The Indian population, especially vegetarians, are known to be deficient in vitamin B12. The vitamin necessary for the formation of blood cells and the functioning of nerve cells is mainly found in foods of animal origin. B12 deficiency during pregnancy is associated with neural tube defects and poor fetal growth, affecting long-term health.
In 1993, Chittaranjan Yajnik, Director, Diabetes Unit, King Edward Memorial Hospital, Pune, conducted the Pune Maternal Nutrition Study (PMNS) to investigate parental determinants of fetal growth. The study showed that low levels of vitamin B12 and high levels of folic acid in women predicted a higher risk of what Dr. Yajnik called it “diabetes,” or insulin resistance and obesity in later life in offspring.
The researchers wondered whether increasing B12 status early, in adolescence, could reduce the risk of diabetes in offspring. The Pune Rural Intervention in Young Adolescents (PRIYA) trial tested this hypothesis in 2012–2020 within the PMNS. Follow-up studies of children of women who were teenagers around 2012 ended in 2025.
This study led to the first in vivo human study in which researchers investigated the molecular aspects of vitamin B12 deficiency through an intergenerational approach.
Researchers gave teenagers in rural areas of Pune vitamin B12 and multimicronutrient supplements (superior care) and followed the birth of their first child. After birth, they isolated cord blood mononuclear cells (CMCs) and examined them to study gene expression. The researchers reported that vitamin B12 and multimicronutrient supplementation in adolescents improved the body mass index, i.e., weight-for-height, later in their newborns and altered gene expression in CMC.
To test how vitamin B12 affects gene expression, researchers conducted a cross-sectional study, the results of which were published in Journal of Developmental Origins of Health and Disease January 12th. They performed a weighted gene co-expression network analysis in cord blood cells and observed that higher cord blood B12 levels positively correlated with the expression of genes encoding methylases – enzymes that add a methyl group to DNA, an epigenetic modification that regulates gene expression.
The role of vitamin B12 in the regulation of methylases was a surprise to the researchers.
“You know, the activity of regulators (methylases) is known to be affected by B12 because B12 is involved in the regeneration of S-adenosyl methionine or SAM for methylation reactions,” said Satyajeet Khare, an associate professor in the Symbiosis School of Biological Sciences and one of the study’s co-corresponding authors. “But who would have imagined that the expression of these regulators themselves is under the control of B12? Our results suggest the presence of a molecular mechanism for the targeted regulation of genes by B12. B12 appears to act as a regulator of regulators.”
The study thus contributes to the “developmental origins of health and disease” hypothesis, which proposes that the intrauterine environment influences the long-term health of the developing fetus, in part through epigenetics.
The researchers noted that the study did not show a causal relationship between vitamin B12 levels and gene expression. This means that in the future they could identify the targets of methylases and demethylases. This study also focused only on cord blood cells, indicating that research on other cell types and the effects of other micronutrients is warranted.
“Right now we’re at cord blood. We don’t know what’s going to happen in the future,” said Dr. Khare.
This study is also exploratory and needs further research for this purpose.
“Replication of this study using existing biobank samples at a global level will be required (to confirm) the mechanism hypothesized in the paper,” Mohan Gupte, founder and director (ret.), ICMR-National Institute of Epidemiology and ICMR School of Public Health, Chennai, said by email.
However, he added: “Dr Yajnik’s PRIYA study demonstrated the effectiveness of the recommended daily dose of 2 micrograms. Even for the group with very low B12 levels, ie less than 100 pmol/l, 2 micrograms of B12 supplementation was found to be extremely helpful.”
Scientists and experts in the field have recommended that national policy include the administration of physiological doses of vitamin B12 in iron and folic acid tablets to improve the nutritional status of adolescents and women of reproductive age.
“It will have beneficial effects on population health, human capital and promote the growth and development of the nation,” said Dr. Yajnik, who is also a co-author of this study.
Rohini Karandikar Works with the TNQ Foundation and is a science communicator and educator.
Published – 30 Jan 2026 07:00 IST
