NAD+ Is Taking Over Skincare—But the Current Science Backs Niacinamide

NAD+ is having a moment. It's in supplements promising to slow aging and, increasingly, in skincare promising to turn back the clock on your skin. But the science behind NAD+ and its precursors like NMN and NR is more nuanced, especially in skincare. Here, we explain what these molecules are, what they do, and why niacinamide is the ingredient we chose to include in our topical products so far.

What is NAD, NAD+, and NADH?

NAD is a coenzyme that sits at the center of how your cells make and use energy. It exists in two interchangeable forms: an oxidized form, NAD+, which accepts electrons, and a reduced form, NADH, which it becomes after picking up a hydride (an electron). This NAD+ ⇆ NADH cycle is fundamental to producing ATP, the energy currency of the cell.¹

NAD+ is also an essential cofactor for a group of "NAD+-consuming" enzymes—sirtuins, CD38, and the PARPs—that govern DNA repair, gene regulation, cellular senescence, and immune function.^1,2

NAD's Precursors: What are NAM, NR, and NMN?

Your body builds NAD from other materials called precursors. The most important ones are all forms or relatives of vitamin B3.³

The main pathway, called the "salvage route", runs roughly: NAM → NMN → NAD⁺, with NR entering by being converted into NMN. Nicotinic acid (NA) takes a separate route to NAD⁺, the Preiss–Handler pathway.

• NAM (nicotinamide, also called niacinamide) — the amide form of vitamin B3.
• NR (nicotinamide riboside) — an NAD+ intermediate that gets converted into NMN. This is one of the two big oral-supplement ingredients.
• NMN (nicotinamide mononucleotide) — another NAD+ intermediate. It sits one enzymatic step from NAD⁺, making it the most downstream precursor.
• NA (nicotinic acid, or niacin) — the original B3 form, effective but prone to causing skin flushing and GI side effects at high doses.⁴

These precursors are ordinary dietary micronutrients, found in foods like meat, liver, fish, yeast, legumes, nuts, grains, leafy greens, coffee, and tea,⁵ as well as cucumber, cabbage, soybeans, broccoli, avocado, and tomato.³ Inside the cell, enzymes convert them into NAD+ through dedicated biosynthetic routes—the salvage pathway, the Preiss–Handler pathway, and the de novo pathway from tryptophan.^3,4

What does NAD do in the body?

NAD+ is a central metabolic hub. As a coenzyme, it drives the redox reactions that turn food into ATP (cellular energy) through glycolysis and oxidative phosphorylation.^1,3 As a co-substrate, it fuels enzymes that maintain genomic stability through DNA repair, regulate gene expression and epigenetics, control inflammation, and manage cellular senescence—many of the processes now recognized as "hallmarks of aging".^1,2,6 Because its roles are so wide-ranging across multiple tissues in the body, NAD+ levels are tightly regulated by a balance of producing and consuming processes.³

Does NAD decline with age?

Yes and no. While much of the recent longevity marketing buzz around NAD+ rests on the assumption that NAD+ levels decrease with age, the scientific evidence is mixed.

The widely repeated claim is that NAD+ declines with age and that this decline drives age-related disease. Several reviews support a version of this: NAD+ depletion is described as "a fundamental feature of aging," detected across neurodegenerative disease, cardiovascular disease, and muscle atrophy, with decrements reported in various tissues during aging.⁶ The proposed mechanism is that NAD+-consuming enzymes ramp up while the replenishing enzyme NAMPT falls with age,² since tissue NAD+ decline has been linked to aging-associated conditions in model organisms and humans.¹ There is even some direct human evidence: intracellular NAD+ has been reported to decline with age in the human brain, and NAD+ negatively correlates with age in post-pubescent males and females.⁶

But there is some nuance. A systematic review across yeast, worms, rats, mice, monkeys, and humans concluded that the evidence for a universal, progressive, whole-body NAD+ decline is "very limited and often restricted to a single tissue or cell type." Some tissues actually show NAD+ increasing with age. Reliable decline appears mainly in skeletal muscle, some fat tissue, and certain brain regions, therefore the "universal decline" narrative is misleading.³

In fact, in a study of 299 healthy adults aged 18–70, blood NAD+ stayed stable across age. Notably, the same study found that muscle NAD+ did decline with age while blood stayed flat—so the decline is tissue-specific, and a drop in circulating NAD+ may signal chronic disease rather than normal aging.⁷ A 2026 peer-reviewed analysis went further, measuring NAD+ across seven independent human cohorts: whole-blood NAD+ stayed remarkably stable with age and across lifestyle interventions—while still rising, as expected, with NR supplementation—leading the authors to question the value of blood NAD+ as a biomarker of aging at all.⁸

For skin specifically, the human data is thin but suggestive: the earliest human evidence came from skin samples, where NAD+ correlated negatively with age, dropping substantially from young adulthood into middle age—though the study did not prove further decline into old age, and it was a small, cross-sectional study.³

In summary, there is solid evidence that NAD+ declines with age in specific tissues—skeletal muscle, parts of the brain (including, by limited human evidence, the human brain and skin), and some fat tissues^1,3,6,9—but credible critics argue the universal, body-wide, progressive decline often implied by the longevity industry is not well supported, and circulating blood NAD+ appears stable in healthy people.^3,7,8

What's the buzz around NAD in supplements?

Restoring NAD+ with the precursors NR and NMN has emerged as a popular longevity tool. While studies show that oral NR and NMN is well tolerated and raises NAD+ blood levels, the resulting health outcomes are less proven.^{1,6,10,11,12,13,14}

So the open question is not whether oral NR/NMN raise NAD+ (they do), but whether that reliably translates into meaningful clinical benefits in healthy people. Recent peer-reviewed meta-analyses point to limited outcomes and show potential harm in higher doses. Pooling eight RCTs in 342 mostly non-diabetic middle-aged and older adults (NMN at 250–2000 mg/day for 2–12 weeks), oral NMN showed no significant benefit on fasting glucose, fasting insulin, HbA1c, insulin resistance (HOMA-IR), or lipid profile.¹⁵ A separate meta-analysis of NMN and NR trials in adults over 60 likewise found they did not significantly improve muscle mass, handgrip strength, or walking speed.¹⁶ The clearest positive human result is relatively narrow: a 10-week RCT found NMN improved muscle insulin sensitivity—but in postmenopausal women with prediabetes who were overweight or obese, an at-risk group rather than the general population.¹⁷ The strongest disease-modifying results otherwise remain largely preclinical (rodent), and long-term human outcomes are still being established.^10,13 There are also dose-dependent metabolic risks. In human data, NAD-boosting via niacin raised blood glucose and insulin resistance above ~500 mg/day, with large person-to-person variation.⁷ And in mice on a mildly obesogenic diet, a high dose of NR specifically induced glucose intolerance, aggravated insulin resistance, and triggered white adipose tissue dysfunction—indicating that "more is better" does not hold for these precursors.¹⁸ There's also a theoretical cancer concern, since NAD+-depleting drugs are being developed as cancer therapies and SIRT1 can be either pro- or anti-cancer depending on context.¹⁰ And some argue that flooding the body with precursors ignores the root causes of NAD+ decline—rising consumption and falling recycling—so precursors alone may not be a durable fix.²

What's the buzz around NAD in skincare?

Supporting the skin's NAD+ system is thought to bolster cellular energy, DNA repair, antioxidant defense, and resistance to the senescence and inflammation that drive visible aging.^2,5,19

The catch is how you raise NAD+ levels. Even if it can stay stable in a skincare formulation, applying NAD+ topically to skin is unlikely to work due to its size—therefore the more effective approach is to provide skin with smaller NAD+ intermediates so cells can build NAD+ internally rather than importing the whole molecule.²⁰ That's why most human skincare studies center on precursors like niacinamide, which is highly stable and easily absorbed.

Researchers are actively experimenting with NAD+. Some have tried to make exogenous NAD+ work on skin by pairing it with helper compounds (quercetin and enoxolone) that inhibit the NAD+-consuming enzyme CD38, showing protection against UV and intrinsic aging in lab-grown human fibroblasts—though the authors note NAD+'s pharmacological activity on skin "has not been elucidated."²¹ Others have shown that NMN, formulated in a yeast-fermented filtrate, can permeate an artificial skin membrane down to the papillary dermis and boost collagen production in fibroblasts.²⁰ These are genuinely promising laboratory signals, but they have not been proven on real humans and the benefits therefore remain speculative.

Why we use niacinamide

We use niacinamide in products like OS-01 FACE MOISTURIZER, OS-01 BODY MOISTURIZER, and OS-01 EYE CREAM for three practical reasons.

1. NAD+ itself is unstable, and so are some of its precursors. Trying to deliver pure, ready-made NAD+ is impractical: NAD+ restoration using pure exogenous NAD+ "is often not practical due to its unstable nature and poor bioavailability to most cell types," which is exactly why the field works with precursors that cells can convert internally instead.² When it comes to NAD precursors, NR is "a rather reactive molecule," "often unstable during manufacture, transport, and storage," to the point that commercial samples have shown degradation and researchers have engineered stabilized versions to compensate.¹⁴ NR and NMN are also "polar and charged," with notoriously challenging bioavailability.⁴ Niacinamide sidesteps much of this—it's a small, chemically stable B3 ingredient that the body readily uses and that humans must obtain from the diet.^5,19,22

2. Niacinamide has a far deeper human clinical track record for skin. Topical niacinamide has a long-standing record of human clinical trials. A 12-week, double-blind, placebo-controlled, split-face trial in 50 women found 5% niacinamide was well tolerated and significantly improved fine lines and wrinkles, hyperpigmentation spots, skin texture, red blotchiness, and yellowing.²³ Topical niacinamide also improves the skin barrier—raising stratum corneum hydration and reducing water loss—and reduces senescence-associated (SASP) gene expression.⁵ Broader reviews compile consistent topical benefits across aging and pigmentation, noting niacinamide is well tolerated by skin,¹⁹ and it reduces pigmentation by blocking melanosome transfer²⁴ and blunts UV- and pollution-induced inflammation.²⁵

By contrast, published human evidence for topical NMN is thin. The encouraging NMN skin data so far come from lab models—reducing melanin in aged melanocytes and reconstructed skin, and permeating an artificial membrane while boosting collagen in cultured fibroblasts^20,26—and the bulk of NR/NMN human research concerns oral supplementation and circulating NAD+, not the skin.^4,11,12 Importantly, this is a gap in the published record, not a head-to-head loss: NMN hasn't been shown to underperform on skin so much as it hasn't yet been tested in published human skin trials. The early signals are positive, and it remains a candidate we continue to study.

3. Permeation and molecular size. Skin is a deliberate barrier, and there's a well-established rule of thumb in dermatology—the "500 Dalton rule"—that a molecule's weight generally must be under about 500 Daltons to be absorbed through the stratum corneum; larger molecules have more trouble crossing it without very favorable chemical properties.²⁷ Beyond being unstable, NAD+ can't simply be absorbed and used—cells import smaller intermediates and rebuild it inside.^2,20 Niacinamide, by contrast, is a small molecule, consistent with its long track record of penetrating skin and producing measurable clinical effects.^5,19

NMN is also a relatively small molecule and was shown to permeate an artificial skin membrane²⁰—so the reason we use niacinamide today isn't that NMN can't get into skin, but that niacinamide has the far deeper human clinical evidence, alongside its stability and practicality.

The Bottom Line

NAD+ is essential to the body's energy regulation system, and supporting it in skin is a reasonable goal. However, the generalized notion that NAD+ declines with age is not fully supported since the decline appears to be tissue-specific.^3,6,7,8 When it comes to boosting levels of NAD+ in skin, pure NAD+ is impractical to deliver topically due to stability concerns and its large size.² For topical use, NMN and NR don't yet have published human skin trials—though early lab data are promising and worth pursuing. Niacinamide, by contrast, is a stable, safe ingredient with a large body of human clinical evidence for visible skin benefits^{5,19,22,23,24,25}—which is why it's the precursor we rely on in our products today, even as we keep studying other precursors as potentially complementary options.

Sources

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