Complementary alternative medicine (CAM) has been described by the National Center for Complementary and Integrative Medicine as “health care approaches that are not typically part of conventional medical care or that may have origins outside of usual Western practice.”1 Although this definition is broad, CAM encompasses therapies such as traditional Chinese medicine, herbal therapies, dietary supplements, and mind/body interventions. The use of CAM has grown, and according to a 2012 National Center for Complementary and Integrative Health survey, more than 30% of US adults and 12% of US children use health care approaches that are considered outside of conventional medical practice. In a survey study of US adults, at least 17.7% of respondents said they had taken a dietary supplement other than a vitamin or mineral in the last year.1 Data from the 2007 National Health Interview Survey showed that the prevalence of adults with skin conditions using CAM was 84.5% compared to 38.3% in the general population.2 In addition, 8.15 million US patients with dermatologic conditions reported using CAM over a 5-year period.3 Complementary alternative medicine has emerged as an alternative or adjunct to standard treatments, making it important for dermatologists to understand the existing literature on these therapies. Herein, we review the current evidence-based literature that exists on CAM for the treatment of atopic dermatitis (AD), psoriasis, and alopecia areata (AA).
Atopic Dermatitis
Atopic dermatitis is a chronic, pruritic, inflammatory skin condition with considerable morbidity.4,5 The pathophysiology of AD is multifactorial and includes aspects of barrier dysfunction, IgE hypersensitivity, abnormal cell-mediated immune response, and environmental factors.6 Atopic dermatitis also is one of the most common inflammatory skin conditions in adults, affecting more than 7% of the US population and up to 20% of the total population in developed countries. Of those affected, 40% have moderate or severe symptoms that result in a substantial impact on quality of life.7 Despite advances in understanding disease pathology and treatment, a subset of patients opt to defer conventional treatments such as topical and systemic corticosteroids, antibiotics, nonsteroidal immunomodulators, and biologics. Patients may seek alternative therapies when typical treatments fail or when the perceived side effects outweigh the benefits.5,8 The use of CAM has been well described in patients with AD; however, the existing evidence supporting its use along with its safety profile have not been thoroughly explored. Herein, we will discuss some of the most well-studied supplements for treatment of AD, including evening primrose oil (EPO), fish oil, and probiotics.5
Oral supplementation with polyunsaturated fatty acids commonly is reported in patients with AD.5,8 The idea that a fatty acid deficiency could lead to atopic skin conditions has been around since 1937, when it was suggested that patients with AD had lower levels of blood unsaturated fatty acids.9 Conflicting evidence regarding oral fatty acid ingestion and AD disease severity has emerged.10,11 One unsaturated fatty acid, γ-linolenic acid (GLA), has demonstrated anti-inflammatory properties and involvement in barrier repair.12 It is converted to dihomo-GLA in the body, which acts on cyclooxygenase enzymes to produce the inflammatory mediator prostaglandin E1. The production of GLA is mediated by the enzyme delta-6 desaturase in the metabolization of linoleic acid.12 However, it has been reported that in a subset of patients with AD, a malfunction of delta-6 desaturase may play a role in disease progression and result in lower baseline levels of GLA.10,12 Evening primrose oil and borage oil contain high amounts of GLA (8%–10% and 23%, respectively); thus, supplementation with these oils has been studied in AD.13
EPO for AD
Studies investigating EPO (Oenothera biennis) and its association with AD severity have shown mixed results. A Cochrane review reported that oral borage oil and EPO were not effective treatments for AD,14 while another larger randomized controlled trial (RCT) found no statistically significant improvement in AD symptoms.15 However, multiple smaller studies have found that clinical symptoms of AD, such as erythema, xerosis, pruritus, and total body surface area involved, did improve with oral EPO supplementation when compared to placebo, and the results were statistically significant (P=.04).16,17 One study looked at different dosages of EPO and found that groups ingesting both 160 mg and 320 mg daily experienced reductions in eczema area and severity index score, with greater improvement noted with the higher dosage.17 Side effects associated with oral EPO include an anticoagulant effect and transient gastrointestinal tract upset.8,14 There currently is not enough evidence or safety data to recommend this supplement to AD patients.
Although topical use of fatty acids with high concentrations of GLA, such as EPO and borage oil, have demonstrated improvement in subjective symptom severity, most studies have not reached statistical significance.10,11 One study used a 10% EPO cream for 2 weeks compared to placebo and found statistically significant improvement in patient-reported AD symptoms (P=.045). However, this study only included 10 participants, and therefore larger studies are necessary to confirm this result.18 Some RCTs have shown that topical coconut oil, sunflower seed oil, and sandalwood album oil improve AD symptom severity, but again, large controlled trials are needed.5 Unfortunately, many essential oils, including EPO, can cause a secondary allergic contact dermatitis and potentially worsen AD.19
Fish Oil for AD
Fish oil is a commonly used supplement for AD due to its high content of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids exert anti-inflammatory effects by displacing arachidonic acid, a proinflammatory omega-6 fatty acid thought to increase IgE, as well as helper T cell (TH2) cytokines and prostaglandin E2.8,20 A 2012 Cochrane review found that, while some studies revealed mild improvement in AD symptoms with oral fish oil supplementation, these RCTs were of poor methodological quality.21 Multiple smaller studies have shown a decrease in pruritus, severity, and physician-rated clinical scores with fish oil use.5,8,20,22 One study with 145 participants reported that 6 g of fish oil once daily compared to isoenergetic corn oil for 16 weeks identified no statistically significant differences between the treatment groups.20 No adverse events were identified in any of the reported trials. Further studies should be conducted to assess the utility and dosing of fish oil supplements in AD patients.
Probiotics for AD
Probiotics consist of live microorganisms that enhance the microflora of the gastrointestinal tract.8,20 They have been shown to influence food digestion and also have demonstrated potential influence on the skin-gut axis.23 The theory that intestinal dysbiosis plays a role in AD pathogenesis has been investigated in multiple studies.23-25 The central premise is that low-fiber and high-fat Western diets lead to fundamental changes in the gut microbiome, resulting in fewer anti-inflammatory metabolites, such as short-chain fatty acids (SCFAs).23-25 These SCFAs are produced by microbes during the fermentation of dietary fiber and are known for their effect on epithelial barrier integrity and anti-inflammatory properties mediated through G protein–coupled receptor 43.25 Multiple studies have shown that the gut microbiome in patients with AD have higher proportions of Clostridium difficile, Escherichia coli, and Staphylococcus aureus and lower levels of Bifidobacterium, Bacteroidetes, and Bacteroides species compared to healthy controls.26,27 Metagenomic analysis of fecal samples from patients with AD have shown a reduction of Faecalibacterium prausnitzii species when compared to controls, along with a decreased SCFA production, leading to the hypothesis that the gut microbiome may play a role in epithelial barrier disruption.28,29 Systematic reviews and smaller studies have found that oral probiotic use does lead to AD symptom improvement.8,30,31 A systematic review of 25 RCTs with 1599 participants found that supplementation with oral probiotics significantly decreased the SCORAD (SCORing Atopic Dermatitis) index in adults and children older than 1 year with AD but had no effect on infants younger than 1 year (P<.001). They also found that supplementation with diverse microbes or Lactobacillus species showed greater benefit than Bifidobacterium species alone.30 Another study analyzed the effect of oral Lactobacillus fermentum (1×109 CFU twice daily) in 53 children with AD vs placebo for 16 weeks. This study found a statically significant decrease in SCORAD index between oral probiotics and placebo, with 92% (n=24) of participants supplementing with probiotics having a lower SCORAD index than baseline compared to 63% (n=17) in the placebo group (P=.01).31 However, the use of probiotics for AD treatment has remained controversial. Two recent systematic reviews, including 39 RCTs of 2599 randomized patients, found that the use of currently available oral probiotics made little or no difference in patient-rated AD symptoms, investigator-rated AD symptoms, or quality of life.32,33 No adverse effects were observed in the included studies. Unfortunately, the individual RCTs included were heterogeneous, and future studies with standardized probiotic supplementation should be undertaken before probiotics can be routinely recommended.
The use of topical probiotics in AD also has recently emerged. Multiple studies have shown that patients with AD have higher levels of colonization with S aureus, which is associated with T-cell dysfunction, more severe allergic skin reactions, and disruptions in barrier function.34,35 Therefore, altering the skin microbiota through topical probiotics could theoretically reduce AD symptoms and flares. Multiple RCTs and smaller studies have shown that topical probiotics can alter the skin microbiota, improve erythema, and decrease scaling and pruritus in AD patients.35-38 One study used a heat-treated Lactobacillus johnsonii 0.3% lotion twice daily for 3 weeks vs placebo in patients with AD with positive S aureus skin cultures. The S aureus load decreased in patients using the topical probiotic lotion, which correlated with lower SCORAD index that was statistically significant compared to placebo (P=.012).36 More robust studies are needed to determine if topical probiotics should routinely be recommended in AD.
Psoriasis
Psoriasis vulgaris is a chronic inflammatory skin condition characterized by pruritic, hyperkeratotic, scaly plaques.39,40 Keratinocyte hyperproliferation is central to psoriasis pathogenesis and is thought to be a T-cell–driven reaction to antigens or trauma in genetically predisposed individuals. Standard treatments for psoriasis currently include topical corticosteroids and anti-inflammatories, oral immunomodulatory therapy, biologic agents, and phototherapy.40 The use of CAM is highly prevalent among patients with psoriasis, with one study reporting that 51% (n=162) of psoriatic patients interviewed had used CAM.41 The most common reasons for CAM use included dissatisfaction with current treatment, adverse side effects of standard therapy, and patient-reported attempts at “trying everything to heal disease.”42 Herein, we will discuss some of the most frequently used supplements for treatment of psoriatic disease.39