Hydroxy acids are a class of organic acid commonly used in skin care products. Made up of two main categories – alpha-hydroxy acids (AHAs) and beta-hydroxy acids (BHAs) – these ingredients form a class of compounds with a diverse range of benefits for the skin and widespread use in cosmetic and therapeutic formulations.
Both AHAs and BHAs have proved popular as active ingredients for skin care products due to their ability to modulate skin structure and performance – offering the power to exfoliate, hydrate and improve the health and appearance of skin, including skin affected by aging, acne and hyperpigmentation. The hydroxy acids also continue to be important topical cosmeceutical and therapeutic tools as they offer significant epidermal and dermal benefits to skin and can help strengthen and restore the skin barrier, and provide support for maintaining a healthy and balanced skin microbiome.
Here we will explore the chemistry and capabilities of AHAs and BHAs, as well as clinical evidence to support their various benefits for the skin and its microbiota.
What are hydroxy acids and where are they found?
AHAs and BHAs are organic compounds commonly used in skin care for their exfoliating properties, but their benefits diverge due to differences chemical structures and the way they work on the skin.
AHAs consist of a carboxylic acid with a hydroxyl group substituent on the adjacent alpha carbon. The molecules are water-soluble and work by breaking down the bonds between dead skin cells, allowing easy removal [1,2]. This can support improved texture and brightness, and has led to common use of AHAs for fine lines, wrinkles, and hyperpigmentation [1]. The most commonly hydroxy acid in skin care is glycolic acid, an AHA used extensively in cosmetic antiaging formulations, moisturizers and peels, and in treatment products to improve hyperpigmentation and acne. However, others include lactic acid, citric acid, mandelic acid and ferulic acid. AHAs can be derived from various sources but many are present in foods such as fruits (e.g. citric acid from citrus fruits) and milk (e.g. lactic acid) [1,2].
BHAs also contain a carboxylic acid and hydroxyl group but the two components are separated by two carbon atoms. In contrast to their water-soluble AHA counterparts, BHAs are oil-soluble acids that can penetrate deep into the pores to unclog them and exfoliate the skin. This makes BHAs particularly well-suited for people with oily or acne-prone skin as they can help improve the appearance of breakouts. Salicylic acid is the most common BHA used in skin care – it is a milder hydroxy acid extracted from plants, primarily willow bark. Some BHAs, such as β-hydroxybutanoic acid, are also present in body tissues as metabolic intermediates and energy sources; however, they have not yet been commercialized in dermatologic formulations [1,2].
It’s important to use both AHAs and BHAs in the right concentration and frequency, as excessive use can cause skin irritation or sensitivity. The level of skin irritation caused by AHAs and BHAs can vary from person to person, but in general AHAs are more likely to cause skin irritation. As AHAs are water-soluble acids that work by breaking down the bonds between dead skin cells, this can cause skin sensitivity and redness if the concentration is too high or if the product is used too frequently. This risk of irritation can also be increased further if the AHA is used in conjunction with other active ingredients or procedures, such as retinoids or chemical peels (see guidance from the FDA on use of AHAs).
However, chemistry does also vary within the two groups, making some acids more suitable for us on skin. Mandelic acid, for example, is an AHA derived from almonds and is considered gentle compared to others such as glycolic acid as it has a larger molecular size that makes it less penetrative and less likely to cause irritation. This makes it a good option for people with sensitive skin or those new to AHAs. As well as this, mandelic acid, along with some other AHAs such as benzilic acid, also contains a phenyl group as a side-chain substituent. This changes the solubility profile of the AHA, providing increased lipophilicity over conventional water-soluble AHAs and making the molecules more primed to target oily and acne-prone skin [1].
BHAs are generally considered to be gentler on the skin and less likely to cause irritation compared to AHAs as the intramolecular hydrogen bridge that adds acidity must cover a longer distance and is less easily formed. As a result, BHAs are associated with reduced risk of irritation. However, BHAs can still cause skin irritation or dryness in some people, especially if the concentration is too high or if the product is used too frequently (see guidance from the FDA on use of BHAs).
Claims and clinical evidence for the use of hydroxy acids in skin care
Anti-aging
AHAs are frequently used for anti-aging due to their ability to exfoliate the skin and promote cell turnover, which can help improve the appearance of photodamage, fine lines, wrinkles and hyperpigmentation. AHAs can also stimulate the production of skin structural components to help maintain skin elasticity, firmness and hydration. In vivo and in vitro observations have shown that AHAs such as glycolic acid increase production of collagen as well as hyaluronic acid and fibroblasts (which contribute to the formation of connective tissue), and can increase dermal thickness [3,4]. Glycolic acid, lactic acid and citric acid, for example, have been shown to increase collagen synthesis and increased skin thickness without detectable inflammation [5,6].
Hyperpigmentation
As well as an increase in total skin thickness and firmness, diminished dyspigmenation and reduced wrinkling has also been observed following application of AHAs – showing their benefit not only for anti-aging but also hyperpigmentation and hypopigmentation [1]. Both AHAs and BHAs offer potential here due to their ability to increase melanogenesis, for example by accelerating epidermal desquamation and melanin turn over (e.g. salicylic acid) or by acting as an antioxidants (e.g. ferulic acid) [7].
Photodamage and photoprotection
Hydroxy acids can also be used to alleviate the effects of photo-damage and to provide photoprotection. One study that investigated the effects of glycolic acid found that topical application to facial skin decreased wrinkling, solar keratoses and rough texture and lightened solar lentigines, along with an enhanced granular layer, epidermal thickening and increase in dermal collagen thickness [2,7,8].
In terms of photoprotection, ferulic acid provides an interesting example of an AHA with diverse uses due to its chemistry. A naturally occurring plant antioxidant also classed as a phenolic acid, ferulic acid is considered a superior antioxidant due to the number of hydroxyl and methoxy groups attached to its phenyl ring. It acts not only as a free radical scavenger, but also an enhancer of scavenger enzyme activity and an inhibitor of enzymes that catalyze free radical generation. This primes it for use against acute or chronic UV radiation, which can induce the production of reactive oxygen species and reactive nitrogen species and cause premature skin aging, erythema, inflammation and photo-carcinogenesis. Hence, ferulic acid can be applied in skin care formulations (also used in combination with other antioxidants such as vitamins C and E) as a photoprotective agent and to delayer skin photoaging processes [9,10,11].
Skin barrier strength and hydration
The chemistry of AHAs can help strengthen the skin barrier by increasing epidermal proliferation and thickness and maintaining or restoring hydration through the production of hyaluronic acid [7,12]. For example, the application of lactic acid, which occurs naturally on our skin as a skin microbiome byproduct, has been shown to increase skin barrier strength [12]. Staphylococcus epidermidis, one of the most common skin commensals, produces lactic acid through the fermentation of glycerol. As well as inhibiting the growth of pathogenic bacteria, lactic acid also hydrates and upregulates the expression of several key genes that are associated with the barrier properties of the skin [13].
The strengthening of the skin barrier and the associated hydration and moisturizing properties mean that AHAs can also be used to help treat xerosis (dry skin). Lactic acid contributes to cell turnover via the cell cycle and is a well-known part of the skin’s natural moisturizing complex, and so is considered an excellent moisturizer [14]. In line with this, topical AHA formulations have been shown to restore the stratum corneum and epidermis to a more normal clinical and histologic state when applied to xerotic skin [1,14].
Acne
The ability of hydroxy acids to help treat acne has been demonstrated widely, with applications of both AHAs (namely glycolic acid) and BHAs (salicylic acid) in cases of mild to moderately severe facial acne shown to decrease acne severity and the number of papules and pustules in multiple clinical trials [2]. Glycolic acid, for example, can help diminish skin marks and unclog pores, and can also inhibit Cutibacterium acnes – bacteria that can act as an acne trigger [15]. However, BHAs such as salicylic acid tend to be more popular for use against acne due to their chemistry and the reduced risk of irritation. By penetrating deep into pores, salicylic acid dissolves the sebum and other impurities that can contribute to acne breakouts and can also help to regulate oil production and prevent the skin from becoming too oily, which can contribute to the formation of new acne pimples [16].
Wound healing and inflammation
As well as supporting the skin barrier and helping to combat dry skin, the topical application of lactic acid bacteria is also a recognized approach to help improve skin health due to the wound healing and anti-inflammatory effects of lactic acid. In one study that analysed several strains of lactic acid bacteria, the bacterial lysates (namely those of Lactobacillus plantarum and Lactobacillus salivarius) accelerated re-epithelization and wound healing via increased production and migration of keratinocytes (skin cells that make up the structural component of the epidermis), and decreased secretion of pro-inflammatory mediators from the keratinocytes. The lactobacilli lysates also modulated the proteome of the exposed keratinocytes, including alterations to proteins and pathways associated with wound healing and anti-inflammatory effects [17].
Skin microbiome benefits
Although long-term effects of certain hydroxy acids on the skin microbiome remain to be investigated and characterized in detail, research has identified potential benefits for our skin microflora. For instance, AHAs and BHAs can help support an acidic environment for skin microbial growth – skin flora depend on an acidic environment that is maintained mostly by lactic acid in sweat and sebum, but hydroxy acids can support this. As well supporting the growth of commensal bacteria, this can also help keep potentially pathogenic bacteria at bay [13,14]. Here lactic acid bacteria such as L. salivarius and Lactobacillus fermentum have demonstrated anti-pathogenic effects against both Staphylococcus aureus and Streptococcus pyogenes, while Lactobacillus brevis and Lactobacillus paracasei were shown to inhibit S. aureus or S. pyogenes, respectively [17].
These acid benefits can also extend beyond the skin – clinical trials have indicated that probiotic bacteria can modulate the immune system at both local and systemic levels, thereby improving immune defence mechanisms and/or down-regulating immune disorders such as allergies and intestinal inflammation. Lactic acid also maintains intestinal microflora through acid-based balancing properties, and accumulating evidence suggests that intestinal microbiota correlate with many health issues such as obesity, diabetes, metabolic syndrome, inflammatory bowel disease, autoimmune disease, colon cancer and atopic dermatitis [14].
However, caution is needed – acids can also cause microbial dysbiosis as it is a delicate balance. Skin pH could be lowered to a point where the acidity inhibits beneficial bacterial growth, and glycolic and other acids used to target C. acnes when used as an acne treatment can also wipe out other bacteria by acting indiscriminately due to its non-specific nature – both mutualistic or commensal and pathogenic strains [15]. Sensitive skin and desquamation can be useful as indicators of skin dysbiosis in such cases. Where issues do arise, lactic acid may also offer a better solution with less risk of skin irritation and microbial disturbance compared with products such as glycolic acid due to its natural presence in the skin and gut [14,15].
References
1. Green, B. A. et al. Clinical and cosmeceutical uses of hydroxyacids. Clinics in Dermatology (2009) 27, 495–501.
2. Babilas, P. et al. Cosmetic and dermatologic use of alpha hydroxy acids. JDDG; 2012 10:488–491.
3. Kim SJ, Park JH, Kim DH, et al. Increased in vivo collagen synthesis and in vitro cell proliferative effect of glycolic acid. Dermatol Surg 1998;24:1054-8.
4. Bernstein EF, Lee J, Brown DB, et al. Glycolic acid treatment increases type I collagen mRNA and hyaluronic acid content of human skin. Dermatol Surg 2001;27:1-5.
5. Souto, E. B. et al. Nanomaterials for Skin Delivery of Cosmeceuticals and Pharmaceuticals. Appl. Sci. 2020, 10(5), 1594.
6. Ditre CM, Griffin TD, Murphy GF, Sueki H, Telegan B, Johnson WC, Yu RJ, van Scott EJ. Effects of alphahydroxy acids on photoaged skin: a pilot clinical, histologic, and ultrastructural study. J Am Acad Dermatol 1996; 34: 187–95.
7. Mohiuddin, A. K. Skin Lightening & Management of Hyperpigmentation. Pharma. Sci. Analyt. Res. J. 2, 2 (2019).
8. Newman N, Newman A, Moy LS, Babapour R, Harris AG, Moy RL. Clinical improvement of photoaged skin with 50 % glycolic acid. A double-blind vehicle-controlled study. Dermatol Surg 1996; 22: 455–60.
9. Bezerra, G. et al. Compatibility study between ferulic acid and excipients used in cosmetic formulations by TG/DTG, DSC and FTIR. J. Therm. Anal. Calor. 10.1007/s10973-016-5654-9 (2016).
10. Zduńska, K. Antioxidant Properties of Ferulic Acid and Its Possible Application. Skin Pharmacol Physiol 2018;31:332–336.
11. Murray JC, Burch JA, Streilein RD, Iannacchione MA, Hall RP, Pinnell SR: A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. J Am Acad Dermatol 2008; 59: 418–425.
12. Algiert-Zielińska, B. et al. Lactic and lactobionic acids as typically moisturizing compounds. Int J Dermatol . 2019 Mar;58(3):374-379.
13. Salganokar, N. et al. Glycerol fermentation by skin bacteria generates lactic acid and upregulates the expression levels of genes associated with the skin barrier function. Exp. Dermatol. 31, 1364-1372 (2022).
14. Tang, S.-C. & Yang, J.-H. Dual Effects of Alpha-Hydroxy Acids on the Skin. Molecules 2018, 23, 863; doi:10.3390/molecules23040863.
15. https://thesecretlifeofskin.com/2020/09/25/glycolic-acid-acne-atopic-dermatitis/
16. https://www.healthline.com/health/skin/salicylic-acid-for-acne#how-to-use
17. Brandi, J. et al. Exploring the wound healing, anti‑inflammatory, anti‑pathogenic and proteomic effects of lactic acid bacteria on keratinocytes. Sci. Rep. (2020) 10:11572
