The Dark Side of the Sunshine Vitamin

Authored by Vera Li, Human Biology, Health, and Society '26

Art by Angela Yuan, Biological Sciences '24

Current health and wellness trends are constantly touting the magical abilities of supplements to treat a myriad of ailments, from thin hair to weak bones. While supplementation may be helpful for those who are deficient in vitamins and minerals, over-supplementation is not discussed enough. Perhaps one of the most commonly misused supplements is vitamin D. Whereas the benefits of vitamin D are commendable, it is crucial to consider the risks associated with its overuse.

Vitamin D deficiency is a global problem [24, 7, 11, 17]. This may have prompted the significant increase in use of vitamin D therapies [5]. Population-based guidelines [18] and advice from chief medical officers [4] have also advocated for increased vitamin D supplementation. However, vitamin D toxicity is a potentially serious adverse effect of treatment that many are unaware of [22].

To understand vitamin D toxicity, one must understand the basic pathology of vitamin D supplementation. Vitamin D is mainly synthesized in the skin [24], where UV rays convert cholecalciferol, also known as vitamin D3, into 7-dehydrocholesterol through a carefully regulated enzymatic process to prevent accumulation of excess cholecalciferol [8]. 7-dehydrocholesterol is then converted into 25-hydroxy-cholecalciferol (25OHD) in the liver [24] and forms the active hormone, calcitriol. Calcitriol is the form that acts on vitamin D receptors in the body’s organs and maintains calcium homeostasis by increasing absorption of calcium and phosphorus from the gut [22]. Thus, as public health officials encourage people to avoid prolonged sun exposure, which reduces cholecalciferol levels, people often meet their vitamin D recommendations through supplements [18].

Excess vitamin D is associated with an increased absorption of calcium from the gut, causing an excess concentration of calcium in the bloodstream, a condition known as hypercalcaemia. Hypercalcaemia can cause a myriad of complications including depression, kidney stones, pancreatitis, irregular heartbeats and depression [19]. Additionally, excess vitamin D may increase bone resorption, or bone breakdown, which further increases calcium levels [20] and worsens by causing thirst and excess urination or more severe symptoms like seizures, coma and death.

There are various potential causes for vitamin D toxicity. Over-supplementation of vitamin D may occur not just through pills, but also through fortified foods if there are formulation or fortification errors. During early and widespread fortification of foods with vitamin D, there were numerous reports of vitamin D intoxication [9], which indicates errors in food manufacturing. Over-fortification of vitamin D in milk, for example, caused hypervitaminosis D in the local population, leading to at least 56 cases, with 41 hospitalizations and two deaths [1]. Unlicensed supplements also have a major impact on vitamin D toxicity. Inaccurate dosing of vitamin D can occur in the formulation of vitamin D supplements as well. Multiple studies have shown discrepancies in the actual dosage versus the stated dose of vitamin D in supplements. For instance, a New Zealand study of 14 (12 unlicensed and 2 licensed) vitamin D3 supplements found that only eight were within 10% of the stated dose [6], and a US study discovered that of the 15 vitamin D3 supplements studied, there was substantial variation compared with the stated dose, both between pills from the same bottle and between separate bottles [15].

Inappropriate prescription or dispensing of vitamin D supplements is also a factor. High vitamin D toxicity is associated with high-dose over-the-counter supplements [3] being taken too frequently, prescribed incorrectly by the physician [10, 12, 23], and filled incorrectly by the pharmacist [2].

Finally, the inappropriate administration of vitamin D is a risk factor for toxicity. Vitamin D cannot and should not be administered without careful thought regarding the population receiving the treatment. For instance, one study found that a mother who was on a vitamin D prescription of 400 IU per 1 mL daily was using a supplement that was 400 IU per drop, meaning she took 30 times more vitamin D than she was supposed to. The excess vitamin D was present in her breast milk [21]. Additionally, most premature infant formulas have high vitamin D levels, which are safe for short durations but must be monitored carefully because prolonged intake could result in excess vitamin D levels [16], which could result in consequences like feeding intolerance, vomiting, and diarrhea [14, 13].

Too much of a good thing exists when it comes to vitamin D. Despite the health benefits that vitamin D can provide, it is important to be cognizant of side effects, and one should always speak with a medical professional before starting any supplement regimen.

Works Cited

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2. Carlton, S., Clopton, D., & Cappuzzo, K. A. (2010). Vitamin D deficiency: appropriate replenishment therapies and the effects of vitamin D toxicity. The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists, 25(3), 171–177. https://doi.org/10.4140/TCP.n.2010.171

3. Chatterjee, R., Chatterjee, K., & Sen, C. (2017). Reversible Parkinsonism Due to Vitamin D Toxicity. Journal of neurosciences in rural practice, 8(2), 305–306. https://doi.org/10.4103/jnrp.jnrp_497_16

4. Davies, S. C., Jewell, T., McBride, M., & Burns, H. (2012). Vitamin D—advice on supplements for at risk groups. London: Department of Health, 1-4.

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6. Garg, S., Sabri, D., Kanji, J., Rakkar, P. S., Lee, Y., Naidoo, N., & Svirskis, D. (2013). Evaluation of vitamin D medicines and dietary supplements and the physicochemical analysis of selected formulations. The journal of nutrition, health & aging, 17(2), 158–161. https://doi.org/10.1007/s12603-012-0090-4

7. Grace, C., Vincent, R., & Aylwin, S. J. (2014). High prevalence of vitamin D insufficiency in a United Kingdom urban morbidly obese population: implications for testing and treatment. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 10(2), 355–360. https://doi.org/10.1016/j.soard.2013.07.017

8. Holick M. F. (1987). Photosynthesis of vitamin D in the skin: effect of environmental and life-style variables. Federation proceedings, 46(5), 1876–1882.

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10. Jacobsen, R. B., Hronek, B. W., Schmidt, G. A., & Schilling, M. L. (2011). Hypervitaminosis D associated with a vitamin D dispensing error. The Annals of pharmacotherapy, 45(10), e52. https://doi.org/10.1345/aph.1Q330

11. Janner, M., Ballinari, P., Mullis, P. E., & Flück, C. E. (2010). High prevalence of vitamin D deficiency in children and adolescents with type 1 diabetes. Swiss medical weekly, 140, w13091. https://doi.org/10.4414/smw.2010.13091

12. Kaur, P., Mishra, S. K., & Mithal, A. (2015). Vitamin D toxicity resulting from overzealous correction of vitamin D deficiency. Clinical endocrinology, 83(3), 327–331. https://doi.org/10.1111/cen.12836

13. Ketha, H., Wadams, H., Lteif, A., & Singh, R. J. (2015). Iatrogenic vitamin D toxicity in an infant--a case report and review of literature. The Journal of steroid biochemistry and molecular biology, 148, 14–18. https://doi.org/10.1016/j.jsbmb.2015.01.022

14. Khadgawat, R., Goswami, R., Gupta, N., Seith, A., & Mehta, A. P. (2007). Acute vitamin d toxicity in an infant. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 16(4), 89–93. https://doi.org/10.1297/cpe.16.89

15. LeBlanc, E. S., Perrin, N., Johnson, J. D., Jr, Ballatore, A., & Hillier, T. (2013). Over-the-counter and compounded vitamin D: is potency what we expect?. JAMA internal medicine, 173(7), 585–586. https://doi.org/10.1001/jamainternmed.2013.3812

16. Nako, Y., Tomomasa, T., & Morikawa, A. (2004). Risk of hypervitaminosis D from prolonged feeding of high vitamin D premature infant formula. Pediatrics international : official journal of the Japan Pediatric Society, 46(4), 439–443. https://doi.org/10.1111/j.1442-200x.2004.01919.x

17. Palacios, C., & Gonzalez, L. (2014). Is vitamin D deficiency a major global public health problem?. The Journal of steroid biochemistry and molecular biology, 144 Pt A, 138–145. https://doi.org/10.1016/j.jsbmb.2013.11.003

18. Scientific Advisory Committee on Nutrition . Vitamin D and Health. London, 2016. Available at https://www.gov.uk/government/groups/scientific-advisory-committee-on-nutrition (last accessed 1 October 2017)

19. Sadiq NM, Naganathan S, Badireddy M. Hypercalcemia. [Updated 2022 Sep 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430714/

20. Selby, P. L., Davies, M., Marks, J. S., & Mawer, E. B. (1995). Vitamin D intoxication causes hypercalcaemia by increased bone resorption which responds to pamidronate. Clinical endocrinology, 43(5), 531–536. https://doi.org/10.1111/j.1365-2265.1995.tb02916.x

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23. Wani, M., Wani, I., Banday, K., & Ashraf, M. (2016). The other side of vitamin D therapy: a case series of acute kidney injury due to malpractice-related vitamin D intoxication. Clinical nephrology, 86 (2016)(11), 236–241. https://doi.org/10.5414/CN108904

24. Zgaga, L., Theodoratou, E., Farrington, S. M., Agakov, F., Tenesa, A., Walker, M., Knox, S., Wallace, A. M., Cetnarskyj, R., McNeill, G., Kyle, J., Porteous, M. E., Dunlop, M. G., & Campbell, H. (2011). Diet, environmental factors, and lifestyle underlie the high prevalence of vitamin D deficiency in healthy adults in Scotland, and supplementation reduces the proportion that are severely deficient. The Journal of nutrition, 141(8), 1535–1542. https://doi.org/10.3945/jn.111.140012