No association between subnormal serum vitamin B12 and anemia in older nursing home patients

  • Jenny Foss AbrahamsenEmail author
  • Anne-Lise Bjorke Monsen
  • Anette Hylen Ranhoff
  • Roy M. Nilsen
  • Einar Engtrø
  • Magne Rekdal
  • Kjell Kruger
Research Paper

Key summary points


To investigate the association between different clinical parameters, particularly subnormal serum vitamin B12 and anemia, in older nursing home patients.


No association was observed between subnormal B12 and anemia, while strong associations were observed between renal failure, inflammation/infection, iron deficiency and anemia.


Vitamin B12 probably plays a limited role in the etiology and treatment of mild/moderate anemia in older patients, living in a Western society, and not suffering from pernicious anemia.



Since evidence of an association between vitamin B12 (B12) deficiency and anemia in older people is limited and inconclusive, we wanted to investigate this association in old, frail nursing home patients.


The study includes patients admitted to short-term, post-acute care (n = 765) and residents in long-term care (LTC) (n = 1665), in the municipality of Bergen. Anemia was defined according to the WHO criteria: Hb < 13 g/dL in men and < 12 g/dL in women, and as Hb < 11 g/dL, in both sex (moderate/severe anemia). The presence of anemia was analyzed in patients with subnormal (< 250 pmol/L), normal (250–650 pmol/L) and high (> 650 pmol/L) B12, and the association between anemia and clinical parameters, and including B12, was analyzed using logistic regression models. The use of B12 supplementation was investigated in the LTC patients.


Mean age of the 2430 patients was 86 ± 7 years. WHO-defined anemia was seen in 1023 (42%), and moderate/severe anemia in 384 (16%) of the patients. In multiple logistic regression analyses, we found no statistically significant associations of subnormal B12 with WHO-defined anemia or moderate/severe anemia. Renal insufficiency, iron deficiency and CRP > 10 mg/L were significantly associated with both types of anemia, (p < 0.001). Among the LTC residents, 405 (24%) received B12 supplements, 112 (7%) of them had elevated B12 > 650 pmol/L.


In older nursing home patients, no association was observed between subnormal B12 and anemia. Older patients in Western societies with mild/moderate anemia should not be treated with B12 supplements without further investigation.


Older Nursing home Anemia Vitamin B12 Supplementation 


Author contributions

JFA is the initiator, project leader and the first author of the manuscript. ALBM is responsible for the biochemical analyses and has contributed in the analyses of data. RMN has been supervising the statistical work. AHR has taken part in the initiation of the study and supervising the ongoing research. MR, EE and KK have been responsible for developing, managing and retrieving adequate data from the electronic database of the LTC patients. All authors have contributed to the manuscript preparation and critical review of the manuscript. All authors read and approved the final manuscript and agree to be accountable for all aspect of the work.


Part of this study, concerning the PAC patients, was funded by Western Norway Regional Health Authority (Grant number 911926). The funding source had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The study protocol of the PAC patients that were enrolled in a prospective study was approved by the Regional Committees for Medical and Health Research Ethics (REC), (2011/1893/REK Vest). For the LTC patients, retrieval of anonymous data (blood samples, age and information on B12 supplements) from electronic patient records for quality surveillance purposes, was approved and performed as regularly by Department of Nursing Home Medicine in the Municipality of Bergen.

Informed consent

Written informed consent was obtained from the PAC patients, and in case of moderate/major cognitive impairment leading to a decline in judgement, from their closest proxy. For the LTC patients, no written informed consent was asked for since the limited dataset was truly anonymous, could not stigmatize any group, and blood sampling were performed routinely as part of half-yearly drug surveillance demanded by national authorities. This is in accordance with national legislation on anonymous data handling ( All patients, (or in the majority of cases their nearest proxy) had accepted that blood tests were taken to get information that would aid a critical medication review.


  1. 1.
    Rohrig G, Gutgemann I, Kolb G, Leischker A (2018) Anemia in the aged is not aging related: position paper on anemia in the aged by the “working group anemia” of the German Geriatric Society (DGG). Eur Geriatr Med. CrossRefGoogle Scholar
  2. 2.
    Gaskell H, Derry S, Andrew Moore R, McQuay HJ (2008) Prevalence of anaemia in older persons: systematic review. BMC Geriatr 8:1CrossRefGoogle Scholar
  3. 3.
    Landi F, Russo A, Danese P, Liperoti R, Barillaro C, Bernabei R, Onder G (2007) Anemia status, hemoglobin concentration, and mortality in nursing home older residents. J Am Med Dir Assoc 8(5):322–327CrossRefGoogle Scholar
  4. 4.
    den Elzen WP, Gussekloo J (2011) Anaemia in older persons. Neth J Med 69(6):260–267Google Scholar
  5. 5.
    Bach V, Schruckmayer G, Sam I, Kemmler G, Stauder R (2014) Prevalence and possible causes of anemia in the elderly: a cross-sectional analysis of a large European university hospital cohort. Clin Interv Aging 9:1187–1196PubMedPubMedCentralGoogle Scholar
  6. 6.
    Abrahamsen JF, Monsen AL, Landi F, Haugland C, Nilsen RM, Ranhoff AH (2016) Readmission and mortality 1 year after acute hospitalization in older patients with explained and unexplained anemia—a prospective observational cohort study. BMC Geriatr 16:109CrossRefGoogle Scholar
  7. 7.
    Merchant AA, Roy CN (2012) Not so benign haematology: anaemia of the elderly. Br J Haematol 156(2):173–185CrossRefGoogle Scholar
  8. 8.
    Ferrucci L, Guralnik JM, Bandinelli S, Semba RD, Lauretani F, Corsi A, Ruggiero C, Ershler WB, Longo DL (2012) Unexplained anaemia in older persons is characterised by low erythropoietin and low levels of pro-inflammatory markers. Br J Haematol 136(6):849–855CrossRefGoogle Scholar
  9. 9.
    Makipour S, Kanapuru B, Ershler WB (2008) Unexplained anemia in the elderly. Semin Hematol 45(4):250–254CrossRefGoogle Scholar
  10. 10.
    Artz AS, Thirman MJ (2011) Unexplained anemia predominates despite an intensive evaluation in a racially diverse cohort of older adults from a referral anemia clinic. J Gerontol A Biol Sci Med Sci 66(8):925–932CrossRefGoogle Scholar
  11. 11.
    Goodnough LT, Schrier SL (2014) Evaluation and management of anemia in the elderly. Am J Hematol 89(1):88–96CrossRefGoogle Scholar
  12. 12.
    Green R (2017) Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood 129(19):2603–2611CrossRefGoogle Scholar
  13. 13.
    Andres E, Serraj K (2012) Optimal management of pernicious anemia. J Blood Med 3:97–103CrossRefGoogle Scholar
  14. 14.
    den Elzen WP, van der Weele GM, Gussekloo J, Westendorp RG, Assendelft WJ (2010) Subnormal vitamin B12 concentrations and anaemia in older people: a systematic review. BMC Geriatr 10:42CrossRefGoogle Scholar
  15. 15.
    Smelt AF, Gussekloo J, Bermingham LW, Allen E, Dangour AD, Eussen SJ, Favrat B, De Groot LC, Kok FJ, Kwok T et al (2018) The effect of vitamin B12 and folic acid supplementation on routine haematological parameters in older people: an individual participant data meta-analysis. Eur J Clin Nutr 72(6):785–795CrossRefGoogle Scholar
  16. 16.
    Abrahamsen JF, Haugland C, Nilsen RM, Ranhoff AH (2016) Three different outcomes in older community-dwelling patients receiving intermediate care in nursing home after acute hospitalization. J Nutr Health Aging 20(4):446–452CrossRefGoogle Scholar
  17. 17.
    Helvik AS, Selbaek G, Saltyte Benth J, Roen I, Bergh S (2018) The course of neuropsychiatric symptoms in nursing home residents from admission to 30-month follow-up. PLoS One 13(10):e0206147CrossRefGoogle Scholar
  18. 18.
    Helvik AS, Engedal K, Benth JS, Selbaek G (2014) A 52 month follow-up of functional decline in nursing home residents—degree of dementia contributes. BMC Geriatr 14:45CrossRefGoogle Scholar
  19. 19.
    Culleton BF, Manns BJ, Zhang J, Tonelli M, Klarenbach S, Hemmelgarn BR (2006) Impact of anemia on hospitalization and mortality in older adults. Blood 107(10):3841–3846CrossRefGoogle Scholar
  20. 20.
    Meziere A, Audureau E, Vairelles S, Krypciak S, Dicko M, Monie M, Giraudier S (2014) B12 deficiency increases with age in hospitalized patients: a study on 14,904 samples. J Gerontol A Biol Sci Med Sci 69(12):1576–1585CrossRefGoogle Scholar
  21. 21.
    Wolters M, Strohle A, Hahn A (2004) Cobalamin: a critical vitamin in the elderly. Prev Med 39(6):1256–1266CrossRefGoogle Scholar
  22. 22.
    Risch M, Meier DW, Sakem B, Medina Escobar P, Risch C, Nydegger U, Risch L (2015) Vitamin B12 and folate levels in healthy Swiss senior citizens: a prospective study evaluating reference intervals and decision limits. BMC Geriatr 15:82CrossRefGoogle Scholar
  23. 23.
    Metz J (2008) A high prevalence of biochemical evidence of vitamin B12 or folate deficiency does not translate into a comparable prevalence of anemia. Food Nutr Bull 29(2 Suppl):S74–S85CrossRefGoogle Scholar
  24. 24.
    den Elzen WP, Westendorp RG, Frolich M, de Ruijter W, Assendelft WJ, Gussekloo J (2008) Vitamin B12 and folate and the risk of anemia in old age: the Leiden 85-plus study. Arch Intern Med 168(20):2238–2244CrossRefGoogle Scholar
  25. 25.
    Berliner N (2013) Anemia in the elderly. Trans Am Clin Climatol Assoc 124:230–237PubMedPubMedCentralGoogle Scholar
  26. 26.
    Lippi G, Franchini M, Salvagno GL, Montagnana M, Targher G, Guidi GC (2010) Determinants of anaemia in the very elderly: a major contribution from impaired renal function? Blood Transfus 8(1):44–48PubMedPubMedCentralGoogle Scholar
  27. 27.
    Robinson B, Artz AS, Culleton B, Critchlow C, Sciarra A, Audhya P (2007) Prevalence of anemia in the nursing home: contribution of chronic kidney disease. J Am Geriatr Soc 55(10):1566–1570CrossRefGoogle Scholar
  28. 28.
    Zulfiqar AA, Sebaux A, Drame M, Pennaforte JL, Novella JL, Andres E (2015) Hypervitaminemia B12 in elderly patients: frequency and nature of the associated or linked conditions. Preliminary results of a study in 190 patients. Eur J Intern Med 26(10):e63–e64CrossRefGoogle Scholar
  29. 29.
    Arendt JF, Nexo E (2013) Unexpected high plasma cobalamin: proposal for a diagnostic strategy. Clin Chem Lab Med 51(3):489–496CrossRefGoogle Scholar
  30. 30.
    Brah S, Chiche L, Mancini J, Meunier B, Arlet JB (2014) Characteristics of patients admitted to internal medicine departments with high serum cobalamin levels: results from a prospective cohort study. Eur J Intern Med 25(5):e57–e58CrossRefGoogle Scholar
  31. 31.
    Stabler SP, Allen RH (2004) Vitamin B12 deficiency as a worldwide problem. Annu Rev Nutr 24:299–326CrossRefGoogle Scholar
  32. 32.
    Azimi S, Faramarzi E, Sarbakhsh P, Ostadrahimi A, Somi MH, Ghayour M (2019) Folate and vitamin B12 status and their relation to hematological indices in healthy adults of Iranians: Azar cohort study. Nutr Health 25(1):29–36CrossRefGoogle Scholar
  33. 33.
    Salles-Montaudon N, Parrot F, Balas D, Bouzigon E, Rainfray M, Emeriau JP (2003) Prevalence and mechanisms of hyperhomocysteinemia in elderly hospitalized patients. J Nutr Health Aging 7(2):111–116PubMedGoogle Scholar
  34. 34.
    Loikas S, Koskinen P, Irjala K, Lopponen M, Isoaho R, Kivela SL, Pelliniemi TT (2007) Renal impairment compromises the use of total homocysteine and methylmalonic acid but not total vitamin B12 and holotranscobalamin in screening for vitamin B12 deficiency in the aged. Clin Chem Lab Med 45(2):197–201CrossRefGoogle Scholar
  35. 35.
    Lewerin C, Ljungman S, Nilsson-Ehle H (2007) Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly. J Intern Med 261(1):65–73CrossRefGoogle Scholar
  36. 36.
    Miller JW (2018) Proton pump inhibitors, H2-receptor antagonists, metformin, and vitamin B-12 deficiency: clinical implications. Adv Nutr 9(4):511S–518SCrossRefGoogle Scholar
  37. 37.
    Rohrig G (2016) Anemia in the frail, elderly patient. Clin Interv Aging 11:319–326CrossRefGoogle Scholar

Copyright information

© European Geriatric Medicine Society 2019

Authors and Affiliations

  1. 1.Department of Nursing Home MedicineMunicipality of BergenBergenNorway
  2. 2.Kavli Research CentreHaraldsplass Deaconess HospitalBergenNorway
  3. 3.Laboratory of Clinical BiochemistryHaukeland University HospitalBergenNorway
  4. 4.Department of Clinical ScienceUniversity of BergenBergenNorway
  5. 5.Western Norway University of Applied SciencesBergenNorway
  6. 6.DIPS ASBergenNorway
  7. 7.Department of Public Health and Primary Health CareUniversity of BergenBergenNorway

Personalised recommendations