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ORIGINAL RESEARCH article

Front. Nutr., 05 January 2026

Sec. Nutritional Epidemiology

Volume 12 - 2025 | https://doi.org/10.3389/fnut.2025.1701661

Vitamin B12 deficiency and its impact on healthcare: a population-level analysis and call for action

Leonardo P. de Carvalho,Leonardo P. de Carvalho1,2Nelson Akamine,Nelson Akamine1,2Marcelo S. Di Pietro,Marcelo S. Di Pietro1,2Carolina Nunes FranaCarolina Nunes França3Rodrigo OliveiraRodrigo Oliveira2Renato D. Lopes,,
Renato D. Lopes1,2,4*
  • 1Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
  • 2BCRI, Brazilian Clinical Research Institute, São Paulo, Brazil
  • 3Health Sciences Post Graduation Program, Santo Amaro University, São Paulo, Brazil
  • 4Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, United States

Introduction: Vitamin B12 deficiency is a growing health concern, affecting millions worldwide. This study aims to evaluate the pattern of vitamin B12 deficiency in a large healthcare system and assess its impact on hospitalizations and associated diseases.

Methods: Vitamin B12 test results were retrospectively collected from administrative datasets of Brazil’s public and private healthcare systems between 2016 and 2023. Data from health campaigns measuring vitamin B12 levels across the country were used to calculate the percentage of abnormal test results. The Mann-Kendall test was applied to assess trends in hospitalizations over time, while the Pearson correlation test was used to evaluate the association between vitamin B12 deficiency and other hospitalization causes.

Results: A total of 84 million vitamin B12 measurements were analyzed, revealing a 12-fold increase in tests performed, rising from two million to 25 million over the study period. Of these, 35 million measurements were from the public and 47·8 million from private healthcare system. The trend of hospitalizations associated with vitamin B12 deficiency increased by 32% over the study period (p < 0·05). Hospitalizations associated with vitamin B12 deficiency were correlated with other B vitamin deficiencies (B1 and B6), as well as hospitalizations due to cardiovascular, hematological, neurological, psychological, and gastrointestinal diseases.

Discussion: This population-based study highlights a progressive increase in vitamin B12 deficiency-related hospitalizations, suggesting a previously underrecognized public health burden. Additionally, these findings underscore the correlation between vitamin B12 deficiency, other B vitamin deficiencies, and relevant clinical diseases.

1 Introduction

Vitamin B12 deficiency has emerged as a global health concern with region-specific determinants and outcomes (1). In Brazil, this issue deserves particular attention due to marked socioeconomic disparities, evolving dietary habits, and the coexistence of both undernutrition and chronic disease burdens. Some of these reasons include changing dietary patterns due to the increased adoption of plant-based diets (2), an aging population (3), and health conditions such as gastrointestinal disorders and long COVID-19 syndrome (4, 5), which can affect nutritional status. Additionally, social inequality and food insecurity—especially in underdeveloped and developing countries like Brazil—also contribute to these challenges (6, 7).

Vitamin B12 is a water-soluble vitamin primarily obtained from animal products such as red meat, dairy, and eggs. Intrinsic factor, a glycoprotein produced by parietal cells in the stomach, is essential for vitamin B12 absorption in the terminal ileum. The recommended daily intake for adults is 2.4 micrograms (8). Since the human body cannot synthesize vitamin B12, it must be obtained through food or supplements.

Once absorbed, the body utilizes vitamin B12 to produce red blood cells, support nerve function, synthesize DNA, and perform other critical functions. Vitamin B12 plays an essential role in erythropoiesis and neural function, acting as a cofactor for DNA synthesis and myelin formation. Its deficiency disrupts hematopoietic and neurological homeostasis, leading to megaloblastic anemia and impaired neural conduction, which can manifest as cognitive decline, neuropathy, or neuropsychiatric disorders, neurological manifestations are consequences of vitamin B12 deficiency. Importantly, the relationship between vitamin B12 deficiency and megaloblastic anemia is bidirectional—hematologic disorders may worsen vitamin utilization, while deficiency precipitates macrocytosis and bone marrow dysfunction (917). Additionally, chronic deficiency is linked to reduced bone density and an increased risk of osteoporosis (18), particularly in older adults. Mental health conditions (12), including depression, mood disorders, and psychosis (9, 10), as well as gastrointestinal diseases like Crohn’s disease (17) and celiac disease, are also associated with B12 deficiency. Furthermore, long-term use of certain medications, such as proton pump inhibitors and metformin (19, 20), can impair B12 absorption, increasing the risk of deficiency.

In the Brazilian context, the prevalence of vitamin B12 deficiency varies across age, region, and socioeconomic strata. National and regional surveys have reported deficiency rates ranging from 6 to 15% in adults and children, with higher prevalence observed in populations experiencing food insecurity, low intake of animal protein, and limited access to fortified foods (6, 7). Most cases of vitamin B12 deficiency can be effectively treated with injections, oral supplements, or sublingual tablets to restore adequate levels (21). Depending on whether the deficiency stems from dietary insufficiency or malabsorption, patients may require B12 supplementation between meals or regular injections. In some cases, lifelong treatment is necessary to prevent chronic and potentially life-threatening complications.

Assessing vitamin B12 status in Brazil also has clinical and economic implications. Deficiency is associated with a broad spectrum of diseases that frequently lead to hospitalization, including cardiovascular, hematological, neurological, psychological, and gastrointestinal disorders (917). Many of these conditions are prevalent and rising in the Brazilian population, particularly among older adults, women, and individuals with chronic comorbidities. Furthermore, vitamin B12 deficiency is both a cause and a marker of systemic disease severity, often coexisting with other vitamin B deficiencies (notably B1 and B6) and metabolic disturbances (19, 20). Thus, understanding the population-level patterns of B12 deficiency can help identify at-risk groups and reduce avoidable hospital admissions.

Despite the growing number of diagnostic tests and awareness campaigns, there remains limited population-based evidence integrating vitamin B12 deficiency data with healthcare outcomes in Brazil. Given that most existing studies are restricted to specific subgroups or local settings, a comprehensive national evaluation is lacking.

The present study therefore aims to fill this gap by examining vitamin B12 deficiency trends across Brazil’s public and private healthcare systems, exploring its association with hospitalizations and related diseases, and identifying key demographic and regional disparities. These findings are intended to inform prevention strategies and strengthen national health policies aimed at early detection and management of vitamin B12 deficiency.

2 Materials and methods

The domain-specific Institutional Review Board of the Galen Academy, based in São Paulo, Brazil, approved the data collection and analysis for this study (approval number 7.293.366, CAEE: 85144924.8.0000.9887).

In Brazil, the public health care system (Sistema Único de Saúde - SUS) provides universal health coverage to 100% of the population, which currently stands at approximately 213 million people. As of 2023, about 75% of the population (~160 million people) rely exclusively on SUS for their health care needs (22). The remaining 25% of the population has private health insurance but still has access to SUS for essential services, including vaccinations, emergency care, and treatments not covered by private plans.

Data collection, cleaning, and monitoring were conducted by the BCRI Statistics Department to ensure accuracy and consistency throughout the study. Data were obtained from administrative datasets encompassing primary, secondary, and tertiary care for Brazilian patients across all five geographic regions (North, Northeast, Central-West, South, and Southeast), with no age restrictions. In our analysis, all tests were de-duplicated by patient ID and testing date when available. Sequential tests performed within the same calendar year were counted once per individual. Vitamin B12 assays were performed using automated chemiluminescence immunoassay platforms (Abbott Architect and Roche Cobas) across reference laboratories reporting to the Brazilian Ministry of Health and accredited private networks. Inter-laboratory calibration is routinely audited, minimizing systematic bias. Vitamin B12 deficiency was categorized as <221 pmol/L accordingly to WHO/CDC criteria (Abnormal value = below 221 pmol/L), however, only results (normal/abnormal) were available.

Eligibility criteria included:

1. Public health care users: Patients registered in the Sistema Único de Saúde (SUS) throughout the entire study period (2016–2023).

2. Private health care users: Patients with private health insurance whose health care records could be linked to national centralized public and private databases.

To standardize comparisons, the number of patients was adjusted per 1,000 inhabitants/users, representing individuals with access to either public or private health care services.

A total of 84 million vitamin B12 measurements were retrospectively obtained, with 99% completeness in age and gender data. Age-gender pyramids were constructed for both health care systems, and the percentage distribution of 10-year age groups, along with mean age and standard deviation (SD), was reported.

The Brazilian Ministry of Health, through its Department of Primary Care and Coordination of Food and Nutrition Management, regularly conducts health campaigns measuring vitamin B12 levels across the five geographic regions in children, adults, and the elderly. Consequently, the percentage of abnormal test results by age and gender was analyzed over the same period for the same population.

These reports, encompassing 1,000 of patients, were used to predict absolute numbers and percentages of abnormal test results in both public and private health care systems.

Hospital admissions were identified using the primary International Classification of Diseases (ICD-10) codes cause in both public and private healthcare systems.

Each hospitalization record in the dataset contains multiple diagnostic fields coded according to the International Classification of Diseases (ICD-10). For this analysis, we identified hospitalizations in which both vitamin B12 deficiency (ICD-10 code E53.8) and a clinical disease of interest (e.g., cardiovascular, hematological, neurological, psychological, or gastrointestinal disorders) were recorded within the same admission episode. To ensure that the two diagnoses referred to the same hospitalization event, we included only records where both codes appeared under the same hospitalization identifier (admission ID or discharge record). The primary diagnosis corresponded to the main reason for admission (e.g., anemia, heart failure, neuropathy), while vitamin B12 deficiency was listed as a secondary or contributing diagnosis in the same record. Because all outcomes were derived from national hospitalization records, the rates of admissions for anemia, dementia, depression, Parkinson’s disease, inflammatory bowel disease, stroke, and myocardial infarction were included as ecological covariates to adjust for temporal and regional differences in comorbidity burden. These categories represent distinct ICD-10 codes and were not overlapping with the vitamin B12 deficiency outcome (ICD-10 D51). B1/B6 deficiency ICD-10 codes (E51.9 and E53.1) were used to extract data from administrative records. To assess hospitalization trends over time (2016–2023), the Mann-Kendall test was applied. Spearman’s rank correlation test was used to examine the linear relationship between vitamin B12 deficiency and other causes of hospitalization.

In addition, the observed correlations may be confounded by multiple factors, including age, sex, socioeconomic status, comorbidities, healthcare access, and regional disparities. Hence, multivariable Poisson regression of regional vitamin B12-deficiency hospitalizations (ICD-10 D51) in Brazil, 2016–2023 was performed. The model includes comorbidity hospitalizations, socioeconomic variables (income per capita, Gini index), and fixed effects for region and year, with population offset. Single summary effect size (pooled RR) from multivariable analysis was generated for vitamin B12-deficiency hospitalizations from 2016 to 2023 of the five major regions-years. Rate ratios (RR) > 1 indicate higher B12-deficiency hospitalization rates per unit increase in the corresponding covariate. For data analysis, we used R, and for data visualization, Prim Plus (version 8·4) was utilized.

3 Results

3.1 Vitamin B12 measurements

From January 2016 to December 2023, a total of 84 million vitamin B12 measurements were obtained from both public and private healthcare systems in Brazil (Figure 1A). Over this period, the annual number of measurements increased more than 12-fold, rising from 2 million in 2016 to 25 million in 2023.

Figure 1
Graph A displays the number of Vitamin B12 exams from 2016 to 2023, showing separate contributions from public and private healthcare systems. A trend line indicates the mean cost per exam, ranging from 16 to 22 Brazilian reais. Graph B illustrates the yearly percentage of exams by each healthcare system, with the private system increasing from 14% in 2016 to 60% in 2023, while the public system's share decreases correspondingly.

Figure 1. Vitamin B12 exams by healthcare systems per year. (A) Number of vitamin B12 exams performed in the study period in Brazil’s public and private healthcare systems. (B) Yearly percentage of exams in each healthcare system.

The distribution of tests between the public and private healthcare systems also shifted significantly. In 2016, 94% of measurements were conducted in the public healthcare system, compared to only 6% in the private sector. By 2023, this ratio had changed to 40% in the public system versus 60% in the private system (Figure 1B).

3.2 Vitamin B12 measurements per geographic distribution

In both public and private healthcare systems, the number of vitamin B12 measurements per 1,000 inhabitants/users was highest in the South compared to the North of Brazil (Figure 2A). Furthermore, the private healthcare system consistently recorded a higher number of exams across all geographic regions. The disparity was particularly pronounced in the Northeast, where the number of exams in the private sector was up to 17 times higher than in the public system. In contrast, the South exhibited a smaller gap, with private healthcare performing, approximately three times more tests than the public system (Figure 2B). This regional variation highlights differences in healthcare access, diagnostic demand, and reliance on private healthcare across Brazil.

Figure 2
Map A shows the public healthcare system's geographic distribution of Vitamin B12 exams in Brazil for 2023, with 213 million people. The exams per 1,000 inhabitants are: North 13, Northeast 15, Central-West 23, Southeast 62, South 95. Map B illustrates the private healthcare system's distribution with 52 million people. The values for exams per 1,000 inhabitants are: North 162, Northeast 258, Central-West 318, Southeast 291, South 361.

Figure 2. Vitamin B12 exams by geographic location in brazil (2023). (A) Vitamin B12 measurements in the 5 geographic regions in the public healthcare system. (B) Vitamin B12 measurements in the 5 geographic regions in the private healthcare system.

3.3 Vitamin B12 measurements by age and gender

A total of 35 million vitamin B12 measurements were obtained from the public healthcare system, with 69% from female patients (24·2 M) and 31% from male patients (10·8 M). In the private healthcare system, 47·8 million measurements were recorded, with a similar gender distribution: 69% female (32·8 M) and 31% male (15 M) (Figure 3A). Across both healthcare systems, female patients underwent approximately 2.3 times more tests than male patients. However, there was a notable age discrepancy in vitamin B12 testing between the two systems. First, in the public healthcare system, the mean age of tested individuals was 54 years. Second, in the private healthcare system, the mean age was 47 years (Figure 3B).

Figure 3
Bar charts comparing Vitamin B12 exams by age and gender in public and private healthcare. Panels A and B show total exams, with more females (69%) than males (31%). Panels C and D show predictions of abnormal exams, with 80% female and 20% male. Public healthcare mean age is 54, private is 47.

Figure 3. Age and gender populational pyramids (2016–2023). (A) Vitamin B12 distribution by age & gender in the public healthcare system. (B) Vitamin B12 distribution by age and gender in the private healthcare system. (C) Prediction of abnormal vitamin B12 exams by age and gender in the public healthcare system. (D) Prediction of abnormal vitamin B12 exams by age & gender in the private healthcare system.

3.4 Prediction of abnormal vitamin B12 tests

An estimated 4 million abnormal vitamin B12 test results (11%) were recorded in the public healthcare system, while 6 million (12%) were observed in the private healthcare system (Figures 3C,D). Female patients accounted for 80% of these abnormal results in both healthcare systems, whereas male patients represented only 20%. The mean age of female patients with abnormal results was 49 years in the public system and 44 years in the private system. In contrast, male patients with abnormal test results tended to be older, with a mean age of 54 years in the public system and 44 years in the private system. These findings highlight gender disparities in testing frequency and age-related differences in vitamin B12 deficiency detection across healthcare systems.

3.5 Hospitalizations associated with vitamin B12 and other B vitamin deficiencies

The trend of all-cause hospitalizations associated with vitamin B12 deficiency showed a statistically significant increase (p < 0·05) over the study period (2016–2023). The lowest hospitalization rate was recorded in 2018, with 598 hospitalizations, which then rose to 870 hospitalizations in 2023, representing a 32% increase (Figure 4). Hospitalizations associated with vitamin B1 (thiamine) and vitamin B12 with Spearman’s rank correlation of 0.952 (p = 0.0003) and B6 (pyridoxine) of 0.857 (p = 0.007) deficiencies also increased over the study period. Correlation analysis further revealed a significant linear correlation between hospital admissions for vitamin B12 deficiency and hospitalizations related to B1 and B6 deficiencies of 0.905 (p = 0.002) (Figure 4). However, concomitant deficiencies cases involving both B12 and B1 or B12 and B6 remained rare and did not show a notable increase throughout the study period (Supplementary Table 1).

Figure 4
Line graph titled

Figure 4. Hospitalizations due to vitamin B12 and others vitamins B deficiencies.

3.6 Hospitalizations associated with vitamin B12 deficiency and clinical diseases

Hospitalizations related to cardiovascular, hematological, neurological, psychological, and gastrointestinal diseases which can be either causes or consequences of vitamin B12 deficiency were analyzed. The primary cause of hospitalization and was the studied disease and Vitamin B12 The Spearman’s rank correlation Vitamin B12 and Anemia was 0.93 (p = 0.001), dementia was 0.95 (p < 0.001), Depression was 0.95 (p < 0.001), Parkinson was 0.95 (p < 0.001), Intestinal inflammatory diseases was 0.90 (p = 0.002), Stroke was 0.98 (p < 0.001) and Heart Attack was 0.98 (p < 0.001), respectively (Supplementary Table 1).

Results showed a statistically significant increase (p < 0·05) in hospitalizations due to vitamin B12 deficiency and all associated diseases over the study period (Figure 5). A notable upward trend was observed after 2018, mirroring the overall increase in vitamin B12-related hospitalizations.

Figure 5
Graph depicting the correlation between Vitamin B12 deficiency and various diseases from 2016 to 2023. Lines represent hospitalization trends for stroke, heart attack, anemia, depression, inflammatory intestinal diseases, dementia, Parkinson's, and Vitamin B12 deficiency. Hospitalizations for each condition are shown on separate colored lines, with different correlation coefficients provided. The graph is divided into two time periods, 2016-2018 and 2019-2023, with all p-values below 0.05, indicating statistical significance.

Figure 5. Hospitalizations associated with vitamin B12 and other clinical diseases.

Additionally, multivariable Poisson regression of regional vitamin B12-deficiency included comorbidity hospitalizations, socioeconomic variables (income per capita, Gini index), and fixed effects for region and year, with population offset. In adjusted analyses, B12-deficiency hospitalization rates remained significantly associated with anemia (RR = 1.09; 95% CI = 1.03–1.15; p = 0.02), dementia (OR = 1.05; 95% CI = 1.01–1.10; p = 0.003), stroke (OR = 1.07; 95% CI = 1.02–1.13; p = 0.012), and myocardial infarction (OR = 1.09; 95% CI = 1.03–1.15; p = 0.02)., independent of regional and temporal fixed effects and socioeconomic covariates. Associations for depression, Parkinson’s disease, and inflammatory bowel disease were directionally positive but did not consistently reach statistical significance after adjustment. The inclusion of income and Gini modestly attenuated the estimates, yet the core associations persisted, supporting robustness to confounding by socioeconomic differences across regions (Table 1).

Table 1
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Table 1. Multivariable Poisson regression for vitamin B12-deficiency hospitalizations (2016–2023, N = 5 major regions-years)*.

4 Discussion

Vitamin B12 deficiency is a significant public health issue with long-term implications for both public and private healthcare systems. Understanding its population-level of impact can help strengthen healthcare strategies, reduce costs, and improve patient outcomes. The key findings of our study include: First, vitamin B12 testing is more frequently requested in the private healthcare system compared to the public system. Second, female patients undergo 2.3 times more B12 tests than male patients and exhibit four times more abnormal results. Third, hospitalizations associated with vitamin B12 deficiency, other B vitamin deficiencies (B1 and B6), and associated diseases are rising over time. Finally, hospitalization data were aggregated by region and year, and correlations were assessed at the population—not individual—level. Therefore, we do not claim direct causality between an individual’s prior B12 test and their hospitalization episode, although a significant correlation exists in large populational level between vitamin B12 deficiency and hospital admissions for cardiovascular, hematological, neurological, psychological, and gastrointestinal diseases. These findings underscore the growing burden of vitamin B12 deficiency and highlight the need for routine screening, early detection, and prevention strategies to potentially mitigate its impact on healthcare systems.

Since healthcare systems are highly context-specific, there is no universal set of best practices that applies to all. However, understanding the public and private healthcare sectors can help identify shared characteristics and system-specific needs, allowing for tailored interventions that improve healthcare delivery and patient outcomes. To our knowledge, this is the first study analyzing both public and private healthcare systems in Brazil in relation to vitamin B12 deficiency trends and hospitalizations. The data presented here can support targeted interventions for at-risk populations and ultimately contribute to better clinical outcomes. A previous study conducted in Brazil reported that 7.2% of participants aged 60 years or older and 6.4% of participants aged 30–59 years were vitamin B12 deficient, highlighting a significant prevalence of deficiency across different age groups. These findings align with global analyses from Europe, North America, and Asia reporting similar population-level increases in vitamin B12 deficiency, where prevalence ranges from 5 to 20% depending on age, diet, and socioeconomic status.

These findings reinforce the importance of continued monitoring, early detection, and intervention strategies to possibly mitigate the growing burden of vitamin B12 deficiency in both public and private healthcare settings (23). In relation to this our study findings demonstrated an increasing of about 5–6%, meaning that in one decade Brazil has double the percentage of patients with vitamin B12 deficiency. This trend suggests a growing demand for vitamin B12 testing, as well as an increasing reliance on private healthcare for diagnostics over time.

Poverty and low maternal education have been identified as key risk factors associated with lower vitamin B12 levels in children. Studies in Amazonian children reported a vitamin B12 deficiency prevalence of 4.2%, with a significantly higher rate of 13.6% in children under 24 months. Similarly, in Brazilian children aged 11–15 months, 15% were found to be vitamin B12 deficient. Several factors contribute to this nutritional deficiency, including: low socioeconomic status and limited access to nutrient-rich foods, low animal protein intake, which is the primary dietary source of vitamin B12, geohelminth infections, which can impair nutrient absorption and further exacerbate deficiency (6). Additionally, genetic ancestry has been identified as an influencing factor in vitamin B12 levels among children and adolescents in Brazil. The pronounced gender differences observed—women undergoing 2.3 times more tests and exhibiting fourfold more abnormal results—may be explained by both biological and behavioral factors. Hormonal influences, reproductive demands, and autoimmune conditions affecting gastric absorption (e.g., pernicious anemia, thyroid disease) may predispose women to deficiency, while greater health-seeking behavior increases test frequency. Conversely, men may be underdiagnosed until more advanced neurological or cardiovascular manifestations occur, suggesting that under-screening contributes to delayed recognition. This suggests that both biological and environmental factors play a role in determining vitamin B12 status, highlighting the need for targeted nutritional interventions in vulnerable populations. These findings emphasize the importance of public health policies that address socioeconomic disparities, improve maternal education, and enhance dietary supplementation to combat vitamin B12 deficiency in at-risk children (6).

While studies do not determine causality between vitamin B12 deficiency and hospitalizations, its serious health complications can lead to medical admissions, particularly when left untreated. Deficiency in vitamin B12 is associated with neurological, cardiovascular, psychological, hematological, and gastrointestinal disorders, many of which require clinical intervention and hospitalization. In Brazil, the overall prevalence of B vitamin deficiencies remains unclear, but a recent study identified a higher prevalence among pregnant and lactating mothers (23). Our study further complements these findings, demonstrating that hospitalizations related to vitamin B12, B1, and B6 deficiencies are increasing over time. However, cases of concomitant deficiencies involving B12 with either B1 or B6 remain rare, suggesting distinct risk factors and clinical presentations for each vitamin deficiency.

Vitamin B12 deficiency is highly prevalent in older adults, particularly among those with impaired vitamin absorption due to conditions such as gastric surgery and atrophic gastritis (24). This deficiency is strongly associated with an increase in hospitalizations due to neurological, hematological, and cardiovascular complications (25). Interestingly, studies have found that in hospitalized patients, elevated vitamin B12 levels were predictive of short, medium, and long-term mortality at six, 12, and 48 months (26). Similarly, in hypertensive adults, elevated B12 levels were linked to higher all-cause and cardiovascular mortality during hospitalization. This risk association was used in our study to evaluate the relationship between hospitalizations and diseases that are either a cause or a consequence of vitamin B12 deficiency. These findings revealed a significant increase in hospitalizations related to associated diseases, further emphasizing the need for early detection and adequate supplementation to mitigate these risks.

From a policy standpoint, our findings have several implications. First, routine screening for vitamin B12 deficiency should be incorporated into primary care for high-risk populations such as older adults, women of reproductive age, vegetarians, and patients with diabetes or chronic use of metformin or proton pump inhibitors. Second, national supplementation and fortification programs could reduce preventable neurological and hematologic complications. Third, the integration of B12 testing into basic health packages and the use of electronic clinical alerts in primary care would facilitate early detection. Finally, linking data between public and private systems could enable continuous surveillance and equitable policy design.

This study has several limitations that should be acknowledged. Firstly, differences in how healthcare providers record diagnoses, treatments, and outcomes can create inconsistencies. For instance, the private system serves a population with higher socioeconomic status and more frequent routine check-ups, which may bias test frequency. Secondly, as a real-world observational study, establishing causal relationships is challenging. Vitamin B12 stores in the liver last 3–5 years, meaning deficiency symptoms may take time to manifest, complicating direct causality assessments. Thirdly, incomplete vitamin B12 measurements during hospitalizations. Although vitamin B12 deficiency is linked to various diseases, in many hospitalized patients, B12 levels were not measured, which could have strengthened the understanding of its causal relationship with associated conditions. Finally, as detailed clinical indications were not consistently available in the national administrative dataset, future research should employ a nested case–control design to enable more precise characterization of these variables.

Despite these limitations, this study conducted on a large-scale, real-world population provides valuable insights into vitamin B12 deficiency and other B vitamin deficiencies. The results offer important evidence that may contribute to shaping healthcare policies and improving early detection, intervention, and treatment strategies.

We concluded that Vitamin B12 deficiency is a public health concern in Brazil, with far-reaching consequences for multiple organ systems. This suggests an increasing burden and underrecognized trend of vitamin B12 deficiency can be an underlying cause of hospitalizations, particularly when left undiagnosed and untreated, possibly leading to severe medical conditions requiring inpatient care. Early detection and timely intervention are crucial to prevent serious complications. Strengthening public health policies, increasing awareness, and improving access to diagnostic and preventive care can help reduce the prevalence of vitamin B12 deficiency and potentially improve overall health outcomes.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement

The studies involving humans were approved by the Institutional Review Board of the Galen Academy, based in São Paulo, Brazil, approved the data collection and analysis for this study (approval number 7.293.366, CAEE: 85144924.8.0000.9887). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin because data were obtained from administrative datasets encompassing primary, secondary, and tertiary care for Brazilian patients across all five geographic regions (North, Northeast, Central-West, South, and Southeast).

Author contributions

LC: Conceptualization, Data curation, Writing – original draft. NA: Conceptualization, Writing – review & editing. MP: Conceptualization, Writing – review & editing. CF: Conceptualization, Writing – review & editing. RO: Conceptualization, Formal analysis, Writing – original draft, Writing – review & editing. RL: Conceptualization, Writing – original draft, Formal analysis.

Funding

The author(s) declared that financial support was received for this work and/or its publication. Marjan S/A Pharma Company for provided financial support for this research. The sponsor had no role in the study design, data collection, data analysis, data interpretation, or writing of the manuscript.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that Generative AI was not used in the creation of this manuscript.

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Supplementary material

The supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2025.1701661/full#supplementary-material

References

1. Green, R, Allen, LH, Bjorke-Monsen, A-L, Brito, A, Guéant, J-L, Miller, JW, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. (2017) 3:17040. doi: 10.1038/nrdp.2017.40,

PubMed Abstract | Crossref Full Text | Google Scholar

2. Jensen, CF. Vitamin B12 levels in children and adolescents on plant-based diets: a systematic review and meta-analysis. Nutr Rev. (2023) 81:951–66. doi: 10.1093/nutrit/nuac096,

PubMed Abstract | Crossref Full Text | Google Scholar

3. Baik, HW, and Russell, RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr. (1999) 19:357–77. doi: 10.1146/annurev.nutr.19.1.357,

PubMed Abstract | Crossref Full Text | Google Scholar

4. Ulloque-Badaracco, JR, Al-Kassab-Cordova, A, Alarcon-Braga, EA, Hernandez-Bustamante, EA, Huyata-Cortez, MA, Cabrera-Guzmán, JC, et al. Association of vitamin B12, folate, and homocysteine with COVID-19 severity and mortality: a systematic review and meta-analysis. SAGE Open Med. (2024) 12:20503121241253957. doi: 10.1177/20503121241253957,

PubMed Abstract | Crossref Full Text | Google Scholar

5. Wee, AKH. COVID-19's toll on the elderly and those with diabetes mellitus - is vitamin B12 deficiency an accomplice? Med Hypotheses. (2021) 146:110374. doi: 10.1016/j.mehy.2020.110374,

PubMed Abstract | Crossref Full Text | Google Scholar

6. Cobayashi, F, Tomita, LY, Augusto, RA, D'Almeida, V, and Cardoso, MATeam AS. Genetic and environmental factors associated with vitamin B12 status in Amazonian children. Public Health Nutr. (2015) 18:2202–10. doi: 10.1017/S1368980014003061,

PubMed Abstract | Crossref Full Text | Google Scholar

7. Augusto, RA, Cobayashi, F, and Cardoso, MATeam AS. Associations between low consumption of fruits and vegetables and nutritional deficiencies in Brazilian schoolchildren. Public Health Nutr. (2015) 18:927–35. doi: 10.1017/S1368980014001244,

PubMed Abstract | Crossref Full Text | Google Scholar

8. Kurpad, AV, Pasanna, RM, Hegde, SG, Patil, M, Mukhopadhyay, A, Sachdev, HS, et al. Bioavailability and daily requirement of vitamin B(12) in adult humans: an observational study of its colonic absorption and daily excretion as measured by [(13)C]-cyanocobalamin kinetics. Am J Clin Nutr. (2023) 118:1214–23. doi: 10.1016/j.ajcnut.2023.08.020,

PubMed Abstract | Crossref Full Text | Google Scholar

9. Edwin, E, Holten, K, Norum, KR, Schrumpf, A, and Skaug, OE. Vitamin B12 Hypovitaminosis in mental diseases. Acta Med Scand. (1965) 177:689–99. doi: 10.1111/j.0954-6820.1965.tb01879.x,

PubMed Abstract | Crossref Full Text | Google Scholar

10. Fuenfgeld, EW. On vitamin B12 therapy of neuropsychiatric diseases. Med Welt. (1962) 25:1423–5.

PubMed Abstract | Google Scholar

11. Grinblat, J, Marcus, DL, Hernandez, F, and Freedman, ML. Folate and vitamin B12 levels in an urban elderly population with chronic diseases. Assessment of two laboratory folate assays: microbiologic and radioassay. J Am Geriatr Soc. (1986) 34:627–32. doi: 10.1111/j.1532-5415.1986.tb04902.x,

PubMed Abstract | Crossref Full Text | Google Scholar

12. Haan, J. Vitamin B12 deficiency: neurologic and psychiatric diseases. Med Monatsschr Pharm. (1982) 5:238–45.

PubMed Abstract | Google Scholar

13. Ia, Z, and Biskina, KN. Vitamin B12 therapy of diseases of the peripheral nervous system. Zdravookhr Beloruss. (1963) 9:71–2.

Google Scholar

14. Loiko, VI. Change in the vitamin B12 level in the blood in certain stomach diseases. Vestn Akad Med Nauk SSSR. (1967) 22:52–5.

PubMed Abstract | Google Scholar

15. Mastroianni, A, Ciniselli, CM, Panella, R, Macciotta, A, Cavalleri, A, Venturelli, E, et al. Monitoring vitamin B12 in women treated with metformin for primary prevention of breast Cancer and age-related chronic diseases. Nutrients. (2019) 11:1020. doi: 10.3390/nu11051020,

PubMed Abstract | Crossref Full Text | Google Scholar

16. Wu, S, Feng, P, Li, W, Zhuo, S, Lu, W, Chen, P, et al. Dietary folate, vitamin B6, and vitamin B12 and risk of cardiovascular diseases among individuals with type 2 diabetes: a case-control study. Ann Nutr Metab. (2023) 79:5–15. doi: 10.1159/000527529,

PubMed Abstract | Crossref Full Text | Google Scholar

17. Yakut, M, Ustun, Y, Kabacam, G, and Soykan, I. Serum vitamin B12 and folate status in patients with inflammatory bowel diseases. Eur J Intern Med. (2010) 21:320–3. doi: 10.1016/j.ejim.2010.05.007,

PubMed Abstract | Crossref Full Text | Google Scholar

18. Herrmann, M, Peter Schmidt, J, Umanskaya, N, Wagner, A, Taban-Shomal, O, Widmann, T, et al. The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12) deficiencies in osteoporosis: a systematic review. Clin Chem Lab Med. (2007) 45:1621–32. doi: 10.1515/CCLM.2007.362,

PubMed Abstract | Crossref Full Text | Google Scholar

19. Aboshaiqah, A, Aboshaiqah, B, Alharbi, NM, Almunyif, TI, Binghanim, SD, and Almejalli, AK. The prevalence of vitamin B12 deficiency among diabetic patients who use metformin. Cureus. (2024) 16:e74559. doi: 10.7759/cureus.74559,

PubMed Abstract | Crossref Full Text | Google Scholar

20. Atkinson, M, Gharti, P, and Min, T. Metformin use and vitamin B12 deficiency in people with type 2 diabetes. What Are the Risk Factors? A Mini-systematic Review. touchREV Endocrinol. (2024) 20:42–53. doi: 10.17925/EE.2024.20.2.7,

PubMed Abstract | Crossref Full Text | Google Scholar

21. Hvas, AM, and Nexo, E. Diagnosis and treatment of vitamin B12 deficiency-an update. Haematologica. (2006) 91:1506–12.

PubMed Abstract | Google Scholar

22. Viacava, F, Oliveira, RAD, Carvalho, CC, Laguardia, J, and Bellido, JG. SUS: supply, access to and use of health services over the last 30 years. Ciênc Saúde Colet. (2018) 23:1751–62. doi: 10.1590/1413-81232018236.06022018,

PubMed Abstract | Crossref Full Text | Google Scholar

23. Xavier, JM, Costa, FF, Annichino-Bizzacchi, JM, and Saad, ST. High frequency of vitamin B12 deficiency in a Brazilian population. Public Health Nutr. (2010) 13:1191–7. doi: 10.1017/S1368980009992205,

PubMed Abstract | Crossref Full Text | Google Scholar

24. Dholakia, KR, Dharmarajan, TS, Yadav, D, Oiseth, S, Norkus, EP, and Pitchumoni, CS. Vitamin B12 deficiency and gastric histopathology in older patients. World J Gastroenterol. (2005) 11:7078–83. doi: 10.3748/wjg.v11.i45.7078,

PubMed Abstract | Crossref Full Text | Google Scholar

25. Levy, J, Rodriguez-Gueant, R-M, Oussalah, A, Jeannesson, E, Wahl, D, Ziuly, S, et al. Cardiovascular manifestations of intermediate and major hyperhomocysteinemia due to vitamin B12 and folate deficiency and/or inherited disorders of one-carbon metabolism: a 3.5-year retrospective cross-sectional study of consecutive patients. Am J Clin Nutr. (2021) 113:1157–67. doi: 10.1093/ajcn/nqaa432,

PubMed Abstract | Crossref Full Text | Google Scholar

26. Cappello, S, Cereda, E, Rondanelli, M, Klersy, C, Cameletti, B, Albertini, R, et al. Elevated plasma vitamin B12 concentrations are independent predictors of in-hospital mortality in adult patients at nutritional risk. Nutrients. (2016) 9:1. doi: 10.3390/nu9010001,

PubMed Abstract | Crossref Full Text | Google Scholar

Keywords: vitamin B12, health care, hospitalization, public health burden, clinical diseases

Citation: de Carvalho LP, Akamine N, Di Pietro MS, França CN, Oliveira R and Lopes RD (2026) Vitamin B12 deficiency and its impact on healthcare: a population-level analysis and call for action. Front. Nutr. 12:1701661. doi: 10.3389/fnut.2025.1701661

Received: 08 September 2025; Revised: 10 November 2025; Accepted: 04 December 2025;
Published: 05 January 2026.

Edited by:

Emanuele Micaglio, IRCCS San Donato Polyclinic, Italy

Reviewed by:

Runzhe Xu, University of Texas Southwestern Medical Center, United States
Husain Alkhaldy, King Khalid University, Saudi Arabia

Copyright © 2026 de Carvalho, Akamine, Di Pietro, França, Oliveira and Lopes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Renato D. Lopes, cmVuYXRvLmxvcGVzQGR1a2UuZWR1

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