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Deep Guide to Niacinamide - How it works and why it should be a part of everyone's skincare routine

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This writeup was lead-authored by our senior technical adviser, Sunbin Song, PhD. Sunbin graduated from MIT with a degree in Biology before receiving a doctorate in neuroscience from Georgetown and becoming a research scientist at the NIH. When Sunbin isn't busy researching the brain, she loves to explore how we can best nurture our body, mind and spirit to live more joyful lives. Sunbin on Google Scholar / on ResearchGate

Hi, everyone! Welcome to our “More than Skin Deep” series. In the first two newsletters, we had discussed the benefits of vitamins, specifically Vitamins A (retinoids) and C (ascorbic acid), for maintaining youthful and healthy skin. In this newsletter, we continue our discussion of vitamins with Vitamin B3 (Niacinamide), an excellent ingredient for maintaining overall skin health.

 

What is Vitamin B3 (Niacinamide) and why does our body need it?

Let’s begin by going over a few key points:

Topical application of niacinamide increases the level of NAD and NADP (nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate) in the skin.

NAD and NADP are critical factors in cell metabolism. Without NAD and NADP cells are less able to fuel ongoing self-maintenance. Basically, lower levels of NAD and NADP make cells age and deteriorate faster.

The level of NAD and NADP naturally decline as we age, so supplementing the skin with niacinamide can increase the level of NAD and NADP to help keep the skin cells healthier and younger.

niacinamide converts to nad

There are two key members of the Vitamin B3 family. Niacinamide (also known as nicotinamide) and niacin (also known as nicotinic acid). You can ingest Vitamin B3 either in the form of Niacinamide or Niacin, and they both eventually get converted into NAD and NADP.

Vitamin B3 is so essential in fact, that without enough in your diet, you would get a gnarly skin condition called Pellagra. Pellagra is a condition where your face and body become covered in scaly sores (see below figure reproduced from Matts et al. 2002). Over time, the skin stiffens, peels and bleeds. In short, skin breaks down without Vitamin B3.

pellagra sufferer

You may be thinking- most of us do not have Pellagra nor a dietary Vitamin B deficiency, so why should we care?

As we age, Vitamin B3 and associated NAD levels in the skin start declining (Berson et al. 2014, Schultz and Sinclair 2016). Less NAD directly correlates to less healthy skin cells, which means less vibrant skin.

In fact, this aging-related NAD decline is so fundamentally natural and pervasive that it occurs in both humans and animals alike (Matts et al. 2002). Hence, the NAD decline occurs at the cellular level over time and cannot be escaped by any behavioral or lifestyle change except supplementation.

[Technically speaking: This decline in NAD due to aging can be measured and quantified. If you create cell lines cultured from mature skin and compare it to a cell line cultured from that of a young person, the cell line from mature skin will have less total NAD and NADP levels (e.g., 28% in 70yo versus 51% in 7yo Matts et al. 2002).

When treated with topical Niacinamide however, these cell lines from mature skin will be restored to higher levels of NAD and NADP intercellularly (Gehring 2004). Ultimately, we know that topical Niacinamide can be used to supplement NAD levels in aging skin (Bissett et al. 2004, Matts et al. 2009).]

 

What can niacinamide do for my skin, and how does it work?

By topical application of niacinamide, you supplement declining levels of NAD and NADP in aging skin cells. This leads to the following key benefits:

Benefit 1 – Niacinamide fortifies the skin barrier and increases its ability to retain moisture and maintain suppleness.

Benefit 2 – Niacinamide can reduce inflammation and hyperpigmentation, and even decrease the risk of melanoma.

Benefit 3 – Niacinamide can lead to smoother and less wrinkled skin by increasing the production of beneficial proteins and lipids that plump up the skin.

Benefit 4 – Niacinamide can help control oily skin and combat acne-causing bacteria. It also helps shrink pores in acne-prone skin.

Sound good? Let’s take a deeper dive into the details of each of these benefits.

 

Benefit 1 – Niacinamide fortifies the skin barrier and increases its ability to retain moisture

The stratum corneum (also referred to as “skin barrier”) is the outermost layer of the skin. It works like shrink wrap around your body -- keeping water in and microbes out.

[Side note: we’ll use “stratum corneum” and “skin barrier” interchangeably. The former being a technical name and the latter being a functional name.]

The way stratum corneum accomplishes its skin barrier function is by utilizing a “brick and mortar” structure of embedding protein in fats.

More specifically, the skin barrier is composed of “bricks” of protein-enriched corneocytes (corneocytes = dead skin cells) embedded in the “mortar” of lipid-enriched intercellular matrices made up of ceramides, free fatty acids, and cholesterol (Elias 1996). This structure works wondrously for the body in keeping water in, and pathogens out.

structure of skin

Unfortunately, as we age the “bricks and mortar” weaken and develop cracks. This is in part because NAD and NADP, which also decline with age, are cofactors in many crucial biological processes that maintain the strength of the skin barrier (including in the synthesis of fatty acids and ceramides as well as proteins like keratin). Therefore, the decline in the levels of NAD and NADP directly leads to the breaking down of the skin barrier.

The skin barrier then starts becoming leaky and makes it easy for moisture to escape. This results in dry and dull-looking skin (increase in trans-epidermal water loss (TEWL) and worsening moisture deficiency in the stratum corneum) (Gehring 2004).

The key benefit of niacinamide address the skin barrier breakdown directly. Niacinamide (by converting into NAD and NADP once absorbed into the skin) can empower regeneration of all the constituents of the skin barrier – proteins such as keratin, involcrin, and fillagrin, as well as good lipids like ceramides, cholesterol, and other free fatty acids. And when you have a good skin barrier, you can keep water in (avoid dry skin)and keep impurities out (avoid sensitivity and irritation). You’ll have better looking, better feeling skin.

 

Sub-topic 1: Niacinamide can alleviate the dryness and redness associated with rosacea.

Niacinamide has been shown to improve skin barrier function and also increase skin moisture levels in those suffering from rosacea (Draelos et al. 2005) and atopic dermatitis (Soma et al. 2005). Niacinamide’s anti-inflammatory effects also lessened reddening of the skin (Draelos et al. 2005).

Interestingly, Soma et al. 2005 showed that a moisturizer with niacinamide improved dryness in those with atopic dermatitis, while white petroleum did not. Although both were better than using nothing, niacinamide was significantly better at hydrating the skin than petroleum jelly. This suggests a lighter weight niacinamide moisturizer is superior to a heavy occlusive like white petroleum (e.g. vaseline) in terms of keeping skin hydrated. 

If you’ve been interested in trying “slugging” (coating your skin in a thin layer of petroleum jelly) to help with dry skin, you might see much better results with niacinamide-infused serums or creams.

 

Sub-topic 2: Niacinamide can alleviate winter skin dryness.

Seasonal variations may also cause damages to the skin barrier, as in the case of winter skin dryness called xerosis.

Studies show topical niacinamide increased skin hydration in those suffering from xerosis (Gehring 2004). Some formulations target winter xerosis by combining niacinamide with panthenol (Vitamin B5) and palmitoylethanolamide, and this combination is well tolerated even in those with self-perceived sensitive skin (Nisbet et al. 2019).

 

To recap, Niacinamide has been shown to boost the health of the skin barrier in a wide range of skin conditions:

- Aging or photo-aged skin

- Atopic dermatitis

- Rosacea

- Winter xerosis (dry skin in winter)

You can read more in-depth technical details in how niacinamide works to improve the skin barrier in Appendix A.

 

Benefit 2 – Niacinamide can reduce inflammation and hyperpigmentation and even decrease the risk of melanoma.

Inflammation is one of the leading causes of hyperpigmentation - so by preventing inflammation, you are also preventing hyperpigmentation.

Niacinamide, in our opinion, is one of the most studied and the best proven topical anti-inflammatory. So, if you’re suffering from acne, try using niacinamide to alleviate inflammation, which in turn helps prevent hyperpigmentation and acne marks from forming. 

Prevent inflammation -> Prevent hyperpigmentation 

how inflammation leads to hyperpigmentation

Alternatively, Vitamin C, hydroxy acids and retinoids (other "bedrock" skincare ingredients we love) aren’t as effective anti-inflammatories.  So if you’re already using these other potent ingredients, adding niacinamide to your skincare routine can boost its overall effectiveness because niacinamide adds a new dimension to the overall skincare treatment.

[Technically speaking: Niacinamide prevents cytokine-mediated induction of nitric oxide synthase, which leads to a decrease in inflammation, making it useful across multiple inflammatory conditions (Sahin et al. 2021).

Niacinamide’s anti-inflammatory effects are mediated by inhibition of NFkB-transcription of pro-inflammatory mediators, and inhibition of expression of interleukins that mediate inflammation (Wohlrahb et al. 2014).

Hyperpigmentation following inflammation from acne is a common problem for many. The P. acnes bacteria has been implicated in this inflammation by activating interleukin-8 (IL-8) secretion. Niacinamide treatment significantly decreased IL-8 production from P. acnes, as well as downstream effects, in a dose-dependent manner, preventing inflamed papules (Grange et al. 2010).]

In addition to its role as an anti-inflammatory, Niacinamide has other mechanisms with which it combats hyperpigmentation. Niacnamide inhibits melanin (melanin is the natural skin color pigment) from spreading throughout the skin. This makes niacinamide the perfect complement to other well-known anti-hyperpigmentation ingredients like Vitamin C, arbutin and kojic acid that work by inhibiting melanin production.

Niacinamide combats hyperpigmentation in both naturally aged and sun-damaged skin, as well as in melasma. However, the results fade when niacinamide usage is discontinued, so routine use of niacinamide is necessary in order to maintain its benefits.

[Technically speaking: Niacinamide prevents the transfer of melanin into keratinocytes. Many agents used to treat hyperpigmentation ( Vitamin C, arbutin, kojic acid, glycolic acid and lactic acid) decrease the activity of tyrosinase leading to less melanin synthesis. On the other hand, niacinamide does not affect tyrosinase (Hakozaki et al. 2002).

Instead, niacinamide inhibits the transfer of melanosomes full of melanin from the melanocyte to the surrounding keratinocytes. This alternative mechanism makes niacinamide a good add-on in fighting hyperpigmentation.

Clinically, this translates into decreased hyperpigmentation and overall skin lightness with niacinamide versus placebo in aging skin (Hakozaki et al. 2002). The benefits of niacinamide on hyperpigmentation has been replicated in sun-damaged skin (Kimball et al. 2009), in melasma (Navarrete-Solis et al. 2011), in axillary hyperpigmentation (Castanedo-Cazares et al. 2016), and has been shown to be dose-dependent with 5% niacinamide more effective than 2% niacinamide in reducing hyperpigmentation (Koshoffer et al. 2005).

This benefit lasts for several weeks even after niacinamide treatment was stopped. Eventually however, after a few months, the benefit faded (Koshoffer et al. 2005). This suggests that continued use of niacinamide is necessary to prevent the transfer of melanin into keratinocytes]

Yet another way in which niacinamide can help pigmentation, is the role niacinamide may play in repairing sun-damaged melanocytes (specialized skin cells that produce melanin). Healthier melanocytes lead to better modulated melanin production, which in turn leads to a more even skin tone.

[Technically speaking: Another mechanism by which niacinamide combats hyperpigmentation is the role niacinamide may play in DNA repair after UV damage in melanocytes. This role is also behind the promise of niacinamide as a chemoprevention agent for melanoma, the most serious type of skin cancer (Thompson et al. 2014).

Though preventing skin cancer may be the more important attribute of this mechanism, there is also another benefit. As DNA becomes methylated in response to UV, the methylated DNA also induces pro-inflammatory and pro-melanogenic genes. In one study, we saw that the ability of niacinamide to reduce methylated DNA also allowed it to reduce melasma based hyperpigmentation after 8 weeks compared to placebo (Campuzana et al. 2019).

In addition to its role in DNA repair, Niacinamide can help prevent skin cancer by being photoprotective and protecting against UV-induced immune suppression (Wohlrahb et al. 2014) as well as by having antioxidant properties and protecting against generation of reaction oxygen species in keratinocytes (Zhen et al. 2019).]

 

Benefit 3 – Niacinamide can lead to smoother and less wrinkled skin, by increasing the production of beneficial proteins and lipids that plump up the skin.

Aging is associated with a loss of collagen and other less well-known proteins such as keratin, filaggrin and involucrin. The loss of these proteins lead to a host of undesirable outcomes such as development of wrinkles and decreased bounciness, just to name a couple. Niacinamide can counteract these changes.

Topical application of niacinamide can increase protein synthesis of collagen. Collagen gives the skin its firmness, so increasing collagen is like strengthening a scaffold for your skin.

niacinamide fuels collagen production

Topical application of niacinamide can also lead to increased production of other beneficial proteins (keratin, filaggrin and involucrin) and lipids (ceramides, free fatty acids, and cholesterol) that make up skin barrier, which promote smoother and firmer skin that’s less prone to dryness and sensitivity.

[Technically speaking: Together, these changes in lipid and protein synthesis support a decrease in wrinkles and increased skin smoothness in aging skin. One study found significant improvement in aging skin with 2.5% Niacinamide. A later study replicated this finding with twice the amount and found 5% Niacinamide had a greater impact on skin smoothness and wrinkle depth reduction compared to 2% Niacinamide in aging skin (Gehring 2004). 

In another study in aging skin, Bisset et al, 2004 found that 5% Niacinamide not only reduced fine lines and wrinkles and improved skin texture, but also reduced skin yellowing and red blotchiness (Bissett et al. 2004). Another follow-up study showed 5% Niacinamide also improved elasticity in aging skin (Bissett et al. 2006).

But wait- there’s more! Other mechanisms beyond protein and lipid synthesis may contribute to these anti-aging effects. These include a reduction in excess dermal glycosaminoglycans (Bissett et al. 2004), and activation of autophagy processes involved in removal of damaged parts of the mitochondria in cells which affects older skin (Oblong et al. 2020).]

 

Benefit 4 – Niacinamide can help control oily skin, fight acne-causing bacteria, and shrink pore size in acne-prone skin.

Draelos et al. (2006) tested a 2% Niacinamide on Caucasian and Japanese skin and reported that it led to a significant reduction in sebum excretion rate and overall sebum levels. The reduction in sebum naturally led to significant decreases in facial shine and oiliness in addition to overall improvements in skin condition.

niacinamide controls oily skin

You might be wondering how this all works. While the exact mechanism is not known, the prevailing theory is that niacinamide alters the reservoir in the duct connecting the sebaceous gland to the skin’s surface.

Niacinamide's influence on sebum is a key reason why it's so effective in reducing blemishes in people with oily, blemish-prone skin (Santos-Caetano et al. 2019), as well as treating mild to moderate acne (Kaymak and Onder 2008).

Niacinamide has also been successfully combined with salicylic acid in treating acne. This combination leads to better skin hydration than using benzoyl peroxide and has comparable acne lesion benefits. This combination of applying niacinamide with salicylic acid is also associated with a decrease in pore size (Berson et al. 2014).

niacinamide and salicylic acid are great for treating acne

Yet another reason why Niacinamide is great for treating acne-prone skin is that Niacinamide is an anti-inflammatory that helps alleviate redness and prevents marks from forming. Niacinamide treatment significantly prevents acne-induced inflammation (by decreasing interleukin production from P. acnes) (Grange et al. 2010). In clinical studies, treatment with 4% niacinamide in acne reduced inflammatory papules (Gehring 2004).

Finally, Niacinamide keeps your skin healthier by killing harmful pathogens (bacteria, virus and fungus). Niacinamide can activate antimicrobial peptides (AMPs) like psoriasin which can kill E. coli, S. Aureas, P. aeruginosa bacteria and P. acnes – bacteria that can reside on the skin and cause sickness, inflammation, and acne (Mathaphathi et al 2017).

Niacinamide also has antiretroviral and fungistatic effects (Wohlrahb et al. 2014). One clinical trial found that 4% niacinamide gel was as effective as the antibiotic Clindamycin in reducing acne lesions and acne severity (Shalita et al. 1995).

 

OK, I’m convinced! What should I look for in a Niacinamide product?

Look for:

  • Minimum 5% concentration (but more is not necessarily better).
  • pH between 4 and 6 (we think between 5 and 6 is best)

Niacinamide is a popular skincare ingredient and has been a mainstay for many anti-aging products on the market. It is safe to use during pregnancy and is quite gentle (generally much better tolerated than Vitamin C, hydroxy acids or retinoids).

Studies have shown that the benefits of Niacinamide are greater for 5% concentrations than for 2% concentrations, so you should look for concentrations that are at least 5%. However, there is no compelling evidence that benefits are meaningfully greater at concentrations higher than 5%.

Clinical studies for irritation have been conducted for up to 10% concentration solutions and 20% concentration solutions for patch tests. These studies showed that even at 20% concentration, there is little to no irritation on skin. Therefore, you’re unlikely to experience irritation when using niacinamide (however most products in the market have niacinamide concentration well below 20%).

Look for a niacinamide solution that has a pH between 4 and 6 (we recommend between 5 and 6) because niacinamide is more stable in that pH range.

 

How do I use niacinamide?

We recommend applying niacinamide twice daily as part of both your AM and PM routines.

Since niacinamide protects against the effects of UV rays (and UV-induced photo-suppression), like Vitamin C, niacinamide can be used to help bolster your skin’s defenses during the day (Wohlrahb et al. 2014). And we all know that when it comes to keeping our skin healthy and youthful, an ounce of prevention really is worth a pound of cure.

Because niacinamide is so well tolerated and has wide-ranging benefits, you can use it round-the-clock to maximize its benefits.

In terms of layering with your other products, the general rule of going from thinnest to thickest in texture works well – serums then gels then creams. With about 60 to 90 seconds of pause between steps to give each product time to sink into the skin.

 

Can Niacinamide be used in combination with Vitamin C or Retinoids?

Yes and Yes!

Niacinamide is complementary to Vitamin C in overall skin health, however, look for these ingredients in two separate products. The reasoning behind this is because niacinamide should be formulated in the pH range of 5 to 6, while Vitamin C products are optimal at a pH range of 3 to 4.

While Niacinamide and Vitamin C work well together in a skincare routine (separately applied in layers), you don’t want a product that combines them both in a single formula. Think of it like peanut butter and jelly- they make a great combination, but you probably don’t want them mixed together in a jar.

Apply your Vitamin C serum first (Vitamin C serums tend to be lighter in texture than niacinamide serums), pat it into the skin thoroughly and let it absorb for 60 to 90 seconds, and then apply your niacinamide product on top.

With retinoids, Niacinamide can alleviate the dryness and irritation that retinoids can induce. So, not only is it possible to use niacinamide with retinoids- it’s recommended!

 

To wrap it all up:

Now that we’ve given you all of this information about niacinamide, let’s recap:

Niacinamide is an extensively studied and proven ingredient that can keep your skin smoother, firmer and better hydrated. It’s also a fantastic anti-inflammatory that can help with redness and hyperpigmentation, and it can combat acne and control oily skin as well.

Niacinamide is a very stable ingredient that has a long shelf life. It is safe to use during pregnancy as it is non-teratogenic (does not cause birth defects). It is well-tolerated even by those with sensitive skin, or by those with skin conditions like winter xerosis, rosacea, and atopic dermatitis.

Niacinamide can truly do it all, and that’s why we recommend it as a key building block in everyone’s skincare regimen.

 

Why we wrote this:

With such a vast amount of information available about skin care on the internet, it can be overwhelming trying to figure out what to believe.

Our aim was to summarize the main, validated, scientific findings on beneficial skincare ingredients in an in-depth but easy to digest manner. That way, you'll be informed about how skin care ingredients and products really work. You’ll also be empowered to filter information, enabling you to have more productive conversations with your physician.

This writeup is in not a sales pitch, but rather it’s meant to provide you with helpful information that can be verified with widely available public information. That’s why there are no mentions of any proprietary research. If you’re curious about Maelove’s niacinamide offering, you can check out our Nia 10 Calming serum.

 

Appendix A – More on how niacinamide strengthens the skin barrier

As Niacinamide boosts NADP concentration, treatment of keratinocytes in cell culture with niacinamide increased the rate of ceramide biosynthesis by 4-5 times depending on niacinamide concentration, and had similar dramatic effects on the synthesis of glucosylceramide and sphingomyelin (both are synthesized from ceramide intercellularly and packaged into vesicles before being reverted back to ceramide extracellularly) as well as the activity of the rate-limiting enzyme responsible for ceramide synthesis (Tanno et al. 2008). Free fatty acid and cholesterol synthesis also increased. In vivo, this resulted in lower TEWL with topical niacinamide (Tanno et al. 2008). The action of Niacinamide on ceramides, free fatty acids, and cholesterol, which are the three components of the lipid-rich mortar, strengthens the skin barrier and helps retain moisture.

Aging is also associated with a loss of proteins such as keratin, filaggrin and involucrin, the losses of which contribute to a reduction of moisture in the stratum corneum. Filaggrin is an antecedent for natural moisturizing factors (NMFs) that help maintain the acid mantle of the stratum corneum corneocytes, while keratin helps build epidermal cell structure and involucrin is involved in the cell envelope and structure of the stratum corneum corneocytes.

By boosting NADP levels in aging skin, it was found that protein synthesis also improved, leading to increases in the synthesis of keratin, filaggrin and involucrin (Gehring 2004). Overall, stratum corneum cells treated with Niacinamide versus vehicle have larger and more mature corneocytes, decreased inflammatory activity and increased stratum corneum thickness (Mohammed et al. 2013).

In other words, Niacinamide strengthens the protein-rich bricks and lipid-rich mortar to strengthen the skin barrier function of the stratum corneum and decreasing TEWL leading to better hydration in aged skin.

 

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