Nutritional epigenetics

Nutritional epigenetics is a science that studies the effects of nutrition on gene expression and chromatin accessibility. It is a subcategory of nutritional genomics that focuses on the effects of bioactive food components on epigenetic events.

History
Changes to children’s genetic profiles caused by fetal nutrition have been observed as early as the Dutch famine of 1944-1945. Due to malnutrition in pregnant mothers, children born during this famine were more likely to exhibit health issues such as heart disease, obesity, schizophrenia, depression, and addiction.

Biologists Randy Jirtle and Robert A. Waterland became early pioneers of nutritional epigenetics after publishing their research on the effects of a pregnant mother’s diet on her offspring’s gene functions in the research journal Molecular and Cellular Biology in 2003.

Research
Researchers in nutritional epigenetics study the interaction between molecules in food and molecules that control gene expression, which leads to areas of focus such as dietary methyl groups and DNA methylation. Nutrients and bioactive food components affect epigenetics by inhibiting enzymatic activity related to DNA methylation and histone modifications. Because methyl groups are used for suppression of undesirable genes, a mother’s level of dietary methyl consumption can significantly alter her child’s gene expression, especially during early development. Furthermore, nutrition can affect methylation as the process continues throughout an individual’s adult life. Because of this, nutritional epigeneticists have studied food as a form of molecular exposure.undefined

DNA methylation is the addition of a methyl group on a cytosine ring of DNA. Without methylation, issues could arise regarding genomic imprinting, X-chromosome inactivation, and suppression of transcription and transposition. When methylation is not present to suppress transcription and transposition, the lack thereof can contribute to the development of cancer.

Bioactive food components that influence epigenetic processes range from vitamins such as A, B6, and B12 to alcohol and elements such as arsenic, cadmium, and selenium. Dietary methyl supplements such as extra folic acid and choline can also have adverse effects on epigenetic gene regulation.

Folate is an essential water soluble vitamin that is naturally occurring in some foods. Folate can be found naturally at high levels in dark green leafy vegetables such as spinach, brussels sprouts and asparagus, as well as in liver. Folic acid is a man made form used to supplement certain foods. Enriched breads, flours, pastas, rice, and breakfast cereals are commonly supplemented with folic acid. In DNA methylation, folate serves as a source of carbon/ methyl group.

Choline is a semi-essential nutrient that can be oxidized to betaine. The betaine then functions as a methyl group donor in the process of DNA methylation. Choline can be found in animal products such as meat, eggs, poultry, fish and dairy as well as potatoes and green leafy vegetables.

Researchers have considered dietary exposure to heavy metals such as mercury and lead primary epigenetic factors leading to increased autism and attention deficit hyperactivity disorder. High-fat and low-protein diets during pregnancy can also increase the risk of obesity in infants. The consumption of phytochemicals can also positively affect epigenetic-based mechanisms that inhibit cancer cells. Research has also suggested a link between nutritional epigenetics and the pathophysiology of major depressive disorder.

Nutritional-Environmental Signals
All life on Earth is influenced by the different flows of its environment, yet in humans, different environmental conditions such as poverty, alcohol, stress, malnutrition, exposure to pollutants, man-made chemicals, and synthetic drugs can lead to epigenetic-related illnesses/diseases with certain disease-specific genes typically being activated or deactivated. The epigenome of an organism can be triggered by just about any environmental signal, including climate change, food/water supply, plant nutrient, temperature etc.

It has been estimated that more than 60% of deaths in humans are related to nutritional or dietary factors rather than environmental triggers. Based on a couple of studies from the Dutch Famine of 1944-1945, it is stated that starvation during pregnancy and subsequent health can result in, but not limited to a some health risks including type II diabetes mellitus, cardiovascular disease, metabolic disorders and decreased cognitive functions later in life.

The maternal lineage or mother's health and nutritional habits during pregnancy isn't the only influence on the offspring's overall health. Further transmission via the paternal line is highly likely to occur by epigenetic modulation of the spermatozoa's nucleus. An example of this is transgenerational transmission by the paternal lineage. There is evidence that both the paternal and maternal diets influence metabolic phenotypes in the offspring through epigenetic information transmission.

Epigenetic Stressors
Evidence of the generational transmission of epigenetic mechanisms in humans was first discussed by Champagne in 2008 in the context of maternal stress with food insecurity being one type of stressor that can impact gene expression via changes in DNA methylation patterns. Another type of stressor is a poor prenatal diet that results in nutritional insufficiency and fetal epigenetic reprogramming that creates the blueprint for the development of diseases later in a child’s life. Depending on geographical region, food quality issues may impact epigenetic inheritance via changes in methylation patterns associated with dietary heavy metal exposures, especially in the case of autism and attention deficit hyperactivity disorders (ADHD).

Food insecurity
Food insecurity refers to the inability to access enough food to meet basic needs and is associated with an increased risk of birth defects associated with DNA methylation patterns. An expectant mother who is food insecure will likely be under financial stress and unable to secure enough food to meet her nutritional needs. Her geographical location may be in a food desert where she is unable to access enough safe and nutritious food. Food deserts are linked to food insecurity and defined as areas of high-density fast-food restaurants and corner stores offering only unhealthy highly processed foods at low prices.

Poor prenatal diet
Poor prenatal diet or unhealthy diet has been shown to affect DNA methylation patterns and contribute to the development of type 2 diabetes, ADHD, and early onset conduct problems in children. Characteristics of an unhealthy prenatal diet leading to changes in DNA methylation patterns include the increased intake of high fat/sugar ultra-processed food products along with the inadequate intake of nutrient rich whole foods (e.g. fruits and vegetables). High-fat and low-protein diets during pregnancy can also increase the risk of obesity in infants. Dietary methyl supplements such as extra folic acid and choline can also have adverse effects on epigenetic gene regulation. The current global food system is plagued by issues that adversely affect human health through multiple pathways with contaminated, unsafe, and altered foods being one of the most common factors associated with unhealthy diet. Low iron diets, or women who suffer from an iron deficiency, have been shown to increase the likelihood of a premature birth, low birth weight, and the increased possibility of postpartum depression.

Food quality
Food quality issues vary from one geographic region to the next depending on country, food safety practices, and manufacturing and agricultural regulations regarding heavy metal, pesticide residues, and other hazardous exposures of concern. To reduce exposures to chemical hazards such as pesticide and heavy metal residues, the World Trade Organization (WTO) sponsored agreements between countries to establish codes of best practices, issued by the Codex Alimentarius Commission, that attempt to guarantee the trade of safe food. Despite the best practices in use, heavy metal and pesticide residues are still found in the food supply. Pre-natal and post-natal dietary exposures to inorganic mercury and lead residues resulting from unhealthy diets have been shown to consistently impact important gene behaviors in children with autism and ADHD. Prenatal organophosphate pesticide exposure has been shown to impact DNA methylation in genes associated with the development of cardio-metabolic diseases. Infection from food is a serious factor during pregnancy. Not in particular of what the mother eats, but that is just as important, but the way the food is prepared. A mother should cook all of the food thoroughly, especially meats. All of the produce should be washed well after washing hands. Pasteurized dairy products should be the type of dairy being consumed by the mother.

Nutritional Epigenetics Model for Autism and ADHD
Renee Dufault developed and published the first nutritional epigenetics model for autism which was initially known as the Mercury Toxicity Model in 2009. The model below shows the impact of dietary mercury (Hg) exposure on the metallothionein (MT) gene when the child is zinc (Zn) deficient.

In 2009, the United States Department of Agriculture (USDA) estimated the average American was consuming 30.4 pounds of high fructose corn syrup (HFCS) each year. Dufault linked the consumption of HFCS to zinc losses and the subsequent impairment of the MT gene which results in the bioaccumulation of mercury in blood and symptoms of autism. A recent clinical trial conducted on human subjects and published in 2020 further strengthens Dufault’s model as it verified the consumption of HFCS does in fact lead to significant zinc losses in Americans.

The term “nutritional epigenetics” was coined one year after publication of Dufault’s “Mercury Toxicity Model.” Farhud et al. described mechanisms involved in “Nutritional epigenetics” in a paper published in 2010. Dufault’s updated nutritional epigenetics model featured in the image below incorporates the constructs of Dufault’s previous models that show the role dietary lead (Pb) and Hg exposures play in PON1 gene inhibition which occurs in both autism and ADHD. Dufault’s updated nutritional epigenetics model was recently used to test a successful intervention in a clinical trial with results published in 2024. Parents of children with autism and ADHD who took part in the intervention improved their diets by significantly reducing their intake of ultra-processed foods and changed their attitude about the role of diet in controlling their child’s behaviors.