J Clin Aesthet Dermatol. 2022;15(3 Suppl 1):S30–S33
by Sara M. Wilchowski, MS, PA-C, and Tommy Lareau, BS, PA-S
Ms. Wilchowski is a board-certified physician assistant who practices at Forefront Dermatology in East Lansing, Michigan. Mr. Lareau is a second-year physician assistant student at Wayne State University in Detroit, Michigan.
FUNDING: No funding was provided for the preparation of this article.
DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.
ABSTRACT: Objective. The use of topical vitamin D in the management of patients with psoriasis has been studied extensively over the past several years. However, research regarding oral vitamin D supplementation as a potential treatment option in this patient population is lacking. The objective of this literature search was to examine if oral vitamin D is a viable option in the treatment of psoriasis and prevention of psoriasis related comorbidities.
Methods. PubMed was searched using the following search terms: vitamin D, psoriasis, magnesium, vitamin K2, and metabolic syndrome.
Results. Collected data from analyzed studies indicated that patients with psoriasis had significantly lower levels of serum vitamin D compared to patients without psoriasis, and that patients with psoriasis who were treated with oral vitamin D achieved greater clinical improvement compared to those who did not receive oral vitamin D therapy. More importantly, data indicated that two key nutrients—vitamin K2 and magnesium—work synergistically with vitamin D, increasing its absorption.
Limitations. The studies did not discuss the optimal dosing of vitamin D or what serum levels were needed to achieve clinical improvement. Moreover, the biochemistry can vary per individual, which may yield conflicting results.
Conclusion. There is insufficient conclusive evidence regarding oral vitamin D as a potential treatment modality in psoriasis; however, current studies have shown promising results. Larger randomized, clinical trials are needed to assess if oral vitamin D is effective in the management of psoriasis and to provide guidance on optimal dosing. Research has indicated that magnesium and vitamin K2 enhance absorption of vitamin D and decrease the risk of coronary artery calcium deposition.
Keywords. Psoriasis, vitamin D, prevention, treatment, magnesium, vitamin k2, inflammation
Psoriasis is a chronic, immune-mediated, inflammatory disease that affects approximately two percent of the population worldwide.1 While the exact mechanism of this disease has yet to be fully elucidated, associations between low vitamin D status and psoriasis have been systematically observed, which is thought to be due to the vitamin’s role in the proliferation and maturation of keratinocytes.2,3 Topical vitamin D derivatives, including calcipotriol and calcitriol, have immunomodulatory effects on monocytes, macrophages, T cells, and dendritic cells, which is why they are extensively used as monotherapy or in combination with steroids for the treatment of psoriasis.4 Keratinocytes and lymphocytes that infiltrate psoriatic lesions express the vitamin D receptor, which explains this effectiveness.5 While these topical formulations have been shown to be beneficial in psoriasis, they do not alter vitamin D serum levels within the body. Since 1987, data have supported the clinical use of supplemental and topical forms of vitamin D in the treatment of psoriasis.6
Vitamin D, despite its name, is more of a pleiotropic pro hormone. While the immune system is a complex interplay between innate and adaptive responses, a number of recent studies indicate that vitamin D can regulate the adaptive and innate immune response in various inflammatory and autoimmune diseases.7,8 Specifically, vitamin D has been shown to be a key modulator of inflammation and function.9 The active metabolite of vitamin D exerts anti-inflammatory effects on the inflammatory profile in human monocytes and macrophages by down-regulating the expression and production of several pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-?), interleukin (IL)-1-beta (1?), IL-6, and IL-8.2 Vitamin D receptors are also highly expressed in activated CD4+ T cells due to the immunomodulatory effects the active form of vitamin D—1,25 dihydroxyvitamin D3—has on CD4+ T cells, including inhibition of Th17 cell function.10 In an in-vitro study, 1, 25-dihydroxyvitamin D3 inhibited Th17 cytokine expression as well as the expression of other Th17 cytokines, IL-17F and IL-22, as determined by ELISA.10 Notably, vitamin D increases T regulatory cells and IL-10, which in turn decreases IL-17 and TNF- ? levels and promotes immune tolerance.11 These data suggest that, for chronic inflammatory disease states, vitamin D supplementation provides immunomodulating effects by downregulating systemic inflammatory cytokines.
Narrowband Ultraviolet Light B (NB-UVB) and Vitamin D
A treatment option in our therapeutic armamentarium for psoriasis is narrow-band ultraviolet light B (NB-UVB). In a study by Ala-Houhala et al,12 NB-UVB exposures given over four weeks increased serum 25(OH)D concentration significantly more than 20?g of oral cholecalciferol daily. Other studies have shown that NB-UVB increases 25(OH)D levels and decreases the disease severity in patients with psoriasis.12-14 This raises the question: Is the major mechanism of action of NB-UVB in the treatment of psoriasis increasing synthesis of 25(OH)D?6 This may explain in part why some patients with psoriasis improve during the summer months and has led to the initiation of oral vitamin D as a therapeutic option.
A study conducted by Bosman et al, the authors investigated whether exposing the skin to NB-UVB light to increase serum vitamin D levels would also modulate the makeup of the human intestinal microbiota.13 Participants were divided into two groups: one group took D supplements and one group did not take vitamin D supplements—throughout the winter prior to the start of the study. Serum vitamin D levels were drawn pre- and post-NB-UVB light exposure. Each participant received three exposures within the same week. Results indicated a significant increase in 25(OH)D concentrations post-light across all participants, with a mean increase of 10.1 percent. The researchers compared pre- and post-light exposure gut microbiome analysis of all participants as well. Prior to NB-UVB light exposure, participants who did not take vitamin D supplements prior to the study showed a significantly lower diversity and richness in their gut microbiome, compared to those who did take the vitamin D. After NB-UVB exposures, the group who did not take vitamin D supplements showed similar richness and diversity in their gut microbiome compared to the group who took vitamin D supplements. This was the first human study to show that deficient levels of vitamin D negatively impact gut microbiome diversity, and exposure to NB-UVB increased gut microbiome diversity in individuals who were vitamin D deficient.13
Vitamin D Oral Supplementation
While psoriasis primarily affects the skin, the implications of the inflammatory process in the disease are revealing it to be more systemic in nature. As research unravels the complexities of the immune response, we are now understanding that the inflammatory process can affect the joints and is associated with a number of different phenotypic expressions of chronic systemic inflammation. These disease states include atherosclerosis-related cardiovascular disease, asthma, inflammatory bowel disease, chronic kidney disease, and nonalcoholic fatty liver disease, all of which are associated with lower vitamin D status.15 Oral vitamin D supplementation represents an important alternative and potential cotreatment option for patients with psoriasis. The first reported case of psoriasis resolving with oral supplementation of vitamin D for treatment of osteoporosis dates back to 1985.16 Moreover, vitamin D supplementation might be important for the prevention of psoriasis-related comorbidities, including hypertension and metabolic syndrome.17
Vitamin D Synthesis
There are two main forms of vitamin D: ergocalciferol, or vitamin D2, and cholecalciferol, or vitamin D3. Both forms are biologically inactive. Vitamin D2 is commonly found in plants, whereas vitamin D3 is derived from animal-based sources. However, vitamin D is produced through cutaneous synthesis via the skin that depends on the intensity of ultraviolet irradiation, which varies with season and latitude.14 Keratinocytes, which express the vitamin D receptor, are not only a source of vitamin D but can also respond to the biologically active form, 1,25 dihydroxyvitamin D3.14 This active form is what has numerous effects on other diverse physiological functions, including inhibition of cancer cell growth and protection against certain immune-mediated disorders.14 Following dietary intake or ultraviolet light exposure, both forms of vitamin D are transported to the liver where they are hydroxylated via 25-hydroxylase to calcidiol or 25-hydroxyvitaminD,25 then to the kidneys by 1 alpha-hydroxylase to form the active metabolite calcitriol or 1,25-dihydroxyvitamin D3.14
Magnesium and Vitamin D
Noteworthy in the metabolism of vitamin D is magnesium. Dai et al18 reported that magnesium supplementation increased vitamin D serum levels and improved levels in those previously unable to be elevated.18 They noted that previous studies indicated a correlation between magnesium status and concentrations of cytochrome P450 enzymes. These enzymes are capable of not only activating, but also inactivating 25-hydroxylase and 1?-hydroxylase and 24-hydroxylase, respectively. In-vivo and in-vitro studies have shown that 1?-hydroxylase and 24-hydroxylase are dependent on magnesium. Therefore, magnesium deficiency decreases vitamin D metabolism and synthesis.
Vitamin K2 and Vitamin D
Vitamin D toxicity, albeit rare, can cause hypercalcemia and, therefore, buildup calcium in the blood stream, leading to deposition in the arterial walls and kidneys, and can also exacerbate osteoporosis.11 Mitigation strategies lie in the biochemistry of the vitamin D pathways and lead to understanding a crucial role of vitamin K2. Studies suggest that vitamin D supplementation that led to hypercalcemia was linked to vitamin K2 deficiency, as this nutrient activates osteocalcin through carboxylation and can lead to calcium deposition in the bones, whereas nonactivation inhibits bone reabsorption.11 As vitamin D levels rise, more K2 is required to balance these biochemical reactions to remineralize bone rather than arterial walls or the kidneys.19
Clinical Trials Evaluating Vitamin D in Patients with Psoriasis
Disphanuarat et al20 compared the efficacy of vitamin D2 60,000 IU administered orally every other week for six months to placebo in patients with psoriasis. Psoriasis Area and Severity Index (PASI) scores were assessed at three and six months, as well as laboratory evaluations of serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone, and C-reactive protein (CRP). After just three months of vitamin D supplementation, PASI scores were significantly improved compared to placebo. While the PASI scores at six months were not statistically significant, there was a trend toward more improvement in the supplementation group. Moreover, the researchers found an inverse relationship between the severity of psoriasis and serum vitamin D levels.
In a review article by Zuccotti et al,21 researchers evaluated the effects of several nutritional strategies for patients with psoriasis, including hypocaloric diet, vitamin D, fish oil, selenium, and zinc supplementation. Researchers concluded that vitamin D supplementation in patients with psoriasis who are deficit in the vitamin might aid in preventing psoriasis-related comorbidities. The authors also noted a hypothetical association between vitamin D deficiency and obesity and psoriasis.21
In a 2019 systematic review and meta-analysis by Pitukweerakul et al,22 researchers sought to determine if there was an association between hypovitaminosis D and psoriasis.22 Their analysis included 10 clinical studies in adults with psoriasis (?18 years of age) in which serum 25(OH)D levels were measured and compared to healthy controls. Their analysis also included prospective cohort, retrospective cohort, case-control, and cross-sectional studies that reported outcomes including serum 25(OH)D levels. The authors concluded that serum vitamin D levels were significantly lower in patients with psoriasis compared to healthy controls.
In a long-term, single-center, open trial, Perez et al23 reported that 88-percent of study participants with psoriasis who received oral vitamin D supplementation had some improvement in their disease, with 26.5 percent achieving complete resolution; the mean baseline PASI score of 18.4±1.0 was reduced to 9.7±0.8 after six months of oral vitamin D treatment and 7.8±1.3 after 24 months.23 These results were confirmed in a review article by Barrea et al2 examining potential bidirectional links between vitamin D and psoriasis, though the authors recognize the need for larger well-designed dietary intervention trials to determine proper dosages of vitamin D in the treatment of psoriasis.2
Ultimately, these data suggest that oral vitamin D is both effective and safe for the management of psoriasis.
Recommendations on Vitamin D Intake
While there are varying clinical guidelines among organizations globally regarding vitamin D supplementation, most clinical studies support the view that serum 25(OH)D3 levels of less than 20ng/mL indicate vitamin D deficiency, serum levels below 30ng/mL indicate insufficiency, and levels between 30 and 60ng/mL are considered sufficient.3 Studies have shown for adults that 1500–2000 IU per day is necessary to consistently raise the serum level of 25(OH)D above 30ng/mL.2 Despite the numerous ongoing studies on the use of vitamin D and immune function, there is no consensus regarding optimal serum levels for the treatment of autoimmune conditions.
Topical vitamin D, a mainstay therapeutic modality in patients with psoriasis, has been well-established over the last few decades. However, oral vitamin D has not often been discussed as a potential therapeutic or supplemental option. Current literature on oral vitamin D as a treatment for psoriasis reveals that this is a potential approach and suggests a correlation between low levels of serum vitamin D and increased severity of disease in patients with psoriasis. Although this certainly does not replace the need for pharmacotherapy, it does bolster our ability to help patients in a variety of ways, including nutraceuticals, and expands our workup for patients with psoriasis. While the number of large randomized, controlled studies evaluating vitamin D’s role in psoriasis management are limited, promising results reported thus far supports the importance of further investigation. Larger randomized, controlled trials are necessary to provide clear guidance on optimal dosing with careful consideration for each patient. Additionally, there should be a consideration for supplementation of magnesium and vitamin K2 with vitamin D. As the paradigm of healthcare is changing, we encourage the mindset that the body is a vast ecosystem rooted in interconnectedness. We must not forget that psoriasis is systemic and that a systemic approach to treatment must be considered.
- Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1475.
- Barrea L, Savanelli MC, Di Somma C, et al. Vitamin D and its role in psoriasis: an overview of the dermatologist and nutritionist. Rev Endocr Metab Disord. 2017;18(2):195-205.
- Gupta A, Arora TC, Jindal A, Bhadoria AS. Efficacy of narrowband ultraviolet B phototherapy and levels of serum vitamin D3 in psoriasis: a prospective study. Indian Dermatol Online J. 2016;7(2):87-92.
- Gisondi P, Rossini M, Di Cesare A, et al. Vitamin D status in patients with chronic plaque psoriasis. Br J Dermatol. 2012;166(3):505-510.
- Stanescu AMA, Simionescu AA, Diaconu CC. Oral vitamin D therapy in patients with psoriasis. Nutrients. 2021;13(1):163.
- Holick MF, Smith E, Pincus S. Skin as the site of vitamin D synthesis and target tissue for 1,25-dihydroxyvitamin D3. Use of calcitriol (1,25-dihydroxyvitamin D3) for treatment of psoriasis. Arch Dermatol. 1987;123(12):1677-1683a.
- Tiosano D, Wildbaum G, Gepstein V, et al. The role of vitamin D receptor in innate and adaptive immunity: a study in hereditary vitamin D-resistant rickets patients. J Clin Endocrinol Metab. 2013;98:1685–1693.
- Olliver M, Spelmink L, Hiew J, et al. Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae. J Infect Dis. 2013;208:1474–1481.
- Gonçalves de Carvalho CM, Ribeiro SM. Aging, low-grade systemic inflammation and vitamin D: a mini-review. Eur J Clin Nutr. 2017;71(4):434-440.
- Chang SH, Chung Y, Dong C. Vitamin D suppresses Th17 cytokine production by inducing C/EBP homologous protein (CHOP) expression. J Biol Chem. 2010;285(50):38751-38755.
- Goddek S. Vitamin D3 and K2 and their potential contribution to reducing the COVID-19 mortality rate. Int J Infect Dis. 2020;99:286-290.
- Ala-Houhala MJ, Vähävihu K, Hasan T, et al. Comparison of narrowband ultraviolet B exposure and oral vitamin D substitution on serum 25-hydroxyvitamin D concentration. Br J Dermatol. 2012;167:160–4.
- Bosman ES, Albert AY, Lui H, et al. Skin exposure to narrow band ultraviolet (UVB) light modulates the human intestinal microbiome. Front Microbiol. 2019;10:2410.
- Christakos S, Ajibade DV, Dhawan P, et al. Vitamin D: metabolism. Endocrinol Metab Clin North Am. 2010;39(2):243-253.
- Yin K, Agrawal DK. Vitamin D and inflammatory diseases. J Inflamm Res. 2014;7:69-87.
- Morimoto S, Kumahara Y. A patient with psoriasis cured by 1 alpha-hydroxyvitamin D3. Med J Osaka Univ. 1985;35(3-4):51-54.
- Orgaz-Molina J, Magro-Checa C, Arrabal-Polo MA, et al. Association of 25-hydroxyvitamin D with metabolic syndrome in patients with psoriasis: a case-control study. Acta Derm Venereol. 2014;94(2):142-145.
- Dai Q, Zhu X, Manson JE, et al. Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial. Am J Clin Nutr. 2018;108(6):1249-1258.
- Yasui T, Miyatani Y, Tomita J, et al. Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women. Gynecol Endocrinol. 2006;22:455–459.
- Disphanurat W, Viarasilpa W, Chakkavittumrong P, Pongcharoen P. The clinical effect of oral vitamin D2 supplementation on psoriasis: a double-blind, randomized, placebo-controlled study. Dermatol Res Pract. 2019;2019:5237642.
- Zuccotti E, Oliveri M, Girometta C, et al. Nutritional strategies for psoriasis: current scientific evidence in clinical trials. Eur Rev Med Pharmacol Sci. 2018;22:8537–8551.
- Pitukweerakul S, Thavaraputta S, Prachuapthunyachart S, Karnchanasorn R. Hypovitaminosis D is associated with psoriasis: a systematic review and meta-analysis. Kans J Med. 2019;12(4):103-108.
- Perez A, Raab R, Chen TC, et al. Safety and efficacy of oral calcitriol (1,25 dihydroxyvitamin D) for the treatment of psoriasis. Br J Dermatol. 1996;134:1070–1078.