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Cystathionine Enzymes in Transsulfuration and HO-1 Production: Impact on Spermatogenic Disorders in Folate and B12 Deficient Mice.

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This study demonstrates that deficiencies in vitamins B12 and B9 impair male fertility in mice by reducing sperm quality, increasing DNA damage, and disrupting testicular architecture, primarily through downregulation of CSE expression and altered homocysteine metabolism, highlighting the importance of B-vitamin intake for reproductive health.

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The 1-carbon metabolic cycle is essential for cellular growth, biomolecule synthesis, and epigenetic regulation. This cycle depends on B-complex vitamins, particularly folate (B9) and cobalamin (B12), which act as cofactors. Deficiencies in these vitamins can disrupt homocysteine metabolism, impair spermatogenesis, and increase oxidative stress, thereby compromising male fertility. To investigate the impact of dietary deficiencies in vitamins B12 and B9 on trans-sulfuration enzymes [cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE)], sperm function, oxidative stress, and DNA methylation in a mouse model. In this experimental study, male mice were fed either a standard chow diet or a diet deficient in vitamins B12 and B9. Sperm parameters, chromatin integrity [via acridine orange (AO) and aniline blue (AB)], lipid peroxidation, and intracellular reactive oxygen species (ROS; assessed using DCFH-DA and BODIPY C11) were evaluated. Sperm DNA methylation was measured using immunofluorescence. Serum levels of folate, vitamin B12, and testosterone were quantified. Expression of CBS, CSE, and HO-1 were analyzed by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and Western blot. Mice on the vitamin B deficient (VBD) exhibited significantly decreased sperm concentration and motility, along with increased morphological abnormalities, DNA damage, histone retention, and lipid peroxidation. Intracellular ROS levels did not differ significantly from controls. The VBD group also showed lower serum folate and B12, elevated homocysteine, and reduced testosterone levels. DNA methylation intensity in sperm was significantly decreased. Histological analysis revealed impaired testicular architecture and reduced spermatogenic indices. CSE gene expression was significantly downregulated, whereas CBS and Heme oxygenase 1 (HO-1) expression remained unchanged. Protein levels of CBS, CSE, and HO-1 showed no significant differences. Deficiencies in folate and vitamin B12 negatively affect sperm quality and testicular function in male mice, likely through disrupted homocysteine metabolism and altered gene expression in the trans-sulfuration pathway. These findings underscore the importance of adequate B-vitamin intake for male reproductive health.

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  • Cite Count Icon 56
  • 10.1136/bmjopen-2017-018007
Prevalence and possible factors associated with anaemia, and vitamin B12 and folate deficiencies in women of reproductive age in Pakistan: analysis of national-level secondary survey data
  • Dec 1, 2017
  • BMJ Open
  • Sajid Soofi + 10 more

ObjectiveTo determine the prevalence and possible factors associated with anaemia, and vitamin B12 and folate deficiencies in women of reproductive age (WRA) in Pakistan.MethodsA secondary analysis was conducted on data...

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  • Cite Count Icon 101
  • 10.1007/s00394-006-0598-7
High frequency of maternal vitamin B12 deficiency as an important cause of infantile vitamin B12 deficiency in Sanliurfa province of Turkey
  • Apr 6, 2006
  • European Journal of Nutrition
  • Ahmet Koc + 6 more

Vitamin B12 deficiency in infancy may cause failure to thrive, severe neurological disorders and megaloblastic pancytopenia. It is well known that infants born with deficient vitamin B12 storage have increased the risk of vitamin B12 deficiency. Vitamin B12 deficiency is more prevalent in infancy in Sanliurfa province (at the southeast region of Turkey). The aim of this study was to determine the frequencies of vitamin B12, folic acid and iron deficiencies in pregnants and their babies at birth and to what extend the mothers' deficiency becomes effective on babies' deficiencies. The study groups were constituted by 180 pregnant women and their single and term babies. Venous blood samples of pregnants were obtained 1-3 h before delivery and babies' cord bloods were collected at birth. Vitamin B12 and folic acid levels were measured with electro chemiluminiscence method; serum iron and iron binding capacities were measured by colorimetric method and complete blood counts were performed by automatic blood counter. Mean vitamin B12 levels in maternal and cord blood serum were 130 +/- 61.7 pg/ml and 207 +/- 141 pg/ml; mean folic acid levels were 8.91 +/- 6.46 ng/ml and 17.8 +/- 11.8 ng/ml; mean serum iron levels were 56.9 +/- 37.5 microg/dl and 147 +/- 43.2 microg/dl; and mean transferrin saturations were 11.8 +/- 8% and 65.6 +/- 24%, respectively. There were vitamin B12 deficiency (<160 pg/ml) in 72% of the mothers and 41% of the babies, and severe deficiency (<120 pg/ml) in 48% of the mothers and 23% of the babies. Folic acid deficiency was found in 12% of the mothers, but was not found in the babies. There were iron deficiency in 62% of the mothers and 1% of the babies. There were statistically significant correlation between maternal and cord blood serum vitamin B12 levels (r = 0.395, P < 0.001) and folic acid levels (r = 0.227, P = 0.017), while there were no correlation between maternal and cord blood iron levels and transferrin saturations. The study results showed that vitamin B12 deficiency is prevalent in pregnants in this region and that 41% of infants have born with deficient vitamin B12 storages. Therefore, prophylactic use of vitamin B12 by pregnant women in Sanliurfa and other poor communities could have considerable benefits to prevent vitamin B12 deficiency and its complications in infants.

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  • Cite Count Icon 23
  • 10.1016/s0002-9343(02)01181-6
Food-cobalamin malabsorption in the elderly
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  • The American Journal of Medicine
  • Emmanuel Andrès + 4 more

Food-cobalamin malabsorption in the elderly

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  • 10.1016/j.jds.2023.01.014
Higher frequencies of anemia, vitamin B12 deficiency, and gastric parietal cell antibody positivity in folic acid-deficient Taiwanese male oral submucous fibrosis patients
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Higher frequencies of anemia, vitamin B12 deficiency, and gastric parietal cell antibody positivity in folic acid-deficient Taiwanese male oral submucous fibrosis patients

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  • Cite Count Icon 356
  • 10.1093/ageing/afg109
Vitamin B12 and folate deficiency in later life.
  • Dec 28, 2003
  • Age and Ageing
  • R Clarke + 14 more

to examine the prevalence of vitamin B12 deficiency and folate deficiency in later life in representative samples of the elderly population in the United Kingdom. a population-based cross-sectional analysis of 3,511 people aged 65 years or older from three studies was used to estimate the age-specific prevalence of vitamin B12 deficiency and of folate deficiency. Vitamin B12 deficiency is conventionally diagnosed if serum vitamin B12 < 150 pmol/l ('low vitamin B12'). We defined 'metabolically significant vitamin B12 deficiency' as vitamin B12 < 200 pmol/l and blood total homocysteine >20 micro mol/l. Folate deficiency, which usually refers to serum folate <5 nmol/l, was defined as 'metabolically significant' if serum folate was <7 nmol/l and homocysteine >20 micro mol/l. the prevalence of vitamin B12 deficiency, whether defined as low vitamin B12 or metabolically significant vitamin B12 deficiency increased with age in all three studies, from about 1 in 20 among people aged 65-74 years to 1 in 10 or even greater among people aged 75 years or greater. The prevalence of folate deficiency also increased with age, and was similar to that for vitamin B12 deficiencies, but only about 10% of people with low vitamin B12 levels also had low folate levels. the high prevalence of vitamin B12 and folate deficiency observed in older people indicates a particular need for vigilance for deficiency of these vitamins. Reliable detection and treatment of vitamin deficiency could reduce the risk of deficiency-related disability in old age.

  • Research Article
  • Cite Count Icon 1
  • 10.35440/hutfd.1254961
The Frequency of Vitamin B12 and Folic Acid Deficiency in Mothers and Their Newborn Infants in Şanlıurfa Province
  • Apr 27, 2023
  • Harran Üniversitesi Tıp Fakültesi Dergisi
  • Nurgül Ataş + 1 more

Background: Vitamin B12 deficiency in pregnant women is an important health issue which not only affects mothers but also their infants. The aim of this study is to reveal the frequency of vitamin B12 and folic acid deficiency in pregnant women and their newborn babies, to evaluate the relationship between maternal and neonatal vitamin B12 and folic acid levels, and to determine the risk factors for vitamin B12 deficiency. Materials and Methods: This prospective study included 600 pregnant women (gestational age: 38-42 weeks) who presented to obstetrics departments in Şanlıurfa Province and their newborn infants without perinatal complication (birth weight≥2500 g). The lower limit for vitamin B12 was defined as 200 pg/mL. Data regarding age, number of child, medication, comorbid disease or being vegetarian or not were recorded in all mothers. Results: Vitamin B12 deficiency was found in 73.8% of the included pregnant women, and folic acid deficiency was found in 10.3%. Again, 70.5% of newborn babies were found to have vitamin B12 deficiency and 3.7% to have folic acid deficiency. It was concluded that vitamin B12 levels in newborn babies were related to maternal levels. Conclusions: As a result, it has been shown that a significant portion of newborns in Turkey have vitamin B12 deficiency. Vitamin B12 levels were quite low in mothers who gave birth recently. The deficiency of vitamin B12, which plays a major role in brain development upon intrauterine period, is a preventable cause of neurological deficit. Thus, it is highly important to screen and treat vitamin B12 deficiency before onset of clinical symptoms. We believe that our study is beneficial in this regard.

  • Research Article
  • Cite Count Icon 5
  • 10.7860/jcdr/2013/4754.3028
Deficiencies of the microelements, folate and vitamin B12 in women of the child bearing ages in gorgan, northern iran.
  • Jan 1, 2013
  • Journal of clinical and diagnostic research : JCDR
  • Maliheh Sedehi + 2 more

The deficiencies of folic acid, vitamin B12, and microelements during pregnancy may affect the health of newborns. To assess the serum levels of folate, vitamin B12, iron, zinc and copper in healthy women of the childbearing ages in Gorgan, northern Iran. This descriptive, cross-sectional study was carried out on 100 women of childbearing ages in northern Iran during November 2007-March 2008. The serum levels of folate, vitamin B12, iron, copper and zinc were evaluated by laboratory tests. Iron, copper , folate, vitamin B12 deficiencies and folate with vitamin B12 deficiency were detected in 13%, 32% , 13% , 32% and 11% women of the childbearing ages, respectively . According to the ethnicity, vitamin B12, folate and iron deficiencies in the Sistani group were observed in 38.3%, 12.9% and 12.9% of the women, respectively. In the native Fars group, the above mentioned deficiencies were found in 31.1%, 13.4% and 7.5% of the subjects. Folate and vitamin B12 deficiencies were observed in the urban habitant in 32.7% and 11.5 % of the subjects as compared to those in the rural habitant (in 30.4% and 15.2%of the subjects respectively). The folate deficiencies in the under and above 18 years old subjects were 22.2% and 9.9%, respectively. This study showed that the deficiency of the micronutrients was considerable in women of the childbearing ages in Gorgan, northern Iran.

  • Research Article
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Association of Vitamin B12 and Folate Deficiency with Vasovagal Syncope: A Case-Control Study
  • Apr 20, 2026
  • The Journal of Tehran University Heart Center
  • Arya Aminorroaya + 9 more

Background: Clinical evidence suggests an association between vitamin B12 deficiency and vasovagal syncope (VVS) in pediatric patients. This study investigated the association of vitamin B12 and folate deficiency with VVS in adults. Methods: In this case-control study, adult patients with VVS who presented to the tertiary syncope unit for head-up tilt table testing comprised the case group. Age- and sex-matched individuals without syncope history from the population-based Tehran Cohort Study served as the control group. Exclusion criteria included but were not limited to the use of vitamin B supplements, carbamazepine, or phenobarbital, and sleeve gastrectomy. Serum vitamin B12, folate, and homocysteine levels were measured and compared. Results: From February 2020 through February 2021, 44 patients comprised the case group, matched with 44 controls (mean age, 37.9 years; 23 [52.3%] females in each group). No statistically significant difference existed between the groups in vitamin B12 or folate deficiency or serum levels. Serum vitamin B12 levels were significantly lower in patients with frequent VVS (≥3 lifetime episodes) than in patients with infrequent VVS (&lt;3 lifetime episodes) (233.8 [80.7] vs 305.2 [118.1] pg/mL; P=0.042), and the association remained significant after adjustment for confounders (P=0.026). Conclusion: No association existed between vitamin B12 or folate deficiency or serum levels and VVS. Frequent VVS was associated with lower serum vitamin B12 levels than infrequent VVS.

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  • Cite Count Icon 8
  • 10.1067/mpd.2002.123899
Vitamin B12 deficiency in childhood and adolescence
  • May 1, 2002
  • The Journal of Pediatrics
  • Jatinder S Goraya

Vitamin B12 deficiency in childhood and adolescence

  • Research Article
  • Cite Count Icon 5
  • 10.7759/cureus.45252
The Effect of Helicobacter pylori Density on Serum Vitamin B12 and Folate Levels in Patients With Non-atrophic Gastritis
  • Sep 14, 2023
  • Cureus
  • Ibrahim E Pinar + 1 more

IntroductionChronic infection with Helicobacter pylori (Hp) is an essential cause of gastrointestinal pathologies in adults. Despite being a microorganism proven to play a role in vitamin B12 deficiency by causing gastric atrophy, Hp’s role in patients with non-atrophic gastritis has not been fully explained. Our study investigated whether the presence and density of Hp is related to vitamin B12 and folate deficiencies in patients with non-atrophic gastritis.MethodsThis retrospective cohort study analyzed the following parameters, vitamin B12, folate, and mean red blood cell volume (MCV) in the hemogram; these were measured simultaneously in patients diagnosed with non-atrophic gastritis who had undergone gastroscopy to investigate Hp levels. Patients with conditions that could have caused vitamin B12 and folate deficiencies were excluded from the study. The study included 244 patients who met the criteria. The Sydney classification was used for histopathologic grading and staging of gastric biopsies of patients with gastritis.ResultsThere was no relationship between the presence and density of Hp with vitamin B12 levels. However, folate levels were significantly lower in Hp-positive patients than in Hp-negative patients (p = 0.017). Folate levels were substantially lower in patients with chronic pan-mucosal gastritis than in patients with chronic inactive gastritis (p = 0.034). Statistically, a significant difference was found between folate levels on the basis of neutrophil activity and inflammation score (p = 0.011 and p <0.001, respectively).ConclusionsAlthough there was no statistically significant relationship between the presence and density of Hp and vitamin B12, our study found an association between folate levels and Hp density. This may be associated with the time for the depletion of vitamin B12 and folate stores and the relatively early stage of gastritis. In cases with vitamin B12 and folate deficiencies, appropriate studies should be performed for specific epidemiological reasons in respective fields.

  • Research Article
  • Cite Count Icon 27
  • 10.4103/2249-4863.152255
A Study of the Prevalence of Serum Vitamin B12 and Folic Acid Deficiency in Western Maharashtra
  • Jan 1, 2015
  • Journal of Family Medicine and Primary Care
  • Sanket K Mahajan + 1 more

Context:This study summarizes the prevalence of vitamin B12 and folic acid deficiency in the population coming to tertiary care center in Western Maharashtra along with the main presenting symptom routinely misinterpreted in daily practice.Aims and Objectives:1. To study the prevalence of vitamin B12 and folic acid deficiency in the population of western Maharashtra. 2. To correlate the symptoms with serum vitamin B12 and folic acid levels.Materials and Methods:The present study is a cross-sectional observation study carried out on patients from western Maharashtra seeking medical attention on outpatient and inpatient basis in the medicine department of a teaching institute in Karad. One-hundred patients were selected on basis of below mentioned symptoms viz. tingling and numbness in extremities, dizziness, unsteady gait, early tiredness, forgetfulness, proximal weakness, distal weakness, chronic headache, less interest in work, chronic loose stools, strict vegetarians, alcoholics, intake of medications like anti-tubercular treatment, surgery involving terminal ileum. Serum vitamin B12 and folic acid levels of these patients were observed. Deficiency of vitamin B12 and folic acid was studied in 4 groups: (a) Absolute vitamin B12 deficiency; (b) Absolute folic acid deficiency; (c) Borderline vitamin B12 deficiency; (d) Combined vitamin B12 and folic acid deficiency.Results:Of the 100 cases, 33% patients were vegetarian. Folic acid deficiency formed the major chunk of deficiency group. Six percent patients had neuropsychiatric manifestations. Depressive illness in 1% patients, dementia in 0% patients, forgetfulness in 1% patients, mania/hallucination in 0% patients each, and chronic headache in 1% patients. Neuropathy in form of loss of reflexes, decreased touch sensation was present in 9% patients. Posterior column involvement viz. Loss of joint position, vibration, positive Romberg's sign were present in 34% patients of vitamin B12 and folic acid deficiency.Conclusion:In a small study, it was found that megaloblastic anemia may have symptoms and signs referable to several systems including hematology, dermatology, gastrointestinal, neurology, and neuropsychiatry.

  • Research Article
  • Cite Count Icon 49
  • 10.1007/s13312-022-2622-2
Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics
  • Oct 1, 2022
  • Indian Pediatrics
  • Jagdish Chandra + 23 more

Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

  • Research Article
  • Cite Count Icon 3
  • 10.2147/jbm.s436673
Assessing Nutritional Anemia Among University Students in Jazan, Saudi Arabia: A Public Health Perspective.
  • Feb 1, 2024
  • Journal of Blood Medicine
  • Waleed Hakami + 16 more

Nutritional anemia is a significant public health concern worldwide, particularly affecting young adults and children in Saudi Arabia, where inadequate nutrition is considered a primary contributing factor. This study aims to (i) examine the levels of serum iron, folate, and vitamin B12 in young adult students, with a focus on identifying any deficiencies and their association with anemia; (ii) explore the prevalence of mixed-deficiency anemia resulting from deficiencies in serum iron, folate, and vitamin B12 (iii) explore how sociodemographic characteristics and dietary habits influence serum iron, folate, and vitamin B12 levels. This cross-sectional study encompassed 158 young adult students at Jazan University, Saudi Arabia. Blood samples were collected following a comprehensive questionnaire addressing sociodemographic and health characteristics. These samples were analyzed for complete blood count, serum iron, folate, and vitamin B12 levels. The findings of this study revealed a significant decrease in serum iron levels, with 70.6% of males and 88% in females exhibiting reduced level. Additionally, low levels of folate were observed in 4% of the study population, while deficiency in vitamin B12 was found in 2.2% of the study population. However, the simultaneous presence of low serum iron levels along with deficiencies in folate or vitamin B12 was not observed in the study participants. The study indicates that there is a high incidence of low serum iron and ferritin levels among university students in Saudi Arabia, which poses a considerable public health concern. Conversely, the prevalence of folate and vitamin B12 deficiencies among the students was comparatively low, and notably, there were no cases where these deficiencies were observed alongside iron deficiency.

  • Research Article
  • Cite Count Icon 19
  • 10.1016/j.exger.2018.12.007
Vitamin B12 and folate deficiencies are not associated with nutritional or weight status in older adults.
  • Dec 11, 2018
  • Experimental Gerontology
  • Pinar Soysal + 5 more

Vitamin B12 and folate deficiencies are not associated with nutritional or weight status in older adults.

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  • Research Article
  • Cite Count Icon 29
  • 10.1186/s40795-017-0173-z
Folate, vitamin B12, ferritin and haemoglobin levels among women of childbearing age from a rural district in South India
  • Jun 26, 2017
  • BMC nutrition
  • Samiksha Singh + 11 more

BackgroundLow folate and vitamin B12 levels have negative effect on pregnancy outcomes but there is paucity of data on their levels among Indian women. Ferritin and haemoglobin are associated with maternal mortality and low birth-weight. Our aim was to estimate the prevalence of deficiency of serum folate and vitamin B12, and low levels of serum ferritin and blood haemoglobin among women of childbearing age from a rural population of South India.MethodsWe conducted a community-based cross-sectional study among 15-35 year women in a rural district. We used multistage stratified random sampling. Trained staff interviewed women to collect socio-demographic information and draw blood samples. We analysed samples for serum folate, vitamin B12, ferritin and blood haemoglobin levels and computed means and medians. We computed the proportion of deficiency based on cut-offs recommended by WHO. We examined the association of levels with age, parity and current pregnancy or breastfeeding by multi-variable regression using Stata 13.0.ResultsWe recruited 979 women. One-fifth (185, 19%) were pregnant and one-fifth (196, 20%)were breastfeeding. Median serum folate levels were 2.5 ng/ml (IQR, 1.2-4.8), median vitamin B12 levels were 228.0 pg/ml (IQR, 121 - 390), median ferritin levels were 13.0 μg/l (IQR, 6.0 - 20.0) and median blood haemoglobin levels were 12.1 mg/dl (IQR, 10.7 – 13.6). Low levels of serum folate, vitamin B12, ferritin and haemoglobin were found in 57% (95% CI, 54-60%), 44% (95% CI, 41-48%), 46% (95% CI, 43-49%) and 28% (95% CI, 25-31%) respectively. Women with folic acid deficiency had two times higher prevalence of having vitamin B12 deficiency. In adjusted regression analysis folate levels were lower in older and breastfeeding women, but not associated with parity and were higher among pregnant women. Similar associations were not found with Vitamin B12 deficiency. Ferritin levels were higher in older women; but not associated with parity, pregnancy or breastfeeding. Haemoglobin levels were lower in pregnant and breastfeeding women.ConclusionOur findings suggest that folic acid, vitamin B12 and iron deficiency are important public health problems in India. We observed that half of the women of childbearing age were deficient in these nutrients. Folic acid and vitamin B12 deficiencies co-exist and should be supplemented together.

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