Table 2.

The role of Vitamin D deficiency in the pathogenesis and clinical progression of skin disorders

Authors	Year	Dermatological diseases	Study design	Sample size	Experimental Methods	Key Findings
Jenssen M et al.[55]	2023	psoriasis	Randomized Controlled Trial(RCT)	122 cases	Participants were proportionally allocated to receive Vitamin D (cholecalciferol, 100,000 IU as a loading dose, followed by 20,000 IU weekly) or placebo for a duration of 4 months.	Supplementation with Vitamin D did not affect the severity of psoriasis.
Lim SK et al.[304]	2016	acne	RTC	160 cases (80 acne patients and 80 healthy controls)	Serum 25(OH)D levels were measured, and demographic data were collected. Patients with Vitamin D deficiency received oral cholecalciferol treatment at a dose of 1000 IU daily for 2 months.	25(OH)D levels are negatively correlated with acne severity and show a significant negative correlation with inflammatory lesions.
Hassan AR et al.[305]	2025	keloids and hypertrophic scars	clinical trial	30 patients with hypertrophic scars and keloids	Group 1: Patients with Vitamin D deficiency or insufficiency received a monthly systemic injection of Vitamin D (cholecalciferol 200,000 IU) for 3 consecutive months, along with oral calcium supplementation. Additionally, intralesional Vitamin D injections were administered at sites of hypertrophic scars and keloids.	The intralesional injection of Vitamin D in patients with hypertrophic scars and keloids enhances vascular distribution and elasticity in those with sufficient serum Vitamin D levels. However, in patients with serum Vitamin D deficiency or insufficiency, systemic Vitamin D administration does not result in changes in scar height or pigmentation.
					Group 2: Patients with sufficient Vitamin D levels received only intralesional Vitamin D injections.
Mohamed AA et al.[306]	2022	CSU	RTC	164 cases(77 patients with CSU and 67 healthy controls)	Seventy-seven CSU patients were randomly assigned to the treatment group and the placebo group. The treatment group received 0.25 µg of alfacalcidol daily, while the placebo group received oral placebo treatment for 12 weeks.	Compared to healthy individuals, patients with CSU are more prone to Vitamin D deficiency; therefore, alfacalcidol may serve as an adjunctive therapy in CSU management, with no reported adverse effects.
Mony A et al.[307]	2020	Chronic urticaria	RTC	120 cases of chronic kidney disease (CKD) patients with Vitamin D deficiency	CU patients received supplementation of 60,000 IU Vitamin D every two weeks for 12 weeks, while the placebo group received matched placebo.	Supplementation of Vitamin D in CU patients with Vitamin D deficiency can significantly reduce disease severity, potentially by mitigating systemic inflammation.
Ahmed Mohamed A et al.[308]	2021	Acne vulgaris	RTC	100 acne patients and 100 healthy controls	One hundred acne patients were randomly assigned to the treatment group and placebo group; the treatment group received 0.25 µg alfacalcidol daily, and the placebo group received placebo orally during the 3-month study period.	Alfacalcidol may exert beneficial effects in acne management, with no reported adverse effects.
Nabavizadeh SH et al.[309]	2023	CSU	RTC	80 patients with chronic spontaneous urticaria	Participants were randomly allocated into low-dose (4200 IU/week, group 1) and high-dose (28,000 IU/week, group 2) Vitamin D3 supplementation groups for 12 weeks.	For patients with chronic spontaneous urticaria, Vitamin D supplementation therapy (28,000 IU/week) can be considered a safe and potentially beneficial treatment option.
Johansson H et al.[310]	2021	Patients with stage II melanoma	RTC	104 newly resected stage II melanoma patients	Participants were randomly assigned to receive adjunctive Vitamin D3 treatment (100,000 IU every 50 days) or placebo for 3 years.	Although evidence suggests that 25-hydroxyVitamin D (25OHD) plays a role in melanoma prognosis, larger-scale Vitamin D supplementation trials in melanoma patients are still warranted.
De Smedt J et al.[311]	2024	cutaneous melanoma	RTC	436 resected melanoma patients from stage IA to III (according to the 8th edition of the American Joint Committee on Cancer staging system).	A total of 218 patients received placebo treatment, while another 218 patients received monthly treatment with 100,000 IU of calcitriol for a minimum of 6 months and a maximum of 42 months (treatment group).	For patients with CM, monthly supplementation of high-dose Vitamin D is safe and can sustain elevated levels of 25-hydroxyVitamin D during the treatment period; however, it does not improve recurrence-free survival, melanoma-specific mortality, or overall survival.
Mansour NO et al.[312]	2020	severe atopic dermatitis	RTC	86 cases	Patients were randomly assigned to receive either Vitamin D3 supplementation at a dose of 1600 IU/day or placebo, in addition to baseline treatment consisting of twice-daily application of 1% hydrocortisone cream for 12 weeks.	Supplementation with Vitamin D may serve as an effective adjunctive therapy to improve clinical outcomes in severe atopic dermatitis.
El-Heis S et al.[313]	2022	atopic eczema	RTC	unknown	In the MAVIDOS trial, pregnant women were randomized to receive cholecalciferol (1000 IU/day) or matching placebo from approximately 14 weeks’ gestation until delivery. The primary outcome measure was neonatal whole-body bone mineral content.	Prenatal supplementation with cholecalciferol has been demonstrated to confer a protective effect against the risk of atopic eczema in infants, potentially mediated by increased levels of cholecalciferol in breast milk.
Rueter K et al.[314]	2019	Eczema	Double-blind randomized controlled trial	unknown	Neonates were randomly assigned to receive either Vitamin D supplementation (400 IU/day) or placebo until 6 months of age. A subset of infants also wore personal UV dosimeters to measure direct ultraviolet radiation exposure (290–380 nm).	This study is the first to demonstrate an association between increased direct ultraviolet (UV) exposure in early infancy and a reduced incidence of eczema and pro-inflammatory immune markers before six months of age.
Maslin D et al.[315]	2020	Eczema	double-blind, randomized, placebo-controlled trial	195 infants born into families with first-degree relatives affected by allergic diseases	Among them, 86 infants were non-randomly assigned personal UV dosimeters to quantify UV exposure (290–380 nm) prior to 3 months of age.	Vitamin D supplementation in high-risk infants effectively elevated Vitamin D levels but did not reduce the incidence of eczema.
						Exploratory post-hoc analysis of a non-randomized subset indicated an association between increased direct UV exposure and decreased eczema occurrence.
Stanley Xavier A et al.[316]	2020	Psoriasiform dermatitis	RTC	72 cases	Patients with atopic dermatitis (AD) were randomly assigned to receive either oral cholecalciferol tablets at a dose of 60,000 IU weekly or a matching placebo for 8 weeks, in addition to standard baseline treatment.	For patients clinically diagnosed with psoriatic dermatitis, supplementation with calcitriol for 2 months did not reduce disease severity. However, plasma IL-10 levels significantly improved after 2 months of treatment in both the placebo and calcitriol groups.
Lara-Corrales I et al.[317]	2019	AD	RTC	130 cases	The first phase of the study enrolled AD patients aged 0 to 18 years, assessing disease severity and serum Vitamin D levels. Patients with renal, hepatic, or other dermatological conditions were excluded. Those with abnormal Vitamin D levels (< 72.7 nmol/L) were eligible for the second phase and were randomly assigned to receive either daily Vitamin D supplementation at 2000 IU or placebo.	Although Vitamin D (VD) levels correlated with atopic dermatitis (AD) severity, VD supplementation did not significantly improve the severity of specific dermatitis.
Cabalín C et al.[318]	2023	AD	RTC	unknown	An open-label supplementation study was conducted in pediatric AD patients, administering weekly oral doses of Vitamin D3 for a duration of six weeks.	After oral VD3 treatment, tslp gene expression remained unchanged. In children with AD, oral VD3 supplementation was associated with improved VD status, reduced AD severity, and increased expression of VDR and cathelicidin in lesional skin, providing mechanistic insights into its effects.
Udompataikul M et al.[319]	2015	AD	Randomized, double-blind, placebo-controlled clinical trial	20 cases	Patients were randomly divided into two groups to receive oral supplementation of 2,000 IU/day Vitamin D or placebo. Staphylococcus aureus cultures from lesion swabs were performed at weeks 0, 2, and 4.	Oral supplementation with Vitamin D can reduce the skin colonization of Staphylococcus aureus and has been shown to correlate with clinical improvement in patients with atopic dermatitis.
Kareem IMA et al.[320]	2019	wart	controlled clinical trial	70 cases	Fifty patients were allocated into two groups: 30 patients in the case group received intralesional injections of 0.2 mL Vitamin D3 (300,000 IU) at the base of the maternal warts, administered in two separate doses; the remaining 20 patients in the control group received saline injections.	Intralesional injection of Vitamin D3 may be considered an effective and safe therapeutic approach for the treatment of common warts.
Ernst MK, Evans ST et al.[321]	2023	rash	Randomized, double-blind, placebo-controlled intervention trial	28 cases	Twenty-eight participants were induced with skin inflammation using topical nitrogen mustard (NM). Over the following week, specific inflammatory responses to NM alone were characterized through clinical assessments, serum analyses, and skin tissue examinations. All participants then received repeated NM treatment on the contralateral arm, followed by intervention with either placebo or 200,000 IU of calcitriol. Comprehensive multi-omics analyses, clinical measurements, and serum studies of the full rash response were conducted over six weeks.	High-dose systemic calcitriol may serve as an effective treatment for severe localized chemotherapy-induced reactions. Our findings have broad implications for the use of calcitriol as an anti-inflammatory intervention to prevent the development of excessive immune responses.
Sánchez-Armendáriz K et al.[322]	2018	AD	Randomized, double-blind, placebo-controlled clinical trial	65 cases AD patients meeting the Hanifin-Rajka criteria and assessed by the SCORAD severity index.	Patients were randomized into two groups: 33 cases received Vitamin D3 treatment at 5000 IU/day, while 32 cases received placebo treatment. Both groups underwent concomitant baseline therapies including topical steroids, soap substitutes, and moisturizers for three months.	Achieving a serum 25(OH)D level > 20 ng/mL in combination with standard therapy is sufficient to reduce the severity of atopic dermatitis (AD) as measured by SCORAD.
Al-Sabak H et al.[323]	2023	wart	Therapeutic clinical trial	40 cases	A solution of Vitamin D3 (600,000 IU) was injected intralesionally at the base of the lesions, with 0.2 mL administered per patient. Up to five warts were injected per session. Injections were performed once every two weeks for a total of four sessions.	Intralesional injection of Vitamin D3 is an effective and low-cost treatment for cutaneous warts.
Raghukumar S et al.[324]	2017	Viral wart	Controlled experiment	60 cases	Approximately 0.2 to 0.5 mL of Vitamin D3 solution (600,000 IU, 15 mg/mL) was injected into the base of the wart lesions. Up to five warts were injected per session, with intervals of three weeks between injections, continued until wart clearance or a maximum of four treatments.	Intralesional Vitamin D3 injection is a safe, effective, and inexpensive therapy for recalcitrant warts.
Abd El-Magid WM et al.[325]	2021	Plantar wart	RTC	40 cases	Patients were randomized to receive either Vitamin D3 or zinc treatment. The Vitamin D3 group received intralesional injections of 0.3 mL Vitamin D3 (100,000 IU, 2.5 mg/mL) into the lesions, while the zinc group received intralesional injections of 2% zinc sulfate.	Intralesional injection of Vitamin D3 and zinc sulfate appear to be effective treatments for plantar warts.
Watabe A, Yamasaki K et al.[326]	2018	vitiligo	Randomized blinded clinical trial	48 cases	A total of 48 female patients with refractory vitiligo were enrolled and randomly assigned to two groups: the Vitamin D (VD) intervention group, which received 5000 IU cholecalciferol daily for 5 months, and the control group.	Daily administration of 5000 IU cholecalciferol to patients with refractory vitiligo is beneficial.
Aldaghi M et al.[327]	2022	AD	RTC	81 cases	Participants were randomly allocated into three groups. The probiotic group received 5 drops of multispecies probiotics daily in addition to standard treatment. The Vitamin D3 group received 1000 IU Vitamin D3 daily in addition to standard treatment. The control group received standard treatment alone.	Findings indicate that multispecies probiotic supplementation combined with Vitamin D3 and conventional treatment may serve as an adjunctive therapy to effectively reduce the severity of infantile atopic dermatitis.
Bakshi S et al.[328]	2022	Congenital ichthyosis	RTC	24 cases	Patients with congenital ichthyosis received either Vitamin D at a dose of 2000 IU/day (Group A) or acitretin at 0.5 mg/kg/day (Group B) for 24 weeks.	Vitamin D may serve as an alternative to acitretin in the treatment of congenital ichthyosis by downregulating RORγt and IL-17 expression.
Elsayed Ghaly N et al.[329]	2021	Plantar wart	RTC	62 cases	Sixty patients with plantar warts were randomly assigned into three groups: Group I received intralesional tuberculin PPD every 2 weeks; Group II received intralesional Vitamin D3 every 4 weeks; and Group III received intralesional normal saline every 2 weeks, until complete clearance or for a maximum of three sessions. The follow-up period was 6 months.	Both intralesional PPD and Vitamin D3 injections are safe and effective, even for recalcitrant or multiple plantar warts, and offer the advantages of no postoperative recovery period, superior therapeutic efficacy, and higher patient satisfaction. Intralesional Vitamin D3 demonstrates greater efficacy compared with PPD.
Zainab Z et al.[330]	2021	wart	RTC	50 cases	Patients were randomly assigned by lottery method. Group A received intralesional Vitamin D3 injection, while Group B underwent cryotherapy. The complete, partial, or no clearance of warts was compared between the groups.	Cutaneous warts are most commonly observed in patients with affected feet. Both treatments yield favorable patient responses; however, intralesional Vitamin D3 injection represents a more effective option for treating these cutaneous warts.
El Sayed MH et al.[331]	2020	wart	RTC	105 cases	Each group comprised 35 patients. The first group received treatment with 2% zinc sulfate solution, the second group received treatment with 2% Vitamin D3 solution, and the third group received normal saline. A total of four treatment sessions were administered at two-week intervals.	Both 2% zinc sulfate and Vitamin D3 intralesional injections are effective for the treatment of plantar warts, with zinc sulfate demonstrating superior efficacy.
Abdelaal MA et al.[332]	2021	wart	RTC	40 cases	Each group comprised 20 patients. Group A received intralesional Vitamin D3 injections, while Group B received Candida antigen injections. Injections were administered every 3 weeks until complete clearance of warts or for a maximum of three sessions.	Intralesional injection of Candida antigen or Vitamin D3 for the management of multiple warts is safe and effective, characterized by high cure rates, favorable safety profiles, low recurrence rates, and comparable statistical significance between the two treatments.