This article originally appeared in the March 2002 Harvard Heart Letter and is provided courtesy of Harvard Health Publications.

Nutrition: Are You Getting Too Much Vitamin A?

Taking a multivitamin pill every day is probably a good habit to get into. It puts a nutritional safety net under our flawed diets. This isn’t just a theory; several studies have shown that people who take multivitamins have a lower risk for coronary artery disease, colon cancer, and breast cancer.

But a study in the Jan. 2, 2002, Journal of the American Medical Association (JAMA) puts a wrinkle in any blanket endorsement of vitamin pills. Building on earlier research from Sweden, researchers at Harvard found that among postmenopausal women, diets rich in vitamin A were associated with a higher risk of hip fracture. But the risk wasn’t from beta-carotene, the source of vitamin A found in carrots, other vegetables, and a few fruits. It came primarily from the form of the vitamin called retinol. Retinol occurs naturally in a few foods like liver, fish-liver oils, eggs, and whole milk. It’s also used to fortify foods like low-fat and skim milk as a replacement for the retinol that is lost when fat is removed, and breakfast cereals. But the single greatest source in these women’s diets was multi- vitamin pills.

This and other studies—as well as recommendations made by the Institute of Medicine last year—may prompt the FDA to lower its vitamin A recommendation. Currently, the recommendation is to get 1,500 micrograms daily, and it’s that number that is used as the basis for the “% Daily Value” you see on nutrition labels. Food and vitamin makers may also start to ratchet down the amount of retinol they use. But in the meantime, consumers, particularly older women, may want to reconsider the vitamin pills that they’re taking and choose a brand that contains no more than 5,000 IU, which is the equivalent of 1,500 micrograms. Moreover, older women may want a product that lists beta-carotene as a source of the vitamin.

What the study found
This JAMA study was another analysis of the trove of data amassed by the Nurses’ Health Study, the continuing study of the health of about 120,000 American nurses that is now in its 26th year. The researchers didn’t report a dangerous cutoff point for vitamin A as such. Instead, they calculated how the risk of hip fracture went up with the level of vitamin A intake. For example, the women in the top 20% of vitamin A intake (who consumed 3,000 micrograms or more per day) had a 48% greater chance of fracturing a hip than the women in the bottom 20% (who consumed 1,250 micrograms or less). The fracture risk was even greater if only retinol intake was considered.

Bear in mind that this study was limited to postmenopausal women. Interestingly, the results showed that retinol intake does not seem to increase hip fracture risk among women on hormone replacement therapy (HRT). The researchers were puzzled by this result and didn’t have a ready explanation for HRT apparently blunting the effect of retinol on bones.

The osteoporosis connection
What you’ve been told about vitamin A being good for your eyes is true, but it misses the larger picture. Vitamin A seems to play a role in everything from gene expression to generation of white blood cells — and, especially, bone health. In large amounts, it seems to stimulate osteoclasts, scavenger cells that break down bone, and to suppress osteoblasts that build it up. It may also interfere with vitamin D, which is crucial to calcium metabolism. Experts may bat around the vitamin A data, but they don’t disagree on the potential that large doses have for causing bone abnormalities.

Beta-carotene vs. retinol
There are two classes of food substances that the body metabolizes to form vitamin A: carotenoids and retinols. Carotenoids, which confer color to plants, are found mainly in food from plants, but small amounts are also found in food from animals. About 10% of the carotenoids make some contribution of vitamin A to the diet, but beta-carotene is the main carotenoid source. Beta-carotene and the other carotenoids are far less potent than retinol: it takes 12 micrograms of beta-carotene to equal the biological activity generated by 1 microgram of retinol. This could explain why beta-carotene consumption wasn’t a factor in this latest hip-fracture study. Absorption and conversion of beta-carotene to vitamin A is influenced by retinol intake: the body’s use of beta-carotene goes up when retinol intake is low and goes down when it’s high.

The retinols require much less processing in the body to generate vitamin A, because they are chemically very similar to vitamin A. Indeed, they are sometimes called preformed vitamin A for that reason. Retinol usually comes in chemical combination with an acid, which is the reason you’ll sometimes see vitamin A acetate, vitamin A palmitate, or even just palmitate listed on a vitamin label.

Food sources
Liver. Beef liver is less popular than it used to be, but no other readily available food has so much vitamin A. A 31/2-ounce portion contains 15,800 micrograms of retinol, which is over ten times the FDA’s recommended daily intake of 1,500 micrograms. In the Nurses’ Health Study, the largest single food source of vitamin A was liver, although the researchers found that consumption levels have fallen since the early 1980s.

Milk. The vitamin A content of milk varies, but, on average, a cup has about 100 micrograms of retinol. In the United States, retinol is added back to low-fat and skim milk, so it can end up containing more
vitamin A than whole milk.

Breakfast cereals. Different brands are fortified with different amounts. Several years ago, a serving may have had as much as 350 micrograms of retinol. But manufacturers have since cut back, and breakfast cereal by itself is no longer a major source of retinol.

Carrots. Carrots are, by far, the biggest source of beta-carotene in the American diet. But because of the 12:1 ratio at which beta-carotene is changed into vitamin A, they don’t pack as much punch as might be expected. The body typically extracts a “dose” of only about 600 micrograms of physiologically active vitamin A from the beta-carotene and other carotenoids contained in a 7 1/2-inch raw carrot.

Multivitamins
In the nurses’ study, multivitamin pills contributed 35%–43% of the total retinol in the diet. Many brands use beta-carotene for 20% of their vitamin A content. (See chart.) But unless it is specified as beta-carotene, the remainder is some form of retinol. Products sold as antioxidants often use 100% beta-carotene, but they lack some of the nutrients of the products sold as multivitamins.

The take-homes

  Good evidence indicates that high intake of retinol may adversely affect bone health, particularly in postmenopausal women.

  The risk is from retinol, not the beta-carotene contained in carrots, leafy green vegetables, and some fruits.

  For most Americans, the single largest source of retinol is multivitamin pills. But this doesn’t mean you should stop taking multivitamins. The evidence of their benefit is persuasive. It does mean, however, you might avoid brands that go overboard with vitamin A doses of 10,000 IU, which is double the daily amount that the FDA currently recommends, and four times the daily amount that the nurses’ study suggests is optimal. A safer choice would be a brand containing 5,000 IU or less.

  Look for brands of multivitamins that use at least some beta-carotene as a source of vitamin A.

  Avoid vitamin A pills. They should be taken under medical supervision.

  Vitamin intake, in general, is not a more-the-merrier proposition. This is particularly true of the fat-soluble vitamins, such as vitamins A, D, E, and K that accumulate in the body. They are more likely to produce adverse effects when taken in large amounts.