The over-the-counter (OTC) acne market is rapidly expanding. According to the Consumer Healthcare Products Association, consumers spent approximately $607 million on OTC anti-acne products in 2017.
As the cost of prescription acne treatments and their availability decreases now that most insurance companies require prior authorization for them, more skin care companies are entering the OTC acne market. With a relatively low cost and considerable mark-up, acne products can be quite profitable for manufacturers and dermatology practices.
Acne products are unique, however, in that many are considered OTC drugs because they make treatment claims based on monographed ingredients. Acne products listing an active ingredient on the back of the packaging are regulated by the FDA as OTC drugs. The currently used monographed ingredients include: benzoyl peroxide, salicylic acid, and sulfur. These ingredients can only be used singly and not in combination, hindering their effectiveness.
There are other ingredients, such as botanicals, minerals, vitamins, probiotics, and prebiotics, that are entering the acne market, but no treatment claims can be made since these substances are not monographed.
Benzoyl peroxide is one of the most effective and most commonly used active ingredients in OTC acne preparations. Twenty-three percent of individuals aged 13 to 27 years have used an OTC benzoyl peroxide product.1 Benzoyl peroxide is manufactured by reacting sodium peroxide with benzoyl chloride to yield benzoyl peroxide and sodium chloride. It is a highly reactive substance capable of producing DNA strand breaks2; however, no correlation has been shown between benzoyl peroxide use and skin cancer in humans.
Current trends in benzoyl peroxide formulation have focused on the use of less irritating hydrogel formulations and smaller particle size benzoyl peroxide.3 Raw benzoyl peroxide is a particulate that must be solubilized into solution. Only the benzoyl peroxide that touches the skin surface is active in the killing of Propionibacterium acnes. Larger particles yield higher concentrations in the formulation, but most of the benzoyl peroxide does not touch the skin. Smaller particle size allows better skin coverage with less irritation, since the concentration is reduced. It is possible to create a 2.5% benzoyl peroxide formulation with equal efficacy to a 10% benzoyl peroxide formulation based on skin contact with the active.
Benzoyl peroxide is problematic, however, as it can cause allergic contact dermatitis in between 1% and 2.5% of consumers who use it, resulting in redness, swelling, oozing, and pain.4 Benzoyl peroxide can also bleach clothing and hair. This has led to a renewed interest in salicylic acid.
The other major active ingredient in OTC acne treatments is salicylic acid, which is used in concentrations of up to 2%.5 It is a ß-hydroxy acid where the OH group is adjacent to the carboxyl group. Salicylic acid may be less effective than benzoyl peroxide in treating acne, but it is also less irritating and less allergenic.6 Salicylic acid has seen renewed popularity in hypoallergenic acne treatments, spot acne treatments, and acne treatments for mature individuals where benzoyl peroxide would cause excessive irritation.
The least drying and irritating monographed acne active is sulfur.7 It is a yellow, nonmetallic element that has been used for centuries to treat various dermatologic conditions. The mechanism of action for sulfur is not totally understood, but it is thought to interact with cysteine in the stratum corneum, causing sulfur to transform into hydrogen sulfide. Hydrogen sulfide in turn degrades keratin, producing the keratolytic effect.8 It is used in concentrations of 3% to 8%, but has a characteristic foul odor and yellow color. The new development of decolorized, deodorized sulfur has increased its popularity, especially in acne spot treatment formulations for mature individuals.
Nonmongraphed Treatments on page 2
Hydroxy acids, such as glycolic acid, have been used as nonmonographed ingredients in acne products, however, no treatment claims can be made. The efficacy of glycolic acid in treating acne is related to the free acid concentration. The free acid is able to dissolve the ionic bonds between the corneocytes forming the stratum corneum. This desquamation can remove the comedonal plugs, however, the water-soluble glycolic acid cannot enter the oily milieu of the pore. For this reason, the monographed ingredient salicylic acid is a much better comedolytic.
Retinoids are used in both prescription and OTC acne treatments. The recent transition of one particular retinoid, adapalene, from a prescription-only medication to an OTC medication has increased the overall efficacy of the OTC acne market, because adapalene is so effective at treating the microcomedone. Other nonmonographed retinoids, such as retinol, can be absorbed by keratinocytes and reversibly oxidized into retinaldehyde. Retinaldehyde is irreversibly converted into all-trans retinoic acid, known as tretinoin, a potent prescription retinoid. Thus, retinol has been shown to be 20 times less potent than topical tretinoin, but exhibits greater penetration than tretinoin and is found in some acne preparations as an inactive ingredient.9
Tea Tree Oil
Botanicals can also be used as an inactive ingredient in acne formulations. Tea tree oil, renowned for its antibacterial properties, is the most common herbal essential oil used for acne treatment. It is extracted from the leaves of the Australian tree Melaleuca alternifolia.10 Tea tree oil has been found to be as effective as 5% benzoyl peroxide based on a reduction in comedones and inflammatory acne lesions, however, the onset of action was slower for tea tree oil.11 Another randomized, double-blind, placebo-controlled study of 60 individuals with mild to moderate acne found 5% topical tea tree oil produced a statistically significant reduction in total lesion count and acne severity index as compared with a placebo.12
Tea tree oil is a known cause of allergic contact dermatitis, however. An Italian study of 725 participants patch tested with undiluted, 1% and 0.1% tea tree oil found that 6% of participants experienced a positive reaction to undiluted tea tree oil, 1 participant experienced an allergic reaction to 1% tea tree oil, and no participants experienced a reaction to the 0.1% dilution.13
Vitamins and Minerals
There has been a resurgence of nonmonographed vitamins and minerals for acne treatment. Zinc salts are bacteriostatic to P acnes, and orally ingested as a homeopathic acne therapy.14 Oral zinc has also been combined with nicotinamide orally for the treatment of acne through a reduction in inflammation by inhibiting leukocyte chemotaxis, lysosomal enzyme release, and mast cell degranulation.15 An OTC nicotinamide-containing vitamin preparation has been shown to produce acne improvement in 8 weeks.16 Topically, nicotinamide 4% was shown to be comparable to clindamycin gel 1% in the treatment of moderate acne.17
Prebiotics and Postbiotics
The newest area of nonmonographed oral and topical acne formulations is the use of prebiotics and postbiotics. Prebiotics are indigestible food substances that promote the growth of healthy bacteria in the gut. There is said to be a gut-skin connection, implying that acne could be improved by modifying the microbiome, which are the bacterial inhibitants of the gut. Injesting prebiotics might normalize the gut microbiome and improve acne.
Postbiotics, on the other hand, are live bacteria that can be applied topically or orally consumed to improve the skin microbiome.18 Lactobacillus acidophilus cultures are used for this purpose. It is thought that microbiome alternations may influence systemic inflammation, oxidative stress, and glycemic control, among other things. Intestinal permeability may be amplified in acne, so the consumption of oral postbiotics could help.19 Refrigerated postbiotic preparations may also create more microbiome diversity, a common finding in normal skin.
Spotting a Trend
After antiaging, acne has to be the biggest expanding skin product frontier, and the growth of the OTC acne market is sure to continue. With acne products now becoming part of boutique spa lines, physician dispensed skin care, cosmetic company offerings, and store brand products, dermatologists would do well to educate themselves about the range of new products available, so they can better advise their patients.
Dr Draelos is a research and clinical board-certified dermatologist and a fellow of the American Academy of Dermatology. She is in solo private practice in High Point, NC, and a consulting professor of dermatology at Duke University, and has authored 14 books. She is also the founder of Dermatology Consulting Services, PLLC, to initiate and perform research in aging skin, acne, rosacea, psoriasis, atopic dermatitis, actinic keratoses, eczema, and aesthetic procedures in the cosmetic, OTC drug, and pharmaceutical arenas.
Disclosure: The author reports no relevant financial relationships.
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