Vitamin D Toxicity: A Comprehensive Review

Authors

  • Barakat Wathiq Alawadi Department of Pharmacology and Toxicology, College of Pharmacy, Ahl Al-Bayt University, Karbala 56001, Iraq Author
  • Zahraa Jasim Abed Department of Pharmacognosy, College of Pharmacy, Ahl Al-Bayt University, Karbala 56001, Iraq Author

DOI:

https://doi.org/10.59675/U324

Keywords:

Vitamin D toxicity; Hypervitaminosis D; Hypercalcemia; Vitamin D overdose; Calcium metabolism

Abstract

Although very infrequent, vitamin D toxicity is an important clinical issue that has serious clinical implications. This is a disease mainly caused by overdosing on the supplement and is expressed through hypercalcemia and the related complications. Clinical manifestation extends from very mild gastrointestinal symptoms to cardiovascular and renal dysfunction that is life-threatening. Healthcare providers need to understand the pathophysiology, risk factors, clinical presentation, and treatment measures. This review will analyze the existing data on vitamin D toxicity with a focus on its biochemical pathways, diagnostic skills, and treatment care.

Downloads

Download data is not yet available.

References

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–281.

Galior K, Grebe S, Singh R. Development of vitamin D toxicity from overcorrection of vitamin D deficiency: a review of case reports. Nutrients. 2018;10(8):953.

Marcinowska-Suchowierska E, Kupisz-Urbańska M, Łukaszkiewicz J, Płudowski P, Jones G. Vitamin D toxicity—a clinical perspective. Front Endocrinol. 2018;9:550.

Koul PA, Ahmad SH, Ahmad F, Jan RA, Shah SU, Khan UH. Vitamin D toxicity in adults: a case series from an area with endemic hypovitaminosis D. Oman Med J. 2011;26(3):201–204.

Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88(2):582S–586S.

Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319–329.

Vieth R. Vitamin D toxicity, policy, and science. J Bone Miner Res. 2007;22(Suppl 2):V64–V68.

Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96(1):365–408.

Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the tumor necrosis factor receptor and ligand families. Endocr Rev. 1999;20(3):345–357.

Tebben PJ, Singh RJ, Kumar R. Vitamin D-mediated hypercalcemia: mechanisms, diagnosis, and treatment. Endocr Rev. 2016;37(5):521–547.

Karhapää P, Pihlajamäki J, Pörsti I, Kastarinen M, Mustonen J, Niemelä O, et al. Diverse associations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with dyslipidaemias. J Intern Med. 2010;268(6):604–610.

Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014;83(10):920–928.

Alon DB, Chaimovitz C, Dvilansky A, Lugassy G, Douvdevani A, Shany S, et al. Novel role of 1,25(OH)₂D₃ in induction of erythroid progenitor cell proliferation. Exp Hematol. 2002;30(5):403–409.

Pietras SM, Obayan BK, Cai MH, Holick MF. Vitamin D₂ treatment for vitamin D deficiency and insufficiency for up to 6 years. Arch Intern Med. 2009;169(19):1806–1808.

Taylor PN, Davies JS. A review of the growing risk of vitamin D toxicity from inappropriate practice. Br J Clin Pharmacol. 2018;84(6):1121–1127.

Kim GH. Renal effects of prostaglandins and cyclooxygenase-2 inhibitors. Electrolyte Blood Press. 2008;6(1):35–41.

Leaf DE, Korets R, Taylor EN, Tang J, Asplin JR, Goldfarb DS, et al. Effect of vitamin D repletion on urinary calcium excretion among kidney stone formers. Clin J Am Soc Nephrol. 2012;7(5):829–834.

Khan AH, Rohra DK, Satyapal KS, Marais D. Correlation of ultrasonographically detectable medullary nephrocalcinosis in AIDS patients and the use of indinavir. Clin Radiol. 2006;61(1):73–80.

Jorde R, Kubiak J. No improvement in depressive symptoms by vitamin D supplementation: results from a randomised controlled trial. J Nutr Sci. 2018;7: e30.

Judd SE, Tangpricha V. Vitamin D deficiency and risk for cardiovascular disease. Am J Med Sci. 2009;338(1):40–44.

Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D₃ intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001;73(2):288–294.

Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington (DC): National Academies Press; 2011.

Vogiatzi MG, Jacobson-Dickman E, DeBoer MD. Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature. J Clin Endocrinol Metab. 2014;99(4):1132–1141.

Bilezikian JP. Management of acute hypercalcemia. N Engl J Med. 1992;326(18):1196–1203.

Kamycheva E, Sundsfjord J, Jorde R. Serum parathyroid hormone level is associated with body mass index: the 5th Tromsø study. Eur J Endocrinol. 2004;151(2):167–172.

Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–612.

Lemann J Jr, Pleuss JA, Worcester EM, Hornick L, Schrab D, Hoffmann RG. Urinary oxalate excretion increases with body size and decreases with increasing dietary calcium intake among healthy adults. Kidney Int. 1996;49(1):200–208.

Goldberger ZD, Whiting SM, Howell MD, Gibbons FK, Lilly CM, Eisenberg MJ, et al. Prevalence of long QT syndrome in unselected area-based population registries. J Am Coll Cardiol. 2011;58(4):392–398.

Sharma LK, Dutta D, Sharma N, Gadpayle AK. The increasing problem of subclinical and overt hypervitaminosis D in India. Nutrition. 2017;34:76–81.

Araki T, Holick MF, Alfonso BD, Charlap E, Romero CM, Rizk D, et al. Vitamin D intoxication with severe hypercalcemia due to manufacturing and labeling errors of dietary supplements. J Clin Endocrinol Metab. 2011;96(12):3603–3608.

Adams JS, Sharma OP, Gacad MA, Singer FR. Metabolism of 25-hydroxyvitamin D₃ by cultured pulmonary alveolar macrophages in sarcoidosis. J Clin Invest. 1983;72(5):1856–1860.

Bikle DD. Extraskeletal actions of vitamin D. Ann N Y Acad Sci. 2016;1376(1):29–52.

Bhattoa HP, Konstantynowicz J, Laszcz N, Wojcik M, Pludowski P. Vitamin D: musculoskeletal health. Rev Endocr Metab Disord. 2017;18(3):363–371.

Pepe J, Colangelo L, Biamonte F, Sonato C, Danese VC, Cecchetti V, et al. Diagnosis and management of hypocalcemia. Endocrine. 2020;69(3):485–495.

LeGrand SB, Leskuski D, Zama I. Furosemide for hypercalcemia: an unproven yet common practice. Ann Intern Med. 2008;149(4):259–263.

Stewart AF. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373–379.

Suki WN, Yium JJ, Von Minden M, Saller-Hebert C, Eknoyan G, Martinez-Maldonado M. Acute treatment of hypercalcemia with furosemide. N Engl J Med. 1970;283(16):836–840.

Adams JS, Gacad MA. Characterization of 1-α-hydroxylation of vitamin D₃ sterols by alveolar macrophages from sarcoidosis patients. J Exp Med. 1985;161(4):755–765.

Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD, et al. Zoledronic acid versus pamidronate in hypercalcemia of malignancy. J Clin Oncol. 2001;19(2):558–567.

Hosking DJ, Cowley A, Bucknall CA. Rehydration in the treatment of severe hypercalcaemia. Q J Med. 1981;50(200):473–481.

Nemeth EF, Shoback D. Calcimimetic and calcilytic drugs for bone and mineral disorders. Best Pract Res Clin Endocrinol Metab. 2013;27(3):373–384.

Tzanakis I, Virvidakis K, Tsomi A, Mantakas E, Girousis N, Karefylakis N, et al. Intra- and interdialytic calcium mass balance in hemodialysis. Am J Nephrol. 2005;25(6):545–549.

Selby PL, Davies M, Marks JS, Mawer EB. Vitamin D intoxication causes hypercalcaemia by increased bone resorption. Clin Endocrinol. 1995;43(5):531–536.

Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85(1):6–18.

Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D. J Clin Endocrinol Metab. 2011;96(1):53–58.

Rosen CJ. Vitamin D insufficiency. N Engl J Med. 2011;364(3):248–254.

Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med. 2001;345(1):66–67.

Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IR. High-dose oral vitamin D₃ supplementation in the elderly. Osteoporos Int. 2009;20(8):1407–1415.

Sharma OP. Hypercalcemia in granulomatous disorders. Curr Opin Pulm Med. 2000;6(5):442–447.

Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, et al. Serum 25-hydroxyvitamin D levels after ergocalciferol and cholecalciferol supplementation. Bone. 2009;45(5):870–875.

Published

30-12-2025

Issue

Section

Articles

How to Cite

Barakat Wathiq Alawadi, & Zahraa Jasim Abed. (2025). Vitamin D Toxicity: A Comprehensive Review. Academic International Journal of Medical Update, 3(02), 28-33. https://doi.org/10.59675/U324
Views: 30 / Download: 12