Sweeping support for nutritional epigenetics from clinical research in rural Bangladesh

13 May 2024 --- The new trial, led by the University of California (UC), Santa Cruz, US, and conducted in rural Bangladesh, provides one of the most comprehensive contributions to scientific knowledge about the effects of nutrition, drinking water, sanitation and handwashing (WASH) on the physiological stress systems of children.

Nutritional epidemiology explores how environmental factors such as diet and nutrition impact health outcomes at the population level. The new findings present measurable evidence on how nutrition and other health interventions reduce oxidative stress in the body and reduce methylation levels of the DNA.

Nutrition Insight speaks to Audrie Lin, Ph.D., co-author of the study and an assistant professor at the department of microbiology and environmental toxicology at UC Santa Cruz.

“The study examines a combined nutrition and WASH intervention. We can hypothesize that the reductions in oxidative stress that we observed may be due to the lipid-based nutrient supplements enhancing antioxidant defenses,” explains Lin. 

“The lipid-based nutrient supplement contained ≥100% of the recommended daily allowance for 12 vitamins, including antioxidants such as vitamins C, A and E and nine minerals including manganese, copper, zinc and selenium. The nutrition intervention could have also strengthened immune defenses, which in turn, could have influenced the HPA (hypothalamic-pituitary-adrenal) axis and epigenetic programming.” 

Research design 
The large-scale randomized controlled trial published in Nature Communications started with more than 5,500 pregnant women living in rural Bangladesh and continued with the children born to them. The participating women were allocated to 720 study clusters and to one of seven groups. 

Nutrition and other health interventions reduce oxidative stress in the body and reduce methylation levels of the DNA.Participants in four of the groups were given either clean drinking water, sanitation, handwashing stations or nutrition counseling, including nutritional supplements. The other three groups received either combined WASH interventions, WASH with nutrition or no interventions at all (the control group).

“To date, research from other studies had suggested that combining too many interventions risked overwhelming the participants. However, we addressed this issue with our intensive intervention delivery system of WASH and nutrition interventions and highly trained community health workers who had frequent visits to the households during the first year of the trial,” details Lin.

“We also used a phased intervention rollout rather than introducing multiple interventions together in the households.”

The researchers assert that the design and scale of the study present some of the most “scientifically rigorous” stress physiology and epigenetic research findings. “Here, we see differences in outcomes between an intervention group and a control group, both of significant size,” says Lin.

Support for targeted interventions
Discussing the implications of these findings for the emerging field of study, Lin argues that they “support the future design and optimization of targeted nutritional and environmental therapeutic approaches that leverage physiologic plasticity to improve children’s health outcomes through the life course.”

She states that it is important to understand how to identify children who are at high risk for poor health outcomes and the optimal timing for interventions to support high-risk children.

“We need to determine if there are nutrition policies and interventions that can be established early in childhood that will have the greatest impact on child stress physiology, which will, in turn, impact child health and development,” she outlines. 

“Another implication of these findings is the idea that combining nutrition policies and interventions with WASH interventions or other psychosocial interventions could result in even greater benefits to child stress physiology and later health outcomes.” 

It is important to understand how to identify children who are at high risk for poor health outcomes and the optimal timing for interventions.“Feasible and scalable”
Lin talks about the feasibility and scalability of implementing similar nutritional interventions in other low-resource regions based on the findings of this study. She highlights that the team was able to achieve high uptake of the nutrition intervention by “taking the time to do formative research to develop nutrition intervention messages that were culturally sensitive.”

“Lipid nutrient supplements were highly acceptable in the settings where we worked, and this nutrition intervention has been used in multiple countries worldwide. Therefore, implementing similar nutritional interventions in other low-resource regions is highly feasible and scalable,” she asserts.

“At a programmatic level, the main foreseeable issues for implementing organizations is that they will need to determine ways to fund product purchase and distribution.”

Elaborating on how the results of this study could inform future research directions in the fields of global health, nutrition and child development, she states: “Because we observed early childhood intervention effects from physical health interventions in rural Bangladesh, future research studies should assess whether these results are generalizable to other geographical contexts.”

“Future research studies should aim to elucidate the complex interplay between nutrition, infection, psychosocial factors, the physiological stress response and child development.” 

The recently released 2024 Global Report on Food Crises revealed that 281 million people experienced high levels of acute food insecurity in 59 countries and territories in 2023. The global woman and girls-focused humanitarian organization CARE highlighted the experiences of people living in zones with ongoing conflicts as being most at risk, with the situations in Haiti, Gaza and Sudan being particularly concerning. 

By Milana Nikolova