Vitamin A and Hip Fractures
Source: Feskanich D, et al. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002;287: 47-54.
Ingestion of toxic amounts of vitamin A affects bone remodeling and can have adverse skeletal effects in animals. The possibility has been raised that long-term intake of large doses of vitamin A could contribute to fracture risk in humans.
To assess the relationship between high vitamin A intake from foods and supplements and risk of hip fracture among postmenopausal women, a prospective analysis was begun in 1980 with 18 years of follow-up within the Nurses’ Health Study. The general community of registered nurses within 11 U.S. states, for a total of 72,337 postmenopausal women ages 34-77 years, was studied.
Incident hip fractures resulting from low or moderate trauma were analyzed by quintiles of vitamin A intake and by use of multivitamins and vitamin A supplements. These assessments were made at baseline and updated during follow-up.
From 1980 to 1998, 603 incident hip fractures resulting from low or moderate trauma were identified. After controlling for confounding factors, women in the highest quintile of total vitamin A intake (³ 3,000 mcg/d of retinol equivalents [RE]) had a significantly elevated relative risk (RR) of hip fracture (RR 1.48; 95% confidence interval [CI] 1.05-2.07; P for trend = 0.003) compared with women in the lowest quintile of intake (< 1,250 mcg/d of RE). This increased risk was attributable primarily to retinol (RR 1.89; 95% CI 1.33-2.68; P for trend < 0.001 comparing ³ 2,000 mcg/d vs. < 500 mcg/d).
The association of high retinol intake with hip fracture was attenuated among women using postmenopausal estrogens. Beta-carotene did not contribute significantly to fracture risk (RR 1.22; 95% CI 0.90-1.66; P for trend = 0.10 comparing ³ 6,300 mcg/d vs. < 2,550 mcg/d). Women currently taking a specific vitamin A supplement had a non-significant 40% increased risk of hip fracture (RR 1.40; 95% CI 0.99-1.99) compared with those not taking the supplement. Among women not taking supplemental vitamin A, retinol from food was significantly associated with fracture risk (RR 1.69; 95% CI 1.05-2.74; P for trend = 0.05 comparing ³ 1,000 mcg/d vs. < 400 mcg/d).
Long-term intake of a diet high in retinol may promote the development of osteoporotic hip fractures in women. The amounts of retinol in fortified foods and vitamin supplements may need to be reassessed.
Comment
The subjects of the well-known Nurses’ Health Study (NHS) are largely white, middle and upper middle class women who already take multivitamins and are interested in their health. Most of these women were taking multivitamins that contained retinol (the form of vitamin A that does the damage, in excess), plus the vitamin A they get from food. The vitamin A supplements that contain retinol (and not all do—many contain a retinyl ester instead) are the forms that "may promote the development of osteoporotic hip fractures in women."
These women, if anyone, should have been able to avoid hip fractures. Their intake of calcium, vitamin K, and vitamin D are all higher than national averages. Their intake of alcohol is lower (alcohol worsens vitamin A toxicity, and in modest doses increases bone density). But they didn’t.
Although some retinol comes from food, most comes from vitamin supplements, especially multivitamins. Few foods have retinol. Liver, fish liver oils, eggs, and whole-milk dairy products are the chief sources. An editorial comment on this study notes: "A 3-oz (84-g) portion of liver contains 100 times the retinol present in one glass of whole milk, 116 times that in one whole egg, and 200 times that in a pat of butter. Vitamin A intake variability is further affected by the three-fold natural seasonal variation in the vitamin A content of milk." In addition, fortified breakfast cereals and meal replacement drinks and shakes often have 100% RDI of vitamin A, and some part of that is retinol.
Paradoxically, vitamin A deficiency is the third most common nutrient deficiency in the world, largely in third world countries. In the United States, these authors believe the elderly, in particular, are at risk for vitamin A toxicity.
Recommendations from the Institute of Medicine for appropriate vitamin A intake are 800 mcg/d for men and 700 mcg/d for women. The safe upper limit is 3,000 mcg/d of retinol. In addition, fetal injury with consistent maternal intake of 10,000 mcg/d of retinol has been reported.
Finally, pro-vitamin A (beta-carotene), which accounts for about one-third of vitamin A intake from food, also was higher in this group than it is nationally, but these nurses eat more fruits and vegetables than the public at large. There is no reason—not even a suggestion—that anyone should cut back on beta-carotene containing foods—just supplements. Actually, deeply colored, carotene-rich fruits and vegetables—mangoes, carrots, and sweet potatoes—only give half as much vitamin A as previously thought.
Recommendation
Adult women who eat healthfully (low in saturated and trans fat; high in fruits and vegetables; and low-fat dairy) should avoid vitamin A supplements, including multivitamins containing retinol, especially if they get plenty of vitamin A and pro-vitamin A from food.
La Puma J. Vitamin A and hip fractures. Altern Med Alert 2002;5:75-76.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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