Nicotinamide Mononucleotide

What is NMN?

NMN is a naturally occurring form of Vitamin B3 that is studied for slowing aging and for preventing diseases of aging. Dietary NMN is converted to nicotinamide adenine dinucleotide (NAD+), a coenzyme in all living cells which is required for numerous biological processes. NAD+ levels naturally decline with age, reaching less than 50% of youthful levels by middle age. Decreased NAD+ levels have been attributed to increased inflammation and oxidative stress as well as to the development of age-related conditions such as hypertension, cognitive decline, and type 2 diabetes. While the anti-aging effects of NMN in rodents are well-established, studies are ongoing to determine whether equally impressive anti-aging effects are possible in humans.

Can NMN be obtained through dietary sources?

Like many other supplements, such as creatine, NMN is naturally present in small amounts in dietary sources, but these amounts are much lower than those found in the supplements used in clinical studies for improving longevity. Trace amounts of NMN (concentrations no more than 0.002% by weight) are found in fruits and vegetables including avocados, broccoli, tomatoes, cucumbers, cabbage, and edamame.

Can I take NADH supplements to increase my NAD+ levels?

Not likely. Although NAD+ and NADH differ by only the respective absence or presence of an electron and NADH is a commercially available supplement, no effects of oral NADH supplements on plasma and/or cellular NAD+ levels have been reported in humans. NADH can be converted to NAD+ via the enzyme NADH reductase, an enzyme present in mitochondria. However, NADH bioavailability is likely low when taken orally, as suggested by a rodent study, which failed to detect absorption of orally administered NADH.

What are NMN’s main benefits?

NMN is taken as a supplement to increase levels of the coenzyme NAD+. It is unknown whether NMN will have the same therapeutic effects in humans as seen in rodent models, but emerging evidence is promising. So far, most randomized controlled trials in humans have focused on proving the safety of NMN supplements and their ability to increase blood NAD+ levels in different populations. Some clinical research has shown that NMN increases physical ability in aging populations, improves cardiovascular disease biomarkers such as arterial stiffness, and increases cellular NAD+/NADH levels. Although these results have been promising, additional large-scale trials are needed to better understand the benefits in humans.

What are NMN’s main drawbacks?

The main drawback to NMN is a lack of long-term studies in humans. NMN has been shown to be safe in doses up to 1200 mg daily for 6 weeks and 900 mg daily for 8 weeks. Doses of 2000 mg daily have been taken for up to 14 days with no adverse effects. Long-term safety of chronic and/or higher doses of NMN hasn’t been tested. It is also important to note that more research is needed to better understand the effects of boosting NAD+ in certain contexts.

Could NMN supplementation have potential drawbacks in people with neurological conditions?

Although NMN has shown positive effects in clinical trials to date, there may be potential drawbacks in particular contexts. NMN’s interactions in neurological health warrant further investigation. NAD+ is also a cofactor for the enzyme sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1), an enzyme that instigates neuronal degeneration after injury. In people with neurological disorders and reduced activity of a specific enzyme that converts NMN to NAD+ (nicotinamide mononucleotide adenylyltransferase 2, or NMNAT2), NMN supplementation could theoretically enhance neuron degeneration by increasing SARM1 activity.

Can NMN promote chronic inflammation?

Under certain conditions NMN can enhance the pro-inflammatory characteristics of senescent cells, promoting chronic inflammation. However, there's currently no evidence that this occurs in humans in the range of NMN supplement doses tested to date. Most research has suggested that NMN supplements reduce inflammation.

What are senescent cells?

Outside of cancer biology, normal, well-behaved cells undergo a finite number of cell divisions. This is thought to be a general anti-cancer mechanism, since tired, older cells with metabolic dysfunction and increased exposure to environmental toxins- if they were to divide- are more likely to accumulate, and pass on mutations that could promote the development of cancer. Because senescent cells have permanently exited the cell cycle, they are no longer at risk for passing along potentially harmful DNA mutations to daughter cells, potentially reducing cancer risk.

Could NMN supplementation potentially promote or enhance SASP?

On one hand, increasing cellular NAD+ levels in non-senescent cells can suppress the transition to senescence by reducing DNA damage and mitochondrial dysfunction. On the other hand, increased NAD+ levels could actually enhance SASP by encouraging senescent cells to develop the SASP, as well as increasing pro-inflammatory cytokine production in cells that already have the SASP.