The initial search of NHP search terms and Vitiligo resulted in 986 citations. A manual review of titles and abstracts was conducted to identify studies appearing to meet the inclusion and exclusion criteria which resulted in 47 articles. The full text of these articles was obtained and reviewed. Studies without a control group, epidemiological reports, and incomplete reports were discarded. This process resulted in 15 articles that met the inclusion and exclusion criteria. Details of these studies are summarized in Table .
Of the 15 trials included in this review 11 were published in English, three in Chinese, and one in French. Trial reports published in Polish, Russian, German, Spanish and Italian were reviewed during the second stage of data collection; however, these were either incomplete, did not involve NHPs, or were uncontrolled and therefore did not meet our inclusion criteria. Of the trials included in this review, ten studied NHPs as an adjunct to UVA or UVB, and five investigated NHPs as the primary treatment. We group the clinical trials into four broad categories of NHP interventions: L-phenylalanine, traditional Chinese medicine (TCM) products, herbs, and vitamins.
The most commonly studied intervention was L-phenylalanine, assessed in three trials as an adjuvant to UVA or UVB phototherapy [20
] (Siddiqui references two trials in one paper), and in one trial with other agents but without phototherapy [22
]. At doses ranging from 50 mg/kg to 100 mg/kg for 6 to 18 months, all trials reported beneficial effects. The studies recruited from 19 to 149 patients. Two of the studies had a Jadad score of 0, and two had a Jadad score of 3. The main problems were lack of randomization and poor control in two studies, high participant dropout in another trial, and inconsistent outcome measures. It is not possible to pool the data from the studies for meta-analytic purposes due to the wide differences in outcome measures. Overall there is moderate evidence that L-phenylalanine has efficacy as an adjunctive agent to phototherapy. Additional controlled research that focuses on L-phenylalanine in conjunction with UVA or UVB phototherapy is necessary to confirm these preliminary findings.
Three trials used traditional Chinese medicinal herbs for the treatment of vitiligo [23
]. Each clinical trial used different remedies, some given by themselves, or in conjunction with phototherapy or sun tan advice. Specifically, Liu used a Xiaobai mixture containing walnut, red flower, black sesame, black beans, zhi bei fu ping, lu lu tong, and plums; details of the products investigated were not provided for the other two trials. All three trials compared the NHP intervention to conventional biomedical treatments of vitiligo (phototherapy, corticosteroids, or psoralen) in the control group. The studies ranged from 74 to 329 patients and 2–3 months. Even though two of the studies are relatively large (329 and 232 participants), participants were divided into multiple groups. No further details of group allocation are provided. All three trials indicate positive results for the NHP intervention. All three trials received a Jadad score of 1. Varying and poorly described treatments, small treatment group size, and inconsistent outcome measures were the main problems with the studies. It is not possible to pool the data from the studies for meta-analytic purposes due to the varying treatments and differences in outcome measures. Overall, there is weak evidence that some traditional Chinese medicinal herbs may be useful for the treatment of vitiligo. None of the treatments' effects have been replicated and overall the studies are of poor methodological quality.
Six trials investigated the use of plants in the treatment of vitiligo. Four of these trials utilized plants as photosensitizing agents (Picorrhiza kurroa
, a khellin extract, and two Polypodium leucotomos
] all given orally in conjunction with UVA or UVB phototherapy; one investigated the use of oral Ginkgo biloba
by itself (40 mg TID) [2
]; and one investigated the topical use of an extract of Cucumis melo
]. Treatments lasted from 3 to 12 months, and the studies were small, ranging from 9 to 50 participants. Only one trial by Middelkamp-Hup utilising Polypodium leucotomos
was of good quality, scoring 5 on the Jadad scale, while the quality of the other four trials was poor, reflected by Jadad scores ranging from 0 to 2. The main problems with the studies were the small sample size, poor study design, and inconsistent outcome measures. Overall, there is weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that Ginkgo biloba
by itself can be useful for vitiligo. Cucumis melo
treatment was not found to be statistically significant over placebo cream. Additional research to confirm these preliminary trials is necessary.
Two trials investigated the use of vitamins as adjuvants to UVA or UVB phototherapy [31
]. Oral cobalamin (1000 mcg BID) and folic acid (5 mg BID) were given in one trial, and oral vitamin E was given in another (900 IU, type of vitamin E not specified). After 12 months of treatment the cobalamin and folic acid study reported no significant difference compared to a phototherapy control. On the other hand, 6 months of treatment with combined vitamin E and phototherapy achieved significantly better repigmentation than phototherapy only. The studies were small, ranging from 27 to 30 participants, and neither had a Jadad score greater than 2. There was a lack of statistical information, and inconsistent outcome measures were used. Overall, there is no evidence for using oral cobalamin and folic acid with phototherapy for the treatment of vitiligo, while the evidence for vitamin E as an adjunct to phototherapy is weak.
Only five trials discussed adverse events, the most common of which were erythema, pruritis, and nausea. Erythema was reported in studies utilizing phototherapy. Pruritis was reported in trials using metoxsalen with Picorrhiza kurroa and Polypodium leucotomos with phototherapy. Nausea and gastrointestinal complaints were reported in trials utilizing Ginkgo biloba, P. leucotomos with phototherapy, and Vitamin E with phototherapy. It is difficult to ascertain whether the NHPs or their concomitant treatments caused these adverse reactions. All reported adverse reactions were minor. Most studies did not adequately report adverse events, and the small sample size of the trials makes generalizations difficult. A complete list of adverse events reported is in Table .