Journal of Dermatologic Science and Cosmetic Technology 3 (2026) 100167 Contents lists available at ScienceDirect Journal of Dermatologic Science and Cosmetic Technology journal homepage: www.keaipublishing.com/en/journals/jdsct Efficacy and safety of integrative and complementary treatments versus conventional therapies in patients with vitiligo: A systematic review Juan Pablo Alzate-Granadosa,⁎, Andrea Carolina Díaz-Manriqueb, Alexandra Maffiold-Novoac, Leidy Vanessa Rodríguez-Moreanod, Yinneth Ruiz-Atencioe, Andrés Felipe Torres-Medinaf, Vanessa Díaz-Granadosg a Universidad Nacional de Colombia, Bogotá 26-85, Colombia b Universidad El Bosque, Bogotá 131 A - 02, Colombia c Universidad del Rosario, Bogotá 12C-13, Colombia d Universidad Cooperativa de Colombia, Pasto 45-150, Colombia e Universidad del Sinú, Montería 31 No. 3-06, Colombia f Universidad de Ciencias Aplicadas y Ambientales U.D.C.A, Bogotá 55-37, Colombia g Universidad del Norte, Barranquilla 081007, Colombia A R T I C L E I N F O Keywords:

Vitiligo Complementary therapies Integrative medicine Microneedling Repigmentation Safety Randomized trials A B S T R A C T Background: Vitiligo is a chronic depigmenting disorder with substantial psychosocial burden. Conventional therapies (topical corticosteroids, calcineurin inhibitors, phototherapy) have variable efficacy and tolerability, prompting growing interest in integrative and complementary treatments (ICTs). Objective: To synthesize evidence on the efficacy and safety of ICTs compared with conventional therapies in vitiligo and to outline their potential role, advantages, and limitations in clinical decision-making. Data Sources and Study Eligibility: We systematically searched MEDLINE (PubMed), Embase, CENTRAL, LILACS, and the ICTRP and ClinicalTrials.gov trial registries from inception to the review date for randomized and quasiexperimental comparative studies evaluating ICTs (e.g., botanicals, fire needle therapy, microneedling-assisted drug delivery) versus conventional topical treatments or placebo in patients with vitiligo. Methods: Two reviewers independently screened records, selected studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. When at least two clinically and methodologically similar trials reported comparable dichotomous outcomes, we pooled effect estimates using random-effects meta-analysis and ex­ pressed results as risk ratios (RRs) with 95% confidence intervals (CIs).

Results: Six randomized controlled trials (total n = 255) met inclusion criteria; no eligible quasi-experimental or observational comparative studies were identified. Interventions included topical turmeric cream, oral Ginkgo biloba, fire needle therapy alone or combined with tacrolimus, microneedling-assisted delivery of calcipotriol plus betamethasone versus tacrolimus, and the traditional Chinese formulation Zengse Pill. Across individual trials, several ICTs achieved statistically significant improvements in repigmentation, lesion area reduction, or disease arrest compared with placebo or active comparators. Three studies were judged at overall low risk of bias and three had some concerns, mainly regarding allocation concealment and blinding. An exploratory metaanalysis of two trials (Zengse Pill and Ginkgo biloba) yielded a nonsignificant pooled RR of 2.05 (95% CI 0.79–5.35; I² = 52.6%), reflecting imprecision and moderate heterogeneity. Adverse events were generally mild and manageable (local irritation, transient erythema/itching, occasional mild nausea), and no serious treatmentrelated events were reported.

Limitations: The evidence base is constrained by small sample sizes, short follow-up, heterogeneity of ICT pro­ tocols and outcome measures, incomplete reporting of key determinants such as Fitzpatrick phototype, and potential confounding by ambient ultraviolet exposure in predominantly tropical or subtropical study settings. Conclusions: Current data suggest that selected ICTs may serve as well-tolerated adjunctive options for patients with vitiligo, particularly when conventional therapies are insufficient or poorly tolerated. However, the cer­ tainty of benefit remains low due to methodological limitations and heterogeneity. Larger, multicenter https://doi.org/10.1016/j.jdsct.2026.100167 Received 6 June 2025; Received in revised form 4 February 2026; Accepted 11 March 2026 Available online 16 March 2026 2950-306X/© 2026 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

]]]] ]]]]]] ⁎ Corresponding author.

E-mail addresses: jpalzategr@unal.edu.co (J.P. Alzate-Granados).

randomized trials with longer follow-up and standardized outcome sets are needed before ICTs can be routinely integrated into vitiligo treatment algorithms.

Registration: PROSPERO: 1141017. PRISMA 2020 guidelines were followed.

1. Introduction

Vitiligo is a chronic acquired disorder characterized by progressive melanocyte loss and well-demarcated depigmented macules, often ac­ companied by substantial psychosocial morbidity, including anxiety, depression, and stigma.1–3 Vitiligo is a chronic acquired disorder characterized by progressive melanocyte loss and well-demarcated de­ pigmented macules, often accompanied by substantial psychosocial morbidity, including anxiety, depression, and stigma.1–3 These gaps translate into persistent cosmetic disfigurement, impaired quality of life, and therapeutic frustration for both patients and clinicians.1–3 The pathogenesis of vitiligo is multifactorial, involving autoimmune cytotoxicity against melanocytes, genetic susceptibility, oxidative stress, and environmental triggers, with autoreactive T cells, redox imbalance, and neuroendocrine factors all contributing to disease onset and progression.3,4 This complex biology has stimulated interest in in­ tegrative and complementary therapies (ICTs)—including botanicals with antioxidant or immunomodulatory properties, acupuncture-de­ rived procedures such as fire needle, and device-facilitated drug de­ livery approaches—as potentially synergistic adjuncts to conventional regimens, with the added promise of addressing stress, coping, and other psychosocial dimensions.1–3 Conventional treatments (including topical corticosteroids, calci­ neurin inhibitors, and narrowband ultraviolet B phototherapy) can offer clinical benefits but are frequently limited by adverse effects, high re­ currence rates, and accessibility issues. These challenges have spurred interest in integrative and complementary therapies, such as acu­ puncture, herbal supplements, and mind–body practices, which may address both the clinical and psychosocial dimensions of vitiligo.3 Despite their increasing use in clinical practice and patient-driven demand for “natural” or holistic options, the evidence base supporting ICTs in vitiligo remains fragmented, with small, heterogeneous trials and variable methodological quality (3).

Recent international expert recommendations emphasize a patientcentered, stepwise treatment algorithm that integrates established modalities (e.g., NB-UVB, topical ruxolitinib, and surgery in carefully selected stable disease) and acknowledges emerging adjunctive ap­ proaches, while simultaneously underscoring that current data on many ICTs are limited and of low certainty.5,6 In this context, a rigorous synthesis of randomized and quasi-experimental studies directly com­ paring ICTs with conventional therapies or placebo is needed to clarify their true efficacy, safety profile, and place within contemporary viti­ ligo management.1–4 Objective: To systematically assess the efficacy and safety of ICTs versus conventional therapies in vitiligo, summarize their advantages/limitations, and situate findings within contemporary guideline frameworks.

2. Methods

2.1. Study type

This systematic review included randomized clinical trials (RCTs), quasi-experimental studies, observational studies (cohort and casecontrol), and relevant descriptive studies to evaluate the efficacy and safety of integrative and complementary treatments compared to con­ ventional therapies in patients with vitiligo.

2.2. PICO question

In children and adults with vitiligo, do integrative and com­ plementary therapies, alone or in combination with conventional treatments, improve repigmentation and other clinically relevant out­ comes compared with conventional therapies alone or placebo?

• Population: Children or adults with clinically or histologically

confirmed vitiligo (any subtype, extent, or stability).

• Interventions (ICTs): Topical turmeric cream; oral Ginkgo biloba;

fire needle therapy; microneedling-assisted transdermal de­ livery (e.g., calcipotriol + betamethasone).

• Comparators: Placebo or conventional therapies (e.g., tacrolimus).

• Outcomes (Primary): ≥ 50% repigmentation; change in lesion

area (e.g., VASI).

• Secondary: Disease arrest; adverse events (AEs); patient-reported

outcomes (VNS, PGA); selected immunologic markers (CD4 +, CD8 +, C3, C4)

2.3. Eligibility criteria

Inclusion: Randomized clinical trials (RCTs), quasi-experimental comparative studies; ICT vs conventional or placebo; report at least one prespecified outcome.

Exclusion: Case reports/series; non-comparative observational de­ signs; non-vitiligo populations; duplicate data; insufficient outcome detail.

2.4. Search methods for study identification

2.4.1. Electronic searches

We searched MEDLINE (PubMed), Embase, CENTRAL, LILACS, and trial registries (ICTRP, ClinicalTrials.gov), from inception to the review date, combining MeSH/keywords for “vitiligo,” “complementary,” “integrative,” and therapy-specific terms. We also screened reference lists of included studies.

2.4.2. Other resource searches

Reference lists of included studies, relevant conference proceedings, and clinical trial registries (ICTRP, ClinicalTrials.gov) were reviewed to identify additional studies.

2.4.3. Data collection and analysis

Two independent reviewers assessed the titles and abstracts of re­ trieved studies. Full texts of potentially eligible studies were evaluated according to inclusion and exclusion criteria.

A standardized form was used for data extraction, collecting in­ formation on study characteristics, participants, interventions, com­ parisons, outcomes, and results. Disagreements were resolved through consensus or consultation with a third reviewer.

2.5. Risk of bias (RoB) assessment

We used Cochrane RoB 2 for randomized comparisons (domains: randomization; deviations from intended interventions; missing out­ come data; outcome measurement; selective reporting). We report do­ main-level judgments and overall RoB2.

2.6. Data synthesis

A meta-analysis was conducted when sufficient data were available, and the included studies were sufficiently homogeneous in terms of participants, interventions, and outcomes. Dichotomous data were analyzed using risk ratios (RRs) with 95% confidence intervals (CIs), while continuous data were synthesized using mean differences (MDs) J.P. Alzate-Granados, A.C. Díaz-Manrique, A. Maffiold-Novoa et al. Journal of Dermatologic Science and Cosmetic Technology 3 (2026) 100167

or standardized mean differences (SMDs), also with 95% CIs. A randomeffects model was employed in the presence of moderate to substantial statistical heterogeneity (I² > 50%).

Two trials were eligible for meta-analysis based on dichotomous outcomes, specifically the efficacy of Zengse Pill and Ginkgo biloba in achieving repigmentation or halting disease progression. Component Details Study Type Systematic review including randomized clinical trials (RCTs), quasi-experimental studies, observational stu­ dies (cohort and case–control), and relevant descrip­ tive studies comparing integrative/complementary treatments to conventional therapies in vitiligo pa­ tients.

Selection Criteria Types of Studies: • RCTs, quasi-experimental designs, cohort studies, case–control studies, descriptive stu­ dies evaluating integrative/complementary versus conventional treatments.

Types of Participants: • Patients diagnosed with vitiligo (any extent or location), pediatric and adult populations, clinically or histologically confirmed. Types of Interventions: • Integrative/complementary treatments (e.g., turmeric, Ginkgo biloba, fire-needle therapy, microneedling combined with calcipotriol + betamethasone). • Conventional therapies (e.g., tacro­ limus ointment, calcipotriol + betamethasone when used alone).

Types of Outcomes:

• Primary: ≥ 50% repigmentation; change in lesion

surface area (e.g., VASI).

• Secondary: Incidence/severity of adverse events;

changes in immunological biomarkers (CD4 +, CD8 +, C3, C4); patient satisfaction (VNS, PGA). Search Methods for Stu­ dy Identification Electronic Searches:

• Databases: MEDLINE (PubMed), Embase, CENTRAL

(Cochrane Library), LILACS (from inception to date of review).

• Search terms: “vitiligo,” “complementary treat­

ments,” “integrative therapies,” “conventional thera­ pies” (using MeSH and keywords).

Other Resource Searches:

• Reference lists of included studies, conference pro­

ceedings, clinical trial registries (e.g., ICTRP, ClinicalTrials.gov).

Data Collection and An­ alysis

• Two independent reviewers screened titles/abstracts;

full texts of potentially eligible studies were assessed against inclusion/exclusion criteria.

• Data extraction via a standardized form capturing

study characteristics, participants, interventions, comparisons, outcomes, and results.

• Disagreements resolved through consensus or third-

party adjudication.

• Risk of bias assessed using the Cochrane Risk of Bias

Tool for RCTs (RoB2), evaluating selection, perfor­ mance, detection, attrition, and reporting biases. Data Synthesis

• Meta-analysis performed when ≥ 2 sufficiently

homogeneous studies existed.

• Dichotomous data: Calculated risk ratios (RRs) with

95% confidence intervals (CIs).

• Continuous data: Synthesized using mean differ­

ences (MDs) or standardized mean differences (SMDs) with 95% CIs.

• Random-effects model applied when moderate to

substantial heterogeneity was present (I² > 50%).

• Two trials (Zengse Pill and Ginkgo biloba) contrib­

uted dichotomous outcomes (repigmentation/disease arrest), enabling calculation of study-level RRs and overall summary estimate.

3. Results

3.1. Study selection

Out of 542 records, 147 were duplicate and removed; 395 were screened. During screening, 351 records were excluded, 44 reports were sought for retrieval (5 not retrieved). Thirty-nine reports were assessed for eligibility; 6 RCTs were included. (Fig. 1).

3.2. Characteristics of included studies

Six RCTs from China, India, Iran, and Egypt evaluated turmeric cream, Ginkgo biloba, fire needle therapy, and microneedling-as­ sisted delivery against placebo or tacrolimus. Only one trial reported Fitzpatrick phototypes (III–IV); others did not. Sample sizes ranged n = 25–65; follow-up 3–6 months. (Tables 1–4). Key reproducibility details added from the primary studies in­ clude: turmeric cream applied twice daily for 4 months, Ginkgo biloba 40 mg three times daily for 6 months, and microneedling sessions every 2 weeks for up to 12 sessions, with calcipotriol 0.05 mg/g + betamethasone 0.5 mg vs tacrolimus 0.03%. The included RCTs enrolled heterogeneous age groups; for example, the turmeric trial included participants aged 8–65 years, and none of the trials re­ ported efficacy stratified by age, limiting assessment of age as an effect modifier

3.3. Risk of bias

Three trials were low risk, and three had some concerns (mainly allocation concealment and lack of blinding of participants/care­ givers). Outcome measurement and completeness were largely low risk. Domain-level judgments are in Table 2, with signaling questions Q1.2, Q2.1, Q2.2, Q3.1, Q4.1, Q5.1 explicitly defined.

3.4. Efficacy

• Fire needle ± tacrolimus (Wang 2024, China). Combination

therapy outperformed monotherapies for lesion area reduction and repigmentation at 6 months (e.g., ≥50% repigmentation in 51.7%

combination vs 31% fire needle vs 6.9% tacrolimus; all p < 0.01).7

• Zengse Pill (Shi 2008, China). Higher composite efficacy vs con­

trol (82.4% vs 54.8%, p < 0.05) with favorable immunologic shifts

(CD4 +/CD8 +).8

• Ginkgo biloba (Parsad 2003, India). Disease arrest in 80% (vs

36.4% placebo, p = 0.006) and marked/complete repigmenta­ tion in 40% (vs 9% placebo); dose: 40 mg TID for 6 months.9

• Topical turmeric (Jalalmanesh 2022, Iran). Significant VASI reduc­

tion and higher patient satisfaction vs placebo over 4 months of twicedaily application; PGA trend favored turmeric (non-significant).10

• Microneedling + Calcipotriol/Betamethasone vs Microneedling

+ Tacrolimus (Ibrahim 2019, Egypt). Greater mean repigmentation

(72.16% ± 31.58 vs 54.16% ± 32.90; p < 0.01), fewer sessions to

improvement (≈4.7 vs 6.0), and higher satisfaction; sessions every

2 weeks (≤12), 3-month follow-up.11

3.5. Meta-analysis

Pooling Zengse Pill and Ginkgo biloba for dichotomous efficacy (re­ pigmentation/disease arrest) produced RR = 2.05 (95% CI 0.79–5.35) with I² = 52.6%, indicating moderate heterogeneity and imprecision (Fig. 2).

3.6. Safety

Across trials, AEs were generally mild (local irritation/burning with tacrolimus; occasional mild nausea with Ginkgo biloba; minimal events with turmeric; transient erythema/itching with microneedling arms). No serious treatment-related AEs were reported (Table 4).

3.7. Advantages and limitations of ICTs vs conventional therapies

From extracted data:

Advantages—signals of repigmentation/disease stabilization, favorable tolerability, and patient satisfaction; procedural syner­ gies (microneedling enhancing transdermal delivery). J.P. Alzate-Granados, A.C. Díaz-Manrique, A. Maffiold-Novoa et al. Journal of Dermatologic Science and Cosmetic Technology 3 (2026) 100167

Fig. 1. PRISMA 2020 Flow Diagram. Identification, screening, eligibility, and inclusion of studies (n = 6). Table 1 Characteristics and Reproducibility Details of Included Trials. Study (Country) Design Population (n) / Key Baseline Intervention (ICT) Dose / Frequency / Duration Comparator Follow-up Wang 2024 (China) (5) Randomized, selfcontrolled lesionlevel RCT Stable non-segmental vitiligo; ≥ 3 similar lesions; adults Fire needle therapy ± 0.1% tacrolimus NR (procedural parameters not reported in abstract); 6-month treatment window 0.1% tacrolimus monotherapy; fire needle monotherapy 6 months.

Shi 2008 (China) (6)

RCT

“Qi-stagnancy/bloodstasis” type (n = 65) Zengse Pill (ZSP) NR in English abstract (treatment 3 months) Cobamamide + Psoralea tincture 3 months.

Parsad 2003 (India) (7) Double-blind RCT Limited, slowly spreading vitiligo (n = 47) Oral Ginkgo biloba

40 mg TID for 6 months

Placebo 6 months.

Jalalmanesh 2022 (Iran) (8) Double-blind RCT Stable, localized vitiligo; 8–65 y (n = 30) Topical turmeric cream Twice daily for 4 months Vehicle/placebo 4 months.

Ibrahim 2019 (Egypt) (9) Split-body RCT Non-segmental vitiligo; Fitzpatrick III–IV (n = 25) Microneedling + Calcipotriol (0.05 mg/g) + Betamethasone (0.5 mg) Sessions q2 weeks (≤12 sessions over 6 months); ointment applied postprocedure; 3-month follow-up Microneedling + Ta­ crolimus 0.03%

6 months + 3

months FU.

Jalalmanesh 2022 (Iran) (8) Double-blind RCT Stable, localized vitiligo; 8–65 y (n = 30) Topical turmeric cream Twice daily for 4 months Vehicle/placebo 4 months.

J.P. Alzate-Granados, A.C. Díaz-Manrique, A. Maffiold-Novoa et al. Journal of Dermatologic Science and Cosmetic Technology 3 (2026) 100167

Limitations—heterogeneous protocols, short follow-up (≤6 months), uncertain durability, incomplete blinding, inconsistent outcome measures, limited phototype reporting, and regional la­ titude/sun-exposure context (tropical settings) limiting external va­ lidity to higher-latitude populations.

BSA: Body Surface Area. NR: Not Reported. mo: month(s). yr: year (s). F: female; M: male. Phototypes III–IV: Fitzpatrick skin type classi­ fication The risk of bias analysis for the included studies is summarized in Table 2. Five domains of bias were evaluated according to the Cochrane Handbook criteria. Overall, three studies were deemed to have a low risk of bias, while the other three showed some concerns in at least one domain. All studies utilized an appropriate randomization sequence, re­ sulting in a low risk of bias for this criterion. However, three studies did not provide sufficient information regarding allocation concealment (question 1.2), raising some concerns. In the remaining three studies, allocation concealment was clear and adequate, resulting in a low risk of bias.

Blinding of participants and caregivers (questions 2.1 and 2.2) was not implemented in most studies, resulting in some concerns in two of them. Three studies effectively controlled for bias in this domain by ensuring blinding and minimizing deviations from assigned interven­ tions, leading to a low risk of bias.

In all studies, data were available for nearly all participants, re­ sulting in a low risk of bias in this domain (question 3.1). The methodology for outcome measurement was appropriate in all studies, resulting in a low risk of bias in this domain (question 4.1). Data analyses were conducted according to pre-specified plans in all studies (question 5.1), leading to a low risk of bias in this domain. In the overall assessment, three studies were classified as having a low risk of bias, while the other three were deemed to have some concerns due to deficiencies in allocation concealment or participant Table 2 Risk of Bias (RoB2) Summary With Signaling-Question Mapping. Domain / Signaling Q Wang (7) Shi (8) Parsad (9) Jalalmanesh (10) Ibrahim (11) Overall Randomization process (Q1.2:

allocation concealment) Low (Some concerns on Q1.2) Some concerns Some concerns Low Some concerns Mixed Deviations from intended interventions (Q2.1/2.2:

blinding participants/ caregivers) Some concerns Some concerns Low Low Low Mixed Missing outcome data (Q3.1) Low Low Low Low Low Low Outcome measurement (Q4.1) Low Low Low Low Low Low Selection of reported results (Q5.1) Low Low Low Low Low Low Overall risk Low Some concerns Some concerns Low Some concerns

3 Low / 3 Some concerns

Abbreviations: Q1.2 = allocation concealment; Q2.1/2.2 = blinding; Q3.1 = completeness; Q4.1 = measurement appropriateness; Q5.1 = pre-specified analyses. Table 3 Efficacy Outcomes Across Trials [Change—clarified endpoints; standardized phrasing; minor typos corrected]. Study Primary Efficacy Signals Time Horizon Wang2024 (7)

Combination (fire needle + tacrolimus) > monotherapies for area reduction and repigmentation; at 6months: ≥ 50%

repigmentation in 51.7% (combo) vs 31% (fire needle) vs 6.9% (tacrolimus); p < 0.01.

6mo Shi2008 (8) Composite clinical efficacy 82.4% vs 54.8% control; immunologic improvement (↑CD4 +, CD4 +/CD8 +). 3mo Parsad2003 (9) Disease arrest 80% vs 36.4% placebo (p = 0.006); marked/complete repigmentation 40% vs 9% placebo. 6mo Jalalmanesh2022 (10)

VASI reduction and higher satisfaction vs placebo (p < 0.001 and p < 0.05, respectively); PGA trend favored turmeric

(NS).

4mo Ibrahim2019 (11)

Mean repigmentation 72.16% vs 54.16% (p < 0.01); fewer sessions (∼4.7 vs ∼6.0) and higher satisfaction with Cal/

BD arm.

6mo + 3mo FU Table 4 Adverse Events (AEs) [Change—standardized AE descriptors and ascertainment methods]. Study Intervention Arms AE Profile (Method) Wang2024 (5) Fire needle; 0.1% tacrolimus; combination Mild local irritation/burning with tacrolimus; no serious AEs (clinical observation).

Shi2008 (6) ZSP vs cobamamide + Psoralea tincture Mild erythema/itching; one constipation episode; none treatment-limiting (clinical observation).

Parsad2003 (7) Ginkgo biloba 40 mg TID vs placebo Occasional mild nausea; otherwise well tolerated (self-report). Jalalmanesh2022 (8) Turmeric vs placebo No specific AEs reported; monthly monitoring (self-report). Ibrahim2019 (9) Microneedling + Cal/BD vs Microneedling + Tacrolimus Transient irritation/erythema/itching; no serious AEs (clinical assessment). Fig. 2. Forest Plot (Random-Effects). Exploratory meta-analysis of dichot­ omous efficacy outcomes from two trials (Ginkgo biloba; Zengse Pill) showing RR = 2.05 (95% CI 0.79–5.35); I² = 52.6%.

J.P. Alzate-Granados, A.C. Díaz-Manrique, A. Maffiold-Novoa et al. Journal of Dermatologic Science and Cosmetic Technology 3 (2026) 100167

and personnel blinding. No study was considered to have a high risk of bias. For additional details on each study, see Table 2.

3.7.1. Synthesis of Results (see Table 3)

Efficacy of Fire Needle Therapy Combined with Tacrolimus (Yuyi Wang,7 China) The study demonstrated that combining fire needle therapy with ta­ crolimus ointmenyuyt was significantly more effective than either treat­ ment alone in reducing vitiligo lesion area and achieving repigmentation over six months. By the fourth month, the combination therapy achieved greater area reduction compared to tacrolimus alone (p = 0.018). At six months, 89.7% of patients in the combination group achieved ≥ 25% repigmentation (mild response), compared to 69% in the fire needle group

and 6.9% in the tacrolimus group (p < 0.01). Additionally, 51.7% of the

combination group achieved ≥ 50% repigmentation (good response),

significantly outperforming the other groups (p < 0.01) (5).

Efficacy of Zengse Pill (SHI Nian,8 China) This study reported higher efficacy in the group treated with Zengse

Pill (82.4% vs. 54.8% in the control group, p < 0.05). Immunological

markers (CD4 +, CD8 +, CD4 +/CD8 + ratio) improved significantly in the treatment group compared to the control group and baseline

levels (p < 0.01). Adverse effects were mild and did not interfere with

treatment (6).

Treatment with Ginkgo biloba (D. Parsad, 2003, India) Ginkgo biloba treatment significantly halted disease progression in 80% of patients compared to 36.4% in the placebo group (p = 0.006). Additionally, 40% of treated patients showed marked or complete re­ pigmentation, compared to only 9% in the placebo group (7). Topical Turmeric Cream (Samin Jalalmanesh,10 Iran)

Turmeric cream significantly reduced lesion size (VASI, p < 0.001)

and improved patient satisfaction (VNS, p < 0.05) compared to pla­

cebo. While there was a trend toward better response in Physician Global Assessment (PGA), it did not reach statistical significance

(p > 0.05) (8).

Microneedling with Calcipotriol + Betamethasone Versus Tacrolimus (Zeinab A. Ibrahim,11 Egypt) Microneedling combined with calcipotriol, and betamethasone re­ sulted in a higher total repigmentation percentage (72.16% vs. 54.16%

with tacrolimus, p < 0.01) and required fewer sessions to observe

improvement (mean of 4.72 ± 2.49 vs. 5.96 ± 1.99 sessions).

Patients treated with calcipotriol + betamethasone also reported higher satisfaction levels (9).

Based on the dichotomous outcomes from two trials—Zengse Pill’s composite efficacy (28/34 vs. 17/31 in control) and Ginkgo biloba’s repigmentation rate (10/25 vs. 2/22) —we calculated study-level risk ratios and performed a random-effects meta-analysis. The resulting forest plot (above) visualizes each study’s effect size with 95% con­ fidence intervals and the overall summary estimate. Heterogeneity across studies was moderate (Q = 2.11, p = 0.15; I² = 52.6%), indicating that about half of the variability in effect estimates is due to between-study differences rather than chance. The random-effects sum­ mary risk ratio was 2.05 (95% CI 0.79–5.35), suggesting a non-significant doubling of efficacy with complementary treatments—but with wide con­ fidence intervals reflecting uncertainty and heterogeneity (Fig. 2).

3.8. Adverse results reported

Across the six studies, the conventional treatment regimens for vitiligo demonstrated efficacy with generally mild and manageable adverse ef­ fects. Yuyi Wang et al.7 reported that 0.1% tacrolimus ointment, whether used alone or in combination with fire needle therapy, produced sig­ nificant repigmentation with only minor local irritation and a burning sensation. In SHI Nian et al8, a regimen combining cobamamide with a Psoralea tincture was employed, and while some patients experienced mild erythema, itching, and one instance of constipation, these effects did not compromise treatment outcomes. D. Parsad et al. (2003) showed that oral Ginkgo biloba extract (administered at 40 mg three times daily) was well tolerated, with only occasional mild nausea. Two studies by Samin Jalalmanesh et al.10 evaluating topical turmeric cream found significant improvements in lesion size and appearance with no reported adverse effects. Lastly, Zeinab A. Ibrahim et al.11 compared a microneedling-as­ sisted calcipotriol–betamethasone combination with 0.03% tacrolimus ointment, revealing that the combination therapy yielded superior re­ pigmentation outcomes, while the tacrolimus arm was associated with mild erythema and itching (Table 4).

4. Discussion

Across six small RCTs (n = 255), the integrative and complementary therapies (ICTs) evaluated in this review—topical turmeric, oral Ginkgo biloba, fire needle therapy, and microneedling-assisted delivery of cal­ cipotriol plus betamethasone—consistently showed signals of benefit for repigmentation, lesion-area reduction, or disease arrest when compared with placebo or conventional topical therapies. Safety pro­ files were acceptable, with mostly mild, local, and reversible adverse effects, and patient-reported satisfaction favored some ICT regimens over controls (7,10–12). However, when interpreted through a critical methodological lens, the certainty of this evidence is low and the magnitude and durability of benefit remain uncertain (1–4). From a risk-of-bias perspective, several trials lacked adequate re­ porting—or implementation—of allocation concealment and blinding, particularly for operator-dependent interventions such as fire needle and microneedling. These design features increase susceptibility to perfor­ mance and detection bias and may inflate treatment effects, especially for subjective or semi-quantitative outcomes (e.g., global repigmentation scores, physician global assessment) (1–3). Sample sizes were modest, follow-up rarely exceeded 6 months, and few studies prespecified primary outcomes or provided formal sample-size calculations, further contributing to imprecision and raising the possibility of selective outcome reporting. Under a GRADE framework, these limitations would likely downgrade the quality of evidence to low or very low for most comparisons (3,4). Clinical and methodological heterogeneity also constrain interpret­ ability. The included trials evaluated different ICTs, doses, treatment schedules, and combinations with conventional therapies, and they used variable thresholds for response (e.g., “marked,” ≥50%, ≥75% re­ pigmentation) and non-standardized VASI reporting. In this context, our exploratory meta-analysis of two small trials (Zengse Pill and Ginkgo bi­ loba) should be considered hypothesis-generating only: wide confidence intervals spanning no effect and moderate statistical heterogeneity (I² > 50%) limit any firm conclusions regarding pooled efficacy. These features also precluded meaningful assessment of publication bias and dose–r­ esponse relationships.

External validity is another concern. Most studies were conducted in Egypt, Iran, India, and China—regions near or intersected by the Tropic of Cancer—with high ambient UV exposure and frequent background be­ haviors that may potentiate repigmentation (e.g., incidental sun exposure, cultural practices) (1–3). Fitzpatrick phototype was incompletely reported; only one trial explicitly documented phototypes III–IV, and none system­ atically stratified outcomes by skin type. This combination of limited phototype reporting and geographically clustered recruitment may restrict generalizability to patients in Europe, North America, or Northern Asia, as well as to very fair or very dark phototypes, in whom the cosmetic and psychosocial impact of vitiligo can differ substantially (1–4). Within these constraints, some signals are nonetheless consistent with prior literature. The benefit of Ginkgo biloba in halting disease progression and inducing marked repigmentation in a proportion of patients mirrors earlier placebo-controlled data, where 40 mg three times daily for 6 months arrested spread in most participants and produced ≥ 75% re­ pigmentation in a relevant subset (7). Mechanistic and translational work suggesting antioxidant, immunomodulatory, and potential IL-6–lowering effects provides biological plausibility for these clinical observations (10,11,23). However, sample sizes are small, replication is limited, and the J.P. Alzate-Granados, A.C. Díaz-Manrique, A. Maffiold-Novoa et al. Journal of Dermatologic Science and Cosmetic Technology 3 (2026) 100167

optimal dose, duration, and target phenotype (e.g., slowly progressive vs. rapidly evolving disease) remain undefined.12 Microneedling-based protocols illustrate similar tensions between promise and uncertainty. Prior series have reported repigmentation rates around 50–60% when microneedling was combined with tacro­ limus alone, whereas the trial included in this review found higher response rates (∼72%) when calcipotriol plus betamethasone were delivered via microneedling, with statistically significant gains over tacrolimus-based comparators (12). Whether this represents a true pharmacologic advantage, an effect of more intensive local inflamma­ tion, or simply trial-specific factors (e.g., baseline disease character­ istics, lesion location, assessment methods) is unclear. Without head-tohead, adequately powered RCTs with standardized endpoints and longer follow-up, it is premature to conclude that one microneedling combination should be preferred over others.13 Contextualizing these findings within contemporary clinical guide­ lines is critical. International consensus statements and task force al­ gorithms published in recent years emphasize a stepwise, patient-cen­ tered approach built primarily around topical corticosteroids, topical calcineurin inhibitors, narrowband UVB phototherapy, and, more re­ cently, topical JAK inhibitors such as ruxolitinib, with surgical techni­ ques reserved for carefully selected, stable cases (4,16–20). National and regional guidelines echo this structure, highlighting phototherapy (especially NB-UVB) as first-line for generalized disease and topical agents and surgery as key options for localized or stable vitiligo (16,19). ICTs as evaluated in our review—botanicals, acupuncture-derived techniques, and device-assisted delivery—are rarely positioned as core components of these algorithms; when mentioned at all, they are framed as experimental or adjunctive options, reflecting the low cer­ tainty and sparse replication of the underlying evidence (4,16–20). Taken together, our results support an adjunctive, rather than sub­ stitutive, role for ICTs in current practice. For selected patients—such as those with contraindications or poor tolerance to topical corticosteroids or calcineurin inhibitors, partial responders seeking incremental benefit, or individuals with strong preferences for “natural” or minimally invasive options—ICTs may be considered as add-ons to guideline-concordant therapy, provided that clinicians emphasize the experimental nature of these interventions and the uncertainty around long-term efficacy, relapse rates, and cost-effectiveness (4,16–20). In parallel, careful attention should be paid to product quality (particularly for herbal preparations), potential drug–herb interactions, and realistic expectation setting, to avoid both therapeutic nihilism and overpromising benefits.14 Several included trials recruited broad age ranges (e.g., 8–65 years), yet age-stratified outcomes were not reported, preventing evaluation of whether age modified treatment response. Evidence from conventional vitiligo phototherapy is mixed: some analyses have found no association between age and response to NB-UVB,15–17 whereas other large cohorts suggest better repigmentation in younger patients under specific clin­ ical patterns (e.g., non-segmental vitiligo involving the trunk).18 Given this inconsistency, future RCTs of integrative/complementary therapies should prespecify age strata (e.g., pediatric vs adult), ensure balanced randomi­ zation by age group, and/or adjust analyses for age and disease duration to improve interpretability and external validity.

Although only a small number of integrative/complementary inter­ ventions in vitiligo have been tested in randomized trials, the RCTs in­ cluded in this review provide several practical lessons for future study design. First, they demonstrate feasibility: short-term randomized eva­ luation of botanicals and procedure-based interventions is achievable across diverse settings, with generally mild adverse events and no serious treatment-related signals, supporting ethical equipoise and safety mon­ itoring frameworks for larger trials.19 Second, the direction and magnitude of effects observed in some trials (e.g., disease arrest/repigmentation sig­ nals) can inform sample-size calculations and help prioritize the most promising candidates for replication.20 Third, the trials highlight recurring methodological vulnerabilities—incomplete allocation concealment/ blinding and heterogeneous outcome definitions—which may inflate effect estimates and limit comparability.21 Accordingly, future RCTs should be multicenter and adequately powered, use standardized core outcomes (e.g., VASI-based thresholds such as VASI50/75 and validated patient-reported outcomes), prespecify analytic plans, and improve re­ porting fidelity (CONSORT). In addition, future protocols should stan­ dardize intervention delivery (especially for operator-dependent proce­ dures), document key effect modifiers (e.g., phototype, lesion location, disease activity), and incorporate longer follow-up to evaluate durability and relapse.4,16–20 Additionally, Ginkgo biloba treatment has been documented to re­ duce interleukin-6 levels, an inflammatory marker associated with vi­ tiligo, and enhance patients’ antioxidant capacity, suggesting a sig­ nificant protective effect on melanocytes. These results support the use of Ginkgo biloba as a complementary therapeutic option for patients with this condition.

However, this study also identifies differences from existing literature regarding therapeutic combinations. For example, the combination of microneedling with tacrolimus has been reported to achieve repigmenta­ tion rates of 50%-60%. In contrast, this review found that adding calci­ potriol and betamethasone to this protocol significantly increased the re­ pigmentation rate to 72%, with robust statistical significance. These differences may be attributed to variations in treatment protocols, followup durations, and patient characteristics across studies. The present meta-analysis (two trials only) is hypothesis-generating. Its imprecision (wide CIs spanning no effect) and moderate heterogeneity underscore the need for larger, harmonized RCTs using standardized endpoints (e.g., VASI50/75, F-VASI) and core safety reporting. While our review focused on comparing integrative and com­ plementary therapies with conventional topical treatments, it is important to acknowledge that the therapeutic landscape for vitiligo is broad. In addition to these approaches, phototherapy (especially narrowband UVB) remains one of the most widely adopted treatments for vitiligo, demon­ strating robust efficacy in stabilizing disease activity and inducing re­ pigmentation, though concerns about long-term exposure persist. Surgical interventions such as melanocyte transplantation and epidermal grafting have emerged as viable options for patients with stable or segmental vi­ tiligo, offering high repigmentation rates but often limited by patient se­ lection criteria, technical complexity, and cost. Moreover, biologic agents targeting specific immune pathways are beginning to show promise for refractory cases; however, their long-term safety and efficacy require further investigation. Future research should incorporate these modalities into comparative studies to provide a more comprehensive assessment of the advantages and disadvantages of each treatment option, ultimately guiding clinicians toward a more personalized management strategy for vitiligo.

5. Conclusions

In this systematic review of six randomized trials, integrative and complementary therapies for vitiligo showed encouraging but low-cer­ tainty signals of benefit for repigmentation, disease stabilization, and pa­ tient satisfaction, with generally favorable short-term safety profiles. However, methodological limitations—including small sample sizes, short follow-up, incomplete blinding, and heterogeneous interventions and outcome definitions—substantially weaken confidence in the estimated effects and limit generalizability beyond the populations and settings studied (1–4,7,10–12). In line with contemporary international and na­ tional guidelines, ICTs should not replace established, evidence-based modalities such as topical corticosteroids, calcineurin inhibitors, narrow­ band UVB, topical ruxolitinib, or surgery in appropriately selected stable disease (4,16–20). Instead, they may be considered as individualized ad­ juncts for carefully selected patients—particularly those with contra­ indications to standard therapies, partial responders seeking incremental improvement, or strong preferences for integrative approaches—after ex­ plicit counselling about the limited and heterogeneous evidence, possible benefits, costs, and uncertainties regarding long-term outcomes. Future J.P. Alzate-Granados, A.C. Díaz-Manrique, A. Maffiold-Novoa et al. Journal of Dermatologic Science and Cosmetic Technology 3 (2026) 100167

research should prioritize adequately powered, multicenter RCTs of the most promising ICTs, embedded within guideline-relevant treatment pathways and using standardized, patient-centered outcome sets with long-term follow-up. Such trials should also address key evidence gaps, including comparative effectiveness against modern standards of care, effects across diverse phototypes and healthcare settings, durability of repigmentation, relapse prevention, and cost-effectiveness. Only when these questions are robustly addressed can ICTs be confidently positioned within vitiligo treatment algorithms and routinely recommended in ev­ eryday clinical practice.

6. Limitations

This review is constrained by the small and diverse evidence base available for integrative and complementary treatments in vitiligo. Only a limited number of randomized trials met eligibility criteria, most enrolled modest samples and followed participants for short periods, and the evaluated interventions varied substantially in composition, dosing, pro­ cedural technique, and concomitant conventional therapy. Outcomes were also reported using non-uniform definitions and thresholds for response, which limited comparability across studies and restricted the feasibility and interpretability of pooled analyses. Consequently, any quantitative synthesis was exploratory and underpowered to provide precise estimates, particularly for therapies represented by single trials. Methodological limitations within the included studies further reduce confidence in the observed effect sizes. Several trials provided incomplete detail regarding allocation concealment and blinding, and operator-depen­ dent procedures such as fire needle therapy and microneedling are espe­ cially vulnerable to performance and detection bias when masking is not feasible. In addition, reporting of potentially important effect modifiers was inconsistent, including disease activity, lesion location, prior treatment ex­ posure, and Fitzpatrick phototype, limiting our ability to assess hetero­ geneity of treatment effects or to conduct meaningful subgroup analyses. We were also unable to reliably evaluate publication bias because the number of eligible trials was small and meta-analysis was possible for only a subset of outcomes. Unpublished or selectively reported results may therefore have influenced the apparent balance of benefit and harm, and the quantity and quality of primary data remain uneven across therapies. Finally, generalizability is limited because most trials were conducted in a small number of regions with potentially different background ultraviolet exposure and healthcare contexts, and the lack of diverse phototype re­ presentation restricts application of these findings to broader patient po­ pulations. Moreover, comparators did not consistently reflect con­ temporary standards of care, so the clinical relevance of these results within modern treatment algorithms should be interpreted cautiously. CRediT authorship contribution statement Juan Pablo Alzate Granados: Writing – review & editing, Writing – original draft, Visualization, Validation. Andrea Carolina Díaz Manrique: Writing – review & editing, Writing – original draft, Resources. Alexandra Maffiold Novoa: Writing – review & editing, Writing – original draft, Visualization, Methodology. Leidy Vanessa Rodríguez Moreano: Writing – review & editing, Writing – original draft, Project administration. Yinneth Ruiz Atencio: Writing – review & editing, Writing – original draft, Visualization. Andrés Felipe Torres Medina: Writing – review & editing, Writing – original draft. Vanessa Díaz Granados: Writing – review & editing, Writing – original draft. Declaration of Competing Interest The authors declare that they have no financial or personal re­ lationships that could inappropriately influence or bias the content of this manuscript. No funding was received specifically for this work. Additionally, the authors have no known competing interests related to the development, implementation, or evaluation of artificial in­ telligence technologies in orthopedic diagnosis.

Appendix A. Supporting information Supplementary data associated with this article can be found in the online version at doi:10.1016/j.jdsct.2026.100167.

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