Frequency of Combined Deficiencies of Vitamin D and Holotranscobalamin in Cancer Patients.
Authors: Plant Ashley S. , Tisman Glenn 
Published: October 2019

Abstract
Low serum levels of vitamin D are associated with a higher frequency of at least eleven different malignancies including breast, colon, and prostate cancer (Holick, M.F. Vitamin D: Millenium Perspective. Journal of Cellular Biochemistry. 2003. 88:296–307). Low levels of vitamin B12 were found to contribute to a 2.5–4.0 times greater likelihood of breast cancer in postmenopausal women (Wu, K. et al. Cancer Epidemiol. 1999. 8:209–17) and hematological and mucosal tissue is more sensitive to chemotherapy in the presence of insufficient levels of B12. Only vitamin B12 that is complexed to transcobalamin as holotranscobalamin (HTCII) is metabolically active. It has been suggested that decreased HTCII serum levels are involved in the failure to methylate DNA resulting in the activation of oncogenes that would normally be dormant (Herbert, V. Methyl Metabolism: Epigenetics, Genomics, Proteomics. 2002 FASEB Summer Research Conference. Snowmass Village, Colarado.).Our study investigated vitamin D, total B12 and HTCII levels in 70 cancer patients. Vitamin D was measured as serum 25 OH-D3 (Nichols Advantage assay) and serum B12 was measured as both total B12 and as the metabolically active HTCII (Immulite B12 assay followed by glass adsorption: Vu, T. et al., Am J. Heme42: 202–211 1993). Vitamin D insufficiency has been defined based on differing physiologic sequelae of insufficiency and varies between values less than 50–75 nMol/L. When vitamin D insufficiency is defined as serum level <75nmol/L, 43 of 60 (72%) of cancer patients were found to be insufficient. At a lower definition of insufficiency, <50nmol/L, 24 of 60 patients (40%) were insufficient. Of 52 patients, only 3 (6%) were found to have insufficient serum levels of total B12 (normal >300pg/mL) while 17 of 52 (34%) were found to be HTCII insufficient (normal >69 pg/mL). Of these 17 patients, 14 (84.4%) had normal total B12 levels. Low levels of vitamin D strongly correlated with low serum HTCII. All 12 HTCII deficient patients were vitamin D insufficient at the <75nmol/L standard. Six of 12 HTCII deficient patients (50%) were vitamin D deficient at the <50nmol/L cut off. Chi-squared test for independence revealed a strong relationship between low levels of vitamin D and HTCII. Deficiency of vitamin D (70%) and holotranscobalamin (34%) is prevalent among newly diagnosed patients with cancer. The standard measurement of total serum B12 alone is inadequate for identifying patients with insufficient levels of metabolically active B12. Low vitamin D and holotranscobalamin levels may play a role in cancer development, progression and host response to tumor and therapy. Possible explanations for combined HTCII and D3 deficiency include age, the presence of atrophic gastritis in 30–50% of the elderly, and lack of sun exposure and deficient production of D3 in the elderly. Since both vitamins are conserved by cubulin/megalin mediated renal tubular reabsorption a defect of this mechanism could contribute to deficiency of both vitamins. Study supported in part by ThinkTwice Technologies. This work is dedicated to the memory of Dr. Victor Herbert whose teachings continue to inspire our research efforts.