NAD+ was a seriously hot topic at a recent Functional Medicine longevity conference attended by our CMO Dr. Sarah. This ‘immortality’ molecule is the new star of anti-aging and longevity medicine due to its critical role in energy production, metabolism, DNA repair, and overall cellular health. As we age, NAD+ levels decline, leading to age-related diseases, dull wrinkled skin and a slower metabolism. Research has shown that enhancing NAD+ levels can activate sirtuins, a family of proteins that promote cellular repair, improve mitochondrial function, regulate inflammation, and boost metabolism, all of which are vital for healthy aging. State of the art medical studies are proving that boosting NAD+ levels can extend lifespan and improve health-span, suggesting that maintaining optimal NAD+ levels is a key strategy for promoting longevity and anti-aging. Whenever a ‘new’ anti-aging therapy is uncovered the wellness world inevitably responds with a plethora of pills, lotions, potions and infusions, all promising to be the best option to reap the benefits of this discovery. While it’s wonderful to have options, this can create confusion for patients when it comes to choosing the best way to support their health goals. This article is for my patient G; hopefully it provides some much needed clarity on which NAD+ is best for you.
Intravenous NAD+
One of the main issues with NAD+ IV therapy is the size of the NAD+ molecule. NAD+ is too large to effectively penetrate cell membranes, which limits it’s ability to be utilized directly by cells when delivered in high doses via the blood stream. Scientific evidence suggests that while intravenous infusions raise the concentration of NAD+ in the blood, they are largely inefficient at increasing intracellular NAD+ levels due to the molecule’s size and charge. The body has a maximum threshold for NAD+ absorption, and exceeding this limits via IV infusion can result in excess NAD+ being filtered out by the kidneys and excreted. This not only wastes the substance but also increases the risk of side effects such as flushing, discomfort, and other adverse reactions. Additionally, the unnatural extracellular levels of NAD+ created by IV infusions can trigger inflammatory immune responses, specifically an increase in CD38, an enzyme that consumes NAD+. While physiological doses of NAD+ and oral NAD+ precoursers typically reduce inflammation, the high extracellular NAD+ levels delivered via IV can shift NAD+ metabolism towards activating this CD38 pathway, leading to increased inflammation and reducing the beneficial effects of NAD+ boosting.
While NAD infusions may be trendy, leading anti-aging professionals and functional medicine specialists recommend using smaller intramuscular doses, or oral precursors, such as Nicotinamide Mononucleotide (NMN) or Nicotinamide Riboside (NR), which can be more efficiently absorbed and converted into NAD+ within the cells;
Oral + Injectable NAD+
There is definitely a use case for subcutaneous NAD+ injections; when slightly greater than physiological doses of NAD+ are administered via injection, it allows from more immediate utilization by the body’s cells. This method also enables more precise dosing tailored to individual needs and reflects what the body is naturally capable of making & absorbing. Our NP at Replete offers NAD+ injections in small doses that do not overwhelm the body, leading to increased energy, metabolic and anti-aging benefits. These injections can definitely be helpful to boost levels initially in your treatment plan, but they are also expensive and painful, so longevity experts generally agree that utilizing smaller precursors such as NR or NMN is a more effective way to elevate intracellular NAD+ levels longterm;
While NAD+ itself is generally not well-absorbed directly through the digestive system, its precursor molecules like Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR) are efficiently absorbed orally and then converted into NAD+ within the body’s cells. NMN and NR oral supplements are both effective at increasing NAD+ levels, but they do differ slightly when it comes to their absorption and utilization.
Nicotinamide Mononucleotide (NMN)
NMN is a nucleotide that converts directly to NAD+ in one metabolic step. It is efficiently absorbed in the small intestine through the Slc12a8 transporter, enhancing its bioavailability. NMN is found in trace amounts in various foods such as broccoli, avocados, and edamame but is best administered in supplement form. Research indicates that NMN effectively raises NAD+ levels in multiple tissues, including the muscles, heart, brain, kidneys, and blood vessels. Some of the proven benefits of NMN supplementation include:
- Improved Insulin Sensitivity: NMN has been shown to enhance insulin sensitivity, which can be pivotal in managing metabolic health and weight loss.
- Enhanced Endurance and Vascular Health: Studies suggest that NMN supplementation may improve exercise endurance and support vascular function.
- Support Against Age-Related Weight Gain: NMN has demonstrated potential in suppressing age-associated weight gain and enhancing energy metabolism.
- Eye Function Improvement
- Location of effect: NMN has broad tissue impact and supports multiple locations in the body.
Nicotinamide Riboside (NR)
Nicotinamide Riboside (NR) is another NAD+ precursor and a form of vitamin B3. Unlike NMN, NR must first convert to NMN before becoming NAD+, which requires an additional metabolic step. NR supplementation has been widely studied, demonstrating health benefits in the liver and blood. NR is phosphorylated by an enzyme called NR kinase (NRK) to form NMN, which then converts to NAD+. This pathway primarily affects NAD+ levels in the liver, with limited impact on other tissues like the brain and muscles. Research-backed benefits of NMN supplementation include:
- Boosting NAD+ Levels: NR effectively raises NAD+ levels, specifically in the liver
- NR is linked to improved mitochondrial function.
- NR has more extensive published human studies due to its earlier discovery and lower production cost. However, NMN research is rapidly expanding, with increasing evidence supporting its benefits.
- NR effects are mostly limited to liver; this precursor has less systemic impacts, but can be the best option for patients who are specifically interested in liver regenerative and cholesterol lowering effects of NAD+.
- One study showed that NR could actually decrease exercise performance in rats. Interestingly the NR group showed a significant loss in physical performance of 35%. Further research in humans is required to resolve contradictory information but this one study is enough to encourage use of NMN over NR if a patient is specifically looking for exercise performance or metabolic effects.
NMN vs. NR
Bottom line – both NMN and NR are effective in raising NAD+ levels; however, NMN’s direct pathway allows for a multi-organ impact, making it potentially more effective for systemic longevity. In contrast, NR’s effects are more concentrated in the liver making it a better choice for lowering cholesterol levels. While NMN is our go-to for most patients due to it’s broader impact on the body, (in this economy!!) we also have to take pricing into account, and NR is still well-studied and cost-effective option for boosting NAD+.
References:
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9512238/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7238909/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8444956/
This information is not intended as a substitute for the advice provided by your Naturopathic doctor or primary care physician. Do not use the information in this document for diagnosing or treating a health problem or disease. Always speak with your Naturopathic doctor before taking any medication or nutritional or herbal or using any treatment for a health problem. If you have or suspect that you have a medical problem, contact your health care provider promptly. Do not disregard professional medical advice or delay in seeking professional advice because of something you have read online.
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