Vitamin D is a hormone created by the body when skin is exposed to ultraviolet rays in sunlight. It is found naturally in a small number of foods and can also be taken as a fat-soluble dietary supplement.
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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.
Clinical practice guidelines
Cancer prevention guidelines
- Individuals treated with a bisphosphonate or denosumab should undergo a dental examination with preventive dentistry prior to the initiation of an agent, and should take supplemental calcium and vitamin D.
- The role of calcium, vitamin D, and a healthy lifestyle in maintaining bone health must be emphasized in healthy postmenopausal women who are receiving exemestane.
Cancer treatment guidelines
- To monitor patients for risks of developing symptomatic osteonecrosis, routine measurements for vitamin D and calcium levels should be obtained, and periodic radiographic evaluation (using plain films or MRI) should be considered. Obtain vitamin D and calcium status and replete as needed.
B-Cell Lymphomas, 2022
- If vitamin D 25-OH is deficient, then replete. In lymphoma patients with current elevations in 1,25-dihydroxyvitamin D, deficient 25(OH)D levels should not be aggressively replaced.
- Calcium intake from food (plus supplements if necessary) should be commensurate with National Academy of Medicine recommendations except in cases of lymphoma-induced hypercalciuria/hypercalcemia due to excessive 1,25-dihydroxyvitamin D production.
Breast Cancer, 2022
- Patients treated with a bisphosphonate or denosumab should undergo a dental examination with preventive dentistry prior to the initiation of therapy and should take supplemental calcium and vitamin D.
- Denosumab, zoledronic acid, or pamidronate (all with calcium and vitamin D supplementation) should be given (category 1) in addition to chemotherapy or endocrine therapy if bone metastasis is present, expected survival is ≥3 months, and renal function is adequate.
- The use of bisphosphonates should be accompanied by calcium and vitamin D supplementation with daily doses of calcium of 1200 to 1500 mg and vitamin D3 of 400 to 800 IU.
Colon Cancer, 2022
- The panel does not currently recommend routine screening for vitamin D deficiency or supplementation of vitamin D in patients with CRC.
- Management of long-term sequelae of disease or treatment:
- Monitor for malnutrition, especially during initial 6 months after surgery.
- Consider monitoring vitamin B, folic acid, vitamin D, and calcium levels.
Gastric Cancer, 2022
- Consider vitamin D testing and replacement as clinically indicated for bone health.
Kidney Cancer, 2022
- The panel recommends a bisphosphonate or a RANK ligand inhibitor for selected patients with bony metastases and creatinine clearance greater than or equal to 30 mL/min. Daily supplemental calcium and vitamin D are strongly recommended
- For a clinical diagnosis of MEN1: Measurement of serum calcium levels is recommended if hyperparathyroidism is suspected. If calcium levels are elevated, parathyroid hormone (PTH) and 25-OH vitamin D levels should be checked.
- Denosumab and bisphosphonate therapy can be associated with severe hypocalcemia; patients with hypoparathyroidism and vitamin D deficiency are at increased risk for hypocalcemia.
Prostate Cancer, 2022
- There are currently no guidelines on how often to monitor vitamin D levels. However, for those who require monitoring with DEXA scans, it makes sense to check the serum vitamin D level at the same time.
- All patients on denosumab should be treated with vitamin D and calcium with periodic monitoring of serum calcium levels.
- A baseline bone mineral density study should be considered for the patients on ADT. The National Osteoporosis Foundation guidelines include: 1) calcium (1000–1200 mg daily from food and supplements) and vitamin D3 (400–1000 IU daily).
- Supplemental calcium and vitamin D are recommended to prevent hypocalcemia in patients receiving either denosumab or zoledronic acid.
Rectal Cancer, 2022
- The panel does not currently recommend routine screening for vitamin D deficiency or supplementation of vitamin D in patients with CRC.
Thyroid Carcinoma, 2022
- Patients whose TSH levels are chronically suppressed should be counseled to ensure adequate daily intake of calcium (1200 mg/day) and vitamin D (1000 IU).
Improving bone mineral density behaviors
Men with prostate cancer receiving androgen deprivation therapy showed higher rate of bone mineral density testing when receiving both a patient bone health pamphlet and support from a bone health care coordinator compared to usual care. Men receiving a patient bone health pamphlet and brief recommendations for their family physician showed more use of calcium and vitamin D and orders of bone mineral density tests in a mid-sized RCT.1Alibhai SMH, Breunis H et al. Improving bone health in men with prostate cancer receiving androgen deprivation therapy: results of a randomized phase 2 trial. Cancer. 2018 Mar sa15;124(6):1132-1140.
Vitamin D receptor and gene polymorphisms
Genetic variants may influence the response of the vitamin D receptor (VDR) to vitamin D treatment.
Vitamin D effects as a whole
- Allelic variants were related to a higher transcription of VDR gene and a higher activity of VDR receptor.2Amadori D, Serra P et al. Vitamin D receptor polymorphisms or serum levels as key drivers of breast cancer development? The question of the vitamin D pathway. Oncotarget. 2017 Feb 21;8(8):13142-13156.
- A link among gene polymorphisms and diseases has been established.3Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clinica Chimica Acta. 2006 Sep;371(1-2):1-12.
- The protein expression level of VDR in entire breast cancer cells evaluated by immunohistochemistry is related to the overall survival of breast cancer patients.4Xu H, Liu Z, Shi H, Wang C. Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis. BMC Cancer. 2020 Nov 1;20(1):1051.
- Better survival among people with advanced non–small-cell lung cancer with the C/C genotype of the FokI polymorphism compared to C/T or T/T genotypes, although 25(OH)D levels had no main effect on survival, in a mid-sized observational study5Heist RS, Zhou W et al. Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer. Journal of Clinical Oncology. 2008 Dec 1;26(34):5596-602.
Risk of recurrence
- Single nucleotide polymorphisms (SNPs) in retinoid-X receptor alpha (RXRA) may be a predictor for disease-free survival with breast cancer.6Pande M, Thompson PA et al. Genetic variants in the vitamin D pathway and breast cancer disease-free survival. Carcinogenesis. 2013 Mar;34(3):587-94.
Risk of cancer
Cancer as a whole
- The rs12785878, rs1790349, and rs12794714 SNPs related to vitamin D-metabolizing enzymes might potentially be biomarkers for cancer susceptibility.7Wen J, Li J, Liang X, Wang A. Association of polymorphisms in vitamin D-metabolizing enzymes DHCR7 and CYP2R1 with cancer susceptibility: a systematic review and meta-analysis. Disease Markers. 2021 May 22;2021:6615001.
- The rs4588 and rs7041 polymorphisms, related to vitamin D metabolism, were significantly associated with overall cancer risk. Stratification analyses of ethnicity indicated that rs4588 polymorphism significantly increased cancer risk in Caucasians and Asians, while rs7041 polymorphism significantly increased cancer risk in Asians.8Zhu M, Tan Z et al. Association of the vitamin D metabolism gene GC and CYP27B1 polymorphisms with cancer susceptibility: a meta-analysis and trial sequential analysis. Bioscience Reports. 2019 Sep 13;39(9):BSR20190368.
- The rs2585428 and rs4809960 polymorphisms, related to vitamin D degradation, were significantly associated with overall cancer risk.9Zhu M, Qiu S et al. The associations between CYP24A1 polymorphisms and cancer susceptibility: a meta-analysis and trial sequential analysis. Pathology, Research and Practice. 2018 Jan;214(1):53-63.
- Some differences were found, partially explained by minor allele frequency (MAF), for colorectal cancer, ovarian and prostate cancer in Caucasian and prostate cancer in Asian populations.10Gnagnarella P, Raimondi S et al. Ethnicity as modifier of risk for Vitamin D receptors polymorphisms: comprehensive meta-analysis of all cancer sites. Critical Reviews in Oncology/Hematology. 2021 Feb;158:103202.
- There is a correlation between the TaqI polymorphism of vitamin D receptor (VDR) and the risk of tobacco-related cancers.11Laczmanski L, Laczmanska I, Lwow F. Association of select vitamin D receptor gene polymorphisms with the risk of tobacco-related cancers—a meta-analysis. Scientific Reports. 2019 Nov 5;9(1):16026.
- The rs4809960 SNP, related to vitamin D degradation, significantly decreased the risk of breast cancer.12Zhu M, Qiu S et al. The associations between CYP24A1 polymorphisms and cancer susceptibility: a meta-analysis and trial sequential analysis. Pathology, Research and Practice. 2018 Jan;214(1):53-63.
- VDR Bsm1, Apa1, Fok1, and Poly (A) gene polymorphisms may be susceptible for breast cancer development.13Iqbal MUN, Khan TA. Association between vitamin D receptor Cdx2, Fok1, Bsm1, Apa1, Bgl1, Taq1, and Poly (A) gene polymorphism and breast cancer: a systematic review and meta-analysis. Tumour Biology. 2017 Oct;39(10):1010428317731280.
- Benefits from vitamin D3 supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype.14Barry EL, Peacock JL et al. Vitamin D receptor genotype, vitamin D3 supplementation, and risk of colorectal adenomas: a randomized clinical trial. Journal of the American Medical Association Oncology. 2017 May 1;3(5):628-635.
- The role of VDR FokI polymorphism may differ based on the type and severity of colorectal disease.15Cho YA, Lee J et al. Vitamin D receptor FokI polymorphism and the risks of colorectal cancer, inflammatory bowel disease, and colorectal adenoma. Scientific Reports. 2018 Aug 27;8(1):12899.
- VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms may confer susceptibility to hepatocellular carcinoma in certain populations.16Quan Y, Yang J, Qin T, Hu Y. Associations between twelve common gene polymorphisms and susceptibility to hepatocellular carcinoma: evidence from a meta-analysis. World Journal of Surgical Oncology. 2019 Dec 12;17(1):216.
- The F variant reduces the risk of cancer by 4%. This effect is particularly evident in female sex-associated cancers, but it is not observed in non-sex-associated cancers.17Laczmanski L, Lwow F et al. Association of the vitamin D receptor FokI gene polymorphism with sex- and non-sex-associated cancers: a meta-analysis. Tumour Biology. 2017 Oct;39(10):1010428317727164.
- The VDR rs2228570 polymorphism increased the risk of ovarian cancer in Caucasian populations in a dominant genetic model.18Chen H, Zhu J. Vitamin D receptor rs2228570 polymorphism and susceptibility to ovarian cancer: an updated meta-analysis. Journal of Obstetrics and Gynaecology Research. 2018 Mar;44(3):556-565.
- The vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype are associated with renal cell carcinoma risk.19Zhou T, Li H et ak. Association of methylenetetrahydrofolate reductase, vitamin D receptor, and interleukin-16 gene polymorphisms with renal cell carcinoma risk. Technology in Cancer Research & Treatment. 2019 Jan 1;18:1533033819859413.
- The VDR Bsm1 and Cdx2 polymorphisms decreased lung cancer risk, while the Taq1 polymorphism increased lung cancer risk. The AA genotype of the Apa1 and Bsm1 variants were protective factors in Asian populations, whereas the Fok1 and Taq1 polymorphisms were risk factors for lung cancer in Asian populations.20Duan GQ, Zheng X et al. The association between VDR and GC polymorphisms and lung cancer risk: a systematic review and meta-analysis. Genetic Testing and Molecular Biomarkers. 2020 May;24(5):285-295.
- Lung cancer risk varies by vitamin D receptor (VDR) genetic polymorphism.21Yu ZH, Chen M, Zhang QQ, Hu X. The association of vitamin D receptor gene polymorphism with lung cancer risk: an update meta-analysis. Combinatorial Chemistry & High Throughput Screening. 2018;21(10):704-710.
- The VDR variants FokI, ApaI and BsmI may influence the susceptibility to developing melanoma.22Birke M, Schöpe J, Wagenpfeil S, Vogt T, Reichrath J. Association of vitamin D receptor gene polymorphisms with melanoma risk: a meta-analysis and systematic review. Anticancer Research. 2020 Feb;40(2):583-595.
- The VDR rs2585428 SNP significantly decreased the risk of pancreas cancer.23Zhu M, Qiu S et al. The associations between CYP24A1 polymorphisms and cancer susceptibility: a meta-analysis and trial sequential analysis. Pathology, Research and Practice. 2018 Jan;214(1):53-63.
- A significant association is seen between VDR rs731236 and prostate cancer risk in Asians and African Americans, but rs1544410 was not associated with prostate cancer under three genetic models.24Liu S, Cai H et al. Association of VDR polymorphisms (Taq I and Bsm I) with prostate cancer: a new meta-analysis. Journal of International Medical Research. 2017 Feb;45(1):3-10.
Body terrain factors
- Genetic variants associated with low plasma 25(OH)D concentrations are associated with type 2 diabetes.25Afzal S, Brøndum-Jacobsen P, Bojesen SE, Nordestgaard BG. Vitamin D concentration, obesity, and risk of diabetes: a Mendelian randomisation study. Lancet Diabetes and Endocrinology. 2014 Apr;2(4):298-306.
- Compared with the controls (noncancer patients), heterozygote and dominant models with the VDR rs1544410 (BsmI) is likely the best genetic model for detecting the risk of ovarian cancer in Caucasian patients.26Li J, Li B et al. Do genetic polymorphisms of the vitamin D receptor contribute to breast/ovarian cancer? A systematic review and network meta-analysis. Gene. 2018 Nov 30;677:211-227.
- Vitamin D and its receptor VDR contribute to the protective process of probiotics.27Shang M, Sun J. Vitamin D/VDR, probiotics, and gastrointestinal diseases. Current Medicinal Chemistry. 2017;24(9):876-887.
- The association between insulin resistance-related diseases and VDR ApaI, BsmI, FokI variant was more obvious in dark-pigmented Caucasians and Asians but not in Caucasians with white skin.28Han FF, Lv Y et al. VDR gene variation and insulin resistance related diseases. Lipids in Health and Disease. 2017 Aug 19;16(1):157.
Notable preclinical evidence; clinical evidence is listed in How can vitamin D help me? What the research says ›
Treating cancer: preclinical evidence
- Vitamin D enhanced antitumor activity of docetaxel in an androgen-independent prostate cancer cell line in a preclinical study.29Ting HJ, Hsu J, Bao BY et al. Docetaxel-induced growth inhibition and apoptosis in androgen independent prostate cancer cells are enhanced by 1alpha, 25- dihydroxyvitamin D3. Cancer Letters. 2007;247:122–9.
- Calcitriol enhanced activity of docetaxel, paclitaxel, and platinum compounds in preclinical studies of prostate cancer.30Beer TM, Hough KM et al. Weekly high dose calcitriol and docetaxel in advanced prostate cancer. Seminars in Oncology. 2001;28(4 Suppl 15):49–55.
- Vitamin D3 with or without docetaxel was similarly effective in reducing CD34(+) cell levels within the spleen, lymph nodes, and tumor.31Young MR, Lathers DM. Combination docetaxel plus vitamin D(3) as an immune therapy in animals bearing squamous cell carcinomas. Otolaryngology—Head and Neck Surgery. 2005;133:611–8.
- Vitamin D signaling inhibits the expression of the tumor progression gene Id1, reducing breast cancer metastasis in preclinical studies.32Williams JD, Aggarwal A et al. Tumor autonomous effects of vitamin D deficiency promote breast cancer metastasis. Endocrinology. 2016 Apr;157(4):1341-7.
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