How to store nicotinamide mononucleotide (NMN) to reduce degradation | David Sinclair
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Two NAD+ precursors, nicotinamide riboside and nicotinamide mononucleotide, have been shown to ameliorate age-associated diseases in animals. They are well-tolerated at high doses and effectively raise NAD+ levels. These molecules are not shelf-stable at high temperatures or in conditions of high humidity, however. They quickly degrade into nicotinamide, which inhibits the activity of sirtuins and PARP, a DNA repair enzyme. In this clip, Dr. David Sinclair discusses the stability issues encountered with nicotinamide riboside and nicotinamide mononucleotide.
David: Actually, you remind me to say something important for the listeners. Make sure your NR and your NMN is kept in the cold. If it's just on the shelf and it's not in a stabilized form, then it will degrade into nicotinamide, which is something you don't want to take high doses of because we've showed in my lab many years ago that nicotinamide will inhibit the sirtuins, and PARP as well, and interfere with DNA repair.
Rhonda: What? Really?
David: Yeah.
Rhonda: Like the form that's in vitamins?
David: Right. It doesn't have a super long shelf life, that's not very well known. So keep it cool, in a freezer or the fridge.
Rhonda: But I mean, like, if you're buying nicotinamide riboside, you know, from a variety of companies that make it, it's certainly not shipped to you cold. So the question is how much of it's already degraded just on the shelf?
David: I don't know.
Rhonda: I mean, it's kind of the case with probiotics. You know, when you get probiotics, you want them to be shipped to you cold, you know, so that they're live.
David: Right. Same thing here. We have to also replace our mouse NMN. We put it in their water. We replace that every week because it goes off, but if it gets wet or it gets a bit of humidity in the bottle, it's only a short time before it's degrading.
Dietary supplements that purportedly increase cellular levels of nicotinamide adenine dinucleotide (NAD+). Examples of potential NAD+ boosters include resveratrol (a plant-based dietary compound found in grapes), metformin (a type of diabetes medication), and nicotinamide mononucleotide (a derivative of niacin).
A coenzyme that is required for the production of energy in cells. NAD+ is synthesized from three major precursors: tryptophan, nicotinic acid (vitamin B3), and nicotinamide. It regulates the activity of several key enzymes including those involved in metabolism and repairing DNA damage. NAD+ levels rise during a fasted state. A group of enzymes called sirtuins, which are a type of histone deacetylase, use NAD+ to remove acetyl groups from proteins and are important mediators for the effects of fasting, caloric restriction, and the effects of the plant compound resveratrol, a so-called caloric restriction mimetic.
A precursor molecule for the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a coenzyme that participates in the production of cellular energy and repair. NMN helps maintain cellular levels of NAD+, thereby facilitating NAD+-dependent cellular activities, such as mitochondrial metabolism, regulation of sirtuins, and PARP activity. Animal studies have demonstrated that NMN administration is effective in increasing NAD+ levels across multiple tissues while improving the outcome of a variety of age-related diseases. Although NMN administration has proven to be safe and to effectively increase NAD+ levels in rodents, the safety and efficacy of NMN supplementation in humans remain unknown. NMN is available in supplement form and is present in various types of food, including broccoli, avocado, and beef. It is also an intermediate compound in the NAD+ salvage pathway, the recycling of nicotinamide into NAD+.
A precursor molecule for the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a coenzyme that participates in the production of cellular energy and repair. NMN helps maintain cellular levels of NAD+, thereby facilitating NAD+-dependent cellular activities, such as mitochondrial metabolism, regulation of sirtuins, and PARP activity. Animal studies have demonstrated that NMN administration is effective in increasing NAD+ levels across multiple tissues while improving the outcome of a variety of age-related diseases. Although NMN administration has proven to be safe and to effectively increase NAD+ levels in rodents, the safety and efficacy of NMN supplementation in humans remain unknown. NMN is available in supplement form and is present in various types of food, including broccoli, avocado, and beef. It is also an intermediate compound in the NAD+ salvage pathway, the recycling of nicotinamide into NAD+.
A family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death (apoptosis). PARP's primary role is to detect and initiate an immediate cellular response to metabolic, chemical, or radiation-induced single-strand DNA breaks by signaling the enzymatic machinery involved in repair. NAD+ is required as substrate for generating ADP-ribose monomers. Evidence suggests that overactivation of PARP may deplete cellular stores of NAD+.
A class of enzymes that influence that influence aging and longevity through multiple molecular pathways. Sirtuins regulate a variety of metabolic processes, including release of insulin, mobilization of lipids, response to stress, and modulation of lifespan. They also influence circadian clocks and mitochondrial biogenesis. Sirtuins are activated when NAD+ levels rise. The dependence of sirtuins on NAD+ links their enzymatic activity directly to the energy status of the cell via the cellular NAD+:NADH ratio, the absolute levels of NAD+, NADH or nicotinamide or a combination of these variables. There are seven known sirtuins, designated as Sirt1 to Sirt7.
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Manufacturers of raw materials have made a lot of progress to synthesize NMN that is more stable. HPLC-based stability tests aren’t that expensive or hard to conduct and you can easily find out these answers. At www.ver.so/stability we showed that our NMN and Resveratrol formula did not degrade after 30 days at 104F (40C).
Since Dr. Sinclair can’t state which products he knows are good sources of supplements and products, can Dr. Patrick help us out on this front??
I wish I knew how important this was earlier. I store my NMN sublingual powder in the fridge, but there have definitely been days where it’s sat out overnight or for several hours during the day. So now am I poisoning myself? Is there any way to know if it has gone bad?
He never clarified what a ‘stabilized’ form of NMN would look like. What would one look for to see if what they’re taking is stabilized and is there a way to tell if the NMN has gone ‘off’? Many thanks in advance!
I found this enlightening. I wonder what % of supplements are already degraded once they are shipped to customers and if in fact some may be doing more hard than good.