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2 Accomplishments in the Nutrition and Food Sciences Throughout history, people have observed connections between food and health. In 400 B.C., Hippocrates wrote of the relationship between diet and health. One hundred years later, beriberi was described in Chi- nese texts, as were other nutrient-deficiency diseases in early writings. Hippocrates and GaTen often used the word diet, but the term nutrition did not come into popular use until the latter half of the nineteenth century. The concept of nutrition that human beings require a steady intake of specific components of food in defined amounts is thus clearly a modern one. Foocl science and technology are concerned with the ve- hicle food in which essential and desirable food components are deliv- ered to the body in adequate amounts and in safe, acceptable forms. The earliest efforts in nutrition science are often attributed to Antoine Lavoisier. This French chemist demonstrated in 1789 that oxygen breathed in from the air is used by the body to produce carbon dioxide and water in what we know today as the central metabolic process in which food is "burned" to provide the energy needecl for all bodily functions. Lavoisier showed that the amount of oxygen used was related to the amount of food consumed and the amount of physical activity. Later, other scientists ob- served that citrus fruits prevented scurvy, iodine prevented goiter, and unmilled rice prevented beriberi. Canning was invented and added to the processor's means of preserving foocl, along with the traditional fermenta- tion, drying, and salting. Louis Pasteur developed the process of pasteur- ization, which saved countless lives and provided milk in a safe and palat 27
as OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES able form. It was only early in this century, however, that scientists de- fined human nutritional requirements, identifying the amino acids, vita- mins, fatty acids, and minerals in foods essential to health. Diseases such as scurvy, beriberi, rickets, and pellagra were found to be caused by vita r. . mln c ~etlclencles. After World War II, people in the United States were generally eating better, thanks to improved transportation systems (which made a wider variety of foods available), home refrigeration, frozen foods, and nutrient- fortified foods such as bread and milk. The war stimulated improvements in dehydration, heat processing, and other technologies to minimize spoil- age of food while maintaining quality and taste. Nutrient-deficiency dis- eases became much less prevalent in the United States and other industri- ali%ed countries. For several decades, nutrition scientists have been examining the re- lationships of modern dietary patterns to deadly chronic diseases such as heart and blood vessel diseases, cancer, and diabetes. Responding to the dietary guidelines developed by the nutrition community, food scientists have developed a wide range of technologies to lower the fat, salt, and sugar in food. In addition, they have developed and implemented a variety of quality control procedures to make processed foods generally safe and of high quality. As the nutrition and food sciences have evolved and expanded in this century, they have assumed a growing role in public policy. By 1979, the federal government was involved in more than 350 programs to ensure an adequate and safe food supply for consumers. These programs covered areas such as support to farmers, food safety and regulation, food fortifi- cation, food assistance, nutrition services and training, monitoring of food intake and nutritional status, food and nutrition research, and food and nutrition education. In the past several decades, the federal government has become the largest funder of research in the nutrition and food sciences, now contrib- uting more than $400 million dollars annually. Much of that research is conducted in academic laboratories at colleges and universities. The land- grant colleges and universities (with their focus on agriculture, rural com- munities, and the needs of consumers) have been largely responsible for the growth of the nutrition and food sciences in the United States. Much of the research in these disciplines has been conducted in departments of animal science, food science, and nutrition in schools of agriculture and home economics. Increasingly, research on diet's role in chronic disease is conducted by scientists in medical schools and schools of public health. Fundamental nutrition research is now conducted as well in more general university and professional school departments. Today, government at all levels, the private sector (particularly the food industry), biomedical re
ACCOMPLISHMENTS IN THE NUTRITION AND FOOD SCIENCES 29 searchers, health-care practitioners, foundations, and others are working individually and together to support research in the nutrition and food sciences, to bring the fruits of that research to the public, and to use it to develop programs and policies that will improve the health of the public. As we rapidly approach a new century, new challenges in the nutrition and food sciences are emerging. Research opportunities that await us in- clude defining and determining "optimal" nutrition (ensuring maximal health and resistance to disease throughout the lifespan), determining the role of nutrition in the expression of our genetic material, learning the role of important substances in food (such as fiber and carotenoids) that are not traditional essential nutrients, and developing more effective strategies for promoting healthful dietary change. To meet these new challenges, the science of human nutrition is becoming more interdisciplinary, draw- ing on food science, biochemistry, molecular biology, genetics, physiology, toxicology, epidemiology, and the social and behavioral sciences (such as sociology, psychology, anthropology, and political science) to understand the role of human nutrition in health and disease. EXAMPLES OF ACCOMPLISHMENTS AND CHALLENGES In the remainder of this chapter, we present examples of how re- search in the nutrition and food sciences has led to discoveries and appli- cations that have substantially improved the health and well-being of people throughout the world. Chapters 3 through 6 describe future research on ·. - 1 1 11 1 ~ portun~es anct cnai~enges that stem from these accomplishments. There are many examples that might be chosen to illustrate the ac- complishments of the nutrition and food sciences. The following eight are representative examples and are organized around three topics: the inter- actions of genes with nutrients, improving the food supply, and nutrient delivery and nutritional assessment. Further research in each of these areas is likely to result in improved health, greater resistance to disease, and better treatments for disease. - 1 Gene-Nutrient Interactions Iron Iron, a constituent of hemoglobin in red blood cells, is essential for carrying oxygen from the lungs to all the body tissues. Several crucial enzymes involved in general metabolism require iron as well. Iron defi- ciency remains one of the most common nutritional deficiencies around the world. Groups most subject to deficiency are pregnant women, in- fants, children, and menstruating women. Iron deficiency impairs physical
30 OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES NOBEL PRIZES FOR RESEARCH APPLICABLE TO THE NUTRITION AND FOOD SCIENCES The Nobel Prize, established by Alfred Nobel at the turn of the century to honor "those who . . . shall have conferred the greatest benefit on mankind," is perhaps the most prestigious award one can receive for one's work in certain fields. We list here Nobel laureates in physiology or medicine and in chemistry whose work falls within the nutrition and food sciences. Year Name 1902 Emil Herman Fischer (Germany) 1904 Ivan P. Pavlov (Russia) 1923 Si r Frederick G. Banting (Canada) and John ].R. MacLeod (Canada) 1928 Adolf O.R. Windaus (Germany) 1929 Christiaan Eijkman (Netherlands) and Sir Frederick G. Hopkins (Britain) 1929 Sir Arthur Harden (Britain) and H. von Euler-Chelpin (Sweden) 1934 George R. Minot, William P. Murphy, and George H. Whipple (U n ited States) 1937 Sir Walter Norman Haworth (Britai n) 1937 Paul Karrer (Switzerland) 1937 Albert Szent-Gyorgy (Hungary) 1938 Richard Kuhn (Germany) 1943 Henrik Dam (Denmark) and Edward A. Doisy (United States) Accomplishment Research on the synthesis of sugars and purines Work on the physiology of . . d ~gest~on Discovered the hormone . , . Insulin Research on sterols and their connection to vitamins Discovered the antineuritic vitamin (thiamin) and several growth-stimulating vitamins Investigated the fermenta- tion of sugars by yeast juice, leading to later studies of the basic metabolic processes of life Discoveries concerning liver therapy against anemia (Years later, it was shown that vita- min B12, found in liver, could prevent or treat pernicious anemia.) Research on carbohydrates and vitamin C Research on carotenoids and vitamins A and B Research on basic metabolic processes, with an emphasis on . . _ vitam ~ n _ Research on carotenoids and . . vltamlns Discovery of vitamin K and research on its chemical natu re
ACCOMPLISHMENTS IN THE NUTRITION AND FOOD SCIENCES 1945 Arttu ri Vi rtan en (Fi n Ian d) 1947 Carl F. Cori and Gerty T. Cori (United States) 1953 Sir Hans Adolf Krebs (Britain) and Fritz A. Lipmann (United States) 1955 Vincent Du Vigneaud (United States) 1957 Sir Alexander Robertus Todd (Britain) 1964 Konrad Bloch (United States) and Feodor Lynen (Germany) 1964 Dorothy Crowfoot Hodgkin (Britain) 1965 Robert Bu rns Woodward (United States) 1967 George Wald (United States) 1970 Luis F. Leloir (Argentina) 1982 Sune K. Bergstrom (Sweden), Bengt 1. Samuelsson (Sweden), and John R. Vane (Britain) 1985 Michael S. Brown and loseph L. Goldstein (United States) Development of several inven- tions in agriculture and nutri- tional chemistry, especially a method to preserve fodder Research on glycogen and . . Its conversions by enzymes Discovery of the citric acid cycle in the metabolism of carbohydrates Studies on the biochemistry of sulphur compounds and con- tributions to knowledge about the vitamin biotin Research on nucleotides and their coenzymes (Early in his career, he synthesized thiamin and worked on vitamins E and B12.) Research on the metabolism of cholesterol and fatty acids Determined the structure of vitamin B12 Developed techniques for synthesis of organic molecules including cholesterol, chloro- phyll, and vitamin B12 Research on vision and the iden- tification of a vitamin A me- tabolite as the critical mole- cule of the visual pigment rhodopsin Discovered sugar nucleotides and their role in the biosyn- thesis of carbohydrates Research on the biochem- istry and physiology of pros- taglandins Research into the regulation of cholesterol metabolism and the development of cholesterol- related diseases 31 a,
32 OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES and work performance as well as immune function. Sustained deficiency eventually leads to anemia. Pregnant women me nf~rhnnc the most at rick nnn''l~ti~n in this Ron_ ~ . ~ lo. . ~ ~ ~ . try tor Iron aeticlency. Iron deficiency and anemia during pregnancy- which are more common in African-American women and those of low socioeconomic status, with multiple gestations, and with limited educa- tion may be harmful to the fetus, but the data are not conclusive. Iron deficiency is of special concern for infants and young children because it may affect permanently their physical and mental development. Infants with even mild iron deficiency anemia have impaired ability to attain skills that involve mental and muscular activity, such as crawling, talking, ant! solving cognitive problems. It is not clear whether these psychomotor delays are ever completely reversed after the deficiency is corrected. In children, iron deficiency can cause apathy, short attention span, irritabii- ity, and reduced ability to learn. Iron deficiency also increases the risk of lead toxicity, which can impair cognitive function permanently. Iron (lefi- ciency is linked with increased concentrations of lead in the blood of preschool children. In contrast, dietary iron toxicity is rare in this country. Several hun- dred children each year experience acute iron poisoning from iron supple- ments, mistaking them for candy. People who carry a gene from both parents (who are homozygous) for hemochromatosis may experience chronic iron toxicity from consuming iron in food. lIemochromatosis is a heredi- tary disorder of iron metabolism that results in the slow accumulation of iron in the tissues. The primary defect appears to lie in the intestine. Intestinal iron absorption is abnormally high, resulting in excess iron be- ing absorbed from food and supplements. If not identified and treated, hemochromatosis can lead to cirrhosis, cardiovascular disease, diabetes, arthritis, impaired immune function, cellular damage (since excess iron is an oxidant that attacks the fat molecules in cell membranes), and possibly liver cancer. While these clinical features represent the end point of a chronic condition of iron overload, children as young as two years of age with this disease may have high concentrations of iron in their blood. lIemochromatosis is believed to be the most common inherited metabolic disorder, with 1 in every 400 to 500 individuals possibly having both genes and being likely to develop the disease. The responsible gene has not been identified. Nutrition scientists are eager to understand this abnor- mality of iron absorption and to explore the molecular mechanisms of iron absorption in normal individuals (see Chapter 31. There is no definitive biochemical marker in the body to diagnose hemochromatosis. The usual method of screening for this disorder in a general population is to draw blood to identify individuals with markedly elevated concentrations of ferritin (the form of iron stored in tissues) or
ACCOMPLISHMENTS IN THE NUTRITION AND FOOD SCIENCES 33 elevated transferrin saturation (a test of the protein that carries iron in the blood). Where possible, these individuals should have the presumptive diagnosis confirmed with a follow-up liver biopsy. The treatment for this disorder is to bleed patients periodically, which removes some red blood cells and forces the body to use some of its stored iron as it replenishes its supply of these cells. Given the relatively high prevalence of hemochromatosis in the U.S. population, it is clear that there are many more people who carry a hemochromatosis gene from one of their two biological parents (that is, who are heterozygous for this gene). These carriers a group that may represent as many as 10 percent of people in the United States are at increased risk of some of the diseases caused by hemochromatosis. lIow- ever, blood tests to determine iron status are not sensitive enough to distinguish between heterozygotes for hemochromatosis and normal indi- viduals. Research is needed to develop noninvasive screening tools to identify the large population of these heterozygotes. Research leading to the iden- tification of the hemochromatosis gene and the metabolic products of its expression could open new vistas both for identifying affected individuals and for improving the treatment. The prevalence of iron deficiency in the United States and the risks of iron overload to a significant minority raise important public policy ques- tions and pose significant challenges for intervention. The iron fortifica- tion policies of this country have been very effective in combating iron deficiency, but we must be vigilant to ensure that iron-fortified foods reach those populations at high risk of deficiency without putting those with hemochromatosis, or those prone to the disorder, at risk. An alterna- tive approach involves identifying the 10 percent of the population that may be at increased risk of iron overload and learning whether they need to decrease their iron intake. Energy Balance and the Risks of Diabetes and Obesity Diabetes exists in various forms, but they all have in common abnor- mal metabolism of carbohydrates, which leads to hyperglycemia (excess sugar, or glucose, in the blood). Non-insulin-dependent diabetes mellitus (NIDDM), the most common form of this clisease, occurs when the body loses its ability to respond to insulin, the hormone produced by the pan- creas to lower blood sugar concentrations. NIDDM is linked to obesity for reasons that are unclear. Researchers assume that at least some obe sity-associated diabetes results from the interaction of the genetic back- grounds of populations and specific genetic traits in individuals, along with a variety of lifestyle factors, including what and how much one eats. These interactions are undoubtedly behind the high prevalence of obesity
34 OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES and diabetes among certain populations, such as the Pima Indians in the Southwest. NIDDM has a strong genetic basis. Several gene mutations linked to NIDDM have been identified recently, including 40 different mutations of the insulin receptor on cells. (This receptor binds insulin, one of sev- eral compounds the body uses to control blood glucose concentrations, and thereby lets glucose into the cells.) Although obesity is also influ ence(1 by genes, no specific human gene mutation has yet been identified. To study the contribution of genetic background and lifestyle to obe- sity, researchers have developed inbred strains of animals that are either very susceptible or very resistant to this disorder. As a result, there is an immense amount of information on the metabolic derangements and al- tered patterns of behavior that accompany the various forms of genetic obesity in animals. To date, however, we do not know the series of events that leads from the presence of a known gene or a specific experimental manipulation (e.g., feeding diets high in fat or sugar) to the development of full-blown obesity. Scientists are using cellular and molecular genetic techniques to iden- tify and isolate genes that promote obesity in laboratory rodents. One animal mode! shows sex-related differences in obesity-associated diabetes. The model is relevant to humans because when men and women are matched for bocly fatness, men are clearly at greater risk for diabetes. Studies suggest that diabetes is linked to the distribution of body fat (where in the body it tends to collect) as well as to how much there is. The type of obesity associate(1 with diabetes and its complications is called central, or android, obesity. In this type, the enlarged fat cells are found primarily in the abdomen. Where in the abdomen the fat is found- just under the skin (subcutaneous) or deeper (visceral) also affects the risk of disease. The more benign form of obesity is known as gynoid obesity, in which excess fat is deposited mainly in the hips and thighs. Obese men tend toward android obesity; obese women are of both types. flow the distribution of excess body fat influences metabolism and the risks of disease is unclear, but stimuli (such as the concentrations of sex hormones) have different effects on fat cells depending on where in the bocly they are. Much more research is needed to define the link between distribution of body fat, insulin resistance, the influence of sex hormones, and the risk of diabetes and other chronic diseases. As will be (1iscussed in Chapters 3 and 5, many opportunities exist to study the underlying causes of these two disorders, particularly the mechanisms through which genetic and dietary factors interact. Progress will be made toward this goal through further research on inbred strains of animals and by using transgenic animals (animals into which DNA from a different
ACCOMPLISHMENTS IN THE NUTRITION AND FOOD SCIENCES 35 species of animal or plant has been inserted; see section on biotechnology later in this chapter). Folate and Neural Tube Defects During this century, we have learned much about the biochemistry and physiology of vitamins in relation to human nutritional requirements, but we continue to learn more. For example, foods or vitamin supple- ments containing the B vitamin folic acid, taken prior to and during the first trimester of pregnancy, can prevent some neural tube defects (NTDs)- birth defects in which the spinal column does not close during embryonic development. We hypothesize that NTDs result from interactions between the genes of the developing embryo and its intrauterine environment. The genetic component, which probably involves several genes, is complex and not well understood. Epidemiological studies (in which population groups are compared) and other evidence indicate a strong environmental compo- nent as well. The nature of these environmental factors, especially the supposed role of micronutrients (vitamins and minerals), is not well un- derstood. Animal models support the hypothesis that vitamin deficiencies contribute to some human NTDs. Growing evidence from observational and intervention studies in hu- mans suggests that supplements of folic acid t0.1 to 4.0 milligrams (mg) per day] taken around the time of conception (one to three months before conception and during the first six weeks of pregnancy) can reduce the risk of NTDs. On the basis of these studies, the federal government has recommencled that fertile women consume 0.4 mg of folic acid each day, slightly more than twice their current recommended dietary allowance (RDA). While it is not difficult to obtain this amount from food with a well-selected diet, most women fail to do so. More research is needed to determine the amount of folic acid that prevents NTDs most effectively, to learn the molecular mechanisms by which folic acid reduces the incidence of NTDs, and to determine the risks to the population at large of significantly increasing folic acid intake. It is known that folic acid converted to forms that participate in reactions that lead to DNA synthesis. Therefore, it may prevent delays in DNA synthesis, delays in fetal development through abnormal expression of genes, and thus the failure of the neural tube to form completely. Recommendations have been made to fortify foods with folic acid so that all women capable of becoming pregnant can more easily consume 0.4 mg per day in their diets. However, this strategy presents some diffi- cult public policy issues, because it would lead to most of the public consuming significantly more folic acid than they do now, and this could
36 OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES pose risks to some. For folate, as for most nutrients, we know little about the Tong-term effects of ingesting considerably more than the RDA, par- ticularly in forms that are very well absorbed by the body. We have no information about how ingesting 1 or more mg of folic acid dafly over months and years may affect inclivicluals with conditions that may predis- pose them to unanticipated harmful effects. For example, approximately one-quarter of the elclerly population may be at risk for vitamin B 2 clefi- ciency because their ability to absorb BE from foods or supplements is impaired. Since folio acid masks the characteristic anemia of vitamin Big, deficiency, widespread fortification of foods with this nutrient could per- mit vitamin BE deficiency to go undiagnosed. We encourage reaclers interested in this topic to peruse Chapter 5, which presents many opportunities for investigating the role of nutrition and its relation to various pregnancy-relatec3 outcomes and conditions ant! the Tong-term consequences of nutritional insults and inadequate nutri- tion on early development. Chapter 6 provides a discussion of the re- search opportunities in assessing growth, development, and nutritional status, as well as understanding the motivations for and barriers to chang- ing food habits. Oxidative Damage to DNA, Proteins, anc] Fats Research using methods that range from the test tube to an entire population suggests that forms of oxygen procluced in our bodies in the course of daily living can cause significant damage, affecting the aging process and increasing our risks of a variety of chronic diseases. These "active oxygen" species include singlet oxygen ant] oxygen raclicals con- taining an unpaired electron, which makes them likely to interact with important molecules in the body and produce undesirable by-products. For example, oxidizecI genetic material (DNA) can initiate or promote the development of cancers of the lung, colon, breast, and uterus ant! cause chromosomal abnormalities. Oxidative damage to proteins is linked to the formation of cataracts. Oxidized fatty acids and the products formed from them are linked to damage to the arteries leading to the buildup of fatty plaques. Oxi(lative damage caused by active oxygen species also may com- promise the immune system. Given the constant, inevitable production of active oxygen species, it is no surprise that the body has evolved mechanisms to prevent their damaging consequences, some of which are influenced by what we eat. The enzymes superoxide dismutase (which contain essential trace miner- als such as copper, manganese, and zinc) en cl glutathione peroxiclase (which contains the essential trace mineral selenium) provide two such mecha- nisms to inactivate these forms of oxygen. Many carotenoids (including
ACCOMPLISHMENTS IN THE NUTRITION AND FOOD SCIENCES 37 those that are precursors of vitamin A) can quench singlet oxygen, and vitamin E can prevent the propagation of oxygen radical-initiatecT reac- tions. Vitamin C regenerates vitamin E that has become oxidized in the course of fighting oxidation, thereby contributing to the efficacy of this fat-soluble vitamin. Several studies of population groups link low intakes and low blood concentrations of these antioxidant nutrients with several diseases, including heart disease, several cancers, and cataracts of the eye. Evidence of health benefits from supplements of these nutrients is sug- gestive but not yet convincing. Each of the diseases mentioned above has important genetic compo- nents. The predisposition to coronary heart disease that occurs in middle age can be explained in significant measure by genetic disorders that in- volve the transport of cholesterol ant! other fats in the bloocT. However, the known risk factors unclerlying heart disease (such as high bloocI cho- lesterol, high blooci pressure, and cigarette smoking) fad! to account for much of the individual susceptibility to this major cause of death in the United States. Although there is considerable evidence that oxidation of blood lipoproteins within the arterial wall, particularly the low-density lipoproteins (LDLs) that carry most of the cholesterol in the blood, un- derTies the early development of atherosclerotic plaques, the factors that regulate formation of oxidized LDL are still largely unknown. That such factors could be critical is supported by observations that the susceptibil- ity of inclividuals with familial hypercholesterolemia, a common genetic disease, to the development of coronary heart disease varies widely among families and cannot be explained simply by the concentrations of LDL in the blood. What may underlie these differing susceptibilities are impor- tant interactions between nutrients and genes that are influenced by diet or how the body metabolizes critical nutrients. Similarly, the genetic de- terminants of metabolism and the way the hotly handles various nutrients may underlie some of the genetic susceptibility to other chronic diseases that can develop as a result of oxidative damage. The fact that one's genetic endowment can influence the aging pro- cess is suggested by observations in the fruit fly. Strains specially bred to be long-lived tend to have a more active form of the enzyme superoxicle dismutase. In one strain into which genetic material was inserted, leading the flies to produce greater than normal amounts of this enzyme, the average life span (though not the maximum life span) was increased. These examples provide some indication of the types of research in antioxidant biology that have considerable potential to improve human health. For further details, see Chapter 3.
38 OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES Improving the Food Supply Sensory Biology and the Development of New Foods The typical person in the United States derives more than one-third of his or her daily calories from fat and one-fourth from sugars, both natural and added. Fat and sugar together account for more than one-half the total daily energy intake. Diets low in carbohydrate and fiber but rich in simple sugars and fat are linked to a high prevalence of obesity and increasect risk of chronic disease, including coronary heart disease, diabe- tes, and some forms of cancers. Excessive fat intake has been called the number-one problem in the U.S. diet, and current dietary guidelines rec- ommend reducing fat consumption to 30 percent or less of total calorie intake. Reclucing fat consumption is no easy task. We generally like the taste of high-fat foods and are reluctant to give them up. EIigh-fat diets are flavorful, varied, and rich. Fats are largely responsible for the texture, mouthfeel, and flavor of many foods anc] play an important role in deter- mining the palatability of the cliet. Poor adherence to low-fat regimens is a clocumented problem in the dietary management of people with high cholesterol counts, while cravings for sweet, high-fat foods are a major obstacle to weight reduction. Even highly motivated cardiac patients often find it difficult to follow diets composed of grains, vegetables, fruit, and low-fat dairy products. One approach to implementing dietary guidelines is to apply existing strategies and models of behavior change to the dietary behavior of com- munities and populations. The National Cholesterol Education Program is a classic example of this approach to lower total fat, saturated fat, and cholesterol consumption in this country. Another approach to implement- ing dietary guidelines is to after the available food supply, because dietary compliance may increase if low-fat foods offer the same eating pleasure as foods high in fat. Recent advances in food technology, particularly the development of fat-replacement products, offer one way of reducing fat consumption while satisfying natural sensory preferences for a varied, pal- atable diet. Similarly, the use of intense sweeteners offers a way of reduc- ing excess sugar consumption. Sensory preferences for sweetness and fat are deeply ingrained and appear to be universal. The pleasure response to sweetness is innate and has been observed in human infants at birth. The pleasure response to fats is most likely learned early on; sensory preferences for high-fat foods have been observed in children, adolescents, and adults. The pleasure response to palatable foods may involve central brain mechanisms. The neurotransmitter serotonin and endogenous opioid peptides may mediate
ACCOMPLISHMENTS IN THE NUTRITION AND FOOD SCIENCES 39 preferences for carbohydrates, sugar, and fat. Taste preference profiles for sugar-fat mixtures also change with age and may be modified further by repeated cycles of weight loss and gain. At the same time, large-scale epidemiological and agricultural studies suggest that the amount of fat in the typical diet is strongly influenced by socioeconomic factors. Indeed, the amount of fat in the typical Western diet may be influenced not so much by physiological variables as by the amount of fat available in the food supply. Consequently, strategies for reducing fat consumption must be planned carefully. The food industry has made impressive progress in increasing the range of palatable yet low-fat products available to consumers. One prom- ising area is the production of leaner beef, leaner pork, and eggs with less cholesterol. The food industry is using new technologies to develop new generations of low-calorie or zero-calorie fat replacement products and new versions of intense sweeteners. Biotechnology Since first domesticating plants and animals, people have exploited the genetic diversity of living systems to improve the food supply. Over the centuries, we have developed well-accepted techniques for selectively breeding plants and animals for desirable characteristics. Producing fer- mented foods such as cheese, bread, and wine in a wide variety of forms depends on an ability to manipulate and alter microorganisms. Biotech- nology provides a new set of tools for improving the variety, productivity, and efficiency of food production and the nutritional quality of foods. Genetic engineering provides a mechanism for producing specific genetic improvements in plants, animals, and microorganisms in less time and with greater precision, predictability, and control than possible with tradi- tional methods of breeding and selection. ~. ~ , ~ Plants Genetic engineering can be used to improve dramatically the nu- tritional quality of plants by making minor modifications in their genetic makeup. For example, cereal grains, which are the main source of protein for the vast majority of the world, are deficient in essential amino acids. Improving their amino acid composition would make them a higher-qual- ity, more complete source of protein. It is now possible to improve the nutritional value of oilseeds, which supply almost half the fat in our diets. Gene transfer technology has been used to alter composition and reduce the degree of saturation of fatty acids sunflower and safflower. The many studies linking diet to cancer have led to research to iden- tify the responsible components in food. Over 600 plant-derived chemi in major oilseed crops such as
40 OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES cats (phytochemicals) have cancer-preventing potential, including antioxi- dants such as beta-carotene and vitamins C and E. In the future, genetic engineering will make it possible to manipulate the amount of these chemicals in food. In addition, plant tissue culture techniques may be used to pro- duce phytochemicals that could be added to processed foods. An emerging technology that promises to have a dramatic effect on the genetic engineering of Plants involves inserting a single gene normaliv v V ~ 1 0 ~ ~ ~ . . 1 . ~ _ ~ present in a plant in the opposite orientation. This antisense technology has already been used to block the expression of single genes involved in the ripening process in tomatoes (thereby reducing Tosses caused by pre- mature spoilage) and in caffeine production in coffee beans. It coulc3 also be used to block the production in food of antinutrients such as phytates and oxalates, which bind to minerals and make them unavailable for ab- sorption. By improving the taste, texture, and shelf life of fresh fruits and vegetables, this technology should entice more consumers to eat more of these nutritious foods. Animals Genetic engineering will be increasingly important in animal agriculture. The most obvious applications involve directly manipulating an animaT's hotly composition, growth rate, and disease resistance. There is also a growing interest in using transgenic animals (which have incorpo- ratecl genetic material from an unrelated animal, plant, or microorganism) to produce novel proteins in milk, blood, and urine that can be extracted and purified. Many complex biological processes affecting fertility, ratios of lean meat to fat, growth rate, and milk yield are regulated by hormones. The genes directing the production of many of these hormones have been cloned, providing opportunities to manipulate the physiology of farm ani- mals. For example, somatotropin (growth hormone) genes from several animal species have been identified, characterized, and integrated into the gene pool of related ancI unrelated animal species. Supplements of bovine somatotropin (BST) improve the feed efficiency of cows and in- crease their milk production without altering the milk's composition. Por- cine somatotropin (PST) enables the pig to form muscle rather than fat, dramatically reducing the fat content of pork. Genetic changes that improve disease resistance and feed digestion in foocl-producing animals will have an indirect but very positive effect on the nutritional quality of their meat and milk. Several economically im- portent diseases might be combated by transgenic strategies, thereby de- creasing dependence on antibiotics and broad-spectrum chemical treat- ments and reducing drug residues in the food supply. Genetic approaches have been proposed to increase the digestive capacity of ruminant ani- mals. One option is to add transgenic bacteria that produce digestive en
ACCOMPLISHMENTS IN THE NUTRITION AND FOOD SCIENCES 41 zymes into the rumen of these animals. For example, enzymes called phytases increase the availability of phosphorus, which is essential for forming bone, in plant foods. Incorporating phytase-producing bacteria in the rumen of cows, for example, would reduce both the amount of expensive phospho- rus needed in their diet and the amount excreted in their feces. The latter would reduce phosphorus contamination of grounc3water from farm wastes. Food-processing biotechnology Bacteria, yeasts, and molds have been used for centuries to produce fermented foods such as cheese, yogurt, sausage, pickles, sauerkraut, wine, beer, soy sauce, and bread. Biotechnology can be used to alter the metabolic processes of these microorganisms in ways that will improve production efficiency and extend shelf life, improve nutritional content, or ensure the safety of the product. Microorganisms with a long history of safe use can be manipulated to produce food flavors and flavor enhancers, sweeteners, thickeners, and nutritive additives such as vitamins, amino acids, and fiber. Biotechnology will enable us to develop systems that rapidly detect pathogenic and spoilage organisms, microbial ant! fungal toxins, and chemical and biological contaminants in foods. In addition, it wfl} provide innova- tive ways of treating food-processing waste with microorganisms and en- zymes to help prevent environmental contamination and convert some of this waste to higher-value food and nonfooc3 products. To make the most of biotechnology, we must learn much more about metabolism in plants, animals, and microorganisms. Many opportunities exist, for example, to study the biochemistry and genetics of carbohydrate, protein, and fat metabolism. There is little doubt that this powerful tech- nology wfll improve dramatically the nutritional quality of the food supply in the coming years. (For further details, see Chapter 4.) Preventing Chilclhoocl Morbidity and Mortality Oral Rehydration Therapy The development of oral rehydration therapy (ORT) represents a milestone in the history of public health nutrition. Use of an oral solution containing sugar and electrolytes to help replenish fluids lost during acute diarrhea can be traced back thousands of years to traditional folk remedies and non-western medical traditions. The scientific rationale for such a therapy emerged with the recognition in the 1800s that the mortality associated with cholera was due primarily to diarrhea and the resulting loss of body fluids and electrolytes. Basic research in the 1950s established the mechanisms by which sodium and organic solutes are transported in intestinal cells. By the 1960s,
49 OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES clinical studies of the effectiveness of ORT were being carried out in several Asian countries. These were followed by studies that confirmed the efficacy of oral rehydration and extended it as a therapy to patients suffering from acute diarrhea of any origin. Diarrhea is the most frequent cause of death of young children in the world. To combat this scourge, the World Health Organization (WHO) in 1971 formulated a simple and standard oral rehydration solution; it began worldwide distribution of packets of this solution and instructions to pre- pare the solution at home. Efforts to promote ORT have targeted the household, as ORT is a simple, inexpensive primary health care interven- tion that can be used effectively by family members. The initial mass health education programs to encourage widespread use of ORT had only limited success. Public health workers have learned that they must recog- nize and work within the health beliefs and childcare practices of various cultures if they are to succeed in increasing the acceptance and use of ORT. Vitamin A The first scientific paper describing the discovery of vitamin A ap- peared in 1913. Investigators soon learned that rats made deficient in this nutrient stopped growing, became more susceptible to infections, and died. Those that managed to survive the longest ultimately developed xerophthalmia, a term for eye problems caused by vitamin A deficiency. Human xerophthaImia is very dramatic; the most severe manifestation is keratomalacia, in which the cornea literally melts, often in just a few hours, causing blindness. Children who develop keratomalacia die at a high rate, because they are not only severely deficient in vitamin A, but also badly malnourished in general, usually suffering from respiratory dis- eases and diarrhea. For many decades, scientists and health workers focused on the ocu- lar changes resulting from vitamin A deficiency. As a result, they did not recognize or become sufficiently alarmed by the other potential conse- quences of this deficiency, particularly in impoverished developing na- tions. This situation began to change in the early 1980s after investigators followed a group of 4,000 pre-school-age children in Indonesia who ap- peared well-nourished and healthy, but who had night blindness and other mild manifestations of xerophthalmia. Over time, the children with mild xerophthalmia died at a greater rate than children whose eyes were clini- cally normal at the beginning of the study. This association had a strong dose-response relationship; that is, the more vitamin A-deficient the child, the more likely he or she was to die, suggesting that the observation went beyond mere coincidence. However, it was always possible that other,
ACCOMPLISHMENTS IN THE NUTRITION AND FOOD SCIENCES ~3 unrecognized factors associated with vitamin A deficiency accounted for the increase in the death rate (mortality). The next logical step was to conduct controlled clinical trials to eliminate potential confounding fac- tors and to determine whether reversing vitamin A deficiency could re- duce mortality. By 1993, these clinical trials had been conducted in several countries in Southeast Asia, Africa, and Central America. The overwhelming con- clusion based on the combined results is that improving vitamin A status can reduce mortality, mainly from diarrhea and respiratory diseases, in childhood by 25 to nearly 40 percent. In fact, some studies suggested that the reduction in mortality might be as high as 72 percent if every child targeted for vitamin A treatment had actually received all the treatments. These phenomena are one side of an emerging equation. The other side concerns measles-related mortality. Measles in Africa is a devastating disease; it has a high mortality and is the major cause of blindness among African children. Studies of children hospitalized for severe measles in Africa have shown that providing vitamin A can save lives and reduce the severity of sickness brought on by the disease. WHO and the United Nations International Children's Emergency Fund (UNICEF) recommend that vitamin A be routinely used to treat children with measles in all countries where vitamin A deficiency is known to be a problem or where the fatality rate from measles exceeds 1 percent. Initiatives must be developed to ensure that all children get enough vitamin A to prevent even subclinical deficiencies (those that are not readily apparent). Among the initiatives proposed or already adopted are encour- aging breastfeeding, promoting cultivation of foods rich in beta-carotene (which the body converts to vitamin A), changing dietary habits, fortifying commonly used ingredients, and providing supplements of vitamin A to children to build up their stores of this nutrient in the liver. We have learned that vitamin A supports the growth and development of body tissues soon after conception and on through life. This nutrient is also required for the health and integrity of the skin and other organs, such as the lung and intestine, that help prevent microorganisms from entering the body. Growing evidence points to the importance of vitamin A and its metabolites (compounds the vitamin is converted into) and to precursors of vitamin A (carotenoids such as beta-carotene) in maintain- ing health and reducing the risk of certain cancers and possibly heart disease. Yet we have much to learn about optimal intakes of vitamin A and the carotenoids as well as the mechanisms by which they promote growth and health. Exciting advances in molecular and developmental biology described in Chapter 3 have led to the discovery that a metabolite of vitamin A, retinoic acid, directs the expression of a large number of genes. Future research will undoubtedly help us to understand how vitamin A
44 OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES acts in organs throughout the body to maintain their health, control infec- tion, and protect against various chronic diseases. New Concepts of Nutrient Requirements Nutrient requirements are currently defined as the amounts of nutri- ents needed to maintain normal body functions. The most widely used methods to determine requirements have been nutritional balance, or depletion- repletion, studies. In such studies, the requirement for a nutrient was assumed to be met if intake equaled output (i.e., balance) or if body functions dependent on that nutrient remained "normal." Recently, we have learned that nutritional balance can be achieved without maintaining normal or optimal function. This was evident, for example, in studies of zinc nutrition in lactating Amazonian women. Although their usual intake of zinc was only S.4 mg per day (about two-thirds of the amount recom- mended), they achieved a positive zinc balance by absorbing a high pro- portion of the intake. When these women were given zinc supplements, their milk supplied adequate zinc and larger amounts of vitamin A, and their nursing infants had less risk of developing diarrhea. Apparently, the usual zinc "balance" of these women was not without cost to them and their infants in terms of other biological functions. We therefore cannot assume that all zinc functions are fully met just because balance is achieved. During the past decade, we have made significant advances in using heavy isotopes as tracers to study the metabolism of nutrients. Methods have been developed to administer these isotopes to humans, as have analytical methods for measuring them in biological samples. These tech- niques have enabled us to measure body stores, turnover, kinetics (move- ment), and recycling of nutrients in people with very different eating habits and physiological states (e.g., adolescence and pregnancy). It is now possible, with the help of computers and appropriate software, to use this information to develop mathematical models that depict the movement of nutrients through the digestive system, into the bloodstream, and to spe- cific sites within tissues. These kinetic models have been built for several nutrients, including zinc, selenium, copper, calcium, and vitamins A and D. A kinetic model can be used, for example, to determine whether par- ticular dietary patterns place individuals at risk of depleting their body stores of zinc by reducing zinc absorption from the intestine or increasing its excretion in urine and sweat. An adequate zinc intake might be defined as the amount required to maintain zinc stores at some specified level at an appropriate rate of absorption from the intestine. A diet poor in zinc could then be defined as one that leads to a drop in body stores or that maintains body stores by forcing the body to substantially increase zinc absorption or markedly decrease excretion. Dietary zinc requirements could
ACCOMPLISHMENTS IN THE NUTRITION AND FOOD SCIENCES 45 then be formulated for a variety of different types of diets consumed around the world, such as cereal-based (moderate-zinc) diets, red-meat- based (high-zinc) diets, or poultry-based (low-zinc) diets. In this way we can begin to individualize dietary zinc requirements and recommend in- takes for populations based on their usual dietary patterns. As we begin to think about possible changes in dietary allowances, we must revisit the criteria for establishing requirements for all nutrients in healthy people in a manner similar to that described above for zinc. Also, these same models and novel approaches can be used to study nutrient requirements of people with various diseases. For example, the wasting syndrome associated with acquired immunodeficiency syndrome (AIDS) places those patients at particular nutritional risk. They could be studied using isotopic tracers to determine how this clisease alters nutrient bal- ance. However, apart from the relevance of such research to specific dis- eases, learning how disease disrupts nutrient balance can provide new insights into nutrient metabolism in health. We have learned a great deal about our vulnerability to specific nutri- ent deficiencies and the detection and consequences of these deficiencies based on a quarter century of experience in delivering nutrients to indi- viduals with various diseases who cannot eat normally. These patients require nourishment delivered entirely through a vein (total parenteral nutrition) or with synthetic formulas either by mouth or via a tube in the stomach or intestine (enteral nutrition). Some receiving this specialized form of nutrition support have developed nutrient deficiencies particu- larly of trace minerals such as zinc, copper, selenium, molybdenum, and chromium that are often clinically dramatic. The good news, however, is that identifying these deficiencies has enabled investigators to determine the essentiality and practical importance of these trace minerals in human nutrition and to design more effective formulations. For example, studies of patients fed entirely intravenously have provided the only evidence that humans are vulnerable to a dietary deficiency of molybdenum and some of the strongest evidence that chromium deficiency may impair our ability to metabolize carbohydrates properly. It is in providing specialized nutrition support that we have also de- tected deficiencies of vitamins, minerals, essential fatty acids, and certain amino acids. The amino acid glutamine is one such example. Glutamine is not regarded to be a dietary essential because it can be synthesized in adequate quantities by our muscles. It then enters the blood circulation and is taken up, in part, by other tissues where it is needed, especially the immune system, kidneys, and the cells lining the intestine. The intestine, which uses glutamine as a source of energy, derives what it needs in part from the diet, as this amino acid is present in protein-containing foods. A patient fed entirely by vein will depend entirely on the supply from his or
46 OPPORTUNITIES IN THE NUTRITION AND FOOD SCIENCES her muscle, as the present generation of intravenous amino acid prepara- tions does not contain glutamine. Patients receiving this form of nutri- tional support who experience trauma or infection may not make enough glutamine in their muscles to meet their needs. Enteral and parenteral nutrition will become increasingly important in the nutritional management of patients with a variety of disabling dis- eases and medical problems. Continuing research in this area in both animals and humans should yield further insights into the occurrence and consequences of deficient and excessive intakes of various nutrients. In the future, it may be possible to use functional tests of nutrient- dependent functions to establish nutrient requirements, either alone or in conjunction with other endpoints (such as body stores or turnover rates). For example, since we need adequate zinc in our diets to detect and discriminate various tastes, requirements for zinc might be defined as the amount that maintains taste acuity and enables the body to store a specific amount of the mineral. In addition, we may wish to broaden the criteria for establishing dietary allowances to encompass the goal of maximizing healthy lifespans through the prevention of chronic diseases and by slow- ing the aging process. Earlier in this chapter, for example, we noted that antioxidant nutrients such as vitamins C and E consumed in adequate amounts from food or taken as supplements might help to protect against heart disease, several cancers, and cataracts. Clinical trials are needed to determine the levels of intake of nutrients and other biologically active constituents in food (such as dietary fiber and carotenoids) that enhance health and reduce the risk of disease. (For further details, see Chapter 6.) CONCLUDING REMARKS In the next four chapters, we describe in detail a variety of current and future opportunities for exciting and challenging research to advance the nutrition and food sciences and to meet critical human needs. Many of these opportunities stem from the accomplishments described above. Chapter 3 presents opportunities in the basic biological sciences appli- cable to nutrition, followed by food science and technology in Chapter 4. In Chapter 5, we present opportunities in clinical nutrition research, fol- lowed by Chapter 6 on public health nutrition. Some opportunities in these latter two areas are clearly dependent on technological advances, but many also depend upon research in basic biology and food science.