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Draft Recommendation Statement


Note: This draft Recommendation Statement is not the final recommendation of the U.S. Preventive Services Task Force. This draft is distributed solely for the purpose of pre-release review. It has not been disseminated otherwise by AHRQ. It does not represent and should not be interpreted to represent an AHRQ determination or policy.

This draft Recommendation Statement is based on an evidence review that was published on December 20, 2011 (available at http://www.uspreventiveservicestaskforce.org/uspstf12/vitamind/vitdart.htm).

The USPSTF makes recommendations about the effectiveness of specific clinical preventive services for patients without related signs or symptoms.

It bases its recommendations on the evidence of both the benefits and harms of the service, and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.

The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decisionmaking to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.

This draft Recommendation Statement was available for comment from June 12 until July 10, 2012, at 5:00 PM ET. A fact sheet that explains the draft recommendations in plain language is available here.


Vitamin D and Calcium Supplementation to Prevent Cancer and Osteoporotic Fractures in Adults: U.S. Preventive Services Task Force Recommendation Statement
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Summary of Recommendations and Evidence

The U.S. Preventive Services Task Force (USPSTF) concludes that the current evidence is insufficient to assess the balance of the benefits and harms of vitamin D supplementation, with or without calcium, for the primary prevention of cancer in adults.

This is an I statement.

The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or in men.

This is an I statement.

The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with >400 IU of vitamin D3 and 1,000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women.

This is an I statement.

The USPSTF recommends against daily supplementation with ≤400 IU of vitamin D3 and 1,000 mg of calcium carbonate for the primary prevention of fractures in noninstitutionalized postmenopausal women.

This is a grade D recommendation.

The USPSTF has previously concluded in a separate recommendation that vitamin D supplementation is effective in preventing falls in community-dwelling adults aged 65 years or older who are at increased risk for falls (B recommendation). The full recommendation statement is available at http://www.uspreventiveservicestaskforce.org

Go to the Clinical Considerations section for suggestions for practice regarding the I statements.

Go to the Figure for a summary of the USPSTF's draft and final recommendations on vitamin D supplementation.

Table 1 describes the USPSTF grades, and Table 2 describes the USPSTF classification of levels of certainty about net benefit.

Rationale

Importance

Cancer is the second most common cause of death in the United States. An estimated 571,950 deaths from cancer occurred in the United States in 2011 (1).

Osteoporotic fractures, particularly hip fractures, are associated with chronic pain and disability, loss of independence, worsened quality of life, and increased mortality. One half of all postmenopausal women will have an osteoporosis-related fracture during their lifetime (2).

Benefits of Preventive Medication

Cancer. There is inadequate evidence to determine the effect of vitamin D supplementation, with or without calcium, on overall cancer incidence and mortality in adults.

Fractures. In postmenopausal women, there is adequate evidence that daily supplementation with 400 IU of vitamin D3 combined with 1,000 mg of calcium carbonate has no effect on the incidence of osteoporotic fractures. However, there is inadequate evidence regarding the effect of higher doses of combined vitamin D and calcium supplementation on fracture incidence in postmenopausal women.

In premenopausal women and in men, there is inadequate evidence to determine the effect of combined vitamin D and calcium supplementation on the incidence of osteoporotic fractures.

Harms of Preventive Medication

There is adequate evidence that supplementation with ≤400 IU of vitamin D3 and 1,000 mg of calcium carbonate increases the incidence of renal stones. The USPSTF assessed the magnitude of this harm as small.

USPSTF Assessment

Noninstitutionalized, community-dwelling postmenopausal women. The USPSTF concludes that evidence is lacking regarding the benefit of vitamin D supplementation, with or without calcium, for the primary prevention of cancer, and the balance of benefits and harms cannot be determined.

The USPSTF concludes that evidence is lacking regarding the benefit of daily supplementation with >400 IU of vitamin D3 and 1,000 mg of calcium for the primary prevention of osteoporotic fractures, and the balance of benefits and harms cannot be determined.

The USPSTF concludes with moderate certainty that daily supplementation with ≤400 IU of vitamin D3 and 1,000 mg of calcium carbonate has no net benefit for the primary prevention of osteoporotic fractures.

Men and premenopausal women. The USPSTF concludes that evidence is lacking regarding the benefit of vitamin D supplementation, with or without calcium, for the primary prevention of cancer and osteoporotic fractures, and the balance of benefits and harms cannot be determined.

Clinical Considerations

Patient Population Under Consideration

This recommendation applies to noninstitutionalized, community-dwelling, asymptomatic adults without previous history of fractures or cancer. “Community-dwelling” is defined as not living in an assisted living facility, nursing home, or other institutional care setting.

Considerations for Practice Regarding the I Statements

Potential preventable burden. The health burdens of osteoporotic fractures and cancer are substantial in the older adult population.

Potential harms. In the Women's Health Initiative (WHI), the only randomized trial reporting a statistically increased incidence of renal stones in women taking supplemental vitamin D and calcium carbonate, one woman was diagnosed with a urinary tract stone for every 273 women who received supplementation over a 7-year followup period.

Costs. Vitamin D and calcium supplements are inexpensive and readily available without a prescription.

Current practice. Vitamin D and calcium supplementation are often recommended for women, especially postmenopausal women, to prevent fractures, although actual use is uncertain.

Useful Resources

The USPSTF recommends vitamin D supplementation to prevent falls in community-dwelling adults aged 65 years and older who are at increased risk for falls (B recommendation) (Figure). The USPSTF recommends screening for osteoporosis in women aged 65 years or older and in younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors. These recommendation statements are available on the USPSTF Web site (http://www.uspreventiveservicestaskforce.org).

Other Considerations

Research Needs and Gaps

Research is needed to determine whether daily supplementation with >400 IU of vitamin D3 and 1,000 mg of calcium reduces fracture incidence in postmenopausal women or older men. The comparative effectiveness of different preparations of vitamin D (D2 versus D3) or different calcium formations should be evaluated. Prospective studies should assess the potential benefits of vitamin D and calcium supplementation in early adulthood on fracture incidence later in life. Large randomized trials are needed to determine if vitamin D supplementation, with or without calcium, reduces breast cancer incidence in women, prostate cancer incidence in men, or overall cancer mortality. Studies are needed to evaluate the effects of vitamin D supplementation on diverse populations. Because most fracture prevention studies are of white women, who have the highest risk for osteoporotic fractures, it is difficult to extrapolate results to secondary outcomes, such as cancer, in nonwhite populations.

Discussion

Burden of Disease

Cancer. In 2011, an estimated 822,300 men and 774,370 women in the United States were diagnosed with cancer, and 571,950 people died from it (1). Cancer incidence and mortality rates vary considerably by sex, race, ethnicity, and other factors.

Fractures. Each year, approximately 1.5 million osteoporotic fractures occur in the United States. Nearly half of all women older than age 50 years will have an osteoporosis-related fracture during their lifetime. Fractures are associated with chronic pain, disability, and decreased quality of life. Hip fractures significantly increase morbidity and mortality. During the first 3 months after a hip fracture, a person's mortality risk is 2.8 to 4 times that of a person of similar age living in the community without a fracture. Nearly 20 percent of hip fracture patients are subsequently institutionalized in long-term care facilities (3).

Scope of Review

The USPSTF used two systematic evidence reviews and an updated meta-analysis on vitamin D supplementation with or without calcium (4-6) to assess the following: 1) the effects of supplementation on cancer and bone health outcomes in community-dwelling adults, 2) the association of vitamin D and calcium levels with cancer and bone health outcomes, and 3) the adverse effects of supplementation. The USPSTF did not consider questions relating to adequate daily intake of calcium and vitamin D, nor did it examine the effect of calcium supplementation alone. The reviews did not examine other health outcomes, such as pregnancy complications, falls prevention, cardiovascular disease, specific cancer types, or overall mortality.

Effectiveness of Preventive Medication

Vitamin D and cancer. Three randomized, controlled trials examined vitamin D and cancer outcomes. One trial was of good quality (WHI) and two trials (9, 10) were of fair quality. The studies had several limitations, including enrollment of a relatively homogeneous population (enrollees were mostly white women), use of different doses and frequency of vitamin D use, use of calcium supplementation, and assessment of secondary outcomes. Because of the heterogeneous nature of the study designs, the results were not pooled.

The largest and best-quality study, WHI (7, 8), enrolled 36,282 healthy postmenopausal women aged 50 to 79 years. Approximately 83 percent of the women enrolled in the trial were white, 9 percent were black, 4 percent were Hispanic, and 4 percent were of other races. The intervention group received 400 IU of vitamin D3 and 1,000 mg of calcium carbonate daily; the control group received placebo. During the 7 years of the trial, total cancer incidence (hazard ratio [HR], 0.98 [95% CI, 0.91 to 1.05]) and cancer mortality (HR, 0.89 [95% CI, 0.77 to 1.03]) did not significantly differ between women in the intervention and placebo groups. Incidence and mortality rates of colorectal cancer and invasive breast cancer were secondary outcomes of interest in the WHI trial. There were no statistically significant differences between intervention and control group rates of these types of cancer.

The Trivedi trial (9) compared 100,000 IU of vitamin D3 administered every 4 months with placebo in 2,686 men and women aged 65 to 85 years in the United Kingdom. Cancer incidence (relative risk [RR], 1.09 [95% CI, 0.86 to 1.36]) and total cancer mortality (RR, 0.86 [95% CI, 0.61 to 1.20]) were statistically comparable after 5 years of followup.

The Lappe trial (10) compared the effect of 4 years of daily supplementation with 1,000 IU of vitamin D3 and calcium (either 1,400 mg calcium citrate or 1,500 mg calcium carbonate) with the same dose of calcium alone or placebo in 1,180 healthy, postmenopausal white women living in Nebraska. There was no statistical difference in total cancer incidence between the vitamin D plus calcium versus calcium alone groups or between women taking 1,500 mg of calcium and women taking placebo. There was a statistically significant difference between the vitamin D plus calcium group compared with the placebo group in total cancer incidence (RR, 0.40 [95% CI, 0.20 to 0.82]). Post hoc analysis, restricted to participants who were cancer free after 1 year, found a 77 percent relative reduction in total cancer incidence (RR, 0.23 [95% CI, 0.09 to 0.60]). The absolute risk for nonskin cancer was 6 percent in the control group and 1.5 percent in the intervention group. An important limitation of this trial was that cancer was not a primary outcome of the study design, and thus incidence may not have been fully ascertained.

Vitamin D and fractures. Sixteen randomized, controlled trials with considerable heterogeneity in populations, settings, and interventions examined the effect of vitamin D supplementation, with or without calcium, on fracture incidence in adults (6). Postmenopausal women represented the largest group of participants in the trials; no trials included women of childbearing age or men younger than age 50 years. Almost all trial participants were white. Six trials reported a history of prior fractures in 10.6 to 26 percent of participants. Two trials included only adults with a history of prior fractures, and five trials included only elderly institutionalized persons.

Vitamin D doses ranged from 300 to 1,370 IU daily, though most trials used at least 800 IU daily. Five trials compared vitamin D with placebo or no treatment, eight trials compared vitamin D and calcium with placebo or no treatment, four trials compared vitamin D and calcium with calcium alone, and one trial compared vitamin D and calcium with vitamin D alone; one trial had multiple arms. Most of the trials used vitamin D3 as the intervention, but three used vitamin D2. Calcium supplementation varied as well. Most trials used calcium carbonate, while others used citrate-, lactate-, or phosphate-based preparations. Methods for fracture ascertainment included self-report, x-ray confirmation, administrative data, physician verification, or some combination.

In the six trials evaluating the population within the scope of the USPSTF (i.e., community-dwelling adults without history of prior fractures), no statistically significant reduction in fractures was seen (pooled RR, 0.89 [95% CI, 0.76 to 1.04]). Trials of vitamin D supplementation alone showed no statistical difference (pooled RR, 1.03 [95% CI, 0.84 to 1.26]). Of the 12 trials reporting baseline levels of vitamin D, five reported mean vitamin D levels below 30 nmol/L, a level that is considered vitamin D–deficient. However, neither baseline vitamin D status nor supplement dose correlated with supplement efficacy.

The largest trial of fracture outcomes included in the meta-analyses is WHI (11), which enrolled 36,282 healthy postmenopausal women aged 50 to 79 years, with the racial and ethnic subgroups noted previously. The intervention group received 400 IU of vitamin D3 and 1,000 mg of calcium carbonate daily; the control group received placebo. This study reported no reduction in hip fracture (HR, 0.88 [95% CI, 0.72 to 1.08]) or total fractures with combined calcium and vitamin D supplementation (HR, 0.96 [95% CI, 0.91 to 1.02]). However, the USPSTF was unable to generalize the results of the WHI trial beyond the specific dose, preparation, and population studied. It is important to note that the dose of vitamin D used in WHI would not be considered sufficient today, and that nearly 30 percent of study participants were already taking supplements of ≥500 mg calcium daily prior to the start of the trial.

Potential Harms of Preventive Medication

Reporting of adverse outcomes in clinical trials and observational studies of vitamin D and calcium supplementation is limited. WHI (12) reported an increased risk for urinary tract stones (HR, 1.17 [95% CI, 1.02 to 1.34]). The absolute risk was 2.5 percent in the intervention group and 2.1 percent in the placebo group, with a number needed to harm of 273. It is uncertain if this adverse effect occurs in vitamin D–deficient populations.

Estimate of Magnitude of Net Benefit

For all noninstitutionalized adults, except postmenopausal women, there is inadequate evidence to estimate the benefits, if any, of vitamin D or calcium supplementation to prevent cancer and fractures. Due to the lack of effect on fracture incidence and the increased incidence of nephrolithiasis in the intervention group of the WHI trial, the USPSTF concludes with moderate certainty that daily supplementation with 400 IU of vitamin D3 and 1,000 mg of calcium carbonate has no net benefit for the primary prevention of osteoporotic fractures in noninstitutionalized postmenopausal women. While enrolled women were predominately of white race, the lower risk for osteoporotic fractures in nonwhite women makes it very unlikely that a benefit would exist in these women.

How Does Evidence Fit With Biological Understanding?

There are two main sources of vitamin D within the human body. Ergocalciferol, or vitamin D2, is consumed in the diet, mainly in the form of plants and fish. Cholecalciferol, or vitamin D3, is synthesized within the skin by ultraviolet B rays from the sun. Vitamin D3 is converted to its active form via enzymatic processes in the liver and kidney. Most cells contain specific receptors for the active form of vitamin D. Stimulation of skeletal muscle receptors promotes protein synthesis, and vitamin D has a beneficial effect on muscle strength and balance. Laboratory studies have suggested that vitamin D may reduce the risk for cancer via regulation of cellular proliferation, differentiation, and inhibition of angiogenesis. Vitamin D controls calcium absorption in the small intestines and interacts with parathyroid hormone to help maintain calcium homeostasis between the blood and bones.

Data from observational studies of vitamin D and cancer suggest that if an effect of vitamin D on cancer exists, it might only be achieved with a vitamin D intake greater than those given in randomized trials to date (13).

Recommendations of Others

The Institute of Medicine (14) (Table 3) and the World Health Organization (15) have set standards for adequate daily intake of calcium and vitamin D as a part of overall health; neither has made specific recommendations for cancer and fracture prevention.

Table 3. Institute of Medicine's 2011 Recommended Dietary Allowances for Vitamin D and Calcium (14)

Population Vitamin D Calcium
Women
19–50 years
51–70 years
>70 years

600 IU/day
600 IU/day
800 IU/day

1000 mg/day
1200 mg/day
1200 mg/day
Pregnant women
<18 years
>18 years

600 IU/day
600 IU/day

1300 mg/day
1000 mg/day
Nursing women
<18 years
>18 years

600 IU/day
600 IU/day

1300 mg/day
1000 mg/day
Men
19–50 years
51–70 years
>70 years

600 IU/day
600 IU/day
800 IU/day

1000 mg/day
1000 mg/day
1200 mg/day

Appendix: U.S. Preventive Services Task Force

Members of the U.S. Preventive Services Task Force* at the time this recommendation was finalized are Virginia A. Moyer, MD, MPH, Chair (Baylor College of Medicine, Houston, Texas); Michael L. LeFevre, MD, MSPH, Co-Vice Chair (University of Missouri School of Medicine, Columbia, Missouri); Albert L. Siu, MD, MSPH, Co-Vice Chair (Mount Sinai School of Medicine, New York, New York; James J. Peters Veterans Affairs Medical Center, Bronx, New York); Linda Ciofu Baumann, PhD, RN (University of Wisconsin, Madison, Wisconsin); Kirsten Bibbins-Domingo, PhD, MD (University of California, San Francisco, San Francisco, California); Susan J. Curry, PhD (University of Iowa College of Public Health, Iowa City, Iowa); Mark Ebell, MD, MS (University of Georgia, Athens, Georgia); Glenn Flores, MD (University of Texas Southwestern, Dallas, Texas); Adelita Gonzales Cantu, RN, PhD (University of Texas Health Science Center, San Antonio, Texas); David C. Grossman, MD, MPH (Group Health Cooperative, Seattle, Washington); Jessica Herzstein, MD, MPH (Air Products, Allentown, Pennsylvania); Joy Melnikow, MD, MPH (University of California Davis, Sacramento, California); Wanda K. Nicholson, MD, MPH, MBA (University of North Carolina School of Medicine, Chapel Hill, North Carolina); Douglas K. Owens, MD, MS (Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Stanford University, Stanford, California); Carolina Reyes, MD, MPH (Virginia Hospital Center, Arlington, Virginia); and Timothy J. Wilt, MD, MPH (University of Minnesota Department of Medicine and Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota). Former USPSTF members who contributed to the development of this recommendation include Diana Petitti, MD, MPH, and Bernadette Melnyk, PhD, RN.

* Members of the Task Force at the time this recommendation was finalized. For a list of current Task Force members, go to http://www.uspreventiveservicestaskforce.org/about.htm.

Table 1: What the Grades Mean and Suggestions for Practice

Grade Definition Suggestions for Practice
A The USPSTF recommends the service. There is high certainty that the net benefit is substantial. Offer or provide this service.
B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Offer or provide this service.
C Note: The following statement is undergoing revision.
Clinicians may provide this service to selected patients depending on individual circumstances. However, for most individuals without signs or symptoms there is likely to be only a small benefit from this service.
Offer or provide this service only if other considerations support offering or providing the service in an individual patient.
D The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Discourage the use of this service.
I Statement The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.


Table 2: Levels of Certainty Regarding Net Benefit

Level of Certainty* Description
High The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies.
Moderate The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by factors such as:
  • The number, size, or quality of individual studies.
  • Inconsistency of findings across individual studies.
  • Limited generalizability of findings to routine primary care practice.
  • Lack of coherence in the chain of evidence.

As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion.

Low The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:
  • The limited number or size of studies.
  • Important flaws in study design or methods.
  • Inconsistency of findings across individual studies.
  • Gaps in the chain of evidence.
  • Findings not generalizable to routine primary care practice.
  • A lack of information on important health outcomes.

More information may allow an estimation of effects on health outcomes.

*The U.S. Preventive Services Task Force defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct." The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit of a preventive service.

References

1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212-36.
2. Nelson HD, Haney EM, Dana T, Bougatsos C, Chou R. Screening for osteoporosis: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;153(2):99-111.
3. Office of the Surgeon General. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General; 2004. Accessed at http://www.ncbi.nlm.nih.gov/books/NBK45513/ on 31 May 2012.
4. Cranney A, Horsley T, O’Donnell S, Weiler H, Puil L, Ooi D, et al. Effectiveness and Safety of Vitamin D in Relation to Bone Health. Evidence Report/Technology Assessment No. 158 (Prepared by the University of Ottawa Evidence-based Practice Center under contract 290-02-0021). AHRQ Publication No. 07-E013. Rockville, MD: Agency for Healthcare Research and Quality; 2007. Accessed at archive.ahrq.gov/downloads/pub/evidence/pdf/vitamind/vitad.pdf on 10 July 2012.
5. Chung M, Balk EM, Brendel M, Ip S, Lau J, Lee J, et al. Vitamin D and Calcium: A Systematic Review of Health Outcomes. Evidence Report No. 183. (Prepared by the Tufts Evidence-based Practice Center under contract HHSA 290-2007-10055-I.) AHRQ Publication No. 09-E105. Rockville, MD: Agency for Healthcare Research and Quality; 2009. Accessed at www.ahrq.gov/downloads/pub/evidence/pdf/vitadcal/vitadcal.pdf on 12 November 2011.
6. Chung M, Lee J, Terasawa T, Lau J, Trikalinos T. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155(12):827-38.
7. Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst. 2008;100(22):1581-91.
8. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354(7):684-96.
9. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326(7387):469.
10. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85(6):1586-91.
11. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669-83.
12. Wallace RB, Wactawski-Wende J, O’Sullivan MJ, Larson JC, Cochrane B, Gass M, Masaki K. Urinary tract stone occurrence in the Women’s Health Initiative (WHI) randomized clinical trial of calcium and vitamin D supplements. Am J Clin Nutr. 2011;94(1):270-7.
13. National Cancer Institute. Fact Sheet. Vitamin D and Cancer Prevention: Strengths and Limits of the Evidence. Bethesda, MD: National Cancer Institute; 2012. Accessed at http://www.cancer.gov/cancertopics/factsheet/prevention/vitamin-D on 31 May 2012.
14. Ross CA, Taylor CL, Yaktine AL, Del Valle HB, eds; Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press; 2011. Accessed at http://www.nap.edu/catalog.php?record_id=13050 on 31 May 2012.
15. World Health Organization and Food and Agriculture Organization of the United Nations. Vitamin and Mineral Requirements in Human Nutrition. 2nd ed. Geneva, Switzerland: World Health Organization; 2004. Accessed at http://www.who.int/nutrition/publications/micronutrients/9241546123/en/index.html on 31 May 2012.

AHRQ Publication No. 12-05163-EF-2
Current as of July 2012


Internet Citation:

U.S. Preventive Services Task Force. Vitamin D and Calcium Supplementation to Prevent Cancer and Osteoporotic Fractures in Adults: Draft Recommendation Statement. AHRQ Publication No. 12-05163-EF-2. http://www.uspreventiveservicestaskforce.org/uspstf12/vitamind/draftrecvitd.htm



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