From: A systematic review of natural health product treatment for vitiligo
Study ID Year & Country | Study Design | JADAD score (0–5) | N (n = total; a = active; c = control) | Dropouts | Inclusion/Exclusion Criteria | Intervention | Main Outcome Measure | Results | |
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Akyol 2002 [32] Turkey | controlled | 0 | n = 30 a = 15 c = 15 | not reported | Inclusion patients with active, extensive & generalized vitiligo 14–60 years old skin type II, III, IV | Active PUVA + vit E (900 IU/day) Control PUVA 3x/wk, 315–400 nm emission spect increased by 20% up to erythema Duration: 6 months | front and back total body photographs pigmentation rated as: - bad (0–25%) - moderate (25–74%) - good (75% or more) | PUVA + Vit E allowed good improvement in 60% of patients, with no significant oxidation. Active bad 3 (20%) moderate 3 (20%) good 9 (60%) | Control bad 5 (33%) moderate 4 (27%) good 6 (40%) |
Bedi 1989 [26] India | placebo, controlled | 0 | n = 32 c = "self controlled" placebo for 1 month every 3 months | 2 participants lost to follow up | Inclusion - male and female - 6–42 years old | - methoxsalen tablets 10–20 mg QD + methoxsalen ointment/lotion-0.75% + P. kurroa rhizomes – 200 mg dried herb BID + exposure to sunlight Duration: 36–1.8 months; 12.13 months average treatment length | response rated as: - 4 = complete cure - 3 = fast & continuous reduction in patches - 2 = slow, continues reduction in patches - 1 = v. slow progress - 0 = 0 progress | 93% responded to treatment, 27% achieved complete cure. 4 = 8/30 3 = 17/30 2 = 2/30 1 = 3/30 |  |
Cheng 1987 [23] China | randomized, controlled | 1 | n = 329 A: 16 = needle B: 9 = medication C: 5 = phototherapy D: 128 = needle + medication E: 61 = needle + medication + suntan F: 110 = needle + medication + phototherapy | not reported | not reported | - needle = 1 g/2 ml bottle, injected 2–4 mL QD - medication = 235 used "Vitiligo medication"; 48 used 8-MOP; 25 used "vitiligo cream"; rest prescribed egg yolk before suntan or phototherapy - suntan = mid-May to end of Sept whole body naked suntan, 1–3 hr per day, 8–10 am, or 4–6 pm - phototherapy = long wave phototherapy, every 2–3 days 5–25 cm2 or 1–10% of body surface | response rated as: - excellent = color of lesion turns to normal - very good = color of lesion turns normal for over 60% of body surface - good = lesion gets smaller and appearance of black granules - bad = lesion identical to that before the treatment | Treatment with suntan effective after 60 days. Group A: 2 = excellent 5 = very good 9 = good Group B 1 = excellent 2 = very good 6 = good Group C 4 = good 1 = bad Group F 16 = excellent 35 = very good 58 = good 1 = bad 109 = overall good result | Group D 8 = excellent 37 = very good 79 = good 4 = bad 124 = overall good result Group E 12 = excellent 26 = very good 23 = good 61 = overall good result |
Cormane 1985 [20] Netherlands | controlled by run in over 4 months | 0 | n = 19 | not reported | Inclusion - male and female - generalized vitiligo - above 18 years old Exclusion - past spontaneous improvement - CI to phenylalanine | l-phe 50 mg/kg after a low protein breakfast + UVA 2x/wk Duration: 6–8 months Controlled by run in with l-phe 50 mg/kg 2x/wk for 4 months | repigmentation was classified as dense, sparse or none | Repigmentation achieved in 94.7% of patients. dense repigmentation in 26.3% (5 pts) sparse 68.4% (13 pts) none 5.2 (1 pt) |  |
Jin 1983 [25] China | randomized, controlled | 1 | n = 232 A: n = 100 B: n = 51 C: n = 52 D: n = 28 | not reported | not reported | A: Chinese Herb/Medicine 1 Ingredients: multi herb formula B: Corticoids 15 mg per day, oral (if effective decrease 5 mg every 2–4 weeks) C: Chinese Herb/Medicine 2 + Corticoids Ingredients different from Chinese Herb/Medicine 1* Group A,B,C also applies 30% Psoralen topically D: Control apply 30% Psoralen topically Duration: 2 months | response rated as: - Excellent = all lesions disappear, normal skin color reappears - Very good = reduction in lesion, >60% of damaged skin surface regains normal skin color - Good = reduction in lesion, 10–60% of damaged skin surface regains normal skin color - Bad = lesion shows no change in appearance or size, <10% of damaged skin surface regains normal skin color | Chinese medicine 2 & corticoids provided the best treatment. Group A 13% = excellent 17% = very good 34% = good 36% = bad Group C 31% = excellent 14% = very good 28% = good 27% = bad | Group B 18% = excellent 13% = very good 29% = good 40% = bad Group D 0% = excellent 6% = very good 27% = good 67% = bad |
Khemis 2004 [30] France | randomized, double blind | 2 | n = 30 self controlled by contralateral side | 13 dropped out | Inclusion participants with 2 vitiliginous lesions each with at least 10 cm in diameter Exclusion unstable vitiligo | Active Vitix + UVB Control Placebo + UVB | primary: - reduction of lesion surface area by 50% - photographs under normal and Woods Lamp | The difference between control and active was not significant 4 participants did not repigment 4 participants received a reduction 6 achieved a reduction of more than 50% of lesion with Vitix and UVB but not with control 3 achieved had a reduction of more than 50% of lesion with control but not with Vitix and UVB. | Â |
Liu 2003 [24] China | randomized, controlled | 1 | n = 74 a = 41 c = 33 | not reported | not reported | Active - Xiaobai mixture orally (30 g walnut, 10 g red flower, 30 g black sesame, 30 g black beans, 10 g zhi bei fu ping, 10 g lu lu tong, 5 plums)1 mL is equivalent to 0.1 g raw medication, 160 mL once a day Control - 10 mg 8-MOP TID Duration: 3 months | repigmentation rated as: - Excellent = normal skin color reappears - Very good = >50% of damaged skin surface regains normal skin color - Good = 10–50% of damaged skin surface regains normal skin color - Bad = <10% of damaged skin surface regains normal skin color | 95% of active and 79% of control group showed good results. Active - 12 = excellent results - 16 = very good results - 11 = good results - 2 = bad results - Overall 95.12% showed good results Control - 3 = excellent results - 14 = very good results - 9 = good results - 7 = bad results |  |
Middelkamp-Hup 2007 [28] Netherlands | placebo controlled, randomized, double blind | 5 | n = 50 a = 25 c = 24 | 1 lost to follow up at last session | Inclusion - 18 years and older - vitiligo vulgaris Exclusion - history of skin cancer - photosensitive - pregnancy or lactation - segmental vitiligo - phototherapy 3 months prior - use of topical treatments - starting vitamins during the study | Active Polypodium leucotomos 250 mg TID + NB-UVB 2x/wk (210–360 j/cm2 at start & gradually increased) Control placebo TID + NB-UVB Duration: 25–26 weeks | severity of vitiligo rated as: - very severe - severe - more severe - less severe - not so severe secondary measures: - digital photography of all vitiligo lesions - patient self assessment scale 0–10 - monitored at w0, w6, w12, w26 - for quality of life used skin index-29 | Clear trend toward increase in repigmentation in head and neck area with NB-UVB and oral P. leucotomos treatment. Percent Repigmentation : Head & Neck active = 44% control = 27% Extremities active = 30% control = 26% | Trunk active = 36% control = 30% Hands and Feet active = 24% control = 19% |
Parsad 2003 [2] India | randomized, placebo controlled, double blind | 2 | n = 52 a = 26 c = 26 | 1 active 2 control "withdrew for reasons unrelated to the study" | Inclusion gradually progressive slow spreading vitiligo Exclusion more than 3 lesions or surface area of depigmentation greater than 10 cm2 over last 1 month | Active 40 mg Ginkgo biloba with 9.6 mg ginkgoflavone glycosides, TID Control sugar capsule TID Duration: 6 months | - photographs at 6-weekly intervals - repigmentation judged as minimal (25%), moderate (50%), marked (75%), complete (100%)- degree of repigmentation was determined by comparison of paper tracings, written descriptions, and actual measurement of vitiliginous areas | Gingko biloba was significantly more effective. Active -20 pts stopped progression of disease (out of 25) - 10 pts showed marked to complete repigmentation (75–100%) (out of 25) Control - 8 pts arrested progression of disease (out of 22) - 2 pts showed marked to complete repigmentation (75–100%) (out of 22) |  |
Rojas-Urdaneta 2007 [22] Venezuela | randomized, double blind | 3 | n = 100 divided into 5 groups | all completed the study | Inclusion - stable vulgar vitiligo - no treatment for 5 months before study - 18 to 50 years old - male or female - no other pathology - provided consent for study and treatment Exclusion - concomitant disease - treatment of vitiligo 5 months prior to study - not complying with instructions | A: antioxidant and mitochondrial stimulating cream & oral antioxidants & phenylalanine B: placebo cream and oral antioxidants and phenylalanine C: oral administration of antioxidants and phenylalanine D: placebo cream E: antioxidant and mitochondrial stimulating cream cream = VitilVenz phenylalanine = 500 mg q12 hrs for 5 months oral antioxidants = Vit A 20,000 IU Vit C 1000 mg Vit E 400 IU Zinc 15 mg Selenium 50 μg Magnesium 2 mg CoQ10 75 mcg pygnogenol 1 mg | main outcome measures: - clinical area of newly formed pigment every 30 days - point system for classifying size - histological presence of melanocytes at beginning and end | The use of antioxidant and mitochondrial cream, and oral antioxidants and phenylalanine provided best results. group A - best results, 10.4 points (p < 0.001) group E - second best results 9.77 points (p < 0.001) group B, C - 4 points (p < 0.05) group D - comparison placebo group |  |
Siddiqui 1994 trial 1 [21] Netherlands | randomized, controlled, open label | 0 | n = 149 A: no tx = 11 B: l-phe +UVA = 132 C: l-phe alone = 6 | out of 132 l-phe + UVA, 60 dropped out because they were unable to attend every 3 months for evaluations) | Inclusion - disseminated vitiligo over 10–40% of body - age 18–61 yrs Exclusion - only distal vitiligo - only acrofacial vitiligo - contraindications (same as Carmane 1985) - patients in the open trial were not enrolled in the blind trial | A: l-phe 50–100 mg/kg + UVA 2x/wk; 30–45 min after l-phe ingestion daily B: l-phe 100 mg alone C: no tx Duration: 1.5 yrs | length & width measures + color photographs every 3 months Repigmentation Classification: - partial 25–40% - incomplete 40–60% - good 60–80% | L-phenylalanine + UVB provided better results than L-phenylalanine alone. Group A positive 94 stable 20 deterioration 18 n = 132 Group C positive 0 stable 7 deterioration 4 n = 11 | Group B positive 0 stable 5 deterioration 1 n = 6 |
Siddiqui 1994 trial 2 [21] Netherlands | placebo controlled, randomized, double blind | 3 | n = 32 | 5 in placebo 3 active (2 stopped for personal reasons) | Inclusion 18–56 years old vitiligo for 1–33 years | l-phe 100 mg/kg/day or placebo UVA 2–3x/wk or no irradiation Duration: 6 months | length and width measured + color photographs every 3 months Repigmentation Classification: - partial 25–40% - incomplete 40–60% - good 60–80% | L-phenylalanine + UVB provided best results. l-phe + UVA positive 6 stable 1 deterioration 1 % repigmentation 30–60 n = 8 dropouts 0 l-phe positive 1 stable 3 deterioration 1 % repig 25 n = 5 dropouts 3 | placebo + UVA positive 0 stable 4 deterioration 2 % repig 0 n = 6 dropouts 2 placebo positive 0 stable 3 deterioration 2 % repig 0 n = 5 dropouts 3 |
Tjioe 2002 [31] Sweden | randomized, open label, controlled | 2 | n = 27 a = 14 c = 13 | 1 active and 1 control did not repigment more than 5% after 4 months and were advised to stop | Inclusion - male & female over 18 yrs - stable vitiligo vulgaris (1 year with no changes) - fitzpatrick's skin II – IV Exclusion - other vitiligo treatment - history of skin cancer - on photosensitizing medications - Psychiatric/epileptic disorders - renal failure or allergies to substances in trial | Active - UVB 3x/wk - oral cobalamin 1000 ug sustained release BID - folic acid 5 mg BID Control - UVB (311 nm) 3x/wk, started at 0.10 J/cm2 increased by 0–30% on individual basis Duration: 12 months | primary: visually scored as percentage of repigmentation of depigmented lesions primary criterion were areas showing most active repigmentation secondary: before and after photographs with % repigmentation visually estimated | No significant difference between the two groups. 25 out of 27 total showed prominent repigmentation in some areas, 1 in each group did not respond more than 5% |  |
Valkova 2004 [27] Bulgaria | controlled (group assignment by alternation) | 0 | n = 33 a = 16 c = 17 | not reported | Inclusion -vitiligo - male & female and 8 kids - age 6–59 (mean 24.3 years) - photo-type II-IV - 2–21 years of disease | Active - local KUVA - 5% khellin in water/oil applied to lesion area - 1 hr later – UVA – 2–2.5 j/cm2 Control - systemic PUVA - oral psoralen (0.4 mg/kg) - 2 hrs later-UVA – 1–1.5 j/cm2 - 3x/wk Duration: 4.1 months | - % of repigmentation measured by planimetry (actual measurement)- % repigmentation according to rule of three | Both KUVA and PUVA treatment lead to similar results, but KUVA is local, therefore with potentially with less adverse events. active n 90–100% 3(18.8%) 60–80% 4(25.0%) 20–50% 7(56.2%) no effect 2 Signs of repigmentation appeared between 10–16 procedures | control n 90–100% 2 (11.8%) 60–80% 7 (41.2%) 20–50% 7 (41.2%) no effect 1 |
anonymous 2006 [29] Japan | randomized, double blind | 0 | n = 19 a = 10 c = 9 | not reported | Inclusion generalized vitiligo Exclusion acral or segmental vitiligo | Active PUVA + Polypodium leucotomos Control PUVA + placebo Duration: 12 wks | repigmentation scored as: - none or minimal (<25% repigmentation) - mild (25–50%) - moderate to excellent (>50%) | Percentage of patients with skin repig. greater than 50% was significantly higher in PUVA + Polypodium active none = 2 mild = 3 moderate = 5 | Control none = 5 mild = 4 moderate = 0 |