How much of an active ingredient to use for optimal skin benefit can be confusion. Formulating with them whilst balancing effectiveness, safety, and regulatory responsibilities can be even more confusing. This is a quick guide to help you muddle through this minefield.

Vitamin C

Vitamin C has various forms of mechanism. It is a potent antioxidant, anti-ageing, photoprotective and anti-pigmentation. In terms of topical use it comes in various forms, both water and oil soluble. Water soluble vitamin C is thought to be the most biologically available for the skin, however it is the most unstable and prone to oxidisation very quickly. Studies have found that the optimum percentage to use vitamin C is between 8-20%, any more than that is simply a waste.

The optimal concentration of vitamin C depends on its formulation. In most cases, for a product to be of biological significance, it needs to have a vitamin C concentration higher than eight percent.4 Studies have shown that a concentration above 20 percent does not increase its biological significance and, conversely, might cause some irritation.4 Reputable products of vitamin C available today are, therefore, in the range of 10 to 20 percent. (Al-Niaimi F, 2017)

Hyaluronic Acid

Hyaluronic Acid, a naturally occurring glycosaminoglycans found throughout the body, helping to form cells into tissue and is found in all connective tissue in the body. In cosmetics it is primarily used to draw and hold moisture to the skin. However some studies have shown that it ‘exhibit remarkable anti-wrinkle, anti-nasolabial fold, anti-aging, space-filling, and face rejuvenating properties. This has been achieved via soft tissue augmentation, improved skin hydration, collagen and elastin stimulation, and face volume restoration.”(Bukhari, 2018). Moreover, depending on the molecular weight it can also be an effective penetration enhancer. Current research suggests that the top use rate for hyaluronic acid is 2%, above which it then becomes pointless (Witting et al 2015)

Glycolic Acid

Glycolic acid (GA) is a alpha-hydroxy acid (AHA) which is a group of organic acids naturally found in fruits, milk, and other natural sources. AHAs have been a very popular ingredient in skincare and dermatological treatments for several years, if not decades as chemical exfoliants. For this reason, GA and other AHAs are well established in terms of research. Glycolic acid is the smallest molecular size of all the AHA’s and therefore has greater penetration into the skin. Depending on the concentration it can cause various levels of skin peeling. The benefits of glycolic acid include revitalizing skin tone, reducing wrinkles, increasing the skin’s moisture levels, improving texture and tactile roughness, and fading hyperpigmentation.

Fabbrocini, in 2009, classified glycolic peels as: very superficial (30%–50% GA, applied for 1–2 minutes); superficial (50%–70% GA, applied for 2–5 minutes); and medium depth (70% GA, applied for 3–15 minutes).8 GA peels have antiinflammatory, keratolytic, and antioxidant effects. GA targets the corneosome by enhancing breakdown and decreasing cohesiveness, causing desquamation.9 (Sharad 2013)

However, due to regulatory reasons (UK/EU/US) concentrations of up to 10% with a pH of 3.5-4 are recommended for commercial use products.

Urea

Urea is often called Carbamide, the primary organic solid of urine, which is waste produced by the body after it metabolises protein. Urea is a hygroscopic molecule (capable of absorbing water) present in the epidermis as a component of the natural moisturizing factor (NMF) and is essential for the adequate hydration and integrity of the stratum corneum (Piquero-Casals, 2021). For cosmetic use urea is synthesised into a white crystalline powder.

Urea has many mechanisms of action. It Increases moisturization of the stratum corneum, Improves skin's barrier function and antimicrobial defence, regulates epidermal proliferation (improved wound healing), has Keratolytic action (peeling/exfoliating), Increases drug penetration (facilitates the delivery of other drugs into the stratum corneum) (ibid). Urea is found in many products ranging from cosmetics to pharmaceutical treatments to drug delivery systems and can be found in concentrations ranging from 2% to 50%. For cosmetic use the recommended concentration for routine maintenance of healthy skin is 2-20% (ibid) but some studies have found that for dry skin treatments there was no significant difference between a 5% concentration and a 10% one.

Salicylic Acid

This beta hydroxy acid is a common exfoliating ingredient indicated in the treatment of acne vulgaris. It is naturally ocuring in Wintergreen. For cosmetic formulation it comes in the form of a white crystalline powder that is oil soluble which allows it to penetrate into the pore to dissolve pimple and acne forming sebum. Although some treatment peels do reach up to 30%, this is only something available from a trained professional. Most acne treatments available at the drug store (pharmacy) will be in the range of 0.5 an 2% due to regulations.

In three placebo-controlled studies and a comedolytic assay, salicylic acid pads reduced the number of primary lesions and thereby the number and severity of all lesions associated with acne. Comparative studies of salicylic acid have shown it to be superior to benzoyl peroxide in reducing the total number of acne lesions (Zander, 1993).

Niacinamide

Niacinamide, a form of vitamin B3, is one of the most popular cosmetic ingredients due to its ability to treat almost all common skin complaints whilst being well tolerated by most people. Niacinamide plays an important role in energy metabolism and as such is naturally occurring in every cell in the human body. It is also available in a variety of foods. Cosmetic niacinamide comes in a crystallised, water soluble, powder and usually added to the water phase of emulsions. In terms of its actions, it has the ability to treat the signs of ageing, improve acne, improve skin barrier function and texture, reduce redness and lastly work as a free radical scavenger (Gehring W., 2004). Most studies where there has been a notable effect on the skin issues mentioned have been with niacinamide concentration of between 2% and 5%

Azelaic Acid

Azelaic acid is a dicarboxylic acid naturally found in grains such as barley, wheat and rye. It is extracted and purified in a lab and is normally supplied as a white powder. Some brands are COSMOS certified.

Studies have proven that azelaic acid can make a huge difference when it comes to reducing and preventing acne breakouts. It also helps fade discolouration and is used for people with various hyperpigmentary skin disorders ‘characterised by hyperactive/abnormal melanocyte function, including melasma and, possibly, lentigo maligna.’(Fitton A, Goa KL., 1991) and in this respect is at least as effective as hydroquinone. Most studies have shown it to be effective for acne and hyperpigmentation (melasma) at the rate of 20%

Azelaic acid used at 15% has also been show to have a significant effect in reducing inflammation of rosacea. Its use as a powerful anti inflammatory have made it very popular for acne treatments in particular. There are also a number of brands cited in the British National Formulary for the treatment of acne and rosacea (Wirth PJ, 2017)

Retinol

Retinoids without a doubt are the go to ingredient for ageing and photo-ageing. It is also considered an effective treatment of acne and associated skin discolouration.

Some classes of retinoids, such as tretonin, can cause some irritation such as burning, scaling and dermatitis (Mukherjee S. et al 2006). As such you will find that in many western countries tretonin and its counterparts are only available on prescription. Retinol (not to be confused with its more potent derivatives such as tretinoin), on the other hand, is much less irritating than tretonin and other first generation retinoids.

Studies have ‘demonstrated that retinol could be as effective as retinoic acid in producing ‘retinoid mediated histological changes’ (like epidermal thickening and keratinocyte proliferation), but with much less irritancy. In a controlled clinical trial of a retinol formulation researchers observed a significant improvement in fine lines and wrinkles following a 12 weeks of treatment (Fisher et al., 1998) Later, Varani (2000) and his colleagues found that topical application of 1% retinol over 7 days ‘reduced MMP (matrix metalloproteinase), collagenase, and gelatinase expression with concomitant increase in fibroblast growth and collagen synthesis in the studied tissue specimens.’ The conclusion reached was that at this level retinol can decrease the signs of ageing and photoageing,

References

Al-Niaimi F, Chiang NYZ. Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications. J Clin Aesthet Dermatol. 2017;10(7):14-17.

Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: A key molecule in skin aging. Dermatoendocrinol. 2012;4(3):253-258. doi:10.4161/derm.21923

Bukhari SNA, Roswandi NL, Waqas M, Habib H, Hussain F, Khan S, Sohail M, Ramli NA, Thu HE, Hussain Z. Hyaluronic acid, a promising skin rejuvenating biomedicine: A review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects. Int J Biol Macromol. 2018 Dec;120(Pt B):1682-1695. doi: 10.1016/j.ijbiomac.2018.09.188. Epub 2018 Oct 1. PMID: 30287361.

Witting M, Boreham A, Brodwolf R, Vávrová K, Alexiev U, Friess W, Hedtrich S. Interactions of hyaluronic Acid with the skin and implications for the dermal delivery of biomacromolecules. Mol Pharm. 2015 May 4;12(5):1391-401. doi: 10.1021/mp500676e. Epub 2015 Apr 22. PMID: 25871518.

Sharad J. Glycolic acid peel therapy - a current review. Clin Cosmet Investig Dermatol. 2013;6:281-288. Published 2013 Nov 11. doi:10.2147/CCID.S34029

Piquero-Casals J, Morgado-Carrasco D, Granger C, Trullàs C, Jesús-Silva A, Krutmann J. Urea in Dermatology: A Review of its Emollient, Moisturizing, Keratolytic, Skin Barrier Enhancing and Antimicrobial Properties. Dermatol Ther (Heidelb). 2021;11(6):1905-1915. doi:10.1007/s13555-021-00611-y

Zander E, Weisman S. Treatment of acne vulgaris with salicylic acid pads. Clin Ther. 1992 Mar-Apr;14(2):247-53. PMID: 1535287.

Gehring W. Nicotinic acid/niacinamide and the skin. J Cosmet Dermatol. 2004 Apr;3(2):88-93. doi: 10.1111/j.1473-2130.2004.00115.x. PMID: 17147561.

Cosmetic Ingredient Review

Dębek, Paula & Piotrowska, Anna & Nastałek, Magdalena & Totko-Borkusiewicz, Natalia & Czerwińska-Ledwig, Olga & Zuziak, Roxana & Pilch, Wanda. (2018). The use of azelaic acid in selected dermatological disorders. 307-314. 10.25121/MR.2018.21.4.307.

Fitton A, Goa KL. Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders. Drugs. 1991 May;41(5):780-98. doi: 10.2165/00003495-199141050-00007. PMID: 1712709.

Wirth PJ, Henderson Berg MH, Sadick N. Real-World Efficacy of Azelaic Acid 15% Gel for the Reduction of Inflammatory Lesions of Rosacea. Skin Therapy Lett. 2017 Nov;22(6):5-7. PMID: 29091380.

Gibson JR. Azelaic acid 20% cream (AZELEX) and the medical management of acne vulgaris. Dermatol Nurs. 1997 Oct;9(5):339-44. PMID: 9392765.

Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clin Interv Aging. 2006;1(4):327-348. doi:10.2147/ciia.2006.1.4.327

Piérard-Franchimont C, Castelli D, Cromphaut IV. Tensile properties and contours of aging facial skin, A controlled double-blind comparative study of the effects of retinol, melibose-lactose and their association. Skin Res Technol. 1998;4:237–43.

Varani J, Warner RL, Gharaee-Kermani M, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol. 2000;114:480–6