Introduction

In the past few decades, different health organizations have highlighted the growing importance of noncommunicable diseases (NCDs) on population health. NCDs, also known as chronic diseases, are not transmitted from person to person, are not acute, and cannot be treated in a short period but generally evolve slowly and tend to remain lifelong. The four main NCDs are cardiovascular disease (including heart attacks and stroke), cancer, chronic respiratory diseases (such as chronic obstructive pulmonary disease and asthma), and diabetes.

NCD impact on life expectancy

In its latest report, the World Health Organization (WHO) acknowledged the impact of deaths due to NCDs. NCDs are responsible for 36 million deaths every year. Of this death toll, nearly 80% (29 million) occur in low- and median-income countries . NCDs are considered to be the leading cause of death in all regions except Africa. However, according to the current estimates, in 2020 the largest increase in mortality from NCDs would be in Africa. The deaths from NCDs in the African countries are expected to exceed the sum of those caused by communicable and nutritional diseases and maternal and perinatal mortality. NCD would be the most common cause of death in 2030 .

In addition, >9 million deaths attributed to NCDs occur in people under 60 years of age, and 90% of these “premature” deaths occur in low- and medium-income countries. Cardiovascular diseases are responsible for most NCD deaths (17.3 million annually), followed by cancer (7.6 million), the respiratory diseases (4.2 million), and diabetes (1.3 million). These four groups of diseases account for about 80% of NCD deaths . It must be emphasized that all of them share four common risk factors: tobacco consumption, insufficient physical activity, excessive use of alcohol, and unhealthy diet.

In terms of attributable deaths, the main NCD risk factor globally is the high blood pressure (attributed to 16.5% of deaths worldwide ), followed by consumption of tobacco (9%), increased blood glucose (6%), insufficient physical activity (6%), and overweight and obesity (5%) . A rapid increase in the number of overweight children is observed in the countries with low and medium incomes.

NCDs affect all age groups and all regions. Children, adults, and seniors are all vulnerable to the risk factors predisposing to NCD, such as unhealthy diets, physical inactivity, exposure to tobacco smoke, or excessive use of alcohol. These diseases are also favored by factors such as aging, rapid and unplanned urbanization seen in certain countries, and the globalization of unhealthy lifestyles. An example of such a factor can be the unhealthy diet, which can be responsible for high blood pressure, increased blood glucose, hyperlipidemia, overweight, and obesity. These factors are called “intermediate risk factors” and they can lead to cardiovascular disease, one of the NCDs.

NCD impact on life expectancy

In its latest report, the World Health Organization (WHO) acknowledged the impact of deaths due to NCDs. NCDs are responsible for 36 million deaths every year. Of this death toll, nearly 80% (29 million) occur in low- and median-income countries . NCDs are considered to be the leading cause of death in all regions except Africa. However, according to the current estimates, in 2020 the largest increase in mortality from NCDs would be in Africa. The deaths from NCDs in the African countries are expected to exceed the sum of those caused by communicable and nutritional diseases and maternal and perinatal mortality. NCD would be the most common cause of death in 2030 .

In addition, >9 million deaths attributed to NCDs occur in people under 60 years of age, and 90% of these “premature” deaths occur in low- and medium-income countries. Cardiovascular diseases are responsible for most NCD deaths (17.3 million annually), followed by cancer (7.6 million), the respiratory diseases (4.2 million), and diabetes (1.3 million). These four groups of diseases account for about 80% of NCD deaths . It must be emphasized that all of them share four common risk factors: tobacco consumption, insufficient physical activity, excessive use of alcohol, and unhealthy diet.

In terms of attributable deaths, the main NCD risk factor globally is the high blood pressure (attributed to 16.5% of deaths worldwide ), followed by consumption of tobacco (9%), increased blood glucose (6%), insufficient physical activity (6%), and overweight and obesity (5%) . A rapid increase in the number of overweight children is observed in the countries with low and medium incomes.

NCDs affect all age groups and all regions. Children, adults, and seniors are all vulnerable to the risk factors predisposing to NCD, such as unhealthy diets, physical inactivity, exposure to tobacco smoke, or excessive use of alcohol. These diseases are also favored by factors such as aging, rapid and unplanned urbanization seen in certain countries, and the globalization of unhealthy lifestyles. An example of such a factor can be the unhealthy diet, which can be responsible for high blood pressure, increased blood glucose, hyperlipidemia, overweight, and obesity. These factors are called “intermediate risk factors” and they can lead to cardiovascular disease, one of the NCDs.

Impact of NCDs on national and global economy

NCDs threaten the progress towards the target of the Millennium Development Goals of the United Nations . Poverty is closely related to the NCDs. It is anticipated that the rapid rise of these diseases will hinder efforts to reduce poverty in low-income countries, because of the increased family expenses for health care. Vulnerable and socially disadvantaged people fall sick and die earlier than people of higher social status, mainly because of the higher risk of exposure to harmful products, such as tobacco or unhealthy foods, and limited access to health services . In resource-poor settings, the health-care expenses for cardiovascular disease, cancer, diabetes, and chronic lung disease, as stated, can quickly exhaust the resources of families and force them into poverty. The exorbitant costs of NCDs, particularly prolonged and expensive treatment, or the demise of the breadwinner, are pushing millions of people into poverty each year, preventing the progress of the country and the society. National economies are suffering considerable losses due to premature death or disability to work resulting from heart disease, stroke, and diabetes. For example, it is expected that India and China will lose about $558 billion from their gross domestic product (GDP) between 2005 and 2015 due to premature deaths . In 2005, heart disease, stroke, and diabetes caused an estimated loss of $9 billion in India and $3 billion in Brazil from the GDP . A study commissioned by the World Economic Forum concluded that the world will sustain a cumulative output loss of $47 trillion between 2011 and 2030 because of NCDs and mental illnesses, about $30 trillion of which will be attributable to cardiovascular diseases, cancers, chronic pulmonary diseases, and diabetes .

Combating NCDs

In many countries, the excessive use of alcohol and consumption of unhealthy foods are affecting both high-income and low-income groups. However, the former can access products and services that protect them from the major risks, while low-income groups are often unable to afford it.

To reduce the impact of NCDs on individuals and the society, we should apply a comprehensive approach that reinforces all sectors, including those related to health, finance, foreign affairs, education, and agriculture and planning, to work together to reduce the risks associated with NCDs and to promote strategies and intervention to prevent and control them.

An important tactic to reduce NCDs is to reduce the risk factors associated with these diseases. Effective and low-cost solutions exist to modify common risk factors (mainly tobacco consumption, unhealthy diets and physical inactivity, and excessive use of alcohol) and to map the epidemic of NCDs and their risk factors .

Another option to combat NCDs is to introduce some essential high-impact interventions with the focus on the primary care in order to improve their early detection and timely treatment. Evidence shows that such interventions are also excellent financial investment, as they can reduce the need for more expensive treatments if introduced early. These measures may also be applied in situations with different levels of resources. For maximum effect, the public policies have to focus on a healthy lifestyle that promotes the prevention and control of NCDs, and reorienting health systems to meet the needs of people suffering from these diseases. However, one must acknowledge that low-income countries tend to have a low capacity for prevention and control of NCDs .

Developmental origins of health and disease

In the past decades, various research areas have suggested that events involved in normal fetal development could have long-term effects and influence health in adulthood . It appears that metabolic changes in utero can influence the physiological and structural patterns that “program” long-term health in adulthood . Early studies by Barker et al. in the 1980s established that the prevalence of some diseases in adulthood, such as atherosclerosis, high blood pressure (hypertension), stroke, type 2 diabetes mellitus, and dyslipidemia are related to the intrauterine environment (“Barker hypothesis”). Moreover, the association has been reported between low weight and height at birth, with an increased risk of subsequently developing diseases such as hypertension, metabolic syndrome, and stroke . Other studies have confirmed this relationship and currently are trying to reveal some of the mechanisms behind it . On an experimental level, for example, nutritional restriction during pregnancy has been shown to irreversibly affect the structure, metabolism, and function in some organs, “programming” their future offspring to develop certain diseases . The result of this research is that today we can talk about the fetal origins of many adult diseases (Developmental Origins of Health and Disease, DOHaD) . Animal experiments and epidemiological observations in humans suggest that nutrition received in the intrauterine environment modulates the metabolic activity of various tissues in postnatal life . An important consequence of intrauterine caloric and nutrient restriction is the accelerated growth in the postnatal period .

In fact, during periods of development, certain epigenetic modifications take place that establish the parameters within which the tissue functions. It should be mentioned that the functional changes made by epigenetic influences need not be phenotypically (physically) visible in order to be significant; however, they usually have long-term health consequences. These functional changes cannot be reliably detected by conventional testing and are observed only when they match certain environmental contexts and are likely to be initially masked by systemic effects.

This developmental plasticity is more important during periods in which the cells are differentiating and forming specific tissues, as happens mainly during pregnancy (for both mother and child), and during early childhood, puberty, and menopause. DOHaD hypothesize that environmental exposures during critical periods of development may cause subtle changes in certain biological functions, although practically invisible, and can increase the risk of disease and dysfunction later in life .

Some of the most striking evidence of developmental plasticity that were also first to be discovered came from the analysis of the consequences of prolonged periods of famine. The Dutch conceiving in the time of famine during the war of 1944–1945 were more likely to develop metabolic syndrome in adulthood . Subsequent research has also confirmed these findings in Chinese famine victims . In both groups, the offspring were more likely to have hypertension, glucose intolerance, and excess weight gain.

The epigenetic programming

The discovery of the epigenetic programming has provided a plausible explanation why and how nutritional characteristics during critical periods of life can have health manifestations much later. At present, there are a number of examples in animal models of how changes in the diet can directly influence the epigenetic machinery by inhibition of enzymes that catalyze the DNA methylation, by histone modifications, or by altering the availability of substrates for enzymatic reactions. These epigenetic alterations cause the expression or suppression of certain genes that can alter the phenotype, depending on the nature of the affected biological process. Epigenetic changes can be both transient or persistent for long periods of time .

Epigenetic phenomena are fundamental features of mammalian development that causes persistent changes in gene expression without altering the DNA sequence. In this way, epigenetic mechanisms shape the phenotype of a cell without changing the genotype. Although causality has not been fully established, epigenetics provides information on the possible mechanisms in utero that may cause a predisposition to diseases in adult life. During development, epigenetic mechanisms may undergo substantial changes caused by various factors. These changes affect genes that are essential for both the development early in life as well as later physiological functions in adult life. An important fact is that epigenetic modifications are stable during cell division and can be transmitted to the next generation. There is increasingly more evidence suggesting that exposure to nutritional imbalances or environmental contaminants – including metals, pesticides, and persistent organic pollutants and chemicals in drinking water, as triethyltin, chloroform, and trihalomethanes – can cause changes in epigenetic mechanisms and this could provide an explanation for their effects on adult health .

The epigenetic, in this sense, can also be understood as a mechanism by which organisms can survive in an unpredictable and changing environment. The fastest adaptation to the environment comes from the immediate demand to maintain the homeostasis – the processes by which the body maintains a constant internal environment in response to external changes, often increasing energy expenditure. These processes are governed mainly by hormonal and neural signals. The other end of the spectrum of evolutionary change is adaptive, that is, long-term adaptations of species that are driven by genetic change and therefore resulting in survival or demise.

The epigenetic can insert influence by turning on and off the gene transcription. Transcription is the process by which an RNA copy of a gene is made, and this RNA copy then governs the cell machinery for the production of a specific protein. The addition or removal of a methyl group to a gene is a way of influencing this process, if a certain gene can be transcribed into RNA and, therefore, whether or not to produce the corresponding protein. Thus, methylation in a group of genes may cause changes in many biological processes occurring in the body and affect the metabolism, causing energy expenditure or conservation. This process could be also responsible for more specific aspects such as eye color or skin.

The discovery of noncoding small RNAs has opened up a new field of microRNAs, which also play an important role in epigenetics by modifying gene expression posttranscriptionally . MicroRNAs indirectly affect translation of key factors or enzymes required for epigenetic processes in the nucleus.

What is also remarkable is that these changes in programming are largely functional. They include alterations in gene expression, protein levels, cell metabolism and differentiation, and the number of cells and their location. Functional changes are not necessarily identifiable as pathological but, due to the changes in gene expression, can lead to dysfunction and disease in adulthood. In such a case, they can be considered as markers of an increased risk of NCDs. As already mentioned, the functional changes are not necessarily apparent at the time of birth and, in some cases, may require a particular environmental or physiological trigger in order to be revealed. For example, certain subtle changes in breast tissue can increase significantly the risk of tumor growth in middle-aged patients without children . A clear positive association between breast cancer and higher birth weight, birth length, and placental weight was reported. Further epidemiologic studies have confirmed these findings. For women who weighed 3500–3999 g at birth, the adjusted odds ratio for breast cancer is 0.86. In comparison, in women with birth weight <2500 g, the adjusted odds ratio is reduced to 0.5 . Another example (as found in famine situations) is that certain changes in some specific metabolic set points can only be established when some types of diet are predominantly used (this could be the reason that fast food, modern lifestyle, and certain chemical exposures may be the perfect “recipe” for obesity).

The essential concept of “gestational programming” means that the nutritional, hormonal, and metabolic environment provided by the mother to the fetus could permanently alter the structure and the cellular responses of various organs, and alter the expression of certain genes that ultimately affect the metabolism and physiology of the offspring. Moreover, these effects vary according to the period of development, and, as such, fetuses and newborns (rapidly growing) are the most vulnerable.

The effects on programming can have immediate effects, for example, the deterioration of organ growth at a critical stage, while other effects are delayed and not apparent until later. In this case, the question is how the memory of the early events is stored and how it is expressed later, despite the continuous cell replication and replacement. This again could be mediated through an epigenetic control of gene expression, which involves modifying the genome without altering the proper sequence of DNA .

In addition, there is currently some controversy if certain nutrients can also modify the programming of the immune systems . Certain dietary patterns increase the risk of altering the immune mechanisms along with metabolic dysregulation and increase the risk of a wide range of NCDs. Besides changes in the nutrients profile and their caloric load, diet-induced changes in the intestinal microflora may also be involved in the pathogenesis and increased susceptibility to many chronic diseases. In this context, it is highly relevant that allergic diseases are one of the first NCDs that may appear. Preventive strategies can, in this sense, enhance immune and metabolic health.

It must be acknowledged that to date most of the research on epigenetic mechanisms induced by nutrients has focused on the identification of single specific genes that somehow limit the complete picture of nutritional effects on the entire epigenetic landscape. Using a genome-wide approach has the advantage and the potential ability to discover the targets of certain novel epigenetic mechanisms, which are sensitive to a specific diet modification.

As observed in other studies of epigenomic associations, epigenetic mechanisms of allergic diseases constitute a major challenge to be studied in greater depth, that is, whether epigenetic variation is the cause or consequence of the disease. However, clarification of the potential link between epigenetic changes in allergic diseases could offer new opportunities for diagnosis and/or therapy.

In addition, our biggest challenge is to identify the stages in the life cycle where the epigenetic machinery is more sensitive to a particular dietary factor in relation to subsequent health outcomes, so that prevention strategies based on changes in the diet could produce maximum benefit. It is important to note that the multiple and complex multisystem interactions require the implementation of an interdisciplinary approach to overcome the growing burden of NCDs.