Excessive vitamin D intake can lead to vitamin D toxicity. The 25-OH metabolite plays a key role in vitamin D intoxication by competing for intracellular receptors, inducing responses normally caused by 1,25-(OH)2-D3. This leads to hypercalcemia through increased calcium absorption and bone resorption, decreasing PTH and kidney function and disrupting calcium homeostasis. Long-term effects include calcinosis, the deposition of calcium and phosphorus in soft tissues like the heart and kidneys. Risk depends on calcium and phosphorus intake in addition to vitamin D exposure.

1. Vitamin D toxicity
Domina Petric, MD

2. Vitamin D toxicity
• Excessive intakes of vitamin D are associated
with increases in circulating levels of 25-OH-D3.
• The 25-OH metabolite is believed to be the
critical metabolite in vitamin D intoxication.
• At high levels, it appears to compete
successfully for intracellular receptors for
1,25-(OH)2-D3, thus inducing the responses
normally produced by the latter metabolite.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
2

3. Vitamin D toxicity
• Hypervitaminosis D involves increased enteric
absorption and bone resorption of calcium,
producing hypercalcemia, with attendant
decreases in serum PTH and glomerular
filtration rate and, ultimately, loss of calcium
homeostasis.
• The mobilization of bone also results in
increased serum concentrations of zinc from
that reserve.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3

4. Signs of hypervitaminosis D
Anorexia
Gastrointestinal
distress
Nausea and
vomiting
Headache Weakness,
lameness
Polyuria,
polydypsia
Nervousness Hypercalcemia Calcinosis
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4

5. Vitamin D toxicity
• With chronically elevated serum calcium
and phosphorus levels, the ultimate
result is calcinosis.
• Calcinosis is the deposition of calcium and
phosphate in soft tissues, especially heart
and kidney, but also the vascular and
respiratory systems and all other tissues.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5

6. Calcinosis cutis
Dermatologyadvisor.com
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

7. Vitamin D toxicity
The risk of hypervitaminosis
D is dependent not only on
exposure to vitamin D, but
also on concomitant intakes
of calcium and phosphorus!
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

8. Vitamin D hypersensitivity
• Vitamin D hypersensitivity has been
proposed as the basis for Williams-Beuren
syndrome.
• It is a rare (1:47,000) condition of
hypercalcemia and calcium hyperabsorption.
• The syndrome is manifested in infancy.
• It is characterized by failure to thrive with
mental handicap and long-term morbidity.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8

9. Vitamin D hypersensitivity
Patients have been found to
have normal circulating levels
of 25-OH-D3, but they appear
to have exaggerated responses
to oral doses of vitamin D3.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

10. Literature
• Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
April 10, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10