Vitamins

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Vitamin B12 – at-risk populations
    • Malabsorption, use of H2 receptor antagonists, proton-pump inhibitors, vegetarian diet, aged adults
  • Vitamin D – at-risk populations
    • Poor nutritional intake, limited sun exposure, malabsorption, liver failure, or renal insufficiency
    • Aged adults
    • Certain medications (eg, antiseizure and AIDS medications, glucocorticoids)
  • Vitamin K – patient with elevated INR and unresponsive to vitamin K supplementation (Choosing Wisely: 5 Things Physicians and Patients Should Question; American Society of Clinical Pathology, 2015)
  • Other vitamins – symptoms consistent with deficiency PLUS risk factor for deficiency

Laboratory Testing

  • Order specific testing based on symptoms and risk assessment
  • For B12 deficiency – consider concurrent testing for folate level; refer to the following for more information
  • For vitamin D deficiency
    • Testing not recommended while patient is ill – levels decrease with inflammation and acute illness but not true deficiency
    • Order test for 25-hydroxy vitamin D by chemiluminescence if available
      • 25-hydroxy vitamin D is the major and most stable circulating form of vitamin D
    • Recommended values – no consensus on optimal concentrations (Institute of Medicine, 2011)
      • 20-30 ng/mL – defined as insufficiency
      • <20 ng/mL – defined as deficiency
    • Do not order 1,25-dihydroxy test unless patient has hypercalcemia or decreased renal function (ASCP's Pathology-Related Choosing Wisely Recommendations, 2015 [Endocrine Society and American Association of Clinical Endocrinologists])
    • Fractionation testing for D2 and D3 not necessary for initial evaluation of vitamin D deficiency
      • Method used should ideally measure D2 and D3 metabolites equally
  • Universal screening
    • Insufficient evidence to assess harms or benefits of universal screening for vitamin D deficiency (USPSTF, 2015)
    • Do not perform as population-based screening (Choosing Wisely: 5 Things Physicians and Patients Should Question, 2015)
    • Other societies recommend against universal screening
      • ACOG (2011)
      • Endocrine Society (2011)
      • American Academy of Pediatrics (2014)
      • American Geriatrics Society (2014)
  • At risk population screening
    • Consider vitamin D deficiency screening for patients at risk
      • Institutionalized refugees
      • Celiac disease
      • Patients with osteoporosis
      • Patients from areas with high vitamin D deficiency
      • Older adults (age is a risk factor)
  • Vitamin D
    • Monitor therapy response – check 25-hydroxy vitamin D 10-12 weeks after initiating therapy
    • Patients who do not appear to be responding to therapy – vitamin D2 or D3 testing may be helpful

Vitamins are required in the diet because they are not adequately synthesized in the human body.

  • Only small amounts are necessary to catalyze essential biochemical reactions
  • Most deficiencies are rare in healthy persons in the U.S.
  • Disease states generally result from poor diet (eg, elderly, alcoholism)
  • Body stores vary by vitamin
    • Thiamine (B1) and folate stores are small and rapidly depleted
    • Cobalamin (B12) stores are large
  • Vitamins play several roles in disease processes
    • Diseases can cause vitamin deficiency
    • Vitamin deficiency or excess can cause disease
    • Therapeutic doses of certain vitamins can be used to manage some diseases
  • Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

    Vitamin B1 (Thiamine), Whole Blood 0080388
    Method: Quantitative High Performance Liquid Chromatography

    Vitamin B2 (Riboflavin) 0081123
    Method: Quantitative High Performance Liquid Chromatography

    Niacin (Vitamin B3) 0092168
    Method: Quantitative High Performance Liquid Chromatography

    Vitamin B5 (Pantothenic Acid), Serum 2006982
    Method: Quantitative Cell Based Assay

    Vitamin B[6] (Pyridoxal 5-Phosphate) 0080111
    Method: Quantitative High Performance Liquid Chromatography

    Vitamin B[7] (Biotin) 2003184
    Method: Bioassay

    Vitamin B12 and Folate 0070160
    Method: Quantitative Chemiluminescent Immunoassay

    Vitamin B12 with Reflex to Methylmalonic Acid, Serum (Vitamin B12 Status) 0055662
    Method: Quantitative Chemiluminescent Immunoassay/Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

    Folate, RBC 0070385
    Method: Quantitative Chemiluminescent Immunoassay

    Vitamin C (Ascorbic Acid), Plasma 0080380
    Method: Quantitative High Performance Liquid Chromatography

    Vitamin A (Retinol), Serum or Plasma 0080525
    Method: Quantitative High Performance Liquid Chromatography

    Limitations 

    This assay does not measure other vitamin A metabolites such as retinaldehyde or retinoic acid

    Vitamin D, 25-Hydroxy 0080379
    Method: Quantitative Chemiluminescent Immunoassay

    Vitamin E, Serum or Plasma 0080521
    Method: Quantitative High Performance Liquid Chromatography

    Vitamin K1, Serum 0099225
    Method: Quantitative High Performance Liquid Chromatography

    Guidelines

    American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

    American Society for Clinical Pathology. Choosing Wisely - Pathology-Related Choosing Wisely Recommendations. An initiative of the ABIM Foundation. [Initial posting Feb 2015; Accessed: Nov 2015]

    Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr. 2011; 94(1): 348S-358S. PubMed

    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad H, Weaver CM, Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96(7): 1911-30. PubMed

    Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, Del Valle HB Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011 :PubMed

    LeFevre ML, U.S. 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. PubMed

    Yetley EA, Coates PM, Johnson CL. Overview of a roundtable on NHANES monitoring of biomarkers of folate and vitamin B-12 status: measurement procedure issues. Am J Clin Nutr. 2011; 94(1): 297S-302S. PubMed

    Yetley EA, Pfeiffer CM, Phinney KW, Bailey RL, Blackmore S, Bock JL, Brody LC, Carmel R, Curtin R, Durazo-Arvizu RA, Eckfeldt JH, Green R, Gregory JF, Hoofnagle AN, Jacobsen DW, Jacques PF, Lacher DA, Molloy AM, Massaro J, Mills JL, Nexo E, Rader JI, Selhub J, Sempos C, Shane B, Stabler S, Stover P, Tamura T, Tedstone A, Thorpe SJ, Coates PM, Johnson CL, Picciano MFrances. Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr. 2011; 94(1): 313S-321S. PubMed

    Yetley EA, Pfeiffer CM, Phinney KW, Fazili Z, Lacher DA, Bailey RL, Blackmore S, Bock JL, Brody LC, Carmel R, Curtin R, Durazo-Arvizu RA, Eckfeldt JH, Green R, Gregory JF, Hoofnagle AN, Jacobsen DW, Jacques PF, Molloy AM, Massaro J, Mills JL, Nexo E, Rader JI, Selhub J, Sempos C, Shane B, Stabler S, Stover P, Tamura T, Tedstone A, Thorpe SJ, Coates PM, Johnson CL, Picciano MFrances. Biomarkers of folate status in NHANES: a roundtable summary. Am J Clin Nutr. 2011; 94(1): 303S-312S. PubMed

    General References

    Chawla J, Kvarnberg D. Hydrosoluble vitamins. Handb Clin Neurol. 2014; 120: 891-914. PubMed

    Davies DJ, Baxter JM, Baxter JN. Nutritional deficiencies after bariatric surgery. Obes Surg. 2007; 17(9): 1150-8. PubMed

    Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014; 349: g5226. PubMed

    LeBlanc ES, Zakher B, Daeges M, Pappas M, Chou R. Screening for vitamin D deficiency: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015; 162(2): 109-22. PubMed

    Marian M, Sacks G. Micronutrients and older adults Nutr Clin Pract. 2009; 24(2): 179-95. PubMed

    Merrigan SD, Owen WE, Straseski JA. Performance characteristics of the ARCHITECT Active-B12 (Holotranscobalamin) assay Clin Lab. 2015; 61(3-4): 283-8. PubMed

    Mooney S, Leuendorf J, Hendrickson C, Hellmann H. Vitamin B6: a long known compound of surprising complexity. Molecules. 2009; 14(1): 329-51. PubMed

    Oberley MJ, Yang DT. Laboratory testing for cobalamin deficiency in megaloblastic anemia. Am J Hematol. 2013; 88(6): 522-6. PubMed

    Orr K, Hume AL. An evidence-based update on vitamins. Med Health R I. 2010; 93(4): 122-4. PubMed

    Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011; 364(3): 248-54. PubMed

    Taylor CL, Thomas PR, Aloia JF, Millard PS, Rosen CJ. Questions About Vitamin D for Primary Care Practice: Input From an NIH Conference. Am J Med. 2015; 128(11): 1167-70. PubMed

    Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011; 86(1): 50-60. PubMed

    Wyness SP, Straseski JA. Performance characteristics of six automated 25-hydroxyvitamin D assays: Mind your 3s and 2s Clin Biochem. 2015; 48(16-17): 1089-96. PubMed

    References from the ARUP Institute for Clinical and Experimental Pathology®

    Barker T, Henriksen VT, Martins TB, Hill HR, Kjeldsberg CR, Schneider ED, Dixon BM, Weaver LK. Higher serum 25-hydroxyvitamin D concentrations associate with a faster recovery of skeletal muscle strength after muscular injury. Nutrients. 2013; 5(4): 1253-75. PubMed

    Barker T, Leonard SW, Trawick RH, Martins TB, Kjeldsberg CR, Hill HR, Traber MG. Modulation of inflammation by vitamin E and C supplementation prior to anterior cruciate ligament surgery. Free Radic Biol Med. 2009; 46(5): 599-606. PubMed

    Barker T, Martins TB, Hill HR, Kjeldsberg CR, Dixon BM, Schneider ED, Henriksen VT, Weaver LK. Circulating pro-inflammatory cytokines are elevated and peak power output correlates with 25-hydroxyvitamin D in vitamin D insufficient adults. Eur J Appl Physiol. 2013; 113(6): 1523-34. PubMed

    Barker T, Martins TB, Hill HR, Kjeldsberg CR, Dixon BM, Schneider ED, Henriksen VT, Weaver LK. Vitamin D sufficiency associates with an increase in anti-inflammatory cytokines after intense exercise in humans. Cytokine. 2014; 65(2): 134-7. PubMed

    Barker T, Martins TB, Hill HR, Kjeldsberg CR, Henriksen VT, Dixon BM, Schneider ED, Dern A, Weaver LK. Different doses of supplemental vitamin D maintain interleukin-5 without altering skeletal muscle strength: a randomized, double-blind, placebo-controlled study in vitamin D sufficient adults. Nutr Metab (Lond). 2012; 9(1): 16. PubMed

    Barker T, Martins TB, Kjeldsberg CR, Trawick RH, Hill HR. Circulating interferon-γ correlates with 1,25(OH)D and the 1,25(OH)D-to-25(OH)D ratio. Cytokine. 2012; 60(1): 23-6. PubMed

    Coelho D, Kim JC, Miousse IR, Fung S, Moulin Mdu, Buers I, Suormala T, Burda P, Frapolli M, Stucki M, Nürnberg P, Thiele H, Robenek H, Höhne W, Longo N, Pasquali M, Mengel E, Watkins D, Shoubridge EA, Majewski J, Rosenblatt DS, Fowler B, Rutsch F, Baumgartner MR. Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat Genet. 2012; 44(10): 1152-5. PubMed

    Genzen JR, Gosselin JT, Wilson TC, Racila E, Krasowski MD. Analysis of vitamin D status at two academic medical centers and a national reference laboratory: result patterns vary by age, gender, season, and patient location. BMC Endocr Disord. 2013; 13: 52. PubMed

    Illson ML, Dempsey-Nunez L, Kent J, Huang Q, Brebner A, Raff ML, Watkins D, Gilfix BM, Wittwer CT, Rosenblatt DS. High resolution melting analysis of the MMAB gene in cblB patients and in those with undiagnosed methylmalonic aciduria. Mol Genet Metab. 2013; 110(1-2): 86-9. PubMed

    Johnson-Davis KL, Moore SJ, Owen WE, Cutler JM, Frank EL. A rapid HPLC method used to establish pediatric reference intervals for vitamins A and E. Clin Chim Acta. 2009; 405(1-2): 35-8. PubMed

    Jovanovich A, Chonchol M, Cheung AK, Kaufman JS, Greene T, Roberts WL, Smits G, Kendrick J, HOST Investigators. Racial differences in markers of mineral metabolism in advanced chronic kidney disease. Clin J Am Soc Nephrol. 2012; 7(4): 640-7. PubMed

    Kushnir MM, Shushan B, Roberts WL, Pasquali M. Serum acylcarnitines and vitamin B12 deficiency. Clin Chem. 2002; 48(7): 1126-8. PubMed

    Laha TJ, Strathmann FG, Wang Z, de Boer IH, Thummel KE, Hoofnagle AN. Characterizing antibody cross-reactivity for immunoaffinity purification of analytes prior to multiplexed liquid chromatography-tandem mass spectrometry. Clin Chem. 2012; 58(12): 1711-6. PubMed

    Lu J, Frank EL. Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem. 2008; 54(5): 901-6. PubMed

    Strathmann FG, Sadilkova K, Laha TJ, LeSourd SE, Bornhorst JA, Hoofnagle AN, Jack R. 3-epi-25 hydroxyvitamin D concentrations are not correlated with age in a cohort of infants and adults. Clin Chim Acta. 2012; 413(1-2): 203-6. PubMed

    Medical Reviewers

    Last Update: August 2016