Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers

Background:

Vitamin D is an important hormone that has multiple genetic effects in different tissue types that are mediated by signaling through the vitamin D receptor.

Recent studies have shown that vitamin D signaling results in decreased innate immunity and increased adaptive immunity.

Multiple epidemiologic studies have suggested that vitamin D may play a role in decreasing the risk of developing multiple types of cancer, including skin cancer.

In the context of the relative success of novel immune-related therapies including PD1 inhibitors, which improves immuno-surveillance, and ipilimumab, which suppresses T cell response, there is increased promise for treatment strategies that activate innate immunity. This led us to ask the question of whether vitamin D could increase immune surveillance for melanoma via increased activity of the adaptive immune system.

Prior studies performed by our group and others have suggested that vitamin D may play a role in decreasing melanoma risk. An epidemiologic study from the Women's Health Initiative showed that women with a prior history of NMSC who received calcium and vitamin D supplementation had a lower risk of subsequently developing melanoma. At the same time, women with a lower serum vitamin D level had a higher risk of developing melanoma. Furthermore, a recent clinical study showed that vitamin D supplementation increases serum vitamin D levels and ultimately results in increased vitamin D receptor signaling in benign nevi.

Taken together, this findings led us to ask whether oral vitamin D supplementation could impact immune signaling in benign nevi and potentially underpin a theoretical chemo-preventive role for vitamin D in melanoma.

Inclusion criteria

• Age 18 - 75
• Female
• White race/ethnicity
• With history of non-melanoma skin cancer
• Has 12-16 moles upon skin examination
• Consents to 6-12 moles biopsies over 2-3 clinic visits (2-4 months)
• Consents to ingesting oral vitamin D3 or placebo daily for 2-4 months
• Consents to abstaining from other multivitamins during study
• Consents to research use of their tissue and blood samples
• Agrees to apply a sunscreen of SPF 45 during study -

Exclusion criteria

• History or current evidence of hyperparathyroidism, hypercalcemia, renal calculi, or other renal disease.
• History or current evidence of malabsorptive illnesses, such as IBD, or liver disease that would impair uptake or metabolism of vitamin D.
• History or current evidence of hyperthyroidism that would increase metabolism of vitamin D.
• History or current evidence of immunosuppression (cancer, autoimmune disease) or taking immunosuppressive drugs.
• Currently taking medications that would affect metabolism of vitamin D (anticonvulsants, corticosteroids, H2-receptor antagonists).
• Currently taking medications that predispose to hypercalcemia (digoxin, lithium, thiazide diuretics) or other electrolyte disturbances (aluminum hydroxide)
• Pregnancy