The Fountain of Youth - NMN Supplementation

Author: Reese Weissenfluh
Editor: Brentsen Wolf, PharmD

Have you ever noticed a decline in your daily energy levels as you get older? There are many possible explanations for why this happens, but a recent study has led to a potential breakthrough in replenishing your vitality! Nicotinamide mononucleotide (NMN) is a potent precursor to one of the body’s main cellular energy sources — nicotinamide adenine dinucleotide (NAD+). The full extent of the effects of NMN in the body is still being studied, however, current research is exploring supplementation of NMN in humans. Some researchers even hypothesize that NMN could act as a partial age-reversal agent!

What is NMN, where does it come from, and how do I get energy from it? NMN is one of the most potent precursors to NAD+ in the body. It can be found in foods like broccoli, avocados, cabbage, edamame, and cucumbers — typically in non-significant levels. Our bodies can readily ingest NMN orally and metabolize it in high quantities, so it already has a strong portfolio for supplementation from a kinetics standpoint. Once the body has metabolized NMN into NAD+ factors, NAD+ is then readily used in cellular processes related to the body’s metabolism and overall energy level.

Why should I care about NMN supplementation? If you like the idea of feeling like a youthful 20- or 30-year-old again, then you should care about the research around NMN supplements. NMN has been the target of aging-based studies for the last decade, primarily in rodents. These studies have asserted truth to claims about NMN increasing muscular endurance and increasing the overall health of aging mice. In an ideal scenario, the evidence from these studies would translate to humans!

Conveniently, the introduction of human studies in NMN did show similar benefits to those observed in rodent models. A recent study even provided evidence that NMN may be able to help increase the longevity of humans and help slow down age-related health conditions. This could be a massive step in the right direction for treatments of conditions that plague the human genome.

Summarize the trials for me!
Many trials around NMN have supported the idea that it causes increased NAD+ levels in the blood, potential increases in aerobic muscular endurance, and maintenance of blood biologic age in study participants. While the introduction of human trials didn’t start until 2016, researchers have continued to air on the side of caution when studying the effects of NMN supplementation in humans. Nearly all of the studies completed with NMN have been with doses <300 mg daily and with fewer than 100 participants total, so the strength of these studies is relatively weak. Still, if the current evidence has any validity, then we may have stumbled onto a goldmine for improving the health of our aging population!

What does the science say?
In a recent study published in Geroscience in December of 2022, participants aged 40-60 were given supplementation of oral NMN in doses of 300 mg, 600 mg, and 900 mg daily. Participants showed statistically significant improvement in a six-minute walking test by walking further than participants that took a placebo for 60 days. Baseline testing was conducted prior to the study, at day zero.

Not only did the participants feel better physically according to a short 36-point questionnaire, but their blood biological age was maintained. The placebo group saw an increase in blood biological age and the results were determined to be statistically significant. In other words, people were feeling more energized and youthful in their day-to-day life! However, you should note that the "biological age" used 19 clinical laboratory test parameters and is not necessarily a great endpoint. Many of these blood biomarkers change acutely and can therefore provide a different "age" from day to day. For instance, the placebo group's mean biological age increased from 39.8 years old to 45.4 years old in just 60 days.

While there are certainly shortcomings in this study like sample size and limited diversity, it is a step in the right direction for NMN. Larger and more diverse study groups are needed before we determine the effects of NMN supplementation in humans.

Buyer Beware!
Before you jump out of your seat and run to the nearest GNC or hop on Amazon to purchase NMN for yourself, you should consider the next couple of points:

1. Many supplement companies see NMN as a goldmine in terms of what it can offer to the market and their own pockets — News flash! They only want your money, so hold it tight!
2. Companies started trying to sell NMN as a supplement intended for use in the gym. It's typically advertised “to help increase muscular endurance” and “set new personal records”. — While it’s certainly possible for this claim to be true, I would exercise caution in believing anything supplement companies are trying to sell you at this time. See the next point for even more on this.
3. Perhaps the most important point of all — The FDA is currently halting the sale of NMN due to potential pharmaceutical and/or clinical benefits. The current research is quite promising, so the federal agency has flexed its muscles on this supplement for the time being.

What does the future of NMN look like?
The future of NMN certainly looks bright, but remember that looks can be deceiving. NMN has awesome potential to be a breakthrough drug — or a bust! For the time being, we will just have to see how the FDA moves forward with the current information in front of them.

But in the meantime, be sure to check out these fitness supplements that have far more science to back their use!

Which Supplements Should You Take to Stay Fit?

The fitness supplement market is MASSIVE. How is one to know what they should and shouldn’t take? There’s so much crap out there, most of which is a total rip-off, that it’s easy to get completely lost. Luckily for you, the true list of supplements worth purchasing is very small.

RxTeachBrentsen Wolf, PharmD

If you're interested, more information on studies and the science of NMN supplementation can be found here.

Author Bio: Reese Weissenfluh is a 4^th year pharmacy student at Ohio Northern University and a part-time nuclear pharmacy intern. His current goal after graduation is to obtain a fellowship in the pharmaceutical industry in clinical trial development to help bring novel treatments to new patient populations. In his free time, he likes to exercise, help build the campus’ E-sports program, and spend time with his brother.

References:
1. Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. 2022 Dec 8:1–15. doi: 10.1007/s11357-022-00705-1. Epub ahead of print. PMID: 36482258; PMCID: PMC9735188.

2. NMN.com: The Official Info Source for Nicotinamide Mononucleotide. [Internet]. |Place unknown|. What is NMN; 2020 May 5; [2023 Jan 30]; [about 1 screen]. Available from: https://www.nmn.com/what-is-nmn.

3. https://www.nmn.com/everything-about-nmn. Accessed 1/25/23.