Some people taking 1 million IU of Vitamin D were hypercalcemic for a while

Created September 2021

Biochemical characteristics and calcium and PTH levels of patients with high normal and elevated serum 25(OH)D levels in Turkey: DeVIT-TOX survey

Arch Osteoporos. 2021 Sep 18;16(1):138. doi: 10.1007/s11657-021-01002-8.

Zafer Pekkolay 1, Dilek Gogas Yavuz 2, Emre Sedar Saygılı 3, Ceyla Konca Değertekin 4, Ömercan Topaloğlu 5, Çağatay Emir Önder 6, Hikmet Soylu 7, Işılay Taskaldıran 6, Ayşe Esen Pazır 8, Kader Uğur 9, Seher Tanrıkulu 10, Sevde Nur Fırat 6, Burcu Meryem Atak 11, Adnan Batman 12, Tülay Omma 6, Eylem Cağıltay 13, Nilüfer Özdemir 14, Seher Çetinkaya Altuntaş 15, Narin Nasıroğlu İmga 16, Ersen Karakılıç 3, Zeliha Hekimsoy 14, Faruk Kılınç 9, Adnan Yay 13, Mustafa Eroğlu 17, Alpaslan Kemal Tuzcu 18

Overview Toxicity of vitamin D has the following chart image Items in both categories Toxicity and Calcium are listed here: {category}

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment.

Purpose: We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels.

Methods: An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149-100 ng/mL; and group 3, 99-88 ng/mL.

Results: A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88-455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1-13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p < 0.05).

The most common cause (73.5%) associated with high serum 25(OH)D levels was the inappropriate prescription of a high dose of oral vitamin D (600.000-1.500.000 IU) for treating vitamin D deficiency/insufficiency in a short time (1-3 months). The cut-off value of 25 (OH) D level in patients with hypercalcemia was found to be 89 ng/mL [median 116.5 (89-216)].

Conclusions: High dose of vitamin D intake is associated with a high serum 25 OH D level, without symptoms of hypercalcemia. Inappropriate prescription of vitamin D is the primary cause for elevated 25(OH) D levels and related hypercalcemia. Hypercalcemia may not be observed in every patient at very high 25(OH) D levels. Adherence to the recommendation of guidelines is essential to ensure safe and effective treatment of vitamin D deficiency.

References

  1. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al (2011) Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930. https://doi.org/10.1210/jc.2011-0385 - DOI - PubMed

  2. Matsui MS (2020) Vitamin D update. Curr Derm Rep 9:323–330. https://doi.org/10.1007/s13671-020-00315-0 - DOI

  3. Berridge MJ (2017) Vitamin D deficiency and diabetes. Biochem J 474:1321–1332. https://doi.org/10.1042/BCJ20170042 - DOI - PubMed

  4. Sassi F, Tamone C, D’Amelio P (2018) Vitamin D: nutrient, hormone, and immunomodulator. Nutrients 10(11):1656. https://doi.org/10.3390/nu10111656 - DOI - PMC

  5. Alfredsson L, Armstrong BK, Butterfield DA, Chowdhury R, de Gruijl FR, Feelisch M, … Young AR (2020) Insufficient sun exposure has become a real public health problem. Int J Environ Res Public Health 17(14):5014. https://doi.org/10.3390/ijerph17145014

  6. Mirhosseini N, Rainsbury J, Kimball SM (2018) Vitamin D supplementation, serum 25(OH)D concentrations and cardiovascular disease risk factors: a systematic review and meta-analysis. Front Cardiovasc Med 12(5):87. https://doi.org/10.3389/fcvm.2018.00087 - DOI

  7. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B et al (2019) Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev 40:1109–1151. https://doi.org/10.1210/er.2018-00126 - DOI - PubMed

  8. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S et al (2019) Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 380:33–44 - DOI

  9. Lips P, Bilezikian JP, Bouillon R (2019) Vitamin D: giveth to those who needeth. JBMR Plus 4(1):e10232. https://doi.org/10.1002/jbm4.10232 - DOI - PubMed - PMC

  10. Holick MF (2017) The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 18(2):153–165. https://doi.org/10.1007/s11154-017-9424-1 - DOI - PubMed - PMC

  11. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281. https://doi.org/10.1056/NEJMra070553 - DOI - PubMed

  12. Pludowski P, Holick MF, Grant WB, Konstantynowicz J, Mascarenhas MR, Haq A et al (2018) Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol 175:125–135. https://doi.org/10.1016/j.jsbmb.2017.01.021 - DOI - PubMed

  13. Jorde R, Sollid ST, Svartberg J, Schirmer H, Joakimsen RM, Njolstad I et al (2016) Vitamin D 20,000 IU per week for five years does not prevent progression from prediabetes to diabetes. J Clin Endocrinol Metab 101:1647–1655. https://doi.org/10.1210/jc.2015-4013 - DOI - PubMed

  14. Scragg R, Khaw KT, Toop L, Sluyter J, Lawes CMM, Waayer D et al (2018) Monthly high-dose vitamin D supplementation and cancer risk: a post hoc analysis of the vitamin D assessment randomized clinical trial. JAMA Oncol 4(11):e182178. https://doi.org/10.1001/jamaoncol.2018.2178 - DOI - PubMed - PMC

  15. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, Staehelin HB, Meyer OW, Theiler R et al (2016) Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med 176(2):175–183. https://doi.org/10.1001/jamainternmed.2015.7148 - DOI - PubMed

  16. Khaw KT, Stewart AW, Waayer D, Lawes CMM, Toop L, Camargo CA Jr et al (2017) Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post-hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial. Lancet Diabetes Endocrinol 5(6):438–447. https://doi.org/10.1016/S2213-8587(17)30103-1 - DOI - PubMed

  17. Pludowski P, Grant WB, Konstantynowicz J, Holick MF (2019) Editorial: classic and pleiotropic actions of vitamin D. Front Endocrinol (Lausanne) 10:341. https://doi.org/10.3389/fendo.2019.00341 - DOI

  18. Marcinowska-Suchowierska E, Kupisz-Urbańska M, Łukaszkiewicz J, Płudowski P, Jones G (2018) Vitamin D toxicity-a clinical perspective. Front Endocrinol (Lausanne) 9:550. https://doi.org/10.3389/fendo.2018.00550 - DOI

  19. Ozkan B, Hatun S, Bereket A (2012) Vitamin D intoxication. Turk J Pediatr 54:93–98 - PubMed

  20. Taylor PN, Davies JS (2018) A review of the growing risk of vitamin D toxicity from inappropriate practice. Br J Clin Pharmacol 84:1121–1127. https://doi.org/10.1111/bcp.13573 - DOI - PubMed - PMC

  21. Varimli D (2021) Ülkemizde D Vitamini Reçetelemesinin ve Tüketiminin Değerlendirilmesi. Thesis, Haceetepe University, Ankara, Turkey

  22. Płudowski P, Karczmarewicz E, Bayer M, Carter G, Chlebna-Sokół D, Czech-Kowalska J et al (2013) Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Endokrynol Pol 64(4):319–327. https://doi.org/10.5603/ep.2013.0012 - DOI - PubMed

  23. Kucukerdem HS, Arslan M, Koc EM, Can H (2017) Retrospective evaluation of family medicine outpatient clinic profile at a tertiary hospital in İzmir. J Acad Res Med 7(3):112–116. https://doi.org/10.5152/jarem.2017.1165 - DOI

  24. Al-Yatama FI, AlOtaibi F, Al-Bader MD, Al-Shoumer KA (2019) The effect of clothing on vitamin d status, bone turnover markers, and bone mineral density in young Kuwaiti females. Int J Endocrinol 2019:6794837. https://doi.org/10.1155/2019/6794837 - DOI - PubMed - PMC

  25. Buyukuslu N, Esin K, Hizli H, Sunal N, Yigit P, Garipagaoglu M (2014) Clothing preference affects vitamin D status of young women. Nutr Res 34(8):688–693. https://doi.org/10.1016/j.nutres.2014.07.012 - DOI - PubMed

  26. Bassil D, Rahme M, Hoteit M, Fuleihan Gel-H (2013) Hypovitaminosis D in the Middle East and North Africa: prevalence, risk factors and impact on outcomes. Dermatoendocrinol. 5(2):274–298. https://doi.org/10.4161/derm.25111 - DOI - PubMed - PMC

  27. Lips P, Cashman KD, Lamberg-Allardt C, Bischoff-Ferrari HA, Obermayer-Pietsch B, Bianchi ML, … Bouillon R (2019) Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society. Eur J Endocrinol 180(4):P23–P54. https://doi.org/10.1530/eje-18-0736

  28. Galior K, Grebe S, Singh R (2018) Development of vitamin D toxicity from overcorrection of vitamin D deficiency: a review of case reports. Nutrients 10(8):953. https://doi.org/10.3390/nu10080953 - DOI - PMC

  29. Amrein K, Sourij H, Wagner G, Holl A, Pieber TR, Smolle KH et al (2011) Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care 15(2):R104. https://doi.org/10.1186/cc10120 - DOI - PubMed - PMC

  30. Balk EM, Adam GP, Langberg VN, Earley A, Clark P, Ebeling PR et al (2017) Global dietary calcium intake among adults: a systematic review. Osteoporos Int 28:3315–3324. https://doi.org/10.1007/s00198-017-4230-x - DOI - PubMed - PMC

  31. Ersoy B, Kizilay DÖ, Yilmaz SK, Taneli F, Gümüşer G (2018) Bone mineral density, vitamin D status, and calcium intake in healthy female university students from different socioeconomic groups in Turkey. Arch Osteoporos 13:135. https://doi.org/10.1007/s11657-018-0482-0 - DOI - PubMed

  32. Kaur P, Mishra SK, Mithal A (2015) Vitamin D toxicity resulting from overzealous correction of vitamin D deficiency. Clin Endocrinol (Oxf) 83:327–331. https://doi.org/10.1111/cen.12836 - DOI

Tags: Calcium Toxicity