Age- and ethnicity-related reference intervals for serum vitamin B12

Clin Biochem. 2023 Jan;111:66-71. doi: 10.1016/j.clinbiochem.2022.10.007. Epub 2022 Oct 17.


Background: Age and ethnicity are known to influence serum vitamin B12 (B12) concentration, yet universal reference intervals (RIs) are typically applied by laboratories. Both lower and upper RI limits for B12 are clinically relevant. Low values suggest deficiency leading to anemia and/or neurological impairment, while high values are not always an innocuous consequence of high B12 intake but are associated with some cancers, autoimmune, liver, and renal diseases. This work aimed to establish age- and ethnicity-related RIs for B12 using a modified indirect method based on Hoffmann's approach.

Methods: A total of 72,091 anonymized B12 results (Jan 2018-Nov 2019) were analyzed from an ethnically-diverse South-East London general practice patient population. Patients belonged to five ethnic groups: Asian, Black, White, Mixed, or Other. Multiple records for the same patient and results with missing ethnicity were excluded from the analysis of adult RIs. B12 analyses were performed using ARCHITECT® (Abbott Diagnostics).

Results: B12 was significantly higher in Black compared with Asian and White adults. There were no differences in B12 between Asian and White adults. Children (all ethnicities) between 2 and 5 years old had the highest B12. Because of the small number of children (up to the age of 13) in each ethnic-related age category, all ethnic groups were combined to obtain age-related RIs. The children's RIs ranged from 159 to 1025 pmol/L for 0-1-year-olds to 276-1102 pmol/L for 2-5-year-olds. The RIs for Black and White/Asian people >13 years of age were 166-805 pmol/L and 134-511 pmol/L respectively.

Conclusions: The application of age- and ethnicity-appropriate RIs into diagnostic practice will provide a more accurate evaluation of B12 status when using the B12 test alone or in combination with other markers.

Keywords: Age; Ethnicity; Haptocorrin; Holotranscobalamin; Reference intervals; Vitamin B(12).

MeSH terms

  • Adult
  • Biomarkers
  • Child
  • Child, Preschool
  • Ethnicity
  • Humans
  • Reference Values
  • Vitamin B 12 Deficiency*
  • Vitamin B 12*
  • Vitamins


  • Vitamin B 12
  • Biomarkers
  • Vitamins