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DRI Dietary Reference Intakes Calcium Vitamin D
G
Cases Studies of Vitamin D Toxicity
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DRI Dietary Reference Intakes Calcium Vitamin D
TABLE G-1 Case Studies of Vitamin D Toxicity
Study
Patient/Population
Preparation; Dose
Duration
Children
Djamil and Tu-Tunji. 1931. Lancet letter to the editor
2-yr-old male
Vigantol (irradiated ergosterol); 3 tsp
1 d
1947. BMJ letter to editor
Not specified
Cod liver oil
Ross. 1952. Journal of Pediatrics :815-822
4 infants ages 8-14 mo
Irradited ergosterol containing an estimated 30,000–40,000 IU vitamin
Daily for 8-12 mo
Jacqz et al. 1985
Infants with hypercalcemia (2 cases with vitamin D toxicity)
Vitamin D and calcium supplementation
Case 1: 3 mo old
Case 2: 7 mo old
300 μg D3
Besbas et al. 1989. Turkish J Pediatrics 31:239-244
Case 1: 3 mo old
Vitamin D: 45,000 IU/d
45 d
Case 2: 4 mo old
Vitamin D: 60,000 IU/d
30 d
Dent. 1964. BMJ letter to editor
6 yr old
Vitamin D (Calciferol Tablets B.P.): 1.25 mg. (~50,000 IU)/d
9 mo
Counts et al. 1975. Ann Internal Med 82:196-200
4-yr-old male
Vitamin D2 (Drisdol): 50,000 up to 100,000 IU/d
2 mo following bilateral nephrectomy
DeWind. 1960. Arch Dis Child 36:373-380
5.5 yr old
Vitamin D: 100,000 IU + cod liver oil-2 T + multivitamin
daily × 2–3 mo; and continued intake of tx vitamin D for 1 yr after hospitalization
Barrueto et al. 2005. Pediatrics 116:e453-e456
2-yr-old male
Vitamin D (ergocalciferol): 2,400,000 IU
4 d
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DRI Dietary Reference Intakes Calcium Vitamin D
Serum Calcium
Serum 25(OH)D
Symptoms/Health Effects
Edema and albuminuria
Response from editor: A toxic dose of more than 200,000 units would only be achieved with ingestion of 2.65 L cod liver oil/d
18–19 mg/dL
All presented with anorexia, weight loss, weakness; 2 infants recovered within 6–9 mo following removal of vitamin D; 2 infants died: autopsy showed fibrotic changes in vascular tissue, calcification of other tissues was noted, particularly lung
Both cases presented with anorexia, diarrhea, and vomiting
10.5 mg/dL
129 ng/ml
10.5 mg/dL
126 ng/ml
19.5 mg/dL
Calcium phosphate crystals in urine; bilateral medullary nephrocalcinosis; vomiting and lethargy; both pts recovered without incident
17.6 mg/dL
Extreme thirst, hypercalcemia, symptoms of diabetes insipidus
17.2 mg/dL
635 ng/ml
Leg pain, cessation of growth resulting from bone resorption; serum calcium, accompanied by nausea and vomiting. Tx with Ca-free dialysate failed to reduce serum Ca; prednisolone for 7 d; calcitonin tx stabilized serum Ca
17 mg/dL
Nausea and non-tender lumps over both tibias; X-rays showed alternating patterns of increased and decreased bone density. Loss of bone density and tissue calcification continued despite removal of vitamin D and the pt died
14.4 mg/dL
470 ng/ml
Constipation and colic; persistent hypertension; no renal, cardiac, neurological symptoms noted. Acute toxicity treated with furosemide, calcitonin, and hydrocortisol
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DRI Dietary Reference Intakes Calcium Vitamin D
Study
Patient/Population
Preparation; Dose
Duration
Adults
Puig. 1998. Ann Internal Med 128(7):601-602
66-yr-old female
Vitamin D: 200 IU + 1,000 mg calcium/twice daily
3 yr
Rizzoli et al. 1994. Bone 15:193-198
7 adults ages 55–84
Vitamin D3: 30,000–60,000 IU/d
3 weeks to 7.5 yr
Davies and Adams. 1976. The Lancet
Case 1: 59-yr-old female post-thyroidectomy for 40 yr
Vitamin D: 50,000–100,000 IU/d
>30 yr
Case 2: 71-yr-old female with Paget’s disease
150,000 IU/d
7 yr
Case 3: 51-yr-old female
100,000 IU/d
10 yr
1950. BMJ letter to editor
Vitamin D2: 100,000 IU/d
3 weeks
Streck et al. 1979. Arch Intern Med 139:974-977
49-yr-old female post-thyroidectomy
Vitamin D: 100,000 units/d; plus high calcium diet
3.8 yr
Sterling and Rupp. 1967. Acta Endocrinologica 54:380-384
69-yr-old male with carcinoma of the larynx
Vitamin D (Calciferol): 100,000 units/d
3 weeks
Aub. 1951. Amer Prac 2(11):976-981
59-yr-old female
Vitamin D: 150,000 units/d
6–8 weeks
Vieth et al. 2002. Lancet 359:672
29- and 63-yr-old related males
Vitamin D poisoning: 12.6 mg D3/g crystalline sugar (~1,700,000 IU/d)
7 mo
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DRI Dietary Reference Intakes Calcium Vitamin D
Serum Calcium
Serum 25(OH)D
Symptoms/Health Effects
4.04 mmol/L (16.2 mg/dL)
696 nmol/L (278.8 ng/ml)
Anemia and dehydration; toxicity treated with milk-free diet
3.30 mmol/L (mean) (13.2 mg/dL) (range = 2.52–4.59 mmol/L) (10.8–18.4 mg/dL)
710 nmol/L (mean) (284.5 ng/ml) (range = 221–1692 nmol/L) (88.5–677.9 ng/ml)
Asthenia, anorexia, nausea, polydipsia, polyuria; hypercalciuria; PTH levels were low normal. Discontinuation of vitamin D normalized calcemia in 3 d and calcidiol levels in 3 mo; bisphosphonate was used to inhibit bone resorption
Pts reported nausea, vomiting; case 3 had extensive arterial and ligamentous calcification; tx with corticosteroids and withdrawal of vitamin D
3.1 mmol/L (12.4 mg/dL
4.5 mmol/L (18 mg/dL)
450 nmol/L (180.3 ng/ml)
3.75 mmol/L (15 mg/dL)
400 nmol/L (160.3 ng/ml)
Pt reported feeling well. Response from editor: Feeling well occurs early in toxicity. Toxic dose varies from 200,000–400,000 IU daily for 10 d.
12.8 mg/dL;
283 ng/mL
Tx with prednisone resolved hypercalcemia via inhibition of bone resorption of calcium
(Urinary calcium: 493–600 mg/24 hr)
3.8–5.1 mEq/L (15.2–20.4 mg/dL)
Nausea, anorexia, polyuria that progressed to dehydration and coma. Removal of vitamin D and tx with corticosteroids resolved elevated calcium and CV abnormality
14.3 mg/dL
Weight loss, memory loss; evidence of renal damage and corneal calcification. Tx not discussed
3.82 mmol/L (15.3 mg/dL)
1,555 nmol/L (623 ng/ml)
Anorexia, fever, chills, vomiting, increased thirst; 5 kg weight loss; conjunctivitis, acute renal failure, PTH <1 pmol/L. Tx with IV hydrocortisone, sodium phosphate, and pamidronic acid; both patients survived.
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DRI Dietary Reference Intakes Calcium Vitamin D
Study
Patient/Population
Preparation; Dose
Duration
Lilienfeld-Toal et al. 1978. Klin Wschr 56:715-717
70 yr old
Vitamin D3: 15 mg/d
3 weeks
Selby et al. (1995)
6 patients (most were hypoparathyroid)
2.5–5.0 mg/d, (80,000 IU to 200,000 IU D2)/d
2–13 yr
Irnell (1969) Acta Med Scand. 185:147-152, 1969)
34-yr old
270,000 IU/d
10 d
45,000 IU/d
6 yr
Accidental or Industrial Poisoning
Scanlon et al. 1995. Am J Public Health 85:1418-1422
234 survey respondents
Milk over-fortified with vitamin D at 70–600X concentration; (>50 IU/100 g)
Intake range: (oz/d)
< 5.5
5.5–11.0
11.1–19.6
≥ 19.7
Blank et al. 1995. Am J Public Health 85:656-659
Hospital discharge, lab, and health dept data from cases of hypervitaminosis D
Milk over-fortified with vitamin D + other risk factors, i.e., use supplements; sun sensitivity, history of cancer
~3 yr
Jacobus et al. 1992. New Engl J Med 326:1173-1177
8 individuals ages 8 mo to 82 yr consumed milk excessively fortified with vitamin D
Milk over-fortified with cholecalciferol at concentrations of 396,400 and 376,800 IU/ml
Variable exposure
Thomson and Johnson. 1986. Postgrad Med J 62:1025-1028
7 family members; 3 adults and 4 children ages 1.5 to 14 yr
Unknown food source containing excessively high vitamin D
Single exposure
Pettifor et al. 1995. Ann Intern Med 122:511-513
10 family members and 1 servant; age range 8-69 yr ingested oil containing a veterinary vitamin D concentrate
Cholecalciferol concentrate in peanut oil = 2 million U/g
Unknown exposure
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DRI Dietary Reference Intakes Calcium Vitamin D
Serum Calcium
Serum 25(OH)D
Symptoms/Health Effects
6.1 mval/L
498 nmol/L (200 ng/ml)
Fatigue and psychotic symptoms; no evidence of 2° osteoporosis was found. Tx with vitamin D was interrupted; the increased body pool of calcium returned to normal when serum vitamin D levels decreased to 200 ng/ml
3.26 mmol/L (mean) (13.04 mg/dL)
842 nmol/L (mean) (337.3 ng/ml)
Admitted for hypercalcemia; renal failure
6.6 mEq/L
Patient exhibited symptoms of toxicity (tiredness, vomiting, diarrhrea, polyuria, weight loss, muscular weakness, headache) at 45,000 IU/d
8.5–9.6 mEq/L
Linear regression model showed a 1 oz increase in milk intake was associated with 1.39 ng/ml increase in serum 25(OH)D. No association was found between milk intake and elevated serum calcium; there was an association with elevated serum 25(OH) D and urinary calcium
mean (mg/dL)
mean (ng/ml)
2.4
32.8
2.3
39.5
2.4
41.3
2.4
44.7
13.1 mg/dL (mean for 35 cases)
224 ng/ml (mean for 35 cases)
Consumption of milk from sources other than the over-fortified milk was not associated with hypervitaminosis D
7 of 8 had hypercalcemia; 1 had hypercalcuria with normocalcemia
Mean for all cases: 731 ± 434 nmol/L (293 ± 174 ng/ml)
Vitamin D3 concentrate in milk that was up to 580 times in excess resulted in elevated serum vitamin D3, but not D2 in consumers. All consumers of the milk had elevated 25(OH)D levels and most had hypercalcemia
2.72–4.08 nmol/L (10.9–16.3 mg/dL)
832–1,287 nmol/L (333.0–515.6 ng/ml)
Serum calcium levels returned to normal within 24 d but 25(OH)D levels remained elevated for 1 yr; 1,25 (OH)D was not significantly elevated in the adults
3.46–4.61 nmol/L (13.8–18.4 mg/dL)
847–1,652 nmol/L (339.3–661.9 ng/ml)
Cholecalciferol poisoning did not elevate total 1-25 (OH)2D in 8 and only marginally in 3 of intoxicated patients; but did elevate free 1-25 (OH)2D in all
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DRI Dietary Reference Intakes Calcium Vitamin D
Study
Patient/Population
Preparation; Dose
Duration
Hodges. 1985. British Med J 290:748-749.
32-yr-old male working with crystalline vitamin D in a laboratory setting
Unknown exposure
Intermittent exposure: 32 d in 1981; 11 d in 1982; 22 d in 1983
Klontz. 2007. New Engl J Med 357:308-309
58-yr-old female diagnosed with diabetes and rheumatoid arthritis
Vitamin D3 overdose in a supplement; 186,906 IU/6 capsules
~2 mo
Down et al. 1979. Postgrad Med J 55:897-902
3 family members; 2 adults ages 24 yr and 1 infant aged 11 mo
Cholecalciferol concentrate in nut oil = 5 million IU/ml
Single exposure
Chiricone et al. 2003. J Nephrol 15:917-921
Case reports:
Multivitamin preparation per injection; 100,000 IU vitamin D/vial
62-yr-old male
3 vials/d per 20 d/3 mo: total exposure estimate = 18,000,000 IU
55-yr-old female
3 vials/d per 20 d/1.5 mo total exposure estimate = 9,000,000 IU
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DRI Dietary Reference Intakes Calcium Vitamin D
Serum Calcium
Serum 25(OH)D
Symptoms/Health Effects
3.5–3.7 mmol/L (~14 mg/dL)
496 ng/ml
Polydypsia, polyuria, anorexia, nausea; tx with IV saline, furosemide; hydrocortisone
3.75 mmol/L (15 mg/dL)
1,171 nmol/L (469.2 ng/ml)
Fatigue, constipation, back pain, forgetfulness, nausea, vomiting; tx with IV saline, furosemide, and pamidronate
3.95 mmol/L (15.8 mg/dL)
58–60 IU/ml (145–150 ng/ml)
Both adults developed renal failure. The female aborted a 10-week fetus at 3 weeks post-diagnosis for hypervitaminosis D. Plasma vitamin D levels were 60 IU/ml 5 weeks post-diagnosis; nephrocalcinosis persisted in the adult male but neither had long-term renal impairment
(mean for adults at 5 weeks post-exposure)
(5 weeks post-exposure)
Renal colic, confusion, lethargy, and weakness; reported passing small stones; tx with IV saline, furosemide, glucocorticoids
15.3 mg/dL
>150 ng/ml
11.3 mg/dL
>150 ng/ml
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DRI Dietary Reference Intakes Calcium Vitamin D
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