A pilot clinical trial to explore the effects of UV exposure on vitamin D synthesis and inflammatory responses in vitamin D-Deficient adults

Abstract

Ultraviolet radiation (UVR) is essential for vitamin D synthesis and influences various biological processes. This study examined the effects of controlled UV exposure on vitamin D synthesis and skin inflammation in healthy adults. In a randomized clinical trial, 24 volunteers received four 5-min standardized UV exposures (UVB: 1.34 mW/cm²; UVA: 27.7 mW/cm²) on representative skin areas. Blood samples were collected before exposure and after every two sessions to assess serum vitamin D, inflammatory markers, vitamin D-related markers, and oxidative stress indicators. Serum vitamin D concentration significantly increased after four exposures (p < 0.001), while calcium, phosphorus, and parathyroid hormone (PTH) significantly decreased (p < 0.05). Reactive oxygen species (ROS) significantly increased (p < 0.001), but no significant changes were observed in nitric oxide (NO) or myeloperoxidase (MPO) levels. Similarly, inflammatory markers such as C-reactive protein (CRP), MPO, and antioxidant enzymes (glutathione peroxidase [GPx] and catalase [CAT], showed no significant alterations. Among the inflammatory cytokines assessed, interleukin (IL)-1β levels showed a slight increase without reaching significance, and the levels of other cytokines such as IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) showed no marked alterations. In addition, post-exposure skin assessment revealed no adverse effects. Our findings demonstrate that UVR exposure can enhance vitamin D synthesis in healthy adults without significant inflammatory responses or adverse effects, providing a basis for optimizing UV-based interventions to improve vitamin D status through risk management.

Introduction

Vitamin D insufficiency has been implicated in a wide range of health conditions, including skeletal disorders, dysregulated glucose metabolism, carcinogenesis, susceptibility to infectious diseases, autoimmune pathologies, and neuropsychiatric disorders such as schizophrenia¹. The primary physiological role of vitamin D and its metabolites is to maintain calcium homeostasis²which is a critical factor in metabolic processes³signaling pathways⁴and neuromuscular functions⁵. The active form of vitamin D, 1,25-dihydroxyvitamin D₃, operates synergistically with parathyroid hormone (PTH) to enhance the intestinal absorption of calcium and phosphorus, promote bone mineralization, and sustain optimal blood calcium levels⁶. Moreover, epidemiological and experimental evidence suggests that vitamin D exhibits anticancer properties, highlighting the potential of vitamin D analogs as innovative therapeutic approaches to reduce the global cancer burden⁷.

In humans, the primary source of vitamin D is endogenous synthesis in the skin, triggered by the absorption of solar UVB radiation (290–320 nm), the portion of the UVB spectrum that reaches the Earth’s surface after atmospheric filtering⁸. It is estimated that up to 90% of the body’s vitamin D is derived from sunlight exposure⁹. Interestingly, ultraviolet radiation (UVR) penetrates the skin and converts 7-dehydrocholesterol into pre-vitamin D3, which is then isomerized to vitamin D3 (cholecalciferol) and subsequently metabolized in the liver¹⁰. Aging and increased melanin levels can adversely affect cholecalciferol synthesis in the skin. Since age and skin type are intrinsic and immutable factors, enhancing skin exposure to UVB radiation remains the most effective method for augmenting vitamin D synthesis.

Nevertheless, contemporary lifestyles often restrict UVB exposure due to widespread sunscreen use, age-related changes, seasonal and latitudinal variations, and predominantly indoor living habits. These factors have contributed to a global increase in vitamin D deficiency. Additionally, dietary sources of vitamin D are generally inadequate, and without fortification, food alone is insufficient to meet the body’s requirements¹¹. Clinical studies have demonstrated that UVB exposure effectively increases serum vitamin D concentrations, alleviating vitamin D deficiency^12–14.

Although increasing vitamin D concentration through UVB exposure is beneficial, it is important to acknowledge the potential risks of UVB radiation. The biological effects of ultraviolet radiation on the skin vary based on wavelength and penetration depth. UVB radiation (320–280 nm) primarily affects keratinocytes and Langerhans cells in the epidermis, which are significant sources of cytokines¹⁵. In contrast, UVA radiation (400–320 nm) penetrates deeper into the dermis and affects fibroblasts and inflammatory cells¹⁶. Although UVA rays do not contribute to vitamin D synthesis, they induce tanning and stimulate nitric oxide (NO) production in the skin, promoting vasodilation, lowering blood pressure, and supporting cardiovascular health¹⁷. The skin is a barrier against environmental insults and can sustain acute damage from excessive UVB exposure. High doses of UVB can lead to painful erythema, fever, and swelling owing to inflammatory responses triggered by damage to the skin barrier. UVB-induced cellular damage includes structural alterations, DNA damage, and disruption of metabolic pathways, which subsequently affect the mechanical integrity of the skin barrier¹⁸. In addition, UVB radiation activates neutrophils and stimulates myeloperoxidase (MPO) activity, resulting in the generation of reactive oxygen species (ROS), such as superoxide anions (O₂^•−) and hydroxyl radicals (•OH). Excessive ROS production can induce cytotoxic effects and oxidative damage to proteins and lipids within the skin barrier¹⁹. Although the skin has a strong antioxidant defense system, including enzymes such as catalase, superoxide dismutase, and glutathione peroxidase (GPx), excessive UVB exposure can surpass these defenses, leading to oxidative stress and systemic inflammation²⁰. UVR stimulates keratinocytes to synthesize and release pro-inflammatory cytokines, including interleukin (IL)−1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α). Elevated levels of these pro-inflammatory cytokines can lead to acute skin inflammation, acting locally and triggering systemic inflammatory responses through circulation²¹. These pro-inflammatory factors regulate C-reactive protein (CRP) synthesis, suggesting that CRP levels may increase following UVB irradiation-induced skin damage and inflammation. Owing to the rapid response characteristics of CRP, it serves as an early inflammatory marker in the context of UVB-induced skin inflammation, allowing the evaluation of the systemic effects of ultraviolet radiation on the human body²².

This study aimed to investigate the effects of short-term repeated UV irradiation on the vitamin D status and related metabolic biomarkers in vitamin D-deficient adults. Additionally, we also evaluated whether this UV exposure system could induce significant skin inflammation while effectively restoring vitamin D concentration, offering an alternative to daily oral vitamin D supplementation.

Materials and methods

Study participants

This study was designed as a prospective randomized, double-blind clinical trial to evaluate the efficacy and safety of this intervention. Healthy adult participants aged 19–65 years were recruited through advertisements in the local community. The initial screening process involved collecting demographic data, including sex, age, BMI, medical history, and current medications. After evaluating these factors for suitability, 24 participants were selected based on specific eligibility criteria. The inclusion criteria required participants to be vitamin D-deficient adults aged 19 years or older, in overall good health, and mentally competent to understand the study procedures. The exclusion criteria included severe systemic dermatological conditions, atopic dermatitis, significant dermatological disorders, pregnancy or breastfeeding status, physical disabilities that could interfere with participation, history of depression or other psychiatric conditions, specialized dietary needs due to diabetes mellitus, liver or renal dysfunction, and any other conditions deemed by the principal investigator to be contraindicated for participation in the study.

Ethical statement

This study was approved by the Institutional Review Board of the Research Review Committee of Severance Christian Hospital, Yonsei University Wonju College of Medicine (IRB Number: CR323149) (03/10/2024) and registered with ClinicalTrials.gov. (National Clinical Trial Number: NCT06625918). This study was conducted from April 29 to May 28, 2024, at Wonju Christian Hospital, Department of Rehabilitation Medicine, Outpatient and Medical Building, Yonsei University, Wonju, South Korea. Written informed consent was obtained from all participants before participation to ensure they were thoroughly informed about the study’s objectives, procedures, potential risks, and rights. All methods were performed in accordance with the relevant guidelines and regulations.

Clinical assessment and follow-up

All 24 participants who met the inclusion criteria underwent comprehensive clinical evaluation and follow-up throughout the clinical trial. Following baseline assessments, the participants received standardized UV irradiation therapy, consisting of four sessions administered once weekly, with each session lasting 5 min. High-resolution skin images were captured before and after each UV exposure using an A-ONE TAB skin measurement device (Bomtech Electronics Co., Ltd., Seoul, South Korea), and the skin barrier score was accurately assessed using a GP Skin device (MSIPCRM-G10 Barrier Sensor; Seoul, South Korea).

In addition to skin assessments, participants’ body temperature, blood pressure, and pulse were closely monitored before and after each exposure to evaluate overall health status and the potential effects of UV exposure on the body. Participants’ health indices, including body weight, BMI, body fat percentage, abdominal fat percentage, and basal metabolic rate, were systematically tracked throughout the study. Venous blood samples were collected at three time points: pre-exposure, mid-exposure (7 days after the second UV irradiation), and post-exposure (7 days after the fourth UV irradiation). UV irradiation was administered once every 7 days, and blood samples were collected 7 days after the final UV session at each respective time point to evaluate delayed systemic effects. Each participant provided two samples: one fresh blood sample for vitamin D analysis and a second sample processed by centrifugation to separate the serum, which was subsequently stored at −80 °C until further analysis. At the final follow-up, all participants completed a satisfaction survey that provided detailed feedback regarding their experiences with the exposure process. The experimental design is illustrated in Fig. 1.

Fig. 1.

Flow diagram of clinical trial.

Phototherapy protocol

The phototherapy protocol was strictly followed, and UV irradiation was administered according to a predetermined schedule. The participants underwent weekly UV irradiation sessions for four weeks, with each lasting 5 min. The sessions were conducted in a phototherapy chamber (DOS & YOUNIQUE Co., Ltd. Seoul, South Korea) designed for full-body irradiation (Fig. 2). The chamber’s UVB irradiance (280–315 nm) was 1.34 mW/cm², while the UVA irradiance (315–400 nm) measured 27.7 mW/cm². These were produced by 100 W lamps with 43 tubes, yielding a UVB/UVA ratio of 4.80%. Participants wore standardized, clean, short undergarments and were provided with protective masks to shield their eyes and face during each session. Prior to UV exposure during each session, participants removed their gowns, leaving only the short undergarments in place. The UV irradiation was then administered to the body, with the exception of areas covered by the undergarments and protective masks to ensure the safety precautions of participants (Fig. 3). If any adverse skin reactions, such as erythema or rash, were observed following the intervention, the use of the device was immediately discontinued, and the affected participant was withdrawn from the study.

Fig. 2.

Schematic design of the phototherapy chamber.

Fig. 3.

Participants undergoing UV irradiation in the phototherapy chamber.

Vitamin D measurement

Four blood tests were performed: at baseline (first visit), after the second exposure, and at the final follow-up (after the fourth exposure). All blood samples were collected during the daytime (between 2:00 PM and 5:00 PM) in a non-fasting state. After collection, samples were centrifuged and transported to a testing facility (Clinical Laboratory Diagnostic Department at Severance Christian Hospital, Yonsei University). All blood tests for each participant were conducted at the same time of day to ensure consistency.

Measurement of ROS levels

ROS levels were measured using 2-4-dichlorodihydrofluorescein diacetate (DCFH-DA) (Sigma, St. Louis, MO, USA) according to the manufacturer’s instructions. Serum samples (50 µL) and 100 µL of 20 µM DCFH-DA were added to each well of a 96-well black plate, mixed thoroughly, and incubated at 37 °C for 30 min. Fluorescence was measured at 488 nm excitation/525 nm emission using a DTX multimode plate reader (Beckman Coulter, Inc., Fullerton, California, USA).

Measurement of NO levels

Griess reagent (iNtRON Biotechnology, Inc. Korea) was used according to the manufacturer’s instructions to measure serum nitrite concentration (NO2−) to assess serum NO levels. Briefly, 100 µL of serum samples were mixed with 50 µL of Griess reagent (containing sulfanilamide and N-1-naphthyl ethylenediamine dihydrochloride [NED]) in a 96-well microplate. After incubating for 10 min at room temperature, protected from light, the absorbance was measured at 540 nm using a SpectraMax^® ABS Plus (Molecular Devices, San Jose, CA, USA). The average absorbance values of each experimental sample were compared to a nitrite standard reference curve to determine the NO concentration.

Measurement of antioxidant enzyme levels

Using a Biomax Assay Kit (Biomax Mall Co., Gyeonggi-do, South Korea), serum catalase levels were measured to assess serum oxidative stress. GPx activity was determined using a Cayman Assay Kit (Cayman Chemical Co., Ann Arbor, MI, USA). All assays were performed according to the manufacturer’s instructions. Briefly, serum samples were appropriately diluted and added to 96-well microplates along with the reagents in the corresponding assay kits. After an incubation period of 30 min, absorbance readings for CAT (570 nm) and GPx (340 nm) were obtained using SpectraMax^® ABS Plus (Molecular Devices, San Jose, CA, USA). Finally, the concentration of each biomarker was determined by comparing the absorbance values to a standard reference curve.

Inflammatory biomarker level detection

Total serum CRP concentration was measured using a human C-reactive protein ELISA kit (Thermo Fisher Scientific Korea Ltd., Seoul, South Korea). Four microliters of serum samples were diluted with standard diluent buffer, and the assay was performed according to the manufacturer’s instructions. The absorbance of the plates was read within 2 h of the addition of the stop solution. According to the manufacturer’s instructions, serum MPO levels were measured using an Abcam MPO ELISA kit (Abcam ab272101, Cambridge, UK). Absorbance readings for CRP and MPO (450 nm) were obtained using SpectraMax ABS Plus (Molecular Devices, San Jose, CA, USA). Total CRP and MPO concentrations were calculated using a linear regression equation obtained from standard absorbance values.

Parathyroid hormone 1–34 (PTH 1–34) levels detection

Serum levels of PTH 1–34 were measured using the FineTest^® Human PTH 1–34 ELISA Kit (Catalogue no.: EH5084), following the manufacturer’s instructions. Briefly, 60 µL of serum was diluted two-fold with the sample diluent for the assay. Each diluted serum sample (100 µL) was added to a 96-well microplate with the appropriate standards and blanks. The addition of the stop solution terminated the reaction, and the absorbance was immediately read at 450 nm using a SpectraMax^® ABS Plus microplate reader (Molecular Devices, San Jose, CA, USA). The concentration of each sample was calculated by comparing the absorbance values with a standard curve generated from known concentrations of PTH 1–34 standards.

Phosphorus levels detection

According to the manufacturer’s protocol, serum inorganic phosphorus levels were assessed using phosphorus (inorganic) Colorimetric Assay Kit (Catalogue #: MA-PHOS-2, RayBiotech Inc., Peachtree Corners, GA, USA). Serum samples were diluted appropriately with the assay buffer. Serum samples were diluted 10-fold with distilled water (5 µL serum per dilution) and added to a 96-well microplate along with standards and blanks. The assay was triggered by adding a color development reagent from the kit and the mixture was incubated at room temperature for 30 min. After incubation, absorbance at 340 nm was recorded using a SpectraMax^® ABS Plus microplate reader (Molecular Devices, San Jose, CA, USA). Phosphorus concentrations in serum samples were calculated by referencing absorbance values against a standard curve generated using known concentrations of inorganic phosphorus. This procedure was followed meticulously to ensure the precision and validity of the results.

Calcium levels detection

Serum calcium levels were measured using a Calcium Assay Kit (Colorimetric, Catalogue #: ab102505, Abcam, Cambridge, MA, USA) according to the manufacturer’s protocol. Serum samples were prepared and diluted as required, with 50 µL of each sample added to a 96-well microplate, calcium standards, and blank controls. The colorimetric reaction was initiated by adding the provided reagent in the kit, followed by incubation in the dark at room temperature for 10 min. Absorbance was measured at 575 nm using a SpectraMax^® ABS Plus microplate reader (Molecular Devices, San Jose, CA, USA), and calcium concentrations were determined by comparing the absorbance values to a standard curve.

Statistical analysis

All data were analyzed and compared using a one-way analysis of variance (ANOVA), followed by a multiple comparison test (Tukey’s post hoc test) using the GraphPad Prism 10.1.2 software package (GraphPad, La Jolla, CA, USA). Differences were considered statistically significant at p < 0.05. Data for each test are presented as the mean ± standard deviation (SD).

Results

Effects of UV exposure on body composition and metabolic activity

The potential impact of UV exposure on body composition and metabolic function was investigated by examining various health parameters before and after UV irradiation (Table 1). There were no significant changes in body weight, body mass index (BMI), or abdominal fat percentage (AFP) following UV exposure. However, a statistically significant reduction in body fat percentage (BFP) was observed after four sessions of UV irradiation (p = 0.008), suggesting an improvement in overall body composition. Additionally, the basal metabolic rate (BMR) increased significantly (p = 0.04), indicating a potential enhancement in metabolic activity associated with the intervention.

Table 1.

Comparison of health metrics before and after UV exposure.

Metric	Baseline	Post-UV (4th)	p-value
Sex (Male)	5	5
Sex (Female)	19	19
Age (years)	44 ± 8	44 ± 8
Body weight	61.8 ± 13.8	61.8 ± 13.9	0.78
BMI	23.5 ± 5.2	23.4 ± 5.1	0.31
BFP	29.3 ± 10.1	28.3 ± 10.3	0.008**
AFP	0.87 ± 0.08	0.87 ± 0.08	0.78
BMR	1295 ± 165	1307 ± 163	0.04*

Values are presented as mean ± SD (n = 24). Statistical analysis was performed using the paired t-test. Statistically significant differences are represented by *p < 0.05, **p < 0.01.

Effects of UV exposure on skin condition

The cutaneous condition of the internal and external aspects of the arm was visually documented in three representative study participants (S-033, S-034, and S-038) before and after UV exposure. Figure 4 presents a comprehensive visual assessment of the lateral and medial aspects of the arm for these participants, captured both pre-UV exposure and after the fourth UV irradiation. A comparative analysis of the images revealed consistent skin texture with no significant visible changes, indicating that the dermal condition remained largely unaffected. These findings suggest the importance of maintaining epidermal barrier function and skin health following UV exposure. Furthermore, they support the hypothesis that UV therapy does not adversely impact cutaneous conditions, reinforcing its safety in preserving skin integrity.

Fig. 4.

Representative high-resolution images depicting skin morphology before and after the fourth UV radiation exposure in the elbow arms of three participants (S-033, S-034, S-038).

Effects of UV exposure on skin barrier score

Skin barrier scores for the lateral and medial regions of the arm were assessed before and after UV exposure, as shown in Table 2. The analysis revealed that the scores remained stable with slight variations, suggesting that UV exposure did not significantly affect the epidermal barrier. A skin barrier score of approximately 80 indicated a healthy skin condition. These results show that controlled UV exposure does not harm the skin barrier, supporting its safety for maintaining dermal health.

Table 2.

The skin barrier scores for the lateral and medial sides of the arms were assessed before and after UV exposure.

Side	Phase 1			Phase 2			Phase 3			Phase 4
	Baseline	Post-UV	P-value	Baseline	Post-UV	P-value	Baseline	Post-UV	P-value	Baseline	Post-UV	P-value
Lateral side	81.6 ± 4.3	80.0 ± 4.7	0.77	82.3 ± 5.7	82.0 ± 4.4	1.00	78.8 ± 4.1	78.8 ± 6.0	1.00	79.5 ± 5.7	80.3 ± 5.8	0.97
Medial side	81.5 ± 3.9	79.8 ± 4.0	0.63	82.4 ± 5.0	82.4 ± 4.3	1.00	82.5 ± 4.1	82.3 ± 4.2	1.00	80.2 ± 5.3	81.0 ± 4.0	0.94

Values are presented as mean ± SD (n = 24). Statistical analysis was performed using the paired t-test.

Effects of UV exposure on vitamin D concentration

Changes in vitamin D concentrations were evaluated in individuals with initially low vitamin D concentrations following UV radiation exposure. This study aimed to determine whether controlled UV therapy could enhance the ability of the skin to produce vitamin D and improve overall vitamin D concentrations in deficient individuals by measuring vitamin D concentrations before and after two and four UV exposures. The vitamin D concentrations at baseline (pre-exposure) and after two and four UV exposures are shown in Fig. 5. Based on baseline measurements, the average vitamin D content was approximately 12 ng/mL, indicating a deficient state. However, evaluations conducted after exposure revealed a marked increase in vitamin D concentrations. The average concentration increased to approximately 18 ng/mL after the second exposure (p < 0.05) and to approximately 25 ng/mL after the fourth exposure (p < 0.001). These results strongly suggest that UV therapy effectively stimulates the production of vitamin D in the skin, increasing the overall vitamin D concentrations.

Fig. 5.

Analysis of serum vitamin D concentration before and after UV exposure (n = 24). Data are presented as mean ± SD. Statistical analysis was performed using one-way analysis of variance (ANOVA), followed by Tukey’s multiple comparison test. *p < 0.05, ***p < 0.001.

Effects of UV exposure on serum calcium, parathyroid hormone (PTH), and phosphorus levels

Serum calcium, PTH, and phosphorus levels were measured at baseline (pre-exposure) and after the second and fourth UV exposure sessions to assess potential effects on calcium-phosphorus metabolism. Serum calcium, PTH, and phosphorus levels were determined at baseline (pre-exposure) after the second and fourth UV exposure sessions, as shown in Fig. 6. Serum calcium levels were approximately 14 mg/dL at baseline. Calcium levels did not noticeably increase after the second UV exposure session. However, after the fourth session, the serum calcium levels decreased significantly to approximately 12 mg/dL (p < 0.05). However, after the fourth session, there was a noticeable drop in serum calcium level to approximately 12 mg/dL (p < 0.05). Similarly, after the first two sessions, the effects of UV radiation on serum PTH and phosphorus levels did not show any significant changes. However, after the fourth session, there was a significant decrease in the PTH and phosphorus levels (p < 0.05). These findings indicate that UV exposure may regulate calcium-phosphorus metabolism by suppressing PTH secretion and promoting phosphorus excretion, potentially via reduced renal reabsorption.

Fig. 6.

Serum calcium (A, n = 24), PTH (B, n = 18), and phosphorus (C, n = 24) levels before and after UV exposure. Data are presented as mean ± SD. Statistical analysis was performed using one-way analysis of variance (ANOVA), followed by Tukey’s multiple comparison test. *p < 0.05.

Effects of UV exposure on oxidative stress markers

Oxidative stress markers, including ROS, NO, catalase, and GPx activities, were measured to evaluate the influence of cumulative UV exposure on oxidative reactions and antioxidant enzyme activities. The ROS, NO, catalase, and GPx activities at baseline (pre-exposure) and during the second and fourth UV exposure sessions are shown in Fig. 7. Following the fourth UV exposure, ROS levels showed a substantial increase above the baseline (p < 0.001), suggesting that increased oxidative stress was linked to cumulative exposure. After the second UV exposure, NO levels increased significantly (p < 0.01), indicating an early oxidative reaction. However, after the fourth UV exposure, NO levels returned to normal, suggesting that this reaction was temporary. No statistically significant differences were observed between baseline and post-exposure catalase and GPx activities at any time point, strongly indicating that UV radiation had no impact on the activity of these antioxidant enzymes during the study period.

Fig. 7.

Analysis of reactive oxygen species (ROS) (A), nitric oxide (NO) (B), catalase (C), and glutathione peroxidase (GPx) activities (D) before and after UV exposure (n = 21). Data are presented as mean ± SD. Statistical analysis was performed using one-way analysis of variance (ANOVA), followed by Tukey’s multiple comparison test. **p < 0.01, ***p < 0.001.

Effects of UV exposure on CRP and MPO levels

CRP and MPO levels were assessed to determine whether UV exposure affected systemic inflammatory responses or neutrophil activation. The CRP and MPO levels at baseline, following the second UV exposure, and following the fourth exposure are shown in Fig. 8. The CRP levels remained consistent at approximately 0.5 mg/L across all time points, with no statistically significant differences observed between the phases of exposure. MPO levels remained unchanged after the second and fourth UV exposures, proving that UV radiation did not induce a systemic inflammatory response or activate neutrophils. This result confirmed that UV exposure did not affect the systemic inflammatory responses under the conditions tested.

Fig. 8.

Analysis of C-reactive protein (CRP)(A) and myeloperoxidase (MPO) (B) levels before and after UV exposure (n = 21). Data are presented as the mean ± SD. Statistical analysis was performed using one-way analysis of variance (ANOVA), followed by Tukey’s multiple comparison test.

Effects of UV exposure on cytokine concentrations

Pro-inflammatory cytokine levels were measured to assess whether UV exposure influenced inflammation or systemic immune regulation under controlled exposure conditions. Cytokines such as IL-1β, IL-6, IL-10, TNF-α, and interferon-γ (IFN-γ) level were assessed at baseline, after the second UV exposure, and after the fourth UV exposure as shown in Fig. 9. All time points showed consistent levels of IL-6, IL-10, TNF-α, and IFN-γ, with no statistically significant variations between the baseline, second exposure, and fourth exposure levels. The consistent levels of IL-6, IL-10, TNF-α, and IFN-γ at all-time points suggest that under the tested conditions, UV exposure has little effect on inflammation or systemic immune regulation. In contrast, IL-1β levels showed a slight increase compared to baseline but without significant difference after the fourth UV exposure, suggesting a mild, possibly cumulative cytokine response. However, the overall effects are limited during the study period. These findings indicate that brief UV exposure did not significantly alter pro-inflammatory cytokine levels and did not induce or exacerbate major inflammation.

Fig. 9.

Analysis of interleukin (IL)−1β (A), IL-6 (B), and IL-10 (C), tumor necrosis factor-α (TNF-α) (D), and interferon-γ (IFN-γ) (E) concentrations before and after UV exposure (n = 18). Data are presented as mean ± SD. Statistical analysis was performed using one-way analysis of variance (ANOVA), followed by Tukey’s multiple comparison test.

Discussion

This study aimed to evaluate the effects of controlled UV exposure on vitamin D synthesis, calcium-phosphorus metabolism, skin barrier function, and immune responses in healthy adults to explore UV radiation’s biological effects and therapeutic potential. This study investigated the effects of UV irradiation on human metabolic activity (Table 1), skin condition (Fig. 4), and skin barrier function (Table 2). Specifically, a statistically significant reduction in body fat percentage was observed after four sessions of UV irradiation (p < 0.01), while no significant changes were found in body weight, BMI, or abdominal fat percentage. Importantly, participants exhibited a significant increase in basal metabolic rate following UV exposure (p < 0.05). The positive influence of UV irradiation on metabolic activity is further corroborated by findings highlighting the role of vitamin D in regulating lipid metabolism, bone health, and immune function. Vitamin D is known to indirectly affect BMR by enhancing insulin sensitivity²³ and regulating energy expenditure²⁴thus potentially improving body fat content and overall metabolic activity by stimulating the secretion of various hormones. Quantitative assessment of epidermal barrier function revealed that four short-duration UV irradiation sessions did not significantly compromise the skin barrier. The skin barrier scores remained in the upper and lower 80 s, indicating that the participants’ skin barrier function was maintained at a healthy level with stable skin defense and moisture retention capabilities throughout the treatment period. Visual assessment of the skin condition demonstrated that the participants’ overall skin texture and appearance remained stable, with no adverse changes before and after UV exposure. Previous studies indicated that moderate UV irradiation can activate keratinocytes and promote epidermal renewal²⁵effectively maintaining the integrity of the skin barrier. ​The results of this study support this notion and suggest that controlled, low-dose UV exposure may help preserve skin barrier stability without inducing photodamage. ​.

The results of this study indicated that weekly exposure to 5 min of UV irradiation for 4 weeks effectively promoted vitamin D synthesis in the skin of vitamin D-deficient adults. The UVB output intensity used in this study was 1.34 mW/cm², generated by 43 lamps of 100 W, each with a UVB/UVA ratio of 4.8%. This setup plays a crucial role in the synthesis of vitamin D. Our experimental data demonstrated a significant increase in serum vitamin D concentrations in both groups of participants after two and four weeks of intervention, confirming that the applied UV irradiation dose effectively elevate serum vitamin D concentrations after short-term exposure (Fig. 5). This is consistent with previous studies that further validated the role of UVB radiation in promoting vitamin D synthesis^26–28. Broad-spectrum UV-B radiation is typically used to investigate the effects of phototherapy on serum vitamin D concentrations. This study supports the efficacy of this experimental device for stimulating vitamin D synthesis using UVB wavelengths (280–315 nm).

Additionally, the experimental results demonstrate the effects of repeated UV exposure on serum calcium, phosphorus, and PTH levels in healthy adults. A transient increase in serum calcium levels was observed after the second UV exposure. However, a significant decrease in serum calcium levels occurred after the fourth UV exposure, accompanied by a sustained decrease in PTH and phosphorus levels. ​These findings reveal the potential role of UV exposure in regulating calcium-phosphorus homeostasis and vitamin D metabolism and provide important new insights into the biological effects of UV light.​.

It is well established that UVB radiation promotes the conversion of 7-dehydrocholesterol in the skin to vitamin D3, which is subsequently hydroxylated in the liver and kidneys to produce the active form 1,25-dihydroxy vitamin D²⁹. The transient elevation in serum calcium levels following the second UV exposure can be attributed to enhanced intestinal calcium absorption facilitated by active vitamin D. However, after the fourth UV exposure, a significant decrease in serum calcium levels was observed (Fig. 6A), along with a sustained reduction in PTH levels (Fig. 6B). Previous studies have suggested that this decline may be explained by elevated serum calcium levels activating the calcium-sensing receptor (CaSR) in the parathyroid gland, which inhibits PTH secretion through a negative feedback mechanism, subsequently leading to reduced PTH levels^30–32. The reduction in PTH levels further decreases calcium release from the bones and calcium reabsorption by the kidneys, resulting in lowered serum calcium levels following prolonged UV exposure. Changes in serum phosphorus levels closely correlated with changes in serum calcium levels, which exhibited a continuous downward trend after repeated UV exposure (Fig. 6C). The decrease in phosphorus levels is primarily attributed to the inhibitory effects of PTH, which normally promotes renal excretion of phosphorus through the downregulation of sodium-phosphate cotransporter proteins in the proximal renal tubules³³. Consequently, decreased PTH levels lead to reduced renal phosphorus reabsorption and increased phosphorus excretion, decreasing serum phosphorus levels. Another possible explanation for this phenomenon is that the significant short-term enhancement of vitamin D concentrations may stimulate bone mineralization, resulting in the deposition of calcium and phosphorus in the bone matrix, further reducing serum levels³⁴. These results indicate that UV exposure enhances vitamin D synthesis while regulating calcium and phosphorus metabolism. However, there are limited reports on the effects of repeated UV exposure on serum calcium and phosphorus levels, which may reflect compensatory mechanisms that maintain calcium-phosphorus homeostasis. The complex interplay between vitamin D, PTH, and mineral metabolism emphasizes the need for deeper mechanistic investigation. Increased vitamin D synthesis enhances bone mineralization, contributes significantly to the prevention of osteoporosis, and strengthens bone structural integrity. Excessive suppression of PTH and persistent decreases in serum calcium and phosphorus levels could lead to adverse outcomes, such as hypocalcemia³⁵ or impaired muscle function³⁶particularly in high-risk populations. These findings emphasize the necessity of optimizing UV exposure to strike a balance between vitamin D synthesis and calcium-phosphorus metabolism.

UVR is a major source of exogenous oxidative stress in the environment. It can directly activate the mitochondrial respiratory chain and NADPH oxidase in skin cells, leading to the overproduction of various oxidative stress markers such as ROS and NO³⁷. Our findings reveal a complex relationship between UV exposure and oxidative stress in skin cells. Initially, in our study ROS levels remained stable after the second UV exposure, suggesting an adaptive response through activation of antioxidant defense mechanisms. However, a significant increase in ROS was observed after the fourth exposure, indicating a potential threshold in the skin’s antioxidant capacity (Fig. 7A). Interestingly, this moderate elevation in ROS levels may not solely be harmful. Recent research suggests that such increases can act as signaling molecules, triggering protective cellular responses. Although ROS are often associated with cellular damage, some studies suggest they may also function as signaling molecules in adaptive responses to stress³⁸. In our study, ROS levels increased after repeated UV exposure, but without immediate evidence of damage, indicating a complex biological response. Nonetheless, it remains unclear whether this response is protective or harmful, and follow-up studies are required to clarify its long-term health implications.

Additionally, NO levels increased significantly after two UV exposures (Fig. 7B) but decreased dramatically following four exposures, approaching baseline values. The initial elevation in NO levels can be attributed to the activation of nitric oxide synthase (NOS) in the skin, contributing to increase NO production³⁹. This result suggests that UV irradiation may trigger an acute release of NO subsequently regulated by NOS activity to restore homeostasis and prevent excessive NO accumulation. Furthermore, UV exposure did not induce significant changes in the activity of catalase (Fig. 7C) and GPx (Fig. 7D), which are crucial antioxidant enzymes that reduce oxidative stress damage. These enzymes primarily break down hydrogen peroxide (H₂O₂) and organic peroxides, thereby protecting cell membranes, proteins, and DNA from oxidative damage⁴⁰. Despite a marked increase in ROS levels, the preserved activity of these enzymes suggests that H₂O₂ detoxification capacity was maintained. However, this does not exclude the possibility of elevated levels of other ROS species, such as hydroxyl radicals (OH⁻) and singlet oxygen (¹O₂). Therefore, further studies are needed to investigate the involvement of these ROS and their potential biological effects to comprehensively evaluate the safety of UV irradiation.

UV radiation is believed to exert multiple immunomodulatory effects⁴¹. UV exposure induces cytokine production at moderate doses and modulates immune cell activity⁴². MPO is a significant marker of neutrophil activation that mediates tissue damage and pathogen elimination by catalyzing the formation of hypochlorous acid (HOCl) from hydrogen peroxide^43,44. CRP is an important acute phase response protein synthesized by the liver, is commonly used to assess systemic inflammatory load, and is regulated by pro-inflammatory cytokines such as IL-6 and TNF-α⁴⁵. In this study, neither MPO nor CRP levels significantly changed after UV exposure (Fig. 8), suggesting that controlled UV exposure used in this study had minimal effects on systemic inflammation. This discrepancy from prior reports may be attributed to differences in irradiation dose, intensity, wavelength composition, and exposure duration. It is also possible that the relatively short follow-up window in our study was insufficient to capture delayed systemic inflammatory responses. Further investigation with extended monitoring and dose-comparative designs is needed to clarify the temporal and dose-dependent effects of UV on systemic inflammation.

Furthermore, the levels of pro-inflammatory cytokines, including IL-10 (Fig. 9C), TNF-α (Fig. 9D) and IFN-γ (Fig. 9E), were not significantly altered following UV exposure. TNF-α, a critical mediator in the early stages of the inflammatory response, promotes inflammatory gene expression by activating the NF-κB pathway and inducing apoptosis and immune cell recruitment, thereby triggering tissue damage⁴⁶. IFN-γ, a key cytokine secreted by Th1 and NK cells, plays a central role in enhancing cellular immune responses and pathogen defense⁴⁷ and has been shown to have a potential therapeutic role in disorders involving Th1 hyperactivation, such as psoriasis⁴⁸ and rheumatoid arthritis⁴⁹under UV exposure conditions. ​These results suggest that low-dose, short-term UV exposure plays a limited role in activating the inflammatory pathways and does not provoke an overactivated immune response. Furthermore, UVB can stimulate keratinocytes and immune cells to release pro-inflammatory cytokines such as IL-1β and IL-6 as part of the acute stress response^50–52. However, this response is often transient and dose-dependent, with mild or chronic exposure sometimes failing to produce statistically significant elevations in these cytokines. Our data showed a nonsignificant trend toward increased IL-1β and IL-6, which may reflect that UVB might stimulate a mild or adaptive response to repeated low-dose UVB exposure (Fig. 9AB). This is consistent with reports indicating that while UVB can initiate local and systemic immune responses, the magnitude of cytokine release can vary based on exposure intensity, duration, and experimental model^53,54. The stable expression of other inflammatory cytokines indicated that UV treatment had a negligible effect on systemic inflammation, reinforcing its safety and clinical applicability.

This study has several limitations. Conducting the clinical experiment in May month may limit generalizability because seasonal variations influence UVR intensity and baseline vitamin D concentrations. The standardized 5-minute UVR dose (UVB: 1.34 mW/cm²; UVA: 27.7 mW/cm²) may not accurately represent real-world exposure patterns, and individual differences in skin type, pigmentation, and UV sensitivity could affect vitamin D synthesis. Moreover, the relatively small sample size (24 participants) may have reduced statistical power and limited the generalizability of the findings. Additionally, environmental factors such as latitude, altitude, and air pollution, which influence UVR penetration, may restrict the applicability of the results to other regions and seasons.

Conclusions

This study demonstrated that moderate, short-term repeated UV irradiation effectively promotes vitamin D synthesis in healthy adults and positively influences calcium-phosphorus metabolism, metabolic activity, and skin health. Participants underwent weekly UV irradiation sessions for 5 min each over 4 weeks, conducted in a full-body phototherapy chamber equipped with 100 W lamps (43 tubes) producing UVB (280–315 nm, 1.34 mW/cm²) and UVA (315–400 nm, 27.7 mW/cm²) with a UVB/UVA ratio of 4.80%. Participants wore standardized short undergarments and protective masks to shield their eyes and face during each session. Under this phototherapy protocol, serum vitamin D concentrations significantly increased, while serum calcium, phosphorus, and PTH levels significantly decreased, providing new insights into regulating calcium-phosphorus metabolism. The study also showed a significant reduction in body fat and a significant increase in basal metabolic rate, confirming the role of vitamin D in energy metabolism. Importantly, UV exposure did not significantly affect skin barrier function or trigger uncontrolled oxidative stress with stable antioxidant enzyme activity. Furthermore, UV exposure did not induce systemic inflammation, suggesting a favorable safety profile and potential clinical benefits for metabolic and immune health, warranting further investigation in specific populations. ​.

Author contributions

CDM: Writing original draft – review & editing, Methodology, Investigation, Visualization, Data curation & Validation. JB: Writing original draft – review & editing, Resources, Investigation & Data curation. MHR: Writing original draft – review & editing, Methodology, Investigation, Validation & Data curation. SCC: Review & editing, Visualization. SAN: Methodology & Investigation. Hui Ma: Methodology & Investigation. WJH: Methodology & Investigation. TTP: Methodology & Investigation. HYZ: Methodology & Investigation. GSH: Methodology, Investigation & Data Curation. KBM: Methodology, Investigation & Data Curation. CSK: Project administration, Funding acquisition, Supervision, Review & editing. KJL: Visualization, Writing – review & editing. ISS: Conceptualization, Project administration, Supervision, Writing – review & editing.

Funding

This work was supported by DOS AND YOUNIQUE Co. Ltd. Seoul, Korea & Research grant from the Yonsei University Wonju College of Medicine (YUWCM 2023-71-0095).

Data availability

The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Consent for publication

Informed consent to be included in the study and subsequent publication of the results was obtained from all individual participants included in the study.