Oral and Topical Vitamin D, Sunshine, and UVB Phototherapy Safely Control Psoriasis in Patients with Normal Pretreatment Serum 25-Hydroxyvitamin D Concentrations: A Literature Review and Discussion of Health Implications
Nutrients 2021, 13(5), 1511; https://doi.org/10.3390/nu13051511
by Patrick J. McCullough 1,2,*,William P. McCullough 3,Douglas Lehrer 2,Jeffrey B. Travers 4ORCID andSteven J. Repas 5ORCID
1 Medical Services Department, Summit Behavioral Healthcare, Ohio Department of Mental Health and Addiction Services, 1101 Summit Rd, Cincinnati, OH 45237, USA
2 Department of Psychiatry, Wright State University Boonshoft School of Medicine, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA
3 Rose-Hulman Institute of Technology, 5500 Wabash Ave, Terre Haute, IN 47803, USA
4 Department of Pharmacology & Toxicology, Wright State University Boonshoft School of Medicine, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA
5 Wright State University Boonshoft School of Medicine, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA
* Author to whom correspondence should be addressed.
Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s, interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitamin D3 (1 (OH) D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/mL). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.
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Summary point of study:
- Four different oral forms of vitamin D are safe and effective treatments for plaque psoriasis
- Normal serum 25(OH)D concentrations (>20 ng/mL) were common pretreatment but insufficient to improve psoriatic lesions
- High serum 25(OH)D concentrations (>100 ng/mL) were often reported with safe control of psoriasis
- Changes in serum 25(OH)D concentrations after treatment vary significantly with the treatment used
- A therapeutic dose response of psoriasis to vitamin D appears to be present
- Calcitriol formation is the common endpoint after treatment with vitamin D, sunshine and UVB phototherapy
- Psoriasis can recur with cessation of treatment with vitamin D, sunshine or UVB phototherapy
- Psoriasis can improve again with resumption of treatment with vitamin D, sunshine or UVB phototherapy
- Post treatment serum 25(OH)D concentrations are higher after UVB phototherapy compared to sunshine
- A paucity of adverse reactions was observed with vitamin D supplementation in the reviewed studies
- Clinical efficacy and safety of oral and topical vitamin D treatments are comparable to UVB phototherapy and sunshine treatments
- All authors reviewed stated unequivocal support for the safety and efficacy of vitamin D in treating psoriasis
- Estimates of vitamin D production in the 1970s are significantly lower than doses used clinically in treating diseases in the 1930s and 1940s— but significantly higher than the doses recommended for use today.
Conclusions and Future Directions (clipped from PDF)
Psoriasis responds safely to treatment with 4 different forms of oral vitamin D: vitamin D2, vitamin D3,1-alpha-hydroxyvitaminD3, and 1,25-dihydroxyvitamin D3 (calcitriol). Pretreatment serum 25(OH)D3 concentrations above 20 ng/mL, ranging up to 67 ng/mL, were common in patients with plaque psoriasis in the oral vitamin D dosing studies reviewed. However, patients showed significant dermatological improvement in their skin without toxicity after daily treatment with four different forms of oral vitamin D. This suggests that serum 25(OH)D3 concentrations > 20 ng/mL are not adequate for many patients with plaque psoriasis, even though they are considered adequate for the majority of the population by the IOM [55] and the Endocrine Society [56], calling into question the definition of an adequate serum 25OHD concentration. Pre-treatment serum 25(OH)D3 concentrations > 20 ng/mL, ranging up to 88 ng/mL, were also commonly observed in patients with plaque psoriasis in the UVB phototherapy studies reviewed, yet these patients still showed significant improvement in their skin after treatment with UVB phototherapy. This was associated with significantly increased serum 25(OH)D3 concentrations posttreatment, with several patients > 100 ng/mL, and ranging up to 159 ng/mL without any adverse events.
Post-treatment serum 25(OH)D3 concentrations > 100 ng/mL were also observed in patients with plaque psoriasis safely treated with 35,000 IU/day of vitamin D3 for 6 months, and in a patient treated with 50,000 IU/day of vitamin D2 for over 3 years, without any adverse events. This was associated with peak serum 25(OH)D3 concentrations of 202 ng/mL and 308 ng/mL respectively. The fact that serum 25(OH)D3 concentrations > 100 ng/mL have been obtained safely after disease control using UVB phototherapy, 35,000 IU/day of vitamin D3, and 50,000 IU/day of vitamin D2 calls into question the safe upper limit of serum 25(OH)D3 concentrations. Currently, a serum 25(OH)D3 concentration > 50 ng/mL is considered potentially dangerous for the majority of the population and is not recommended by the IOM [55] and a serum 25OHD concentration > 100 ng/mL is considered high by the Endocrine Society [56]. In contrast, several reviews [57-59] and case reports [60] on vitamin D toxicity have suggested that serum 25OHD concentrations > 100 ng/mL and ranging up to 400 ng/mL may be safe. This needs further clarification. A recent review on vitamin D safety suggests that "Vitamin D is not as toxic as was once thought" [307]
The exact range of total serum 250HD concentrations needed to be achieved to improve psoriasis is currently unknown and is speculative at this time. Dose response studies need to be performed with all four forms of oral vitamin D to clarify the time response to treatment with varying doses and the therapeutic index. However, as mentioned elsewhere in this review, current "normal" levels for vitamin sufficiency are not likely to be effective in treating psoriasis. We suggest that total serum 250HD concentrations closer to 100 ng/mL might be needed when oral vitamin D2 or vitamin D3 are used. However, because there will be no change in total serum 250HD concentrations when either 1(0H)D or calcitriol are used, as total serum 250HD concentrations are not affected when these agents are used (Figure S1, Table S2, Supplementary Materials), measurement of free and bioavailable serum 250HD may prove to be better markers of disease control in psoriasis, as previously discussed [259,260]. In addition there maybe differences in responses between males and females, as a correlation between vitamin D deficiency and insulin resistance was recently reported in females, but not in males [322].
Vitamin D toxicity was absent in the reviewed clinical reports. When it occurs, it is manifested by complications related to hypercalcemia, renal insufficiency, hypercalciuria, calcium crystal formation, and undetectable serum parathyroid hormone concentrations, which have been shown to be reversible by simply stopping the vitamin D and providing supportive care with no long-term sequelae. Several such complications induced by excessive vitamin D intake (hypercalcemia, renal insufficiency, hypercalciuria, and undetectable serum PTH) were shown to resolve when serum 25(0H)D3 concentrations dropped below 400 ng/mL in 2 case reports in 2011 after accidental ingestion of massive amounts of vitamin D over a period of 1 to 2 months [60]. Due to labeling and manufacturing errors of over the counter supplements, one patient took 1,864,000 units (46,000 pg) of vitamin D3 daily for 2 months and achieved a peak serum 250HD concentration of 1220 ng/mL. The second took 970,000 units of vitamin D3 a day for one month and achieved a peak serum 250HD concentration of 645 ng/mL. Both recovered uneventfully after cessation of vitamin D intake. Our clinical experience is consistent with this, as we have not observed hypercalcemia, renal insufficiency, hypercalciuria, undetectable serum parathyroid hormone concentrations or any other toxicity in patients with serum 25(0H)D3 concentrations ranging from 202 ng/mL to 384 ng/mL [28].
Vitamin D has a much safer toxicity profile than methotrexate, cyclosporine and biologics such as Humira and Enbrel, which are more commonly used for the treatment of psoriasis. Biologics are among the most frequently reported drugs for adverse events to the FDA, and many have FDA mandated black box warnings for risk of cancers such as lymphoma, serious infections such as tuberculosis and invasive fungal infections, and death [323-335]. In contrast, vitamin D was shown in the 1940s to safely cure tuberculosis infections as a single agent using daily oral intake of 100,000 to 150,000 units for 2 to 3 months [33-39], most likely by turning on genes that make antimicrobial peptides active against TB [39,282,289]. More recently, vitamin D has been shown to have anticancer properties [28,284,287,295,298,301,310], and appears to reduce the risk for developing cancer, and not increase it as biologics do. More clinical research utilizing a range of vitamin D intakes is needed to confirm these findings and to see if a dose response exists in cancer prevention, in light of the recent clinical trial reviewed earlier that showed no clinical benefit in cancer prevention after daily intake of 2000 units of vitamin D3 over five years [318]. Vitamin D also appears to have a safer toxicity profile than sunshine, UVB phototherapy, and even acetaminophen, one of the most commonly used over the counter medications, and a leading cause of liver failure [336,337].
The fact that both oral and topical vitamin D were able to produce the same clinical outcomes as seen with sunshine and UVB phototherapy is compelling evidence that the effects of sunshine and UVB phototherapy in treating psoriasis is mediated by vitamin D production in the skin. The mechanism of action explaining how vitamin D works to clear psoriasis skin lesions is currently unknown but appears likely to be related to the documented effects vitamin D has on stimulating the production and maintenance of regulatory T lymphocytes (Tregs), which have been characterized as master regulators of the immune system due to their ability to control autoimmune diseases [239]. This also needs further clarification. However, consistent with this notion, Tregs have been shown to be dysfunctional in a state of vitamin D deficiency, and can have their functional status restored by sunshine, phototherapy and oral or topical vitamin D [153-233]. Vitamin D causes the formation of Tregs to occur indirectly through direct effects on antigen presenting cells, which then cause naïve T cells to transform into Tregs [143].
Placebo controlled, blinded clinical trials using oral vitamin D3 for the treatment of patients suffering from psoriasis are warranted based on the results of the studies reviewed in this paper. There is strong evidence that physiologic doses in the range of 10,000 to 25,000 IU/day, and ranging up to 50,000 IU/day, should be able to be administered safely in a clinical trial setting. Serum calcium and PTH concentrations, renal function and urine calcium concentrations can be easily monitored and readily corrected without long-term risk if they become abnormal by simply stopping vitamin D supplementation. The vitamin D could then be resumed again at a lower dose to monitor clinical efficacy and safety. There is potentially much to gain if these dose-response clinical trials are successful. Oral vitamin D is the most affordable treatment option for psoriasis by a wide margin, especially when compared to biologics. The potential cost savings to the health care system by the increased use of oral vitamin D in treating psoriasis is enormous, in the range of billions of dollars/year, with improved patient safety and satisfaction. It is not clear why the four forms of oral vitamin D discussed in this review are not currently being used to treat psoriasis, after being endorsed as safe and effective treatments by the authors of the clinical trials reviewed.
The failure of clinical trials that used sub-physiologic doses of vitamin D and achieved inadequate serum 25(OH)D concentrations has created doubt about the importance of vitamin D in the prevention and treatment of human disease. The fear of causing toxicity by using excessive amounts of vitamin D has led to the unintended consequence of causing needless suffering by perpetuating uncontrolled disease states that might otherwise be controlled by sufficient vitamin D intake or exposure to UVB radiation. Clinical trials examining the dose response of oral vitamin D3 using 10,000 to 25,000 IU/day or higher may prove beneficial in controlling plaque psoriasis and other vitamin D related diseases without causing harm. It may have major promise in treating COVID-19 infections, where therapy with "higher than usual" doses probably need to be given only short term given the nature of the clinical course of COVID-19 infections. This was shown to be a successful treatment strategy for chronic tuberculosis infections in the 1940s. Current definitions of normal and excessive serum 25OHD concentrations need to be re-evaluated based on the clinical data reviewed in this manuscript. The therapeutic index of vitamin D in the treatment of human disease needs to be better defined.
VitaminDWiki – Psoriasis category contains
Some of the- Psoriasis is most strongly associated with low vitamin D (15 things were evaluated) – July 2022
- Long-term Psoriasis cured by 30,000 to 60,000 IU of Vitamin D daily (pictures and video) – early 2022
- Psoriasis paradigm shift – use topicals, like Vitamin D – Aug 2021
- Low Vitamin D plus psoriasis equals 8 times more likely to die – Dec 2020
- UV has treated psoriasis for over a century, guidelines finally agreed upon – Aug 2019
- Psoriasis severity associated with low vitamin D (10 studies) – meta-analysis Jan 2018
- Psoriasis reduced for those getting Vitamin D levels above 50 ng – RCT Feb 2018
- 35,000 IU vitamin D daily for 6 months helped ALL psoriasis suffers (106 ng) – Brazil March 2013
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