Vitamin A - Toxicity

Smith, F.R. & Goodman, D.S. 1976.Vitamin A transport in Human vitamin A toxicity. N. Engl. J. Med., 294: 805–808. 

Because vitamin A is fat soluble and can be stored, primarily in the liver, routine consumption of large amounts of vitamin A over a period of time can result in toxic symptoms, including liver damage, bone abnormalities and joint pain, alopecia, headaches and vomiting, and skin desquamation. Hypervitaminosis A appears to be due to abnormal transport and distribution of vitamin A and retinoids caused by overloading of the plasma transport mechanisms.

Hathcock, J.N. Evaluation of vitamin A toxicity. Am. J. Clin. Nutr., 52: 183–202.

Hathcock, J.N. 1997. Vitamins and minerals: efficacy and safety. Am. J. Clin. Nutr., 66: 427–437.

The smallest daily supplement associated with liver cirrhosis that has been reported is 7500 μg taken for 6 years. 

Very high single doses can also cause transient acute toxic symptoms that may include bulging fontanels in infants; headaches in older children and adults; and vomiting, diarrhoea, loss of appetite, and irritability in all age groups. Rarely does toxicity occur from ingestion of food sources of preformed vitamin A. When this occurs, it usually results from very frequent consumption of liver products. Toxicity from food sources of pro-vitamin A carotenoids is not reported except for the cosmetic yellowing of skin.

Humphrey, J.H. 1998. Neonatal vitamin A supplementation: effect on development and
growth at 3 y of age. Am. J. Clin. Nutr., 68: 109–117.

Baqui, A.H. 1995. Bulging fontanelle after supplementation with 25,000 IU vitamin A in
infancy using immunisation contacts. Acta Paediatrica, 84: 863–866.

de Francisco, A. 1993. Acute toxicity of vitamin A given with vaccines in infancy. Lancet, 342: 526–527.

Infants, including newborns, administered single doses equivalent to 15 000– 30 000 μg retinol (50 000–100 000 IU) in oil generally show no adverse symptoms. However, daily prophylactic or therapeutic doses should not exceed 900 μg, that is well above the mean requirement of about 200 μg daily for infants. An excess of bulging fontanels occurred in infants under 6 months of age in one endemically deficient population given two or more doses of 7500 μg or 15 000 μg preformed vitamin A in oil, 

WHO/CHD Immunisation-Linked Vitamin A Supplementation Study Group. 1998. Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy. Lancet, 352: 1257–1263.

but other large-scale controlled clinical trials have not reported excess bulging after three doses of 7500 μg given with diptheria-pertussis-tetanus immunisations at about 6, 10, and 14 weeks of age.  

Humphrey, J.H. 1998. Neonatal vitamin A supplementation: effect on development and growth at 3 y of age. Am. J. Clin. Nutr., 68: 109–117.

Humphrey, J.H. 1998. Neonatal vitamin A supplementation: effect on development and growth at 3 y of age. Am. J. Clin. Nutr., 68: 109–117.

No effects were detected at 3 years of age that related to transient vitamin A–induced bulging that had occurred before 6 months of age. 

Hathcock, J.N. Evaluation of vitamin A toxicity. Am. J. Clin. Nutr., 52: 183–202.

Most children 1–6 years of age tolerate single oral doses of 60 000 μg (200 000 IU) vitamin A in oil at intervals of 4–6 months without adverse symptoms.  Occasionally diarrhoea or vomiting is reported but is transient with no lasting sequelae. Older children seldom experience toxic symptoms unless they habitually ingest vitamin A in excess of 7500 μg (25 000 IU) for prolonged periods of time. 

Hathcock, J.N. 1997. Vitamins and minerals: efficacy and safety. Am. J. Clin. Nutr., 66:

427–437.

When taken by women at early stages of gestation at daily levels of more than 7500 μ g (25 000 IU), foetal anomalies and poor reproductive outcomes are reported. 

WHO. 1998. Safe vitamin A dosage during pregnancy and lactation. pp.34. WHO/NUT/98.4. Geneva, World Health Organization.

One report suggests an increased risk of teratogenicity at intakes as low as 3000 μg (10 000 IU) but this is not confirmed by other studies.  

Women who are pregnant or might become pregnant should avoid taking excessive amounts of vitamin A. A careful review of the latest available information by a WHO Expert Group recommended that daily intakes in excess of 3000 μg (10 000 IU) or weekly intakes in excess of 7500 μg (25 000 IU), should not be taken at any period during gestation. High doses of vitamin A (60 000 μg, or 200 000 IU) can be safely given to breast-feeding mothers for up to 2 months postpartum and for 6 weeks for women who are not breast-feeding.