
Niacinamide, also known as nicotinamide, is a water-soluble form of vitamin B3 (molecular formula: C₆H₆N₂O) that has become a popular skincare ingredient due to its versatility and proven efficacy. Numerous clinical studies support its beneficial effects, contributing to its rise in popularity in the past few years.
It is interesting to note that despite the numerous documented benefits, niacinamide is officially listed only under the function "smoothing" in the EU's CosIng database. This limited categorization reflects regulatory classification rather than the comprehensive scientific evidence available.

### Benefits of Niacinamide in Skincare

**1. Anti-inflammatory and Acne Management**  
Niacinamide exhibits significant anti-inflammatory properties, which help reduce redness and irritation associated with acne and rosacea. Studies have shown that topical niacinamide can effectively decrease inflammatory lesions and sebum production, making it an excellent choice for acne-prone skin (1)(5)(8). One clinical trial even found it to be as effective as clindamycin in treating inflammatory acne (8).

**2. Improving Skin Barrier Function**  
A healthy skin barrier prevents moisture loss and shields against irritants. Niacinamide enhances barrier function by stimulating the synthesis of ceramides and fatty acids, thus helping to reduce transepidermal water loss (TEWL) and improving skin hydration (2).

**3. Reduction of Hyperpigmentation**  
Niacinamide can effectively lighten dark spots and hyperpigmentation by inhibiting melanosome transfer from melanocytes to keratinocytes. Clinical trials demonstrated significant improvements in hyperpigmentation after consistent topical application of niacinamide (3),(4),(7). In one study, niacinamide 4% showed comparable efficacy to hydroquinone 4% in treating melasma, with fewer side effects (7).

**4. Anti-aging Effects**  
Niacinamide contributes to anti-aging by enhancing collagen production, reducing fine lines and wrinkles, and improving skin elasticity. One double-blind clinical trial found visible improvements in wrinkle reduction and skin elasticity after 12 weeks of niacinamide treatment (4).

**5. Sebum Regulation**  
In addition to reducing inflammation, niacinamide regulates sebum production, beneficial for managing oily skin. A study demonstrated that applying 2% niacinamide significantly reduced sebum excretion rates after two weeks (1).

### Optimal Concentrations and Usage

The optimal concentration of niacinamide for skincare ranges between 2% and 5%, with higher concentrations generally well-tolerated but occasionally causing mild irritation in sensitive skin. Daily use is safe and often recommended for ongoing skin improvement (6).

### Potential Side Effects

Niacinamide is generally well-tolerated; however, in rare cases, high concentrations may cause redness or irritation. To minimize potential side effects, it is advisable to begin with lower concentrations and gradually increase if needed (6).

### Pin it!

![Niacinamide Summary Infographic](https://images.skinclasshub.com/ingredients/niacinamide/niacinamide_infographic_skinclasshub.png)

### Conclusion

Niacinamide is a scientifically supported skincare ingredient offering multiple dermatological benefits, including anti-inflammatory, skin barrier enhancement, hyperpigmentation reduction, anti-aging effects, and sebum regulation. Its proven **safety profile and broad-spectrum efficacy** make it an excellent choice for inclusion in skincare routines targeting diverse skin concerns.

### References

1. **Draelos, Z. D., Matsubara, A., & Smiles, K. (2006).** The effect of 2% niacinamide on facial sebum production. *Journal of Cosmetic and Laser Therapy, 8*(2), 96-101. [The effect of 2% niacinamide on facial sebum production: Journal of Cosmetic and Laser Therapy: Vol 8 , No 2 - Get Access](https://doi.org/10.1080/14764170600717704)
  
2. **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. *British Journal of Dermatology, 143*(3), 524-531. [https://academic.oup.com/bjd/article-abstract/143/3/524/6691624?redirectedFrom=fulltext](https://academic.oup.com/bjd/article-abstract/143/3/524/6691624?redirectedFrom=fulltext)
  
3. **Hakozaki, T., Minwalla, L., Zhuang, J., et al. (2002).** The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. *British Journal of Dermatology, 147*(1), 20-31. [https://doi.org/10.1046/j.1365-2133.2002.04834.x](https://doi.org/10.1046/j.1365-2133.2002.04834.x)
  
4. **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 skin. *International Journal of Cosmetic Science, 26*(5), 231-238. [Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin - PubMed](https://pubmed.ncbi.nlm.nih.gov/18492135/)
  
5. **Walocko, F. M., et al. (2017).** The role of nicotinamide in acne treatment. *Dermatologic Therapy, 30*(5), e12481. [The role of nicotinamide in acne treatment - Walocko - 2017 - Dermatologic Therapy - Wiley Online Library](https://doi.org/10.1111/dth.12481)
  
6. **Rolfe, H. M. (2014).** A review of nicotinamide: treatment of skin diseases and potential side effects. *Journal of Cosmetic Dermatology, 13*(4), 324–328. [https://pubmed.ncbi.nlm.nih.gov/25399625](https://pubmed.ncbi.nlm.nih.gov/25399625)
  
7. **Navarrete-Solís, J., et al. (2011).** A double-blind, randomized clinical trial of niacinamide 4% versus hydroquinone 4% in the treatment of melasma. *Dermatology Research and Practice, 2011*, 379173. [A Double‐Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma - Navarrete-Solís - 2011 - Dermatology Research and Practice - Wiley Online Library](https://doi.org/10.1155/2011/379173)
  
8. **Shalita, A. R., et al. (1995).** Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris. *International Journal of Dermatology, 34*(6), 434-437. [TOPICAL NICOTINAMIDE COMPARED WITH CLINDAMYCIN GEL IN THE TREATMENT OF INELAMMATORY ACNE VULGARIS - SHALITA - 1995 - International Journal of Dermatology - Wiley Online Library](https://doi.org/10.1111/j.1365-4362.1995.tb04449.x)


A versatile, well-tolerated ingredient with proven benefits for acne, pigmentation, skin barrier repair, and aging.

Niacinamide


**Linalool** (C₁₀H₁₈O) is a naturally occurring **monoterpene alcohol** found in essential oils such as lavender, coriander, basil, and thyme. In cosmetics, it is primarily used as a **fragrance ingredient**, prized for its floral, slightly citrusy scent. While linalool is widespread in personal care products, its biological activity and safety profile warrant closer scrutiny.

## Antimicrobial Activity

Linalool has demonstrated **antimicrobial properties**, particularly against Gram-negative bacteria such as *Pseudomonas fluorescens*. Its mechanism of action appears to involve the disruption of bacterial membranes and interference with key metabolic processes. These findings suggest that linalool may contribute to the microbial stability of cosmetic formulations [1].

## Safety and Sensitization Concerns

Despite being commonly used, linalool poses **safety concerns** related to **oxidation**. When exposed to air, linalool can oxidize and form **hydroperoxides**, which are recognized as **potent skin sensitizers**. These oxidation products, rather than linalool itself, are responsible for most allergic reactions associated with linalool exposure [2].

In clinical settings, linalool is one of the 26 fragrance allergens that must be labeled on cosmetic packaging in the European Union. Sensitization typically occurs with repeated exposure, especially in leave-on products or when formulations are poorly stabilized.

## Conclusion

Linalool is a widely used fragrance compound with **some antimicrobial potential**, but its **oxidation byproducts are well-established allergens**. Formulas should ensure antioxidant protection or encapsulation strategies to reduce oxidation, and consumers with sensitive skin may benefit from avoiding products containing linalool.

## References

1. **Guo, F., Chen, Q., Liang, Q., Zhang, M., Chen, W., Chen, H., Yun, Y., Zhong, Q., & Chen, W. (2021).** Antimicrobial activity and proposed action mechanism of linalool against *Pseudomonas fluorescens*. *Frontiers in Microbiology, 12*, 562094.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875898](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875898)
  
2. **Kuresepi, S., Vileno, B., Lepoittevin, J.-P., & Giménez-Arnau, E. (2020).** Mechanistic insights on skin sensitization to linalool hydroperoxides: EPR evidence on radical intermediates formation in reconstructed human epidermis and 13C NMR reactivity studies with thiol residues. *Chemical Research in Toxicology, 33*(7), 1922–1932.  
  [https://pubmed.ncbi.nlm.nih.gov/32441093](https://pubmed.ncbi.nlm.nih.gov/32441093)  


A fragrance compound with mild antimicrobial effects, but its oxidized forms are known skin sensitizers.

Linalool


Caffeine (1,3,7-trimethylxanthine) is a naturally occurring alkaloid found in coffee, tea, and cocoa. In skincare, it is used for its potential vasoconstrictive, antioxidant, and lipolytic properties. It is commonly included in formulations targeting under-eye puffiness, dark circles, and cellulite.

## Clinical Evidence of the Effects on Under-Eye Puffiness

A randomized, double-blind, placebo-controlled study evaluated the efficacy of a 3% caffeine gel in reducing under-eye puffiness [1]. The study involved 34 volunteers who applied either the caffeine gel or a placebo gel. Both groups experienced reduced puffiness, but the **difference between them was not statistically significant.** However, 23.5% of participants responded better to the caffeine gel than to the placebo, suggesting individual variation. The authors concluded that the reduction in puffiness was more likely due to the cooling action of the gel base than to caffeine itself.

## Cellulite and Lipolysis

Caffeine is frequently used in topical products marketed for the appearance of cellulite. Mechanistically, it is thought to promote lipolysis (the breakdown of stored fat) by inhibiting phosphodiesterase (an enzyme that deactivates fat-burning signals), which increases intracellular levels of cyclic adenosine monophosphate, or cAMP (a chemical messenger that activates fat metabolism). Elevated cAMP levels can trigger the breakdown of triglycerides (fat molecules stored in cells). [2].

Clinical studies evaluating its effect on cellulite include:

- **Byun et al. (2015):** In a six-week open-label study, 15 women applied a cream containing 3.5% water-soluble caffeine and xanthenes to their thighs and upper arms twice daily. Statistically significant reductions in thigh (−0.7 cm) and upper-arm (−0.8 cm) circumference were reported, along with improved cellulite grading scores. The study lacked a control group and had a small sample size [3].
  
- **Dupont et al. (2014):** In a double-blind, randomized, placebo-controlled trial, 44 women applied a topical gel containing caffeine and multiple other actives twice daily for 84 days. Compared to the placebo group, the active gel significantly improved skin tonicity and reduced the orange-peel appearance and stubborn cellulite. Circumference measurements also decreased. No adverse events were reported. The contribution of caffeine alone could not be determined due to the presence of multiple actives [4].
  

The current evidence suggests that topical formulations containing caffeine may improve the appearance of cellulite in some users, but results depend on formulation, treatment duration, and the presence of additional ingredients. Studies specifically isolating caffeine’s contribution are limited.

## Antioxidant Activity

Caffeine has demonstrated antioxidant activity in both in vitro and in vivo models. It can scavenge reactive oxygen species (ROS) and reduce oxidative stress in skin cells exposed to ultraviolet radiation or pollution [5].

## Safety and Irritation

Topical caffeine is generally well tolerated. Mild irritation or dryness may occur, particularly in alcohol-based formulas or at high concentrations. No systemic effects have been reported in cosmetic use. In safety assessments, caffeine showed low irritation and sensitization potential [6].

## Conclusion

Caffeine has documented biological actions on the skin like lipolysis and antioxidant activity. Its effect on under-eye puffiness has been studied, but clinical evidence remains limited and results vary. Studies on cellulite reduction show small but measurable improvements in some individuals, though effects are formulation-dependent and often modest. Caffeine is generally safe for topical use and continues to be widely used in formulations targeting transient puffiness, localized fat, and oxidative stress.

## References

1. **Amnuaikit, T., Maneenuan, D., & Boonme, P. (2011).** Evaluation of caffeine gels on physicochemical characteristics and in vivo efficacy in reducing puffy eyes. *Journal of Applied Pharmaceutical Science, 1*(2), 56–59.  
  [https://www.japsonline.com/admin/php/uploads/20_pdf.pdf](https://www.japsonline.com/admin/php/uploads/20_pdf.pdf)
  
2. **Elias, M. L., Israeli, A. F., & Madan, R. (2023).** Caffeine in skincare: Its role in skin cancer, sun protection, and cosmetics. *Indian Journal of Dermatology, 68*(5), 546–550.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10718232/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10718232/)
  
3. **Byun, S.-Y., Kwon, S.-H., Heo, S.-H., Shim, J.-S., Du, M.-H., & Na, J.-I. (2015).** Efficacy of slimming cream containing 3.5% water-soluble caffeine and xanthenes for the treatment of cellulite: Clinical study and literature review. *Annals of Dermatology, 27*(3), 243–249.  
   [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466275/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466275/)
  
4. **Dupont, E., Journet, M., Oula, M.-L., Gomez, J., Léveillé, C., Loing, E., & Bilodeau, D. (2014).** An integral topical gel for cellulite reduction: Results from a double-blind, randomized, placebo-controlled evaluation of efficacy. *Clinical, Cosmetic and Investigational Dermatology, 7*, 73–88.  
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933246](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933246)
  
5. **Herman, A. (2013).** Caffeine's mechanisms of action and its cosmetic use. *Skin Pharmacology and Physiology, 26*(1), 8–14.  
   [https://pubmed.ncbi.nlm.nih.gov/23075568/](https://pubmed.ncbi.nlm.nih.gov/23075568/)
  
6. **Cherian, P. A., Bergfeld, W. F., Belsito, D. V., Hill, R. A., Klaassen, C. D., Liebler, D. C., Marks, J. G. Jr., Shank, R. C., Slaga, T. J., Snyder, P. W., Fiume, M., & Heldreth, B. (2024).** Safety Assessment of Methylxanthines as Used in Cosmetics. *International Journal of Toxicology, 43*(4_suppl), 42S–77S.  
  [https://journals.sagepub.com/doi/10.1177/10915818241260282](https://journals.sagepub.com/doi/10.1177/10915818241260282)
  

A circulation-boosting compound that may help reduce the appearance of cellulite and protects against oxidative stress.

Caffeine


Zinc oxide is a white, inorganic compound used extensively in topical skincare, most notably as a **broad-spectrum UV filter**. It is a mineral sunscreen agent that reflects and scatters both **UVA and UVB radiation**, protecting the skin from sunburn and long-term photodamage [1]. In addition to its sun-protective properties, it has recognized **anti-inflammatory** effects [2].

---

### UV Protection

Zinc oxide functions as a **physical (mineral) sunscreen**, forming a protective barrier on the skin’s surface that blocks and scatters UV rays. It provides **broad-spectrum protection**, covering both **UVB (290–320 nm)** and **UVA (320–400 nm)** wavelengths [1]. Unlike chemical filters, zinc oxide starts working immediately after application and is photostable — it does not degrade significantly upon sun exposure [3].

Micronized or nano-sized forms of zinc oxide are commonly used to reduce the white cast on skin without compromising UV protection. Studies have confirmed that these particles remain on the skin's surface and pose minimal risk of systemic absorption when used in cosmetic formulations [4].

### Anti-Inflammatory and Wound Healing Properties

Zinc oxide has been shown to reduce inflammation, making it useful in treating skin irritation, diaper rash, and acne lesions [5]. It promotes epithelialization and granulation tissue formation, supporting skin regeneration in wound care settings [6]. Some studies also suggest that zinc oxide has antimicrobial properties, helping reduce bacterial colonization in compromised skin [7].

### Safety Profile

Zinc oxide is considered **safe and well-tolerated**, even for sensitive skin. The Cosmetic Ingredient Review (CIR) and the U.S. FDA classify zinc oxide as safe for use in OTC sunscreen products at concentrations up to **25%** [8]. Studies show negligible systemic absorption, even when applied to damaged skin [4].

### Conclusion

Zinc oxide is a highly effective, broad-spectrum UV filter with additional benefits for inflamed or irritated skin. Its safety, photostability, and low risk of systemic exposure make it a reliable option in both daily sun protection and therapeutic skincare.

---

## References

1. **Beasley, D. G., & Meyer, T. A. (2010).** Characterization of the UVA protection provided by avobenzone, zinc oxide, and titanium dioxide in broad-spectrum sunscreen products. *American Journal of Clinical Dermatology, 11*(6), 413–421.  
  [https://pubmed.ncbi.nlm.nih.gov/20806994/](https://pubmed.ncbi.nlm.nih.gov/20806994/)
  
2. **Ågren, M. S., Phothong, N., Burian, E. A., Mogensen, M., Hædersdal, M., & Jorgensen, L. N. (2021).** Topical zinc oxide assessed in two human wound-healing models. *Acta Dermato-Venereologica, 101*, adv00400.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367036/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367036/)
  
3. **Mitchnick, M. A., Fairhurst, D., & Pinnell, S. R. (1999).** Microfine zinc oxide (Z-Cote) as a photostable UVA/UVB sunblock agent. *Journal of the American Academy of Dermatology, 40*(1), 85–90.  
  [https://doi.org/10.1016/S0190-9622(99)70532-3](https://doi.org/10.1016/S0190-9622(99)70532-3)
  
4. **Gulson, B., et al. (2010).** Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin. *Toxicological Sciences, 118*(1), 140–149.  
  [https://academic.oup.com/toxsci/article/118/1/140/1658967](https://academic.oup.com/toxsci/article/118/1/140/1658967)
  
5. **Gupta, M., Mahajan, V. K., Mehta, K. S., & Chauhan, P. S. (2014).** Zinc therapy in dermatology: a review. *Dermatology Research and Practice, 2014*, 709152.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120804/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120804/)
  
6. **Ågren, M. S. (1990).** Studies on zinc in wound healing. *Acta Dermato-Venereologica. Supplementum, 154*, 1–36.  
  [https://www.medicaljournals.se/acta/content/issue/70-154](https://www.medicaljournals.se/acta/content/issue/70-154)
  
7. **Reddy, K. M., et al. (2007).** Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems. *Applied Physics Letters, 90*(213902).  
  [https://aip.scitation.org/doi/10.1063/1.2742324](https://aip.scitation.org/doi/10.1063/1.2742324)
  
8. **Kim, K.-B., Kim, Y. W., Lim, S. K., Roh, T. H., Bang, D. Y., et al. (2017).** Risk assessment of zinc oxide, a cosmetic ingredient used as a UV filter of sunscreens. *Journal of Toxicology and Environmental Health, Part B: Critical Reviews, 20*(3), 155–182.  
  [https://pubmed.ncbi.nlm.nih.gov/28509652/](https://pubmed.ncbi.nlm.nih.gov/28509652/)

A broad-spectrum mineral UV filter with additional skin-soothing and antimicrobial benefits.

Zinc Oxide


Tocopherol, commonly known as **vitamin E**, is a fat-soluble [antioxidant](https://www.skinclasshub.com/theknowledgehub/cosmetic-glossary/antioxidant) widely used in dermatology and cosmetic formulations. Among its various forms, alpha-tocopherol is the most biologically active and is recognized for its ability to protect the skin from oxidative stress, support barrier function, and enhance moisturization [1].

## Skincare Benefits

### Antioxidant and Photoprotective Properties

Tocopherol acts as a potent antioxidant, neutralizing free radicals generated by environmental stressors such as ultraviolet (UV) radiation and pollution. This activity helps prevent lipid peroxidation in cell membranes, thereby protecting skin cells from oxidative damage [2]. When combined with vitamin C, tocopherol has been shown to provide synergistic photoprotection, reducing UV-induced [erythema](https://www.skinclasshub.com/theknowledgehub/cosmetic-glossary/erythema) and DNA damage [3].

### Skin Barrier Support and Moisturization

Topical application of tocopherol has been demonstrated to improve skin hydration by enhancing the water-binding capacity of the [stratum corneum](https://www.skinclasshub.com/theknowledgehub/cosmetic-glossary/stratum-corneum). This effect contributes to the maintenance of skin elasticity and smoothness [4]. Additionally, tocopherol supports the integrity of the skin barrier, reducing transepidermal water loss and improving overall skin resilience [1].

### Anti-Inflammatory Effects and Wound Healing

Tocopherol exhibits anti-inflammatory properties by inhibiting the release of pro-inflammatory cytokines and reducing oxidative stress in the skin. These effects can aid in the management of inflammatory skin conditions and support the wound healing process [2]. However, clinical evidence regarding its efficacy in scar reduction remains inconclusive [5], with some evidence that topical vitamin E may worsen the appearance of scars or cause contact dermatitis in certain individuals.

## Safety Profile

The Cosmetic Ingredient Review (CIR) Expert Panel has assessed tocopherol and its derivatives, concluding that they are safe for use in cosmetics at concentrations up to 5% [6]. While tocopherol is generally well-tolerated, rare cases of allergic contact dermatitis have been reported, particularly with tocopheryl acetate [7].

## Conclusion

Tocopherol is a well-established ingredient in skincare, offering antioxidant protection, barrier support, and moisturization. Its inclusion in topical formulations can enhance skin health and resilience.

## References

1. **Pinto, C. A. S. de O., Martins, T. E. A., Martinez, R. M., Freire, T. B., Velasco, M. V. R., & Baby, A. R. (2021).** Vitamin E in Human Skin: Functionality and Topical Products. *IntechOpen*.  
   [https://www.researchgate.net/publication/352470124_Vitamin_E_in_Human_Skin_Functionality_and_Topical_Products](https://www.researchgate.net/publication/352470124_Vitamin_E_in_Human_Skin_Functionality_and_Topical_Products)
  
2. **Keen, M. A., & Hassan, I. (2016).** Vitamin E in dermatology. *Indian Dermatology Online Journal, 7*(4), 311–315.  
   [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976416/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976416/)
  
3. **Lin, J. Y., Selim, M. A., Shea, C. R., Grichnik, J. M., Omar, M. M., Monteiro-Riviere, N. A., & Pinnell, S. R. (2003).** UV photoprotection by combination topical antioxidants vitamin C and vitamin E. *Journal of the American Academy of Dermatology, 48*(6), 866–874.  
  [https://www.jaad.org/article/S0190-9622(03)00781-3/fulltext](https://www.jaad.org/article/S0190-9622(03)00781-3/fulltext)
  
4. **Gehring, W., Fluhr, J., & Gloor, M. (1998).** Influence of vitamin E acetate on stratum corneum hydration. *Arzneimittelforschung, 48*(7), 772–775.  
  [https://pubmed.ncbi.nlm.nih.gov/9706379/](https://pubmed.ncbi.nlm.nih.gov/9706379/)
  
5. **Baumann, L., & Spencer, J.(1999).** The effects of topical vitamin E on the cosmetic appearance of scars. *Dermatologic Surgery, 25*(4), 311–315.  
  [https://journals.lww.com/dermatologicsurgery/Abstract/1999/04000/The_Effects_of_Topical_Vitamin_E_on_the_Cosmetic.13.aspx](https://journals.lww.com/dermatologicsurgery/Abstract/1999/04000/The_Effects_of_Topical_Vitamin_E_on_the_Cosmetic.13.aspx)
  
6. **Fiume, M. M., Bergfeld, W. F., Belsito, D. V., et al. (2018).** Safety Assessment of Tocopherols and Tocotrienols as Used in Cosmetics. *International Journal of Toxicology, 37*(2_suppl), 61S–94S.  
  [https://journals.sagepub.com/doi/pdf/10.1177/1091581818794455](https://journals.sagepub.com/doi/pdf/10.1177/1091581818794455)
  
7. **Kosari, P., Alikhan, A., Sockolov, M., & Feldman, S. R. (2010).** Vitamin E and allergic contact dermatitis. *Dermatitis, 21*(3), 148–153.  
  [https://pubmed.ncbi.nlm.nih.gov/20487657/](https://pubmed.ncbi.nlm.nih.gov/20487657/)
  

A skin-protecting antioxidant that supports the skin barrier and fights oxidative damage.

Tocopherol


**Primary INCI Name**: *Ascorbic Acid*  
Vitamin C is a water-soluble antioxidant naturally found in the skin, where it supports collagen synthesis, protects against oxidative stress, and reduces hyperpigmentation [1]. While ascorbic acid is the purest form, its instability in formulations has led to the development of numerous derivatives with greater shelf life and skin compatibility [2].

### Skincare Benefits

Evidence supports the following primary roles for vitamin C in topical formulations:

- **Collagen synthesis**: Topical application of vitamin C has been shown to increase collagen synthesis, stabilize collagen fibers, and decrease collagen degradation, contributing to its anti-aging effects [3].
  
- **Antioxidant defense**: vitamin C protects the skin from UV and pollution-induced oxidative stress [3].
  
- **Reduction of hyperpigmentation**: Vitamin C can inhibit tyrosinase, an enzyme involved in melanin production, leading to improved skin tone and fading of dark spots [1].
  
- **Photoprotection**: While not a sunscreen, vitamin C enhances the efficacy of UV filters and mitigates UV-induced skin damage when used in combination with SPF [4].
  

---

### Stability and Delivery Challenges

Ascorbic acid is unstable in aqueous solutions and rapidly oxidizes when exposed to air, light, or high temperatures. It also requires a low pH (~3.5) to remain active and penetrate the [stratum corneum](https://www.skinclasshub.com/theknowledgehub/cosmetic-glossary/stratum-corneum), which may be irritating to some users [5,6]. These limitations have led to the development of **vitamin C derivatives** that aim to improve stability, solubility, and skin compatibility.

### Common Derivatives

Several derivatives are used in skincare, each with different chemical properties and levels of clinical evidence:

| INCI Name | Solubility | Main distinction |
| --- | --- | --- |
| [Sodium Ascorbyl Phosphate (SAP)](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/sodium-ascorbyl-phosphate) | Water-soluble | Studied for anti-acne effects |
| [Magnesium Ascorbyl Phosphate (MAP)](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/magnesium-ascorbyl-phosphate) | Water-soluble | Gentler on skin |
| [Ascorbyl Glucoside](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/ascorbyl-glucoside) | Water-soluble | Gentler on skin |
| [3-O-Ethyl Ascorbic Acid](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/3-o-ethyl-ascorbic-acid) | Water-soluble | Good stability and penetration |
| [Ascorbyl Palmitate](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/ascorbyl-palmitate) | Oil-soluble | Low conversion |
| [Ascorbyl Tetraisopalmitate](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/ascorbyl-tetraisopalmitate) | Oil-soluble | High stability; used in anti-aging |
| [Tetrahexyldecyl Ascorbate (THD)](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/tetrahexyldecyl-ascorbate) | Oil-soluble | Highly penetrating |
| [Sodium Ascorbate](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/sodium-ascorbate) | Water-soluble | Gentler on skin |

---

### Safety and Regulatory Status

Vitamin C and its derivatives are generally well-tolerated and widely used in cosmetic products. Ascorbic acid may cause stinging at high concentrations, especially on sensitive skin [7]. No major safety concerns exist for approved derivatives at standard concentrations in leave-on formulations.

Regulatory bodies such as the **EU** and **FDA** do not currently impose strict limits on vitamin C in cosmetics, though each derivative must comply with general safety regulations.

### Conclusion

Vitamin C is a well-studied skincare ingredient with strong evidence for antioxidant, collagen-supporting, and brightening effects. While ascorbic acid is effective, its instability has led to the rise of more stable derivatives, each with unique properties. Choosing the right form depends on skin type, formulation goals, and clinical data supporting the specific derivative.

---

### References

1. **Sanadi, R. M., & Deshmukh, R. S. (2020).** The effect of Vitamin C on melanin pigmentation – A systematic review. *Journal of Oral and Maxillofacial Pathology, 24*(2), 374–382.  
  [https://pmc.ncbi.nlm.nih.gov/articles/PMC7802860/](https://pmc.ncbi.nlm.nih.gov/articles/PMC7802860/)
  
2. **Elhabak, M., Ibrahim, S., & Abouelatta, S. M. (2021).** Topical delivery of l-ascorbic acid spanlastics for stability enhancement and treatment of UVB induced damaged skin. *Drug Delivery, 28*(1), 445–453.  
  [https://pmc.ncbi.nlm.nih.gov/articles/PMC7909477/](https://pmc.ncbi.nlm.nih.gov/articles/PMC7909477/)
  
3. **Al-Niaimi, F., & Chiang, N. Y. Z. (2017).** Topical vitamin C and the skin: Mechanisms of action and clinical applications. *The Journal of Clinical and Aesthetic Dermatology, 10*(7), 14–17.  
   [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605218/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605218/)
  
4. **Jesus, A., Mota, S., Torres, A., Cruz, M. T., Sousa, E., Almeida, I. F., & Cidade, H. (2023).** Antioxidants in sunscreens: Which and what for? *Antioxidants, 12*(1), 138.  
  [https://pmc.ncbi.nlm.nih.gov/articles/PMC9854756/](https://pmc.ncbi.nlm.nih.gov/articles/PMC9854756/)
  
5. **Kim, S., & Lee, T. G. (2018).** Stabilization of L-ascorbic acid in cosmetic emulsions. *Journal of Industrial and Engineering Chemistry, 57*, 193–198.  
  [https://www.sciencedirect.com/science/article/abs/pii/S1226086X17304422](https://www.sciencedirect.com/science/article/abs/pii/S1226086X17304422)
  
6. **Martinović, L. S., et al (2023).** Antioxidant activity, stability in aqueous medium and molecular docking/dynamics study of 6-amino- and N-methyl-6-amino-L-ascorbic acid. *International Journal of Molecular Sciences, 24*(2), 1410.  
  [https://www.mdpi.com/1422-0067/24/2/1410](https://www.mdpi.com/1422-0067/24/2/1410)
  
7. **Telang, P. S. (2013).** Vitamin C in dermatology. *Indian Dermatology Online Journal, 4*(2), 143–146.  
  [https://pmc.ncbi.nlm.nih.gov/articles/PMC3673383/](https://pmc.ncbi.nlm.nih.gov/articles/PMC3673383/)
  

Vitamin C is a powerful but unstable antioxidant that boosts collagen, brightens skin, and protects against oxidative stress—leading to the widespread use of more stable derivatives in skincare.

Vitamin C


**Camphor** is a naturally occurring monoterpenoid obtained from the wood of the camphor tree (*Cinnamomum camphora*) or synthesized from turpentine oil. It has a long history of medicinal use for its antimicrobial, analgesic, and anti-pruritic properties [1]. It is commonly used as a fragrance agent in cosmetics and personal care products [1].

### Skin Benefits

Evidence suggests that camphor may offer the following **potential benefits** when used topically:

- **Antimicrobial activity**: Camphor has demonstrated antibacterial and antifungal effects in vitro, including activity against pathogens relevant to skin infections [1,3].
  
- **Analgesic and anti-itch effects**: Camphor can activate and then desensitize sensory receptors (e.g., TRPV1, TRPM8) thereby having an analgesic action [4,5].
  
- **Possible acne benefit**: Due to its antimicrobial and anti-inflammatory effects, camphor shows theoretical promise for acne-prone skin, although clinical studies specifically evaluating camphor for acne treatment are limited [2].
  
- **Atopic dermatitis**: Camphor may help manage atopic dermatitis by reducing inflammation, reinforcing the skin barrier, and limiting microbial overgrowth. While these properties are promising, more clinical data is needed to confirm its effectiveness in this context [2].
  

---

### Safety and Toxicity

Despite its potential benefits, camphor poses significant risks. Camphor’s biological effects are highly dose-dependent.

Camphor is highly toxic if ingested and can cause seizures, respiratory distress, or even death at high doses [1].

In vitro studies on rat thymocytes have shown reduced cell viability and signs of oxidative stress at elevated camphor concentrations, highlighting potential cytotoxic effects even at the cellular level - that is, camphor may harm or kill cells when used at high enough doses in laboratory settings. [6].

In the United States, the **FDA limits camphor concentrations in over-the-counter (OTC) products to a maximum of 11%** [7].

#### Fragrance allergen status

In 2023, camphor was officially added to the European Union’s list of regulated fragrance allergens under Annex III of Regulation (EC) No 1223/2009 (as amended by Regulation (EU) 2023/1545). This list identifies substances that must be disclosed on cosmetic labels when present above 0.001% in leave-on products or 0.01% in rinse-off products. The inclusion of camphor reflects growing recognition of its potential to cause skin sensitization or allergic reactions in some individuals. While it continues to be used for its fragrance and antimicrobial properties, its **classification as a fragrance allergen underscores its drawbacks** and raises further questions about its suitability for sensitive skin or daily-use cosmetic products [8].

### Conclusion

Camphor offers antimicrobial, analgesic, and anti-inflammatory activity, but these benefits are overshadowed by its safety concerns. It is toxic at high concentrations, can cause skin irritation, and is now officially recognized as a fragrance allergen in the European Union. While it remains in use, camphor is a controversial ingredient with limited relevance for modern skincare, particularly for sensitive skin. Future clinical studies may clarify its role, but at present, it is best regarded with caution.

---

### References

1. **Chen, W., Vermaak, I., & Viljoen, A. (2013).** Camphor—A Fumigant during the Black Death and a Coveted Fragrant Wood in Ancient Egypt and Babylon—A Review. *Molecules*, 18(5), 5434–5454.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270224/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270224/)
  
2. **Duda-Madej, A., Viscardi, S., Grabarczyk, M., Topola, E., Kozłowska, J., Mączka, W., & Wińska, K. (2024).** Is Camphor the Future in Supporting Therapy for Skin Infections? *Pharmaceuticals*, 17(6), 715.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11206849/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11206849/)
  
3. **Abdollahi, A., Fereydouni, N., Moradi, H., Karimivaselabadi, A., Zarenezhad, E., & Osanloo, M. (2024).** Nanoformulated herbal compounds: Enhanced antibacterial efficacy of camphor and thymol-loaded nanogels. *BMC Complementary Medicine and Therapies*, 24, 44.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985855/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985855/)
  
4. **Xu, H., Blair, N. T., & Clapham, D. E. (2005).** Camphor activates and strongly desensitizes the transient receptor potential vanilloid subtype 1 channel in a vanilloid-independent mechanism. *The Journal of Neuroscience*, 25(39), 8924–8937.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6725586/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6725586/)
  
5. **Fazmiya, M. J. A., et al. (2022).** Current Insights on Bioactive Molecules, Antioxidant, Anti-Inflammatory, and Other Pharmacological Activities of Cinnamomum camphora Linn. *Oxidative Medicine and Cellular Longevity*, 2022, 9354555.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568346/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568346/)
  
6. **Cherneva, E., Pavlovic, V., Smelcerovic, A., & Yancheva, D. (2012).** The effect of camphor and borneol on rat thymocyte viability and oxidative stress. *Molecules*, 17(9), 10258–10266.  
  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268831/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268831/)
  
7. **U.S. Food and Drug Administration. (2024).** Title 21—Food and Drugs, §310.545. Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. *Electronic Code of Federal Regulations (eCFR)*.  
  [https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-310/section-310.545](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-310/section-310.545)
  
8. **European Commission. (2023).** Commission Regulation (EU) 2023/1545 of 26 July 2023 amending Annex III to Regulation (EC) No 1223/2009 on cosmetic products.  
  [Regulation - 2023/1545 - EN - EUR-Lex](https://eur-lex.europa.eu/eli/reg/2023/1545/oj)


A fragrance ingredient with antimicrobial and soothing properties, but also toxic at high doses and now classified as a fragrance allergen in the EU.

Camphor


**Retinyl palmitate** is an ester of [retinol](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/retinol) and palmitic acid—a storage form of vitamin A that is naturally found in the skin and liver. In skincare, it functions as a **pro-retinoid**, meaning it must first be converted into [**retinol**](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/retinol), then [**retinal**](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/retinaldehyde), and finally [**retinoic acid**](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/tretinoin) to exert its biological effects [1,2]. This multi-step process makes retinyl palmitate **less potent** than retinol [1,2].

---

### How It Compares to Retinol

| Feature | Retinol | Retinyl Palmitate |
| --- | --- | --- |
| **Potency** | High | Low |
| **Conversion** | Retinol → Retinal → RA | Palmitate → Retinol → Retinal → RA |
| **Stability** | Low | Slightly Higher |
| **Regulatory limits (EU)** | 0.3% RE for face/leave-on | Same (0.3% RE max) [3] |

RA = Retinoic Acid

Retinyl palmitate is **slightly more stable** than retinol under oxidative conditions, according to the European Scientific Committee on Consumer Safety (SCCS). However, it still undergoes significant degradation in the presence of light and heat unless protected by stabilizing agents [3].

As for efficacy, the question of whether retinyl palmitate delivers meaningful results in vivo remains controversial. While it acts as a **storage form of vitamin A** and is enzymatically hydrolyzed in the skin to release retinol [1], its **multi-step conversion** means its impact on wrinkle depth or pigmentation is likely minimal at typical cosmetic concentrations.

One preclinical study in [keratinocytes](https://www.skinclasshub.com/theknowledgehub/cosmetic-glossary/keratinocytes) found that retinyl palmitate alone did not upregulate retinoid-responsive genes, but when **combined with retinol**, it enhanced retinol’s effects and reduced UVB-induced DNA damage [4]. In contrast, **another preclinical study** reported that retinyl palmitate alone **reduced collagen degradation**, suppressed UVB-induced inflammatory [cytokines](https://www.skinclasshub.com/theknowledgehub/cosmetic-glossary/cytokines) and improved cell migration and viability following UV damage [5]. These studies suggest retinyl palmitate may have some **independent photoprotective and anti-inflammatory activity** in addition to potential **synergistic effects** when combined with retinol.

### Controversy: Photocarcinogenesis in Animal Studies

In 2010, a draft report from the U.S. National Toxicology Program (NTP) found that **topical retinyl palmitate accelerated photocarcinogenesis in hairless mice** when combined with UV exposure [6]. The Environmental Working Group (EWG) raised public concerns about the photocarcinogenic potential of retinyl palmitate in sunscreens, referencing those rodent studies by the U.S. National Toxicology Program (NTP).

However, dermatology experts have criticized the interpretation of these findings, noting that the **UV exposure conditions used in the NTP study were excessive and not representative** of real-world use. They also argued that the in vitro results from that study may not reflect the complex antioxidant environment of human skin, and that there is **no clinical evidence in humans supporting photocarcinogenicity from retinyl palmitate in sunscreens** [7]. Major regulatory bodies, including the **FDA and EU SCCS**, have reviewed the data and **did not ban the ingredient**, though they recommend concentration limits to ensure overall vitamin A exposure remains safe [4].

### Conclusion

Retinyl palmitate is a low-potency, stable vitamin A derivative; while its standalone efficacy is limited, it may enhance retinol’s effects and offer some photoprotective benefits. Despite past controversy over photocarcinogenicity in animal studies, no human risk has been confirmed, and regulatory agencies in the US, EU, and other regions continue to allow its use within established safety limits.

---

### References

1. **Mukherjee, S., Date, A., Weindl, G., et al. (2006).** Retinoids in the treatment of skin aging: An overview of clinical efficacy and safety. *Clinical Interventions in Aging, 1*(4), 327–348.  
  [https://pmc.ncbi.nlm.nih.gov/articles/PMC2699641/](https://pmc.ncbi.nlm.nih.gov/articles/PMC2699641/)
  
2. **Zasada, M., Budzisz, E. (2019).** Retinoids: Active molecules influencing skin structure formation in cosmetic and dermatological treatments. *Advances in Dermatology and Allergology, 36*(4), 392–397.[[https://pmc.ncbi.nlm.nih.gov/articles/PMC6791161/]](https://pmc.ncbi.nlm.nih.gov/articles/PMC6791161/)
  
3. **Scientific Committee on Consumer Safety (SCCS). (2022).** Opinion on vitamin A (retinol, retinyl acetate, retinyl palmitate) – SCCS/1639/21.  
  [https://ec.europa.eu/health/system/files/2023-08/sccs_o_261.pdf](https://ec.europa.eu/health/system/files/2023-08/sccs_o_261.pdf)
  
4. **Zhong, J., et al. (2025).** Synergistic effects of retinol and retinyl palmitate in alleviating UVB-induced DNA damage and promoting the homologous recombination repair in keratinocytes. *Frontiers in Pharmacology*, 16:1562244.  
  [https://pmc.ncbi.nlm.nih.gov/articles/PMC12058701/](https://pmc.ncbi.nlm.nih.gov/articles/PMC12058701/)
  
5. **Shu, M. et al. (2023).** Efficacy and mechanism of retinyl palmitate against UVB-induced skin photoaging. *Frontiers in Pharmacology, 14*, 1278838. https://pmc.ncbi.nlm.nih.gov/articles/PMC10622759/
  
6. **National Toxicology Program (NTP). (2012).** *NTP Technical Report on the Photocarcinogenesis Study of Retinyl Palmitate (CAS No. 79-81-2) in B6C3F1 Mice (Simulated Solar Light and Topical Application Studies)*. **NTP Technical Report 568.** U.S. Department of Health and Human Services, Public Health Service.  
  [https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr568_508.pdf](https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr568_508.pdf)
  
7. **Wang, S. Q., Dusza, S. W., & Lim, H. W. (2010).** *Safety of retinyl palmitate in sunscreens: A critical analysis*. Journal of the American Academy of Dermatology, 63(5), 903–906.  
  [https://www.jaad.org/article/S0190-9622(10)00850-9/abstract](https://www.jaad.org/article/S0190-9622(10)00850-9/abstract)


A storage form of vitamin A with low potency but higher stability than retinol.

Retinyl Palmitate


**Sodium Ascorbyl Phosphate (SAP)** is a stable, water-soluble derivative of [vitamin C](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/vitamin-c) offering superior formulation stability, antioxidant effects, and clinically demonstrated anti-acne benefits [1].

### Formulation Advantages & Skin Benefits

- **Enhanced Stability**: SAP exhibits greater stability than L-ascorbic acid in aqueous solutions, particularly due to its resistance to oxidation [2]. ​
  
- **Anti-Acne Effects**: Clinical studies have demonstrated that SAP possesses antimicrobial properties effective against acne-causing bacteria, making it beneficial for individuals with acne-prone skin [1]. ​
  

### Safety and Tolerability

Sodium Ascorbyl Phosphate is generally well-tolerated. In animal studies, high-dose dermal application caused only mild, temporary irritation, and eye exposure resulted in slight, reversible conjunctival irritation. Sensitization potential was low, with only mild reactions observed in a small percentage of animals during initial testing and none upon re-challenge [3].

### Conclusion

Sodium Ascorbyl Phosphate stands out among vitamin C derivatives due to its potential anti-acne effects. It is also more stable than L-ascorbic acid in formulations, particularly because it resists oxidation and does not degrade as readily in aqueous environments.

---

### References

1. **Klock, J. et al.** (2005). Sodium ascorbyl phosphate shows in vitro and in vivo efficacy in the prevention and treatment of acne vulgaris. *International Journal of Cosmetic Science*, 27(3), 171–176.[https://pubmed.ncbi.nlm.nih.gov/18492184/](https://pubmed.ncbi.nlm.nih.gov/18492184/)
  
2. **Sasidharan, O., Gholap, A., & Rastogi, R. (2023).** A review of clinical efficacy of topical vitamin C and its derivatives. *Pharmaceutical Science and Technology, 7*(2), 20–26.  
  [https://pdfs.semanticscholar.org/ed04/b17732da7c54b3ed727b1f66aad421f6fa94.pdf](https://pdfs.semanticscholar.org/ed04/b17732da7c54b3ed727b1f66aad421f6fa94.pdf)
  
3. **Cosmetic Ingredient Review Expert Panel. (2024).** Safety assessment of ascorbic acid and ascorbates as used in cosmetics. *Cosmetic Ingredient Review*, Re-Review for Panel Consideration, September 6, 2024.  
   [https://www.cir-safety.org/sites/default/files/Ascorbic%20Acid.pdf](https://www.cir-safety.org/sites/default/files/Ascorbic%20Acid.pdf)  
   

A stable, water-soluble vitamin C derivative with antioxidant properties and clinically supported anti-acne benefits.

Sodium Ascorbyl Phosphate


**Magnesium Ascorbyl Phosphate (MAP)** is a water-soluble derivative of [vitamin C](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/vitamin-c) developed to improve on the limitations of pure ascorbic acid, especially its instability and potential to cause irritation. MAP offers superior stability and gentler skin compatibility, making it a valuable option for cosmetic formulations [1].

---

### Formulation Advantages & Skin Benefits

Scientific evidence indicates several **distinct advantages** of MAP:

- **Stability in Formulations**: MAP demonstrates excellent stability in topical formulations. Its chemical modification protects against rapid oxidation, and it retains stability even in neutral pH conditions (pH 7), unlike ascorbic acid which requires low pH (~3.5) for activity [2].
  
- **Gentler on Skin**: MAP is significantly less irritating than L-ascorbic acid. Animal studies confirmed no irritation after topical application, even at high doses, and sensitization testing showed no allergic reactions [3]. Its compatibility with neutral pH formulations further reduces the risk of low-pH-induced irritation, making it suitable for sensitive skin.
  

### Safety and Tolerability

MAP is well-tolerated and considered safe for use in leave-on cosmetic products. It demonstrated no dermal irritation in animal models at standard application doses, no sensitization or allergic response in guinea pig maximization tests, no genotoxicity in bacterial and mammalian cell studies and no systemic toxicity in acute dermal exposure studies [3].

### Conclusion

Magnesium Ascorbyl Phosphate is a stable and water-soluble vitamin C derivative that offers clear formulation and skin tolerability advantages over ascorbic acid. Its neutral pH compatibility and low irritation potential make it especially attractive for use in sensitive skin formulations, while maintaining the antioxidant benefits of vitamin C.

---

### References

1. **Kandil, S. M., Soliman, I. I., Diab, H. M., Bedair, N. I., Mahrous, M. H., & Abdou, E. M. (2022).** Magnesium ascorbyl phosphate vesicular carriers for topical delivery; preparation, in-vitro and ex-vivo evaluation, factorial optimization and clinical assessment in melasma patients. *Drug Delivery, 29*(1), 534–547.  
   [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040897/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040897/)
  
2. **Ravetti, S., Clemente, C., Brignone, S., Hergert, L., Allemandi, D., & Palma, S. (2019).** Ascorbic acid in skin health. *Cosmetics, 6*(4), 58.  
  [https://www.mdpi.com/2079-9284/6/4/58](https://www.mdpi.com/2079-9284/6/4/58)
  
3. **Cosmetic Ingredient Review Expert Panel. (2024).** Safety assessment of ascorbic acid and ascorbates as used in cosmetics. *Cosmetic Ingredient Review*, Re-Review for Panel Consideration, September 6, 2024.  
  [https://www.cir-safety.org/sites/default/files/Ascorbic%20Acid.pdf](https://www.cir-safety.org/sites/default/files/Ascorbic%20Acid.pdf)
   

A stable, water-soluble vitamin C derivative known for its antioxidant effects, neutral pH compatibility, and excellent tolerability on sensitive skin.

Magnesium Ascorbyl Phosphate


**Ascorbyl Glucoside (AG)** is a water-soluble [vitamin C](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/vitamin-c) derivative formed by combining ascorbic acid with glucose. This modification enhances its stability and reduces potential skin irritation compared to pure ascorbic acid [1].

### Formulation Advantages & Skin Benefits

Scientific studies highlight the following **distinct advantages** of AG:​

- **Enhanced Stability**: Ascorbyl Glucoside (AG) exhibits improved stability compared to ascorbic acid, especially in aqueous solutions. According to a review of vitamin C derivatives, the conjugation of glucose at the 2nd position protects the ascorbic acid structure from degradation triggered by pH, temperature, and metal ions. Studies have shown AG retains its stability at elevated temperatures and at pH 6.4, unlike ascorbic acid, which is highly unstable and rapidly oxidizes under similar conditions [2]. ​
  
- **Reduced Skin Irritation**: AG is significantly less irritating than L-ascorbic acid. Clinical evaluations, including human repeat insult patch tests (HRIPT), have shown that AG-containing formulations do not induce skin sensitization or irritation, even at concentrations up to 10% [1].
  

### Safety and Tolerability

AG is well-tolerated and considered safe for use in cosmetic products. It has demonstrated no dermal irritation in animal models following topical application, no sensitization or allergic responses in human clinical studies, and no genotoxicity in standard in vitro and in vivo assays [1].

### Conclusion

Ascorbyl Glucoside is a stable and water-soluble vitamin C derivative that offers clear advantages over ascorbic acid in terms of formulation stability and skin tolerability. Its compatibility with a neutral pH level and low irritation potential make it especially suitable for sensitive skin formulations, while delivering the antioxidant benefits of vitamin C.

---

### References

1. **Johnson, W. Jr., et al. (2024).** Safety assessment of ascorbyl glucoside and sodium ascorbyl glucoside as used in cosmetics. *International Journal of Toxicology, 44*(Supplement 1), 5S–16S.  
  [https://cir-reports.cir-safety.org/view-attachment/?id=3db8c16b-406c-8081-890e-1a57001b130c](https://cir-reports.cir-safety.org/view-attachment/?id=3db8c16b-406c-8081-890e-1a57001b130c)
  
2. **Oormila Sasidharan et al.** A Review of Clinical Efficacy of Topical Vitamin C and Its Derivatives. *Pharmaceutical Science and Technology*, 2023; 7(2): 20-26. [(PDF) A Review of Clinical Efficacy of Topical Vitamin C and Its Derivatives](https://www.researchgate.net/publication/373795104)
   

A stable, water-soluble vitamin C derivative that offers antioxidant benefits with significantly lower irritation risk, making it ideal for sensitive skin formulations.

Ascorbyl Glucoside


**3-O-Ethyl Ascorbic Acid** is a stable, water-soluble [vitamin C](https://www.skinclasshub.com/theknowledgehub/ingredient-dictionary/vitamin-c) derivative that offers notable advantages over pure ascorbic acid, particularly in terms of skin penetration, pH compatibility, and antioxidant longevity [1].​

### Formulation Advantages & Skin Benefits

Recent studies have highlighted several unique properties of 3-O-Ethyl Ascorbic Acid:​

- **Enhanced Stability**: This derivative exhibits greater resistance to oxidation compared to L-ascorbic acid. Optimal stability has been observed at a pH of 5.46 and a temperature of 36.3°C, making it suitable for formulations closer to the skin's natural pH [2].
  
- **Effective Skin Penetration**: In vitro studies using porcine skin models have demonstrated that 3-O-Ethyl Ascorbic Acid can penetrate the stratum corneum effectively [3].
  
- **Anti-Aging Effects**: A cosmetic serum containing 30% 3-O-Ethyl Ascorbic Acid and 1% lactic acid demonstrated improvements in skin elasticity and a reduction in pigmentation in both in vitro cell cultures and 3D reconstructed tissue models [1].
  

### Safety and Tolerability

3-O-Ethyl Ascorbic Acid is generally well-tolerated in topical applications. Patch tests with concentrations up to 2% showed no skin irritation, and a human repeat insult patch test (HRIPT) at 100% concentration indicated no sensitization. However, in vitro eye irritation studies suggested moderate irritation potential, indicating that care should be taken to avoid contact with the eyes [4].

### Conclusion

3-O-Ethyl Ascorbic Acid stands out among vitamin C derivatives due to its enhanced stability and effective skin penetration. Its compatibility with formulations at a pH closer to that of the skin reduces the risk of irritation, making it a valuable ingredient in cosmetic products aimed at improving skin tone and combating signs of aging.

---

### References

1. **Zerbinati, N., et al. (2021).** The anti-ageing and whitening potential of a cosmetic serum containing 3-O-ethyl-l-ascorbic acid. *Life, 11*(5), 406.  
   [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146548/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146548/)
  
2. **Liao, W. C., Huang, Y. T., Lu, L. P., & Huang, W. Y. (2018).** Antioxidant ability and stability studies of 3-O-ethyl ascorbic acid, a cosmetic tyrosinase inhibitor. *Journal of Cosmetic Science, 69*(4), 233–243.  
  [https://pubmed.ncbi.nlm.nih.gov/30311899/](https://pubmed.ncbi.nlm.nih.gov/30311899/)
  
3. **Iliopoulos, F., et al. (2019).** 3-O-ethyl-l-ascorbic acid: Characterisation and investigation of single solvent systems for delivery to the skin. *International Journal of Pharmaceutics: X, 1*, 100025.  
   [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733298/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733298/)
  
4. **National Industrial Chemicals Notification and Assessment Scheme (NICNAS). (2016).** Public report: L-Ascorbic acid, 3-O-ethyl- (INCI name: 3-O-ethyl ascorbic acid). *NICNAS Public Report LTD/1879*.  
  [https://www.industrialchemicals.gov.au/sites/default/files/LTD1879%20Public%20Report%20PDF.pdf](https://www.industrialchemicals.gov.au/sites/default/files/LTD1879%20Public%20Report%20PDF.pdf)   
  

A stable, water-soluble vitamin C derivative with superior skin penetration and pH compatibility, offering brightening and anti-aging benefits with low irritation risk.

Niacinamide - A versatile, well-tolerated ingredient with proven benefits for acne, pigmentation, skin barrier repair, and aging.
Linalool - A fragrance compound with mild antimicrobial effects, but its oxidized forms are known skin sensitizers.
Caffeine - A circulation-boosting compound that may help reduce the appearance of cellulite and protects against oxidative stress.
Zinc Oxide - A broad-spectrum mineral UV filter with additional skin-soothing and antimicrobial benefits.
Tocopherol - A skin-protecting antioxidant that supports the skin barrier and fights oxidative damage.
Vitamin C - Vitamin C is a powerful but unstable antioxidant that boosts collagen, brightens skin, and protects against oxidative stress—leading to the widespread use of more stable derivatives in skincare.
Camphor - A fragrance ingredient with antimicrobial and soothing properties, but also toxic at high doses and now classified as a fragrance allergen in the EU.
Retinyl Palmitate - A storage form of vitamin A with low potency but higher stability than retinol.
Sodium Ascorbyl Phosphate - A stable, water-soluble vitamin C derivative with antioxidant properties and clinically supported anti-acne benefits.
Magnesium Ascorbyl Phosphate - A stable, water-soluble vitamin C derivative known for its antioxidant effects, neutral pH compatibility, and excellent tolerability on sensitive skin.
Ascorbyl Glucoside - A stable, water-soluble vitamin C derivative that offers antioxidant benefits with significantly lower irritation risk, making it ideal for sensitive skin formulations.
3-O-Ethyl Ascorbic Acid - A stable, water-soluble vitamin C derivative with superior skin penetration and pH compatibility, offering brightening and anti-aging benefits with low irritation risk.

The Knowledge Hub

Ingredient Dictionary