Vitamin D Toxicity–A Clinical Perspective

Abstract

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.

Activation of vitamin D in the gingival epithelium and its role in gingival inflammation and alveolar bone loss

“…While oral supplementation of vitamin D can lead to vitamin D sufficiency in vitamin D‐deficient individuals, including those with chronic periodontitis, the natural feedback mechanism based on the induction of the vitamin D 24‐hydroxylase enzyme guarantees that high concentrations of 1,25(OH) 2 D 3 will not occur in the gingival epithelium. Because of this, hypervitaminosis D and other side effects of high levels of supplementation are rare . However, to avoid both systemic feedback regulation and any potential systemic effects of supplementation, we propose that a topical administration of vitamin D could be useful.…”

“…Differences are significant, *P < 0.0001, by t test effects of high levels of supplementation are rare. 44 However, to avoid both systemic feedback regulation and any potential systemic effects of supplementation, we propose that a topical administration of vitamin D could be useful. However, 1,25(OH) 2 D 3 is highly labile and does not provide a strong foundation for a therapeutic agent.…”

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

“…Hypervitaminosis D is associated with hypercalcemia and other severe complications [442] and vitamin D overdoses can be fatal [443]. No current data support that rapid acute correction of VDD is an effective treatment in septic shock or improves outcomes of septic children.…”

An Evidence-Based Review of Efficacy and Safety of Dietary, Natural Supplements and Sunlight in Vitamin D Deficiency

“…Vitamin D toxicity can occur when blood 25(OH)D levels are 88 ng/mL or greater [15]. Symptoms may include sleepiness, vomiting, weakness, headache, nausea and constipation, and acute toxicity may cause hypercalcaemia and hypercalciuria.…”