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.
Vitamin D is a fat-soluble vitamin that performs an important role in calcium homeostasis and bone metabolism. It 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 defines deficiency, and no consensus exists regarding the precise serum levels of vitamin D that represent optimal health or sufficiency. The National Academy of Medicine (formerly the Institute of Medicine) states that 97.5% of the population will have their vitamin D needs met at a serum level of 20 ng/mL and that risk for deficiency, relative to bone health, begins to occur at levels less than 12 to 20 ng/mL.1, 4 According to the 2014 National Health and Nutrition Examination Survey (NHANES), 5% of the population age 1 year or older had very low 25-hydroxyvitamin D, or 25-(OH)D, levels (<12 ng/mL) and 18% had levels between 12 and 19 ng/mL.5
The 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).
For more details on the methods the USPSTF uses to determine the net benefit, see the USPSTF Procedure Manual.6
Patient Population Under Consideration
This recommendation applies to community-dwelling, nonpregnant adults who have no signs or symptoms of vitamin D deficiency or conditions for which vitamin D treatment is recommended. This recommendation focuses on screening (i.e., 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 ultraviolet B (UVB) exposure (e.g., because of winter season, high latitude, or sun avoidance) is also associated with an increased risk for low vitamin D levels.8-12 Obesity is associated with lower 25-(OH)D levels,13 translating into 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 individuals than in non-Hispanic white individuals.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 two commonly available forms of vitamin D—vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Both are available as either a prescription 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 the NHANES, which used the liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to measure 25-(OH)D levels during the 2011 to 2014 survey, 5% of the population age 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
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 cut points to define a low vitamin D level, or that vitamin D requirements and the optimal cut point 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. The 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, it 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.
Screening may misclassify persons with a vitamin D deficiency because of the uncertainty about the cut point 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.
The prevalence of screening for vitamin D deficiency by primary care clinicians in the United States 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 more than an 80-fold increase in Medicare reimbursement volumes for vitamin D testing from 2000 through 2010.21
Other Related USPSTF Recommendations
The USPSTF has published recommendations on the use of vitamin D supplementation for the prevention of falls22 and fractures,23 and vitamin supplementation for the prevention of cardiovascular disease or cancer,24 all available at https://uspreventiveservicestaskforce.org. These recommendations differ from the current recommendation statement in that they address vitamin D supplementation without first determining a patient's vitamin D status, i.e., regardless of whether they have a deficiency.
When final, this recommendation will replace the 2014 USPSTF recommendation statement on screening for vitamin D deficiency in asymptomatic adults. In 2014, the USPSTF concluded that the evidence was insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency.25 For the current draft recommendation statement, the USPSTF again concludes that the evidence is insufficient to assess the balance of benefits and harms of screening vitamin D deficiency in asymptomatic adults.
To update its 2014 recommendation statement, the USPSTF commissioned a systematic review26 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 age 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 U.S. National Institutes of Health’s Office of Dietary Supplements, in collaboration with other organizations, initiated the Vitamin D Standardization Program (VDSP).27, 28 The primary goal of the program has been to promote the standardized measurement of 25-(OH)D. 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, 29, 30
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 and one nested case-control study that reported on the effectiveness of treatment of vitamin D deficiency (variably defined as a level of <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
Eight randomized clinical trials and one 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 eight trials (n=2,006), 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 to 3.28]).26 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.31, 32
Six randomized clinical trials reported on fracture outcomes in community-dwelling adults. Study duration ranged from 12 weeks to 7 years. A pooled analysis of the six trials (n=2,186) 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 to 1.21]).26 The USPSTF found only one trial reporting on hip fracture in community-dwelling adults. In that study, only one hip fracture occurred, leading to a very imprecise effect estimate.33 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.31
Five randomized clinical trials reported on incident diabetes. Study duration ranged from 1 year to 7 years. A pooled analysis of the five trials (n=3,356) 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 to 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 followup.
Two trials, VITamin D and OmegA-3 TriaL (VITAL) (n=2,001 in trial subgroup)34 and Vitamin D Assessment Study (ViDA) (n=1,270 in trial subgroup),35 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 followup, while the ViDA trial had only 3.3 years of followup. 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, VITAL34 and a post-hoc analysis of the ViDA trial,36 and the WHI nested case-control study37, 38 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 followup, which may be a short time period to detect an effect on cancer incidence. In the WHI Calcium-Vitamin D nested case-control study, the adjusted odds ratios for incident breast or colorectal cancer over 7 years of followup did not demonstrate a statistically significant association between exposure to active treatment and incidence of cancer among participants with vitamin D deficiency at baseline.37, 38
Eight trials reported fall outcomes in community-dwelling adults.26 Some trials reported only falls, others only the number of participants who experienced one or more falls (i.e., “fallers”), and some trials reported both outcomes. A pooled analysis of six trials found no association between vitamin D treatment and fallers (RR, 0.90 [95% CI, 0.75 to 1.08]), while a pooled analysis of five trials found a significant association between vitamin D treatment and falls (incidence rate ratio, 0.76 [95% CI, 0.57 to 0.94]).26 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.
Two trials reported depression outcomes; both reported no significant difference in depression measures between vitamin D treatment and placebo.39, 40 Both were relatively small trials and of short duration. Two trials reporting on physical functioning measures reported conflicting results.41, 42 An unplanned subgroup analysis of one 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.43
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
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 it, there was only one case of kidney stones.26
- 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 cut point that defines vitamin D deficiency, and whether that cut point 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.
No organization recommends population-based screening for vitamin D deficiency, and the American Society for Clinical Pathology recommends against it.44 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.45 The Endocrine Society46 and the American Association of Clinical Endocrinologists47 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.46
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.
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.
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.
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.
6. U.S. Preventive Services Task Force. Procedure Manual. 2018. https://uspreventiveservicestaskforce.org/uspstf/procedure-manual. Accessed September 8, 2020.
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.
8. Orwoll E, Nielson CM, Marshall LM, et al. Vitamin D deficiency in older men. J Clin Endocrinol Metab. 2009;94(4):1214-1222.
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.
10. Linos E, Keiser E, Kanzler M, et al. Sun protective behaviors and vitamin D levels in the US population: NHANES 2003-2006. Cancer Causes Control. 2012;23(1):133-140.
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.
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.
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.
14. Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54.
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.
16. Theodoratou E, Tzoulaki I, Zgaga L, et al. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348: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.
18. Barrett-Connor E, Siris ES, Wehren LE, Miller PD, Abbott TA, Berger ML, et al. Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res. 2005;20:185-94.
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.
20. Marcinowska-Suchowierska E, Kupisz-Urbańska M, Łukaszkiewicz J, et al. Vitamin D toxicity–a clinical perspective. Front Endocrinol (Lausanne). 2018;9:550.
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.
22. US Preventive Services Task Force. Interventions to prevent falls in community-dwelling older adults: US Preventive Services Task Force recommendation statement. JAMA. 2018;319(16):1696-1704.
23. 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.
24. 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.
25. 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.
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. AHRQ Publication No. 20-05270-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2020.
27. Sempos CT, Vesper HW, Phinney KW, et al. Vitamin D status as an international issue: national surveys and the problem of standardization. Scand J Clin Lab Invest Suppl. 2012;243:32-40.
28. Binkley N, Sempos CT. Standardizing vitamin D assays: the way forward. J Bone Miner Res. 2014;29(8):1709-1714.
29. 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.
30. 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.
31. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669-683.
32. 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.
33. Pfeifer M, Begerow B, Minne HW, et al. 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.
34. Manson JE, Cook NR, Lee IM, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33-44.
35. 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.
36. 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.
37. Chlebowski RT, Johnson KC, Kooperberg C, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst. 2008;100(22):1581-1591.
38. Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354(7):684-696.
39. 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.
40. 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.
41. 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.
42. 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.
43. Jorde R, Sollid ST, Svartberg J, et al. Vitamin D 20,000 IU per week for five years does not prevent progression from prediabetes to diabetes. J Clin Endocrinol Metab. 2016;101(4):1647-1655.
44. American Society for Clinical Pathology. Twenty Things Physicians and Patients Should Question. 2017. https://www.ascp.org/content/docs/default-source/get-involved-pdfs/20-things-to-question.pdf?sfvrsn=4. Accessed September 8, 2020.
45. American Academy of Family Physicians. Clinical preventive service recommendation: vitamin D deficiency. https://www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/vitamin-D-deficiency.html. Accessed September 8, 2020.
46. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930.
47. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis - 2016. Endocr Pract. 2016;22(Suppl 4):1-42.
|Benefits of Early Detection and Intervention and Treatment||
|Harms of Early Detection and Intervention and Treatment||
|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=U.S. Preventive Services Task Force.