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Clinical Guidelines |

Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale FREE

U.S. Preventive Services Task Force*
[+] Article and Author Information

From the U.S. Preventive Services Task Force, Agency for Healthcare Research and Quality, Rockville, Maryland.


Disclaimer: The USPSTF recommendations are independent of the U.S. government. They do not represent the views of the Agency for Healthcare Research and Quality, the U.S. Department of Health and Human Services, or the U.S. Public Health Service.

Requests for Single Reprints: Reprints are available from the USPSTF Web site (http://www.preventiveservices.ahrq.gov) and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (800-358-9295).


Ann Intern Med. 2003;139(1):51-55. doi:10.7326/0003-4819-139-1-200307010-00013
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This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on routine vitamin supplementation to prevent cancer and cardiovascular disease and the supporting scientific evidence. Part of the information on which this statement is based, including evidence tables and references, is available in the accompanying article on vitamins to prevent cardiovascular disease in this issue. More complete information can be found in the summaries of the evidence on vitamins to prevent cancer and vitamins to prevent cardiovascular disease, available on the USPSTF Web site (www.preventiveservices.ahrq.gov) and through the National Guideline Clearinghouse (www.guideline.gov). The summaries of the evidence on these topics and the recommendation statement are also available in print through subscription to the Guide to Clinical Preventive Services, Third Edition: Periodic Updates. A subscription costs $60 U.S. and can be ordered through the Agency for Healthcare Research and Quality Publications Clearinghouse (call 800-358-9295 or e-mail ahrqpubs@ahrq.gov).

*For a list of the members of the U.S. Preventive Services Task Force, see the Appendix.

The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A, C, or E; multivitamins with folic acid; or antioxidant combinations for the prevention of cancer or cardiovascular disease. This is a grade I recommendation. (See Appendix Table 1 for a description of the USPSTF classification of recommendations.)

The USPSTF found poor evidence to determine whether supplementation with these vitamins reduces the risk for cardiovascular disease or cancer. (See Appendix Table 2 for a description of the USPSTF classification of levels of evidence.) The available evidence from randomized trials is either inadequate or conflicting, and the influence of confounding variables on observed outcomes in observational studies cannot be determined. As a result, the USPSTF could not determine the balance of benefits and harms of routine use of supplements of vitamins A, C, or E; multivitamins with folic acid; or antioxidant combinations for the prevention of cancer or cardiovascular disease.

The USPSTF recommends against the use of beta-carotene supplements, either alone or in combination, for the prevention of cancer or cardiovascular disease. This is a grade D recommendation.

The USPSTF found good evidence that β-carotene supplementation provides no benefit in the prevention of cancer or cardiovascular disease in middle-aged and older adults. In two trials restricted to heavy smokers, β-carotene supplementation was associated with higher incidence of lung cancer and higher all-cause mortality. The USPSTF concludes that β-carotene supplements are unlikely to provide important benefits and might cause harm in some groups.

The USPSTF did not review evidence regarding vitamin supplementation for patients with known or potential nutritional deficiencies, including pregnant and lactating women, children, elderly persons, and people with chronic illnesses. Dietary supplements may be appropriate for people whose diet does not provide the recommended dietary intake of specific vitamins. Individuals may wish to consult a health care provider to discuss whether dietary supplements are appropriate.

With the exception of vitamins for which there is compelling evidence of net harm (for example, beta-carotene supplementation in smokers), there is little reason to discourage people from taking vitamin supplements. Patients should be reminded that taking vitamins does not replace the need to eat a healthy diet. All patients should receive information about the benefits of a diet high in fruits and vegetables, as well as information on other foods and nutrients that should be emphasized or avoided in their diet (see the 2002 USPSTF recommendations on counseling to promote a healthy diet [1]).

Patients who choose to take vitamins should be encouraged to adhere to the dosages recommended in the Dietary Reference Intakes of the Institute of Medicine. Some vitamins, such as A and D, may be harmful in higher doses; therefore, doses greatly exceeding the Recommended Dietary Allowance or Adequate Intake should be taken with care while considering whether potential harms outweigh potential benefits. Vitamins and minerals sold in the United States are classified as “dietary supplements,” and there is a degree of quality control over content if they have a U.S. Pharmacopeia seal (2). Nevertheless, imprecision in the content and concentration of ingredients could pose a theoretical risk not reflected in clinical trials using calibrated compounds.

The adverse effects of beta-carotene on smokers have been observed primarily in those taking large supplemental doses. There is no evidence to suggest that beta-carotene is harmful to smokers at levels occurring naturally in foods.

The USPSTF did not review evidence supporting folic acid supplementation among pregnant women to reduce neural tube defects. In 1996, the USPSTF recommended folic acid for all women who are planning, or capable of, pregnancy (see the 1996 USPSTF chapter on screening for neural tube defects [3]).

Clinicians and patients should discuss the possible need for vitamin supplementation when taking certain medications (for example, folic acid supplementation for patients taking methotrexate).

The USPSTF reviews (46) focused on the quality of the evidence regarding the effect of routine supplementation with certain vitamins on primary prevention of cancer and cardiovascular disease. These reviews were undertaken because of the growing epidemiologic evidence that dietary factors may play a role in the etiology of these diseases (79). The reviews focused on prospective trials of vitamin supplementation and observational studies of associations between the use of specific supplements and the risk for cancer or cardiovascular disease. The value of vitamins naturally occurring in food, the use of vitamin supplements for the prevention of other conditions (for example, neural tube defects), and the use of vitamin supplements for the secondary prevention of complications in patients with existing disease were outside the scope of these reviews.

Vitamin A

No prospective trials have examined the effect of vitamin A supplements alone on the risk for cancer. Observational studies provide no evidence that such supplements prevent cancer in men. In women, observational studies have reported a statistically significant inverse association between use of vitamin A supplements and risk for colon and breast cancer (1011). Despite efforts to adjust for confounding variables, the observational, nonrandom design of these studies makes it difficult to assess the extent to which the reduced cancer risk is attributable to vitamin A or to other characteristics of women who take vitamin A supplements. No evidence from prospective trials is available regarding the benefits of vitamin A alone in preventing cardiovascular disease. One good-quality cohort study found no effect of vitamin A supplementation in reducing cardiovascular disease mortality (12).

Vitamin C

No primary prevention trial of the effect of vitamin C supplementation alone on cancer or cardiovascular disease has been reported. Observational studies have generally shown no statistically significant associations between use of vitamin C supplements and risk for cancer of the breast, prostate, colon, or lung (1214). The observational cohort studies examining the effects of vitamin C on cardiovascular disease have produced inconsistent results (12, 1516).

Vitamin E

Only a few trials have examined the effects of vitamin E on the primary prevention of cancer or cardiovascular disease. A randomized, controlled trial (RCT) involving Finnish male smokers found that vitamin E supplementation is not protective against lung cancer but may have a beneficial impact on prostate cancer (14). Because prostate cancer was not a primary end point of the trial and the trial had other limitations, further evidence is needed to confirm this finding. Observational studies have shown no statistically significant association between use of vitamin E supplements and risk for prostate, lung, or breast cancer (5). One study suggested that vitamin E protects against colon cancer, but the influence of confounding variables cannot be fully excluded (17). Among primary prevention trials, two good-quality trials (14, 18) and one fair-quality trial (19) found no statistically significant benefit of vitamin E supplementation in preventing cardiovascular disease (20). Only one of seven trials of vitamin E supplementation for secondary prevention demonstrated a statistically significant reduction in cardiac events (4). Some prospective cohort studies have suggested a significant benefit, but the results are mixed and the influence of confounding variables cannot be excluded (4).

β-Carotene

A consistent body of evidence from clinical trials suggests that beta-carotene supplementation does not decrease the risk for lung, prostate, colon, breast, or nonmelanoma skin cancer (14, 2125). β-Carotene supplements were associated with an increased risk for lung cancer among smokers, especially heavy smokers, in two RCTs (14, 25). Results from four RCTs demonstrated no reduced risk for cardiovascular events or death after beta-carotene supplementation (14, 2122, 2628).

Antioxidant Vitamin Combinations

Studies of the effects of antioxidant vitamin combinations to prevent cancer have yielded mixed results. A recent RCT reported no statistically significant effect of daily supplementation with a combination of antioxidants: vitamin E, vitamin C, and beta-carotene (29). Some studies have suggested an adverse effect of antioxidant combinations on cancer, but the results may have been confounded by the inclusion of beta-carotene (5). Some observational studies of antioxidant vitamin combinations have suggested a benefit in preventing cardiovascular disease (13, 3031), but other studies, including well-designed RCTs, have shown no benefit (29, 3233). One secondary prevention trial showed an increase in all-cause mortality among women taking antioxidant supplements (34).

Multiple Vitamin Combinations

The incremental benefit of taking supplemental doses of folic acid and B vitamins has been examined by comparing the outcomes of observational studies while controlling for the total intake of antioxidant vitamin supplements (35). In these analyses, folic acid supplementation was associated with significantly decreased risk for colon cancer, but the protective effect requires confirmation in prospective trials. There is conflicting evidence regarding the use of multivitamins and the risk for cardiovascular disease. Among cohort studies, one good-quality study reported a statistically significant reduction in coronary events (36), two good-quality studies reported no statistically significant effect on mortality (16, 37), and one fair-quality study reported an increase in all-cause mortality in men (31). No trial has examined the effect of folate or multivitamins on the primary prevention of cardiovascular disease, but such studies are currently under way.

Several known adverse effects are caused by excessive doses of vitamins. For example, moderate doses of vitamin A supplements may reduce bone mineral density and high doses may be hepatotoxic or teratogenic. A small but statistically significant increase in lung cancer mortality observed in trials of smokers has been ascribed to beta-carotene supplementation; adverse effects of beta-carotene supplementation have not been observed in other trials. The adverse effects of vitamin supplementation were not reported in most studies reviewed by the USPSTF. More studies are needed to better understand the harms of vitamin supplementation.

The findings of these USPSTF reviews must be placed in context because they focused only on vitamin supplements and their role in preventing cancer and cardiovascular disease. The value of taking vitamin supplements for other purposes, such as folic acid supplementation by women capable of pregnancy to prevent the birth of babies with neural tube defects, has stronger scientific support. Although the health benefits of vitamin supplementation remain uncertain, there is more consistent evidence that a diet high in fruit, vegetables, and legumes has important benefits; other constituents besides vitamins may account for the benefits of such diets.

Dietary supplementation with folic acid, vitamin B6 (pyridoxine), and vitamin B12 (alone or in combination) appears to lower plasma homocysteine levels, and higher levels of homocysteine may be an independent risk factor for cardiovascular disease (38). However, definitive evidence of the role of vitamin supplementation on altering cardiovascular outcomes is lacking. The results of a secondary prevention trial will be available within the next few years.

The American Academy of Family Physicians states, “The decision to provide special dietary intervention or nutrient supplementation must be on an individual basis using the family physician's best judgment based on evidence of benefit as well as lack of harmful effects. Megadoses of certain vitamins and minerals have been proven to be harmful” (39). The Canadian Task Force on Preventive Health Care is reviewing the role of vitamin E supplementation in the prevention of cardiovascular disease and cancer (40). The American Cancer Society recommends a well-balanced diet and does not recommend the use of vitamin and mineral supplements as a preventive or therapeutic intervention (41). The American Heart Association Dietary Guidelines: Revision 2000 recommends that vitamin and mineral supplements not be considered a substitute for a balanced and nutritious diet designed to emphasize intake of fruits, vegetables, and grains (42).

Appendix

Members of the U.S. Preventive Services Task Force are Alfred O. Berg, MD, MPH (Chair) (University of Washington, Seattle, Washington); Janet D. Allan, PhD, RN, Vice-Chair (University of Maryland—Baltimore, Baltimore, Maryland); Paul Frame, MD (Tri-County Family Medicine, Cohocton, and University of Rochester, Rochester, New York); Charles J. Homer, MD, MPH (National Initiative for Children's Healthcare Quality, Boston, Massachusetts)*; Mark S. Johnson, MD, MPH (University of Medicine and Dentistry of New Jersey–New Jersey Medical School, Newark, New Jersey); Jonathan D. Klein, MD, MPH (University of Rochester School of Medicine, Rochester, New York); Tracy A. Lieu, MD, MPH (Harvard Pilgrim Health Care and Harvard Medical School, Boston, Massachusetts)*; Cynthia D. Mulrow, MD, MSc (University of Texas Health Science Center, San Antonio, Texas)*; C. Tracy Orleans, PhD (The Robert Wood Johnson Foundation, Princeton, New Jersey); Jeffrey F. Peipert, MD, MPH (Women and Infants' Hospital, Providence, Rhode Island)*; Nola J. Pender, PhD, RN (University of Michigan, Ann Arbor, Michigan)*; Albert L. Siu, MD, MSPH (Mount Sinai School of Medicine, New York, New York); Steven M. Teutsch, MD, MPH (Merck & Co., Inc., West Point, Pennsylvania); Carolyn Westhoff, MD, MSc (Columbia University, New York, New York); and Steven H. Woolf, MD, MPH (Virginia Commonwealth University, Fairfax, Virginia).

*Members of the Task Force at the time these recommendations were finalized.

Table Jump PlaceholderAppendix Table 1.  U.S. Preventive Services Task Force Grades and Recommendations
Table Jump PlaceholderAppendix Table 2.  U.S. Preventive Services Task Force Grades for Strength of Overall Evidence
Pignone MP, Ammerman A, Fernandez L, Orleans CT, Pender N, Woolf S, et al..  Counseling to promote a healthy diet in adults: a summary of the evidence for the U.S. Preventive Services Task Force. Am J Prev Med. 2003; 24:75-92. PubMed
CrossRef
 
U.S. Pharmacopeia Dietary Supplement Verification Program. Accessed athttp://www.usp-dsvp.orgon 30 April 2002.
 
Screening for neural tube defects. In: U.S. Preventive Services Task Force. Guide To Clinical Preventive Services. 2nd ed. Washington, DC: Office of Disease Prevention and Health Promotion; 1996:467-83. Available athttp://www.ahrq.gov/clinic/uspstf/uspsneur.htm. Accessed 7 May 2003.
 
Morris CD, Carson S.  Vitamin supplementation to prevent cardiovascular disease: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003; 139:56-70.
 
Ritenbaugh C, Streit K, Helfand M.  Routine vitamin supplementation to prevent cancer: a summary of the evidence from randomized trials for the U.S. Preventive Services Task Force. Available athttp://www.preventiveservices.ahrq.gov.
 
Shetty P, Atkins D.  Routine vitamin supplementation to prevent cancer: update of evidence from randomized controlled trials during 2000–2002. Available athttp://www.preventiveservices.ahrq.gov.
 
Steinmetz KA, Potter JD.  Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc. 1996; 96:1027-39. PubMed
 
Ross R.  The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362:801-9. PubMed
 
Diaz MN, Frei B, Vita JA, Keaney JF Jr.  Antioxidants and atherosclerotic heart disease. N Engl J Med. 1997; 337:408-16. PubMed
 
Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE, Colditz GA, et al..  Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst. 1999; 91:547-56. PubMed
 
Bostick RM, Potter JD, McKenzie DR, Sellers TA, Kushi LH, Steinmetz KA, et al..  Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study. Cancer Res. 1993; 53:4230-7. PubMed
 
Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM.  Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med. 1996; 334:1156-62. PubMed
 
Hunter DJ, Manson JE, Colditz GA, Stampfer MJ, Rosner B, Hennekens CH, et al..  A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med. 1993; 329:234-40. PubMed
 
.  The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994; 330:1029-35. PubMed
 
Enstrom JE, Kanim LE, Klein MA.  Vitamin C intake and mortality among a sample of the United States population. Epidemiology. 1992; 3:194-202. PubMed
 
Losonczy KG, Harris TB, Havlik RJ.  Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996; 64:190-6. PubMed
 
Kushi LH, Fee RM, Sellers TA, Zheng W, Folsom AR.  Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women's Health Study. Am J Epidemiol. 1996; 144:165-74. PubMed
 
Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P.  Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000; 342:154-60. PubMed
 
de Gaetano G.  Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet. 2001; 357:89-95. PubMed
 
Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al..  Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996; 334:1150-5. PubMed
 
Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al..  Lack of effect of long-term supplementation with beta-carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996; 334:1145-9. PubMed
 
Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH.  Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst. 1999; 91:2102-6. PubMed
 
Frieling UM, Schaumberg DA, Kupper TS, Muntwyler J, Hennekens CH.  A randomized, 12-year primary-prevention trial of beta-carotene supplementation for nonmelanoma skin cancer in the physician's health study. Arch Dermatol. 2000; 136:179-84. PubMed
 
Cook NR, Stampfer MJ, Ma J, Manson JE, Sacks FM, Buring JE, et al..  Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate carcinoma. Cancer. 1999; 86:1783-92. PubMed
 
Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al..  Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996; 88:1550-9. PubMed
 
Greenberg ER, Baron JA, Karagas MR, Stukel TA, Nierenberg DW, Stevens MM, et al..  Mortality associated with low plasma concentration of beta-carotene and the effect of oral supplementation. JAMA. 1996; 275:699-703. PubMed
 
Rapola JM, Virtamo J, Haukka JK, Heinonen OP, Albanes D, Taylor PR, et al..  Effect of vitamin E and beta-carotene on the incidence of angina pectoris. A randomized, double-blind, controlled trial. JAMA. 1996; 275:693-8. PubMed
 
Virtamo J, Rapola JM, Ripatti S, Heinonen OP, Taylor PR, Albanes D, et al..  Effect of vitamin E and beta-carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease. Arch Intern Med. 1998; 158:668-75. PubMed
 
.  MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360:23-33. PubMed
 
Klipstein-Grobusch K, Geleijnse JM, den Breeijen JH, Boeing H, Hofman A, Grobbee DE, et al..  Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr. 1999; 69:261-6. PubMed
 
Watkins ML, Erickson JD, Thun MJ, Mulinare J, Heath CW Jr.  Multivitamin use and mortality in a large prospective study. Am J Epidemiol. 2000; 152:149-62. PubMed
 
Knekt P, Reunanen A, Jarvinen R, Seppanen R, Heliovaara M, Aromaa A.  Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol. 1994; 139:1180-9. PubMed
 
.  A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta-carotene for age-related cataract and vision loss: AREDS report no. 9. Arch Ophthalmol. 2001; 119:1439-52. PubMed
 
Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, et al..  Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA. 2002; 288:2432-40. PubMed
 
Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA, et al..  Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med. 1998; 129:517-24. PubMed
 
Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, et al..  Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998; 279:359-64. PubMed
 
Muntwyler J, Hennekens CH, Manson JE, Buring JE, Gaziano JM.  Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality. Arch Intern Med. 2002; 162:1472-6. PubMed
 
Taylor BV, Oudit GY, Evans M.  Homocysteine, vitamins, and coronary artery disease. Comprehensive review of the literature. Can Fam Physician. 2000; 46:2236-45. PubMed
 
American Academy of Family Physicians.  AAFP Clinical Recommendations: Vitamins. Accessed athttp://www.aafp.org/x2590.xmlon 28 April 2003.
 
Canadian Task Force on Preventive Health Care.  Accessed athttp://www.ctfphc.org/Whats%20New/reviews_in_progress.htmon 28 April 2003.
 
American Cancer Society.  Prevention and Early Detection: Food and Fitness. Accessed athttp://www.cancer.org/docroot/PED/ped_3.asp?sitearea=PED&level=1on 28 April 2003.
 
American Heart Association.  Vitamins and Mineral Supplements: AHA Scientific Position. Accessed athttp://216.185.112.5/presenter.jhtml?identifier=4788on 27 March 2002.
 

Figures

Tables

Table Jump PlaceholderAppendix Table 1.  U.S. Preventive Services Task Force Grades and Recommendations
Table Jump PlaceholderAppendix Table 2.  U.S. Preventive Services Task Force Grades for Strength of Overall Evidence

References

Pignone MP, Ammerman A, Fernandez L, Orleans CT, Pender N, Woolf S, et al..  Counseling to promote a healthy diet in adults: a summary of the evidence for the U.S. Preventive Services Task Force. Am J Prev Med. 2003; 24:75-92. PubMed
CrossRef
 
U.S. Pharmacopeia Dietary Supplement Verification Program. Accessed athttp://www.usp-dsvp.orgon 30 April 2002.
 
Screening for neural tube defects. In: U.S. Preventive Services Task Force. Guide To Clinical Preventive Services. 2nd ed. Washington, DC: Office of Disease Prevention and Health Promotion; 1996:467-83. Available athttp://www.ahrq.gov/clinic/uspstf/uspsneur.htm. Accessed 7 May 2003.
 
Morris CD, Carson S.  Vitamin supplementation to prevent cardiovascular disease: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003; 139:56-70.
 
Ritenbaugh C, Streit K, Helfand M.  Routine vitamin supplementation to prevent cancer: a summary of the evidence from randomized trials for the U.S. Preventive Services Task Force. Available athttp://www.preventiveservices.ahrq.gov.
 
Shetty P, Atkins D.  Routine vitamin supplementation to prevent cancer: update of evidence from randomized controlled trials during 2000–2002. Available athttp://www.preventiveservices.ahrq.gov.
 
Steinmetz KA, Potter JD.  Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc. 1996; 96:1027-39. PubMed
 
Ross R.  The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362:801-9. PubMed
 
Diaz MN, Frei B, Vita JA, Keaney JF Jr.  Antioxidants and atherosclerotic heart disease. N Engl J Med. 1997; 337:408-16. PubMed
 
Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE, Colditz GA, et al..  Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst. 1999; 91:547-56. PubMed
 
Bostick RM, Potter JD, McKenzie DR, Sellers TA, Kushi LH, Steinmetz KA, et al..  Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study. Cancer Res. 1993; 53:4230-7. PubMed
 
Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM.  Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med. 1996; 334:1156-62. PubMed
 
Hunter DJ, Manson JE, Colditz GA, Stampfer MJ, Rosner B, Hennekens CH, et al..  A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med. 1993; 329:234-40. PubMed
 
.  The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994; 330:1029-35. PubMed
 
Enstrom JE, Kanim LE, Klein MA.  Vitamin C intake and mortality among a sample of the United States population. Epidemiology. 1992; 3:194-202. PubMed
 
Losonczy KG, Harris TB, Havlik RJ.  Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996; 64:190-6. PubMed
 
Kushi LH, Fee RM, Sellers TA, Zheng W, Folsom AR.  Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women's Health Study. Am J Epidemiol. 1996; 144:165-74. PubMed
 
Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P.  Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000; 342:154-60. PubMed
 
de Gaetano G.  Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet. 2001; 357:89-95. PubMed
 
Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al..  Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996; 334:1150-5. PubMed
 
Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al..  Lack of effect of long-term supplementation with beta-carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996; 334:1145-9. PubMed
 
Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH.  Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst. 1999; 91:2102-6. PubMed
 
Frieling UM, Schaumberg DA, Kupper TS, Muntwyler J, Hennekens CH.  A randomized, 12-year primary-prevention trial of beta-carotene supplementation for nonmelanoma skin cancer in the physician's health study. Arch Dermatol. 2000; 136:179-84. PubMed
 
Cook NR, Stampfer MJ, Ma J, Manson JE, Sacks FM, Buring JE, et al..  Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate carcinoma. Cancer. 1999; 86:1783-92. PubMed
 
Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al..  Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996; 88:1550-9. PubMed
 
Greenberg ER, Baron JA, Karagas MR, Stukel TA, Nierenberg DW, Stevens MM, et al..  Mortality associated with low plasma concentration of beta-carotene and the effect of oral supplementation. JAMA. 1996; 275:699-703. PubMed
 
Rapola JM, Virtamo J, Haukka JK, Heinonen OP, Albanes D, Taylor PR, et al..  Effect of vitamin E and beta-carotene on the incidence of angina pectoris. A randomized, double-blind, controlled trial. JAMA. 1996; 275:693-8. PubMed
 
Virtamo J, Rapola JM, Ripatti S, Heinonen OP, Taylor PR, Albanes D, et al..  Effect of vitamin E and beta-carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease. Arch Intern Med. 1998; 158:668-75. PubMed
 
.  MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360:23-33. PubMed
 
Klipstein-Grobusch K, Geleijnse JM, den Breeijen JH, Boeing H, Hofman A, Grobbee DE, et al..  Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr. 1999; 69:261-6. PubMed
 
Watkins ML, Erickson JD, Thun MJ, Mulinare J, Heath CW Jr.  Multivitamin use and mortality in a large prospective study. Am J Epidemiol. 2000; 152:149-62. PubMed
 
Knekt P, Reunanen A, Jarvinen R, Seppanen R, Heliovaara M, Aromaa A.  Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol. 1994; 139:1180-9. PubMed
 
.  A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta-carotene for age-related cataract and vision loss: AREDS report no. 9. Arch Ophthalmol. 2001; 119:1439-52. PubMed
 
Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, et al..  Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA. 2002; 288:2432-40. PubMed
 
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American Academy of Family Physicians.  AAFP Clinical Recommendations: Vitamins. Accessed athttp://www.aafp.org/x2590.xmlon 28 April 2003.
 
Canadian Task Force on Preventive Health Care.  Accessed athttp://www.ctfphc.org/Whats%20New/reviews_in_progress.htmon 28 April 2003.
 
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American Heart Association.  Vitamins and Mineral Supplements: AHA Scientific Position. Accessed athttp://216.185.112.5/presenter.jhtml?identifier=4788on 27 March 2002.
 

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Summary for Patients

Taking Vitamin Supplements To Prevent Cardiovascular Disease and Cancer: Recommendations from the U.S. Preventive Services Task Force

The summary below is from the full reports titled “Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale” and “Routine Vitamin Supplementation To Prevent Cardiovascular Disease: A Summary of the Evidence for the U.S. Preventive Services Task Force.” They are in the 1 July 2003 issue of Annals of Internal Medicine (volume 139, pages 51-55 and pages 56-70). The first report was written by the U.S. Preventive Services Task Force; the second report was written by C.D. Morris and S. Carson.

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