It is known that the Indian population, particularly vegetarians, is deficient in vitamin B12. The vitamin essential for the formation of blood cells and the functioning of nerve cells is mainly found in animal-derived food. B12 deficiency during pregnancy has been associated with neural tube defects and poor foetal growth, affecting long-term health.
In 1993, Chittaranjan Yajnik, Director, Diabetes Unit, King Edward Memorial Hospital, Pune, undertook the Pune Maternal Nutrition Study (PMNS) to investigate the parental determinants of foetal growth. The study showed that low vitamin B12 and high folate among women predicted a higher risk of what Dr. Yajnik called “diabesity”, or insulin resistance and obesity in offsprings’ later life.
Researchers asked if increasing the B12 status early on, in adolescence, could reduce the risk of diabesity in offspring. The Pune Rural Intervention in Young Adolescents (PRIYA) trial tested this hypothesis in 2012-2020, within PMNS. The follow-up studies on the babies of the women who were adolescents around 2012 ended in 2025.
This trial led to the first in vivo human study in which researchers investigated the molecular aspects of vitamin B12 deficiency through an intergenerational approach.
Investigators gave adolescents in the rural areas of Pune vitamin B12 and multi-micronutrient supplements (over and above standard care) and followed up to the delivery of their first child. Following delivery, they isolated the cord blood mononuclear cells (CMCs) and investigated them to study gene expression. The researchers reported that supplementation with vitamin B12 and multi-micronutrients in adolescents improved the ponderal index, i.e. weight in proportion to height, later in their neonates and altered gene expression in the CMCs.
To test how vitamin B12 was affecting gene expression, the researchers performed a cross-sectional study, whose findings were published in the Journal of Developmental Origins of Health and Disease on January 12. They conducted a weighted gene co-expression network analysis in cord blood cells and observed that higher levels of B12 in the cord blood correlated positively with the expression of genes encoding methylases — enzymes that add a methyl group to DNA, an epigenetic modification that regulates gene expression.
Vitamin B12’s role in the regulation of methylases came as a surprise to researchers.
“You see, the activity of regulators [methylases] is known to be affected by B12, as B12 is involved in regenerating S-adenosyl methionine, or SAM, for methylation reactions,” Satyajeet Khare, associate professor at Symbiosis School of Biological Sciences, and one of the co-corresponding authors of the study, said. “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 targeted regulation of genes by B12. B12 appears to act as a regulator of regulators.”
Thus, the study contributes to the ‘developmental origins of health and disease’ hypothesis, which proposes that the intrauterine environment affects the long-term health of a developing foetus, in part through epigenetics.
The researchers noted that the study doesn’t establish a causal link between vitamin B12 levels and gene expression. That said, in future, they could identify targets of methylases and demethylases. The present study also focused only on cord blood cells, showing that research on other cell types and the effects of other micronutrients is warranted.
“We are only at cord blood right now. We do not know what is going to happen in the future,” Dr. Khare said.
The present study is also exploratory and needs additional research to that end as well.
“Replication of the present study by using existing biobank samples at the global level will be required [to confirm] the mechanism hypothesised in the paper,” Mohan Gupte, founder-director (retd.), ICMR-National Institute of Epidemiology and the ICMR School of Public Health, Chennai, said by email.
That said, he added, “The PRIYA study of Dr Yajnik has demonstrated the effectiveness of the recommended daily allowance of 2 micrograms. Even for the group with very low levels of B12, i.e. less than 100 pmol/L, 2 micrograms of B12 supplementation was found to be extremely useful.”
Researchers and experts in the field recommended that the national policy should include giving physiological doses of vitamin B12 in iron and folic acid tablets to improve the nutritional status of adolescents and women of reproductive age.
“This will have beneficial effects on the health of the population, human capital, and promote growth and development of the nation,” Dr Yajnik, also a co-corresponding author of this study, said.
Rohini Karandikar works with the TNQ Foundation and is a science communicator and educator.
Published – January 30, 2026 07:00 am IST
