Challenging the Vitamin A–Hip Fracture Link

Long-term consumption of a diet high in vitamin A can increase the risk of hip fractures in postmenopausal women, according to a recent study in the Journal of the American Medical Association.¹ However, after carefully reviewing the new research, this scientist is not convinced.

In 1980, some 72,337 postmenopausal women participating in the Nurses' Health Study filled out a questionnaire concerning diet and use of nutritional supplements; the information was then updated periodically in subsequent years. In the 18-year follow-up period, 603 hip fractures resulting from low or moderate trauma (i.e., fractures presumably due to osteoporosis) occurred among study participants. Women who consumed the most vitamin A from food and supplements (i.e., those in the top 20%) had an 89% higher risk of hip fracture, compared with those consuming the least vitamin A (bottom 20%). Among women not taking vitamin A supplements, those with the highest dietary intake had a 69% higher risk of hip fracture, compared with those ingesting the least vitamin A. When vitamin A from supplements was considered separately, there was no statistically significant association with fracture risk, although there was a trend toward increased risk with increasing levels of supplementation.

Surprisingly small amounts of vitamin A were needed to increase a woman's fracture risk: as little as 6,667 IU per day when considering food in addition to supplements, and 3,333 IU per day when considering diet alone. Beta-carotene, a dietary constituent similar to vitamin A, was not associated with fracture risk and was not included in the analysis of vitamin A intake.

If the results of this study are to be taken at face value, then vitamin A can cause adverse effects on bone health at a level well below that which is typically associated with toxicity. Even 10,000 IU of supplemental vitamin A (an amount found in many multiple-vitamin preparations) would be above the safety threshold, and as little as 5,000 IU per day of supplemental vitamin A would be bordering on too much. Eating as little as one three-ounce serving of liver every ten days would, by itself, put a woman's dietary vitamin A intake over the top.

However, there is reason to question the assertion that relatively small amounts of vitamin A might lead to osteoporosis and hip fractures, because that conclusion is not consistent with the known actions of the vitamin. While vitamin A toxicity does adversely affect bone, the amounts required to produce such effects are extremely large. For example, in a study in rats, supplementation with vitamin A in amounts equivalent to a human dose of 20 million IU per day for five weeks inhibited the healing of fractures and resulted in the formation of fragile bones. However, half that amount (equivalent to a human dose of approximately 10 million IU per day for five weeks) actually accelerated fracture healing.² Well-known consequences of chronic vitamin A toxicity in humans, which requires long-term intake of at least 33,300 IU per day, include hair loss, neurological problems, headaches, liver damage, visual impairment, and dry skin. Osteoporosis, on the other hand, has not been previously reported. It is difficult to believe, therefore, that intakes more than 80% lower than the chronic toxicity threshold would lead to bone loss.

A more likely explanation for the recent findings is that vitamin A intake is merely a marker for certain dietary patterns associated with osteoporosis. The main food sources of vitamin A in the American diet, aside from liver, are fortified skim and low-fat milk (5,000 IU per liter), fortified breakfast cereals (up to 1,250 IU per serving), and fortified margarine (approximately 500 IU per tablespoon). A daily diet that includes two cups of fortified milk plus either one serving of fortified breakfast cereal or two tablespoons of margarine would put a person in the top category of vitamin A intake.

There is circumstantial evidence that some or all of the foods high in vitamin A can promote the development of osteoporosis, for reasons unrelated to their vitamin A content. For example, fortified breakfast cereals often contain large amounts of added sugar. A high intake of refined sugar has been shown to increase urinary calcium excretion in humans and to cause bone loss in experimental animals.^{3 4} Most brands of margarine contain substantial quantities of compounds known as trans-fatty acids, which are produced during the manufacturing process. Ingestion of these trans-fatty acids can promote a deficiency of essential fatty acids,⁵ nutrients essential for normal bone health.⁶ Fortified milk, another significant dietary source of vitamin A, may also be a less-than-perfect food for the bones, despite its high calcium content. Milk is one of the major sources of dietary phosphorus, a mineral that is often present in excessive amounts in the American diet. Consumption of too much phosphorus can impair bone health, particularly in older women.⁷ In addition, dairy products are the only significant dietary source of naturally occurring trans-fatty acids.⁸ Studies examining the relationship between milk consumption and bone health have yielded conflicting results,⁹ and one study (using data from the same Nurses' Health Study described above) showed an increased risk of fractures in women who consumed two or more glasses of milk per day, compared with women consuming one glass or less per week.¹⁰

Liver, the other major dietary source of vitamin A, accumulates various environmental toxins, including lead and cadmium,¹¹ both of which can cause osteoporosis. In addition, some environmental chemicals that might concentrate in the liver may conceivably promote bone loss through their capacity to inhibit the activity of certain hormones (androgens).¹²

Based on these considerations, it is difficult to conclude that the reported association between vitamin A intake and hip fractures represents a cause-effect relationship. Perhaps the real culprits are refined sugar, trans-fatty acids, milk, and environmental toxins.

References:

1. Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002;287:47–54.
2. Udupa KN, Gupta LP. Role of vitamin A in the repair of fracture. Indian J Med Res 1966;54:1122–30.
3. Lemann J Jr, Piering WF, Lennon EJ. Possible role of carbohydrate-induced calciuria in calcium oxalate kidney-stone formation. N Engl J Med 1969;280:232–7.
4. Saffar JL, Sagroun B, de Tessieres C, Makris G. Osteoporotic effect of a high-carbohydrate diet (Keyes 2000) in golden hamsters. Arch Oral Biol 1981;26:393–7.
5. Holman RT, Aaes-Jorgensen E. Effects of trans fatty acid isomers upon essential fatty acid deficiency in rats. Proc Soc Exp Biol Med 1956;93:175–9.
6. Odutuga AA. Effects of low-zinc status and essential fatty acid deficiency on bone development and mineralization. Comp Biochem Physiol 1982;71A:383–8.
7. Calvo MS, Park YK. Changing phosphorus content of the U.S. diet: potential for adverse effects on bone. J Nutr 1996;126:1168S–80S.
8. Oomen CM, Ocke MC, Feskens EJM, et al. Association between trans fatty acid intake and 10-year risk of coronary heart disease in the Zutphen Elderly Study: a prospective population-based study. Lancet 2001;357:746–51.
9. Weinsier RL, Krumdieck CL. Dairy foods and bone health: examination of the evidence. Am J Clin Nutr 2000;72:681–9.
10. Feskanich D, Willett WC, Stampfer MJ, Colditz GA. Milk, dietary calcium, and bone fractures in women: a 12-year prospective study. Am J Public Health 1997;87:992–7.
11. Boyer KW, Jones JW, Linscott D, et al. Trace element levels in tissues from cattle fed a sewage sludge-amended diet. J Toxicol Environ Health 1981;8:281–95.
12. Sohoni P, Sumpter JP. Several environmental oestrogens are also anti-androgens. J Endocrinol 1998;158:327–39.

Alan R. Gaby, MD, an expert in nutritional therapies, served as a member of the Ad-Hoc Advisory Panel of the National Institutes of Health Office of Alternative Medicine. He is the Medical Editor for Clinical Essentials Alert, is the author of Preventing and Reversing Osteoporosis (Prima, 1994), and co-author of The Natural Pharmacy, 2nd Edition (Healthnotes, Prima, 1999), the A–Z Guide to Drug-Herb-Vitamin Interactions (Healthnotes, Prima, 1999), Clinical Essentials Volume 1 and 2 (Healthnotes, 2000), and The Patient’s Book of Natural Healing (Prima, 1999). Currently he is the Endowed Professor of Nutrition at Bastyr University of Natural Health Sciences, Kenmore, WA.

Copyright © 2002 Healthnotes, Inc. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.