Status of Diet and Nutrition Research in the United States
Diet and nutrition research goes on in almost every medical school, university, and pharmaceutical laboratory throughout the world. Thus, the knowledge of how to prevent illness and maintain health through nutrition grows every year. However, for such areas as reversing the effects of chronic disease through dietary or nutritional intervention or determining levels of nutrients required to achieve optimal metabolic or immune system functioning, there often is no critical mass of researchers or funds to follow up promising initial experimental results. In fact, the history of nutrition research is marked by examples where, for one reason or another, preliminary reports of a positive therapeutic effect of a certain vitamin, mineral, or nutritional manipulation appear but are often not followed up by the overwhelming majority of the medical community. In cases where such therapies eventually are proven to be safe ~and effective, it is sometimes not until years or even decades after the initial reports. The result is that many individuals may die or suffer needlessly, while effective interventions are available but not yet validated. For example, in the 1930s, Australian psychiatrist John Cade began a series of crude experiments on guinea pigs in which he injected them with the urine of psychiatric patients to test his hypothesis that mania--a mood disorder characterized by, among other things, periods of euphoria--might represent a state of intoxication resulting from an excess of some commonly occurring metabolite. Depression, on the other hand, might represent the effects of abnormally low levels of the same metabolite (Johnson, 1984). Although all the urine samples proved toxic to the guinea pigs--Cade traced the toxicity to the urea component of the urine--the urine from the manic patients was far more toxic than urine from the schizophrenic or depressive patients. In his attempts to find out what was increasing the toxicity of the urea in the manic patients' urine, Cade happened upon the compound lithium citrate, which he eventually began ~injecting by itself into the guinea pigs to judge its effect. To his amazement, the guinea pigs became lethargic and unresponsive for several hours after receiving lithium, before fully recovering. In 1949, Cade published the results of a crude clinical trial, stating that lithium salts given to 10 manic patients resulted in a dramatic improvement in each one's condition (Cade, 1949). Unfortunately for Cade, just as his results were reaching the United States, a number of table salt substitutes containing lithium chloride had just been recalled by the Food and Drug Administration (FDA) due to toxic side effects and, in some cases, death with heavy use. So much publicity was given to the toxicity associated with these salt substitutes--which were marketed for use by people on salt-restricted diets--that for 5 years after Cade's original report, relatively little work with lithium was undertaken (Georgotas and Gershon, 1981). According to medical historian Frederick Johnson (1984), "Cade's report of lithium treatment of mania might well have succumbed to the same fate as that suffered by many proposed therapeutic techniques before and after that time ... had lithium salts been at all expensive or hard to come by...." Instead, because canisters of lithium salts were to be ~found in most hospitals and pharmacies at the time, many psychiatrists in the mid-1950s, for lack of adequate treatments for manic disorders, simply started experimenting with lithium on their own. By the mid-1960s, a spate of reports appeared in the medical literature reporting on the effectiveness of lithium in the treatment of manic and other psychiatric disorders (Gershon and Yuwiler, 1960; Schlagenhauf et al., 1966). Today lithium, in some patients with bipolar disorders (i.e., mood swings), is the most successful therapeutic drug of the five major types of drugs currently used in psychiatry (Horrobin, 1990), often producing normalization in acute mania patients in 1 to 3 weeks. A situation analogous to the lithium story occurred in the late 1980s in the United States. Just as reports were emerging that suggested the effectiveness of the amino acid L-tryptophan in treating mild depression (Boman, 1988), chronic insomnia (Demisch et al., 1987), and mood disorders (Maurizi, 1988), there was a severe outbreak of a sometimes deadly inflammatory disorder called eosinophilia myalgia syndrome (EMS). The cause of the EMS outbreak was linked by epidemiologists to the over-the-counter use of tryptophan (Varga et al., 1993). Although all cases of this disorder were eventually found to be caused by contaminants in ~batches of tryptophan produced by a single manufacturer in Japan (Barnhart et al., 1990) and not by the effects of tryptophan itself, this nutritional supplement was taken off the market by the FDA and is no longer available over the counter. Just as with lithium, the publicity about toxicities associated with tryptophan may have hindered rational scientific discourse about the effectiveness of this nutritional therapy for some time to come. In fact, FDA uses the tryptophan example to justify its efforts to regulate as drugs most dietary and nutritional supplements whose manufacturers make any health claims (U.S. Food and Drug Administration, 1992). There have been numerous other instances in recent decades when individuals or groups of individuals have advocated nutritional interventions or alternative dietary lifestyles as a means of preventing or even treating disease and have met not only indifference but often hostility. This was especially true for those advocating vegetarianism or an extremely low-fat diet as a means of preventing or treating illnesses such as heart disease (see below). As was the case with John Cade and lithium, it took many decades for the facts to win out over misconceptions and biases.~The rest of this chapter discusses a number of areas of diet and nutrition research in which there is at least preliminary scientific evidence indicating the need for more in-depth studies, but for which there often is no critical mass of researchers or funds to follow up promising initial experimental results. However, it should be noted that only an overview of the field is presented, and it is by no means comprehensive. This field of research is so complex and diverse that no more than a few examples can be offered for each subsection. First, however, it is instructive to discuss briefly the evolution of the modern affluent diet and evidence relating chronic disease with its excesses and micronutrient deficiencies. Also presented is a discussion of the evolution of present dietary guidelines and why some consider them inadequate. Evolution of the Modern "Affluent" Diet Over the course of evolution, human beings (and their primate predecessors) adapted gradually to a wide range of naturally occurring foods, but the types of food and mix of ~nutrients (in terms of carbohydrates, fats, and proteins) remained relatively constant. Food supplies were often precarious, and the threat of death from starvation was a constant preoccupation for most of the Earth's inhabitants. About 12,000 years ago, an agricultural revolution brought profound dietary changes to many human populations. The ability to produce and store foods became widespread, and some foods, such as grains, were preferentially cultivated. These new techniques and the overabundance of some foods they produced presented novel challenges to the human digestive system. The Industrial Revolution, which began about 200 years ago in Europe and soon spread to North America, introduced more radical changes in the human diet due to advances in food production, processing, storage, and distribution. Recent technological innovations, along with increased material well-being, or affluence, and lifestyles that have allowed people more freedom in deciding what and when they wish to eat (amplified by modern marketing techniques), have led to even further major dietary changes in developed countries. Indeed, ~such innovations as sugared breakfast cereals and a variety of snack items were unheard of before World War II; Hampe and Wittenberg (1964) estimated that 60 percent of the items on supermarket shelves in 1960 came into existence in the 15 years following World War II. Health Consequences of the Modern Affluent Diet Because changes in the dietary patterns of the more technologically developed countries, such as the United States, have been so dramatic and rapid, the people consuming these affluent diets have had little time to adapt biologically to the types and quantities of food available to them today. The longer term adverse health effects of the affluent diets prevailing in these countries--characterized by an excess of energy-dense foods rich in animal fat, partially hydrogenated vegetable oils, and refined carbohydrates but lacking in whole grains, fruits, and vegtables--have become apparent only in recent decades. Comparisons of population groups have demonstrated a close and consistent relationship between the adoption of this affluent diet and the emergence of a range of chronic, ~noninfectious diseases, such as coronary heart disease, cerebrovascular disease, various cancers, diabetes mellitus, gallstones, dental caries (cavities), gastrointestinal disorders, and various bone and joint diseases (World Health Organization, 1990). Some nutrition and health experts believe that the relationship between rapid changes in a population's diet and rapidly changing disease and mortality profiles is reflected in many recently acculturated (i.e., adapted to the dominant culture) groups in the United States who are now eating a diet more akin to that of the northern European and U.S. general populations (see the sidebar on page 214). For example, increasing rates of diabetes mellitus have been reported in Native American and other populations that suddenly switch from a traditional to a more modern lifestyle (West, 1974). This disease has only recently become a major health problem for Native Americans, who now often have rates much higher than those found in either U.S. Caucasian or African-American populations. Indeed, although the overall rate of diabetes in the general U.S. population is between 1 and 3 percent, and 5 to 6 percent for those over age 35, it ranges from 10 to 50 percent among Pima Indians 35 years of age and older (Bennett et al., ~1979; Neel, 1976). Furthermore, in Hawaii, the incidence of breast cancer for Caucasians is similar to U.S. mainland rates, but the incidence among Hawaii's Japanese population is more than twice the rate in Japan and approaches the rate for Caucasians (Muir et al., 1987). The reasons for these abnormally high disease rates in American Indian and other non-Caucasian populations are complex; however, they include obesity related to changes in activity patterns and, probably, the increased consumption of refined carbohydrates and sugar. Also, intake of dietary fiber has decreased dramatically. Excessive caloric consumption in some of these populations also may be a major contributor; one study found that obese American Indians consumed 250 to 1,600 more calories than were recommended for persons of their height, gender, age, and level of activity (Joos, 1984). In one of the few studies of its kind, a group of Native Hawaiians with multiple risk factors for cardiovascular disease believed to be related to consuming a nontraditional diet were placed on a "pre-Western contact," or traditional, Hawaiian diet to assess its effect on ~obesity and cardiovascular risk factors. Twenty individuals were placed on a diet low in fat (7 percent), high in complex carbohydrates (78 percent), and moderate in protein (15 percent) for 21 days. The subjects were encouraged to eat as much as they wanted. At the end of the diet modification period, the average weight loss was 7.8 kilograms (approximately 17 lbs.), and the average serum cholesterol dropped by about 14 percent. Blood pressure decreased an average of 11.5 mm Hg systolic and 8.9 mm Hg diastolic (Shintani et al., 1991). Evolution of Federal Dietary Guidelines Due to the rapid rise in chronic illness related to diet in recent decades, the focus of nutrition research has shifted from eliminating nutritional deficiency resulting from undernutrition to dealing with chronic diseases caused by nutritional excess, or "overnutrition." Since the 1950s, researchers have identified a number of types of dietary excess that appear to influence the incidence and course of specific chronic diseases. ~Another growing concern among nutrition researchers is the accumulation of evidence indicating that inadequate intakes of some micronutrients over a long time may increase the risk of developing a variety of disease conditions, including coronary heart disease, many cancers, cataracts, and birth defects. Earlier, many of these conditions were not even considered diet-related. Furthermore, many other components of foods, in addition to those traditionally considered nutrients, may be important in achieving optimal health. Unfortunately, the "standard" American diet, while rich in calories, contains processed foods deficient in many important micronutrients and other components of the original unrefined foods. The Federal Government has been involved in developing nutrition guidelines for the American public since the mid-1800s, when the U.S. Department of Agriculture (USDA) was established. However, such guidelines traditionally had dealt with how to prevent nutritional deficiencies, as well as how to promote the consumption of U.S. agricultural products. Only in the past several decades, as the focus of public health policy has shifted from preventing disease caused by nutritional deficiencies to preventing disease caused by ~overnutrition or nutritional imbalances, have Federal dietary guidelines attempted to address the latter. Today, such guidelines are becoming more difficult to develop and often meet fierce resistance from various lobbying groups when they are disseminated (Nestle, 1993). Nevertheless, since the early 1970s, USDA and other Federal agencies and advisory groups have periodically released diet and nutrition guidelines dealing with preventing chronic illness related to nutrition. This material typically targets public health policymakers, medical doctors, or the general public. Two of the better known current Federal dietary and nutritional guidelines, from which public health policy is made, are the recommended daily allowances (RDAs) and the Food Guide Pyramid. RDAs are defined as the average daily amounts of essential nutrients estimated, on the basis of available scientific knowledge, as adequate to meet the physiological needs of practically all healthy persons (Monsen, 1990). (See figure 1.) To establish the standards for RDAs, which are updated periodically (most recently with the 10th edition in 1989; see Monsen, 1990), the Food and Nutrition Board of the National Academy of Sciences critically ~evaluates the literature on human requirements for each nutrient, examines the individual variability of requirements, and tries to estimate the efficiency with which the nutrients are biologically available and used from foods consumed. The RDAs are levels that should be reached as averages in a period of several days, not necessarily daily. RDAs are not meant to be guidelines for consumers; they were initially designed to serve as standards for planning food supplies for population groups (National Research Council, 1989). However, they are used as a partial basis for the development of other guidelines that are intended for consumers, such as the Food Guide Pyramid, which was released by USDA in 1992 to replace the old "basic four" food groups. The Food Guide Pyramid is designed to give consumers information on how to eat a "balanced" diet that will provide them with the RDAs for essential nutrients while lowering their risks of chronic illness due to nutritional excesses (Journal of the American Dietetic Association, 1992). Sweets, fats, and oily foods are at the top of the pyramid, indicating that they should be consumed in small amounts. Dairy products such as milk, yogurt, and cheese, and meats, poultry, fish, dried beans, eggs, and nuts are just below, indicating they should be consumed in moderation. ~Fruits and vegetables follow; bread, cereal, rice, and pasta are at the bottom of the pyramid, indicating that they should be consumed in rather large amounts in comparison with the foods at the top of the pyramid (see figure 2). Guidelines such as the Food Guide Pyramid are intended to inform consumers, as well as public health policymakers, about what kinds and amounts of certain foods are best suited for maintaining health and lowering the risks of nutrition-related illnesses. Generally, this approach to affecting health through diet and nutrition interventions involves manipulating the "typical," or mainstream, diet so that foods with less nutritional value are eaten less and foods with more nutritional value are eaten more. The Federal Government's approach to dietary intervention, which has been formulated over the years by boards composed of nutrition scientists, generally does not recommend supplementing this "typical" diet with vitamins or nutritional supplements (National Research Council, 1989). It also does not take a "good food" or "bad food" approach (Herron, 1991) or suggest that certain foods are "off limits" because of their propensity to cause chronic ~disease (Nestle, 1993). However, this is only one approach to promoting health and preventing illness through dietary intervention. There are many "alternative" dietary approaches that contend that no matter how much one manipulates the typical American diet, it is not enough to promote optimal health or stave off eventual chronic illness. Alternative approaches represent a continuum of philosophies, from the idea that diet supplementation somewhat beyond RDAs is necessary to promote optimal health to the idea that supplementation well above RDAs is often required to treat some chronic disorders. Further along this continuum is the approach advocating drastic modification of patients' diets--either completely eliminating or adding certain types of foods--to treat specific types of conditions, such as cancer and cardiovascular disease. Finally, there is the approach that promotes eating a less refined, more "naturalistic" diet as the only way to promote optimal health and prevent illness. This last approach holds that staples of the typical American diet (e.g., meat and dairy products) are basically unhealthful and should be avoided altogether. The remainder of this chapter describes representative alternative therapies along this continuum.Alternative Approaches to Diet and Nutrition That May Prevent or Control Chronic Illness as Well as Promote Health
The Use of Vitamins and Other Nutritional Supplements in the Prevention of Chronic Disease Vitamins are organic substances required by all living organisms for healthy life and growth. Among their many properties, vitamins function as coenzymes (helpers to the primary enzyme) in metabolic reactions. Higher animals, particularly humans, cannot synthesize vitamins and therefore must ingest them as part of their diet. Deficiency in a particular vitamin results in a specific vitamin deficiency disease, such as rickets (a bone deformity from lack of vitamin D) and scurvy (the infamous sailors' deficiency disease of old, caused by lack of vitamin C-containing fruits and vegetables on sailing ships). Each type of deficiency disease is typically characterized by a "classic" set of symptoms. Vitamins of the B complex and vitamin C are water soluble (i.e, they dissolve readily in ~water). The B complex vitamins are found in food sources such as whole wheat bread, fruits, green and yellow leafy plants, and animal sources such as eggs, dairy products, and liver. They include B1 (thiamine), B2 (riboflavin), B3 (nicotinic acid, or niacin), pantothenic acid, B6 (pyridoxine), biotin, folic acid, and B12. Certain other substances, such as choline, also may be considered as belonging to the B complex. Vitamin C (ascorbic acid) is present in certain fruits and green vegetables. All the remaining vitamins (A, D, E, and K) are fat, or lipid, soluble (i.e., they dissolve more readily in oil than in water). Vitamin A (in the form of carotenoids) occurs naturally in green leafy and yellow vegetables; spinach, collards, kale, chard, carrots, and sweet potatoes are particularly good sources. Vitamin E (tocopherol) is found in many plant oils, such as corn oil. In adults vitamin K is supplied by intestinal bacteria. A number of other minerals and nutrients, such as iron, calcium, magnesium, selenium, and zinc, have been found essential for preventing deficiency diseases. For example, magnesium, which is required for the activation of more than 300 enzymes in the body and for the use of ~some vitamins and minerals, is required for normal function and structure of the arteries, heart, kidneys, and bone (Seelig, 1980), and for the neuromuscular system (Durlach, 1988; Galland, 1991). There also are a number of "essential" amino acids and fats (that is, humans cannot synthesize them). Some other amino acids are considered "semiessential" because humans cannot synthesize them fast enough to meet metabolic needs. Research base. The relatively few studies that have explicitly investigated the role of vitamin and mineral supplements in promoting health and preventing disease have generally found benefits from the supplements. In fact, evidence is increasing rapidly for a beneficial role of supplementation with a number of nutrients, including vitamins B6, C, and E; beta-carotene and other carotenes; folic acid; calcium; magnesium; and other factors. Although there is little dispute about the importance and functions of many vitamins and nutrients, questions arise regarding the levels necessary to produce optimum health. Many contend that the optimal levels of these compounds can be obtained in a normal diet and that the effect of additional amounts is negligible (National Research Council, 1989). To answer such questions, it is first necessary to compare some nutrient levels in the typical American diet with current RDAs as ~well as with what some now consider to be optimal levels based on the most recent research. The following includes data from recent studies on the minerals calcium, iron, and magnesium as well as the vitamins C, D, E, beta-carotene, and folic acid. Calcium. Some authorities have recommended that women (including young women) consume 1,000 to 1,500 milligrams (mg) of calcium per day to develop and maintain bone health and prevent osteoporosis (Office of Medical Applications of Research, 1984). Although it is technically feasible to achieve this level by diet alone, most people in the United States do not get that much calcium in their diet. In fact, the median intake among American women is only 600 mg per day, or around half the optimal level. Furthermore, 25 percent of women consume less than 400 mg per day (based on an average of 4 nonconsecutive days over 1 year) (U.S. Department of Agriculture, 1988). Iron. Approximately 8 percent of low-income women and 10 to 20 percent of low-income children are believed to be iron deficient (Public Health Service, 1989). While the RDA for women is 15 mg per day, only slightly more than 10 percent of women achieve this goal ~from diet alone; less than 10 percent of low-income women achieve this level (Block and Abrams, 1993; U.S. Department of Agriculture, 1988). Iron deficiency is not an important public health problem among men; indeed, some evidence suggests that iron overload in men may be a source of illness, such as heart disease (Sullivan, 1992). Absorption of iron from supplements and plant sources is quite low if body stores of iron are adequate; however, iron from red meat continues to be absorbed even if body stores of iron are plentiful (Ascherio and Willett, 1994). Therefore, until this hypothesis can be more fully studied, it may be prudent for men to avoid daily consumption of red meat. Magnesium. Extensive metabolic balance studies done by the USDA Research Service showed that the ratio of dietary calcium to magnesium that best maintained equilibrium (i.e., output equaling intake) was 2:1 (Hathaway, 1962). This ratio is achieved at the median magnesium intake of approximately 600 mg per day. However, dietary surveys taken in the last decade have found that most Americans' diets provide less than 300 mg/day (Lakshmanan et al., 1984; Morgan and Stampley, 1988; Spillman, 1987). Thus, like that of calcium, the median daily intake of magnesium in the United States appears to be ~inadequate. Long-term magnesium deficiency causes damage to arteries and the heart in all species of animals tested--rodents, cats, dogs, cattle, and monkeys (Seelig, 1980; Seelig and Heggtveit, 1974). It also adversely affects fat metabolism, increasing the "bad" lipids--low-density lipoprotein (LDL) cholesterol and triglycerides, which are associated with atheromas (fat deposits in arteries)--and decreasing the levels of "good" lipids--high-density lipoprotein (HDL) cholesterol, which remove fat deposits from the arterial wall (Altura et al., 1990; Rayssiguier, 1981, 1984, 1986; Rayssiguier et al., 1993). On the other hand, magnesium supplementation appears to be effective in reversing this process. For example in a double-blind, placebo-controlled study, 47 patients with coronary artery disease and heart attacks were treated with oral magnesium or placebo for 3 months. Those who received the magnesium experienced a 27-percent decrease in the "bad" lipids in contrast to a slight increase in the placebo group. There was also a tendency toward increased HDL in the magnesium group (Rasmussen et al., 1989a). The investigators ~observed that these findings support the assumption that magnesium deficiency might be involved in the causation of coronary artery disease. Oral magnesium preparations have also favorably influenced blood lipids in diabetes mellitus, lowering high levels of LDL and raising low levels of HDL (Corica et al., 1994). In another study in which about half of 374 men at high risk for serious cardiovascular disease were put on a diet high in magnesium (a predominantly vegetarian diet containing 900 to more than 1,200 mg of magnesium daily) and half were put on a regular diet (containing about 300 to 500 mg of magnesium daily), sudden cardiac deaths were 1.5 times more common in the low-magnesium group. Total complications occurred in 60 percent of the low-magnesium group versus 28.6 percent of the high-magnesium group (Singh, 1990). Total mortality was 18 percent and 10.7 percent in the low-and high-magnesium groups, respectively. Furthermore, in a 6-week study of 206 non-insulin-dependent diabetic patients there was significant lowering of LDL levels and slight raising of HDL levels on a high-magnesium diet versus no change in 194 comparable patients on their usual diets (Singh et al., 1991).~Epidemiological evidence also supports the premise that magnesium protects against cardiovascular disease in humans. Areas of the world where the intake of magnesium is high from either drinking water or diet have low prevalence of cardiovascular disease (Anderson et al., 1980; Durlach et al., 1989; Eisenberg, 1992; Hopps, 1981; Leary, 1986; Marier, 1978). In the United States, the Southeast (where water is soft and is low in magnesium) is known as the heart attack-kidney stone belt, whereas the northern Midwest Plains states (where water is hard and is high in magnesium) have lower cardiovascular disease rates and longer life expectancies (Hopps, 1981; Hopps and Feder, 1986).

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