Women who faithfully consume plenty of vitamin A from foods and supplements may not be doing themselves much of a favor, says a group of Harvard researchers. Their study, published in the Journal of the American Medical Association, suggests that a high intake of vitamin A may actually increase an older woman's risk of hip fracture.

Diet analyses

The researchers analyzed the diets of more than 72,000 participants of the ongoing Nurses' Health Study and tallied their intake of vitamin A from both food and dietary supplements. They then tracked the women for 18 years, noting the number of women who suffered a hip fracture due to low or moderate trauma (slipping or tripping, or falling from the height of a chair) during that time.

They found that women who consumed in excess of 3,000 micrograms (µg) of vitamin A per day from foods and supplements were over 40% more likely to suffer a hip fracture when compared with women who consumed less than 1,250 µg per day (RR=1.48, 95% CI 1.05-2.07; p for trend=0.003). This effect was most pronounced in those who did not receive hormone replacement therapy (HRT).

The increased risk was associated with the intake of retinal - the form of vitamin A obtained from animal sources - rather than from carotenoids (plant compounds with provitamin A activity). Looking only at retinol intake, women who consumed at least 1,500 µg per day were over 60% more likely than those consuming less than 500 µg per day to suffer a hip fracture (RR=1.64, 95% CI 1.14-2.35).

Scientists need time to unravel these results

About 86% of the women were consuming the recommended amount of at least 700 µg of vitamin A per day. More than 20% of the women, though, were consuming more than 3000 µg per day, the level determined by US health officials to be the "tolerable upper limit", the amount that most healthy adults can consume without risk of adverse effects. This is apparently fairly easy to do for those who routinely take vitamin supplements and eat a large amount of vitamin A-rich foods, including liver, eggs, dairy foods, and fish oils. In the United States, foods fortified with vitamin A -low-fat milk, margarine, and many cereals - add to the total.

A possible explanation

Sustained high doses of vitamin A, as would occur in patients using retinoid-based skin preparations, have been associated with calcification of ligaments, bone remodeling abnormalities, and osteoporosis. Further, research in animals has shown that high doses of retinoic acid inhibit osteoblast activity, increase osteoclast formation, and interfere with the ability of vitamin D to control calcium stasis, all of which may accelerate bone demineralization. It is not yet clear, though, why this study found an increased rate of hip fracture among women consuming what is currently considered to be a reasonable intake of vitamin A.

Advice to patients

The study's authors stress that older women who use vitamin A preparations for therapeutic reasons should not discontinue using them, nor should they stop taking multivitamins if they require them to meet nutrient needs. They do advise clinicians, though, to monitor changes in bone density in their patients, a wise precaution for all older women regardless of how much vitamin A they consume.

Note: The authors conclude their article with a call to US health officials to reconsider the amount of vitamin A that is added to foods, suggesting that consumption of vitamin A-fortified foods is harmful to bone health in older women. But basic foods - milk, margarine, and cereal - are fortified with vitamin A to guard against deficiency in children, a group not considered in this study.

How does it measure up?

Vitamin A is measured in Retinol Activity Equivalents (RAE) in the literature, but in International Units (IU) on multivitamin labels. Here's how to do the conversion:

1 RAE =

1 µg of retinol 12 µg beta-carotene

1 IU =

0.3 µg vitamin A from retinol 3.6 µg vitamin A from beta-carotene