Table 1.
Characteristics of the included studies and the Newcastle–Ottawa Scale (NOS) Quality Assessment Table.
| Authors (publication year, country/region) | Studies | Sample size | Intervention | Study design | Duration | Main results | NOS |
|---|---|---|---|---|---|---|---|
| Juhlin et al. (1997, Sweden) (9) | Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure | Patients with vitiligo, 100 | Test: tablets containing vitamin B12 (1 mg cyanocobalamin) and folic acid (5 mg) should be taken twice daily for 3 months. Goal: to expose their skin to the sun in summer and UVB irradiation in winter | Single-arm study | NR | Repigmentation was clearly noted in 52 patients; 37 had been exposed to sunlight from April to September in Sweden, and six had been exposed to UVB lamps once or twice weekly in the winter. Repigmentation was most evident in sun-exposed areas, where 38% of the patients had previously noted repigmentation during the summer months. Total repigmentation was observed in six patients. The spread of vitiligo stopped in 64% of the patients after treatment. | 2 |
| Lajevardi et al. (2015, Providence) (10) | Vitiligo and associated pigmentation, sun exposure, and lifestyle factors in women | 63,315 women | Pigmentation, sun exposure, and lifestyle factors | Cohort study | 12 years | Women who had a painful burn/blistering skin reaction after 2 h of sun exposure as children/adolescents had a higher risk of vitiligo than those with no reaction or only redness after sun exposure. Women with strong tanning abilities had a higher risk of developing vitiligo compared to those without the ability to tan. In this study, no correlation was observed between the risk of vitiligo and body mass index, physical activity, or alcohol intake. | 9 |
| Kulkarni et al. (2016, India) (11) | A cross-sectional study to assess the incompatible dietary behaviors of patients suffering from skin diseases: A pilot study | 32 patients with vitiligo aged 18–60 years with disease duration of up to 6 months, and 32 healthy controls | Incompatible diet | Case–control study | NR | The scores for consumption of incompatible diet and dietary habits in patients with vitiligo were similar to those of their respective controls. | 7 |
| Liu et al. (2021, China) (12) | Location, spreading, and oral corticosteroids are associated with insomnia in patients with vitiligo: a case–control study | Patients with vitiligo with insomnia, 204; patients with vitiligo without insomnia, 205 | With or without insomnia | Case–control study | NR | Vitiligo on the face and neck, progression of vitiligo, and oral corticosteroids remained risk factors for insomnia in patients with vitiligo. | 5 |
| Lee et al. (2021, Korea) (13) | Height and risk of vitiligo: a nationwide cohort study | 15,980,754 individuals | Height | Cohort study | Participants were followed until vitiligo diagnosis or until the end of 2015 | Findings from this nationwide cohort study suggest that adult height positively correlates with the risk of vitiligo in Koreans. The association was stronger in the elderly population. | 8 |
| Sanad et al. (2020, Egypt) (14) | Serum zinc and inflammatory cytokines in vitiligo | Patients with vitiligo, 50; healthy controls, 100 | Zinc | Case–control study | NR | The mean serum levels of zinc were significantly reduced in patients with vitiligo | 7 |
| Lee et al. (2020, Korea) (15) | Association between vitiligo and smoking: a nationwide population-based study in Korea | Patients with vitiligo, 22,811 | Smoking | Cohort study | NR | The results suggested there are suppressive effects of smoking on the development of vitiligo. | 8 |
| Derakhshandeh-Rishehri et al. (2019, Iran) (16) | Role of fatty acid intake in generalized vitiligo | Patients with vitiligo, 100; controls, 110 | Total fat, PUFA, MUFA, SFA, linoleic acid, linolenic acid, oleic acid, EPA, DHA, and cholesterol | Case–control study | NR | Total fat intake was associated with an increased risk of vitiligo. | 7 |
| Hussein et al. (2019, Egypt) (17) | Role of vitamin B12, folic acid, and oxidative damage in the serum of patients with vitiligo | Patients with vitiligo, 42; controls, 36 | Vitamin B12 and folic acid | Case–control study | 6 months | The results declared significant decreases in vitamin B12 and folic acid levels in patients with vitiligo compared to those in controls. | 8 |
| Iraji et al. (2017, Iran) (18) | Comparing the improvement of unstable vitiligo in patients treated by topical PUVA therapy alone, topical PUVA therapy and oral vitamin D, and topical PUVA therapy and oral vitamin D and vitamin B12 | 60 patients with active vitiligo | Vitamin D and B12 | Randomized controlled trial | 6 months | The group receiving vitamin D demonstrated higher reductions in the extent and area of lesions compared to that in the control group. | 6 |
| Akhter et al. (2017, Pakistan) (19) | Estimation of serum vitamin B12, folic acid, homocysteine, and ferritin levels in subjects with vitiligo | Patients with vitiligo, 50; controls, 50 | Vitamin B12 and folic acid | Case–control study | 12 months | Serum vitamin B12 and folic acid levels were significantly lower in patients with vitiligo than in controls. | 8 |
| Dass (2016, India) (20) | Search for clinical and laboratory markers of severity and instability of vitiligo: a cross-sectional observational hospital-based study | Patients with vitiligo, 40; controls, 40 | Vitamin B12, folic acid, and Hcy | A cross-sectional observational study | Elevated serum Hcy levels and reduced serum vitamin B12 levels were significantly associated with vitiligo. No significant association was observed with reduced serum folic acid levels. | 6 | |
| Wu et al. (2015, Providence) (21) | Use of permanent hair dyes and risk of vitiligo in women | 254 incident vitiligo cases among 68,176 participants | Permanent hair dyes | Cohort study | NR | After adjusting for multiple covariates, there was a borderline increased risk of vitiligo associated with using permanent hair dyes. This association was more pronounced in individuals who used hair dyes for a longer duration, initiated use before the age of 30, and had a longer usage period since their first use. | 8 |
| Manisha et al. (2015, India) (22) | Epidemiological study of svitra (vitiligo) with special reference to viruddha ahara (incompatible diet) | Patients with vitiligo, 242 | Incompatible diet | Observational studies | NR | The study observed that among the 242 patients with vitiligo, 100% had an incompatible combination of food, and 100% had an incompatible food sequence. In addition, 95.45% of patients exhibited an incompatible cooking method, and 71.90% reported an incompatibility of palatability. Based on the analysis of the data, the researchers concluded that incompatible food is the most potent etiological factor of vitiligo and should be avoided. | 2 |
| Ghiasi et al. (2015, Iran) (23) | Serum levels of vitamin B12, folic acid, and homocysteine in patients with vitiligo | Patients with vitiligo, 30; controls, 30 | Vitamin B12 and folic acid | Case–control study | NR | No significant differences were observed in the levels of serum homocysteine, vitamin B12, and folic acid between patients with vitiligo and healthy controls. Moreover, there were no associations between these factors and age, body weight, or sex, nor with the extent, duration, and type of vitiligo. | 7 |
| Colucci et al. (2015, Italy) (24) | Evaluation of an oral supplement containing Phyllanthus emblica fruit extracts, vitamin E, and carotenoids in vitiligo treatment | Patients with vitiligo, 65; controls, 65 | Group A included patients treated with oral antioxidants, and group B included individuals not treated with antioxidants. Group A patients took one tablet of an oral supplement containing P. emblica (100 mg), vitamin E (4.7 mg), and carotenoids (10 mg) three times a day for 6 months and were asked to stop the treatment in case of side effects. Both groups were treated at the same time with a comparable topical therapy and/or phototherapy | Case–control study | 10 months | Group A patients showed significantly mild repigmentation in the head and neck region and on the trunk compared to other body sites. Although the repigmentation was not statistically significant for each individual body site, it was higher overall. Additionally, patients in Group A exhibited a higher level of disease stability. | 6 |
| Khurrum et al. (2014, Saudi Arabia) (25) | Is there a real relationship between serum levels of homocysteine and vitiligo? | Patients with vitiligo, 153; controls, 153 | Vitamin B12, Hcy, and folic acid | Case–control study | NR | The results of this study revealed that there was no association between serum levels of Hcy and vitamin B12 and vitiligo. However, the folic acid levels were higher in patients with vitiligo than in controls. | 6 |
| Kim et al. (2015, Korea) (26) | Childhood facial vitiligo: How intractable is it? | Medical data and photos of 111 children with facial vitiligo who were followed up for more than 1 year. | Nutritional education, vitamin E (α-tocopherol 100–400 IU/day), folic acid (1–2 mg/day), multivitamin intake, and antioxidant cosmetics are the mainstay of treatment. Conventional therapies, including oral, topical, and/or intralesional corticosteroids, topical macrolactam, excimer lasers, and epidermal grafts, were employed | Single-arm experiment | NR | 9% of patients demonstrated no improvement regardless of treatment modality, whereas 91% showed improvement in lesions. | 2 |
| Araujo et al. (2014, Brazil) (27) | The relation between vitamin B12 levels and vitiligo repigmentation | Thirty-three patients were treated for vitiligo lesions using either 308 nm excimer light or NB UVB 311 nm (depending on the expansion of the lesion). They were given vitamin B12 before treatment began. | Vitamin B12 | Single-arm experiment | NR | An association between vitamin B12 levels (upper than 365) and better repigmentation was not found in any of the subjects. | 1 |
| Finamor et al. (2013, Brazil) (28) | A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis | Serum 25(OH)D3, PTH | 16 patients with vitiligo received vitamin D3 35,000 IU once daily for 6 months in association with a low-calcium diet (avoiding dairy products and calcium-enriched foods like oats, rice, or soy “milk”) and hydration (minimum 2.5 L daily) | Before–after study in the same patient | NR | Following the treatment, there was a significant increase in the levels of 25(OH)D3 and a significant decrease in the levels of PTH among patients with vitiligo. The serum concentrations of PTH and 25(OH)D3 were inversely correlated. Of the 16 patients with vitiligo, 14 achieved a repigmentation level ranging from 25% to 75%. | 4 |
| Yaghoobi et al. (2011, Iran) (29) | Original article title: “Comparison of therapeutic efficacy of topical corticosteroid and oral zinc sulfate-topical corticosteroid combination in the treatment of patients with vitiligo: a clinical trial” | 35 patients with vitiligo were randomized into two groups, with the first group receiving topical corticosteroids and the second group receiving a combination of oral zinc sulfate-topical corticosteroids | Zinc | Randomized controlled trial | 1 year | The mean response in the corticosteroid group was 21.43%, while in the zinc sulfate-corticosteroid combination group, it was 24.7%. However, there was no statistically significant difference between the two groups regarding therapeutic efficacy. | 7 |
| Silverberg et al. (2011, United States) (30) | Serum homocysteine is associated with the extent of vitiligo vulgaris | 31 adult and 24 pediatric patients with vitiligo vulgaris | Homocysteine and vitamin B12 | Cohort study | 3 years | Active vitamin B12 supplementation may be beneficial for patients with vitiligo. | 7 |
| Gonul et al. (2010, Turkey) (31) | Serum vitamin B12, folate, ferritin, and iron levels in Turkish patients with vitiligo | Patients with vitiligo, 42; controls, 36 | Vitamin B12 and folic acid | Case–control study | NR | The vitamin B12 and folate levels in patients with vitiligo did not differ from those of controls. | 7 |
| Khan et al. (2009, India) (32) | Circulatory levels of antioxidants and lipid peroxidation in Indian patients with generalized and localized vitiligo | Patients with vitiligo, 30; controls, 30 | Vitamin C and vitamin E | Case–control study | NR | The vitamin C and E levels of the patients with vitiligo were significantly lower compared to those in the controls. | 7 |
| Mouzas et al. (2008, Greece) (33) | Increased frequency of self-reported parasomnias in patients suffering from vitiligo | Group A, 116 patients with vitiligo; Group B, 52 patients suffering from other dermatological disorders without psychogenic involvement (such as acne). The control group (Group C) consisted of 48 partners and relatives of the patients without dermatological disorders | Nocturnal enuresis, sleepwalking, night illusions, sleep terrors, and nightmares | Case–control study | NR | Vitiligo sufferers reported significantly more sleep disorders compared to that in the controls, especially sleepwalking, nocturnal enuresis, night illusions, sleep terrors, and nightmares. In contrast, individuals with other dermatological diseases showed a statistically significant difference compared to that in the control group only in nightmares and nocturnal enuresis. Additionally, when comparing vitiligo sufferers to those with other dermatological diseases, significant differences were observed in nightmares, night illusions, and sleepwalking. However, these two groups had no statistically significant difference in sleep terrors and nocturnal enuresis. |
6 |
| Agrawal et al. (2004, India) (34) | Study on the antioxidant status of patients with vitiligo at different age groups in Baroda | Patients with vitiligo, 63; controls, 60 | Vitamin E | Case–control study | NR | No significant change in plasma vitamin E levels was observed in vitiliginous patients compared to that in controls. | 6 |
| Akyol et al. (2002, Turkey) (35) | The effects of vitamin E on the skin lipid peroxidation and the clinical improvement in patients with vitiligo treated with PUVA | Patients were assigned to receive either only PUVA (first group: 15) or PUVA and vitamin E (900 IU daily perorally) (second group: 15) for 6 months | Vitamin E | Case–control study | 6 months | Vitamin E may prevent oxidative distress caused by PUVA therapy. However, it does not have a significant impact on the clinical improvement of vitiligo lesions. | 5 |
| TJIOE et al. (2002, Sweden) (36) | Erratum: Treatment of vitiligo vulgaris with narrow-band UVB (311 nm) for one year and the effect of the addition of folic acid and vitamin B12 | Patients with vitiligo, 27 | The first group received narrow-band UVB phototherapy, and the second group received vitamin B121000 mg sustained-release tablets and folic acid 5-mg tablets twice a day and received narrow-band UVB phototherapy. | Randomized controlled trial | 12 months | The study reconfirmed the efficacy of narrow-band UVB phototherapy in vitiligo. However, it did not demonstrate any additional benefits from adding vitamin B12 and folic acid. | 5 |
| Picardo et al. (1994, Italy) (37) | Antioxidant status in the blood of patients with active vitiligo | Patients with vitiligo, 62; controls, 60 | Vitamin E | Case–control study | NR | The blood levels of vitamin E in individuals with vitiligo were not significantly different from those of healthy age-matched controls. | 6 |
| Bashrahil et al. (2022, SAU) (38) | Association between vitamin D, zinc, and thyroid biomarker levels with vitiligo disease: a retrospective cohort study in a tertiary care center | Patients with vitiligo, 297 | Vitamin D and zinc | Cohort study | NR | No significant association was observed between vitamin D or zinc levels and any of the characteristics or treatments of vitiligo. | 5 |
| Memon et al. (2021, Pakistan) (39) | Effect of vitamin B12 and folic acid in patients with vitiligo | Patients with vitiligo, 155 | Vitamin B12 and folic acid | Cross-sectional study | 6 months | Serum vitamin B12 and folic acid levels significantly affected the duration of vitiligo in patients. | 5 |
| Boisseau-Garsaud et al. (2002, France) (40) | Increase in total blood antioxidant status and selenium levels in black patients with active vitiligo | Patients with vitiligo, 11 Healthy controls, 11 |
Selenium | Case–control study | NR | Total blood antioxidant status and selenium levels were significantly increased in vitiligo patients, compared to those in sex- and age-matched controls | 6 |
NR, not reported; NOS, Newcastle–Ottawa Scale; UVB, ultraviolet B-rays; Hcy, homocysteine; SFA, saturated fatty acid; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; PTH, parathormone.
NOS scores ranged from 0 to 9 points. A star scoring system was used to semi-quantitatively assess study quality. Each numbered item has been adjusted to a maximum of four stars in the selection and exposure categories. A maximum of two stars was assigned for comparison purposes. We considered studies achieving ≥7, 4–6, and <4 stars as having high, medium, and poor quality, respectively.