Vitamin A, Beta-Carotene, and Cancer

Dietary intake studies suggest an association between diets rich in beta-carotene and vitamin A and a lower risk of many types of cancer.1 A higher intake of green and yellow vegetables or other food sources of beta carotene and/or vitamin A may decrease the risk of lung cancer.2 Similar results were seen in the Carotene and Retinol Efficacy Trial (CARET), a lung cancer chemoprevention study that provided subjects with supplements of 30 mg beta-carotene and 25,000 IU retinyl palmitate (a form of vitamin A) or a placebo. This study was stopped after researchers discovered that subjects receiving beta-carotene had a 46% higher risk of dying from lung cancer.3 4</p> <blockquote><p>The <a title=">IOM states that "beta-carotene supplements are not advisable for the general population," although they also state that this advice "does not pertain to the possible use of supplemental beta-carotene as a provitamin A source for the prevention of vitamin A deficiency in populations with inadequate vitamin A."5

Vitamin A and Osteoporosis

Osteoporosis, a disorder characterized by porous and weak bones, is a serious health problem for more than 10 million Americans, 80% of whom are women. Another 18 million Americans have decreased bone density which precedes the development of osteoporosis. Many factors increase the risk for developing osteoporosis, including being female, thin, inactive, at advanced age, and having a family history of osteoporosis. An inadequate dietary intake of calcium, cigarette smoking, and excessive intake of alcohol also increase the risk.6 7 8</p> <blockquote><p>Researchers are now examining a potential new <a title=">risk factor for osteoporosis: an excess intake of vitamin A. Animal, human, and laboratory research suggests an association between greater vitamin A intake and weaker bones.9 10 To further test the association between excess dietary intakes of vitamin A and increased risk for <a title=">hip fractures, researchers in Sweden compared bone mineral density and retinol intake in approximately 250 women with a first hip fracture to 875 age-matched controls. They found that a dietary retinol intake greater than 1,500 mcg/day (more than twice the recommended intake for women) was associated with reduced bone mineral density and increased risk of hip fracture as compared to women who consumed less than 500 mcg/day.11</p> <p>This issue was also examined by researchers with the <a title=">Nurses Health Study, who looked at the association between vitamin A intake and hip fractures in over 72,000 postmenopausal women. Women who consumed the most vitamin A in foods and supplements (3,000 mcg or more per day as retinol equivalents, which is over three times the recommended intake) had a significantly increased risk of experiencing a hip fracture as compared to those consuming the least amount (less than 1,250 mcg/day). The effect was lessened by use of estrogens. These observations raise questions about the effect of retinol because retinol intakes greater than 2,000 mcg/day were associated with an increased risk of hip fracture as compared to intakes less than 500 mcg.12</p> <p>A <a title=">longitudinal study in more than 2,000 Swedish men compared blood levels of retinol to the incidence of fractures in men. The investigators found that the risk of fractures was greatest in men with the highest blood levels of retinol (more than 75 mcg per deciliter [dL]). Men with blood retinol levels in the 99th percentile (greater than 103 mcg per dL) had an overall risk of fracture that exceeded the risk among men with lower levels of retinol by a factor of seven.13

High vitamin A intake, however, does not necessarily equate to high blood levels of retinol. Age, gender, hormones, and genetics also influence these levels. Researchers did not find any association between blood levels of beta-carotene and risk of hip fracture. Researchers' findings, which are consistent with the results of animal, in vitro (laboratory), and epidemiologic studies, suggest that intakes above the UL, or approximately two times that of the RDA for vitamin A, may pose subtle risks to bone health that require further study.

The Centers for Disease Control and Prevention (CDC) reviewed data from NHANES III (1988-94) to determine whether there was any association between bone mineral density and blood levels of retinyl esters, a form of vitamin A.14 No significant associations between blood levels of retinyl esters and bone mineral density in 5,800 subjects were found.</p> <p>There is no <a title=">evidence of an association between beta-carotene intake, especially from fruits and vegetables, and increased risk of osteoporosis. Current evidence points to a possible association with vitamin A as retinol only. If you have specific questions regarding your intake of vitamin A and risk of osteoporosis, discuss this information with your physician or other qualified healthcare provider to determine what's best for your personal health.

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  1. Fontham ETH. Protective dietary factors and lung cancer. Int J Epidemiol 1990;19:S32-S42. [PubMed abstract] [↩]
  2. Gerster H. Vitamin A-functions, dietary requirements and safety in humans. Int J Vitam Nutr Res 1997;67:71-90. [prevention did not find them to protect against the disease. In the Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study, more than 29,000 men who regularly smoked cigarettes were randomized to receive 20 mg beta-carotene alone, 50 mg alpha-tocopherol alone, supplements of both, or a placebo for 5 to 8 years. Incidence of lung cancer was 18% higher among men who took the beta-carotene supplement. Eight percent more men in this group died, as compared to those receiving other treatments or placebo. ((Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M, Hartman AM, Palmgren J, Freedman LS, Haapakoski J, Barrett MJ, Pietinen P, Malila N, Tala E, Lippo K, Salomaa ER, Tangrea JA, Teppo L, Askin FB, Taskinen E, Erozan Y, Greenwald P, Huttunen JK. Alpha-tocopherol and beta-carotene supplement and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: Effects of base-line characteristics and study compliance. J Natl Cancer Inst 1996;88:1560-70. [PubMed abstract] [↩]
  3. Redlich CA, Blaner WS, Van Bennekum AM, Chung JS, Clever SL, Holm CT, Cullen MR. Effect of supplementation with beta-carotene and vitamin A on lung nutrient levels. Cancer Epidemiol Biomarkers Prev 1998;7:211-14. [↩]
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  5. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001. [↩]
  6. National Institutes of Health. Osteoporosis prevention, diagnosis, and therapy. NIH Consensus Statement Online, 2000 March 27-29, 2000:1-36. [↩]
  7. National Osteoporosis Foundation. NOF osteoporosis prevention-risk factors for osteoporosis. 2003. http://www.nof.org/prevention/risk.htm. [↩]
  8. Binkley N, Krueger D. Hypervitaminosis A and bone. Nutr Rev 2000;58:138-44. ↩]
  9. Binkley N, Krueger D. Hypervitaminosis A and bone. Nutr Rev 2000;58:138-44. ↩]
  10. Forsyth KS, Watson RR, Gensler HL. Osteotoxicity after chronic dietary administration of 13-cis-retinoic acid, retinyl palmitate or selenium in mice exposed to tumor initiation and promotion. Life Sci 1989;45:2149-56. <a href=">biosynthesis of vitamin D associated with lower levels of sun exposure in this population may also contribute to this finding.

    One small study of nine healthy individuals in Sweden found that the amount of vitamin A in one serving of liver may impair the ability of vitamin D to promote calcium absorption. ((Johansson S, Melhus H. Vitamin A antagonizes calcium response to vitamin D in man. J Bone Miner Res 2001;16:1899-1905. ↩]

  11. Melhus H, Michaelsson K, Kindmark A, Bergstrom R, Holmberg L, Mallmin H, Wolk A, Ljunghall S. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk of hip fracture. Ann Intern Med 1998;129:770-8. ↩]
  12. Feskanich D, Singh F, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. J Am Med Assoc 2002;287:47-54. ↩]
  13. Michaelsson K, Lithell H, Vessby B, Mehus H. Serum retinol levels and the risk of fracture. N Engl J Med 2003;348:287-94. [↩]
  14. 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, 1988-94. J Bone Miner Res 2001;16:2306-12. ↩]

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