symptoms of vitamin d toxicity

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eMedicine Specialties > Emergency Medicine > Toxicology
-------------------------------------------------------

Toxicity, Vitamin
=================

Author: Mark Rosenbloom, MD, MBA, FACEP, Fellow of the American
Academy of Emergency Medicine; Overseas Fellow of the Royal Society of
Medicine; Chief Executive Officer and Editiorial Director, PEPID, LLC;
Founder and Chairman, The Unicorn Children's Foundation
Contributor Information and Disclosures

Updated: Apr 20, 2009

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Overview

Differential Diagnoses & Workup

Treatment & Medication

Follow-up

References

Keywords

Introduction
------------

Background

Every day 44% of Americans take vitamins and dietary supplements.1  In
2007, vitamin C, vitamin E, and multivitamins were among 5
best-selling supplements.2  As many as 84% of Americans consider
vitamins and supplements safe,2 thus, increasing the risk for vitamin
toxicity. Iron-containing vitamins are the most toxic, especially in
pediatric acute ingestions (see Toxicity, Iron). Fat-soluble vitamins
have higher potential for toxicity due to their capability to
accumulate in the body.

Frequency

United States

The 2007 Annual Report of the American Association of Poison Control
Centers' National Poison Data System document the total number of
exposures for each class of vitamins, the number of patients with
major adverse outcomes, and the number of fatalities from that
ingestion,3 as follows:

Adult multiple vitamins without iron or fluoride - 3,000 total
 exposures, 3 major outcomes, and 0 deaths

Adult multiple vitamins with iron but without fluoride - 7798
 total exposures, 2 major outcomes, and 0 deaths

Pediatric multiple vitamins without iron or fluoride - 20,774
 total exposures, 0 major outcomes, and 0 deaths

Pediatric multiple vitamins with iron but without fluoride -
 15,407 total exposures, 0 major outcome, and 0 deaths

Vitamin A - 550 total exposures, 0 major outcomes, and 0 deaths

Niacin - 2,303 total exposures, 4 major outcomes, and 0 deaths

Pyridoxine - 212 total exposures, 0 major outcomes, and 0 deaths

Other B complex vitamins - 2,546 total exposures, 3 major
 outcomes, and 0 deaths

Vitamin C - 1,531 total exposures, 2 major outcomes, and 0 deaths

Vitamin D - 596 total exposures, 1 major outcome, and 0 deaths

Vitamin E - 740 total exposures, 0 major outcome, and 0 deaths

Overall, 58,622 exposures to different types of vitamins were
 reported to the poison control centers across the United States in
 2007, accounting for 17 major adverse outcomes and 1 death. Of the
 total exposures, 45,498 incidents occurred in children younger
 than 6 years old and 7,693 involved individuals aged 6-19 years.

Mortality/Morbidity

Morbidity and mortality from pure vitamins are rare. According to the
American Association of Poison Control Centers' National Poison Data
System, in 2007, more than 58,000 acute or chronic vitamin overdoses
were documented, with 17 major adverse outcomes and 1 death.3

Race

No scientific data indicate that outcomes of vitamin overdose are
dependent on race.

Sex

No scientific data indicate that outcomes of vitamin overdose are
dependent on sex.

Clinical
--------

Physical

Nonspecific symptoms, such as nausea, vomiting, diarrhea, and rash,
are common with any acute or chronic vitamin overdose. Vitamin-caused
symptoms may be secondary to those associated with additives (eg,
mannitol), colorings, or binders; these symptoms usually are not
severe. The following are symptoms of specific vitamin overdose:

Vitamin A

Acute toxicity effects include headache, photophobia,
 anorexia, nausea, vomiting, abdominal pain, drowsiness,
 irritability, seizures, and desquamation after 24 hours.

Chronic toxicity affects the skin, the mucous membranes, and
 the musculoskeletal and neurologic systems.

Skin and mucous membrane effects include erythema, eczema,
 pruritus, dry and cracked skin, angular cheilitis,
 conjunctivitis, palmar and plantar peeling, and alopecia.

Musculoskeletal effects include pain and tenderness,
 particularly in the long bones of the upper and lower
 extremities, which may be exacerbated by exercise;
 epiphyseal capping and premature epiphyseal closure may
 occur in children.

Neurologic effects include blurred vision and frontal
 headache, which is often the first sign of toxicity.

Findings also include idiopathic intracranial hypertension
 (IIH), hepatomegaly, ascites, erythematous dermatitis,
 migratory arthritis, craniotabes in children, or bulging
 fontanelle in infants.

Recent studies suggest that elevated levels of vitamin A may
 cause increased bone resorption and promote development of
 osteoporosis.4,5

Vitamin D

Acute toxicity effects are characteristic of hypercalcemia and
 may include muscle weakness, apathy, headache, anorexia,
 irritability, nausea, vomiting, and bone pain.

Chronic toxicity effects include the above symptoms and
 constipation, anorexia, abdominal cramps, polydipsia,
 polyuria, backache, hyperlipidemia, and hypercalcemia.

Findings may also include calcinosis, followed by hypertension
 and cardiac arrhythmias (due to shortened refractory period).

Vitamin E

Acute toxicity effects include nausea, gastric distress,
 abdominal cramps, diarrhea, headache, fatigue, easy bruising
 and bleeding (prolonged prothrombin time PT and activated
 partial thromboplastin time aPTT), inhibition of platelet
 aggregation, diplopia (at dosages as low as 300 IU), muscle
 weakness, and creatinuria.

Chronic toxicity effects include all of the above, suppression
 of other antioxidants, and increased risk of hemorrhagic
 stroke.

Vitamin K

This particular toxicity is typically associated with
 formula-fed infants or those receiving synthetic vitamin K-3
 (menadione) injections. Because of its toxicity, menadione is
 no longer used for treatment of vitamin K deficiency.

Effects may include jaundice in newborns, hemolytic anemia,
 and hyperbilirubinemia.

Toxicity also blocks the effects of oral anticoagulants.

Vitamins B-1, B-2, B-12, and folate

Effects may be minimal and nonspecific.

Vitamin B-2 turns the urine yellow-orange.

Vitamin B-1 (ie, thiamine) toxicity effects may include the
 following:

Tachycardia

Hypotension

Cardiac dysrhythmias

Headache

Anaphylaxis

Vasodilation

Weakness

Convulsions

Single acute toxicity is rare.

Vitamin B-3 (ie, niacin, nicotinic acid)

Acute toxicity effects are prostaglandin-mediated and include
 flushing, pruritus, wheezing, vasodilation, headache,
 increased intracranial blood flow, headache, diarrhea, and
 vomiting.

Chronic toxicity effects include jaundice, abnormal liver
 function test results, signs and symptoms of liver toxicity
 (most common with sustained-release preparations), and
 acanthosis nigricans (rare).

Vitamin B-6 (ie, pyridoxine)

Effects include tachypnea and sensory neuropathies, such as
 burning pains, paresthesias, ataxia, clumsiness, paralysis,
 and perioral numbness.

Findings range from normal CNS function to progressive sensory
 ataxias, profound impairment of position and vibration sense,
 and diminished tendon reflexes.

Vitamin C

Effects may be renal colic (ie, nephrolithiasis), diarrhea,
 nausea, rebound scurvy in infants born to women taking high
 doses, hemolysis if glucose-6-phosphate dehydrogenase (G-6-PD)
 deficiency is present, possible dental decalcification, and
 increased estrogen levels.

Findings may include occult rectal bleeding.

Causes

Vitamin A (ie, retinol) - Found in green and yellow vegetables,
 liver, egg yolks, fish oil, and margarine

US recommended dietary allowance (RDA)

Males (>14 y): 900 mcg retinol activity equivalents (RAE)
 (3,000 IU)

Females (>14 y): 700 mcg RAE (2,300 IU)

Pregnancy: 750-770 mcg RAE (2,500-2,600 IU)

Lactation: 1,200-1,300 mcg RAE (4,000-4,300 IU)

Children

0-6 mo: 400 mcg RAE (1,300 IU)

7-12 mo: 500 mcg RAE (1,700 IU)

1-3 y: 300 mcg RAE (1,000 IU)

4-8 y: 400 mcg RAE (1,320 IU)

9-13 y: 600 mcg RAE (2,000 IU) 

Supplements are typically 10,000-50,000 IU per capsule.
 Fish-liver oils may contain more than 180,000 IU/g.

Acute toxic dose is 25,000 IU/kg, and chronic toxic dose is
 4000 IU/kg every day for 6-15 months.

Beta-carotene (ie, provitamin A) is converted to retinol but
 not rapidly enough for acute toxicity. Vitamin A is highly
 teratogenic in pregnancy, especially in the first 8 weeks with
 daily intake more than 10,000 IU; however, it is also a
 cofactor in night vision and bone growth.

Vitamin D (ie, cholecalciferol) is present in most dairy products,
 egg yolks, liver, and fish.

Adequate intake (AI) for children and adults younger than 50
 years is 5 mcg (200 IU) per day, 10 mcg (400 IU) per day for
 those aged 51-70 years, and 15 mcg (600 IU) per day for those
 71 years and older.

Supplements usually are 400 IU per tablet.

Acute toxic dose is not established, and chronic toxic dose is
 more than 50,000 IU/d in adults. In children, 400 IU/d is
 potentially toxic. A wide variance in potential toxicity
 exists.

Vitamin D increases serum calcium levels by facilitating
 calcium absorption and mobilizing calcium from bone.

Vitamin E (ie, alpha-tocopherol) is found in vegetable oil, nuts,
 sunflower, wheat, green leafy vegetables, and fish.

RDA is 15 mg (22.5 IU) for adults and pregnant women, 19 mg
 (28.5 IU) during lactation, 7 mg (10.5 IU) for children 4-8
 aged years, and 6 mg (9 IU) for those aged 1-3 years.

Supplements usually are 100-1000 IU per capsule.

Upper tolerable limit is 1,000 mg (1,500 IU) per day.

Vitamin E has antioxidant and anticoagulant properties. It may
 block absorption of vitamins A and K. Vitamin E decreases
 low-density lipoprotein (LDL) cholesterol level at doses more
 than 400 IU/d.

Vitamin K (ie, phytonadione) is produced by intestinal bacteria
 (vitamin K-2) and is found in green leafy vegetables, cow's milk,
 and soy oil (vitamin K-1).

Vitamin K-1 supplements are usually 2.5-10 mg.

A toxic dose amount is not established.

Vitamin K-3 (menadione) supplements have been banned by the
 FDA because of their high toxicity.

Phytonadione promotes liver synthesis of factors II, VII, IX,
 and X.

Vitamin B-1 (ie, thiamine) is found in organ meats, yeast, eggs,
 and green leafy vegetables.

RDA is 1.5 mg (0.7 mg for children aged 1-4 y).

Supplements usually are 50-500 mg per tablet.

Thiamin generally is nontoxic.

Vitamin B-1 is a cofactor for pyruvate dehydrogenase in the
 Krebs cycle.

Vitamin B-2 (ie, riboflavin)

RDA is 1.7 mg (0.8 mg for children aged 1-4 y).

Supplements usually are 25-100 mg.

Vitamin B-2 generally is nontoxic.

Vitamin B-3 (ie, niacin) is found in green vegetables, yeast
 (pumpernickel bagels may contain 190 mg of niacin), animal
 proteins, fish, liver, and legumes.

RDA is 20 mg (9 mg for children aged 1-4 y) with an upper
 limit of 35 mg per day.

Supplements are usually 20-500 mg per tablet.

Toxic dose is more than 1000 mg/d.

Vitamin B-3 synthesis requires tryptophan.

Niacin is converted to nicotinamide adenine dinucleotide (NAD)
 or nicotinamide adenine dinucleotide phosphate (NADP). NAD and
 NADP are coenzymes for dehydrogenase-type reactions. In large
 doses, niacin decreases synthesis of LDL cholesterol level.

Toxicity may occur from prolonged administration of nicotinic
 acid.

Vitamin B-6 (ie, pyridoxine) is found in poultry, fish, pork,
 grains, and legumes.

RDA is 1.3 mg per day for adults (1.7 mg/d for men >50 y, and
 1.5 mg/d for women >50 y).

Supplements usually are 5-500 mg per tablet.

Over time, 300-500 mg/d may be neurotoxic (patients with
 impaired renal function may be more susceptible). Acute toxic
 dose generally is not established.

Vitamin B-6 functions in protein and amino acid metabolism.
 Pyridoxine is the treatment of choice for isoniazid overdose.
 Also, it is used by bodybuilders, as well as, for the
 treatment of premenstrual syndrome (PMS), carpal tunnel
 syndrome, schizophrenia, childhood autism, and attention
 deficit hyperactivity disorder (ADHD) with variable results.

Vitamin B-12 (ie, cyanocobalamin) is found in milk products, eggs,
 fish, poultry, and meat.

Vitamin B-12 requires intrinsic factor for absorption.

RDA is 2.4 mcg for adults and adolescents, and 0.9 mcg for
 children aged 1-3 years. RDA is 2.6 and 2.8 mcg during
 pregnancy and lactation, respectively.

Supplements are usually 25-250 mcg per tablet.

Toxic dose is not established.

Vitamin B-12 is a treatment of pernicious anemia and cyanide
 poisoning.

Vitamin C (ie, ascorbic acid) is found in citrus fruits and
 vegetables.

RDA is 90 mg per day for adult males and 75 mg for adult
 females. Children aged 1-3 years should receive 15 mg of
 vitamin C per day.

Supplements are usually 100-2000 mg per capsule.

Chronic toxic dose is more than 2 g/d.

Acute toxic dose is not determined.

Vitamin C is an antioxidant and reducing agent. Vitamin C is
 used to treat (controversial) upper respiratory infections
 (URIs) and cancer.

Folic acid is found in leafy green vegetables and oranges.

RDA is 0.4 mg (0.2 mg in children aged 1-4 y).

Pregnant women, acutely ill persons, and/or malnourished
 patients may require larger RDA.

Toxic dose is not established. Folic acid is generally
 nontoxic. Intakes more than 5000 mcg/d mask pernicious anemia.

Folic acid decreases risk of neural tube defects and may
 decrease serum homocysteine levels (coronary artery disease
 CAD risk factor).

Folic acid may have a therapeutic role as an adjuvant therapy
 for the treatment of methanol toxicity (enhances the
 elimination of formate).

More on Toxicity, Vitamin

Overview: Toxicity, Vitamin

Differential Diagnoses & Workup: Toxicity, Vitamin

Treatment & Medication: Toxicity, Vitamin

Follow-up: Toxicity, Vitamin

References

Next Page »

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References
----------

1. 

North America, Asia lead vitamin and supplement usage. Nielsen
Wire. Available at
http://blog.nielsen.com/nielsenwire/consumer/north-america-asia-lead-vitamin-and-supplement-usage/. Accessed
March 20, 2009.

2. 

Griffin RM, Hoffman H. Live well vitamins & supplements
center. WebMD. Available at http://gnc.webmd.com/vitamin-facts. Accessed
March 22, 2009.

3. 

Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH,
Heard SE. 2007 Annual Report of the American Association of Poison
Control Centers' National Poison Data System (NPDS): 25th Annual
Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. Medline. Full Text.

4. 

Dietary Supplement Fact Sheet: Vitamin A and Carotenoids. National
Institutes of Health - Office of Dietary Supplements. Available at
http://ods.od.nih.gov/factsheets/vitamina.asp. Accessed July 5,
2007.

5. 

Pazirandeh S, Burns DL. Overview of vitamin A. UpToDate. Available
at www.uptodate.com. Accessed July 5, 2007.

6. 

Bakerman S. ABC's of Interpretive Laboratory Data. 4th
ed. Scottsdale, AZ: Interpretive Laboratory Data, Inc; 2002.

7. 

Brody JE. In vitamin mania, millions take a gamble on health. In:
New York Times. October 26, 1997:1, 20.

8. 

Cristoph RA. Vitamins. In: Manual of Toxicologic Emergencies. Year
Book Medical Publishers; 1989:490-5.

9. 

Dietary Supplement Fact Sheet: Vitamin E. National Institutes of
Health - Office of Dietary Supplements. Available at
http://ods.od.nih.gov/factsheets/vitamine.asp. Accessed March 20,
2009.

10. 

Fischbach F. A Manual of Laboratory and Diagnostic Tests. 7th
ed. Lippincott Williams & Wilkins; 2004.

11. 

Food and Nutrition Board. Recommended Dietary Allowances. 10th
ed. National Academy Press: Washington, DC; 1989.

12. 

Goldfrank L, Lewis R. Vitamins. In: Goldfrank's Toxicologic
Emergencies. 5th ed. Prentice Hall; 1994:535-44.

13. 

Hathcock JN. Vitamins and minerals: efficacy and safety. Am J Clin
Nutr. Aug 1997;66(2):427-37. Medline.

14. 

Hoffman RS. Thiamine hydrochloride. In: Goldfrank L, ed. Goldfrank's
Toxicologic Emergencies. 5th ed. New York: Prentice
Hall; 1997:825-6.

15. 

Med Lett Drugs Ther. Toxic effects of vitamin overdosage. Med Lett
Drugs Ther. Aug 3 1984;26(667):73-4. Medline.

16. 

Meyers DG, Maloley PA, Weeks D. Safety of antioxidant vitamins. Arch
Intern Med. May 13 1996;156(9):925-35. Medline.

17. 

NIH Clinical Center. Vitamin E. National Institutes of Health -
Office of Dietary Supplements. Available at
http://ods.od.nih.gov/factsheets/vitamine.asp. Accessed July 5,
2007.

18. 

Sachter JJ. Vitamins. In: Handbook of Medical Toxicology. Little
Brown & Co Inc; 1993:399-402.

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Further Reading
---------------

CLOSE WINDOW 

Keywords
--------

vitamin A, retinol, vitamin D, cholecalciferol, vitamin E,
alpha-tocopherol, vitamin K, phytonadione, vitamin B-1, thiamine,
vitamin B-2, riboflavin, vitamin B-3, niacin, vitamin B-6, pyridoxine,
vitamin B-12, cyanocobalamin, vitamin C, ascorbic acid, folic acid, B
complex vitamins, nicotinic acid, beta-carotene, provitamin A, vitamin
K-3, menadione

vitamin toxicity, iron-containing vitamins, fat-soluble vitamins,
multiple vitamins, acute vitamin overdose, chronic vitamin overdose,
craniotabes, bulging fontanelle, osteoporosis, angular cheilitis,
alopecia, epiphyseal capping, premature epiphyseal closure, frontal
headache, blurred vision, papilledema, hepatomegaly, ascites,
erythematous dermatitis, migratory arthritis, increased bone
resorption, bone pain

calcinosis, hypercalcemia, jaundice, hemolytic anemia,
hyperbilirubinemia, sensory neuropathies, burning pains, paresthesias,
ataxia, paralysis, perioral numbness, sensory ataxias, nephrolithiasis,
renal colic, occult rectal bleeding, dental decalcification

diminished tendon reflexes, impairment of position sense, impairment
of vibration sense

CLOSE WINDOW 

Contributor Information and Disclosures
---------------------------------------

Author

Mark Rosenbloom, MD, MBA, FACEP, Fellow of the American Academy of
Emergency Medicine; Overseas Fellow of the Royal Society of Medicine;
Chief Executive Officer and Editiorial Director, PEPID, LLC; Founder
and Chairman, The Unicorn Children's Foundation
Mark Rosenbloom, MD, MBA, FACEP is a member of the following medical
societies: Alpha Omega Alpha, American Academy of Emergency Medicine,
American College of Emergency Physicians, American College of Sports
Medicine, American Medical Association, and Royal Society of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Richard Lavely, MD, JD, MS, MPH, Lecturer in Health Policy and
Administration, Department of Public Health, Yale University School of
Medicine
Richard Lavely, MD, JD, MS, MPH is a member of the following medical
societies: American College of Emergency Physicians, American College
of Legal Medicine, and American Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart
& St. Joseph's Hospitals
John T VanDeVoort, PharmD is a member of the following medical
societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

Fred Harchelroad, MD, FACMT, FAAEM, FACEP, Chair, Department of
Emergency Medicine, Director of Medical Toxicology - Allegheny General
Hospital, Associate Professor, Department of Emergency Medicine,
Drexel University College of Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard
Medical School, Beth Israel Deaconess Medical Center; Chief
Information Officer, CareGroup Healthcare System and Harvard Medical
School; Attending Physician, Division of Emergency Medicine, Beth
Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies:
American College of Emergency Physicians, American Medical Informatics
Association, Phi Beta Kappa, and Society for Academic Emergency
Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Director, Medical Toxicology,
Department of Emergency Medicine, Yale University School of Medicine;
Consulting Staff, Department of Emergency Medicine, Yale-New Haven
Hospital
Disclosure: Nothing to disclose.

Search for CME/CE on This Topic »

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