Many of you may have read headlines about possible fractures due to excess Vitamin A. Here is a series of communications to the Journal of the American Medical Association on that topic: Does High Intake of Vitamin A Pose a Risk for Osteoporotic Fracture? To the Editor: Dr Feskanich and colleagues1 found that high intake of dietary retinol (ie, vitamin A) was related to risk of hip fracture in postmenopausal women. They interpret these data as supportive of but not conclusive of a causal relationship. The possible risks associated with high intake of retinol were reviewed in 2001 by the Food and Nutrition Board (FNB) of the Institute of Medicine,2 which found the relevant studies "provocative but conflicting" and concluded that "they are not useful for setting a UL [upper limit] for vitamin A." Thus, the FNB suggested an upper limit for vitamin A of 3000 µg/d of retinol (equivalent to 10 000 IU/d) based on other effects, such as risk of birth defects, recognized as related to excess vitamin A. After the FNB review was completed in 2001, other studies, including the third National Health and Nutrition Examination Survey (NHANES III)3 and a smaller study in Iceland,4 have failed to find any relationship between serum retinyl esters, a marker of excessive retinol intake, and bone mineral density, a marker of bone strength. A recent double-blind, crossover clinical trial5 showed that a large single daily dose of 15 mg of retinyl palmitate (providing 8190 µg[27 260 IU] of retinol) decreased the serum calcium response to a single dose of the activated form of vitamin D (2 µg of 1,25-dihydroxyvitamin D3) several hours after administration of both vitamins together. This study suggested a more complex mechanism for possible adverse effects of massive intakes of retinol on bone health. The issue for vitamin A and bone health is not whether mechanisms exist, however, but instead whether the effect occurs at the usual levels of retinol intake experienced by most persons. Overall, the evidence relating to a possible relationship between moderately high retinol intake and possible adverse effects on bone health remains inconclusive. John N. Hathcock, PhD Council for Responsible Nutrition Washington, DC 1. Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA. 2002;287:47-54. 2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001:65-126. Available at: http://books.nap.edu/books/0309072794/html/index.html. 3. Ballew C, Galuska D, Gillespie C. High serum retinyl esters are not associated with reduced bone mineral density in the third National Health and Nutrition Examination Survey, 1988-1994. J Bone Miner Res. 2001;16:2306-2312. 4. Sigurdsson G, Franzson L, Thorgeirsdottir H, Steingrimsdottir L. A lack of association between excessive dietary intake of vitamin A and bone mineral density in seventy-year-old Icelandic women. In: Burckhardt P, Dawson-Hughes B, Heaney RP, eds. Nutritional Aspects of Osteoporosis. San Diego, Calif: Academic Press; 2001:295-302. 5. Johansson S, Melhus H. Vitamin A antagonizes calcium response to vitamin D in man. J Bone Miner Res. 2001;16:1899-1905. The Council for Responsible Nutrition is an association of the dietary supplement industry.ED. In Reply: We agree with Dr Hathcock that dietary guidance must be based on collected evidence from various scientific sources. With this in mind, we analyzed data from the Nurses' Health Study after a Swedish study reported that retinol intake was positively associated with risk of hip fracture and inversely associated with femoral bone mineral density in women.1 Our finding of a significant increase in risk of hip fracture with higher retinol intakes in postmenopausal women was very similar to that observed in the Swedish study. Although we recognize the inherent limitations of observational research, laboratory data come with their own strengths and weaknesses. An analysis of data from NHANES III showed no association between serum retinyl esters and bone mineral density,2 although this finding is difficult to interpret because there was a single measurement of blood retinyl esters without evidence that this reflects long-term retinol intake. Also, although bone mineral density is a major factor in osteoporotic fracture, it is not synonymous with fracture, which is the outcome of public health concern. The small Icelandic study that Hathcock cites3 also assessed bone mineral density rather than fracture and did not control for vitamin D intake, which confounds the observed effects of retinol. Without absolute certainty about whether higher retinol intakes within the range consumed by the US population can lead to bone loss and fracture with long-term intake, and in a situation such as this, where a randomized trial is unlikely to be done, we believe that the principle of reasonable certainty of no harm is appropriate. That is, because we cannot be certain that retinol intake of approximately of 1500 µg/d [5000 IU/d] is without adverse consequences, we recommend judicious supplementation and fortification with vitamin A. Retinol levels in multivitamins and processed foods can easily be lowered or partially replaced with beta carotene without risk of deficiency. This would be facilitated by a lowering of the US recommended daily allowance labeling standards for vitamin A from the current 1500 µg (5000 IU) to a value more comparable with the adequate intake level for retinol (700 µg for women and 900 µg for men) recently set by the Food and Nutrition Board. Some of the major multivitamin producers are already moving in this direction. Diane Feskanich, ScD Walter C. Willett, MD, DrPH Graham A. Colditz, MD, DrPH Brigham and Women's Hospital and Harvard Medical School Boston, Mass 1. Melhus H, Michaelsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med. 1998;129:770-778. 2. Ballew C, Galuska D, Gillespie C. High serum retinyl esters are not associated with reduced bone mineral density in the third National Health and Nutrition Examination Survey, 1988-1994. J Bone Miner Res. 2001;16:2306-2312. 3. Sigurdsson G, Franzson L, Thorgeirsdottir H, Steingrimsdottir L. A lack of association between excessive dietary intake of vitamin A and bone mineral density in seventy-year-old Icelandic women. In: Burckhardt P, Dawson-Hughes B, Heaney RP, eds. Nutritional Aspects of Osteoporosis. San Diego, Calif: Academic Press; 2001:295-302. JAMA letters, March 20, 2002 Vol 287 No. 11 J Nutrition, 6/02 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.