profile iconIngredient Profile
Common Name
N-Acetylglucosamine (NAG)
INCI
Acetyl Glucosamine
Source
Fermentation of Corn or Shellfish
Present in
Level
Benefits
Brightening
Hydration
Anti-aging

MOLECULE

klingman iconKligman Ingredient Evaluation
Penetration
Good Penetration
Biochemical Mechanism
  • Inhibits glycosylation of pro-tyrosinase to tyrosinase
  • Suppresses inflammatory messengers
  • Stimulates HA production
  • Up-regulates antiox enzymes
Level of evidence
Level B, Good Quality Evidence

Regimen Lab Skincare Encyclopedia

N-Acetyl Glucosamine (NAG)

V 1.0 last edited 08Aug2020

TLDR

  • NAG is a glucosamine (amino acid + sugar) that exists throughout the body and in skin
  • A signalling molecule involved in a range of processes, notably in wound repair, anti-inflammatory action, and infection detection
  • Hyaluronic Acid, a better-known ingredient, is essentially a linked chain of NAG

Regimen's Take

NAG is a major component of the skin, and like many "skin-identical" ingredients, used in skincare it can have strong benefits and is generally highly compatible with a range of skin types. NAG is perhaps best known for its hydration properties (through its ability to stimulate Hyaluronic Acid production), but new evidence has shown it to have excellent properties for hyperpigmentation, collagen production, and skin elasticity. Some of the best studies of NAG show its synergistic effect with Niacinamide. While many studies of NAG are of high quality, we would like to see more independent clinical trials and in particular studies with longer treatment periods. (Side Note: Our NAG is derived from the fermentation of Corn rather than shellfish)

What is N-acetylglucosamine?

N-acetylglucosamine is an amino acid monosaccharide present in human tissues. It is the precursor for heparan sulfate and hyaluronic acid. It is usually derived from the exoskeleton of crustaceans as a byproduct of the seafood industry.

What are the benefits of NAG?

How does it work?

Antioxidant and Anti-inflammatory

Inflammation is a localized condition in which the area appears to be red, swollen, hot, and painful as a response to infection or injury. When you have a pimple, it is usually inflamed as a reaction to bacterial or fungal infection. When your skin detects the presence of acne-causing bacteria, your skin cells release various free radicals to kill the bacteria. However, this is usually an exaggerated response that leads to the rapid release of high amounts of free radicals (causes damage to nearby proteins and DNA), cytokines (substances that promote more inflammation), and other pro-inflammatory compounds. All of these lead to the production of an inflammatory lesion. NAG’s anti-inflammatory effect is owed to its:

  • suppression of neutrophil function (superoxide generation, phagocytosis, granule enzyme lysozyme release and neutrophil chemotaxis)[2:1]
  • suppresses interleukin 1-induced nitric oxide (NO) production and
  • suppresses the production of IL-1beta-induced cyclooxygenase-2 and IL-6[4:1]
  • decreases NO production by inhibiting inducible NO synthase (iNOS) protein expression[3:1]

What the heck does that mean? Neutrophils are one type of white blood cells. They are your primary defenders in bacterial infections. During inflammation, they migrate towards the infected site and produce free radicals and cytokines to amplify the inflammatory reaction. This exaggerated immune response usually leads to a destructive response that damages nearby cells and extracellular matrix. Regulating neutrophil function through NAG is achieved by the inhibition of several neutrophil functions.

Side note: dead neutrophils, as one of the white blood cells, are components of pus. Accumulation of dead white blood cells, debris, cell fragments, living and dead microbes.

NAG’s antioxidant ability is owed to its:

  • superoxide/hydroxyl-radical scavenging ability[5:1]
  • upregulation of Antioxidant enzymes (catalase, GSH S-transferase, peroxiredoxin, glutathione peroxidase, paraoxonase)[13:1]

When your skin is exposed to UV or experiences inflammation and other environmental factors, your skin undergoes oxidative stress characterized by the increase in free radicals. These free radicals can damage proteins and DNA in your skin, leading to premature aging. Your body has a natural defense against oxidative stress, but it can be overloaded. NAG promotes the production of these natural antioxidants in the body to combat the harmful effects of free radicals. In addition, it is also capable of scavenging superoxide/hydroxy-radical on its own.

Promotion of Wound Healing

Supplementation of keratinocytes with NAG led to a dose-dependent increase of Hyaluronic acid.[17] The wound healing properties of NAG is likely owed to its ability to increase HA in the skin.

HA can serve as a scaffold to which Fibroblasts can migrate during wound repair. It also promotes cell proliferation, cell migration, and angiogenesis, which accounts for its role in the promotion of wound healing.

Anti-aging

We know that UV exposure can lead to the formation of wrinkles, but how exactly? There are three types of UV, but for this article’s purpose, let’s discuss the two classes concerning aging. UV-A exposure leads to the formation of ROS (radical oxygen species), leading to molecular damage and the degradation of the extracellular matrix. Your extracellular matrix is composed of collagen, elastin, hyaluronic acid, and other proteins. The ECM is a gel-like substance that serves as a scaffold and is responsible for the smooth, elastic skin that you have. When exposed to UV-A, the ECM gets degraded, which leads to the formation of wrinkles and fine lines.

Upon exposure to UV-B, on the other hand, leads to an increase of MMP-1 and MMP-13. MMPs (matrix metalloproteinases) are responsible for the degradation of collagen. MMP-1, in particular, is mainly responsible for the degradation of dermal collagen during the aging process. NAG can reduce the amount of MMPs in the skin through the following actions:[18]

  • Suppressing UVB induced activation of NF-kB and AP-1
  • inhibition of Ca2± dependant Akt, ERK and p38 MAPK signaling
  • decreasing Ca2+ concentration to prevent activation of CAMKs

What does that mean? NAG can prevent the formation of MMPs and this inhibition prevents your collagen and other ECM from being degraded.

MMPs have become one of the targets of anti-aging products as they are mainly responsible for the degradation of collagen.

Reduction of Hyperpigmentation

Pigmentation of the skin is a complex cycle that involves several key components. One of these is Tyrosinase, which is a rate-limiting enzyme that catalyzes the hydroxylation of monophenol l-tyrosine to the o-diphenol 3,4-dihydroxyphenylalanine (DOPA) and the oxidation of DOPA to the o-quinone DOPAquinone.

This only means that Tyrosinase is responsible for converting Tyrosine to DOPA and DOPAquinone, which ends up as Melanin. Without Tyrosinase, Tyrosine would not end up as Melanin. For this reason, inhibiting Tyrosinase is one of the most common ways to prevent hyperpigmentation. The effectiveness of NAG against hyperpigmentation is due to its inhibition of glycosylation of pro-tyrosinase to active Tyrosinase. Since pro-tyrosinase is not converted to its active form, there would be less Tyrosine ending up as Melanin in the skin.

Increase of Moisturization

NAG was also beneficial to skin moisturization, decreasing flakiness, and improving skin exfoliation. Skin exfoliation is an essential process in maintaining a well-moisturized skin. In cases where exfoliation is degreased, dead cells can re-aggregate on the skin’s surface, leading to a rough and flaky appearance. NAG may competitively bind to CD44, which regulates cellular adhesion. NAG is able to normalize the adhesion of cells so that they slough off properly during exfoliation, leading to a smooth flake-free surface.[14:1]

Clinical Studies

 In vivo & In vitro
Topical formulations containing NAG were shown to improve skin moisturization, decrease skin flaking, and normalization of SC exfoliation.[14:2]
 In vivo
Another cream containing NAG showed significant firming and reduction in pigmentation in a 16-week treatment period.[19]
In vivo
In an 8-week, double-blind, placebo-controlled, left-right randomized, split-face clinical test, 2% NAG significantly reduced pigmentation.[13:2]
In vivo
In the same study, 2% NAG was combined with 4% Niacinamide, and a greater significant difference was observed in terms of pigmentation.[13:3]
In vivo
Finally, a 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.[20]

Does it penetrate the skin?

There are only a couple of studies on whether NAG penetrates the skin. One study on Franz diffusion cells and fresh porcine skin found out that aqueous NAG solutions were able to penetrate the cells.[15] Another study using snakeskin found that the addition of penetration enhancers such as DMSO or ethanol increases NAG’s permeation.[16] In another in-vitro Franz cell testing, NAG showed excellent penetration, comparable to Niacinamide.[12:1]

References:

  1. Weindl, G., Schaller, M., Schäfer-Korting, M., & Korting, H. C. (2004). Hyaluronic acid in the treatment and prevention of skin diseases: molecular biological, pharmaceutical and clinical aspects. Skin Pharmacology and Physiology, 17(5), 207–213. ↩︎

  2. Hua, J., Sakamoto, K., & Nagaoka, I. (2002). Inhibitory actions of glucosamine, a therapeutic agent for osteoarthritis, on the functions of neutrophils. Journal of Leukocyte Biology, 71(4), 632–640. ↩︎ ↩︎

  3. Meininger, C. J., Kelly, K. A., Li, H., Haynes, T. E., & Wu, G. (2000). Glucosamine inhibits inducible nitric oxide synthesis. Biochemical and Biophysical Research Communications, 279(1), 234–239. ↩︎ ↩︎

  4. Shikhman, A. R., Kuhn, K., & Alaaeddine, N. (2001). N-acetylglucosamine prevents IL-1β-mediated activation of human chondrocytes. The Journal of. https://www.jimmunol.org/content/166/8/5155.short ↩︎ ↩︎

  5. Xing, R., Liu, S., Guo, Z., Yu, H., Li, C., Ji, X., Feng, J., & Li, P. (2006). The antioxidant activity of glucosamine hydrochloride in vitro. Bioorganic & Medicinal Chemistry, 14(6), 1706–1709. ↩︎ ↩︎

  6. Green, B., Wildnauer, R., & Edison, B. (2007). Topical n-acetylglucosamine provides fast acne-reducing benefits and mildness demonstrating its potential utility in enhancing conventional Rx or OTC acne treatments: P125. Journal of the American Academy of Dermatology, 56(2). ↩︎

  7. Weindl, G., Schaller, M., Schäfer-Korting, M., & Korting, H. C. (2004). Hyaluronic acid in the treatment and prevention of skin diseases: molecular biological, pharmaceutical and clinical aspects. Skin Pharmacology and Physiology, 17(5), 207–213. ↩︎

  8. Adzick, N. S., & Longaker, M. T. (1992). Scarless fetal healing. Therapeutic implications. Annals of Surgery, 215(1), 3–7. ↩︎

  9. Połubinska, A., Cwalinski, J., Baum, E., & Bręborowicz, A. (2013). N-Acetylglucosamine modulates function of the skin fibroblasts. International Journal of Cosmetic Science, 35(5), 472–476. ↩︎

  10. Osborne, R., Mullins, L., & Robinson, L. (2006). Topical N-acetyl glucosamine and niacinamide increase hyaluronan in vitro: P1124. Journal of the American Academy of Dermatology, 54(3). https://insights.ovid.com/american-academy-dermatology/jaade/2006/03/002/topical-acetyl-glucosamine-niacinamide-increase/423/00004725 ↩︎

  11. Green, B. A., Edison, B. L., Wildnauer, R. H., & Hwu, R. H. (2004). Derivatives of sugar compounds provide anti-aging effects. JOURNAL-AMERICAN ACADEMY OF DERMATOLOGY, 50, P81–P81. ↩︎

  12. Bissett, D., Kimball, A., Robinson, L., & Li, J. (2006). Topical formulation containing N-acetyl glucosamine and niacinamide reduces the appearance of photoaging on human facial skin: P235. Journal of the American Academy of Dermatology, 54(3). https://insights.ovid.com/american-academy-dermatology/jaade/2006/03/002/topical-formulation-containing-acetyl-glucosamine/169/00004725 ↩︎ ↩︎

  13. 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. ↩︎ ↩︎ ↩︎ ↩︎

  14. Mammone, T., Gan, D., Fthenakis, C., & Marenus, K. (2009). The effect of N-acetyl-glucosamine on stratum corneum desquamation and water content in human skin. In International Journal of Cosmetic Science (Vol. 32, Issue 3, pp. 234–234). ↩︎ ↩︎ ↩︎

  15. Wuttikul, K., Boonme, P., Thammarat, C., & Khongkow, P. (2020). N-acetylglucosamine microemulsions: Assessment of skin penetration, cytotoxicity, and anti-melanogenesis. Journal of Cosmetic Dermatology. https://onlinelibrary.wiley.com/doi/abs/10.1111/jocd.13431 ↩︎

  16. Garner, S. T., Israel, B. J., Achmed, H., Capomacchia, A. C., Abney, T., & Azadi, P. (2007). Transdermal Permeability of N-Acetyl-D-Glucosamine. In Pharmaceutical Development and Technology (Vol. 12, Issue 2, pp. 169–174). https://doi.org/10.1080/10837450701212560 ↩︎

  17. Sayo, T., Sakai, S., & Inoue, S. (2004). Synergistic effect of N-acetylglucosamine and retinoids on hyaluronan production in human keratinocytes. Skin Pharmacology and Physiology, 17(2), 77–83. ↩︎

  18. Hwang, Y. P., Kim, H. G., Han, E. H., Choi, J. H., Park, B. H., Jung, K. H., Shin, Y. C., & Jeong, H. G. (2011). N-Acetylglucosamine suppress collagenases activation in ultraviolet B-irradiated human dermal fibroblasts: Involvement of calcium ions and mitogen-activated protein kinases. Journal of Dermatological Science, 63(2), 93–103. ↩︎

  19. Schlessinger, J., Green, B., Edison, B. L., Murphy, L., & Sabherwal, Y. (2016). A Firming Neck Cream Containing N-Acetyl Glucosamine Significantly Improves Signs of Aging on the Challenging Neck and Décolletage. Journal of Drugs in Dermatology: JDD, 15(1), 47–52. ↩︎

  20. 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 ↩︎