Written by Chrystal Moulton, Staff Writer. Participants with Breslow thickness <3mm doubled in 25O HD serum levels after 3 years.
Vitamin D (cholecalciferol) is made in the skin when ultraviolet light (UV-B) activates pre-vitamin D cholesterol derivatives. The liver converts chcolecalciferol to 25-OHD and the kidney subsequently converts 2-OHD to its active form, 1,25(OH)2D . The best indicator of vitamin D status is serum 25-hydroxyvitamin D (25-OHD) the most abundant intermediate metabolite of vitamin D 1. Vitamin D has been shown to attenuate inflammation caused by sunburn 2. Furthermore, research has shown that those with continuous patterns of sun exposure are less likely to develop melanoma compared to those with intermittent patterns of sun exposure 3. The assumption is that the production of vitamin D during continuous patterns of sun exposure could possibly serve as a protective measure against developing melanoma 3,4. In fact, some studies show a reduced incidence and mortality by cancer in patients with high serum vitamin D concentration 5 while other clinical data specifically show a correlation between high serum vitamin D and better clinical outcomes in melanoma patients 1.
In a double-blind placebo-controlled trial, researchers evaluated the effect a vitamin D supplementation on patients with stage II melanoma 1. A total of 104 adults 75 years or younger with malignant stage II melanoma that had recent resection were recruited for this trial. Patients with normal liver, kidney, and blood parameters were included in this trial. Participants were randomized to receive 100,000 IU of vitamin D3 (average 2000 IU / day) or placebo every 50 days for three years. Participants returned to the clinic for routine laboratory tests at the 4th, 8th, 12th, 16th, 20th, 24th, 28th, 32nd, 36th, 42nd, 48th, 54th, and 60th month. Serum samples were collected and tested for parathyroid hormone concentrations, lactate dehydrogenase, neutrophil- lymphocyte ratio, C-reactive protein, and serum 25OHD. Genomic DNA was also extracted to test for SNPs related to DNA expression of melanoma. Patients were characterized based on Breslow thickness which indicates the depth and size of tumor on the skin. The main objective of the study was to assess the effect of vitamin D supplementations on the reoccurrence of stage II melanoma.
The median age of melanoma diagnosis across both the placebo and treatment group was 51 years. 80% of the participants had low serum vitamin D and, although not statistically significant, patients with larger tumor size tended to have low serum 25OHD levels. Serum vitamin D levels increased in the treatment group. However, researchers found that increase in serum vitamin D was based on tumor size. Participants with Breslow thickness <3mm doubled in 25O HD serum levels after 3years (4mos: 14.23ng/mL, p<0.0001 vs. 36mos: 30.50 ng/mL, p<0.0001) but patients with Breslow thickness ≥ 3mm experienced lower increases in 25OHD serum levels after 3years (4mos: 10.75 ng/mL, p=0.003 vs. 36mos: 14.51 ng/mL, p=0.0002). Hazard ratios for patients with Breslow scores <3 was 0.26 (P = 0.033) after adjusting for age serum D levels at 12 months and study allocation. Participants with low serum vitamin D and Breslow ≥3mm were significantly more likely to relapse than patients with high 25OHD levels and Breslow <3mm, high 25OHD levels and Breslow ≥3mm, and low 25OHD levels and Breslow <3mm (p=0.02). The hazard ratio for recurrence of melanoma in patients with Breslow score >3mm and low serum 25O HD levels was 4.81 (P = 0.011). Genotype did not interact with treatment effects. No interactions were observed for C-reactive protein, lactate dehydrogenase, and neutrophil-lymphocyte ratio. Parathyroid hormone decreased with vitamin D supplementation. No severe adverse events occurred during the trial. 7% of participants encountered level 1 and 2 adverse events but it was not linked to serum vitamin D levels or associated with treatment allocation (P = 0.24).
In conclusion, the research showed that patients with Breslow thickness ≥3mm at diagnosis saw lower increase in serum 25OHD despite supplementation with 100,000IU of vitamin D every 50 days. Participants with Breslow thickness ≥3mm at diagnosis were also prone to relapse compared with patients with Breslow thickness <3mm. More research is needed to understand why tumor size effects serum vitamin D levels despite prolonged supplementation.
Source: Johansson, Harriet, Giuseppe Spadola, Giulio Tosti, Mario Mandalà, Alessandro M. Minisini, Paola Queirolo, Valentina Aristarco et al. “Vitamin D Supplementation and Disease-Free Survival in Stage II Melanoma: A Randomized Placebo Controlled Trial.” Nutrients 13, no. 6 (2021): 1931.
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
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Posted August 9, 2021.
Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.
References:
- Scott, Jeffrey F., et al. “Oral vitamin D rapidly attenuates inflammation from sunburn: an interventional study.” Journal of investigative dermatology10 (2017): 2078-2086.
- Caini, Saverio, et al. “Meta-analysis of risk factors for cutaneous melanoma according to anatomical site and clinico-pathological variant.” European journal of cancer17 (2009): 3054-3063.
- Johansson, Harriet, et al. “Vitamin D Supplementation and Disease-Free Survival in Stage II Melanoma: A Randomized Placebo Controlled Trial.” Nutrients6 (2021): 1931.
- Keum, N., et al. “Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials.” Annals of Oncology5 (2019): 733-743.
- Newton-Bishop, Julia A., et al. “Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at presentation and survival from melanoma.” Journal of clinical oncology32 (2009): 5439.
