Vitamin D Deficiency in Metastatic Melanoma

Retrospective study finds association

By Michael Traub, ND, DHANP, FABNO, and Miranda LaBant, ND

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Reference

Timerman D, McEnery-Stonelake M, Joyce C, et al. Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma. Oncotarget. 2017;8(4):6873-6882.

Study Objective

To determine whether vitamin D deficiency and repletion are associated with melanoma outcome. Patients with 25-hydroxyvitamin D3 (25[OH]D3) <21 ng/mL were advised to take 50,000 IU vitamin D3 per week for 8 weeks and then continue with 4,000 IU per week.

Design

Retrospective single-center study of medical records from January 2007 through June 2013.

Participants

Records from 252 individuals with a 25(OH)D3 level recorded within 1 year after histopathological diagnosis of melanoma were included in the study. Individual and melanoma characteristics such as age, sex, Breslow’s thickness, ulceration, stage, mitotic rate, and lactate dehydrogenase (LDH) levels were obtained from medical records. Subgroup analysis included 168 patients with a subsequent 25(OH)D3 level that had been recorded at any time (ie, patients with more than 1 vitamin D level in their records).

Study Parameters Assessed

Vitamin D deficiency status was based on current practice guidelines from the Endocrine Society. For comparison, the analysis included effects of changes in 25(OH)D3 levels on survival.

Primary Outcome Measures

Vitamin D levels, markers of melanoma growth (LDH levels, mitotic growth, ulceration, stage), and survival/death.

Key Findings

Patients who died were more likely to have vitamin D deficiency (<21 ng/mL; P=0.012), LDH>240 U/L (P<0.001), older age (>50 years; P=0.007), higher stage (P<0.001), ulceration (P=0.001), and higher mitotic rate (P=0.001) compared to those who were alive or lost to follow-up at the end of the study. Patients with vitamin D deficiency (<21 ng/mL) were more likely to have a higher stage of disease (P=0.01) as well as higher mortality (P=0.012). Patients with metastatic melanoma who were deficient and taking vitamin D but did not obtain ≥20 ng/dL increase in serum levels had a worse prognosis (hazard ratio [HR]: 4.68; 95% confidence interval [CI]: 1.05-20.88) than those who were vitamin D replete and had >20 ng/mL increase in vitamin D. Collectively, these results suggest that initial vitamin D deficiency and insufficient repletion is associated with a worse prognosis in patients with metastatic melanoma.

Practice Implications

Melanoma diagnoses in the United States increased at a rate of 3.1% per year from 1992 to 2004.1 Lifetime risk of melanoma in the United States is 1 in 39 for Caucasian men and 1 in 58 for Caucasian women.2 The increased risk for this commonly fatal skin cancer has driven research in both prevention and treatment.

Much debate surrounds the relationship between vitamin D and cancer, including melanoma.3-5 This study confirms earlier studies that found lower serum 25(OH)D levels were associated with increased melanoma risk, greater Breslow thickness, and worse overall survival,6 and that 25(OH)D level during follow-up was an independent prognostic marker.7 The association of vitamin D and risk of melanoma, however, is confounded by other studies showing no association between vitamin D levels and mortality, and studies that show increased melanoma incidence in patients with high levels of vitamin D.8,9 Yet in this regard, it is important to consider that melanoma risk is related to repeated overexposure to ultraviolet B (UVB) radiation (blistering sunburns) rather than cumulative lifetime exposure.

Collectively, these results suggest that initial vitamin D deficiency and insufficient repletion is associated with a worse prognosis in patients with metastatic melanoma.

Given that patients with melanoma are counseled to avoid sun exposure and take supplemental vitamin D, this study provides an evidence basis for such a recommendation. One of these reviewers (Traub) has published a study providing evidence that a repletion strategy of 10,000 IU of vitamin D3 for 3 months is safe and effective.10

The authors of the study reviewed here suggest that since serum 25(OH)D has been associated with a robust immune response, it might be considered a marker of immune sufficiency in patients with metastatic melanoma. Similarly, UV radiation, in particular the UVB range, is known to be immunosuppressive to the skin. DNA damage induced by UVB is not only a carcinogen but also a major trigger of UV-induced immunosuppression.11

We were unable to verify the sources and dosage of vitamin D supplements taken by participants in the study. We also acknowledge that large prospective clinical trials of patients with melanoma receiving vitamin D supplementation are necessary to prove a causal relationship.

The main takeaway is that we should obtain 25(OH)D3 levels for all patients with melanoma, and for those who are deficient, supplement with vitamin D3 until repletion. We should maintain repletion with 2,000 to 4,000 IU daily. Use the same strategy for patients with a history of melanoma, to prevent recurrence.

About the Authors

Michael Traub, ND, DHANP, FABNO, completed pre-med studies at the University of California at Irvine. He graduated from National University of Naturopathic Medicine in 1981 and completed a residency there in Family Practice and Homeopathy. In 2006, Traub was honored with the American Association of Naturopathic Physicians (AANP) Physician of the Year Award in recognition for his many years of service, which included serving as AANP president from 2001 to 2003. His father was a dermatologist, and this inspired Traub to undertake extra study in this subject and become the leading expert in dermatology in the naturopathic profession. He has taught dermatology at 5 of the 7 accredited naturopathic medical schools in North America and is the author of Essentials of Dermatologic Diagnosis and Integrative Therapeutics. A fellow of the American Board of Naturopathic Oncology, Traub has been actively engaged in clinical research throughout most of his career and is currently a co-investigator in the Canadian/US Integrative Oncology Study. His most recent major publication, “Impact of Vitamin D3 Dietary Supplement Matrix on Clinical Response,” appears in a 2014 issue of the Journal of Clinical Endocrinology and Metabolism. Traub has served as medical director of Lokahi Health Center in Kailua Kona, Hawaii for the past 31 years.

Miranda LaBant, ND, graduated from National University of Health Sciences in Illinois. She completed a 1-year Council on Naturopathic Medical Education-accredited residency in integrative oncology under the direction of Michael Traub, ND. LaBant earned her master of health sciences degree from Cleveland State University. She is an active member of the Oncology Association of Naturopathic Physicians and New Hampshire Association of Naturopathic Doctors. LaBant is currently practicing at North Coast Family Health in Portsmouth, NH, where she focuses on integrative oncology, Lyme disease, endocrine health, gastrointestinal health, and preventative care.

References

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