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What is NAD+? The Overlooked, Crucial Molecule That Increases Energy, Lifespan, & Performance
The body is so unimaginably complex that you can go your entire life without ever hearing about some of its most important processes. While we talk a lot about glucose, insulin, and ATP; energy metabolism alone is infinitely more nuanced and mysterious than most of us recognize. And we’re still discovering new things about it all the time!
The end result is that countless articles, videos, and influencers miss out on some of the most important factors that can influence our health. NAD+ is just such an example.
The closest thing we have to an “elixir of youth.”
What is NAD+, you ask? This is a molecule that’s absolutely essential to energy production, sleep regulation, and DNA health. There are ways to raise and lower NAD+; and an increasing amount of evidence suggests that doing so could help us live longer, build more muscle, lose fat, and increase energy. In fact, some people believe that supplements like NMN, that elevate levels of NAD+, could be the closest thing we have to an “elixir of youth.”
So, what exactly is this molecule? Should you care? And how do you get more of it?
See also: Surprising Creatine Benefits: How it Improves Energy, IQ, Healing, DNA Function, Aging, & More!
What is NAD+? How Does it Work?
So, just what is NAD+?
NAD+, or nicotinamide adenine dinucleotide, is a coenzyme and cofactor that exists in all human cells and plays a hugely important role in cellular metabolism. Similarly to oxygen, it drives a number of critical reactions, and we simply cannot survive without NAD+.
NAD+ aids with the conversion of food to energy, it maintains healthy mitochondrial function, and maintains the integrity of DNA.
What is NAD+ used for, specifically? NAD+ is responsible for aiding with the transfer of electrons between cellular molecules. It plays a role in many important metabolic reactions that involve electron exchanges. These reactions are, among other things, required for producing ATP (adenosine triphosphate), the energy currency of life, produced by the mitochondria. This is achieved through NADH, which is actually made from NAD+, and used during glycolysis and the Krebs cycle.
The subsequent electron transport chain uses NAD+ directly, producing H+ along with additional electrons. That H+ is used as a kind of “pump” working alongside the mitochondria. Finally, the leftover H+ is combined with oxygen to form water.
All three stages of respiration provide us with more ATP.
In this way, more NAD+ means more energy. Thus, many people taking NAD+ boosting supplements (like NMN), report feeling energized and overcoming fatigue.
But there’s a lot more that NAD+ can do for you!
NAD+, Sirtuins, and Longevity
Sirtuins also rely on NAD+ (study). Sirtuins are proteins that regulate the cells and are hugely important for our longevity and energy metabolism. There are actually seven types of sirtuins, three in the mitochondria, three in the nucleus of the cell (where the DNA is housed), and one in the cytoplasm. These are lovingly named SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and Bill… okay, SIRT7…
While these various sirtuins all have multiple functions, their biggest job is removing acetyl groups from other proteins (a process called deacetylation). Acetyl groups control reactions, too. These act like “tags” that prep those proteins for action.
A prominent example of this, is histone. Histone is a protein that chromatin (a form of condensed DNA) can wrap itself around to protect itself (ceasing transcription). However, histone can’t be used this way until the sirtuin has removed the its acetyl group – marking it ready to go.
More Roles for Sirtuins
There are countless more examples, but a large number are heavily involved in DNA repair and maintenance. For example, SIRT6 is a chromatin-associated protein that is used for base excision repair and double-strand break repair.
Then there are PARPs, proteins found in the nuclei which are also important for DNA maintenance – specifically, the repair of single-strand DNA breaks (SSBs).
See also: DNA Analysis Can Help You Optimize Training and Nutrition: My Experience With SelfDecode
But the key thing to understand here is that neither sirtuins NOR PARPS can do any of their jobs without NAD+. For these reasons, increasing NAD+ can improve DNA health and might therefore be an effective way to combat the deleterious effects of aging. Particularly interesting, is the role of SIRT6 in maintaining telomere length (study). These are the “buffers” at the ends of our DNA strands, which otherwise wear down over time causing a loss of information and many age-related conditions. Longer telomeres = longer life.
Indeed, a number of studies have found that supplements such as NMN, which raises NAD+, can promote longevity in animal studies (study). Overexpression of NAD+ biosynthesis genes (NPT1 and PNC1) can extend lifespan by more than 50%… in yeast. This has led many individuals to follow in kind, despite the lack of human trials.
Other roles for sirtuins include the reduction of inflammation, and formation of new mitochondria.
Through these many different roles, it seems that NAD+ has the potential to confer a wide range of benefits. From increased muscle mass (study), to weight loss (study), and more.
How NAD+ Levels Rise and Fall
Levels of NAD+ rise and fall throughout the day in response to numerous factors. Exercise, food intake, and even the time of day can have a big impact. In fact, we now think that NAD+ plays an important role in maintaining our body clock and managing our circadian rhythms.
Prominent advocate for researching and elevating NAD+, Dr. David Sinclair, suggests that this could contribute to experiences of jetlag. He explains anecdotally, that taking an NAD+ booster helps him to cope when travelling to Australia for work (in this interview). I have personally had similar experiences: of everything I have ever tried, NAD+ has been by far the best tool for combating sleep deprivation when my daughter has kept me up all night! We have seen studies that demonstrate this effect in mice (study).
We know that “energetic stress” can increase NAD+ production. Such stimuli include exercise, heat exposure (e.g. sauna), cold exposure (study), calorie restriction, and fasting. This may, in fact, be one of the principle ways in which these activities achieve their well-established longevity-promoting benefits.
We know that “energetic stress” can increase NAD+ production.
How NAD+ Falls With Age
The problem, though, is that NAD+ levels fall as we age. In fact, by the time you are middle-aged, your NAD+ levels will have fallen to half the levels they were at during your youth (reference). We aren’t entirely sure what causes this change, but it’s believed to be the result of oxidative stress and DNA damage. Seeing as lowering NAD+ is also a cause for these things, this relationship creates a destructive cycle.
The logical conclusion, then, is that by elevating NAD+ as we age, we might be able to recapture some of our youthful vigor and combat age-related decline. Is it that simple? How do you go about it?
What is NAD+ increased by?
How to Elevate NAD+ (And Should You?)
It seems that tweaking just this one pathway has the ability to help us live longer, gain more energy, fight sleep deprivation, and build muscle. How can one molecule have such a huge list of benefits? What is NAD+’s secret?
Dr. Sinclair explains that this is simply to do with the fundamental nature of NAD+. He explains that, like ATP and amino acids, NAD+ was likely one of the very first building blocks of life, billions of years ago. It should be no surprise, then, that altering those levels can have such wide-reaching effects.
Seeing as fasting, exercising with HIIT, and calorie restriction can all help to increase NAD+ levels, it follows that this should be an effective tool for combating aging and boosting energy. Indeed, a lot of evidence (anecdotal and research-based) suggest this is the case (study). In terms of the best form of exercise, it follows that high intensity training would be the most effective at incurring that “energetic stress” and thus slowing the effects of aging. This is an area currently being researched (study).
NAD+ was likely one of the very first building blocks of life, billions of years ago.
Increasing NAD+ in these ways can be considered safe, natural, and highly beneficial. Exercise incurs a great deal of additional benefits, of course, so there is little reason not to try this “anti-aging” strategy.
Supplementing With NR and NMN
Those looking to go further could consider supplementing with either NMN or NR. NAD+ is too large a molecule to be effective when consumed directly. Instead, we could aim to increase precursors like Nicotinamide Riboside (NR), nictonic acid (vitamin B3), nicotinamide, niacin, and tryptophan – these being substances that the body uses to synthesize its own NAD+. Studies show that supplementing with NR specifically, can increase NAD levels (study). Also popular is NMN (nicotinamide mononucleotide) which has an additional phosphate group. This makes NMN a larger molecule than NR and some scientists previously believed NMN to be too large to cross the cellular membrane, and there is very little human data. Nor is NMN officially recognized as safe. However, more recent research appears to support the effectiveness of NMN in raising NAD+ levels (study).
This same study also found NMN to be safe over a ten week period. NMN also has other effects. It also increased insulin sensitivity in muscle for prediabetic women, potentially making it a useful tool for combating diabetes and even building muscle. The study also found increased mTOR production in the muscles, although there was no increase in muscle NAD or mitochondrial function. NMN did not increase fat-free muscle mass, which is something NR has been found to accomplish. Dr. Brad Stanfield suggests this could be a different story were NMN combined with a comprehensive strength training program.
NMN and NR – Precautions and Risks
In short, it’s not clear whether NMN or NR is more effective (or why they seem to affect the body differently). Many people are currently experimenting with both these supplements and reporting increased energy, but of course, this is anecdotal and could simply be a placebo effect.
(Also common is to supplement with resveratrol and quercetin, which can have beneficial and complementary effects.)
Long-term safety information is still limited, however it is true that NMN exists naturally in foods like broccoli, avocado, tomatoes, and milk. We likely only consume around 2mg of NMN per day, however.
There is, however, some concern that strategies such as this, could protect the growth of cancerous tumors. The logic here, is that seeing as sirtuins protect DNA, they could also protect damaged DNA, helping it to proliferate. Those without any cancerous tissue would actually be reducing cancer risk (theoretically), but unless you could be 100% sure, this would represent a risk.
Like anything, there is also such thing as “too much” NAD+. Too much NAD+ can lead to disrupted sleep, hunger, and other issues.
The other issue with NR or NMN supplementation? They’re expensive!
Conclusions: What is NAD+ Research Saying?
In conclusion then: NAD+ is really interesting. It also has the potential to improve energy, extend lifespan, and regulate sleep cycles. But this is cutting edge stuff, and it’s unclear exactly what we should do with that information.
Many people are taking a gamble on NMN, NR, and quercetin/resveratrol supplementation. I’ve experimented with this and found the effects to be noticeable and pleasing – though this says nothing of long-term efficacy, safety, etc.
Those looking for a safer, more sustainable solution, might turn to the usual recommendations of high-intensity exercise, fasting, hot and cold exposure, and a nutritious diet.
What is NAD+ research going to tell us in the years to come? Who knows! But I have a feeling this will be an important area of health and wellbeing moving forward. It’s certainly one to watch!1
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Super interesting Adam, the fountain of youth, or another “dead end”?
Thanks for this.