 | This article may present fringe theories, without giving appropriate weight to the mainstream view and explaining the responses to the fringe theories.(August 2024) |
Nutritional epigenetics is a science that studies the effects of nutrition on gene expression and chromatin accessibility. [1] [2] It is a subcategory of nutritional genomics that focuses on the effects of bioactive food components on epigenetic events. [3]
Changes to children’s genetic profiles caused by fetal nutrition have been observed as early as the Dutch famine of 1944-1945. [4] [5] [6] [7] [8] 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. [4] [5] [6]
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. [9] [10]
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. [10] [11] [12] Nutrients and bioactive food components affect epigenetics by inhibiting enzymatic activity related to DNA methylation and histone modifications. [13] 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. [14] 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. [1]
DNA methylation is the addition of a methyl group on a cytosine ring of DNA. [15] Without methylation, issues could arise regarding genomic imprinting, X-chromosome inactivation, and suppression of transcription and transposition. [15] 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. [3] Dietary methyl supplements such as extra folic acid and choline can also have adverse effects on epigenetic gene regulation. [1] [10]
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. [16] 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. [17] In DNA methylation, folate serves as a source of carbon/ methyl group. [18]
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. [19] Choline can be found in animal products such as meat, eggs, poultry, fish and dairy as well as potatoes and green leafy vegetables. [20]
Researchers have considered that high-fat and low-protein diets during pregnancy can increase the risk of obesity in infants. [21] The consumption of phytochemicals can also positively affect epigenetic-based mechanisms that inhibit cancer cells. [22] Research has also suggested a link between nutritional epigenetics and the pathophysiology of major depressive disorder. [23]
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. [12] 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. [12] [8] 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. [7]
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. [7] 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. [7] [12]
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. [24] 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. [25] [26] 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). [27]
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. [28] [8] 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. [29]
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. [30] [31] 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. [32] Dietary methyl supplements such as extra folic acid and choline can also have adverse effects on epigenetic gene regulation. [1] [10] 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. [33] 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. [34]
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. [35] 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. [35] Despite the best practices in use, heavy metal and pesticide residues are still found in the food supply. [36] [37] 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. [38] Prenatal organophosphate pesticide exposure has been shown to impact DNA methylation in genes associated with the development of cardio-metabolic diseases. [39] 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. [40]
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division and maturation of blood cells. As the human body cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements.
A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources, or that are synthetic. The classes of nutrient compounds in supplements include vitamins, minerals, fiber, fatty acids, and amino acids. Dietary supplements can also contain substances that have not been confirmed as being essential to life, and so are not nutrients per se, but are marketed as having a beneficial biological effect, such as plant pigments or polyphenols. Animals can also be a source of supplement ingredients, such as collagen from chickens or fish for example. These are also sold individually and in combination, and may be combined with nutrient ingredients. The European Commission has also established harmonized rules to help insure that food supplements are safe and appropriately labeled.
Choline ( KOH-leen) is an essential nutrient for humans and many other animals, which was formerly classified as a B vitamin (vitamin B4). It is a structural part of phospholipids and a methyl donor in metabolic one-carbon chemistry. The compound is related to trimethylglycine in the latter respect. It is a cation with the chemical formula [(CH3)3NCH2CH2OH]+. Choline forms various salts, for example choline chloride and choline bitartrate.
A maternal effect is a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother. In genetics, maternal effects occur when an organism shows the phenotype expected from the genotype of the mother, irrespective of its own genotype, often due to the mother supplying messenger RNA or proteins to the egg. Maternal effects can also be caused by the maternal environment independent of genotype, sometimes controlling the size, sex, or behaviour of the offspring. These adaptive maternal effects lead to phenotypes of offspring that increase their fitness. Further, it introduces the concept of phenotypic plasticity, an important evolutionary concept. It has been proposed that maternal effects are important for the evolution of adaptive responses to environmental heterogeneity.
Trimethylglycine is an amino acid derivative that occurs in plants. Trimethylglycine was the first betaine discovered; originally it was simply called betaine because, in the 19th century, it was discovered in sugar beets.
Nutritional genomics, also known as nutrigenomics, is a science studying the relationship between human genome, human nutrition and health. People in the field work toward developing an understanding of how the whole body responds to a food via systems biology, as well as single gene/single food compound relationships. Nutritional genomics or Nutrigenomics is the relation between food and inherited genes, it was first expressed in 2001.
Nutrition and pregnancy refers to the nutrient intake, and dietary planning that is undertaken before, during and after pregnancy. Nutrition of the fetus begins at conception. For this reason, the nutrition of the mother is important from before conception as well as throughout pregnancy and breastfeeding. An ever-increasing number of studies have shown that the nutrition of the mother will have an effect on the child, up to and including the risk for cancer, cardiovascular disease, hypertension and diabetes throughout life.
Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo begin to change shape and form the neural tube. When the neural tube does not close completely, an NTD develops.
Agouti-signaling protein is a protein that in humans is encoded by the ASIP gene. It is responsible for the distribution of melanin pigment in mammals. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte produces phaeomelanin, or eumelanin. This interaction is responsible for making distinct light and dark bands in the hairs of animals such as the agouti, which the gene is named after. In other species such as horses, agouti signalling is responsible for determining which parts of the body will be red or black. Mice with wildtype agouti will be grey-brown, with each hair being partly yellow and partly black. Loss of function mutations in mice and other species cause black fur coloration, while mutations causing expression throughout the whole body in mice cause yellow fur and obesity.
Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. This may result in megaloblastic anemia in which red blood cells become abnormally large, and folate deficiency anemia is the term given for this medical condition. Signs of folate deficiency are often subtle. Symptoms may include fatigue, heart palpitations, shortness of breath, feeling faint, open sores on the tongue, loss of appetite, changes in the color of the skin or hair, irritability, and behavioral changes. Temporary reversible infertility may occur. Folate deficiency anemia during pregnancy may give rise to the birth of low weight birth premature infants and infants with neural tube defects.
Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have few or absent symptoms. In moderate deficiency, feeling tired, headaches, soreness of the tongue, mouth ulcers, breathlessness, feeling faint, rapid heartbeat, low blood pressure, pallor, hair loss, decreased ability to think and severe joint pain and the beginning of neurological symptoms, including abnormal sensations such as pins and needles, numbness and tinnitus may occur. Severe deficiency may include symptoms of reduced heart function as well as more severe neurological symptoms, including changes in reflexes, poor muscle function, memory problems, blurred vision, irritability, ataxia, decreased smell and taste, decreased level of consciousness, depression, anxiety, guilt and psychosis. If left untreated, some of these changes can become permanent. Temporary infertility, reversible with treatment, may occur. A late finding type of anemia known as megaloblastic anemia is often but not always present. In exclusively breastfed infants of vegan mothers, undetected and untreated deficiency can lead to poor growth, poor development, and difficulties with movement.
Metabolic imprinting refers to the long-term physiological and metabolic effects that an offspring's prenatal and postnatal environments have on them. Perinatal nutrition has been identified as a significant factor in determining an offspring's likelihood of it being predisposed to developing cardiovascular disease, obesity, and type 2 diabetes amongst other conditions.
Nutritional neuroscience is the scientific discipline that studies the effects various components of the diet such as minerals, vitamins, protein, carbohydrates, fats, dietary supplements, synthetic hormones, and food additives have on neurochemistry, neurobiology, behavior, and cognition.
Nutriepigenomics is the study of food nutrients and their effects on human health through epigenetic modifications. There is now considerable evidence that nutritional imbalances during gestation and lactation are linked to non-communicable diseases, such as obesity, cardiovascular disease, diabetes, hypertension, and cancer. If metabolic disturbances occur during critical time windows of development, the resulting epigenetic alterations can lead to permanent changes in tissue and organ structure or function and predispose individuals to disease.
Relatively speaking, the brain consumes an immense amount of energy in comparison to the rest of the body. The mechanisms involved in the transfer of energy from foods to neurons are likely to be fundamental to the control of brain function. Human bodily processes, including the brain, all require both macronutrients, as well as micronutrients.
Developmental origins of health and disease (DOHaD) is an approach to medical research factors that can lead to the development of human diseases during early life development. These factors include the role of prenatal and perinatal exposure to environmental factors, such as undernutrition, stress, environmental chemical, etc. This approach includes an emphasis on epigenetic causes of adult chronic non-communicable diseases. As well as physical human disease, the psychopathology of the foetus can also be predicted by epigenetic factors.
Randy Jirtle is an American biologist noted for his research in epigenetics, the branch of biology that deals with inherited information that does not reside in the nucleotide sequence of DNA. Jirtle retired from Duke University, Durham, NC in 2012. He is Professor of Epigenetics in the Department of Biological Sciences at North Carolina State University, Raleigh, NC, and Senior Visiting Scientist at the McArdle Laboratory of Cancer Research, University of Wisconsin, Madison, WI. Jirtle is noted for his research on genomic imprinting, and for his use of the Agouti mouse model to investigate the effect of environmental agents on the mammalian epigenome and disease susceptibility.
Epigenetic effects of smoking concerns how epigenetics contributes to the deleterious effects of smoking. Cigarette smoking has been found to affect global epigenetic regulation of transcription across tissue types. Studies have shown differences in epigenetic markers like DNA methylation, histone modifications and miRNA expression between smokers and non-smokers. Similar differences exist in children whose mothers smoked during pregnancy. These epigenetic effects are thought to be linked to many of negative health effects associated with smoking.
Gene-environment interplay describes how genes and environments work together to produce a phenotype, or observable trait. Many human traits are influenced by gene-environment interplay. It is a key component in understanding how genes and the environment come together to impact human development. Examples of gene-environment interplay include gene-environment interaction and gene-environment correlation. Another type of gene-environment interplay is epigenetics, which is the study of how environmental factors can affect gene expression without altering DNA sequences.
The first 1,000 days describes the period from conception to 24 months of age in child development. This is considered a "critical period" in which sufficient nutrition and environmental factors have life-long effects on a child's overall health. While adequate nutrition can be exceptionally beneficial during this critical period, inadequate nutrition may also be detrimental to the child. This is because children establish many of their lifetime epigenetic characteristics in their first 1,000 days. Medical and public health interventions early on in child development during the first 1,000 days may have higher rates of success compared to those achieved outside of this period.