Final Recommendation Statement

Vitamin D Deficiency in Adults: Screening

April 13, 2021

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Recommendation Summary

Population Recommendation Grade
Asymptomatic, community-dwelling, nonpregnant adults The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults. See the Practice Considerations section for additional information regarding the I statement. I

Clinician Summary

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Recommendation Information

Full Recommendation:

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

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Vitamin D is a fat-soluble vitamin that performs an important role in calcium homeostasis and bone metabolism and also affects many other cellular regulatory functions outside the skeletal system.1-3 Vitamin D requirements may vary by individual; thus, no one serum vitamin D level cutpoint defines deficiency, and no consensus exists regarding the precise serum levels of vitamin D that represent optimal health or sufficiency. According to the National Academy of Medicine, an estimated 97.5% of the population will have their vitamin D needs met at a serum level of 20 ng/mL (49.9 nmol/L) and risk for deficiency, relative to bone health, begins to occur at levels less than 12 to 20 ng/mL (29.9-49.9 nmol/L).1,4 A report based on data from the 2014 National Health and Nutrition Examination Survey found that 5% of the population 1 year or older had very low 25-hydroxyvitamin D (25[OH]D) levels (<12 ng/mL) and 18% had levels between 12 and 19 ng/mL.5

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The US Preventive Services Task Force (USPSTF) concludes that the overall evidence on the benefits of screening for vitamin D deficiency is lacking. Therefore, the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults cannot be determined (Table).

See the Table for more information on the USPSTF recommendation rationale and assessment. For more details on the methods the USPSTF uses to determine the net benefit, see the USPSTF Procedure Manual.6

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Patient Population Under Consideration

This recommendation applies to community-dwelling, nonpregnant adults who have no signs or symptoms of vitamin D deficiency, such as bone pain or muscle weakness, or conditions for which vitamin D treatment is recommended. This recommendation focuses on screening (ie, testing for vitamin D deficiency in asymptomatic adults and treating those found to have a deficiency), which differs from USPSTF recommendation statements on supplementation.

Assessment of Risk

Although there is insufficient evidence to recommend for or against screening for vitamin D deficiency, several factors are associated with lower vitamin D levels. Low dietary vitamin D intake may be associated with lower 25(OH)D levels.7 Little or no UV B exposure (eg, because of winter season, high latitude, or sun avoidance) and older age are also associated with an increased risk for low vitamin D levels.8-12 Obesity is associated with lower 25(OH)D levels,13 and people who are obese have a 1.3- to 2-fold increased risk of being vitamin D–deficient, depending on the threshold used to define deficiency.8,9,13,14 The exact mechanism for this finding is not completely understood.

Depending on the serum threshold used to define deficiency, the prevalence of vitamin D deficiency is 2 to 10 times higher in non-Hispanic Black persons than in non-Hispanic White persons, likely related to differences in skin pigmentation.7-9,14 However, these prevalence estimates are based on total 25(OH)D levels, and controversy remains about whether this is the best measure of vitamin D status among different racial and ethnic groups.

A significant proportion of the variability in 25(OH)D levels among individuals is not explained by the risk factors noted above, which seem to account for only 20% to 30% of the variation in 25(OH)D levels.11,15

Treatment and Interventions

Vitamin D deficiency is usually treated with oral vitamin D. There are 2 commonly available forms of vitamin D—vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Both are available as either a prescription medication or an over-the-counter dietary supplement.

Suggestions for Practice Regarding the I Statement

Potential Preventable Burden

The prevalence of vitamin D deficiency varies based on how deficiency is defined. According to data from the 2011 to 2014 National Health and Nutrition Examination Survey, which used the liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay to measure 25(OH)D levels, 5% of the population 1 year or older had very low 25(OH)D levels (<12 ng/mL) and 18% had levels between 12 and 19 ng/mL.5 (To convert 25[OH]D values to nmol/L, multiply by 2.496.)

In some observational studies, lower vitamin D levels have been associated with risk for fractures, falls, functional limitations, some types of cancer, diabetes, cardiovascular disease, depression, and death.16,17 However, observations of these associations are inconsistent. This inconsistency may be because of different studies using different cutoffs to define a low vitamin D level or because vitamin D requirements and the optimal cutoff that defines a low vitamin D level or vitamin D deficiency may vary by individual or by subpopulation. For example, non-Hispanic Black persons have lower reported rates of fractures18 despite having increased prevalence of lower vitamin D levels than White persons.7-9,14 Further, it is unknown whether these associations are linked to causality.

The goal of screening for vitamin D deficiency would be to identify and treat it before associated adverse clinical outcomes occur. Total 25(OH)D level is currently considered the best marker of vitamin D status.4,19 A variety of assays can be used to measure 25(OH)D levels; however, levels can be difficult to measure accurately, and assays may underestimate or overestimate 25(OH)D levels. Additionally, the current evidence is inadequate to determine whether screening for and treatment of asymptomatic low 25(OH)D levels improve clinical outcomes in community-dwelling adults.

Potential Harms

Screening may misclassify persons with a vitamin D deficiency because of the uncertainty about the cutoff for defining deficiency and the variability of available testing assays. Misclassification may result in overdiagnosis (leading to nondeficient persons receiving unnecessary treatment) or underdiagnosis (leading to deficient persons not receiving treatment).

A rare but potential harm of treatment with vitamin D is toxicity, which is characterized by marked hypercalcemia as well as hyperphosphatemia and hypercalciuria. However, the 25(OH)D level associated with toxicity (typically >150 ng/mL)20 is well above the level considered to be sufficient. In general, treatment with oral vitamin D does not seem to be associated with serious harms. 

Current Practice

The prevalence of screening for vitamin D deficiency by primary care clinicians in the US has not been well studied. Data suggest that laboratory testing for vitamin D levels has increased greatly over the last several years or longer. One study reported a more than 80-fold increase in Medicare reimbursement volumes for vitamin D testing from 2000 to 2010.21

Other Related USPSTF Recommendations

The USPSTF has published recommendations on the use of vitamin D supplementation for the prevention of falls22 and fractures23 and vitamin supplementation for the prevention of cardiovascular disease or cancer.24 These recommendations differ from the current recommendation statement in that they address vitamin D supplementation without first determining a patient's vitamin D status (ie, regardless of whether they have a deficiency).

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Scope of Review

To update its 2014 recommendation statement, the USPSTF commissioned a systematic review26,27 of the evidence on screening for vitamin D deficiency, including the benefits and harms of screening and early treatment. The review focused on asymptomatic, community-dwelling, nonpregnant adults 18 years or older who do not have clinical signs of vitamin D deficiency or conditions that could cause vitamin D deficiency, or for which vitamin D treatment is recommended, and who were seen in primary care settings.

Accuracy of Screening Tests

Total 25(OH)D levels can be measured by both binding and chemical assays. Serum total 25(OH)D levels are difficult to measure accurately, and different immunoassays can lead to underestimation or overestimation of total 25(OH)D levels.19 LC-MS/MS is considered the reference assay. However, LC-MS/MS is a complicated process and is subject to variation and error, including interference from other chemical compounds.19

In 2010, the National Institutes of Health Office of Dietary Supplements, in collaboration with other organizations, initiated the Vitamin D Standardization Program.28,29 The primary goal of the program has been to promote the standardized measurement of 25(OH)D levels. Most of the trials reviewed for this recommendation precede this standardization program. When previously banked samples have been reassayed using these standardized methods, both upward and downward revisions of 25(OH)D levels have been observed, depending on the original assay that was used.19,30,31

Benefits of Early Detection and Treatment

The USPSTF found no studies that directly evaluated the benefits of screening for vitamin D deficiency. The USPSTF did find 26 randomized clinical trials (RCTs) and 1 nested case-control study that reported on the effectiveness of treatment of vitamin D deficiency (variably defined as a level <20 ng/mL to <31.2 ng/mL) on a variety of health outcomes, including all-cause mortality, fractures, incidence of diabetes, cardiovascular events and cancer, falls, depression, physical function, and infection.26,27

Eight RCTs and 1 nested case-control study reported on all-cause mortality in community-dwelling adults. Study duration ranged from 16 weeks to 7 years. In a pooled analysis of the 8 trials (n = 2006), there was no difference in all-cause mortality in persons randomized to vitamin D treatment compared with controls (relative risk [RR], 1.13 [95% CI, 0.39-3.28]).26,27 In the Women’s Health Initiative (WHI) Calcium–Vitamin D nested case-control study, there was no association between treatment with vitamin D and calcium and all-cause mortality among participants with baseline vitamin D levels between 14 and 21 ng/mL and among participants with baseline levels less than 14 ng/mL.32,33

Six RCTs reported on fracture outcomes in community-dwelling adults. Study duration ranged from 12 weeks to 7 years. A pooled analysis of the 6 trials (n = 2186) found no difference in the incidence of fractures among those randomized to vitamin D treatment compared with placebo (RR, 0.84 [95% CI, 0.58-1.21]).26 The USPSTF found only 1 trial reporting on hip fracture in community-dwelling adults. In that study, only 1 hip fracture occurred, leading to a very imprecise effect estimate.34 In the WHI Calcium–Vitamin D nested case-control study, there was no association between treatment with vitamin D and calcium and clinical fracture or hip fracture incidence.32

Five RCTs reported on incident diabetes. Study duration ranged from 1 year to 7 years. A pooled analysis of the 5 trials (n = 3356) found no difference in the incidence of diabetes among participants randomized to vitamin D treatment compared with placebo (RR, 0.96 [95% CI, 0.80-1.15]).26

For several outcomes, the USPSTF found inadequate evidence on the benefit of treatment of asymptomatic vitamin D deficiency. Limitations of the following evidence include few studies reporting certain outcomes and, for some outcomes, variable methods of ascertainment, variable reporting of outcomes, small study size, or short duration of follow-up.

Two trials, the Vitamin D and Omega-3 Trial (VITAL) (n = 2001 in trial subgroup)35 and the Vitamin D Assessment Study (ViDA) (n = 1270 in trial subgroup),36 reported on cardiovascular events. Both trials observed no statistically significant differences in cardiovascular events between the treatment and placebo groups among the subgroup of participants with serum vitamin D levels less than 20 ng/mL at baseline. VITAL had 5.3 years of follow-up, while the ViDA trial had only 3.3 years of follow-up. The ViDA trial also used a heterogeneous definition of cardiovascular events, which included venous thromboembolism, pulmonary embolism, inflammatory cardiac conditions, arrhythmias, and conduction disorders.

Two trials, VITAL35 and a post hoc analysis of the ViDA trial,37 and the WHI nested case-control study38,39 reported on the effect of vitamin D treatment on the incidence of cancer. Both trials reported no difference in cancer incidence between participants randomized to treatment and placebo among the subgroup of participants with serum 25(OH)D levels less than 20 ng/mL at baseline. The ViDA trial had only 3 years of follow-up, which may be a short period to detect an effect on cancer incidence. In the WHI Calcium–Vitamin D nested case-control study, the adjusted odds ratios (ORs) for incident breast or colorectal cancer over 7 years of follow-up did not demonstrate a statistically significant association between exposure to active treatment and incidence of cancer among participants with vitamin D deficiency at baseline.38,39

Nine trials reported fall outcomes in community-dwelling adults.26,27 Some trials reported only falls, others only the number of participants who experienced 1 or more falls (ie, “fallers”), and some trials reported both outcomes. A pooled analysis of 6 trials found no association between vitamin D treatment and number of fallers (RR, 0.90 [95% CI, 0.75-1.08]), while a pooled analysis of 5 trials found a significant association between vitamin D treatment and falls (incidence rate ratio, 0.76 [95% CI, 0.57-0.94]).26,27 However, heterogeneity was high in both analyses, ascertainment methods for falls and fallers were variable across studies, and the variable reporting of falls, fallers, or both outcomes raises the possibility of selective outcome reporting. One trial reported on the incidence of 2 or more falls, a different definition of “fallers” than in the trials included in the pooled analysis above. It found no significant difference between participants randomized to vitamin D or placebo among the subgroup of participants with baseline vitamin D levels less than 12 ng/mL (adjusted OR, 1.03 [95% CI, 0.59-1.79]) or among those with levels between 12 and 20 ng/mL (adjusted OR, 1.13 [95% CI, 0.87-1.48]).40

Three trials reported depression outcomes. One, VITAL-DEP (Depression Endpoint Prevention), was an ancillary study to the VITAL trial. Among the subgroup of participants with baseline serum vitamin D levels less than 20 ng/mL (n = 1328), there was no difference in the change in Personal Health Questionnaire Depression Scale scores between those randomized to vitamin D compared with placebo over a median follow-up of 5.3 years.41 The other 2 trials were relatively small and of short duration. Both reported no significant difference in depression measures between vitamin D treatment and placebo.42,43 Two trials reporting on physical functioning measures reported conflicting results.44,45 An unplanned subgroup analysis of 1 trial conducted in persons with impaired fasting glucose found no difference in incidence of a first urinary tract infection in participants with vitamin D deficiency who were treated with vitamin D compared with placebo.46

As noted, the studies comprising the body of evidence cited above did not uniformly define vitamin D deficiency. Different studies enrolled participants with vitamin D levels that ranged from less than 20 ng/mL to less than 31.2 ng/mL. For those outcomes with sufficient data (mortality, fractures, and falls), findings were similar between studies using a lower threshold and studies using a higher threshold.26,27

Harms of Screening and Treatment

The USPSTF found no studies that directly evaluated the harms of screening for vitamin D deficiency. The USPSTF found 36 studies that reported adverse events and harms from treatment with vitamin D (with or without calcium) compared with a control group. The absolute incidence of adverse events varied widely across studies; however, the incidence of total adverse events, such as gastrointestinal symptoms, fatigue, musculoskeletal symptoms, and headaches, and serious adverse events was generally similar between treatment and control groups. In the 10 trials that reported incidence of kidney stones, there was only 1 case.26,27

Response to Public Comment

A draft version of this recommendation statement was posted for public comment on the USPSTF website from September 22, 2020, to October 19, 2020. Some comments requested the USPSTF to evaluate the evidence on or make a recommendation regarding vitamin D supplementation. In response, the USPSTF wants to clarify that this recommendation focuses on screening for vitamin D deficiency. The USPSTF does have separate recommendations that address vitamin D supplementation (ie, providing vitamin D to all persons without testing, and regardless of vitamin D level) for a variety of conditions.22-24 In response to comments, the USPSTF also wants to clarify that this recommendation applies to asymptomatic, community-dwelling adults. It does not apply to persons in institutional or hospital settings, who may have underlying or intercurrent conditions that warrant vitamin D testing or treatment. The USPSTF also wants to clarify that it did not review the emerging evidence on COVID-19, the disease caused by the new coronavirus SARS-CoV-2, and vitamin D.

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More studies are needed that address the following areas:

  • More research is needed to determine whether total serum 25(OH)D levels are the best measure of vitamin D deficiency and whether the best measure of vitamin D deficiency varies by subgroups defined by race, ethnicity, or sex.
  • More research is needed to determine the cutoff that defines vitamin D deficiency and whether that cutoff varies by specific clinical outcome or by subgroups defined by race, ethnicity, or sex.
  • When vitamin D deficiency is better defined, studies on the benefits and harms of screening for vitamin D deficiency will be helpful.
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No organization recommends population-based screening for vitamin D deficiency, and the American Society for Clinical Pathology recommends against it.47 The American Academy of Family Physicians supports the USPSTF 2014 recommendation, which states that there is insufficient evidence to recommend screening the general population for vitamin D deficiency.48 The Endocrine Society49 and the American Association of Clinical Endocrinologists50 recommend screening for vitamin D deficiency in individuals at risk. The Endocrine Society does not recommend population screening for vitamin D deficiency in individuals not at risk.49

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The US Preventive Services Task Force members include the following individuals: Alex H. Krist, MD, MPH (Fairfax Family Practice Residency, Fairfax, Virginia, and Virginia Commonwealth University, Richmond); Karina W. Davidson, PhD, MASc (Feinstein Institute for Medical Research at Northwell Health, Manhasset, New York); Carol M. Mangione, MD, MSPH (University of California, Los Angeles); Michael Cabana, MD, MA, MPH (Albert Einstein College of Medicine, New York, New York); Aaron B. Caughey, MD, PhD (Oregon Health & Science University, Portland); Esa M. Davis, MD, MPH (University of Pittsburgh, Pittsburgh); Katrina E. Donahue, MD, MPH (University of North Carolina at Chapel Hill); Chyke A. Doubeni, MD, MPH (Mayo Clinic, Rochester, MN); Martha Kubik, PhD, RN (George Mason University, Fairfax, Virginia); Li Li, MD, PhD, MPH (University of Virginia, Charlottesville); Gbenga Ogedegbe, MD, MPH (New York University, New York, New York); Douglas K. Owens, MD, MS (Stanford University, Stanford); Lori Pbert, PhD (University of Massachusetts Medical School, Worcester); Michael Silverstein, MD, MPH (Boston University, Boston, Massachusetts); James Stevermer, MD, MSPH (University of Missouri, Columbia); Chien-Wen Tseng, MD, MPH, MSEE (University of Hawaii, Honolulu); John B. Wong, MD (Tufts University School of Medicine, Boston, Massachusetts).

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1. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011.
2. Pludowski P, Holick MF, Pilz S, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality: a review of recent evidence. Autoimmun Rev. 2013;12(10):976-989. Medline:23542507 doi:10.1016/j.autrev.2013.02.004
3. Autier P, Mullie P, Macacu A, et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017;5(12):986-1004. Medline:29102433 doi:10.1016/S2213-8587(17)30357-1
4. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53-58. Medline:21118827 doi:10.1210/jc.2010-2704
5. Herrick KA, Storandt RJ, Afful J, et al. Vitamin D status in the United States, 2011-2014. Am J Clin Nutr. 2019;110(1):150-157. Medline:31076739 doi:10.1093/ajcn/nqz037
6. Procedure Manual. U.S. Preventive Services Task Force. Published 2018. Accessed February 10, 2021. https://uspreventiveservicestaskforce.org/uspstf/procedure-manual.
7. Schleicher RL, Sternberg MR, Lacher DA, et al. The vitamin D status of the US population from 1988 to 2010 using standardized serum concentrations of 25-hydroxyvitamin D shows recent modest increases. Am J Clin Nutr. 2016;104(2):454-461. Medline:27385610 doi:10.3945/ajcn.115.127985
8. Orwoll E, Nielson CM, Marshall LM, et al; Osteoporotic Fractures in Men (MrOS) Study Group. Vitamin D deficiency in older men. J Clin Endocrinol Metab. 2009;94(4):1214-1222. Medline:19174492 doi:10.1210/jc.2008-1784
9. McCullough ML, Weinstein SJ, Freedman DM, et al. Correlates of circulating 25-hydroxyvitamin D: cohort consortium vitamin D pooling project of rarer cancers. Am J Epidemiol. 2010;172(1):21-35. Medline:20562191 doi:10.1093/aje/kwq113
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11. Millen AE, Wactawski-Wende J, Pettinger M, et al. Predictors of serum 25-hydroxyvitamin D concentrations among postmenopausal women: the Women's Health Initiative Calcium plus Vitamin D clinical trial. Am J Clin Nutr. 2010;91(5):1324-1335. Medline:20219959 doi:10.3945/ajcn.2009.28908
12. Jacques PF, Felson DT, Tucker KL, et al. Plasma 25-hydroxyvitamin D and its determinants in an elderly population sample. Am J Clin Nutr. 1997;66(4):929-936. Medline:9322570 doi:10.1093/ajcn/66.4.929
13. Samuel L, Borrell LN. The effect of body mass index on optimal vitamin D status in U.S. adults: the National Health and Nutrition Examination Survey 2001-2006. Ann Epidemiol. 2013;23(7):409-414. Medline:23790345 doi:10.1016/j.annepidem.2013.05.011
14. Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54. Medline:21310306 doi:10.1016/j.nutres.2010.12.001
15. Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006;98(7):451-459. Medline:16595781 doi:10.1093/jnci/djj101
16. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035. Medline:24690624 doi:10.1136/bmj.g2035
17. Newberry SJ, Chung M, Shekelle PG, et al. Vitamin D and calcium: a systematic review of health outcomes (update). Evid Rep Technol Assess. 2014;(217):1-929. Medline:30313003 doi:10.23970/AHRQEPCERTA217
18. Barrett-Connor E, Siris ES, Wehren LE, et al. Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res. 2005;20:185-94. Medline:15647811 doi:10.1359/JBMR.041007
19. Sempos CT, Heijboer AC, Bikle DD, et al. Vitamin D assays and the definition of hypovitaminosis D: results from the First International Conference on Controversies in Vitamin D. Br J Clin Pharmacol. 2018;84(10):2194-2207. Medline:29851137 doi:10.1111/bcp.13652
20. Marcinowska-Suchowierska E, Kupisz-Urbańska M,  Łukaszkiewicz J, Płudowski P, Jones G. Vitamin D toxicity–a clinical perspective. Front Endocrinol (Lausanne). 2018;9:550. Medline:30294301 doi:10.3389/fendo.2018.00550
21. Shahangian S, Alspach TD, Astles JR, Yesupriya A, Dettwyler WK. Trends in laboratory test volumes for Medicare Part B reimbursements, 2000–2010. Arch Pathol Lab Med. 2014;138(2):189-203. Medline:23738761 doi:10.5858/arpa.2013-0149-OA
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23. Grossman DC, Curry SJ, Owens DK, et al; US Preventive Services Task Force. Vitamin D, calcium, or combined supplementation for primary prevention of fractures in community-dwelling adults: US Preventive Services Task Force recommendation statement. JAMA. 2018;319(15):1592-1599. Medline:29677309 doi:10.1001/jama.2018.3185
24. Moyer VA; US Preventive Services Task Force. Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160:558-564. Medline:24566474 doi:10.7326/M14-0198
25. LeFevre ML; US Preventive Services Task Force. Screening for vitamin D deficiency in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;162(2):133-40. Medline:25419853 doi:10.7326/M14-2450
26. Kahwati LC, LeBlanc E, Weber RP, et al. Screening for Vitamin D deficiency in Adults: An Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 201. Agency for Healthcare Research and Quality; 2021. AHRQ publication No. 20-05270-EF-1.
27. Kahwati LC, LeBlanc E, Palmieri Weber R, et al. Screening for vitamin D deficiency in adults: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. Published April 13, 2021. doi:10.1001/jama.2020.26498
28. Sempos CT, Vesper HW, Phinney KW, Thienpont LM, Coates PM; Vitamin D Standardization Program (VDSP). Vitamin D status as an international issue: national surveys and the problem of standardization. Scand J Clin Lab Invest Suppl. 2012;243:32-40. Medline:22536760
29. Binkley N, Sempos CT; Vitamin D Standardization Program (VDSP). Standardizing vitamin D assays: the way forward. J Bone Miner Res. 2014;29(8):1709-1714. Medline:24737265 doi:10.1002/jbmr.2252
30. Rabenberg M, Scheidt-Nave C, Busch MA, et al. Implications of standardization of serum 25-hydroxyvitamin D data for the evaluation of vitamin D status in Germany, including a temporal analysis. BMC Public Health. 2018;18(1):845. Medline:29980236 doi:10.1186/s12889-018-5769-y
31. Binkley N, Dawson-Hughes B, Durazo-Arvizu R, et al. Vitamin D measurement standardization: the way out of the chaos. J Steroid Biochem Mol Biol. 2017;173:117-121. Medline:27979577 doi:10.1016/j.jsbmb.2016.12.002
32. Jackson RD, LaCroix AZ, Gass M, et al; Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669-683. Medline:16481635 doi:10.1056/NEJMoa055218
33. LaCroix AZ, Kotchen J, Anderson G, et al. Calcium plus vitamin D supplementation and mortality in postmenopausal women: the Women's Health Initiative calcium-vitamin D randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2009;64(5):559-567. Medline:19221190 doi:10.1093/gerona/glp006
34. Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res. 2000;15(6):1113-1118. Medline:10841179 doi:10.1359/jbmr.2000.15.6.1113
35. Manson JE, Cook NR, Lee IM, et al; VITAL Research Group. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33-44. Medline:30415629 doi:10.1056/NEJMoa1809944
36. Scragg R, Stewart AW, Waayer D, et al. Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the Vitamin D Assessment Study: a randomized clinical trial. JAMA Cardiol. 2017;2(6):608-616. Medline:28384800 doi:10.1001/jamacardio.2017.0175
37. Scragg R, Khaw KT, Toop L, et al. Monthly high-dose vitamin D supplementation and cancer risk: a post hoc analysis of the Vitamin D Assessment Randomized Clinical Trial. JAMA Oncol. 2018;4(11):e182178. Medline:30027269 doi:10.1001/jamaoncol.2018.2178
38. Chlebowski RT, Johnson KC, Kooperberg C, et al; Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst. 2008;100(22):1581-1591. Medline:19001601 doi:10.1093/jnci/djn360
39. Wactawski-Wende J, Kotchen JM, Anderson GL, et al; Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354(7):684-696. Medline:16481636 doi:10.1056/NEJMoa055222
40. LeBoff MS, Murata EM, Cook NR, et al. VITamin D and OmegA-3 TriaL (VITAL): effects of vitamin D supplements on risk of falls in the US population. J Clin Endocrinol Metab. 2020;105(9):2929-2938. Medline:32492153 doi:10.1210/clinem/dgaa311
41. Okereke OI, Reynolds CF III, Mischoulon D, et al. Effect of long-term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: a randomized clinical trial. JAMA. 2020;324(5):471-480. Medline:32749491 doi:10.1001/jama.2020.10224
42. Jorde R, Kubiak J. No improvement in depressive symptoms by vitamin D supplementation: results from a randomised controlled trial. J Nutr Sci. 2018;7:e30. Medline:30510695 doi:10.1017/jns.2018.19
43. Kjaergaard M, Waterloo K, Wang CE, et al. Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial. Br J Psychiatry. 2012;201(5):360-368. Medline:22790678 doi:10.1192/bjp.bp.111.104349
44. Hansen KE, Johnson RE, Chambers KR, et al. Treatment of vitamin D insufficiency in postmenopausal women: a randomized clinical trial. JAMA Intern Med. 2015;175(10):1612-1621. Medline:26237520 doi:10.1001/jamainternmed.2015.3874
45. Arvold DS, Odean MJ, Dornfeld MP, et al. Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. Endocr Pract. 2009;15(3):203‐212. Medline:19364687 doi:10.4158/EP.15.3.203
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47. Twenty Things Physicians and Patients Should Question. American Society for Clinical Pathology. Published 2017. Accessed February 10, 2021. https://www.ascp.org/content/docs/default-source/get-involved-pdfs/20-things-to-question.pdf?sfvrsn=4.
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Rationale Assessment
Detection
  • Vitamin D requirements may vary by individual, and there is no one 25(OH)D level that defines deficiency for all individuals.
  • Total 25(OH)D levels are currently considered the best marker of vitamin D status; however, levels are difficult to measure accurately.
  • Evidence suggests that results vary by testing method and between laboratories using the same testing methods.
Benefits of early detection and intervention and treatment
  • No direct evidence on the benefits of screening for vitamin D deficiency.
  • Adequate evidence that treatment of asymptomatic vitamin D deficiency has no benefit on mortality, risk for fractures in persons selected solely on the basis of low vitamin D levels (as opposed to clinical risks such as low bone density), or incidence of type 2 diabetes mellitus.
  • Inadequate evidence on the benefit of treatment of asymptomatic vitamin D deficiency on other outcomes, including falls, cancer, cardiovascular events, depression, infection, or physical functioning.
  • Despite adequate evidence to conclude no benefit for a few health outcomes, evidence on the benefits of treatment of asymptomatic vitamin D deficiency in adults for other health outcomes remains inadequate. The overall evidence on the benefits of treatment of asymptomatic vitamin D deficiency in adults is inadequate.
Harms of early detection and intervention and treatment
  • No direct evidence on the harms of screening for vitamin D deficiency.
  • Adequate evidence that the harms of treatment of vitamin D deficiency are small to none.
USPSTF assessment The overall evidence on the benefits of screening for vitamin D deficiency is lacking. Therefore, the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults cannot be determined.

Abbreviations: 25(OH)D, 25-hydroxyvitamin D; USPSTF, US Preventive Services Task Force.

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