Vitamin A // Retinol

Safety

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 effects 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 effects on BMD or fracture risk (43, 44, 45). A significant number of elderly people have insufficient 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 flawed 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 find convincing evidence that antioxidant supplements have beneficial effects 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 flawed meta-analysis pooling data from trials with varied populations (healthy and diseased individuals) and different 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) UL (mg/day)  
 1–3 0.8  
 4–6 1.1  
 7–10 1.5  
 11–14 2.0  
 15–17 2.6  
 Adults 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

UL in mg/day (IU/day)
 Infants 0–12 months 0.6 (2,000 IU)
 Children 1–3 years 0.6 (2,000 IU)
 Children 4–8 years 0.9 (3,000 IU)
 Children 9–13 years 1.7 (5,667 IU)
 Adolescents 14–18 years 2.8 (9,333 IU)
 Adults 19 years and older 3.0 (10,000 IU)

Pregnancy risk

Normal fetal development requires sufficient 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 first talking to a knowledgeable healthcare provider.