Vitamin B12 deficiency: epidemiological trends and risk factors

Vitamin B12 deficiency is one of the most common micronutrient deficiencies worldwide, and a new narrative review published in Frontiers in Nutrition on 16 October 2026 synthesizes five decades of epidemiological evidence to argue that India carries one of the highest documented burdens of cobalamin deficiency anywhere in the world. The review, authored by Gurudayal S. Toteja of Jamia Hamdard University and Nishant Toteja of the Hamdard Institute of Medical Sciences and Research in New Delhi, consolidates evidence from studies published between January 1966 and July 2026, drawing on PubMed/MEDLINE, Scopus, and Google Scholar, and prioritizing systematic reviews, meta-analyses, and nationally representative surveys such as the Comprehensive National Nutrition Survey (CNNS) of 2016–2018. Its central finding is stark: pooled meta-analytic estimates indicate that approximately 50 percent of the Indian population is deficient in vitamin B12, compared with clinical deficiency rates of roughly 3 to 6 percent among adults and adolescents in North America and Europe.

The biochemistry of cobalamin explains why deficiency matters so much. Vitamin B12 is a water-soluble vitamin synthesized only by microorganisms, and it is found almost exclusively in animal-derived foods such as red meat, fish, eggs, and milk, with a very small contribution from foods or water exposed to B12-producing bacteria. Within the body, cobalamin serves as a critical cofactor in two reactions: the conversion of homocysteine to methionine via methionine synthase, and the conversion of methylmalonyl-CoA to succinyl-CoA via methylmalonyl-CoA mutase. These reactions make the vitamin essential for DNA synthesis, red cell production, and the maintenance of nerve myelin. Deficiency can therefore manifest as megaloblastic anemia and glossitis, peripheral neuropathy, subacute combined degeneration of the spinal cord, and cognitive impairment. In pregnancy, low maternal B12 has been associated with neural tube defects and other adverse birth outcomes, as well as longer-term metabolic risk in the offspring.

The life-course pattern reported in India is striking. According to the CNNS, the first nationally representative estimate of pediatric B12 status, deficiency affects 13.8 percent of pre-school children aged 1 to 4 years and 17.3 percent of school-age children aged 5 to 9 years, with little difference between boys and girls at these ages. The rate roughly doubles in adolescence: 31.0 percent of adolescents aged 10 to 19 years were deficient in the CNNS, and a pooled meta-analytic estimate for the 0 to 17-year age band was higher still, at 57 percent, though based on fewer studies and a wider confidence interval. Among adults, the pooled prevalence across the largest meta-analysis was 48 percent, with a 95 percent confidence interval of 35 to 62 percent, and one Indian study reported deficiency as high as 78.5 percent in healthy adults depending on the serum cut-off used. Among the elderly, a review of Indian adults reported 61.7 percent deficiency using varied cut-offs, and hospital series show diagnosed cases increasing with age and peaking around 50 to 65 years.

Pregnant women represent a particularly vulnerable group. A synthesis of 46 studies on B12 status among pregnant and lactating women in India found deficiency prevalence ranging from 40 to 70 percent, and a meta-analysis estimated that approximately 67 percent of pregnant women are affected. International meta-analyses have similarly found insufficient B12 during pregnancy to be common globally and associated with lower birth weight. In Indian cohorts, low maternal B12 alongside adequate-to-high folate has been associated with neural tube defects, recurrent pregnancy loss, gestational diabetes, pre-eclampsia, intrauterine growth restriction, and adverse metabolic and cognitive outcomes in the child, although the review emphasizes that these data derive from observational cohorts and should be interpreted as associations rather than demonstrated causal pathways. The risk persists into lactation, since low maternal stores lower breast-milk B12 and place exclusively breastfed infants at risk, yet current Indian antenatal policy supplements only iron and folate, not vitamin B12.

Diet is the single most important determinant of B12 status in India. Individuals consuming a lacto-vegetarian diet, a substantial share of the Indian population, have significantly lower cobalamin levels than those consuming a mixed diet, and reviews consistently show several-fold higher deficiency among lacto-vegetarians than non-vegetarians. In one study of healthy young vegetarian adults, approximately 50 percent had serum B12 below the deficiency threshold, 70 percent of men and 50 percent of women had low holotranscobalamin, and 92 percent of men and 50 percent of women had hyperhomocysteinaemia. Dietary insufficiency, not pernicious anemia, is the dominant cause of B12 deficiency in India, reflecting the combined effects of a largely cereal-based lacto-vegetarian diet, low consumption of animal-based foods, and high rates of poverty. Beyond diet, the most consistently reported associated factors are low socioeconomic status, advancing age, and female sex, with age-related malabsorption from atrophic gastritis, reduced gastric acid secretion, and Helicobacter pylori infection adding to the burden among older adults.

Regional heterogeneity within India is substantial. In the CNNS, B12 deficiency prevalence was highest in the central region of India across every pediatric age band assessed: 21.0 percent in pre-schoolers, 29.1 percent in school-age children, and 42.7 percent in adolescents, each substantially above the corresponding national estimates. Despite this marked regional gradient, the same survey found no consistent difference in B12 deficiency between rural and urban locations at the national level, a pattern that sits alongside inconsistent rural/urban findings from individual state-level studies. Studies from Pune comparing middle-aged men in rural, slum, and middle-class urban settings found a high frequency of low B12 across all three settings, with rural and slum residents faring worse than urban middle-class residents, suggesting that dietary intake and socioeconomic status appear to be stronger determinants of B12 status than geographic setting per se.

Outside India, B12 deficiency follows clear geographic and economic lines. High-income populations with adequate access to animal-source foods have lower deficiency prevalence, while low- and middle-income populations are more affected owing to both scarcity of animal-source foods and a higher burden of malabsorptive conditions. A widely cited compilation of national and regional datasets found serum B12 deficiency in 11 to 15 percent of women in Germany and the United Kingdom, 31 percent of elderly individuals in the UK, 49 percent of adults in India, 40 percent of children in Kenya, 28 percent of pregnant women in Nepal, and 20 percent of the same demographic group in New Zealand. In Latin America and the Caribbean, an analysis of 41 studies suggested up to 61 percent of individuals in Mexico and Central/South America had inadequate B12 stores. In sub-Saharan Africa, available national micronutrient surveys indicate 54 percent, 35 percent, and 15 percent B12 deficiency among reproductive-age women in Malawi, Kenya, and Ethiopia respectively, with a lower prevalence of 7 percent in Ghana. The Indian subcontinent and neighboring South Asian countries report the highest deficiency prevalence worldwide, 70 to 80 percent in some series, primarily reflecting a predominantly vegetarian, carbohydrate-based diet.

A key constraint on reconstructing a 50-year trend is that no single longitudinal, nationally representative cobalamin survey exists in India, or indeed anywhere else, spanning this period. Most available estimates are cross-sectional snapshots using different biomarkers, cut-offs, and populations. Evidence from the 1970s and 1980s was largely clinical and descriptive, with early recognition that asymptomatic Indian lacto-vegetarians had lower B12 than non-vegetarian counterparts and observations of anemia among Asian immigrants in London raising the possibility of a population-level problem. Systematic biochemical assessment began at the turn of the millennium with the Pune studies, which documented a high prevalence of low cobalamin with concomitantly elevated homocysteine across sampled Indian populations. Since 2000, the evidence base has grown substantially, with clinic and community studies through the 2010s consistently showing an adult prevalence of approximately 47 percent, the CNNS providing the first national pediatric and adolescent estimates, and two independent meta-analyses synthesizing studies to 2020 and 2023 reporting pooled adult prevalence of 51 to 53 percent. A large 2024 health-check dataset of over 15,000 asymptomatic adults across seven northern Indian states reported a considerably lower figure of 24.2 percent, which most plausibly reflects a higher serum cut-off and a more affluent, urban, self-selected sample rather than a genuine decline in burden.

A limitation running through every prevalence estimate cited in the review is the absence of biomarker and cut-off harmonization. Total serum/plasma B12 thresholds used across the cited studies range from below 150 pmol/L to below 211 pg/mL, and most studies rely on total B12 rather than on functional markers such as holotranscobalamin or methylmalonic acid, which more directly reflect tissue cobalamin status. Total serum B12 is itself an indirect marker that can be influenced by recent dietary intake, by pregnancy-related haemodilution, and by inter-laboratory assay variability. A concrete illustration of the resulting inconsistency comes from a single cohort of healthy young Indian vegetarians, in which roughly 50 percent were deficient by total serum B12, but 70 percent of men and 50 percent of women had low holotranscobalamin, and 92 percent of men and 50 percent of women had hyperhomocysteinaemia, meaning a 20-percentage-point-or-greater spread in deficiency depending solely on which biomarker was used. Consequently, differences between surveys, such as the 24.2 percent from the 2024 health-check sample versus 51 to 53 percent from pooled meta-analyses, are driven substantially by differences in cut-points, biomarkers, and sampling frames in addition to any true temporal change.

The review concludes that vitamin B12 deficiency is a largely preventable, straightforward-to-treat disorder whose continued neglect in India’s public health programming is difficult to attribute to anything other than insufficient prioritization relative to its documented scale. From a public health perspective, the authors call for harmonized diagnostic criteria for B12 deficiency, ideally combining total circulating B12 with a functional marker such as holotranscobalamin or methylmalonic acid, and routine screening particularly for pregnant and lactating women, adolescents, the elderly, and strict vegans and vegetarians. Evidence-based strategies to reduce the burden include dietary diversification, food fortification, and the addition of B12 to existing antenatal and adolescent supplementation programmes, which currently contain only iron and folic acid. On fortification specifically, the evidence is directionally supportive but implementation-dependent: India’s current 2018 FSSAI fortification standards for folic acid and vitamin B12 are set at roughly 90 percent below WHO-recommended levels for Indian consumption patterns, having been lowered from stronger 2016 standards, and a recent review identifies concrete barriers to more effective scale-up, including uneven regulatory enforcement, continued reliance on voluntary fortification of open-market atta, variable miller-level capacity and quality assurance, and insufficient long-term monitoring of nutritional outcomes among beneficiaries. Large-scale staple fortification has also drawn published concerns from Indian public-health researchers regarding the strength of the underlying evidence base and potential safety considerations at higher fortification levels, so any revision of national standards should be accompanied by the monitoring and evaluation infrastructure needed to track both benefit and safety at population scale. Regional data gaps, particularly the absence of CNNS-scale state-level surveillance in adults, should also be prioritized in future national nutrition surveys.

Subject of Research: Vitamin B12 deficiency epidemiology in India and worldwide

Article Title: Vitamin B12 deficiency: epidemiological trends and risk factors

Article References: Toteja, G. S., & Toteja, N. (2026). Vitamin B12 deficiency: epidemiological trends and risk factors. Frontiers in Nutrition, 13, Article 1930037. https://doi.org/10.3389/fnut.2026.1930037

Image Credits: AI Generated

DOI: 10.3389/fnut.2026.1930037

Keywords: vitamin B12, cobalamin, micronutrient deficiency, India, epidemiology, vegetarian diet, pregnancy, food fortification, Vitamin, deficiency, epidemiological, trends