¯

Another way to potentially increase lifespan that has some momentum are MAO-B inhibitors such as selegiline.

Although eating cheese with that can kill you, so is there not an R-MAOI like moclobemide but for MAO-B?

Although eating cheese with that can kill you, That's a non issue at low dose selegiline (1mg per day) and low doses are likely to be more effective.

There is also the emsam version of selegiline that solve the problem.

Good question, RIMB does not exists on the market (but probably exists on some natural compounds) however it's not needed for reason aboves, there are also purely selective MAO-B inhibitors such as rasagiline which don't have the cheese effect, however I believe it isn't as effective for fighting ageing (the main effect does not come from MAO-BI)

I wonder if this is because it lowers the production of H2O2...?

https://www.uniprot.org/uniprot/P27338

So maybe supplements that promote glutathione production would be a better avenue.

Selegiline/BPAP decrease ageing by multiple mechanisms:

1) at non-low doses it increase dopamine level/synthesis, dopamine reduce with aging (15% less at 40, 45% less at 70) and this accelerate ageing (can be said of many things, and it also a strong reason for testosterone replacement therapy)

2) it is a potent antioxydant and is pro apoptotic at the mytochondrial level. This massively reduce accumulation of ROS and is shown to be highly beneficial in many conditions (such as myopathies, and neurodegenerations)

3) there is a third mechanism (effective at low dose) That is apparently more important than the 2 first mechanisms (at least in rats) and show extreme results such as X2 lifespan in rats and X3-4 learning ability

https://www.sciencedirect.com/science/article/pii/S002432051...

1) Correlation is not causation. It could be that the dope mean just coincides with the reduce levels of Hydrogen peroxide.

2) But I explained how it’s an antioxidant , it doesn’t have any antioxidant properties on its own, it just prevents the creation of hydrogen peroxide.

3) It really isn’t much to deduce from the third study.

1) Correlation is not causation. It could be that the dope mean just coincides with the reduce levels of Hydrogen peroxide. MAO-B degrade dopamine it is clearly causative.

But you’re saying is the dopamine, I’m saying is the hydrogen peroxide that is not produced when the dopamine is not metabolize. Dopamine has no real function in the body other than neurological. But oxidative stress is critically important especially to lifespan.

A little late to this conversation, but I want to point out that it appears dopamine does have functions other than neurological.[1] Of course one might take the view that immune function is regulated by the nervous system and thus it may not be a direct pathway.

[1] https://www.hindawi.com/journals/jir/2016/3160486/

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