Regimen Lab Skincare Encyclopedia ?

Niacinamide

Version 1.0 (last edited 08 Aug 2020)

Ingredient Profile

Common Name: Niacinamide
INCI: Niacinamide
Source: Fish, nuts, mushrooms, and root vegetables, chemically synthesized
Niacinamide Molecule

kligman ingredient evaluation

Penetration: Excellent penetration on skin
Biochemical Mechanism: Modulates PAR-2 to inhibit melanosome transfer, increases SPT to increase ceramides, increases desquamation rate, decreases GAGs and increases NADH & NADPH to prevent glycation, influences GPCR-related lipogenesis and exfoliates follicular ostia
Level of Evidence: Level A; Good Quality

Regimen's Take

Niacinamide is known as a ‘hero ingredient’ for a reason: it has a wide range of uses in skincare and minimal drawbacks. It has been well established in controlling hyperpigmentation, but we’ve been paying attention to more recent studies on it’s role in regulating sebum production, mild exfoliation properties, and its implications in stimulating ceramide production. An important study has shown that when combined with NAG, it is seen to increase the body’s production of Hyaluronic Acid.

TLDR

  • Naturally present in the body, niacinamide serves as a “building block” for other critical components required by skin’s natural processes, such as ceramides and intrinsic antioxidants.
  • It’s a multifunction skincare ingredient with uses in: increasing hydration, barrier repair, improving fine lines, elasticity, wrinkles, pigmentation, preventing collagen loss, reducing acne, etc..
  • Some of its strongest studied benefits are associated with properties of smooth skin, including improving pigmentation, reducing rough patches, and controlling acne.

What is Niacinamide?

Niacinamide, also known as B3, is a water-soluble vitamin that readily penetrates human skin. It can be found in trace amounts in fish, nuts, mushrooms, and root vegetables. It is a precursor to the cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is a cofactor for the synthesis of fatty acids and lipids such as ceramides, which explains why Niacinamide’s topical application enhances skin barrier lipids and improves barrier function.[1]

Benefits of Niacinamide:

  • Enhances moisture barrier repair and increases skin hydration[2][3][4]
  • Improves fine lines, wrinkles, pigmented spots, texture and blotchiness comparable to Hydroquinone[5]
  • Prevents loss of collagen[6]
  • Reduces the severity of acne[7][8]
  • Improved skin wrinkles[9], yellowing, and skin elasticity[10]
  • Lowers sebum[11]
  • Pigment improvement in melasma[12]

Does it penetrate the skin?

Several studies were able to prove sufficient percutaneous penetration of topical Niacinamide in human skin.[13][14] Levels of NAD in skin cells were used as evidence of Niacinamide’s percutaneous absorption.[15]

How does it work?

Hyperpigmentation

There are several pathways that can be targeted to regulate pigmentation.

Niacinamide targets the interaction between keratinocytes and melanocytes through inhibition of melanosome transfer.

Although exact mechanisms are not yet known, Niacinamide reduced melanosome transfer by 35-68% in-vivo, possibly due to its modulating effect on protease-activated receptor-2.[16] This possible mechanism could explain the improvement in hyperpigmented spots in countless studies involving 2-5% Niacinamide. The other potential contributing factor is its ability to decrease UV-related damages and morphologic changes.[17]

Barrier repair and hydration

Intercellular lipids (Ceramides, Fatty acids, and cholesterol) are arguably one of the most, if not the most, important components of the moisture barrier.

Niacinamide can increase ceramide, glucosylceramides, sphingomyelin in vivo.

It is also able to increase Serine Palmitoyl Transferase (SPT) and SPT mRNA in cultured cells. SPT is the rate-limiting step in the production of ceramides, increasing SPT results in an increase in ceramide content. In human subjects, Niacinamide decreased Trans-epidermal Water Loss (TEWL) by 23%, accompanied by a 67% increase in Free-fatty acids and 34% increase in total ceramides.[18]

In contrast to Vitamin C, Niacinamide increased total ceramides compared to only Cer 6 and Cer 7 by Vitamin C.

In addition to the increase in intercellular lipids, Niacinamide also accelerates cornified envelope formation, contributing to increased Stratum corneum (SC) hydration. In cultured cells, Niacinamide also increases epidermal biopolymers (keratin, filaggrin, and involucrin), further contributing to the hydration effect.[19][20]

Another factor that adds to SC’s hydration is the desquamation rate; Niacinamide increases desquamation, which is correlated with increased hydration in SC.[21][22]

Anti-aging

As a precursor to NAD, Niacinamide provides a localized supply of substrate to aged cutaneous cells to restore intracellular nicotinamide coenzyme homeostasis. Thus, a 54% increase in total collagen, a 41% increase in proteins, and a 20% increase in the total number of cells were seen in a culture incubated with Niacinamide.[10:1]

It is also postulated that Niacinamide has an inhibitory effect on glycation.

Glycation is the oxidation of protein and sugars to form Amedori products, which are yellow-brown substances that accumulate with aging resulting in a yellowish skin sallowness. Since Niacinamide increases NADH and NADPH (potent antioxidants), these two could prevent protein oxidation and glycation, thereby inhibiting the skin’s yellowing. Niacinamide was also able to decrease glycosaminoglycans (GAG), which contribute to the appearance of wrinkles

(Fun fact: Increased GAG is the reason why Shar-Pei dogs have that distinct wrinkled face).[5:1]

Sebum

Sebum reduction in clinical trials is a puzzling conundrum. Results can be misleading as the mere enrollment of a subject to a sebum clinical trial can decrease the subject’s sebum levels. Nevertheless, investigators found some interesting data with Niacinamide reducing Sebum Excretion Rate and Casual Sebum levels in subjects.

Niacinamide can alter the flow of sebum to the skin’s surface by changing the connecting duct at the Follicular Ostia.

Since Niacinamide is known for its epithelialization and exfoliation ability, it could also exfoliate the ducts, so sebum flows more quickly to the surface of the skin, leading to a more even and controlled sebum excretion.[11:1]

Its lipid reducing effect on cultured cells was investigated, and investigators found that its influence on adipocytes is via G-protein-coupled receptors.[23] In another experiment on cultured cells,

Niacinamide showed a dose-dependent reduction in total sebaceous lipogenesis, resulting in decreased triglyceride fractions.[24]

Acne and inflammation

Niacinamide exhibits anti-inflammatory effects through several mechanisms:

  • PDE4 inhibitor[21:1]
  • Inhibition of cytokine release (Il-1,6,8 and TNF-α) and suppression of T-cells[25][26]
  • Inhibits chemotaxis and degranulation of immune cells[27]
  • Blockade of histamine receptors[28]
  • Suppression of lymphocyte transformation[29]
  • Inhibition of phosphodiesterase activity[30]

For these actions, it is not surprising that 4% Niacinamide was comparable to 1% Clindamycin in the treatment of inflammatory acne vulgaris due to Niacinamide’s down-regulatory effects on the afferent and efferent divisions of the humoral immune response.[21:2]

Aside from Niacinamide’s anti-inflammatory effects, it also exhibits photoprotective capability because of its ability to reduce photo-immunosuppression and photocarcinogenesis in mice.[31]

It acts as an antioxidant due to its ability to inhibit poly-adenosine diphosphate ribose polymerase (PARP).

Upon activation of PARP in case of damage, NAD+ gets depleted as a result leading to cell dysfunction. Niacinamide inhibition of PARP leads to the protection of cells from necrosis.[32]

Clinical Studies

 5% Niacinamide
In an eight-week split-face trial, 5% Niacinamide significantly lightened pigmentation compared to vehicle control.[18:1]
2.5% Niacinamide
Another in-vivo study using the back of the hand, 2.5% Niacinamide, was shown to significantly correct skin damage resulting from aging.[33]
2% Niacinamide
In another study done on 120 subjects, an SPF formulation with 2% Niacinamide significantly lightened the skin compared to a vehicle without Niacinamide.[3:1]
5% Niacinamide
 In a randomized, double-blind, split-face, placebo-controlled, clinical trial on 50 subjects, 5% Niacinamide significantly reduced fine lines and wrinkles, hyperpigmented spots, red blotchiness, skin sallowness, and improved skin elasticity.[5:2]
2% NAG + 4% Niacinamide
 2% NAG was combined with 4% Niacinamide and a greater significant difference was observed in terms of pigmentation.[34]
2% NAG + 4% Niacinamide
 10-week, double-blind, vehicle-controlled, full-face, parallel group clinical study of 101 subjects showed that a formulation with 2% NAG and 4% Niacinamide is more effective than vehicle in reducing pigmentation.[35]
4% Niacinamide
4% Niacinamide was comparable to 1% Clindamycin in the treatment of inflammatory acne vulgaris

  

Possible Side Effects

Since it increases epithelialization and keratinocyte differentiation, it can accelerate the emergence of formed acne. This means that upon Niacinamide’s usage, one can expect the occurrence of acne formation that will go away after subsequent use. To add to that, Niacinamide is also known to exfoliate the ducts in the Follicular Ostia. Acne-causing bacteria are known to form biofilms that are tucked away inside the pores. When the biofilm is disturbed, the immune cells can detect these acne-causing bacteria and mount an immune response resulting in acne formation. Thus, users should expect purging lasting for a few days to weeks, upon commencement of a Niacinamide product.

Another known side effect of Niacinamide is slight tingling and irritation, although it is more common for Niacin to cause those reactions. Most of these reactions and irritations in the aforementioned clinical trials go away after a few days of subsequent usage.

References:


  1. Azizzadeh, B., Murphy, M. R., Johnson, C. M., Massry, G. G., & Fitzgerald, R. (2018). Master Techniques in Facial Rejuvenation E-Book. Elsevier Health Sciences. ↩︎

  2. Ertel, K. D., Berge, C. A., Mercurio, M. G., & Fowler, T. J. (2000). New facial moisturizer technology increases exfoliation without compromising barrier function. 58th Annual Meeting of the. ↩︎

  3. Tanno, O., Ota, Y., Hikima, R., Matsumoto, M., & Ota, M. (2000). An increase in endogenous epidermal lipids improves skin barrier function. 20th IFSCC International. ↩︎ ↩︎

  4. Zackheim, H. S. (1975). Treatment of psoriasis with 6-aminonicotinamide. In Archives of Dermatology (Vol. 111, Issue 7, pp. 880–882). https://doi.org/10.1001/archderm.111.7.880 ↩︎

  5. Bissett, D. L., Miyamoto, K., Sun, P., Li, J., & Berge, C. A. (2004). Topical Niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin1. International Journal of Cosmetic Science, 26(5), 231–238. ↩︎ ↩︎ ↩︎

  6. Yu, J. M., Liu, Y., Xie, N., Sun, W., Wang, J. J., & Li, H. Q. (2002). Effects of nicotinamide on levels of dermis hydroxyproline in photoaging skin. Huanjing Yu Jiankang Zazhi, 19, 102–104. ↩︎

  7. GRIFFITHS, & CEM. (1995). Nicotinamide 4% gel for the treatment of inflammatory acne vulgaris. The Journal of Dermatological Treatment, 6, 8–10. ↩︎

  8. Shalita, A. R., Graham Smith, J., Parish, L. C., Sofman, M. S., & Chalker, D. K. (1995). TOPICAL NICOTINAMIDE COMPARED WITH CLINDAMYCIN GEL IN THE TREATMENT OF INFLAMMATORY ACNE VULGARIS. In International Journal of Dermatology (Vol. 34, Issue 6, pp. 434–437). https://doi.org/10.1111/j.1365-4362.1995.tb04449.x ↩︎

  9. Levin, J., & Del Rosso, J. Q. (2011). A randomized, controlled comparative study of the wrinkle reduction benefits of a cosmetic niacinamide/peptide/retinyl propionate product regimen vs. a prescription 0·02% tretinoin product regimen. In Yearbook of Dermatology and Dermatologic Surgery (Vol. 2011, pp. 257–258). https://doi.org/10.1016/j.yder.2011.01.069 ↩︎

  10. Bissett, D. L., Oblong, J. E., & Berge, C. A. (2006). Niacinamide: A B Vitamin that Improves Aging Facial Skin Appearance. In Dermatologic Surgery (Vol. 31, pp. 860–866). https://doi.org/10.1111/j.1524-4725.2005.31732 ↩︎ ↩︎

  11. Draelos, Z. D., Matsubara, A., & Smiles, K. (2006). The effect of 2% niacinamide on facial sebum production. Journal of Cosmetic and Laser Therapy: Official Publication of the European Society for Laser Dermatology, 8(2), 96–101. ↩︎ ↩︎

  12. Navarrete-Solís, J., Castanedo-Cázares, J. P., Torres-Álvarez, B., Oros-Ovalle, C., Fuentes-Ahumada, C., González, F. J., Martínez-Ramírez, J. D., & Moncada, B. (2011). A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma. Dermatology Research and Practice, 2011, 379173. ↩︎

  13. Feldmann, R. J., & Maibach, H. I. (1970). Absorption of some organic compounds through the skin in man. The Journal of Investigative Dermatology, 54(5), 399–404. ↩︎

  14. Franz, T. J. (1975). Percutaneous absorption on the relevance of in vitro data. The Journal of Investigative Dermatology, 64(3), 190–195. ↩︎

  15. Elsner, P., & Maibach, H. I. (2005). Cosmeceuticals and Active Cosmetics: Drugs vs. Cosmetics. CRC Press. ↩︎

  16. Hakozaki, T., Minwalla, L., Zhuang, J., Chhoa, M., Matsubara, A., Miyamoto, K., Greatens, A., Hillebrand, G. G., Bissett, D. L., & Boissy, R. E. (2002). The effect of Niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. The British Journal of Dermatology, 147(1), 20–31. ↩︎

  17. Shen, S. C., Takasli, Y., Chen, Y. C., Tsai, C. H., Hu, C. H., Lee, W. R., & Others. (2002). Reduciton of DNA damage by nicotinamide after reactive oxygen species treatment. IFSCC. ↩︎

  18. Tanno, O., Ota, Y., Kitamura, N., Katsube, T., & Inoue, S. (2000). Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier. The British Journal of Dermatology, 143(3), 524–531. ↩︎ ↩︎

  19. Oblong, J. E., Bissett, D. L., Ritter, J. L., Kurtz, K. K., & Schnicker, M. S. (2001). Niacinamide stimulates collagen synthesis from human dermal fibroblasts and differentiation marker in normal human epidermal keratinocytes: potential of Niacinamide to normalize aged skin cells to correct homeostatic balance. 59th Annual Meeting American Academy of Dermatology, Washington. ↩︎

  20. Oblong, J. E., Bissett, D. L., Ritter, J. L., Kurtz, K. K., & Schnicker, M. S. (2002). Effect of Niacinamide on collagen synthesis and markers of keratinocyte differentiation. 60th Annual Meeting of the American Academy of Dermatology. ↩︎

  21. Iraji, F., & Banan, L. (2010). The efficacy of nicotinamide gel 4% as an adjuvant therapy in the treatment of cutaneous erosions of pemphigus vulgaris. Dermatologic Therapy, 23(3), 308–311. ↩︎ ↩︎ ↩︎

  22. Soma, Y., Kashima, M., Imaizumi, A., Takahama, H., Kawakami, T., & Mizoguchi, M. (2005). Moisturizing effects of topical nicotinamide on atopic dry skin. International Journal of Dermatology, 44(3), 197–202. ↩︎

  23. Gehring, W. (2004). Nicotinic acid/niacinamide and the skin. In Journal of Cosmetic Dermatology (Vol. 3, Issue 2, pp. 88–93). https://doi.org/10.1111/j.1473-2130.2004.00115.x ↩︎

  24. Biedermann, K., Lammers, K., & Mrowczynski, E. (2002). és mtsai: Regulation of sebum production by Niacinamide. 60th Annual Meeting American Academy of Dermatology, New Orleans. ↩︎

  25. Chaffins, M. L., Collison, D., & Fivenson, D. P. (1993). Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. Journal of the American Academy of Dermatology, 28(6), 998–1000. ↩︎

  26. Ungerstedt, J. S., Blömback, M., & Söderström, T. (2003). Nicotinamide is a potent inhibitor of proinflammatory cytokines. Clinical and Experimental Immunology, 131(1), 48–52. ↩︎

  27. Bekier, E., & Maśliński, C. (1974). Antihistaminic action of nicotinamide. In Agents and Actions (Vol. 4, Issue 3, pp. 196–196). https://doi.org/10.1007/bf01970274 ↩︎

  28. Berk, M. A., & Lorincz, A. L. (1986). The treatment of bullous pemphigoid with tetracycline and Niacinamide. A preliminary report. Archives of Dermatology, 122(6), 670–674. ↩︎

  29. Burger, D. R., Vandenbark, A. A., Daves, D., Anderson, W. A., Jr, Vetto, R. M., & Finke, P. (1976). Nicotinamide: suppression of lymphocyte transformation with a component identified in human transfer factor. Journal of Immunology , 117(3), 797–801. ↩︎

  30. Shimoyama, M., Kawai, M., Hoshi, Y., & Ueda, I. (1972). Nicotinamide inhibition of 3′,5′- cyclic AMP phosphodiesterase in vitro. Biochemical and Biophysical Research Communications, 49(4), 1137–1141. ↩︎

  31. Gensler, H. L., Williams, T., Huang, A. C., & Jacobson, E. L. (1999). Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice. Nutrition and Cancer, 34(1), 36–41. ↩︎

  32. Otte, N., Borelli, C., & Korting, H. C. (2005). Nicotinamide - biologic actions of an emerging cosmetic ingredient. In International Journal of Cosmetic Science (Vol. 27, Issue 5, pp. 255–261). https://doi.org/10.1111/j.1467-2494.2005.00266.x ↩︎

  33. Matts, P. J. (2001). Predicting visual perception of human skin surface texture using multiple-angle reflectance spectrophotometry. 59th Annual Meeting of the American Academy of Dermatology, Washington, 2001. https://ci.nii.ac.jp/naid/10023919174/ ↩︎

  34. Bissett, D. L., Robinson, L. R., Raleigh, P. S., Miyamoto, K., Hakozaki, T., Li, J., & Kelm, G. R. (2007). Reduction in the appearance of facial hyperpigmentation by topical N-acetyl glucosamine. Journal of Cosmetic Dermatology, 6(1), 20–26. ↩︎

  35. Kimball, A. B., Kaczvinsky, J. R., Li, J., Robinson, L. R., Matts, P. J., Berge, C. A., Miyamoto, K., & Bissett, D. L. (2010). Reduction in the appearance of facial hyperpigmentation after use of moisturizers with a combination of topical niacinamide andN-acetyl glucosamine: results of a randomized, double-blind, vehicle-controlled trial. In British Journal of Dermatology (Vol. 162, Issue 2, pp. 435–441). https://doi.org/10.1111/j.1365-2133.2009.09477.x ↩︎

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The Skincare Encyclopedia aims to improve public understanding of the biology and chemistry of skincare. The Encyclopedia is rooted in core scientific principles and extensive research, in many cases in collaboration with the authors of the original studies referenced. This is a project of Regimen Lab, maintained by a group of multidisciplinary scientists, MDs, and researchers.