Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports

Galior, Kornelia; Grebe, Stefan K.; Singh, Ravinder J.

doi:10.3390/nu10080953

Cited by 139 publications

(105 citation statements)

References 35 publications

(35 reference statements)

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“…An overview of VDT cases caused by vitamin D formulation or administration errors that resulted in excessive dosing confirmed that intoxication is extremely rare. However, VDT should always be considered as a differential diagnosis in patients with hypercalcemia ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Toxicity–A Clinical Perspective

Marcinowska-Suchowierska

et al. 2018

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Confusion, apathy, recurrent vomiting, abdominal pain, polyuria, polydipsia, and dehydration are the most often noted clinical symptoms of vitamin D toxicity (VDT; also called vitamin D intoxication or hypervitaminosis D). VDT and its clinical manifestation, severe hypercalcemia, are related to excessive long-term intake of vitamin D, malfunctions of the vitamin D metabolic pathway, or the existence of coincident disease that produces the active vitamin D metabolite locally. Although VDT is rare, the health effects can be serious if it is not promptly identified. Many forms of exogenous (iatrogenic) and endogenous VDT exist. Exogenous VDT is usually caused by the inadvertent or improper intake of extremely high doses of pharmacological preparations of vitamin D and is associated with hypercalcemia. Serum 25-hydroxyvitamin D [25(OH)D] concentrations higher than 150 ng/ml (375 nmol/l) are the hallmark of VDT due to vitamin D overdosing. Endogenous VDT may develop from excessive production of an active vitamin D metabolite – 1,25(OH)2D in granulomatous disorders and in some lymphomas or from the reduced degradation of that metabolite in idiopathic infantile hypercalcemia. Endogenous VDT may also develop from an excessive production of 25(OH)D and 1,25(OH)2D in congenital disorders, such as Williams–Beuren syndrome. Laboratory testing during routine clinical examinations may reveal asymptomatic hypercalcemia caused by the intake of vitamin D even in doses recommended for the general population and considered safe. That phenomenon, called hypersensitivity to vitamin D, reflects dysregulated vitamin D metabolism. Researchers have proposed many processes to explain VDT. Those processes include elevated activity of 1α-hydroxylase or inhibited activity of 24-hydroxylase, both leading to increased concentration of 1,25(OH)D; increased number of vitamin D receptors; and saturation of the capacity of vitamin D binding protein. Increased public awareness of vitamin D–related health benefits might increase the risk of VDT due to self-administration of vitamin D in doses higher then recommended for age and body weight or even higher than the established upper limit intake values. Consequently, the incidence of hypercalcemia due to hypervitaminosis D might increase.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Toxicity–A Clinical Perspective

Marcinowska-Suchowierska

et al. 2018

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“…Vitamin D intoxication is rare and usually only occurs at very high supplementation doses [109]. However, various mutations in vitamin D metabolizing enzymes that may lead to increased sensitivity to standard vitamin D supplementation or even endogenous vitamin D intoxication with hypercalcemia, hypercalciuria, and nephrocalcinosis/ chronic renal insufficiency have been described [110].…”

Section: Vitamin D Intoxication and Hypersensitivitymentioning

confidence: 99%

Vitamin D deficiency 2.0: an update on the current status worldwide

et al. 2020

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Vitamin D testing and the use of vitamin D supplements have increased substantially in recent years. Currently, the role of vitamin D supplementation, and the optimal vitamin D dose and status, is a subject of debate, because large interventional studies have been unable to show a clear benefit (in mostly vitamin D replete populations). This may be attributed to limitations in trial design, as most studies did not meet the basic requirements of a nutrient intervention study, including vitamin D-replete populations, too small sample sizes, and inconsistent intervention methods regarding dose and metabolites. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] < 50 nmol/L or 20 ng/ml) is associated with unfavorable skeletal outcomes, including fractures and bone loss. A 25(OH)D level of >50 nmol/L or 20 ng/ml is, therefore, the primary treatment goal, although some data suggest a benefit for a higher threshold. Severe vitamin D deficiency with a 25(OH)D concentration below <30 nmol/L (or 12 ng/ml) dramatically increases the risk of excess mortality, infections, and many other diseases, and should be avoided whenever possible. The data on a benefit for mortality and prevention of infections, at least in severely deficient individuals, appear convincing. Vitamin D is clearly not a panacea, and is most likely efficient only in deficiency. Given its rare side effects and its relatively wide safety margin, it may be an important, inexpensive, and safe adjuvant therapy for many diseases, but future large and well-designed studies should evaluate this further. A worldwide public health intervention that includes vitamin D supplementation in certain risk groups, and systematic vitamin D food fortification to avoid severe vitamin D deficiency, would appear to be important. In this narrative review, the current international literature on vitamin D deficiency, its relevance, and therapeutic options is discussed.

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“…Of course, well-documented human trials examining the effect of excessive doses of vitamin D are ethically impossible so that there is a paucity of evidence regarding the exact mechanism by which vitamin D intake causes toxicity. From published reports, though, it is clear that vitamin D toxicity can occur via ingestion of over the counter products such as Soladex, that contains over 800,000 IU of vitamin D per dose [38]. Genetic disorders in which vitamin D is not normally metabolized can lead to excessive amounts of 1,25(OH)2D, despite normal intake of vitamin D [39].…”

Section: Threshold For Defining Vitamin D Excessmentioning

confidence: 99%

Consensus statement from 2nd International Conference on Controversies in Vitamin D

Giustina

Adler

Binkley

et al. 2020

Rev Endocr Metab Disord

224

169

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The 2 nd International Conference on Controversies in Vitamin D was held in Monteriggioni (Siena), Italy, September 11-14, 2018. The aim of this meeting was to address ongoing controversies and timely topics in vitamin D research, to review available data related to these topics and controversies, to promote discussion to help resolve lingering issues and ultimately to suggest a research agenda to clarify areas of uncertainty. Several issues from the first conference, held in 2017, were revisited, such as assays used to determine serum 25-hydroxyvitamin D [25(OH)D] concentration, which remains a critical and controversial issue for defining vitamin D status. Definitions of vitamin D nutritional status (i.e. sufficiency, insufficiency and deficiency) were also revisited. New areas were reviewed, including vitamin D threshold values and how they should be defined in the context of specific diseases, sources of vitamin D and risk factors associated with vitamin D deficiency. Non-skeletal aspects related to vitamin D were also discussed, including the reproductive system, neurology, chronic kidney disease and falls. The therapeutic role of vitamin D and findings from recent clinical trials were also addressed. The topics were considered by 3 focus groups and divided into three main areas: 1) "Laboratory": assays and threshold values to define vitamin D status; 2) "Clinical": sources of vitamin D and risk factors and role of vitamin D in non-skeletal disease and 3) "Therapeutics": controversial issues on observational studies and recent randomized controlled trials. In this report, we present a summary of our findings.

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Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports

Cited by 139 publications

References 35 publications

Vitamin D Toxicity–A Clinical Perspective

Vitamin D Toxicity–A Clinical Perspective

Vitamin D deficiency 2.0: an update on the current status worldwide

Consensus statement from 2nd International Conference on Controversies in Vitamin D

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