HPLC Measurement of Serum Vitamin D: Insights into Malignancy and Lung Metastases

While deficiencies in vitamin D has been linked to increased cancer risk and death, the effects of vitamin D substitution on the prognosis of patients with malignant disease has long been debatable.A Czech Republic study aimed to investigate the serum vitamin D3 levels in patients with a history of malignancy and confirmed lung metastases, with serum levels measured with high-performance liquid chromatography (HPLC). A paper based on their research has been published by Biomedical Papers (1).

Vitamin D plays many important roles in the human body, including the building and maintenance of bones and teeth and immunomodulatory and antitumor effects. In doses greater than the amount normally found in the human body, the vitamin exhibits preventive and differentiating properties, inhibits angiogenesis, induces apoptosis, arrests the cell cycle, and enhances cell adhesion and intercellular communication (2-5). Active vitamin D (1,25(OH)₂D) exerts its effects through nuclear receptors located in the intestine, bones, and kidneys, with its genomic action involving the binding of the 1,25(OH)₂D and the activated vitamin D receptor/retinoid X receptor (VDR/RXR) complex to specific DNA sequences (6). A deficiency in Vitamin D is often linked to poor cancer outcomes in humans, while its supplementation or analogs has been shown to reduce tumor progression and metastasis in animal models, suggesting that doses of 1,25(OH)₂D may result in a reduction in the aggressiveness of osteosarcoma cells (7,8). The effect of vitamin D substitution on the prognosis of patients with malignant disease remains a debatable issue, however, as the results of studies are inconsistent; it is this inconsistency that inspired the team to carry out their research (1).

In this study, the team measured serum Vitamin D2 (25-hydroxyergokalciferol) and D3 (25‑hydroxycholekalciferol) levels in 38 patients (28 with and 10 without lung metastases) with HPLC. Serum levels in the subset of patients with lung metastases were analyzed with respect to season, the number of metastases, the number of malignancies in the history, value according to The American Society of Anesthesiologists (ASA) physical status classification, and then compared to patients with a history of malignancy without confirmed lung metastasis (1).

The researchers reported that mean serum vitamin D3 levels overall were significantly higher in summer (summer vs. winter; 85.06 nmol/L vs. 61.01 nmol/L; P=0.013). There was no significant difference in vitamin D3 levels in summer or winter between patients with or without lung metastases, nor was there any significant difference in vitamin D3 levels in the summer months between patients with a history of one malignancy versus those with two or more. The researchers found, however, that, in the winter, patients with a history of one malignancy had significantly higher vitamin D3 levels (mean, 75.25 nmol/L) than those with two or more malignancies (mean 44.6 nmol/L) (P=0.027). The differences between vitamin D3 levels in patients with ASA 2 and 3 were not statistically significant (1)..

Vitamin D supplementation may be advisable for patients with a history of multiple malignancies, especially during the winter months, the researchers wrote. However confirmation of this through a clinical trial with a larger patient cohort is necessary before firm recommendations can be made (1).

References

1. Hanslik, T.; Klikovits, T.; Soska, V. et al. Serum vitamin D levels in patients with lung metastases. Biomed. Pap. Med Fac Univ Palacky Olomouc Czech Repub. 2025.DOI: 10.5507/bp.2025.024
2. Vitamin D- Health Professional Fact Sheet.National Institutes of Health website.https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ (accessed 2025-09-04)
3. Norton, R.; O'Connell, M. A. Vitamin D: Potential in the Prevention and Treatment of Lung Cancer. Anticancer Res. 2012, 32 (1), 211-221.
4. Garland, C. F.; Garland, F. C.; Gorham, E. D. et al. The Role of Vitamin D in Cancer Prevention. Am. J. Public Health 2006, 96 (2), 252-261. DOI: 10.2105/AJPH.2004.045260
5. Akiba, T.; Morikawa, T.; Odaka, M. et al. Vitamin D Supplementation and Survival of Patients with Non-small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin. Cancer Res. 2018, 24 (17), 4089-4097. DOI: 10.1158/1078-0432.CCR-18-0483
6. Christakos, S.; Dhawan, P.; Verstuyf, A. et al. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol. Rev. 2016, 96 (1), 365-408. DOI: 10.1152/physrev.00014.2015
7. Li, J.; Luco, A. L.; Camirand, A. et al. Vitamin D Regulates CXCL12/CXCR4 and Epithelial-to-Mesenchymal Transition in a Model of Breast Cancer Metastasis to Lung. Endocrinology 2021, 162 (7), bqab049. DOI: 10.1210/endocr/bqab049
8. Tahbazlahafi, B.; Paknejad, M.; Khaghani, S. et al. Vitamin D Represses the Aggressive Potential of Osteosarcoma. Endocr. Metab. Immune Disord. Drug Targets 2021, 21 (7), 1312-1318. DOI: 10.2174/1871530320666200821155756