Human Studies Show That NAD+ Protects Your Skin
UV exposure causes cell damage, mutations, stress, inflammation, lowered immunity, and skin cancer. But replenishing NAD can protect your skin.
How Sun Exposure Damages Skin
Ensuring adequate NAD levels matters for skin care.
Sun exposure is dangerous for skin, because every ultraviolet sun ray has the potential to do harm.
Of course, your skin has been exposed to sunlight most days of your entire life. So there's a sense in which your skin is ready for the challenge of sunlight. It has built-in repair mechanisms that come into play as soon as skin damage is detected.
However, those repair mechanisms rely on NAD to work. If your body is short on NAD, the repairs might not get done. As a result, sun could cause minor harm, like freckles or reduced elasticity -- or major harm, like DNA damage.
Why would your natural NAD levels be inadequate? It could just be because you are getting older. NAD levels decline naturally with age, in all organisms.
But even if you're not that old, your skin could be competing with other parts of your body that are demanding NAD -- for example if you are fighting infection or experiencing inflammation -- and there might not be enough to go around right when you need it. Of course, the sun exposure itself, if severe, could temporarily create demand for NAD in excess of supply.
How Vitamin B3 Can Help
It has long been known that replenishing NAD could protect against skin cancer. Rodent studies in the 1990's showed the effect:
Early studies by Gensler et al in 1997 and 1999 found that topical and oral NAM prevented UV-induced immune suppression and tumor formation in mice...Several years later, a number of studies from our group were able to translate Gensler’s early murine findings to humans.
The mechanisms by which UV radiation caused skin cancer were also clear, and one of them involved a cellular "energy crisis" that prevented cellular repair:
Exposure to UV radiation (UVA and UVB wavebands) causes photo-aging of the skin and the development of skin cancers via a range of mechanisms including direct cell damage (via substitutions in DNA of pyrimidines, gene mutations and oxidative stress), the activation of local inflammatory responses, suppression of cutaneous antitumor immunity, and the creation of an “energy crisis” in skin cells which hinders effective DNA repair
Although the NAM proved to be protective, it did not lead to permanent improvements. Rather, the protection lasted during the period of NAM supplementation, and if supplementation ended, so did the protection:
The effect of NAM in reducing NMSCs was not maintained at 6-month follow-up, indicating no long-term efficacy after ceasing nicotinamide, and that NAM needs to be administered continuously to maintain its photoprotective effects.
The New England Journal of Medicine is arguably the most prestigious medical journal in the world, and in 2015 it reported that some types of skin cancer are primarily caused by exposure to UV radiation, but that Vitamin B3 is protective:
Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.
The reason the New England Journal of Medicine said that is because it was reporting a big, Phase 3 clinical human study with hundreds of participants that showed exactly that:
In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months.
They found that "Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients."
The researchers were very clear about how the skin cancers were being prevented. They said that UV radiation damages DNA, suppresses immunity, and depletes the cellular energy needed for repairs. But taking vitamin B3 enhanced NAD, which in turn prevented energy depletion, which boosted cellular energy, and that enhanced DNA repair.
UV radiation increases the risk of skin cancer by damaging DNA, suppressing cutaneous antitumor immunity, and inhibiting DNA repair by depleting cellular ATP. Nicotinamide is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+), an essential cofactor for ATP production. Nicotinamide prevents ATP depletion and glycolytic blockade induced by UV radiation, thereby boosting cellular energy and enhancing DNA repair.
It's all there, in black and white, in perhaps the most prestigious medical journal in the world.
Newer, Better NAD Precursors
But that was published almost ten years ago. When the study was conducted, nicotinamide (NAM) was state-of-the-art for B vitamins.
But since then nicotinamide riboside (NR) has become available, a better NAD precursor. You can read here why NR is a better choice than the others, but suffice it to say that NR can work in circumstances where the others can't, and avoids negative side effects that the others show at higher doses. So NR might be able to provide more protection in more circumstances.
You don't have to take my word for it. In a journal article published a few months ago, a molecular biologist who specializes in aging told plastic and reconstructive surgeons (who care a lot about skin), not only that NAD replenishment can protect skin in a number of ways, for a number of reasons, but that nicotinamide -- the form of Vitamin B3 used in the NEJM study -- declines in effectiveness with age, and that other techniques should be considered as well, including newer precursors like nicotinamide riboside:
There is also growing evidence that NAD+ decline plays a critical role in the biology of skin aging....Decreasing NAD+ levels therefore contribute to reduced DNA repair and an accumulation of DNA damage...Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in this recycling process [the process used to create NAD from nicotinamide], and it is now known that NAMPT levels decline with age in parallel with the decline of NAD+ in aged tissues. This reduction in NAD+ biosynthesis via the salvage pathway is a significant factor in older cells because, as NAD+ consumption increases concurrently with age and demands for NAD+ replenishment and recycling increase, the resulting degraded NAD+ is no longer efficiently recycled, exacerbating a situation of declining NAD+ levels.
So the NAM or "salvage" pathway for replenishing NAD may not be optimal.
Similarly, the Journal of Drugs and Dermatology noted the same week that NAD replenishment via Nicotinamide has been shown to be protective against skin cancer, but that the newer NAD precursors like NR are likely to be even more protective against skin cancer:
Research into cellular metabolism and aging suggests that NR and NMN can lead to greater increases in NAD+ vs NAM. NR and NMN are safe and well-tolerated and are consequently currently undergoing investigation as agents able to protect against age-associated disease caused by NAD+ depletion. We hypothesize that oral supplementation with NR or NMN may lead to greater reductions in KC than NAM....recent work using animal models has shown that both NR and NMN supplementation can mitigate DNA damage, improve cellular metabolic function, and reduce age-associated disease more effectively than NAM supplementation.
So should you be taking an NAD precursor if you are going to be out in the sun? You shouldn't even go out in the sun, at least not without extra-strong UV protection. But if you do go out in the sun, the science says that your skin might be protected by an NAD precursor.
NAD replenishment is no substitute for sunscreen. But they work together -- protecting your cells from both the outside and the inside.
Should you use Nicotinamide, because that's what they used in the human clinical study 10 years go? It's not a bad idea; it should help.
Or should you use a newer NAD precursor like Nicotinamide Riboside? We don't yet have a clinical study showing how well NR protects skin, and we certainly do not have a double-blind, placebo-controlled study comparing NAM and NR in this respect.
However, we do know that the NAM metabolic pathway is down-regulated under some circumstances, including age, so there is a decent chance that NR will perform better in some people or in some circumstances.
Is it worth the extra money? After all, NAM costs less, and it does seem to work.
It depends on how you like to gamble while we wait for the science to come in. The other risks of NAM that do not seem to be present for NR are described here (Is NAM the Best Way to Boost NAD?). In short, NAM's effect can be limited, and at higher doses it can have negative side effects.
I never do understand people who would spend $1,000 for a week's vacation on the beach and then refuse to spend $7 -- $1/day -- to protect themselves against the harmful effects of the sun. I don't know if they have powerful sunscreen on at all times, or if they just underestimate how much they value healthy skin until after it's too late.
I know I am in the latter category. I have too many wrinkles, and too many spots on my skin, for my age. My dermatologist tells me I should always, always, always be using sun protection. I'm sure someone told me that thirty years ago, too, but I didn't take it seriously. And back then we didn't even know about NR.
But, happily, now we do know about NR.