INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

More than 100 million Americans regularly use vitamins. In the United States, consumer spending on vitamins and minerals has doubled in the last 6 years, reaching $6.5 billion annually. 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

Data from the 2005 American Association of Poison Control Centers' Toxic Exposure Surveillance 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,¹ as follows:

• Adult multiple vitamins without iron or fluoride - 2,852 total exposures, 8 major outcomes, and 0 deaths
• Adult multiple vitamins with iron but without fluoride - 7,644 total exposures, 6 major outcomes, and 0 death
• Pediatric multiple vitamins without iron or fluoride - 15,332 total exposures, 1 major outcomes, and 0 deaths
• Pediatric multiple vitamins with iron but without fluoride - 19,014 total exposures, 6 major outcome, and 0 deaths
• Vitamin A - 641 total exposures, 1 major outcomes, and 0 deaths
• Niacin - 3,109 total exposures, 12 major outcomes, and 0 deaths
• Pyridoxine - 391 total exposures, 10 major outcomes, and 1 death
• Other B complex vitamins - 3,343 total exposures, 18 major outcomes, and 0 deaths
• Vitamin C - 2,324 total exposures, 2 major outcomes, and 0 death
• Vitamin D - 369 total exposures, 0 major outcomes, and 0 deaths
• Vitamin E - 1,292 total exposures, 1 major outcome, and 0 deaths
• Overall, 62,446 exposures to different types of vitamins were reported to the poison control centers across the United States in 2005, accounting for 73 major adverse outcomes and 1 death. Of the total exposures, 48,604 exposures occurred in children younger than age 6 years.

Mortality/Morbidity

Morbidity and mortality from pure vitamins are rare. According to the American Association of Poison Control Centers' Toxic Exposure Surveillance System, in 2005, there have been over 62,000 acute or chronic vitamin overdoses with reported 73 major adverse outcomes and 1 death.¹

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.²,³
• 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 (1,300 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 than50 years is 5 mcg (200 IU) per day, 10 mcg (400 IU) per day for those 51-70 years old, 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, and 6 mg (9 IU) for children ages 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 1-3 years old. 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).

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Acetaminophen and aspirin levels (on every suspected ingestion)
• Electrolytes (in patients with severe vomiting or diarrhea)
• Vitamin A
• • Retinol
  • • Reference range is 20-60 mcg/dL.
    • A toxic vitamin A level is higher than 60-100 mcg/dL. Obtain a CBC to rule out leukopenia. Perform calcium, glucose, and liver function tests (LFTs).
    • Levels are affected by liver stores and dietary intake of vitamin A.
  • Serum carotene
  • • Normal range is 50-300 mcg/dL.
    • Reflects dietary intake of vitamin A.
• Vitamin D
• • Obtaining calcium levels is mandatory; they are usually above 11 mg/dL but may be much higher. Phosphate levels may increase with calcium.
  • Renal function tests (ie, BUN, creatine, urinalysis [UA]) are necessary to rule out possible kidney damage from hypercalciuria.
• Vitamin E: Measure PT, aPTT, and bleeding times, especially if any evidence of bruising or bleeding is present. Platelet aggregation studies may be performed if bleeding time results are abnormal.
• Vitamin K: Measure PT if the patient is taking oral anticoagulants.
• Vitamins B-1, B-2, and B-12 require no specific laboratory tests.
• Vitamin B-3 (ie, niacin)
• • Perform LFTs.
  • Uric acid may be increased, leading to gouty arthritis.
  • Glucose level is occasionally elevated.
• Vitamin B-6
• • Vitamin B-6 toxicity does not require laboratory or other tests.
  • Lumbar puncture (LP) may be considered to rule out other causes if the patient has a peripheral neuropathy.
• Vitamin C
• • Perform UAs to rule out uricosuria. False-negative test results for glucosuria are possible.
  • Perform renal function tests. Measure PT if the patient is taking warfarin (Coumadin); vitamin C may interfere with Coumadin.
  • Measure serum iron levels because vitamin C also enhances the absorption of iron.

Imaging Studies

• Obtain skeletal radiographs to look for calcifications in chronic vitamin A and vitamin D toxicity.
• Obtain a helical CT scan or an intravenous urogram (IVU) for suspected nephrolithiasis (ie, oxalate stones) in patients with vitamin C toxicity.
• A kidneys, ureters, bladder (KUB) film is indicated for suspected toxicity from iron-containing pills.

Other Tests

• Obtain an ECG to evaluate for effects of hypercalcemia in patients with vitamin D toxicity.

Procedures

• An LP may be indicated to rule out increased intracranial pressure (ICP) in patients with vitamin A toxicity.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Emergency Department Care

All ingestions require supportive management and an intravenous line. Serious ingestions require hydration if vomiting or diarrhea is present. Oxygen, monitoring, and ABCs are essential if potential life-threats are present. If potentially lethal co-ingestions are present, perform gastric lavage if the patient presents within 1 hour postingestion. Other care is symptomatic and supportive.

• Vitamin A
• • Symptoms usually resolve after stopping vitamin A and instituting supportive therapy.
  • Increased ICP may require daily therapeutic LPs or further increased ICP treatment (diuretics, mannitol).
  • Symptomatic hypercalcemic patients may require fluids or electrolyte correction.
• Vitamin D
• • Place patients with vitamin D toxicity on a low-calcium diet.
  • Consider calcium disodium edetate orally to increase fecal excretion of calcium.
  • In severe hypercalcemia, patients may require hydration, diuretics, steroids (hydrocortisone 100 mg IV q6h), calcitonin (4-8 IU/kg q6-12h), and/or mithramycin (25 mcg/kg qd IV over 4-6 h for 1-4 d). Peritoneal or hemodialysis may be necessary if large amounts of fluids cannot be given.
• Vitamins E, K, B-1, B-2, B-6, B-12, and C, and folate usually require only supportive measures.
• Vitamin B-3 (ie, niacin)
• • Provide supportive treatment as needed.
  • Aspirin taken 30 minutes before niacin decreases the flush response.

Consultations

Consult the regional poison control center or a local medical toxicologist (certified through the American Board of Medical Toxicology or the American Board of Emergency Medicine) for additional information and patient care recommendations.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Care is generally symptomatic and supportive. Gastrointestinal decontamination may be helpful to minimize amount of vitamin absorbed systemically. Administer charcoal for acute overdoses. Antiemetics or antidiarrheals are helpful if needed.

Drug Category: GI decontaminant

Empirically used to minimize systemic absorption of the toxin. May only benefit if administered within 1 h of ingestion.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit patients with the following conditions:
• • Risk for suicide
  • Intractable emesis
  • Altered mental status
  • Neurologic symptoms
  • Serious co-ingestions
  • Severe dehydration
  • Metabolic derangements (eg, hypercalcemia, severe electrolyte abnormalities, ECG changes, renal or liver damage)

Complications

• For complications of vitamin toxicity, see Physical.

Prognosis

• The prognosis is generally excellent. According to the American Association of Poison Control Centers' Toxic Exposure Surveillance System, in 2005, more than 62,000 acute or chronic vitamin overdoses were reported, with 73 major adverse outcomes and 1 death.¹

Patient Education

• Remind parents of children who ingested vitamins of the appropriate ways to childproof their homes and emphasize the need to use child-resistant bottles.
• Instruct adults who have unintentionally overdosed on vitamins as part of their megavitamin regimen on the serious adverse effects of such chemicals.
• For excellent patient education resources, visit eMedicine's Drug Overdose Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Iron Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to identify other potentially lethal co-ingestants, such as acetaminophen, aspirin, and dangerous prescription drugs (ie, digoxin, lithium, phenothiazines)
• Failure to always check if the vitamin overdose included iron supplements and failure to manage such an overdose aggressively
• Failure to be wary of large or chronic ingestions of all vitamins in children, especially the fat-soluble vitamins A and D
• Failure to note that vitamin K is dangerous in neonates
• Failure to abstain from administering vitamin C to anyone with G-6-PD deficiency (hemolysis)
• Failure to note that vitamin A potentially is very teratogenic in pregnancy
• Failure to note that folic acid may mask pernicious anemia
• Failure to include vitamin A toxicity in patients who present with headaches

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. 2005 Annual Report of the American Association of Poison Control Centers' National Poisoning and Exposure Database. Annual Reports of the National Poisoning and Exposure Database. Available at http://www.aapcc.org/annual.htm. Accessed July 5, 2007.
2. 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.
3. Pazirandeh S, Burns DL. Overview of vitamin A. UpToDate. Available at www.uptodate.com. Accessed July 5, 2007.
4. Bakerman S. ABC's of Interpretive Laboratory Data. 4^th ed. Scottsdale, AZ: Interpretive Laboratory Data, Inc; 2002.
5. Brody JE. In vitamin mania, millions take a gamble on health. In: New York Times. October 26, 1997:1, 20.
6. Cristoph RA. Vitamins. In: Manual of Toxicologic Emergencies. Year Book Medical Publishers; 1989:490-5.
7. Fischbach F. A Manual of Laboratory and Diagnostic Tests. 7^th ed. Lippincott Williams & Wilkins; 2004.
8. Food and Nutrition Board. Recommended Dietary Allowances. 10^th ed. National Academy Press: Washington, DC; 1989.
9. Goldfrank L, Lewis R. Vitamins. In: Goldfrank's Toxicologic Emergencies. 5^th ed. Prentice Hall; 1994:535-44.
10. Hathcock JN. Vitamins and minerals: efficacy and safety. Am J Clin Nutr. Aug 1997;66(2):427-37. [Medline].
11. Hoffman RS. Thiamine hydrochloride. In: Goldfrank L, ed. Goldfrank's Toxicologic Emergencies. 5^th ed. New York: Prentice Hall; 1997:825-6.
12. Med Lett Drugs Ther. Toxic effects of vitamin overdosage. Med Lett Drugs Ther. Aug 3 1984;26(667):73-4. [Medline].
13. Meyers DG, Maloley PA, Weeks D. Safety of antioxidant vitamins. Arch Intern Med. May 13 1996;156(9):925-35. [Medline].
14. 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.
15. Sachter JJ. Vitamins. In: Handbook of Medical Toxicology. Little Brown & Co Inc; 1993:399-402.
16. Watson WA, Litovitz TL, Klein-Schwartz W, Rodgers GC Jr, Youniss J, Reid N, et al. 2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2004;22(5):335-404. [Medline]. [Full Text].

Article Last Updated: Dec 12, 2007