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Acne is the number one reason that patients visit a dermatologist. It affects an estimated 50 million Americans every year. While we have both topical and oral prescription medications to treat acne, many patients are interested in alternative options instead of or alongside traditional acne treatments. While more studies are needed, there is data to suggest that certain alternative therapies may be useful options for our acne patients.

Here, I review the available data on several alternative therapies for the treatment of acne.

Zinc. Zinc is an element involved in proper skin functioning, and zinc deficiency is associated with skin rashes such as acrodermatitis enteropathica. Both oral and topical zinc therapies have been used to treat conditions ranging from seborrhea to warts.1 Zinc levels have also been shown to be significantly lower in acne patients compared to controls. Several studies have shown improvement in acne with use of both topical and oral zinc therapies. The mechanism of action in treating acne is unclear but may be related to the regulation of lipid metabolism and immune responses, suppressing sebaceous gland activity or inhibiting the production of DHT.2

Omega-3 Fatty Acids. Omega-3 fatty acids are compounds that make up the membranes around cells in our bodies. They provide energy to our bodies and are essential for the functioning of our cardiovascular, immune, and endocrine systems. Omega-3s are commonly taken as a supplement to address a variety of health concerns, including heart disease, elevated triglycerides, macular degeneration, and rheumatoid arthritis.3 EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are omega-3s found in fish and fish oil supplements, while ALA (alpha-linolenic acid) is found in certain plant oils.

Omega-3 fatty acid supplements have been demonstrated to improve acne. In a 10-week study, 45 participants with mild to moderate acne were randomized to take oral omega-3 fatty acid supplements (EPA + DHA), a γ-linoleic acid, or a placebo. Acne lesions and patient subjective assessment improved in the omega-3-treated group. In addition, histologic evaluation showed decreases in interleukin-8 staining.4

Omega-3 fatty acids are thought to address acne by balancing activity of SREBP, a messenger activated by insulin-like growth factor 1 (IGF-1).5 SREBP is thought to activate sebaceous glands, increasing sebum and driving inflammation that leads to acne.6 High glycemic index food is thought to be a driving factor in this pathway, raising blood sugar and levels of IGF-1.7

Saw Palmetto. Saw palmetto (Serenoa repens) is an extract from the palm plant indigenous to the Eastern part of the United States. Because of its high concentration of phytosterols, it has been evaluated for its anti-androgen effects. Studies have been performed using saw palmetto supplements for the treatment of androgenic alopecia, benign prostatic hyperplasia, and polycystic ovary syndrome.8 Saw palmetto has also been suggested as a treatment for acne, and it has been incorporated topically in preparations to treat acne and oily skin. One study of 20 participants showed significant reduction in sebum levels after 4 weeks of use.9

Skullcap. Skullcap is a botanical extract from a flowering plant traditionally used in Eastern medicine for allergies, infections, inflammation, cancer, headaches, and boosting heart health. It is most commonly known for its benefits in relieving stress and is considered a nervine tonic. Nervines are botanicals used to support the central nervous system, restore balance, relieve anxiety, and support feelings of wellness.10

Skullcap may act as an alternative treatment for acne due to its anti-inflammatory effects.11

Skullcap extract has been shown to balance activity of 5-lipoxygenase (5-LOX),12,13 an enzyme involved in sebaceous gland activation. Inhibition of 5-LOX is a novel therapeutic target for acne, and both experimental and clinical studies have been performed using Zileutin, an asthma medication known to block 5-LOX activity.14 5-LOX controls synthesis of leukotriene B4 (LTB4), which drives tissue inflammation and contributes to acne.15,16

Linoleic Acid. Individuals with acne are known not only to produce more oil than non-acne-prone patients but also compositionally different oil. The sebum in acne-prone patients is known to have low concentrations of linoleic acid, a fatty acid building block used to make certain ceramides.17,18 Moreover, the skin of acne-prone patients has been shown to be ceramide deficient, with a correlation between acne severity and degree of ceramide deficiency.19 This ceramide deficiency and subsequent skin barrier dysfunction is thought to directly contribute to the follicular hyperkeratinization that creates bottlenecks in the follicles that trap sebum and lead to comedone formation. Replacing linoleic acid may be of benefit to acne patients, and one study evaluating the topical application of linoleic acid showed clinical improvement in acne lesions.20

Vitamin C. Vitamin C is perhaps the most commonly used topical antioxidant to treat aging skin. It has antioxidant effects and neutralizes environmental free radical damage. In addition, it blocks the production of abnormal pigmentation and serves as a cofactor for the production of collagen. Topical application of Vitamin C has been shown to be beneficial in treating acne.

While the sebum in acne-prone individuals is known to be deficient in linoleic acid, it contains higher than normal levels of squalene.21 As sebum reacts with environmental aggressors, squalene is transformed into high-energy compounds known as squalene peroxide, in a process known as lipid peroxidation.22,23 These squalene epoxides are thought to stimulate sebaceous glands, drive inflammation, and promote the development of acne. The skin naturally possesses its own antioxidant defenses, primarily through natural Vitamin E in the sebum.24 This system is often not enough to neutralize lipid peroxidation. Studies have shown that topical application of a stabilized form of Vitamin C, known as sodium ascorbyl phosphate, resulted in the improvement of acne lesions.25 The mechanism of action is thought to be due to the antioxidant effects of Vitamin C.

Black Cumin. Extracts from black cumin (Nigella sativa) seed have been used for centuries to treat skin issues due to its antimicrobial effects.26 In fact, there’s data showing that black cumin is effective in killing C. acnes bacteria, making it an option in addressing acne.27C. acnes is an anaerobic bacteria that lives normally within the sebaceous glands as part of the skin’s natural microbiome. C. acnes plays a central role in the pathogenesis of acne, promoting inflammation that drives comedone formation. Clinical studies have shown comparable improvements in mild to moderate acne using a black cumin seed extract containing lotion compared to 5% benzoyl peroxide.28

Options to Consider

Consensus guidelines recommend combination therapies of FDA-approved acne treatments as first-line therapy for acne. These agents include benzoyl peroxide, topical retinoids, topical antibiotics, and newer options like topical dapsone and clascoterone. For moderate to severe acne, or in cases where patients may be developing scarring, oral medications are recommended as well. However, many patients are looking for alternative options as adjunctive treatment or to take the place of these prescriptions. While further studies are needed to fully assess the efficacy and safety of the options reviewed in this paper, they provide treatment recommendations we can consider for our interested patients.

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2. Cervantes J, et al. Dermatol Ther. 2018 Jan;31(1).

3.The National Advisory Council for Complementary and Integrative Health Omega-3 Supplements: In Depth. (accessed 8/14/22)

4.Jung JJ, et al. Acta Derm Venereol. . 2014 Sep;94(5):521-5.

5.Fukumitsu, S et al. Cytotechnology. 2013 Dec; 65( 6): 899-907.

6. Smith T, et al. J Invest Dermatol. 2008 May; 128( 5): 1286–1293.

7. Melnik B. Clin Cosmet Invertig Dermatol. 2015; 8: 371–388.

8. Grant, P et al. Int J Endocrinol Metab. 2012 Spring; 10( 2): 497–502.

9. Dobrev H, et al. J Cosmet Dermatol, 2007 Jun;6(2):113-8.

10. Upton R. J Herbal Med. 2012, 2 (3): 76-96.

11. Romm A et al. CHAPTER 5 - Menstrual Wellness and Menstrual Problems, Editor(s): Aviva Romm, Mary L. Hardy, Simon Mills, Botanical Medicine for Women’s Health, Churchill Livingstone, 2010, Pages 97-185.

12. Burnett BP. J Med Food. 2007 Sep;10(3):442-51.

13. Altavilla, D. Br J Pharmacol. 2009 Aug;157(8):1410-8.

14. Zouboulis CC. Dermatoendocrinol. 2009 May-Jun; 1( 3): 188–192.

15. Chen S et al. Cell Prolif. 2001 Oct; 34( 5): 293-304.

16. Butenko, IG. Comparative Study Agents Actions. 1993;39 Spec No:C49-51.

17, Pappas A, et al. 2009 May-Jun; 1(3 ): 157–161.

18. Ottaviani, M et al. Mediators Inflamm. 2010; 2010: 858176.

19. Yamamoto A. Arch Dermatol Res. 1995;287(2):214-8

20. Letawe C, et al. Clin Exp Dermatol. 1998 Mar;23(2):56-8.

21. Pappas A, et al. 2009 May-Jun; 1(3 ): 157–161.

22. Bowe, WP et al. Lipids Health Dis 9, 141 (2010).

23.Shimizu, N et al. Sci Rep 8, 9116 (2018).

24, Ottaviani, M et al. Mediators Inflamm. 2010; 2010: 858176.

25. Klock, J et al. Int J Cosmet Sci. 2005 Jun;27( 3):171-6.

26. Ahmad F, et al. J Herb Med. 2021 Feb; 25: 100404.

27. Eid AM. J Trop Med. 2017; 2017: 7092514.

28. Hadi NA et al. Iraqi Postgraduate Medical Journal. 2010. 9 (4): 371–376.

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