Introduction

The knowledge gained on the human genome at the turn of this millennium, plus that acquired on the genomes of dozens of other species in the following 2 years, has rapidly improved our understanding of nutrition (Aparicio et al, 2002).

Genomics, proteomics, and other rapidly developing fields of biochemistry are providing new knowledge on chemical compounds that define the activities of living organisms, namely receptors, transcription factors, enzymes, and so forth. These work between the genes and the nutritional promoters (nutrients and other food components). It might be said that nutrigenomics is the study of the molecular relationships between nutritional stimuli and the response of the genes.

Nutrition and gene interactions

Nutrition depends not only on food consumption but on energy expenditures such as basal metabolic rate, physical activity, body composition, and metabolic conditions. Nutritional differences exist between individuals, different age groups, different life styles, and under different food consumption conditions. The nutrition–health relationship depends on the way the adaptive capacity of the metabolic system adjusts. This adjustment is easier the more the food consumed agrees with the functional capacity of metabolic genes and messengers. The greater the efficiency of the system, the lower the wear—and better the health enjoyed over longer periods of time.

Humans need to daily nourish about 3 10¹² cells in a balanced way. Each type of cell has distinct characteristics, frequently with large metabolic differences. A balance has to be struck between the quantity and quality of nutrients consumed and the capacity of genes to respond—most genes work in groups as coordinated networks, since this is the only way to metabolise nutrients rapidly (Guet et al, 2002).

With very few exceptions, there is full compatibility between the genetic, anatomic, and metabolic structure of organisms, and the diets provided by their food niches. This balance between food, metabolism, and genes is true not only in terms of essential nutrients but also with regard to many other important compounds, for example, bioactive phytochemicals.

It is also known that nearly all species have sufficient capacity to adapt to new food sources. Under special circumstances, such as captivity, animals may eat foods that do not normally make up their diet. However, this frequently occurs at the cost of their health.

Man has progressively expanded his food niche: our intelligence and technology have made it more varied. However, our anatomical, physiological, and genetic–metabolic structure has not changed as rapidly. We are still primates and there is no more than a 2% difference between our genome and that of a chimpanzee (Hedges & Kumes, 2002). This means that 98% of our cell macromolecules are the same. Thus, both species must require roughly the same compounds. But in the modern world, Man is drifting further and further away from a primate-like diet.

Importance of nutrition–gene congruity

Most people no longer eat the diet that might be expected from their genetic structure. Our stomachs are very large, our small intestines very long and our livers enormous in order to break down and absorb very low-fat foods. The large intestine is capable of holding over 1kg of fibre—yet only a few grams reach it. And perhaps more importantly from the point of view of health, the cells receive compounds different from those they expect. This might underlie obesity, diabetes, hypertension, atherosclerosis, thrombosis, and cancer.

But noncommunicable chronic diseases are not new. Indeed, they are rather ancient—especially among members of the higher socioeconomic strata who are used to eating a lot of meat. These people did not live to reach old age—partially at least because of unknown chronic diseases. No doubt, when many noblemen died suddenly, and people said they had been poisoned, they had suffered a heart attack or a stroke. There were—and there are—no poisons capable of causing death as suddenly as described.

Genes and their transcription factors are inherited, but they are not immutable. The best known interaction between genes and food is the metabolic imprinting seen especially during the perinatal period (Waterland & Garza, 1999).

Malnutrition and metabolic imprinting

Evidence of metabolic imprinting is known in laboratory animals but several human epidemiological studies suggest that it can also occur in Man (Joseph & Kramer, 1996). What seems to affect genetic performance most is a lack of food early in life. Malnutrition affects the future human being mainly when still in the mother's womb during the first semester of pregnancy. This was shown in Dutch army recruits whose mothers had eaten very poorly while carrying them at end of the war (Stein & Susser, 1975). Poor nutrition during the last trimester is also very important—in this case, whether individuals are over- or underfed. Generally, the mother–child nutrition status affects birth weight and weight during infancy. Low weight at these times favours several chronic diseases (Barker, 1992; Leon, 1998). In a small town in Mexico, young adults who were poorly nourished when very young were found to be malnourished and to have significantly higher body weights, total and LDL cholesterol, lower HDL cholesterol, and a higher systolic blood pressure than similar young adults who received food supplements, including milk, from the womb until 10 years of age (Chávez et al, 2001).

Other nutrition–gene interactions

However, metabolic imprinting conditioned by malnutrition, and perhaps by food in general at an early age, is not the only cause of early adaptation/nonadaptation between genes and food. It is also possible that changes in the food consumption pattern between early ages and later stages of life cause nonadjustment leading to altered metabolism and, perhaps, chronic disease (León & Ben-Slomo, 1997). This may be seen more often in populations migrating from rural to urban areas, who suddenly change food consumption habits.

Among the large variety of other food–gene nonadaptation mechanisms are several described in animals, which could also perfectly well exist in Man. A mechanism that might explain many chronic diseases is the trend towards an imbalance in gene networks regulating metabolic function when confronted with a diet consistently not that of the species (Russo et al, 1996). Under such circumstances, genetic networks tend to perform in an uncoordinated manner and, to a certain extent, some enzymes begin to fail. This might explain why chronic diseases appear late in life, and why, once they occur, they cannot be cured. A clear example is the high incidence of diabetes among certain groups of Native Americans whose previous generations lived in regions with great seasonal variations in weather and food availability, and consequently in the physical efforts required to find food. The need to survive selected those metabolically able to store energy very quickly when conditions were favourable. Today, this population, under new conditions, consistently consuming foods rich in carbohydrates, fats and salt, often becomes fat, has insulin resistance, and runs serious risks of developing more serious diseases (Cruickshank, 1989). Perhaps, this mechanism of selection and transgenerational adaptation works only in the early years of life—the so-called metabolic window—and through the above-mentioned genetic imprinting phenomenon. Perhaps, it also operates at different stages of life, with a continuing effect caused by food consumption pattern changes.

Gene silencing may be important in many health and disease situations. Usually, cells silence exogenous DNA or RNA molecules, whether viral, transposons or aberrant. DNA methylation may also be involved in access restriction to some nutrients This might involve the DNA protein binding function (Plasterk, 2002).

Genetic compensation may also be important and perhaps useful in many chronic diseases. Some vitamins or phytochemicals, such as folic acid, can replace or compensate for the functions of dysfunctional or absent genes (Kappen, 2002).

Phenomena such as gene–nutrient feedback, the occurrence of metabolic windows (Joseph & Kramer, 1996), the presence of gene multiplication by cell reproduction or polyploidisation (Couzin, 2002) may also be important.

The possibilities of transgenic foods

Of great significance in nutrition is the lateral transfer of genes—artificially caused by recombinant genes used to change the organoleptic or nutritional characteristics of foods (Bouis et al, 2002). Currently, most recombinant foods have been made for economic reasons, but some genes have already been identified that might help achieve better quality or higher nutritional value. Recombinant genes might also be implanted in people to better adapt them to a given diet, for instance to people suffering from certain chronic diseases such as diabetes. These genes might also be used for prevention purposes.

There are reports suggesting that in soy beans, wheat, and corn, several changes have been introduced for digestibility, higher nutritional value, and even acceptance by consumers. The literature mentions about 70 modified foods (Khush, 2002). Some might be taken as nearly 'perfect', such as a variety of soy that is free of stachyose and other gas-producing carbohydrates, but high in methionine and isoflavones, and easy to cook. Similar changes have been achieved with corn and rice. There are also certain fruits that have been engineered to have shelf lives of several weeks.

The best diet for human genes

Many recent studies provide much detail on what they consider the best foods for Man. Currently, it is thought that we should eat a lot of fruits and vegetables, and that cereals should be whole-grain because of their fibre and phytochemical content (Expert Panel of American Institute for Cancer Research, 1997). It is also known that sugars and starches with high glycaemic indices, such as those found in refined cereals, potatoes, and other roots, are undesirable, as is a lot of fat, especially saturated or trans fatty acids (Willett, 2001).

Human diets should essentially be vegetarian. Humans need to match then food intake to their genes. Fortunately, they are able to adapt—although insufficiently, perhaps not so easily—to other kinds of food consumption patterns. Clearly, it is relatively easy to adapt to sugars and starches, but less so to fats, meat, and salt. Despite many epidemiological studies of the cohort type, it is not fully known which foods can be tolerated and in what quantities they should to be taken (Blot et al, 1993). Quite possibly, moderate quantities of most of the usual animal-origin foods can be tolerated, especially in the case of white meat, fish, eggs, and the milk of other mammals. These foods can be freely consumed over the first 2 years of life and possibly for longer.

It is very likely that genes could resist for some time an excess of refined products including foods rich in starches, sugars, and fat. These products, and salted products, are very palatable to most population groups all over the world and (in fact, by all primates), perhaps because of the low-energy concentration and lack of salt in their original diet.

The future of nutrigenomics

Recent molecular biology studies show that the so-called modern food consumption pattern is different from Man's original food niche. Most of what is now on offer may be basically incompatible with our genes and the entire machinery depending on them. This, plus our prolonged life expectancy, increases the chance of developing some type of chronic disease. This may be the reason for obesity, diabetes, cancer, and atherosclerotic disease occurring in times of abundance.

In the short term, nutrigenomics will undoubtedly discover new, tasty, readily acceptable, and more appropriate foods. It should also help us find nutraceutic phytochemicals to compensate for imbalances due to either foods or genes. It may also be possible to transfer genes to people with certain deficiencies.

Perhaps, the most important problem of these biotechnological solutions is that they may only favour members of the more affluent social groups and countries. The future of large populations in less developed areas of the world is less positive. For a long time, these will undoubtedly have to subsist on refined cereals poorly supplemented with other foods. Unfortunately, most of these are not those required by the genes of a primate species such as ourselves.

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