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Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011.

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Dietary Reference Intakes for Calcium and Vitamin D.

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GCases Studies of Vitamin D Toxicity

TABLE G-1Case Studies of Vitamin D Toxicity

StudyPatient/PopulationPreparation; DoseDurationSerum CalciumSerum 25(OH)DSymptoms/Health Effects
Children
Djamil and Tu-Tunji. 1931. Lancet letter to the editor2-yr-old maleVigantol (irradiated ergosterol); 3 tsp1 dEdema and albuminuria
1947. BMJ letter to editorNot specifiedCod liver oilResponse 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
Ross. 1952. Journal of Pediatrics :815-8224 infants ages 8-14 moIrradited ergosterol containing an estimated 30,000–40,000 IU vitaminDaily for 8-12 mo18–19 mg/dLAll 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
Jacqz et al. 1985Infants with hypercalcemia (2 cases with vitamin D toxicity)Vitamin D and calcium supplementationBoth cases presented with anorexia, diarrhea, and vomiting
Case 1: 3 mo old10.5 mg/dL129 ng/ml
Case 2: 7 mo old300 μg D310.5 mg/dL126 ng/ml
Besbas et al. 1989. Turkish J Pediatrics
31:239-244
Case 1: 3 mo oldVitamin D: 45,000 IU/d45 d19.5 mg/dLCalcium phosphate crystals in urine; bilateral medullary nephrocalcinosis; vomiting and lethargy; both pts recovered without incident
Case 2: 4 mo oldVitamin D: 60,000 IU/d30 d17.6 mg/dL
Dent. 1964. BMJ letter to editor6 yr oldVitamin D (Calciferol Tablets B.P.): 1.25 mg. (~50,000 IU)/d9 moExtreme thirst, hypercalcemia, symptoms of diabetes insipidus
Counts et al. 1975. Ann Internal Med 82:196-2004-yr-old maleVitamin D2 (Drisdol): 50,000 up to 100,000 IU/d2 mo following bilateral nephrectomy17.2 mg/dL635 ng/mlLeg 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
DeWind. 1960. Arch Dis Child 36:373-3805.5 yr oldVitamin D: 100,000 IU + cod liver oil-2 T + multivitamindaily × 2–3 mo; and continued intake of tx vitamin D for 1 yr after hospitalization17 mg/dLNausea 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
Barrueto et al. 2005. Pediatrics 116:e453-e4562-yr-old maleVitamin D (ergocalciferol): 2,400,000 IU4 d14.4 mg/dL470 ng/mlConstipation and colic; persistent hypertension; no renal, cardiac, neurological symptoms noted. Acute toxicity treated with furosemide, calcitonin, and hydrocortisol
Adults
Puig. 1998. Ann Internal Med 128(7):601-60266-yr-old femaleVitamin D: 200 IU + 1,000 mg calcium/twice daily3 yr4.04 mmol/L
(16.2 mg/dL)
696 nmol/L
(278.8 ng/ml)
Anemia and dehydration; toxicity treated with milk-free diet
Rizzoli et al. 1994. Bone 15:193-1987 adults ages 55–84Vitamin D3: 30,000–60,000 IU/d3 weeks to 7.5 yr3.30 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
Davies and Adams. 1976. The LancetCase 1: 59-yr-old female post-thyroidectomy for 40 yrVitamin D: 50,000–100,000 IU/d>30 yr3.1 mmol/L
(12.4 mg/dL
Pts reported nausea, vomiting; case 3 had extensive arterial and ligamentous calcification; tx with corticosteroids and withdrawal of vitamin D
Case 2: 71-yr-old female with Paget's disease150,000 IU/d7 yr4.5 mmol/L
(18 mg/dL)
450 nmol/L
(180.3 ng/ml)
Case 3: 51-yr-old female100,000 IU/d10 yr3.75 mmol/L
(15 mg/dL)
400 nmol/L
(160.3 ng/ml)
1950. BMJ letter to editorVitamin D2: 100,000 IU/d3 weeksPt 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.
Streck et al. 1979. Arch Intern Med 139:974-97749-yr-old female post-thyroidectomyVitamin D: 100,000 units/d; plus high calcium diet3.8 yr12.8 mg/dL

(Urinary calcium: 493– 600 mg/24 hr)
283 ng/mLTx with prednisone resolved hypercalcemia via inhibition of bone resorption of calcium
Sterling and Rupp. 1967. Acta Endocrinologica 54:380-38469-yr-old male with carcinoma of the larynxVitamin D (Calciferol): 100,000 units/d3 weeks3.8–5.1 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
Aub. 1951. Amer Prac 2(11):976-98159-yr-old femaleVitamin D: 150,000 units/d6–8 weeks14.3 mg/dLWeight loss, memory loss; evidence of renal damage and corneal calcification. Tx not discussed
Vieth et al. 2002.
Lancet 359:672
29- and 63-yr-old related malesVitamin D poisoning: 12.6 mg D3/g crystalline sugar (~1,700,000 IU/d)7 mo3.82 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.
Lilienfeld-Toal et al. 1978. Klin Wschr 56:715-71770 yr oldVitamin D3: 15 mg/d3 weeks6.1 mval/L498 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
Selby et al. (1995)6 patients
(most were hypoparathyroid)
2.5–5.0 mg/d, (80,000 IU to 200,000 IU D2)/d2–13 yr3.26 mmol/L
(mean)
(13.04 mg/dL)
842 nmol/L
(mean)
(337.3 ng/ml)
Admitted for hypercalcemia; renal failure
Irnell (1969)
Acta Med Scand.
185:147-152, 1969)
34-yr old270,000 IU/d10 d6.6 mEq/LPatient exhibited symptoms of toxicity (tiredness, vomiting, diarrhrea, polyuria, weight loss, muscular weakness, headache) at 45,000 IU/d
45,000 IU/d6 yr8.5–9.6 mEq/L
Accidental or Industrial Poisoning
Scanlon et al. 1995. Am J Public Health 85:1418-1422234 survey respondentsMilk 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
mean (mg/dL)
2.4
2.3
2.4
2.4
mean (ng/ml)
32.8
39.5
41.3
44.7
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
Blank et al. 1995. Am J Public Health 85:656-659Hospital discharge, lab, and health dept data from cases of hypervitaminosis DMilk over-fortified with vitamin D + other risk factors, i.e., use supplements; sun sensitivity, history of cancer~3 yr13.1 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
Jacobus et al. 1992. New Engl J Med 326:1173-11778 individuals ages 8 mo to 82 yr consumed milk excessively fortified with vitamin DMilk over-fortified with cholecalciferol at concentrations of 396,400 and 376,800 IU/mlVariable exposure7 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
Thomson and Johnson. 1986. Postgrad Med J 62:1025-10287 family members; 3 adults and 4 children ages 1.5 to 14 yrUnknown food source containing excessively high vitamin DSingle exposure2.72– 4.08 nmol/L
(10.9–16.3 mg/ dL)
832–1,287 nmol/L
(333.0–b 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
Pettifor et al. 1995. Ann Intern Med 122:511-51310 family members and 1 servant; age range 8-69 yr ingested oil containing a veterinary vitamin D concentrateCholecalciferol concentrate in peanut oil = 2 million U/gUnknown exposure3.46–4.61 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
Hodges. 1985. British Med J 290:748-749.32-yr-old male working with crystalline vitamin D in a laboratory settingUnknown exposureIntermittent exposure: 32 d in 1981; 11 d in 1982; 22 d in 19833.5–3.7 mmol/L
(~14 mg/dL)
496 ng/mlPolydypsia, polyuria, anorexia, nausea; tx with IV saline, furosemide; hydrocortisone
Klontz. 2007. New Engl J Med 357:308-30958-yr-old female diagnosed with diabetes and rheumatoid arthritisVitamin D3 overdose in a supplement; 186,906 IU/6 capsules~2 mo3.75 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
Down et al. 1979. Postgrad Med J 55:897-9023 family members; 2 adults ages 24 yr and 1 infant aged 11 moCholecalciferol concentrate in nut oil = 5 million IU/mlSingle exposure3.95 mmol/L
(15.8 mg/dL)

(mean for adults at 5 weeks post-exposure)
58–60 IU/ml
(145–150 ng/ml)

(5 weeks post-exposure)
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

Chiricone et al. 2003. J Nephrol 15:917-921Case reports:

62-yr-old male
Multivitamin preparation per injection; 100,000 IU vitamin D/vial3 vials/d per 20 d/3 mo: total exposure estimate = 18,000,000 IU15.3 mg/dL>150 ng/mlRenal colic, confusion, lethargy, and weakness; reported passing small stones; tx with IV saline, furosemide, glucocorticoids
55-yr-old female3 vials/d per 20 d/1.5 mo total exposure estimate = 9,000,000 IU11.3 mg/dL>150 ng/ml
Copyright © 2011, National Academy of Sciences.
Bookshelf ID: NBK56076
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