The Uplifted Insider

"To keep the body in good health is a duty, otherwise we shall not be able to keep our mind strong and clear." -Buddha

An Emerging Popular Supplement

At this point, you don’t even have to be a fitness or wellness fanatic to have heard someone mention NAD+. Over the past few years, it has become one of the most talked about molecules in the anti-aging, health optimization, and athletic performance industries. Countless supplement companies have popped up making bold claims about it and wellness clinics charge top dollar to drip it into people’s veins. All while researchers at major institutions such as Harvard and Stanford continue to study it.

In today’s article, I want to paint a clear picture of what NAD+ actually is, whether or not it is worthy of the hype and some observations that I made while personally trying the supplement for three months. My purpose is to bring clarity to this trendy supplement, not convince you whether or not to take it. As always, you should consult your doctor before trying any new supplement because everybody has unique health considerations. With that being said, let’s learn about it!

So What Is NAD+?

NAD+ stands for nicotinamide adenine dinucleotide. That’s unnecessary to say more than once, so NAD+ will suffice from here on out. It is a molecule that exists in every single cell in your body and it is absolutely essential to life. You would not be reading these words right now if you didn’t have it in your cells.

NAD+ plays two major roles in your body. The first and more dominant role that it fulfills is as what is called a coenzyme. Think of a coenzyme as a molecule that helps facilitate hundreds of chemical reactions inside your cells without being consumed in the process. For example, NAD+ is key to the process of converting the food you eat into usable energy, in the form of ATP. Your mitochondria, which are the energy-producing powerhouses inside your cells, depend heavily on NAD+ to do their job. So when people talk about cellular energy, mitochondrial health, and metabolic function, NAD+ is a central character.

The secondary role NAD+ plays is even more exciting and thought-provoking from a longevity standpoint. This is because NAD+ is actually consumed as a raw material by proteins called sirtuins. Sirtuins are sometimes referred to as longevity genes because they are involved in DNA repair, reducing inflammation, and supporting mitochondrial health. When your cells suffer DNA damage, which happens constantly throughout your life, sirtuins use NAD+ to facilitate the repair process. The problem, as you are about to find out, is that your body has less and less NAD+ available to fuel this process as you age.

The “Decline As We Age” Problem

This is where the “need” for this supplement is created. Research has consistently shown that NAD+ levels decline gradually as we age. Studies measuring NAD+ in human tissue have found significant reductions across decades of adult life. Skin tissue shows the most dramatic decline of around 50–60% over a lifetime, while brain tissue appears to decline somewhere in the range of 10–20%. However, there is debate about NAD+ levels in the blood, as recent studies have shown that these levels remain stable in older healthy individuals.

Why does this matter? Less NAD+ means that your mitochondria become less efficient, your cells have less capacity to repair damaged DNA, and your sirtuins essentially run low on the fuel they need to do their jobs. This age-related decline is believed to be a contributing factor to many of the things we associate with getting older: reduced energy, slower recovery, cognitive decline, and increased susceptibility to disease.

With all the aforementioned information in mind, I bet you want to ask the following question: If NAD+ levels decline as we age, can we just take more of it and reverse or slow those effects? Well, that is exactly the question researchers are spending huge amounts of time and money trying to answer. The honest conclusion right now is that it is complicated. But there is enough here to make it worth understanding.

The Research-Backed Benefits

Energy and Mitochondrial Function

The most widely seen benefit of boosting NAD+ levels, in research settings and among people who supplement with it, is improved energy. This makes biological sense since NAD+ is integral to the process of cellular energy production and replenishing its levels should theoretically help your mitochondria run more efficiently.

DNA Repair and Cellular Health

As I mentioned earlier, sirtuins depend on NAD+ to repair damaged DNA. Since DNA damage accumulates naturally throughout your life, maintaining adequate NAD+ levels is thought to support your body's ability to keep up with that repair process. The theoretical possibility of NAD+ being an “anti-aging molecule” is one of its main excitement amplifiers.

Cognitive Function

Emerging research suggests that NAD+ may play a meaningful role in brain health. Since your brain consumes roughly 20% of your body's total energy despite being only about 2% of your body mass, it is highly dependent on efficient mitochondrial function. Preliminary research has shown potential benefits for memory, processing speed, and cognitive resilience, particularly in older adults and in situations involving mental stress like sleep deprivation.

Skin Health and Cancer Prevention

Perhaps the most surprising part of all the NAD+ research involves clinical trials using the NAD+ precursor, nicotinamide (also known as niacinamide). These trials have shown that nicotinamide has remarkable skin related benefits. It works inside your body to create and boost NAD+ levels and is an amide form of Vitamin B3. Amide, in broad terms, just denotes that it is a nitrogen-containing molecule.

The 2015 Phase 3 ONTRAC Trial took 386 high-risk patients (those that have had two non-melanoma skin cancers in the past five years) and gave them 500 mg of nicotinamide twice daily for twelve months. The nicotinamide group saw a 23% lower rate of new non-melanoma skin cancers (basal-cell and squamous-cell carcinomas) compared to the placebo group during the intervention period. Additionally, participants taking nicotinamide also experienced a statistically significant reduction in actinic keratoses (precancerous skin growths) at 3, 6, 9, and 12 months.

The 2025 Veterans Affairs Cohort Study analyzed data from over 33,000 veteran patients who took 500 mg of nicotinamide twice daily. Due to occupational sun exposure, veterans experience a roughly 70% higher risk of skin cancer than the general public. This massive study found an overall 14% reduced risk of developing new skin cancer. Furthermore, patients who started taking the supplement after their first skin cancer saw a 54% reduction in the rate of new occurrences. The protective effect was most pronounced against cutaneous squamous cell carcinoma (cSCC), the second most common type of skin cancer. These findings validate the thought that nicotinamide, a direct precursor to NAD+, can reduce the risk of skin cancer.

Given that skin tissue experiences the greatest age-related decline in NAD+ of any tissue in the body, this association might be more than just a coincidence. Additional research is needed, but this is an evolving topic worth keeping an eye on. Again, the two studies cited above were done using nicotinamide, which is a precursor to NAD+ but is not NAD+. Nicotinamide is inexpensive and has high oral bioavailability.

Which Form Should You Take?

If you decide to explore NAD+ supplementation, this is what you need to know about the different forms available:

You cannot take NAD+ orally as a pill and expect it to do anything for you. NAD+ is a large molecule and is very poorly absorbed by the digestive tract.

So what are the remaining options? Well, you can take what are called precursors, which are smaller molecules that your body can absorb and convert into NAD+. The previously discussed nicotinamide is a precursor but is not that efficient at raising NAD+ levels.

The two top precursors are NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide).

1) NR (nicotinamide riboside)- This precursor enters cells directly without any additional conversion steps, making it highly bioavailable. It has more published human clinical trials behind it than NMN and a strong safety record. Most importantly, it has been shown to reliably raise NAD+ levels in the blood.

2) NMN (nicotinamide mononucleotide)- Chemically, NMN is one step closer to NAD+ than NR. However, because NMN carries a charge, it must often convert into NR to cross cell membranes, whereas NR utilizes direct pathways into the cell. Despite this, Dr. Sinclair's research at Harvard has shown that NMN can significantly increase NAD+ levels when taken orally and more strong support for NMN’s ability to efficiently increase NAD+ levels has continually emerged.

The scientific consensus right now is that both NMN and NR raise NAD+ levels and both appear safe. Furthermore, at equivalent doses they both produce similar results, though NR may be slightly more efficient per milligram. Also, if NMN gives you digestive issues, NR might be a better alternative.

For dosing, most research and clinical use points to 300 to 500 milligrams per day of NR or 500 to 1,000 milligrams per day of NMN as reasonable starting ranges for general wellness. As always, consult your physician before starting any new supplement, particularly if you have existing health conditions.

Let me say this again: Avoid pills labeled NAD+ because the NAD+ molecule is too large and fragile to survive stomach acid or pass through cell membranes intact when taken orally. So direct NAD+ pills are an extremely inefficient way to raise NAD+ levels in your body. Efficient cellular delivery of NAD+ must bypass digestion. That being said, there are ways to get NAD+ directly into your body.

The three most common ways to get NAD+ directly into your system are:

1) NAD+ IV Infusions- These do raise blood levels of NAD+ significantly and achieve near 100% bioavailability but this option will be expensive, with sessions costing at least a few hundred dollars each. Besides the cost, there are three more negatives about NAD+ IV infusions that you should be aware of. First, some individuals report that they are quite uncomfortable during the administration of the IV infusion. This is most likely due to the fact that NAD+ stimulates cellular energy (ATP) production and widens blood vessels, so rapid administration can cause symptoms such as nausea, stomach cramping, chest pressure, headaches, and flushing.

Second, despite near 100% bioavailability into the bloodstream, NAD+ still faces the obstacle of getting into your cells. There is an enzyme called CD38 that sits on the surface of cells and will break down extracellular NAD+. This enzyme accounts for over 90% of NAD+ degradation in the body. While IV infusions do flood the blood with massive concentrations of NAD+, it is still unclear how much NAD+ actually gets into the cell, as intracellular NAD+ levels are very difficult to measure.

Lastly, it is important to note that there is no clinically proven advantage that NAD+ infusions have over the cheaper and easier to use oral PRECURSORS for the average healthy person. 

2) NAD+ Subcutaneous Injections- These injections bypass the digestive tract and are injected directly into fat tissue (usually in the abdomen or thigh) for slower, more sustained absorption. Fat tissue has a smaller network of blood vessels compared to muscle or veins. This allows the NAD+ to be absorbed more gradually into the bloodstream over the course of hours. However, this method runs into the same obstacles as IV infusions do when getting NAD+ into the cell, such as enzyme CD38.

3) Liposomal NAD+- There is one more form of NAD+ supplementation worth discussing, and it is one that I have personally used. I’m referring to liposomal NAD+ which allows you to take actual NAD+, not a precursor, orally in liquid form. The challenge with oral administration of NAD+ has always been that NAD+ is a large molecule that breaks down quickly in the digestive tract before it can reach your cells. Liposomal technology addresses that problem by wrapping the NAD+ inside tiny phospholipid spheres, which are essentially the same material that makes up your cell membranes. These microscopic protective bubbles shield the NAD+ from digestive breakdown and help carry it into the bloodstream intact.

Despite this sounding amazing in theory, there is a definite lack of scientific evidence supporting this fairly new breakthrough. Liposomal NAD+ also encounters the same cellular barriers as the IV infusions and injections when trying to get into the cell. This delivery system does show genuine promise though. However, more clinical evidence is needed to support the marketing “data” given by supplement companies selling liposomal NAD+.

My Experience With NAD+

For three months this year, from January 1st through the end of March, I decided to give liposomal NAD+ a solid try. My goal was to cut back on caffeine during the darkest, coldest months in Central New York and the hope was that switching it out with NAD+ would help me achieve that goal. So every morning I mixed my Rho (the brand I used) liposomal NAD+, with water and drank that instead of brewing coffee.

I thought NAD+ might help a little, but to my surprise it actually helped quite a bit. Now, my experience is purely anecdotal, but I hardly felt the need for caffeine at all. Maybe it was partially a placebo effect, maybe it wasn’t. The truth is, I only felt the need to have about five caffeine drinks per month during that three-month period. Contrast this to at least one every day before the new year and after my experiment was complete. I would also say that those deep winter months are the ones where the need for extra energy is at a yearly highpoint.

Again, anecdotal evidence, but liposomal NAD+ seemed to definitely improve my daily energy levels.

My Final Thoughts

Liposomal technology is very appealing because you simply have to mix the NAD+ with water and drink it. Easy Peasy! Shielding NAD+ so that it can get to the cell intact sounds great on paper but there is still a major lack of human clinical trials verifying its efficacy. With that being said, NAD+ is a genuinely fascinating molecule and the science surrounding it is evolving rapidly. It is one of the most important molecules in your body and its decline with age is reality. Whether supplementing with it meaningfully reverses that decline is still to be determined. But the emerging research is promising enough to warrant a keen eye.

There is legitimate reason to believe that supporting your NAD+ levels through supplementation may improve your energy, support cellular repair, and potentially offer some meaningful health benefits. Whether it can extend your life with long-term supplementation is still an unanswered question.

What is not a question is the importance of training consistently, eating well, sleeping enough, and managing your stress. Those are the things that will move the needle most dramatically on your health and longevity. If you have those locked in and you want to explore NAD+ supplementation on top of that foundation, the risk is low and the potential upside is fairly high.

While liposomal, subcutaneous injection and IV infusion delivery methods aim to bypass the digestive system to increase bioavailability, clinical consensus on the long-term efficacy and superiority of one method over another for general health is still evolving. So due to the plethora of clinical evidence backing up the efficiency of the precursors NR and NMN to synthesize NAD+ and the lack of such evidence to support the efficacy of direct NAD+ delivery, added to the ease and inexpensiveness of consumption, I would have to say that the wisest choice for NAD+ supplementation would be to use NR or NMN. 

However, I had good results with Rho Liposomal NAD+ and others I know have had success with IVs and injections. That is my experience but don’t just take my word for it. Do some further research on your own if this supplement interests you. My hope is that I gave you a good introduction to NAD+. Regardless of whether you decide to take it or not, be aware that supplementing with NAD+ precursors or using direct delivery methods of NAD+ involves complex biological pathways and every individual is unique. Therefore, it is essential to consult with a healthcare professional to discuss its safety, potential interactions with other medications, and whether it is appropriate for you.

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