Vitamin B12 deficiency is a notable concern among the Indian population, especially among vegetarians. This essential vitamin is critical for the production of blood cells and the proper functioning of nerve cells, but it is primarily found in animal-based foods. Insufficient levels of B12 during pregnancy have been linked to neural tube defects and hindered fetal growth, which can have lasting health implications.
In 1993, Dr. Chittaranjan Yajnik, Director of the Diabetes Unit at King Edward Memorial Hospital in Pune, initiated the Pune Maternal Nutrition Study (PMNS). This study aimed to explore the parental determinants of fetal growth. Results indicated that women with low levels of vitamin B12 and high levels of folate faced a greater risk of what Dr. Yajnik termed “diabesity,” a condition characterized by insulin resistance and obesity in their offspring later in life.
This led researchers to wonder if enhancing vitamin B12 levels during adolescence could mitigate the risk of diabesity in future generations. The Pune Rural Intervention in Young Adolescents (PRIYA) trial, conducted between 2012 and 2020 as part of the PMNS, examined this hypothesis. Follow-up studies on the children of the women who participated as adolescents are expected to conclude in 2025.
This trial paved the way for the first in vivo study in humans, where researchers took an intergenerational approach to examine the molecular implications of vitamin B12 deficiency.
Researchers provided vitamin B12 and multi-micronutrient supplements to adolescents in rural Pune, in addition to standard care, and monitored outcomes up to the birth of their first child. After delivery, they isolated cord blood mononuclear cells (CMCs) and analyzed gene expression. Findings revealed that the supplementation improved the ponderal index (a measure of weight relative to height) in their newborns and positively influenced gene expression in the CMCs.
To delve deeper into how vitamin B12 affected gene expression, researchers conducted a cross-sectional study, the results of which were published in the Journal of Developmental Origins of Health and Disease on January 12. Using weighted gene co-expression network analysis in cord blood cells, they observed a positive correlation between higher B12 levels in cord blood and the expression of genes encoding methylases — enzymes that add methyl groups to DNA, playing a crucial role in gene expression regulation.
The revelation about vitamin B12’s involvement in regulating methylases surprised the researchers. “It is known that B12 affects the activity of these regulators, as it helps regenerate S-adenosyl methionine (SAM), a compound essential for methylation reactions,” explained Satyajeet Khare, an associate professor at the Symbiosis School of Biological Sciences and a co-author of the study. “However, we did not anticipate that the expression of these regulators would themselves be influenced by B12. Our findings suggest a molecular mechanism where B12 regulates these genetic factors.”
This research enhances the ‘developmental origins of health and disease’ hypothesis, which posits that a developing fetus’s intrauterine environment can influence long-term health outcomes, partially through epigenetic mechanisms.
While the study does not establish a direct causal relationship between vitamin B12 levels and gene expression, the researchers anticipate identifying the targets of methylases and demethylases in future investigations. The current study focused solely on cord blood cells, indicating the need for further research involving diverse cell types and the impact of other micronutrients.
“Currently, our focus is on cord blood, and we are uncertain about the future findings,” Dr. Khare remarked.
The present study serves as an exploratory investigation that requires additional research to validate its findings.
Mohan Gupte, the retired founder-director of the ICMR-National Institute of Epidemiology and ICMR School of Public Health in Chennai, emphasized the need for replication of this research using global biobank samples to confirm the proposed mechanisms.
Nonetheless, he acknowledged that “the PRIYA study by Dr. Yajnik has shown the effectiveness of the recommended daily allowance of 2 micrograms of B12. Even among individuals with very low levels of B12, specifically those below 100 pmol/L, 2 micrograms of supplementation were found to be highly beneficial.”
Researchers and health experts advocate for national policies that include administering physiological doses of vitamin B12 alongside iron and folic acid supplements to enhance the nutritional status of adolescents and women of reproductive age.
“This could significantly improve population health, boost human capital, and foster the nation’s growth and development,” concluded Dr. Yajnik, who also co-authored this study.
Rohini Karandikar serves with the TNQ Foundation as a science communicator and educator.
Published – January 30, 2026 07:00 am IST