High-dose vitamin D may be a ray of sunshine for treating sunburn

By Warren R. Heymann, MD, FAAD
June 4, 2025
Vol. 7, No. 22

Rightly or wrongly, I attribute my melanoma to a blistering sunburn at the Sahara Hotel in Miami Beach in 1958. I recall my mother shmearing Noxzema on my back — the distinctive smell of Noxzema (from eucalyptus, menthol, and camphor) has left an indelible impression on my olfactory senses. Dermatologists do everything possible to extol the benefits of sun avoidance and protection to prevent sunburn and the risk of skin cancer. Despite these efforts, people will get sunburned — even with the best of intentions, people may be in the mid-day sun, not have proper attire, and may have forgotten to apply (or reapply) sunscreen. Holman et al. performed a survey about sun protection practices from the 2015 National Health Interview Survey-Cancer Control Supplement. Of 31,162 respondents (mean age, 47.0 years; 13,932 male [44.7%] and 17 230 female [55.3%]), 34.2% experienced sunburn. (1)

Guerra and Crane succinctly summarize the pathophysiology of sunburn. “Exposure to UVA rays, between 320 and 400 nm wavelengths, and UVB rays, between 295 and 320 nm wavelengths, can cause sunburn and DNA damage. UVA rays cause oxidative DNA damage, whereas UVB rays are absorbed directly by DNA and induce the formation of thymine-thymine cyclobutane dimers. These dimers trigger the body to initiate a DNA repair response, which includes inducing cell apoptosis and releasing inflammatory markers such as prostaglandins, reactive oxygen species, and bradykinin. As a result, this leads to vasodilation, edema, and pain, which manifest as the characteristic red and painful skin associated with sunburn. Furthermore, UVB ray exposure to the skin can elevate chemokines, such as C-X-C motif chemokine 5 (CXCL5), and activate peripheral nociceptors, ultimately resulting in overactivation of the skin's pain receptors.” (2)

Once the inflammatory cascade is triggered and sunburn is present, treatments are ineffective and are mostly directed to supportive and symptomatic control. Soothing emollients, topical corticosteroids, oral NSAIDs, or acetaminophen provide comfort as the curative tincture of a couple of days’ time takes hold. (3)

I was intrigued by an editorial by McGrath and Lu titled “Single high-dose vitamin D3: a promising sunburn therapy.” (4) High-dose vitamin D (HDVD) therapy is having its moment. We have discussed the role of HDVD in toxic erythema of chemotherapy (TEC) in DWI&I (based on the work from Lu and colleagues in 6 patients (JAMA Dermatol 2023 Feb 1;159(2):219-222). (5) (Anecdotally, in my limited experience, using HDVD for TEC has been beneficial.) HDVD may also be helpful in managing acute radiation dermatitis. In the two cases reported by Nguyen and Lu, HDVD resulted in symptomatic improvement of pain and swelling in 3 to 7 days following HDVD intervention. (6)

As noted in the DWI&I commentary, according to Ernst et al, “Cholecalciferol (vitamin D3 [VitD3]) has recently emerged as a critical immunomodulatory hormone with regulatory roles in the innate and adaptive immune systems. The biologically active form of VitD, calcitriol (1,25[OH]2D3), binds to the ubiquitously expressed VitD receptor and has mechanisms of inflammatory control including expansion of anti-inflammatory M2 macrophages, inhibition of proinflammatory NF-κB signaling, and upregulation of arginase-1, an anti-inflammatory factor involved in tissue repair.” (7) AlGhamdi et al demonstrated that a single bolus of 80,000 IU reduces levels of IL-6, IL-8, and tumor necrosis factor within a month in both men and women. (8,9) In a randomized controlled trial, Annweiler et al observed that early administration of high-dose (400,000 IU) versus standard-dose (50,000 IU) vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at 14 days, however the effect was no longer observed after 28 days. (10)

Scott et al. performed a double-blinded, placebo-controlled interventional trial of 20 healthy adults who were randomized to receive either placebo or a high dose of vitamin D3 (cholecalciferol) one hour after an experimental sunburn was induced by an erythemogenic dose of ultraviolet radiation (UVR). Compared with placebo, participants receiving vitamin D3 (200,000 IU) demonstrated reduced expression of proinflammatory mediators tumor necrosis factor-α (P = 0.04) and inducible nitric oxide synthase (P = 0.02) in skin biopsy specimens 48 hours after the experimental sunburn. A blinded, unsupervised hierarchical clustering of participants based on global gene expression profiles revealed that participants with significantly higher serum vitamin D3 levels after treatment demonstrated a significantly increased skin expression of the anti-inflammatory mediator arginase-1 and a significantly sustained reduction in skin redness (P = 0.02), correlating with significant expression of genes related to skin barrier repair. In contrast, participants with lower serum vitamin D3 levels had significant expression of proinflammatory genes. (11)

As McGrath and Lu note in their editorial based on Scott et al, HDVD in doses of up to 600,000 IU has been used safely, without toxicity, or changes in serum calcium or phosphate levels. On a practical level, HDVD might be considered as a single oral dose 1-12 hours after excessive sun exposure. “However, the pharmacokinetics of single high-dose vitamin D3 are complex and optimal dosing levels for achieving immunomodulatory effects remain under investigation. Does taking vitamin D3 before sun exposure offer the same benefits? The answer remains unclear, although it is likely that vitamin D3’s immunomodulatory effects are most potent after injury has occurred. Can we recommend single high-dose vitamin D3 for general sunburn treatment? Not just yet, although anecdotal and off-label use are increasing. The prudent course is to await further studies that replicate these findings across larger and more diverse populations before incorporating vitamin D3 into routine clinical practice for sunburn.” (4)

The bottom line is that people should do everything possible to avoid sunburn in the first place. Regardless, sunburns will happen. Perhaps HDVD will be “a ray of sunshine” to alleviate sunburned skin.

Point to Remember: High-dose vitamin D, which has shown benefit in toxic erythema of chemotherapy and acute radiation dermatitis, may also be helpful for treating sunburn.

Our expert’s viewpoint

Kurt Q. Lu, MD, FAAD
Eugene & Gloria Bauer Professor of Dermatology
Northwestern University Feinberg School of Medicine
Chicago, Illinois

Eighty years ago, the team of Drs. Dowling and Thomas at St. Thomas’s Hospital in London gave detailed accounts of good outcomes in two cases of lupus vulgaris treated with high-dose daily vitamin D (150,000 I.U.) for 2-3 months. The pair of doctors successfully treated 40 cases with similar striking results while acknowledging their counterparts in France had similar observations during the WWII era. (12) Early investigative reports recognized a relationship exists between immune function and vitamin D. It was not until the definitive work from Dr. Modlin and colleagues that connected the link between vitamin D and induction of innate immune responses. (13) This subsequently opened the exploration of vitamin D and immunomodulation beyond its known roles in endocrinology and metabolism.

Our group has benefitted from these seminal observations. Working in animal models we observed that vitamin D mitigated the damaging acute inflammatory effects of chemotherapy by suppressing skin activated macrophages. (14) These findings were eventually translated into humans in a clinical trial where administration of oral vitamin D rapidly relieved skin pain for CTCL patients undergoing treatment with topical chemotherapy. (15) Skin biopsies confirm that indeed patients with adverse skin effects from chemotherapy had high iNOS and TNFa macrophages in the skin.

These observations prompted us to perform a dose finding double-blind placebo controlled trial. In the first study, healthy volunteers were subjected to a small experimental sunburn using a solar simulator (11). Since vitamin D requires metabolization, distribution, and storage in adipose tissue, a single dose will have variable responses from person to person. The study however revealed that given a high enough dose, 200,000 IU vitamin D uniformly had a demonstrable shift in inflammatory gene profiles. Notably, subjects who had a rise in vitamin D serum levels had upregulation of the arginase-1 gene, an enzyme that characterizes reparative macrophages and is important in the resolution of inflammation. Those subjects had rapid reduction in skin erythema from the sunburn and on histology had only mild sunburn effects. Our follow-up studies in animal models confirmed that vitamin D generates reparative macrophages by inducing the cell-recycle process of autophagy. (16)

In the second clinical trial, subjects were patch tested to a small area containing the topical chemotherapeutic nitrogen mustard and were either treated with 200,000 IU vitamin D or placebo. Like the sunburn study, high-dose vitamin D suppressed skin erythema and histological changes. Analysis of the skin biopsies revealed suppression of macrophages, T cells, and numerous chemokines and cytokines involved in IL-17 signaling. These findings gave us optimism to pursue the clinical management of toxic erythema of chemotherapy (17), acute radiation dermatitis (6), and combined chemical and radiation-induced skin injury during cancer therapy. (18)

A few takeaways to remember: High-dose vitamin D therapy and skin diseases have a long history. The use of high-dose oral vitamin D remains off-label, warranting additional studies. In our experience, throughout these studies, a common observation by patients and physicians is the rapid resolution of skin erythema and alleviation of skin pain. In one case series, 6 of 6 patients reported 1 day as the time of initial symptom improvement. Lastly, dose and clinical context matter. Molecular and cellular analysis of the skin following sunburn and exposure to chemicals or radiation share pathways of acute immune activation. This may help explain the common beneficial response from high-dose vitamin D intervention in acute skin injury.

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References

1. Holman DM, Ding H, Guy GP Jr, Watson M, Hartman AM, Perna FM. Prevalence of Sun Protection Use and Sunburn and Association of Demographic and Behavioral Characteristics With Sunburn Among US Adults. JAMA Dermatol. 2018 May 1;154(5):561-568. doi: 10.1001/jamadermatol.2018.0028. PMID: 29541756; PMCID: PMC5876912.

2. Guerra KC, Crane JS. Sunburn. 2023 Oct 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30521258.

3. Dermatoses resulting from physical factors. In Andrews’ Diseases of the Skin, Twelfth edition. Elsevier, Philadelphia, 2016, pp 18-44.

4. McGrath JA, Lu KQ. Single high-dose vitamin D3: a promising sunburn therapy. Br J Dermatol. 2025 Jan 24;192(2):181-182. doi: 10.1093/bjd/ljae359. PMID: 39270729.

5. Heymann WR. Taming toxic erythema of chemotherapy with high-dose vitamin D. Dermatology World Insights and Inquiries. Feb 28, 2024, vol.6 no. 9 https://staging.aad.org/dw/dw-insights-and-inquiries/archive/2024/toxic-erythema-chemotherapy-vitamin-d

6. Nguyen CV, Zheng L, Lu KQ. High-dose vitamin D for the management acute radiation dermatitis. JAAD Case Rep. 2023 Jul 8;39:47-50. doi: 10.1016/j.jdcr.2023.07.001. PMID: 37583837; PMCID: PMC10423998.

7. Ernst MK, Evans ST, Techner JM, Rothbaum RM, Christensen LF, Onay UV, Biyashev D, Demczuk MM, Nguyen CV, Honda KS, McCormick TS, Tsoi LC, Gudjonsson JE, Cooper KD, Lu KQ. Vitamin D3 and deconvoluting a rash. JCI Insight. 2023 Jan 24;8(2):e163789. doi: 10.1172/jci.insight.163789. PMID: 36692020.

8. AlGhamdi SA, Enaibsi NN, Alsufiani HM, Alshaibi HF, Khoja SO, Carlberg C. A Single Oral Vitamin D3 Bolus Reduces Inflammatory Markers in Healthy Saudi Males. Int J Mol Sci. 2022 Oct 9;23(19):11992. doi: 10.3390/ijms231911992. PMID: 36233290; PMCID: PMC9569869.

9. Alsufiani HM, AlGhamdi SA, AlShaibi HF, Khoja SO, Saif SF, Carlberg C. A Single Vitamin D3 Bolus Supplementation Improves Vitamin D Status and Reduces Proinflammatory Cytokines in Healthy Females. Nutrients. 2022 Sep 24;14(19):3963. doi: 10.3390/nu14193963. PMID: 36235615; PMCID: PMC9570631.

10. Annweiler C, Beaudenon M, Gautier J, Gonsard J, Boucher S, Chapelet G, Darsonval A, Fougère B, Guérin O, Houvet M, Ménager P, Roubaud-Baudron C, Tchalla A, Souberbielle JC, Riou J, Parot-Schinkel E, Célarier T; COVIT-TRIAL study group. High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial. PLoS Med. 2022 May 31;19(5):e1003999. doi: 10.1371/journal.pmed.1003999. PMID: 35639792; PMCID: PMC9154122.

11. Scott JF, Das LM, Ahsanuddin S, Qiu Y, Binko AM, Traylor ZP, Debanne SM, Cooper KD, Boxer R, Lu KQ. Oral Vitamin D Rapidly Attenuates Inflammation from Sunburn: An Interventional Study. J Invest Dermatol. 2017 Oct;137(10):2078-2086. doi: 10.1016/j.jid.2017.04.040. Epub 2017 May 30. PMID: 28576736; PMCID: PMC5610950.

12. Dowling GB, Prosser Thomas EW. Treatment of lupus vulgaris with calciferol. Lancet. 1946 Jun 22;1(6408):919-22. doi: 10.1016/s0140-6736(46)90616-2. PMID: 20991437.

13. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006 Mar 24;311(5768):1770-3. doi: 10.1126/science.1123933. Epub 2006 Feb 23. PMID: 16497887.

14. Au L, Meisch JP, Das LM, Binko AM, Boxer RS, Wen AM, Steinmetz NF, Lu KQ. Suppression of Hyperactive Immune Responses Protects against Nitrogen Mustard Injury. J Invest Dermatol. 2015 Dec;135(12):2971-2981. doi: 10.1038/jid.2015.322. Epub 2015 Aug 19. PMID: 26288355; PMCID: PMC4648631.

15. Tacastacas JD, Chan DV, Carlson S, Gerson SL, Dowlati A, Fu P, Lu K, Groft S, Rosenjack J, Honda K, McCormick TS, Cooper KD. Evaluation of O6-Benzylguanine-Potentiated Topical Carmustine for Mycosis Fungoides: A Phase 1-2 Clinical Trial. JAMA Dermatol. 2017 May 1;153(5):413-420. doi: 10.1001/jamadermatol.2016.5793. Erratum in: JAMA Dermatol. 2017 May 1;153(5):479. doi: 10.1001/jamadermatol.2017.0712. PMID: 28199478; PMCID: PMC5817489.

16. Das LM, Binko AM, Traylor ZP, Peng H, Lu KQ. Vitamin D improves sunburns by increasing autophagy in M2 macrophages. Autophagy. 2019 May;15(5):813-826. doi: 10.1080/15548627.2019.1569298. Epub 2019 Jan 24. PMID: 30661440; PMCID: PMC6526871.

17. Nguyen CV, Zheng L, Zhou XA, Ernst MK, Kye Y, Choi JN, Lu KQ. High-Dose Vitamin D for the Management of Toxic Erythema of Chemotherapy in Hospitalized Patients. JAMA Dermatol. 2023 Feb 1;159(2):219-222. doi: 10.1001/jamadermatol.2022.5397. PMID: 36542397; PMCID: PMC9856756.

18. Nguyen CV, Lu KQ. Vitamin D3 and its Potential to Ameliorate Chemical and Radiation-Induced Skin Injury During Cancer Therapy. Disaster Med Public Health Prep. 2024 Jan 15;18:e4. doi: 10.1017/dmp.2023.211. PMID: 38224262.

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