What are the side effects of NAM, NR, NMN, and NAD supplements?
Posted at Aug. 11, 2022, 2:26 p.m.
When we talk about side effects of NMN we have to be very clear about the terminology. NMN means Nicotinimide mononucleotide. Which can be confused with nicotinamide riboside (NR) Nicotinamide (NAM), or NAD. These are all molecules related each other but are not the same. In this article we are going to look at the side effects of these longevity supplements.
Even-tough I am biologist I normally do not like to explain biological pathways because it makes things often unnecessary complicated. But in this case it is necessary to clearly explain what the side effects are.
First of all lets start with the molecule NAM and NR which both are precursors of NMN, and NMN on its turn is a precursor of NAD+. And it is the NAD+ that is used as a battery to kick start molecular process.
A nice analogy I often use is for example a small House which in this case represent NAM and NR when you change the walls with lighter materials and remove the foundation, it becomes a the static caravan, which in this case represent NMN. And when you put wheels on the static caravan it becomes a Touring Caravans which represents NAD and when we put a motor in it and add fuel you have a motorhome. Now you can go travel or in the case of cell perform cellular process. But you have to be careful when the fuel is finished the motorhome converts automatically in a small house with heavy walls and foundation. And you have to start all over again. Which happens a lot in cells during a lifetime however research has concluded that as we age it is the motorhome’s the NAD+ that decline. The decline of NAD seems to be the reason we age and if you want to restore these NAD+ levels you can take supplements. So you can go buy some more small houses (Niacin, NR) or you can go strait to buy more static caravans (NMN).
But you could ask yourself why not buy directly the Motorhomes the NAD+ straight away. Well it happens to be that unfortunately, NAD+ as a straight supplement is very difficult to maintain in capsule form. The molecule degrades quickly when exposed to light and heat, and deteriorates when exposed to water.
Now you know the main molecules involved in the salvage pathway. And you also know how these molecules related to each-other and that they are not the same. One last thing I have to mention is that that NAD+ is involved in many many biological process from circadian rhythms, DNA methylation to mitochondrial function. But it all boils down to energy almost all cell processes that need energy needs NAD+ to get their process activated.
So if you followed along you will realize that all these molecules are not the same but related each other, so when we talk about side effects of NAD boosters you need to include all side effects of NAM, NR and NMN because they all are involved in the Salvage pathway.
And if you dive into the data and extract only the human clinal trails where they researched NAM, NMN, and NR you will realize that no long term studies have been performed. So if someone claims to know the longterm risks or claims that NMN and NR can extend live span it is utterly nonsense. That data is just not generated yet. It could well be the case but we just do not have the data. On the other hand we do have data in mice and there, it has been proven many times that increasing your NAD+ levels extend live span. But in humans it has been proven that some biological processes related to aging have been improved or even reversed during NMN ingestion.
Let’s start with the side effects of Niacin supplement which contains NAM, but also NA and it is the NA that often causes problems that is way NA is rarely used in clinical practice and this is because of cutaneous flushing. Flushing occurs because the blood vessels in the skin dilate, which causes the skin to become red. Since NA and NAM also fails to penetrate trough all tissues in the body it is less effective and therefore the main reason it is not promoted as a supplement to increase your NAD levels. By the way if you take high doses of only NAM it seems to lead to the the development of a fatty liver. Which is a big problem of course.
But what about NR, well in all clinical trails in humans no side effects have been found. But since this article is about side effects we need a bit more. So within biology every molecule given to an organism at very very high levels will eventually show side effects. And that is exactly what researchers did in a few mice and rat experiments where they found in rats that NR is a very well-tolerated molecule, with side effects only observed at doses as high as (1000 mg/kg of body weight/day)). Similarly, a mother mouse study showed at the same concentrations impaired glucose tolerance and promoted white adipose tissue inflammation. Keep in mind that translating these concentrations to humans it would mean that a human needs to take 10000mg per day to reach the same levels. In humans high doses of NR have been administered up to 2000 mg/day, without any apparent side effects.
And finally NMN in all clinical trails in humans no side effects have been reported. In humans high doses of NMN have been administered in a range of 100 up to 1200 mg/day, without any apparent side effects. Since we also want to know at which levels the first side effects will start we have to turn back to mice agin. In a rat studies where they gave rats 90 days of repeated oral administration at 375, 750 and 1500 mg/kg/d. They found no real side effects. Translated to humans it means a person needs to take 15000mg per day.
As for now it seems that we have two supplements that are worth exploring which is NMN and NR both have shown to have low or no side effects in humans. But if we also take toxicity profiles from animal data into account it seems that at very high doses NR will start to show some side effects which are not present in NMN even at same or higher doses. This indicates that NMN is better tolerated in mice.
In addition it seems that NMN in mice studies showed to be more effective at increasing lifespan than NR. NR also does not lead to improvements in insulin sensitivity, pancreatic function skeletal muscle mitochondrial content or respiratory capacity. Maybe that is also the reason that some supplements brands are starting to make the transition from NR too NMN.
Anyway these and many more reasons is way I personally take 500 mg NMN each day. Not to be cheap I am the CEO of Cellulim and we sell NMN, I have unlimited access to NMN. But the reason is I tested different doses and felt most comfortable at 500mg day (it also seems to be backed by since and with NAD precursor it seems that more is not alway better).
But I think the biggest safety concern, though, surrounds the number of fake imitations supplements out there. Many of these products are not pure NMN but have been bulked out with other compounds. These could have safety issues if the manufacturer has not been clear about what’s in there. To be safe go for a good brand or just with Cellulim because all our batches are third party tested and again in our lab.
That is it for now, by the way we also have a give away, and all you have to do is, send us an email (firstname.lastname@example.org). We will make sure that you receive free bottle with high quality NMN .
That is it for now thanks for watching and start living again, because it is over before you even started.
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