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Dietary Reference Intakes for Calcium and Vitamin D (2011)

Chapter: Appendix G: Cases Studies of Vitamin D Toxicity

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Page 1025 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

G
Cases Studies of Vitamin D Toxicity

Page 1026 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

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

Page 1027 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

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

Page 1028 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

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

Page 1029 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

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.

Page 1030 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

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

Page 1031 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

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

Page 1032 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

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

Page 1033 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

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

 

Page 1034 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×

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Page 1025 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1025
Page 1026 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1026
Page 1027 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1027
Page 1028 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1028
Page 1029 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1029
Page 1030 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1030
Page 1031 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1031
Page 1032 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1032
Page 1033 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1033
Page 1034 Cite
Suggested Citation:"Appendix G: Cases Studies of Vitamin D Toxicity." Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. doi: 10.17226/13050.
×
Page 1034
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Calcium and vitamin D are essential nutrients for the human body. Establishing the levels of these nutrients that are needed by the North American population is based on the understanding of the health outcomes that calcium and vitamin D affect. It is also important to establish how much of each nutrient may be "too much."

Dietary Reference Intakes for Calcium and Vitamin D provides reference intake values for these two nutrients. The report updates the DRI values defined in Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride, the 1997 study from the Institute of Medicine. This 2011 book provides background information on the biological functions of each nutrient, reviews health outcomes that are associated with the intake of calcium and vitamin D, and specifies Estimated Average Requirements and Recommended Dietary Allowances for both. It also identifies Tolerable Upper Intake Levels, which are levels above wish the risk for harm may increase. The book includes an overview of current dietary intake in the U.S. and Canada, and discusses implications of the study. A final chapter provides research recommendations.

The DRIs established in this book incorporate current scientific evidence about the roles of vitamin D and calcium in human health and will serve as a valuable guide for a range of stakeholders including dietitians and other health professionals, those who set national nutrition policy, researchers, the food industry, and private and public health organizations and partnerships.

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