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Acute vitamin A toxicity (hypervitaminosis), caused by preformed vitamin A (retinol), which is rapidly absorbed and
slowly cleared from the body, is relatively rare. Symptoms include nausea, headache, fatigue, loss of appetite,
dizziness, dry skin, and brain swelling (cerebral edema) (1).
Chronic toxicity results from the ingestion of high amounts of preformed vitamin A for months or years. Intakes of
more than 25,000 IU/day for over 6 years, or more than 100,000 IU/day for over 6 months are considered toxic,
but there is wide interindividual variability (35). Severe cases of hypervitaminosis A may result in liver damage,
bleeding (hemorrhage), and coma.
There is evidence that some populations may be more susceptible to toxicity at lower doses, including the elderly
and chronic alcohol users (36).
Osteoporose risk
Results of some prospective studies suggest that long-term intakes of preformed vitamin A in excess of 1.5 mg/day
(5,000 IU/day) are associated with increased risk of osteoporotic fracture and decreased bone mineral density
(BMD) in older men and women (38, 39, 40). Only excess intakes of preformed vitamin A (retinol), not
beta-carotene, were associated with adverse eects on bone health.
Although these observational studies cannot provide the reason for the association between excess retinol intake
and osteoporosis, limited experimental data suggest that excess retinol may stimulate bone loss (resorption) (41) or
interfere with the ability of vitamin D to maintain calcium balance (42).
However, results of other studies indicate that vitamin A intake is not associated with detrimental eects on BMD or
fracture risk (43, 44, 45). A signicant number of elderly people have insucient vitamin A intakes, which have also
been associated with decreased BMD. One study of elderly men and women found that BMD was optimal at vitamin A
intakes close to the RDA (39).
Vitamin A plus other antioxidants
An evaluation of data from the VITamins And Lifestyle (VITAL) cohort study discussed the connection between
antioxidant supplements and the incidence of lung cancer (46). The authors speculated that longer duration of use
of individual vitamin A (retinol), beta-carotene, and lutein supplements was associated with elevated risk of total
lung cancer. However, experts commented that the retrospective study was awed due to an invalid design, biased
questionnaire methodology, and questionable statistical evaluations (see also Expert Opinion).
In addition, a meta-analysis of 67 studies concluded that it did not nd convincing evidence that antioxidant
supplements have benecial eects on mortality. Additionally, it stated that vitamin A, beta-carotene, and vitamin E
seem to increase the risk of death (11). However, experts raised serious doubts about the conclusions as they were
drawn from a awed meta-analysis pooling data from trials with varied populations (healthy and diseased
individuals) and dierent methodologies (47) (see also Expert Opinion).
Pregnancy risk: (see Tolerable upper intake levels)

Tolerable upper intake levels

The European Food Safety Authority has established tolerable upper intake levels (UL) for preformed vitamin A
(retinol) intake (37):
Age (years)
13
46
710
1114
1517
Adults

UL (mg/day)
0.8
1.1
1.5
2.0
2.6
3.0

The U.S. Food and Nutrition Board (FNB) of the Institute of Medicine has set tolerable upper levels (UL) for
preformed vitamin A (retinol) intake (24):
Age Group
Infants 012 months
Children 13 years
Children 48 years
Children 913 years
Adolescents 1418 years
Adults 19 years and older

UL in mg/day

(IU/day)

0.6
0.6
0.9
1.7
2.8
3.0

(2,000 IU)
(2,000 IU)
(3,000 IU)
(5,667 IU)
(9,333 IU)
(10,000 IU)

Pregnancy risk
Normal fetal development requires sucient vitamin A intake. Based on animal studies with retinoic acid it has been
suggested that consumption of high doses of retinol during pregnancy may cause malformations in the newborn.
No increase in the risk of vitamin A-associated birth defects has been observed at doses of preformed vitamin A from
supplements below 3 mg/day (10,000 IU/day) (24).
Pregnant women should avoid multivitamin or prenatal supplements that contain more than 1.5 mg/day (5,000 IU)
of vitamin A.
Vitamin A from beta-carotene is not known to increase the risk of birth defects.
Some synthetic derivatives of retinol (e.g. tretinate, isotretinoin, and tretinoin) are known to cause serious birth
defects and should not be taken during pregnancy or if there is a possibility of becoming pregnant.

Drug interactions
Please note:
Because of the potential for interactions, dietary supplements should not be taken with medication without rst
talking to a knowledgeable healthcare provider.