Enhancing Longevity: NMN vs NAD + via Oral or IV Routes?

In recent years, the interest in NAD+ (nicotinamide adenine dinucleotide) and its precursor NMN (nicotinamide mononucleotide) has surged due to their potential benefits in promoting longevity, enhancing energy metabolism, and improving overall health. These compounds play crucial roles in cellular processes, and their supplementation has garnered significant attention. Understanding the bioavailability of NMN and NAD+ when administered orally or intravenously (IV) is essential for determining the most effective method of supplementation.

Understanding NAD+ and NMN

NAD+ is a derivative of vitamin B3 (niacin) and is essential for metabolism, signaling pathways, and DNA repair. NAD+ levels are maintained in the body by continuous recycling of NAD+ from various precursors in the cells. This recycling reduces oxidative stress and increases NAD+ levels. Higher NAD+ levels slow down aging, improve cardiac health and immunity, and reduce the risk of cancer and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease (Palmer et al., 2021).  

NMN is one of the precursors of NAD+, meaning it is an important molecule that the body converts into NAD+. NMN is a naturally occurring compound found in small amounts in foods like broccoli, avocado, and cabbage. NMN causes a rapid rise in NAD+ levels, reversing age-related decline of NAD+. Therefore, NMN is labelled as an effective supplement for anti-aging therapies and improving human health (Song et. al., 2023; Nadeeshani et al., 2022). 

Optimal NAD+ levels are pivotal in maintaining youth and health. Maintaining optimal NAD+ levels improves the ability to combat damage caused by free radicals which disrupt the body’s internal clock (circadian rhythm). Supplementation also helps slow down the progress of metabolic disorders like diabetes, and neurogenerative disorders such as Alzheimer’s disease, Parkinson’s disease and cancers (Xie et al., 2020). It improves skeletal mass and muscle strength in older adults and improves their quality of life (Igarashi et al., 2022). Thus, increasing NAD+ levels enhances metabolism and increases longevity and vitality. 

 Figure 1: Shows NAD+ levels’ effect on human physiology. This figure shows how NAD+ levels affect functioning of the different organs of the body and means of increasing NAD+ levels (Figure 1 sourced from Palmer et al., 2021)

Since NAD+ is crucial for energy metabolism, the manipulation of NAD+ levels through various precursors sets the stage for potential therapies. Of these, NMN supplementation has been shown to be the most effective and instantaneous in increasing energy levels. 

NAD+ levels are maintained in the body through the synthesis, consumption and recycling of the precursors, including NMN, into NAD+ via the salvage pathways. These processes take place in the cells (Xie et al., 2020) and NMN is rapidly absorbed through the small intestine. It has been shown that gut microbiota play a vital role in NAD+ metabolism (Huang, 2022). Bioavailability refers to the availability of the supplement for its intended use in the body. The route of administration of the supplement affects the rate of bioavailability. A supplement that is taken orally has to be stable and absorbable in the digestive tract (also known as the gastrointestinal tract). Dr. Okabe and his colleague conducted a recent clinical trial where they gave NMN oral supplementation to healthy volunteers for 12 weeks after which they measured the level of metabolites. They observed that NAD+ levels were significantly increased and were sustained throughout the intervention periods. There was an increase in the pulse rate, which corresponds to increased metabolism. There were no adverse side effects (Okabe et al., 2022). 

Another method to boost NAD+ levels is to combine NMN supplementation with certain geroprotectors such as Resveratrol which have been shown to increase longevity and energy levels independently, as well as when supplemented with NMN in mouse models (Sharma et al., 2023). 

There are few studies that examine the effect of intravenous administration of NMN supplements on NAD+ levels. A clinical trial was conducted on 10 Japanese men and women with an injection of 300mg NMN in 100mL of saline. NAD+ levels were significantly increased from 0.5 to 3 hours post administration. There were no significant effects on any biomarkers of the liver, heart, kidneys and pancreas, but triglycerides were elevated from 0.5 to 5 hours, after which it returned to the normal level. (Kimura et al., 2022) Another study investigated an intravenous infusion of 750mg NAD+ in normal saline over a six-hour period. This resulted in elevated NAD+ levels after the 6-hour period with no adverse events (Grant et al., 2019). Larger studies are needed to verify the above results.

When choosing between oral and IV administration, the time required for the supplementation to be bioavailable must be considered.  Oral supplementation has to be absorbed by the digestive tract, thus taking a longer time for it to be bioavailable. By contrast, IV administration delivers the supplement directly into circulation, making it bioavailable faster.

Oral NMN supplementation from 250 mg to 1250 mg per day for up to four weeks has been shown to increase NAD+ levels and sustain it, increase insulin sensitivity and improve well-being in healthy adults and pre-diabetic women. There were no reported adverse events of NMN oral supplementation (Huang, 2022; Yoshino et al., 2021). However, NAD+ supplementation is primarily through various NAD+ precursors such as NMN. 

Very few studies have explored the intravenous administration of NMN and NAD+. Supplements were injected as 300 mg/100mL and 750 mg in saline. These studies have shown that NAD+ and triglyceride levels temporarily increase, and  then return to normal.  No adverse events were reported during these studies (Grant et al., 2019; Kimura et al., 2022).

Another point to consider is that NMN oral supplements are generally administered as powders, liquid or capsules to be taken with water at home without requiring clinical prescription. By contrast, an NAD+ intravenous infusion requires a six-hour infusion in a clinical setting over a period of time.   

When considering the cost of supplements, oral supplements will be lower as the only cost incurred will be that of the supplements. Since intravenous supplements need to be taken in clinical settings, cost of kits, personnel and the supplements will increase the overall cost of these infusions.  

Conclusion

Both NMN and NAD+ play essential roles in maintaining cellular health and combating age-related decline. When it comes to bioavailability, NMN has a clear advantage over NAD+ for oral administration, as it is more effectively absorbed and converted into NAD+. However, IV administration of either compound ensures complete bioavailability and rapid increases in NAD+ levels.

For those seeking convenient, everyday supplementation, oral NMN is a practical choice with proven efficacy. On the other hand, individuals looking for immediate and significant boosts in NAD+ levels might consider IV administration, albeit at a higher cost and with the need for medical supervision. Understanding these differences can help individuals make informed decisions about how best to support their health and longevity through NAD+ and NMN supplementation.

Here at Pristine’s, we care about your health. Therefore, Pristine’s recommends that you consult with your doctor before embarking on any significant alterations in your eating habits, nutritional supplement intake, or exercise routine. Our blogs are not able, nor intended, to substitute for professional, personalized medical advice. We ask that you discuss any points of interest raised in these blogs with a trusted medical professional.

We wish you optimal longevity and health.

References

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