eMedicine Specialties > Endocrinology > Metabolic Disorders

Vitamin A Toxicity

Author: Mohsen S Eledrisi, MD, FACP, FACE, Consultant, Department of Internal Medicine, Division of Endocrinology and Metabolism, King Abdulaziz National Guard Medical Center, Saudi Arabia
Coauthor(s): Kevin McKinney, MD, Assistant Professor, Department of Medicine, Division of Endocrinology and Metabolism, University of Texas Medical Branch at Galveston; Mohammad S Shanti, MD, ABEM, Chair, Department of Emergency Medicine, King Faisal Specialist Hospital and Research Center
Contributor Information and Disclosures

Updated: Sep 2, 2009

Introduction

Background

Vitamin A is an important fat-soluble vitamin. Its basic molecule is a retinol, or vitamin A alcohol. After absorption, retinol is transported via chylomicrons to the liver, where it is either stored as retinol ester or re-exported into the plasma in combination with retinol-binding protein for delivery to tissue sites.

Dietary vitamin A is obtained from preformed vitamin A (or retinyl esters), which is found in animal foods (liver, milk, kidney, and fish oil), fortified foods, and drug supplements. Dietary vitamin A is also obtained from provitamin A carotenoids from plant sources, principally carrots. Dietary vitamin A is available mainly as preformed vitamin A in western countries and as provitamin A carotenoids in developing countries.

The bioavailability of retinol is generally more than 80%, whereas the bioavailability and bioconversion of carotenes are lower. These may be affected by species, molecular linkage, amount of carotene, nutrition status, genetic factors, and other interactions. While in general the body absorbs retinoids and vitamin A very efficiently, it lacks the mechanisms to destroy excessive loads. Thus, the possibility of toxicity exists unless intake is carefully regulated.¹ Revision of earlier estimates of daily human requirements of vitamin A has been suggested; the suggestion is that estimates ought to be revised downwards. Concerns exist about the teratogenicity of vitamin A.²

Pathophysiology

The recommended daily allowance for vitamin A is 5000 international units (IU) for adults and 8000 IU for pregnant or lactating women. Being fat-soluble, vitamin A is stored to a variable degree in the body, making it more likely to cause toxicity when taken in excess amounts.³ In contrast, water-soluble vitamins are generally excreted in the urine and stored only to a limited extent; hence, adverse effects occur only when extremely large amounts are taken.

Frequency

United States

Nutritional surveys indicate that about 35-50% of adults regularly consume vitamin and mineral supplements. Data are not available for consumption of vitamins in children.

Mortality/Morbidity

• Mortality is rare from vitamin A toxicity.
• Morbidity is evident by the wide range of complications observed in this condition.

Race

The use of supplements is generally higher in whites, as well as in individuals with higher levels of education and income.

Sex

The use of vitamin supplements is more common among females.

Age

Single vitamins are consumed more often by adults, while multivitamins are administered more frequently to children.

Clinical

History

• Carotenemia, the ingestion of excessive amounts of vitamin A precursors in food, mainly carrots, is manifested by a yellow-orange coloring of the skin, primarily the palms of the hands and the soles of the feet. It differs from jaundice in that the sclerae remain white.
• In acute vitamin A toxicity, a history of some or all of the following may be obtained:
  • Nausea
  • Vomiting
  • Anorexia
  • Irritability
  • Drowsiness
  • Altered mental status
  • Abdominal pain
  • Blurred vision
  • Headache
  • Muscle pain with weakness
• In chronic vitamin A toxicity, a history of some or all of the following may be obtained:
  • Anorexia
  • Hair loss
  • Dryness of mucus membranes
  • Fissures of the lips
  • Pruritus
  • Fever
  • Headache
  • Insomnia
  • Fatigue
  • Irritability
  • Weight loss
  • Bone fracture⁴
  • Anemia
  • Bone and joint pains
  • Diarrhea
  • Menstrual abnormalities
  • Epistaxis

Physical

• Manifestations of acute toxicity
  • Muscle and bone tenderness, especially over the long bones of the upper and lower extremities
  • Neurologic manifestations with signs of increased intracranial pressure (eg, children may have bulging fontanelles)
• Manifestations of chronic toxicity
  • Alopecia
  • Skin erythema
  • Skin desquamation
  • Brittle nails
  • Exanthema
  • Cheilitis
  • Conjunctivitis
  • Petechiae
  • Liver cirrhosis
  • Premature epiphysial closure in children
  • Hepatosplenomegaly
  • Peripheral neuritis
  • Benign intracranial hypertension
  • Ataxia
  • Papilledema
  • Diplopia
  • Hyperostosis
  • Edema
  • Hepatic hydrothorax⁵

Causes

• Causes of carotenemia  
  • Carotenemia is the result of excessive intake of vitamin A precursors in foods, mainly carrots.
  • Other than the cosmetic effect, carotenemia has no adverse consequences because the conversion of carotenes to retinol is not sufficient to cause toxicity.
• Causes of vitamin A toxicity are generally categorized into acute and chronic.
  • Acute toxicity occurs within a few hours or days after a very large intake as a result of accidental over-ingestion or inappropriate therapy. The estimated toxic dose is about 25,000 IU/kg.
  • Chronic toxicity appears after ingestion of 25,000 IU or more daily for prolonged periods.

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