Vitamin B12 Deficiency

Vitamin B12 deficiency usually occurs when the intake of vitamin B12 is insufficient—which is found only in animal source foods or in fortified foods or supplements. Vitamin B12 deficiency can also be caused by poor absorption or excessive loss of the vitamin. A severe deficiency of vitamin B12, which is required for the synthesis of red blood cells, results in megaloblastic anemia, characterized by oversized and malformed red blood cells (Balarajan et al. 2011). Vitamin B12 deficiency can also induce clinical and sub-clinical neurological and other disorders (Shipton and Thachil 2015). At-risk groups for vitamin B12 deficiency include pregnant and lactating women, infants, young children, and the elderly (Benoist 2008). Vitamin B12 deficiency is especially prevalent in populations that consume low quantities of animal-source foods, including not only strict vegetarians but also those with low access to or intake of animal source foods for economic or cultural reasons. The global burden of vitamin B12 deficiency is unknown, but available data suggest that it could be widespread in both developed and developing countries and across all ages and physiological groups (Allen et al. 2017).

How is vitamin B12 deficiency measured?

Vitamin B12 concentrations in serum/plasma provide the most useful and least expensive measure to determine the status of populations. Serum/plasma vitamin B12 levels can be determined using a venous blood sample, which requires a cold chain. Electrochemiluminescence immunoassay is the most widely recommended method for measuring vitamin B12 in serum/plasma.

Biomarkers of adequacy for metabolic function are also available, including plasma homocysteine and serum methylmalonic acid. Holotranscobalamin, a serum protein that transports vitamin B12, is also reduced in B12 deficiency. Recently, equations to combine two, three, or four vitamin B12 biomarkers into one diagnostic parameter called “combined indicator of vitamin B-12 status (cB-12)” have been reported. This indicator provides the best prediction for associated anemia, and poorer cognitive function in the elderly (Fedosov et al. 2015).

Typically, biochemical assessment of functional metabolic markers of vitamin B12 status require more significant resources and are rarely conducted in low- and middle-income countries, except to meet specific research objectives.

How is vitamin B12 deficiency categorized?

A definition for what constitutes a public health problem for vitamin B12 deficiency has not been established. Cut-offs for defining vitamin B12 deficiency are described in Table 8 and apply to all segments of the population, although they may not be as valid for pregnant women or infants because of physiological effects on the biomarkers (e.g., levels usually decline during pregnancy).

Table 8: Vitamin B12 Deficiency Cut-offs in Serum/Plasma B12 (picomole per liter)

Vitamin B12 StatusCut-Off Value Indicating Vitamin B12 Deficiency
Low serum/plasma B12<148 pmol/L
Marginal B12148—221 pmol/L
Adequate B12>221 pmol/L

Source: Allen et al. 2017

Where can we get these data?

Vitamin B12 deficiency is measured in population-based surveys and research studies, among women of reproductive age, children, and the elderly. Of the commonly administered population-based surveys, the National Micronutrient Survey is usually the only one that collects and analyzes information on the prevalence of B12 deficiency.

Methodological issues

  • Cut-offs for pregnant women are not established because of the physiological fluctuations in vitamin B12 biomarkers in the perinatal period.
  • High folate status can detrimentally influence vitamin B12 status, especially in the lowest distribution of vitamin B12 status (Selhub et al. 2009; Brito et al. 2016).