The Case Against NMN

There is so much disinformation going around about NMN, it's time for a tweetorial /1

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

My primary motivation is for people not to be harmed. I also think it is horrible for people to be fooled or hoodwinked /3

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

I will explain all, starting with the basic chemistry /5

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

Nucleosides are molecules with a base linked to a sugar. When the base is adenine (abbreviated A) and the sugar is ribose, you have adenosine. When the base is nicotinamide and the sugar is ribose, you have NR /7

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

NR also circulates, though it is difficult to detect. When we draw blood, an enzyme that is normally inside cells spills out and breaks the NR into nicotinamide plus ribose. We know NR circulates because every cell has NR kinase (some cells have NR kinase 1 and 2) /9

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

What NMN advocates are saying is that NMN is closer to NAD+ than NR is. They are saying that NR has to be converted to NMN and then to NAD+ and this makes NMN more powerful than NR because it is already has one of the phosphates on it toward rebuilding cellular NAD+ /11

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

If NMN entered cells as NMN, then it would not need NR kinase to elevate NAD+. We knocked out NR kinase. As expected, NR could not be used by cells from these mice to make NAD+. We and others showed that NMN loses its phosphate outside cells, becoming NR /13

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

NMN proponents further claimed that sodium channel Slc12a8 is an NMN transporter. Their data did not show this. Their data showed that there is no cellular increase in NMN after extensive incubation with NMN. Remarkably, their false paper has been cited more than 20 times /15

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

@davidasinclair also knows this. That's why his company modified the phosphate on NMN to make it cellularly available. Everything in this thread is supported by public data /17

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

No. SARM1 protein is turned on by NMN to produce cADPribose that leads to cell death. Remember when I said that in a healthy cell, NMN is converted to NAD+, NADH, NADP+ and NADPH? In a damaged neuron, NMN cannot be converted to NAD+ and is a death signal /19

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

Is this why I think that NMN is potentially dangerous as a supplement? No /21

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

The problem is you literally have no idea what you are getting when you buy NMN. I would bet that there's caffeine in most NMN supplements. There is likely a large amount of nicotinamide and residual solvents. There's been no NDI on any NMN source. There are no safety data /23

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020

What keeps me up at night is the idea that someone will be hurt by taking NR. Safety first. People taking NMN are not been safe. And they've also been hoodwinked by the people asserting that it's closer to NAD+ than NR /end

— Charles Brenner, PhD (@CharlesMBrenner) January 13, 2020