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The Role of Nutrition in Epigenetic Stress Programming in Children
By Heather Davis, MS, RDN, LDN
Many studies examining the stress response and its role in health outcomes tend to focus primarily on the impact of psychosocial stressors such as family dynamics, the presence or absence of social support, or workplace stress.1,2 However, psychosocial factors represent only one source of physiological stress among many others. Additional sources of stress may include nutritional imbalances, exposure to pathogens or environmental antigens, and more.3 How the body processes and responds to stressors from any source influences a great deal about long-term health outcomes.4
Research reveals that a well-regulated stress response is essential for healthy child growth and development. In a landmark study published in April of this year in Nature Communications, authors examine the impact of a variety of stressors—including nutritional stressors—on childhood epigenome.5
Study authors highlight that children living in low-income settings often experience recurrent infections and undernutrition due to inadequate water, sanitation, and food insecurity. All these elements may exert chronic high stress and have lasting impacts on the developing stress response system.
Researchers also point to what sets this experimental study apart from others looking at stress reduction interventions: the assessment of the effects of specific nutritional and environmental stress reduction interventions as opposed to focusing solely on psychosocial stress reduction interventions such as behavioral therapy or parental coaching.5
These experts also hypothesize that by demonstrating how interventions targeting nutrition and sanitation change a child's stress-related physiology, those measures might be easier for government agencies to employ at scale compared with psychosocial interventions.5
A Closer Look at the Study
The large-scale randomized controlled trial was conducted in rural Bangladesh, intentionally targeting a low-resource region that may better represent most of the world’s population. This study began with more than 5,500 pregnant women and their soon-to-be newborn children. The women were placed in 720 study clusters situated in one of seven groups. Participants in four of the groups received either clean drinking water, sanitation, handwashing stations, or nutrition counseling, plus nutrient supplements. The remaining three groups received either combined interventions of water/sanitation/handwashing or water/sanitation/handwashing/nutrition or no interventions (control group), respectively.5
Stress outcomes were assessed in 688 children (51% female) at age 14.3 months and 759 children (52% female) at age 28.2 months. At the time of enrollment, household characteristics were similar across intervention and control arms. Stress response was measured via cortisol and salivary alpha-amylase reactivity.
The research team found that an integrated intervention including clean drinking water, sanitation, handwashing, and nutrition support positively affected the set point, reactivity, and regulation of the physiological stress system in early childhood.
Where the Epigenetic Rubber Meets the Road
Early research has demonstrated that higher levels of chronic stress in the form of undernutrition, infection, and psychosocial adversity may cause irreversible harm if occurring under the age of 2, which marks a period of rapid growth and development.6 During this period, the neuroendocrine-immune network forms in response to exposure to environmental stimuli.7 These stimuli shape the set point, reactivity, and regulation of the two primary neuroendocrine axes, the hypothalamic-pituitary-adrenocortical (HPA) and sympathetic adrenomedullary (SAM) systems. These axes help regulate dozens of systems throughout the body.7
The HPA axis modulates the SAM system through the production of glucocorticoids, like cortisol, which regulates the immune system, growth factors, genes involved in oxidative stress pathways, and neurodevelopment.5 Cortisol production also follows a circadian rhythm that is developed during the first year of life.8 Chronic stress may disrupt the tight regulation of this circadian rhythm.9 Exposure to chronic stress may even alter a child’s cortisol response to an acute physical stressor, which could exacerbate HPA axis dysregulation.5
Chronic stressors such as ongoing infections and undernutrition may negatively affect the transcriptional activation of the glucocorticoid receptor.10 Cortisol binds to the glucocorticoid receptor, encoded by the NR3C1 gene. Studies suggest strong associations between stress and epigenetic modulation of the NR3C1 gene.11 This, and other similar pathways, may influence immune function and other critical areas of development over time.
Heightened oxidative stress has been implicated in pediatric disorders such as asthma, protein-energy malnutrition, and diarrheal diseases.12 Micronutrients serve a central role in the body’s antioxidant defense system, either directly as antioxidants, such as vitamins C, A, and E, or indirectly as cofactors of antioxidant enzymes, such as copper, zinc, and manganese.13 For those children receiving the nutrition intervention, researchers proposed that adequate antioxidant support helped positively impact stress response regulation.
Many variables may impact how an individual responds to and processes stress of any kind. Acute and transient stress may have a very different, including potentially beneficial, effect compared with chronic high stress, which is a risk factor for many diseases.14
Study authors note that all mechanisms by which nutrition modulates the HPA axis are not yet fully understood.5 More research is needed to articulate the complex relationship between nutrition, infection, psychosocial factors, and the underlying physiological stress response development.
— Heather Davis, MS, RDN, LDN, is editor of Today’s Dietitian.
References
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2. Bui T, Zackula R, Dugan K, Ablah E. Workplace stress and productivity: a cross-sectional study. Kans J Med. 2021;14:42-45.
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14. Epel ES. The geroscience agenda: toxic stress, hormetic stress, and the rate of aging. Ageing Res Rev. 2020;63:101167