Carbohydrates are the most important source of calories for the world's population because of their relatively low cost and wide availability. This chapter discusses the role of digestible (simple and complex) carbohydrates in the etiology and prevention of chronic diseases. The indigestible carbohydrates (components of dietary fiber) are considered in Chapter 10.
Simple carbohydrates are sugars and include monosaccharides, which consist of one sugar (saccharide) unit per molecule, and disaccharides, which contain two sugar units per molecule. The monosaccharides glucose and fructose and the disaccharides sucrose, maltose, and lactose occur naturally. Glucose and fructose are found in honey and fruits, whereas sucrose (common table sugar) is found in molasses, maple syrup, and in small amounts in fruits. Sucrose is made up of 1 unit each of glucose and fructose per molecule, whereas lactose (milk sugar) consists of 1 glucose and 1 galactose unit per molecule. Maltose consists of two glucose molecules and is present in sprouting grains, malted milk, malted cereals, and some corn syrups.
Sugars added during food processing include sucrose, fructose, and syrups that contain glucose or fructose. Ordinary corn syrups are made by hydrolyzing corn starch and contain glucose, maltose, and higher polymers of glucose. High-fructose corn syrups (HFCSs), which are made by the isomerization of glucose-containing syrups, contain both fructose and glucose in varying amounts. The most commonly used HFCSs contain from 42 to 55% fructose on a dry weight basis (Glinsmann et al., 1986).
Complex carbohydrates, or polysaccharides, are large molecules consisting of many sugar units. Starches (polymers of glucose) are the most abundant polysaccharides in the diet and occur in many foods, including cereal grains, legumes, and potatoes. Glucose, fructose, and galactose are produced during the digestion of the carbohydrate mixture found in the usual diet. After absorbtion, fructose and galactose are converted in the liver to glucose, the blood sugar. Although liver and muscles can store excess glucose as glycogen (animal starch), small amounts of glycogen remain in muscle meats after slaughter. Consequently, practically all dietary carbohydrates come from plant sources, except for lactose, which comes from milk.
Dietary Intake of Carbohydrates
Historical trends in the amounts of carbohydrates in the food supply since 1909 have been reported by the U.S. Department of Agriculture (Marston and Raper, 1987). These data do not represent the amount of carbohydrates actually consumed, however, because there are no esti-
mates of losses or waste and no measurements of actual intake. Total carbohydrate availability has declined since 1909; per-capita amounts fell from 493 g/day during 1909-1913 to a low of 378 g/day during 1967-1969 and rose to 413 g/day in 1985 (Chapter 3, Table 3-3). The decline was due to decreased use of flour and cereal products.
From the early part of this century to the 1980s, there was a notable shift in the proportion of total carbohydrate derived from starch and sugars. During 1909-1913, 68% of total carbohydrates came from starch, in comparison to 47% in 1980. Conversely, the contribution of sugars increased from 32% during 1909-1913 to 53% in 1980 (Welsh and Marston, 1982).
Over the past 20 years, the relative contribution of sugars to the food supply has changed. In 1965, sucrose predominated, comprising 85% of total sugars; sugars in corn syrups comprised only 13%. There were no HFCS sweeteners at that time. By 1985, the use of all types of corn syrups had increased to 47% of total sugars but there was a concomitant decline in sucrose use. The marked increase in corn syrup use during the last decade was due chiefly to greater use of HFCSa popular sweetener of soft drinks and other processed foods. In 1985, HFCS accounted for 30% of the total sugar supply (Glinsmann et al., 1986).
The 1977-1978 Nationwide Food Consumption Survey (NFCS) (USDA, 1984) indicated that carbohydrates furnished an average of 43% of calories, whereas the NFCS Continuing Survey of Food Intakes by Individuals (CSFII) (USDA, 1986, 1987, 1988) suggested that women and children derived closer to 47% of their calories from carbohydrates. Both surveys indicated that children had higher proportionate intakes of carbohydrates than did adults and that women had higher intakes of carbohydrates compared to men of the same age group. Because these surveys did not take into account the percentage of calories from alcohol, the reported percentages of calories from carbohydrates, fats, and proteins are inaccurate. Carbohydrate intake was not affected by region, urbanization, or season; however, it was higher for those below than above the poverty level (USDA 1984, 1987, 1988).
In 1986, the Food and Drug Administration (FDA) estimated that the average daily intake of all sugars by the U.S. population accounted for 21% of total calorieshalf coming from added sugars and half from naturally occurring sugars. On the average, approximately 4% of calories came from fructose, 9% from sucrose, and 5% from sugars in corn syrups (see Chapter 3, Tables 3-6 and 3-7, and Glinsmann et al. 1986).
Evidence Associating Carbohydrate Intake with Chronic Diseases
Noninsulin-Dependent Diabetes Mellitus
Most epidemiologic studies were conducted at the time when distinction was still made between juvenile-onset and adult-onset diabetes rather than the most recently adopted more distinct classifications of Type I, or insulin-dependent diabetes mellitus (IDDM), and Type II, or noninsulin-dependent diabetes mellitus (NIDDM), respectively. Although the studies referenced here generally concern adult-onset diabetes, it seems reasonable to extend the results to all cases of diabetes.
Increased intake of sugars or total carbohydrates is not associated with increased risk of NIDDM. In a prospective study of 9,494 male Israeli government employees who were nondiabetic and 40 years of age or older at baseline, Medalie et al. (1974) found no association between calories from sugars or intake of total carbohydrates and incidence of diabetes mellitus over a 5-year follow-up. In a cross-sectional study of 3,454 employed people in England, Keen et al. (1979) observed that intake of carbohydrates, fats, and protein tended to be inversely correlated with concentration of blood sugar and indices of glucose tolerance; they inferred that the correlations probably were confounded by caloric expenditure. Baird (1972) reported an inverse association between sugar intake and prevalence of previously undetected diabetes among the siblings of diabetic propositi. West et al. (1976) found no association between sugar consumption and occurrence of diabetes in 286 Plains Indians, whose intake of refined sugar ranged from less than 70 g/day to more than 200 g/day.
In a study involving 22 countries, Yudkin (1964) reported a correlation of 0.73 between mean per-capita supply of sugars from 1934 to 1938 and risk of death due to diabetes from 1955 to 1956. West (1978) pointed out that this result was not consistently observed; in a sample of 44 countries, the correlation was only 0.18 for sugar intake in 1951 and diabetes mortality in 1971. Furthermore, sugar consumption is high in several coun-
tries where rates of diabetes are low (Walker, 1977). In a correlation analysis study of data obtained from 1894 to 1934 in several countries, Himsworth (1935-1936) observed an inverse association between rates of death from diabetes and the mean percentage of total calories obtained from carbohydrates in the diets of urban working-class families. West (1978) reported an inverse correlation between prevalence of diabetes and mean percentage of calories from carbohydrates in surveys of persons 35 years of age and older in seven countries. To the extent that such correlations do exist, it seems reasonable to infer that they do not reflect direct associations but, rather, that they reflect confounding by variables such as caloric expenditure and obesity.
No long-term prospective studies have attempted to alter the incidence of NIDDM by changing the carbohydrate content of the diet. On the other hand, shifts in the proportion of carbohydrates in the diet have been used in the clinical management of both types of diabetes and have had a controversial history (Bierman, 1979). High-carbohydrate diets have been recommended for the management of diabetes, because they appear to improve glucose tolerance and insulin sensitivity, and with a change to such a diet, there is a concomitant reduction in the proportion of calories as fat, which reduces risk of atherosclerosisa major cause of death among diabetics (American Diabetes Association, 1987). There have been no prospective studies on the influence of diet on the complications of diabetes, and the role of diet in the increased prevalence and severity of atherosclerosis among diabetics has not been documented. In studies of high-carbohydrate, low-fat diets given to people with NIDDM, investigators have observed reduced incidence of hyperglycemia, hypercholesterolemia, and hypertriglyceridemia, and decreased treatment requirements (Anderson and Ward, 1979; Blanc et al., 1983; Kiehm et al., 1976; Simpson et al., 1979a,b; Stone and Connor, 1963; Story et al., 1985). An increase in insulin sensitivity observed in vivo after high-carbohydrate diets (Kolterman et al., 1979) is consistent with enhanced insulin action at the cellular level (Olefsky and Saekow, 1978).
A change from a diet of average composition to a very-high-carbohydrate, low-fat diet (more than 60% of calories as carbohydrates and moderate to large amounts of sucrose, i.e., up to 220 g/day) is associated with short-term (2- to 4-week) increases in fasting plasma very-low-density lipoprotein (VLDL) and triglyceride levels in NIDDM patients (Emanuele et al., 1986; Jellish et al., 1984; Reaven, 1986) similar to those seen in nondiabetics. A 5-week study in which a diet high in complex-carbohydrates (65% of total calories) was substituted for saturated fat in NIDDM patients with normal lipid levels failed to show an increase in fasting serum triglyceride levels (Abbott et al., 1989). In a study by Reiser et al. (1981a,b), graded amounts of sucrose (up to 33% of total calories) were fed for 6 weeks in a gorging pattern (most of the daily calories at dinner) to subjects preselected on the basis of exaggerated insulin responses to a sucrose load. Higher fasting glucose, insulin, and triglyceride levels were observed at higher sucrose intakes. In contrast to fasting levels, postprandial triglyceride levels have been shown to decrease in hypertriglyceridemic NIDDM patients on high-sucrose, high-carbohydrate diets (Emanuele et al., 1986). However, in part based on their short-term metabolic studies (15-day periods comparing 60% and 40% carbohydrate diets in nine subjects), Reaven and colleagues (Coulston et al., 1987; Reaven 1988) have cautioned against using this type of diet for long-term management of NIDDM on the basis of observed increases in postprandial glucose and insulin levels and in basal triglyceride levels. Recently, these studies were repeated with longer (6-week) dietary periods yielding similar findings (Coulston et al., 1989). These diets were already reduced in saturated fat and cholesterol.
Studies in which smaller amounts of mixed carbohydrate (de Bont et al., 1981; Weinsier et al., 1974) or sucrose (Peterson et al., 1986) were substituted for fat in diets tested on diabetics failed to show elevations of fasting triglyceride levels. This was confirmed in a recent metabolic ward study comparing a 60% mixed-carbohydrate diet with a 50% carbohydrate baseline diet in 10 subjects with NIDDM, but fasting triglyceride levels were increased in comparison to a high monounsaturated (50% fat, 33% monounsaturated) fat diet (Garg et al., 1988). Thus, evidence from some short-term metabolic studies suggests that normolipidemic diabetics whose diet is changed from one that is high in saturated fat to a diet containing very high carbohydrate levels and moderate to large amounts of sucrose respond with an increase in fasting triglyceride levels but do not consistently have increased postprandial triglyceride levels. Lesser degrees of substitution of carbohydrate for saturated fat usually do not increase fasting triglyceride levels. The increase in fasting
triglyceride levels in hypertriglyceridemic diabetics is exaggerated; after 2 weeks, these levels tend to revert toward control levels. High-carbohydrate, low-saturated fat diets lower both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels (Abbott et al., 1989; Katan, 1984) and usually the degree of hyperglycemia as well.
Diabetic populations, such as those in Asia, that subsist on high-carbohydrate diets have lower levels of plasma cholesterol, LDL cholesterol, and plasma triglycerides and higher levels of HDL cholesterol and apolipoprotein A1 than do persons with diabetes in the United States (Pan et al., 1986). The relatively low frequency and severity of atherosclerotic disease among these diabetic populations compared to Western diabetics have long been known (West, 1978; WHO, 1985). Studies in migrant populations have shown that diabetic men adopting a higher-fat, lower-carbohydrate diet after moving from Japan to Hawaii have increased triglyceride and cholesterol levels and a higher incidence of cardiovascular diseases (Kawate et al., 1979). Nevertheless, although some diet-specific effects on the complications and severity of already diagnosed diabetes may continue to be suspected or remain controversial, there is little evidence to implicate dietary carbohydrates, either complex or simple, in the etiology of diabetes.
Evaluation of the hypothesis that a high-carbohydrate diet is an independent risk factor in the development of glucose intolerance or diabetes is complicated by such factors as hyperphagia and meal patterns (ad libitum versus meal feeding), which can influence plasma insulin curves, body weight, and fat pad weight (Glinsmann et al., 1986). Data derived from studies in several animal species have been somewhat difficult to interpret and are frequently contradictory. For example, in a prediabetic line of female Yucatan miniature swine genetically selected for diminished glucose tolerance, a diet containing 42% of calories as sucrose or starch for 3 months appeared to improve glucose tolerance (Phillips et al., 1982). In contrast, a strain of the spiny mouse (Acomy cahirinus), a desert animal with pancreatic beta-cell hyperplasia and abnormal carbohydrate metabolism, developed decreased glucose tolerance, increased plasma triglycerides and cholesterol levels, and an increase in liver enzymes involved in lipid metabolism after consuming a diet containing 55% sucrose for 4 months (Obell, 1974).
In a study by Cohen (1978), genetically selected prediabetic rats (Hebrew University) were fed diets containing 72% (by weight) of sucrose, fructose, glucose, or starch for 8 months. Rats fed the high-sucrose and high-fructose diets had high glucose peaks, relatively higher tissue insulin resistance, and increased serum cholesterol, but those on the high-starch diet did not. The high-fructose diet also resulted in elevated triglyceride levels. None of these adverse effects was noticed in the normal rat strains used as controls. Prediabetic male rats developed proteinuria (nephropathy) and testicular atrophy and lost weight after eating these high-sucrose (72% by weight) diets (Rosenmann et al., 1974). In pregnant females, this diet caused an increase in fetal malformations (Ornoy and Cohen, 1980). Thus, although these studies suggest that glucose intolerance may be worsened or provoked in animals predisposed to that condition, their results have to be extrapolated with caution because of the very high levels of sugar used, which far exceed levels in the common U.S. diet, especially the usual diets of patients with diabetes.
The desert sand rat (Psammomys obesus) has been used as a laboratory model for both adult-onset diabetes and spontaneous obesity, since it overeats when given free access to food and becomes obese and hyperinsulinemic (Kalderon et al., 1986). In a study by Rice and Robertson (1980), sand rats fed a sucrose-rich (56%) diet for 18 months did not differ from sand rats fed a starch-rich (56%) diet in development of obesity and insulin resistance; diabetes was not reliably produced in either case.
A new rodent model of NIDDM was described by Ikeda et al. (1981). This Wistar rat (now designated WDF/Ta-fa/fa) was produced by transferring the mutant gene Fa (fatty) from the obese, hyperinsulinemic but normoglycemic Zucker fatty rat to a lean albino Wistar Kyoto background rat using a combination of inbreeding and backcrossing. Unlike the obese Zucker rat, which becomes insulin resistant and hyperinsulinemic but does not become hyperglycemic or glucosuric, the WDF/ Ta-fa/fa male becomes frankly diabetic. If the obese male is fed a diet high in sucrose, it becomes diabetic earlier and the hyperglycemia is worsened in the already hyperglycemic animal (Greenwood et al., 1988). The female WDF/Ta-fa/fa rat does not respond to the high sucrose diet by developing hyperglycemia. Thus, this new strain provides a sexually dimorphic rodent model in which to examine the interaction of diet with sex-associated obesity and diabetic traits.
Genetically obese young male SHR/N-cp/cp (corpulent) rats fed diets containing 54% (by weight) sucrose or cornstarch for 9 weeks had increased body weight, hyperlipidemia, hyperinsulinemia, and abnormal glucose tolerance. Their lean litter mates (+/cp) had increased blood insulin levels but were normoglycemic (Michaelis et al., 1984). Thus, it seems that obesity may be the most important dietary factor in the development of diabetes in this and other animal models.
In a study by Stearns and Smith (1985), female WDF/Ta-fa/fa rats were fed diets containing 77% (by weight) sucrose or cornstarch for 60 days. The sucrose-fed rats had increased body weight, but exhibited no differences from cornstarch-fed rats in their plasma glucose, insulin, or triglyceride levels, triglyceride secretion rates, or pancreatic insulin content. That study shows that hyperglycemia, hypertriglyceridemia, and hyperinsulinemia do not necessarily accompany sucrose feeding of rats.
Insulin-Dependent Diabetes Mellitus
The role of carbohydrates has not been examined in epidemiologic studies, at least in recent years, because there is considerable consensus that the etiology of IDDM is not diet dependent.
Alterations in carbohydrate intake have been used as an adjunct to the management of IDDM patients with the goal of preventing chronic diseases, especially atherosclerosis. As with NIDDM, increasing the proportion of total calories from carbohydrates improves insulin sensitivity; lowers glucose, triglyceride, and cholesterol levels; and decreases insulin requirements (Simpson et al., 1979b; Stone and Connor, 1963). Also, as with NIDDM, very-long-term clinical studies have not been performed.
Some short-term metabolic studies on high-carbohydrate diets have shown transient increases in basal triglyceride levels (Bierman and Hamlin, 1961; Hollenbeck et al., 1985), but others have not (Riccardi et al., 1984). Female patients with IDDM who were fed a 65% carbohydrate, low-cholesterol diet for 6 weeks had slightly increased triglyceride levels, reduced cholesterol, apolipoprotein B, and apolipoprotein A1 levels but did not have altered glycemic control (Hollenbeck et al., 1985). These observations are similar to those described for NIDDM patients and nondiabetics.
In a diabetic strain of mice (C57BL/KsJ-db/db), pancreatic islet destruction results in insulin insufficiency and glucose intolerance, but the relevance of this model to humans is not yet known. Diets containing 60% (by weight) simple sugars (e.g., sucrose, fructose, or glucose) caused additional obesity, hyperglycemia, atrophy of pancreatic islets, and early death in this strain, whereas dextrin or meals without carbohydrates did not. In normal littermates (+/db), no adverse effects were observed (Leiter et al., 1983).
Other animal models of IDDM are created by chemical destruction of insulin-producing cells with streptozotocin, which produces moderate diabetes (hyperglycemia with glycosuria). Sucrose-rich diets fed to such animals usually produce increased adiposity and variable deterioration of glucose tolerance, making it difficult to determine whether observed effects are due to differences in adiposity or to specific effects of sucrose on glucose homeostasis (Goda et al., 1982; Gray and Olefsky, 1982; Hallfrisch et al., 1979). It appears that in animals, as in humans, carbohydrate-rich diets given in the untreated diabetic state may lead to further deterioration of glucose homeostasis. In contrast to studies of humans, few dietary studies have been conducted in animal models of IDDM during treatment of hyperglycemia.
Carbohydrates have been implicated in the development of microvascular changes in diabetic rodents. Studies of eye changes showed that there were increases in sorbitol, fructose, and lactate levels in the retina when either sucrose or cornstarch at 68% of the diet was fed for 15 days to streptozotocin-diabetic Wistar rats (Heath and Hamlett, 1976; Heath et al., 1975). Six months of feeding the same high-sucrose diet to normal Wistar rats produced retinopathy similar in severity to retinal changes in diabetic rats on high-starch diets (Papachristodoulou et al., 1976). Fructose alone was found to cause comparable retinal changes in the same strain of diabetic rats (Boot-Hanford and Heath, 1981). Thornber and Eckhert (1984) suggest that retinopathy following high-sucrose diets may be due to dietary deficiencies, since supplementation of experimental diets containing 68% (by weight) of sucrose with chromium, selenium, and corn oil prevented capillary damage.
Increased kidney weight and glomerulosclerosis were observed in streptozotocin-diabetic Wistar rats on cornstarch diets and in normal rats consuming 68% of their diet as sucrose or fructose for
6 months (Boot-Hanford and Heath, 1981). Other authors also reported kidney changes in diabetic rats fed high levels of sucrose or cornstarch and in normal rats fed high levels of sucrose (Kang et al., 1982; Taylor et al., 1980).
Streptozotocin-diabetic Sprague-Dawley rats, but not normal rats, fed diets containing 66% (by weight) sucrose for 13 weeks had elevated HDL, VLDL, and total cholesterol (Bar-On et al., 1981). Sucrose fed at 66% of the diet for 21 days caused hypertriglyceridemia in diabetic male Sprague-Dawley rats, but not when the rats exercised daily (Dallaglio et al., 1983). The presence of 12% bran in a high-sucrose (32 or 72%) diet fed to Sprague-Dawley rats for 14 to 32 days reduced the plasma triglyceride levels to normal (Lin and Anderson, 1977).
The effects of high-sucrose diets on serum triglyceride and cholesterol levels seem to depend on the animal model used. For example, diabetic Wistar rats had increased lipid levels, whereas genetically diabetic mice had no change (Gonnermann et al., 1982).
Caution needs to be exercised in extrapolating the results of these animal studies to humans because very high levels of sugars were used, species appeared to differ in their responses, chronic effects on glycemia and metabolic changes often were not monitored, metabolic responses were not tested for reversibility, and some of the reported changes may have been due to nutrient deficiencies that also produce glucose intolerance (Glinsman et al., 1986).
Atherosclerotic Cardiovascular Diseases
Variations in the prevalence of coronary heart disease (CHD) among populations correlate directly with the proportion of calories derived from fats (Chapter 7) and, therefore, inversely with the proportion of calories derived from carbohydrates. Yudkin (1964) compared the per-capita sugar consumption in various countries with mortality from CHD and proposed that sugar contributes to the occurrence of heart disease. However, several subsequent studies have failed to substantiate this. Recent animal and epidemiologic data were reviewed in the 1986 report of the Sugars Task Force of the FDA, Evaluation of Health Aspects of Sugars Contained in Carbohydrate Sweeteners (Glinsmann et al., 1986). This task force stated, ''There was no conclusive evidence that dietary sugars are an independent risk factor for coronary artery disease in the general population."
A change from a Western-type diet to a very-high-carbohydrate, low-fat diet (60% or more of calories from any type of carbohydrate, e.g., simple sugars or starches) has been shown in short-term studies to cause a reduction of HDL (Gonen et al., 1981; Katan, 1984) and LDL (Abbott et al., 1989; Nestel et al., 1979) and a transient increase in fasting plasma triglyceride levels (Jellish et al., 1984; Reaven, 1986). Glucose, sucrose, fructose, and starch appear to have comparable effects on fasting triglyceride levels in short-term metabolic studies (Dunnigan et al., 1970; Mann and Truswell, 1970; McDonald, 1972; Nikkilä and Kekki, 1972; Porte et al., 1966; Turner et al., 1979). The increased basal triglyceride levels decline after several weeks to months on the high-carbohydrate diets, whereas reduced HDL levels persist (Katan, 1984). A high mixed carbohydrate diet (65% of calories) fed to normolipidemic subjects did not increase basal triglyceride levels after 4 to 6 weeks (Grundy et al., 1988). The transient increase in basal circulating triglycerides may be exaggerated in hypertriglyceridemic people (Ahrens, 1986; Liu et al., 1983) regardless of the type of carbohydrate and appears to be greater in men than in women (McDonald, 1985). High-carbohydrate diets lead to a short-term increase in overnight triglyceride levels, whereas postprandial triglyceride levels are actually lower in normal and hypertriglyceridemic subjects given high-carbohydrate diets than when fed high-fat diets (Barter et al., 1971; Schlierf and Dorow, 1973; Schlierf et al., 1971).
On the other hand, long-term feeding of diets high in carbohydrates and soluble fiber (e.g., oat bran) do not raise and may actually lower fasting triglyceride levels in hypertriglyceridemic people (Anderson and Tietyen-Clark, 1986). Such effects have not been observed in hypertriglyceridemic subjects consuming high levels of insoluble fiber (e.g., wheat bran). High-complex-carbohydrate diets (60% of total calories) fed to hypertriglyceridemic subjects for as long as 3 months have also been shown to reduce fasting triglyceride levels (Cominacini et al., 1988). Increased levels of cholesterol-rich and triglyceride-rich lipoproteins are not found in some populations, such as vegetarians or people living in parts of Asia, who have adapted to very-high-carbohydrate and low-fat intakes (Cerqueria et al., 1979) and who also have low levels of HDL, LDL, and VLDL as well as a low prevalence of CHD. The low HDL levels
(Connor et al., 1978; Katan, 1984; Knuiman et al., 1987) do not appear to adversely influence their low CHD prevalence rate.
A prospective study of the relationship of dietary intake to subsequent CHD was undertaken in Puerto Rico by Garcia-Palmieri et al. (1980). A 6-year follow-up of 10,000 men age 45 to 64 years in that study indicated that urban men who developed new CHD had significantly lower carbohydrate intakes. Similar results have been reported for populations in Framingham, Massachusetts (Gordon et al., 1981) and in Hawaii (Yano et al., 1978). In the Hawaii study, men who developed CHD during a 6-year follow-up consumed less total carbohydrates, starches, and sugars than did those without CHD. Thus the development of CHD does not appear to be associated with high-carbo, hydrate diets, and no differences among types of carbohydrate have been demonstrated.
Experimental studies such as the classic 5-year cohort study of 436 institutionalized mental patients in Vipeholm, Sweden (Gustafsson et al., 1954), have established that sugars consumed in sticky form, particularly between meals, increases the risk of dental caries. Restricting the intake of sugars (Becks, 1950) or substituting a nonfermentable sugar alcohol (xylitol) for sucrose (Scheinin et al., 1975) decreases the incidence of caries.
Cross-sectional studies support the inference that consumption of sugars is an important determinant of the incidence of dental caries. In 47 countries from which data were available in the late 1960s and 1970s, Sreebny (1982) found a correlation of 0.72 between the prevalence of dental caries in 12-year-old children and the mean per-capita supply of sugars. For 6-year-olds in 23 countries, the correlation was 0.31. The prevalence of dental caries in Japanese children decreased precipitously during the 1940s in conjunction with the severe reduction in supply of sugars (Takeuchi, 1961). Similar changes were noted in Europe (Sognnaes, 1948; Toverud, 1957).
Many clinical studies of diet and its association with plaque formation and composition are confounded by such variations in oral hygiene as brushing of teeth (Glinsmann et al., 1986). The bulk of the evidence from clinical studies, however, is consistent, indicating that all dietary carbohydrates are potentially cariogenic (Brown, 1975).
Telemetry analysis of plaque in situ demonstrates that plaque pH is lowered not only after consumption of a sugar cube (Geddes et al., 1977) and after rinsing with sucrose solutions (Tenovuo et al., 1984) but also after ingestion of starch (Mormann and Muhlemann, 1981). Abelson and Pergola (1984) determined the effects of three sucrose concentrations (10, 40, and 70%) on in vivo plaque pH in caries-prone 18- to 26-year-old adults. Above a certain concentration, additional sucrose did not heighten the acidogenic response. Schachtele and Jensen (1983) inserted a pH electrode in teeth to measure oral pH after consumption of various foods and found that several foods high in starch produced a marked decline in oral pH. These foods (white bread, white rice, and cooked carrots) are notable in that they contain either none or only low levels of individual sugars such as sucrose, glucose, and fructose; most of their carbohydrate content is starch.
The preponderance of clinical evidence, however, indicates that dietary sugars are of major etiologic importance in caries formation. Sucrose in solution has been shown to stimulate plaque formation (Geddes et al., 1978) and to alter the composition of plaque and saliva to a form suggestive of increased mineral resorption from the teeth (Tenovuo et al., 1984). In five subjects, who frequently rinsed their mouths with a sucrose solution for 2 months, there were changes characteristic of early demineralization of tooth surfaces (Geddes et al., 1978). Slabs of bovine enamel mounted in the human mouth likewise underwent demineralization when frequently exposed to sucrose (Pearce and Gallagher, 1979; Tehrani et al., 1983).
Sucrose in foods has also been shown to be cariogenic. In one clinical trial (Scheinin et al., 1975), three groups consuming diets containing sucrose, frutose, or xylitol were followed for 2 years. By the study's end, the average number of decayed, missing, or filled teeth (DMFT) was higher in the sucrose group than in the fructose group. Subjects consuming only xylitol had virtually no DMFT. The authors attributed the low cariogenicity of xylitol to the fact that it is not metabolized by oral microbes (Scheinin, 1976; Scheinin et al., 1975). The inability of other studies to demonstrate a cariogenic effect of presweetened cereals in schoolchildren (Finn and Jamison, 1980; Glass and Fleisch, 1974) may
reflect differences in the specific sugars added to the cereals (Glinsmann et al., 1986).
The form of dietary carbohydrates also appears to influence cariogenicity. Consumption of canned pears and apples, for example, lowers plaque pH to a greater degree than do sugars alone (Imfeld et al., 1978; Jensen and Schachtele, 1983). Edgar et al. (1975) found that there was a wide variation in the ability of different snack foods to increase plaque acid formation. However, the extent of plaque acid formation from foods does not necessarily indicate either the amount of enamel destruction that will occur or the number and severity of the related caries.
The sequence in which carbohydrate-containing foods and other foods are eaten also appears to influence caries formation. A sharp increase in oral hydrogen-ion concentration and in plaque scraped at regular intervals from the mouth has been noted after use of a sugar rinse; the concentration of hydrogen ions returns to baseline after approximately 30 minutes. If cheese is consumed 5 minutes after the sugar rinse, however, the sharp increase in hydrogen-ion concentration is diminished and the concentration returns quickly to baseline (Edgar, 1981; Edgar et al., 1982; Schachtele and Jensen, 1983). The frequency of carbohydrate consumption also appears to influence caries formation. In the Vipeholm study, caries activity in adult patients was monitored over several years while their diet and eating schedule were controlled. There were two important findings. First, the extent of caries activity appeared to be influenced more by the frequency of sucrose intake than by total amount consumed. Second, consumption of solid forms of sugar appeared to be more cariogenic than liquid forms (Gustafsson et al., 1954).
In summary, clinical evidence suggests that all carbohydrates are cariogenic to various degrees, but that the form of carbohydrate-containing foods, as well as their sequence and frequency of consumption, can substantially influence their cariogenicity. Beyond this observation, little is known about the cariogenic potential of specific carbohydrate-containing foods because of the complex and interactive role of diet in caries formation. Dental caries is a multifactorial bacterial disease; dietary factors, host resistance, fluoride exposure, and the nature of bacterial flora in the mouth all play important roles (Shaw, 1987). In addition, most clinical studies have involved adults whose teeth are much less caries-prone than those of children, which suggests caution in generalizing such findings.
Rats exhibit a dose-dependent increase in caries formation as sucrose is added to the diet; a cariogenic effect is observed at dietary levels as low as 0.1% (by weight) of diet (Michalek et al., 1977). However, a saturation point on the dose-response curve has been noted at anywhere from 8% (Kreitzman and Klein, 1976) to 40% dietary sucrose (Hefti and Schmid, 1979); there is no increase in caries formation above these levels. The cariogenic potential of sucrose is greater than that of equivalent amounts of glucose, fructose, or invert sugars (mixture of dextrose and fructose obtained by hydrolyzing sucrose) (Birkhed et al., 1981; Horton et al., 1985).
Frequency, form, and composition of the diet appear to influence the cariogenicity of dietary carbohydrates in animals as in humans. For example, frequent consumption of carbohydrates markedly accelerates caries formation (Firestone et al., 1982; Skinner et al., 1982). Certain carbohydrate-containing foods, such as bananas, are much more cariogenic than sucrose alone or even frequently fed sucrose-topped chocolate (Shrestha and Kreutler, 1983). Consumption of an unsweetened cereal to which sucrose has been added has been shown to cause fewer caries than consumption of cereals presweetened with equal sucrose levels (McDonald and Stookey, 1977), and carbohydrates in the form of maize or wheat starch have virtually no cariogenic activity (Beighton and Hayday, 1984; Horton et al., 1985). With respect to dietary composition, addition of cheese to a cariogenic diet has been shown to be protective against buccal (cheek side) decay in some studies (Edgar et al., 1982; Harper et al., 1987) and against buccal as well as sulcal (toward the linear depression or valley in the occlusal surface of the tooth) caries in others (Rosen et al., 1984).
The rat is the most favored animal species in studies of dietary carbohydrates and dental caries. This is due to the rapidity with which it develops experimentally induced dental caries and to the similarity of its sulcal and smooth-surface carious lesions to those of humans (Glinsmann et al., 1986). Most findings in rats seem likely to be applicable to humans. Generalizations should still be made with caution, however, since feeding patterns and oral physiology differ. For example, microbial flora, oral pH, salivary composition, flow rate, and buffering capacity are known to differ between the two species (McDonald, 1985). Also, rats nibble throughout the day, and it is known that meal frequency correlates positively, and
strongly, with caries formation in animals (Firestone et al., 1982; Skinner et al., 1982) and in humans (Gustafsson et al., 1954). Also, assessment of the cariogenicity of foods in animals is complicated by the fact that foods must be given in powdered form and not in the physical form usually consumed by humans (Krasse, 1985). Differences in oral physiology further complicate the issue. For example, most types of phosphates effectively reduce caries in rats when added to sucrose-containing diets, whereas phosphate supplemention of the human diet has been markedly unsuccessful in reducing caries incidence (Nizel and Harris, 1964). Although some caution is warranted in interpreting evidence obtained from the rat model, animal studies are essential to our understanding of the role of dietary carbohydrates in cariogenesis.
The cariogenic action of dietary sucrose is influenced by other dietary constituents. For animals (Edgar et al., 1982; Harper et al., 1987) and humans (Edgar, 1981; Edgar et al., 1982; Schachtele and Jensen, 1983), cheese exerts a protective effect by blunting the short-term increase in hydrogen-ion concentration characteristically associated with a cariogenic diet. Cheese extracts administered after sucrose rinses have also been shown to inhibit demineralization of bovine enamel blocks fitted into the mouths of volunteers (Silva et al., 1987). Dietary substances inhibiting sucrose cariogenicity in animals include cheddar cheese (Rosen et al., 1984); mineral concentrates containing protein, calcium, and phosphate (Harper et al., 1987); cocoa (Paolino, 1982); lycasin, a hydrogenated corn syrup product (Leach et al., 1984); xylitol (Leach and Green, 1981; Shyu and Hsu, 1980); and saccharin (Linke, 1980). The mechanisms by which these substances inhibit sucrose cariogenicity are not fully understood; they may include enzyme inhibition in oral bacteria (Paolino, 1982), the stimulation of saliva, which maintains plaque pH in a neutral range (Krasse, 1985), and, for cheeses, the influences of texture and the casein or calcium-phosphate content (Harper et al., 1987).
Epidemiologic and Clinical Studies
An inverse association between caloric intake and body fatness has been found in some epidemiologic studies (Baeke et al., 1983; Johnson et al., 1956; Keen et al., 1979; Keys et al., 1967; Kromhout, 1983a,b; Lincoln, 1972; Maxfield and Konishi, 1966; McCarthy, 1966; Stefanik et al., 1959; Wilkinson et al., 1977) but not in others (Morris et al., 1977). It is likely that variation in caloric intake along with variation in amount of physical activity are factors in the causation of obesity (Sopko et al., 1984). This issue is discussed in Chapter 6.
Studies in which the influence of calorie sources was assessed indicate that compared to lean people, fatter people generally have a lower mean intake of calories from all sources including carbohydrates (but excluding alcohol). Keen et al. (1979) found small inverse correlations (-0.01 to -0.31) of body mass index with intake of total energy, protein, fats, total carbohydrates, and sucrose in three samples of employed men and women in Great Britain. These results show that in the general population obese adults do not consume more sugars or more complex carbohydrates than lean people; in fact, they seem to consume less.
Psychophysical taste testing in obese and normal humans also consistently indicates that obese subjects do not have stronger preferences for sucrose or sweet solutions (Drewnowski et al., 1985; Grinker, 1978; Malcolm et al., 1980). Interpretation of the epidemiologic results is complicated, however, by the association of physical activity as well as total caloric intake with body fatness (see Chapter 6).
In contrast to the clinical and epidemiologic data, studies in animals show that various types of high-carbohydrate diets can lead to obesity. For example, a diet containing sucrose produced greater weight gains in lean and corpulent (SHR/ N-cp/cp) rats than did a diet containing cooked cornstarch (Michaelis et al., 1984). Although the sweet taste of sugar has been thought to encourage overeating in rats, Hill et al. (1980) found no differences in carbohydrate or caloric intake when adult male rats were offered either a sweet-tasting sucrose solution or a bland dextrin powder in addition to a chow diet, but the sucrose group gained more weight. In a similar experiment, Sclafani and Xenakis (1984) compared solutions of sucrose, Polycose (a bland-tasting polysaccharide), or Polycose sweetened with saccharin. They concluded that sweetness was not essential for production of carbohydrate-induced obesity, although it did increase the intake of polysaccharide.
Kanarek and Hirsch (1977) have described a method of producing obesity in rats by feeding
them sucrose solutions. In later experiments, Kanarek and Orthen-Gambill (1982) observed that obesity could also be induced by supplementing the standard diet with solutions of glucose or fructose. Rattigan and Clark (1984) reported that the effect of a sucrose solution depends on the composition of the solid diet. Body weight and body fat increased without a significant increase in total caloric intake in rats given a low-fat, high-carbohydrate diets and the sucrose solution. Body weight, body fat, and total caloric intake were all decreased, however, in rats given high-fat, low-carbohydrate diets and the sugar solution.
Epidemiologic and Clinical Studies
There is little epidemiologic evidence to support a role for carbohydrates per se in the etiology of cancer. No definitive conclusion is justified, however, because carbohydrates have often been reported in epidemiologic studies only as a component of total energy and not analyzed separately.
In several international correlation studies, investigators have evaluated the role of sugar and sometimes carbohydrates in the etiology of some cancers. Armstrong and Doll (1975) found that sugar intake was positively correlated with both the incidence of and mortality from cancer of the colon, rectum, breast, and ovary, and with the incidence of cancer of the corpus uteri. Similar positive correlations were found between sugar intake and the incidence of and mortality from cancer of the prostate, kidney, and nervous system and the incidence of cancer of the testes. Sugar intake was inversely correlated with liver cancer incidence, but positively correlated with mortality from pancreatic cancer in women. Armstrong and Doll (1975) also reported a weak association between liver cancer incidence and the intake of potatoesa starch-rich vegetable. For most of the sites reported, however, particularly the colon, rectum, and breast, the positive correlations with fat intake were greater than for sugar intake. Other investigations have produced similar findings. For example, Hems (1978) and Carroll (1977) found a positive correlation between breast cancer and sugar intake. Subsequently, however, Carroll (1986) found that whereas breast cancer mortality is positively correlated with the percent of calories derived from dietary fat, it varies inversely with the percent of calories from carbohydrates. This mirrors an earlier finding by Hems and Stuart (1975), who also found an inverse relationship between breast cancer incidence and starch consumption.
Hakama and Saxen (1967) reported a strong correlation between the per-capita intake of cereal used as flour and mortality from stomach cancer. The possible association of carbohydrate intake with gastric cancer was further evaluated by Modan et al. (1974), who found that high-starch foods were consumed more frequently by cases than by controls. Similarly, in a case-control study of diet and stomach cancer in Canada, Risch et al. (1985) found an increasing risk with total carbohydrate consumption but the relative risk for each 100-g/day increase in carbohydrates was only 1.53.
The effect of monosaccharides was evaluated in two studies of colorectal cancer. In a case-control study conducted in Marseilles (Macquart-Moulin et al., 1986), there appeared to be no evidence of increasing risk with increasing consumption of monosaccharides. However, in another case-control study conducted in Belgium (Tuyns et al., 1987), with essentially the same dietary survey technique, increasing monosaccharide and disaccharide intake was related to increasing risk of both colon and rectal cancer. The relative risks for the highest compared to the lowest consumption level was 1.7 for colon cancer and 2.4 for rectal cancer.
In an extensive survey of the literature, the National Research Council's Committee on Diet, Nutrition, and Cancer (NRC, 1982) found relatively few animal studies dealing with the effects of dietary carbohydrates on carcinogenesis, and those studies provided little evidence of significant effects. Two research groups investigated the effects of diets containing different starches and sugars on mammary tumors induced by 7,12-dimethylbenz(a)anthracene (Hoehn and Carroll, 1978; Klurfeld et al., 1984). The results provided some evidence that rats fed sucrose or dextrose developed tumors more readily than those fed lactose or starch. Gridley et al. (1983) found that mice had a much higher incidence of spontaneous mammary tumors when fed a diet containing sucrose than when given a diet with dextrin.
Two other studies focused on the effects of dietary carbohydrates on liver carcinogenesis. Hei and Sudilovsky (1985) used diethylnitrosamine to induce hepatocarcinogenesis and found more g-glutamyltranspeptide-positive foci in rats fed a sucrose-containing diet compared to those on a diet containing glucose. In other experiments on
liver carcinogenesis induced by 3'-methylaminoazobenzene in rats fed liquid or powdered diets, Sato et al. (1984) found that tumorigenesis was enhanced by reducing sugar intake.
Several reports examined the effects on human behavior of reactive or postprandial hypoglycemia, which is defined by decreased blood glucose after eating coupled with a characteristic group of clinical symptoms. Hypoglycemia in children has been alleged to be associated with hyperkinesis, attention-deficit disorders, juvenile delinquency, and criminality (Harper and Gans, 1986; Kruesi and Rapoport, 1986; Milich, 1986). Furthermore, hypoglycemia has been specifically associated with the ingestion of sucrose. A review by Harper and Gans (1986) points to a lack of scientific experimentation or support of claims in this area.
There have been suggestions that dietary components, particularly sugars, cause changes in the behavior of children and adults. Some reports (e.g., Prinz et al., 1980) have linked sugar consumption to hyperactivity in children (hyperkinesis). This has some biologic plausibility, since experimental evidence in animals indicates that sugars as well as other dietary components may affect the level of brain neurotransmitters. Sugar consumption by humans, however, results in increased levels of serotonin (Crane and Ladene, 1983; Fernstrom and Wurtman, 1971), which should reduce activity levels.
Studies to determine whether there is a relationship between blood glucose levels and behavioral change failed to find any correlation (Behar et al., 1984; Brody and Wolinsky, 1983). The subjects of these studies included normal children as well as hyperactive children who, according to their parents, had behavioral deterioration following intake of sugars. Glucose and fructose were compared to a placebo (saccharin) by using standard tests for memory and attention as the dependent variables. There was no evidence for behavioral excitation and some weak evidence for a calming effect of sugars. These studies cast doubt on the hypothesized clinical significance of sugar intake in the etiology of behavioral disturbances (Prinz et al., 1980). A similar experimental design was used in a study by Wolraich et al. (1985) to test the effects of sucrose and aspartame on behavioral and cognitive parameters in 16 hyperactive boys. No differences were observed. Based on a review of the literature, several investigators (e.g., Kruesi and Rapoport, 1986; Milich, 1986) have concluded that there is no scientific basis for a relationship between sugar consumption and hyperactivity or other behavioral changes in children.
Some people claim that juvenile delinquency as well as aggressive, antisocial, and even criminal behavior can result from reactive or postprandial hypoglycemia following the ingestion of sucrose and other carbohydrates (Gray, 1987; Harper and Gans, 1986; Schauss, 1980). Schoenthaler (1982) contends that a high proportion (up to 90%) of prison inmates are hypoglycemic and attributes that to a particularly high consumption of refined sugar. Studies undertaken to support this contention are characterized by inadequate diagnosis of hypoglycemia and lack of valid control groups (Gray, 1987). Another set of studies of violent adult male habitual offenders in Finland failed to support a relationship between violent behavior and hypoglycemia (Virkunen, 1982; Virkunen and Huttunen, 1982). Thus, the claims that high sugar intake can cause aggressive, antisocial behavior are based largely on conclusions drawn from anecdotal evidence and inadequately designed studies (Gray, 1987; Harper and Gans, 1986).
Documented reactive hypoglycemia based on accepted criteria (American Diabetes Association, 1982) is an uncommon condition (Cahill and Soeldner, 1974; Yager and Young, 1974) and occurs only in a very small percentage of people who commit crimes (Gray and Gray, 1983; Jukes, 1986). Apparently, no objective studies have been published to support the contention that aggressive or criminal behavior is influenced by sugar or carbohydrate intake. Despite the absence of any supporting data, however, some prison authorities have altered their institutional diets (Gray, 1987).
Primary lactose intolerance is the inability to digest the disaccharide lactose (the main carbohydrate in milk), breaking it down into glucose and galactose. This results from a progressive decrease, early in childhood, of the enzyme lactase, which is normally present at birth. As described in Chapter 4, some adults maintain lactase activity, which is controlled by a single gene. Lactose ingestion (milk drinking) will not induce lactase activity after its decrease nor will lactose restriction reduce enzyme activity if still present. Thus, the ingestion of lactose plays no role in the genetic expression of
primary lactose intolerance. However, symptoms of lactose intolerance can be ameliorated by restriction of lactose-containing dairy products. Total elimination of lactose is rarely necessary, since most affected individuals can tolerate 1 to 2 glasses of milk daily (Gray, 1983).
Secondary lactose intolerance is associated with chronic gastrointestinal disease in people with persistent lactase activity. This condition will lessen as the disease is reversed. Also, chronic alcoholics without malnutrition have an increase in lactase deficiency, which is reversible with alcohol abstinence (Perlow et al., 1977).
Sucrose intolerance due to sucrase deficiency is a rarer genetic disorder. Its symptoms are indistinguishable from those of lactose intolerance, except that they are elicited by table sugar rather than by milk. Starch is usually well tolerated and digested. Dietary sucrose plays no role in the expression of this disorder, but its restriction will ameliorate symptoms (Gray, 1983).
The role of sugar-containing foods in the etiology of a variety of disorders and disabilities in humans has generated considerable attention. Carbohydrates are still believed by some to be fattening beyond their contribution to total calories, and sugars themselves are sometimes regarded as contributors to diabetes and heart disease. Sugars have also been implicated in a variety of behavioral aberrations associated with hypoglycemia, but rarely confirmed by acceptable criteria as discussed earlier.
Epidemiologic studies have shown that populations eating high-carbohydrate diets usually have a lower prevalence of NIDDM and CHD compared to populations eating lower-carbohydrate and higher-fat diets. The role of carbohydrates has not been completely established, but it seems reasonable to infer that the correlations of NIDDM and CHD with carbohydrates do not reflect a direct association but, rather, are due to confounding by variables such as caloric expenditure and obesity. Paradoxically, obesity also is associated with lower caloric intake, including low carbohydrate intake, in population studies. Evidence supports the contention that consumption of sugars, in particular sucrose, is the major dietary factor associated with the incidence of dental caries. Population studies suggesting a link between carbohydrate intake and colorectal cancer have been inconclusive.
With the exception of dental caries, clinical studies of carbohydrate intake and chronic diseases have focused more on dietary management of chronic diseases than on the role of diet in causation. High-carbohydrate, low-fat diets have been recommended both for the management of diabetes mellitus and for lowering glucose and lipid levels and reducing insulin requirements. However, short-term metabolic studies suggest that for some individuals, such diets may raise glucose and triglyceride levels, thereby pointing to the need for further long-term population studies and for intervention trials.
The scientific data supporting beliefs that high-carbohydrate diets are associated with hypoglycemia, hyperactivity, or criminality are inadequate. Controlled clinical studies to test the carbohydrate-hypoglycemia-hyperactivity connection have been negative.
Directions for Research
· Long-term prospective studies are needed to evaluate the effects of increasing the proportion of carbohydrate calories in the diet on morbidity and mortality from CHD among diabetics.
· Longer-term clinical studies are needed to characterize the metabolic adaptive changes in lipoproteins associated with switching from a low-carbohydrate to a high-carbohydrate diet from various dietary sources.
· Additional studies should be conducted to test for a possible link between intake of total or individual carbohydrates and the incidence of colorectal and other cancers.
· Research on the effect of fluoridation on dental caries among people with a wide spectrum of carbohydrate intakes would help elucidate whether the contributory role of carbohydrates in the pathogenesis of caries can be effectively offset by fluoride.
Abbott, W.G.H., V.L. Boyce, S.M. Grundy, and B.V. Howard. 1989. Effects of replacing saturated fat with complex carbohydrate in diets of subjects with NIDDM. Diabetes Care 12:102-107.
Abelson, D.C., and G. Pergola. 1984. The effect of sucrose concentration on plaque pH in vivo. Clin. Prev. Dent. 6: 23-26.
Ahrens, E.H. 1986. Carbohydrates, plasma triglycerides and coronary heart disease. Nutr. Rev. 44:60-64.
American Diabetes Association. 1982. Statement on hypoglycemia. Diabetes Care 5:72-73.
American Diabetes Association. 1987. Nutritional recommendations and principles for individuals with diabetes mellitus: 1986. Diabetes Care 10:126-132.
Anderson, J.W., and J. Tietyen-Clark. 1986. Dietary fiber: hyperlipidemia, hypertension, and coronary heart disease. Am. J. Gastroenterol. 81:907-919.
Anderson, J.W., and K. Ward. 1979. High carbohydrate, high-fiber diets for insulin-treated men with diabetes mellitus. Am. J. Clin. Nutr. 32:2312-2321.
Armstrong, B.K., and R. Doll. 1975. Environmental factors and cancer incidence and mortality in different countries with special reference to dietary practices. Int. J. Cancer 15: 617-631.
Baeke, J.A.H., W.A. van Staveren, and J. Burema. 1983. Food consumption, habitual physical activity, and body fatness in young Dutch adults. Am. J. Clin. Nutr. 37:278-286.
Baird, J.D. 1972. Diet and development of clinical diabetes. Acta Diabetol. Lat. 9 suppl. 1:621-637.
Bar-On, H., Y.I. Chen, and G.M. Reaven. 1981. Evidence for a new cause of defective plasma removal of very low density lipoproteins in insulin-deficient rats. Diabetes 30: 496-499.
Barter, P.J., K.F. Carroll, and P. Nestel. 1971. Diurnal fluctuations in triglyceride, free fatty acids and insulin during sucrose consumption and insulin infusion in man. J. Clin. Invest. 50:583-591.
Becks, H. 1950. Carbohydrate restriction in the prevention of dental caries using the L.a. count as one index. J. Calif. State Dent. Assoc. 26:53-58.
Behar, D., J.L Rapoport, A.J. Adams, C.J. Berg, and M. Cornblath. 1984. Sugar challenge testing with children considered behaviorally "sugar reactive." Nutr. Behav. 1: 277-288.
Beighton, D., and H. Hayday. 1984. The establishment of the bacterium Streptococcus mutans in dental plaque and the introduction of caries in macaque monkeys (Macaca fascicularis) fed a diet containing cooked wheat flour. Arch. Oral Biol. 29:369-372.
Bierman, E.L. 1979. Nutritional management of adult and juvenile diabetics. Pp. 107-117 in M. Winick, ed. Nutritional Management of Genetic Disorders. Wiley, New York.
Bierman, E.L., and J.T. Hamlin III. 1961. The hyperlipemic effect of a low-fat, high-carbohydrate diet in diabetic subjects. Diabetes 10:432-437.
Birkhed, D., V. Topitsoglou, S. Edwardsson, and G. Frostell. 1981. Cariogenicity of invert sugar in long-term experiments. Caries Res. 15:302-307.
Blanc, M.H., O.P. Ganda, R.E. Gleason, and J.S. Soeldner. 1983. Improvement of lipid status in diabetic boys: the 1971 and 1979 Joslin Camp lipid levels. Diabetes Care 6:64-66.
Boot-Hanford, R.P., and H. Heath. 1981. The effect of dietary fructose and diabetes on the rat kidney. Br. J. Exp. Pathol. 62:398-406.
Brody, S., and D.L. Wolinsky. 1983. Lack of mood changes following sucrose loading. Psychosomatics 24:155-162.
Brown, A.T. 1975. The role of dietary carbohydrates in plaque formation and oral disease. Nutr. Rev. 33:353-361.
Cahill, G.F., Jr., and J.S. Soeldner. 1974. A non-editorial on nonhypoglycemia. N. Engl. J. Med. 291:905-906.
Carroll, K.K. 1977. Dietary factors in hormone-dependent cancers. Pp. 25-40 in M. Winick, ed. Current Concepts in Nutrition, Vol. 6: Nutrition and Cancer. Wiley, New York.
Carroll, K.K. 1986. Experimental studies on dietary fat and cancer in relation to epidemiological data. Pp. 231-248 in C. Ip, D.F. Birt, A.E. Rogers, and C. Mettle, eds. Progress in Clinical and Biological Research, Vol. 222: Dietary Fat and Cancer. Alan R. Liss, Inc., New York.
Cerqueria, M.P., M. McMurry, and W.E. Connor. 1979. The food and nutrient intakes of the Tarahumara Indians of Mexico. Am. J. Clin. Nutr. 32:905-913.
Cohen, A.M. 1978. Genetically determined response to different ingested carbohydrates in the production of diabetes. Horm. Metab. Res. 10:86-92.
Cominacini, L., I. Zocce, U. Gorbin, A. Doviol, R. Compri, L. Brunetti, and O. Bosello. 1988. Long-term effect of a low-fat, high-carbohydrate diet on plasma lipids of patients affected by familial endogenous hypertriglyceridemia. Am. J. Clin. Nutr. 48:57-65.
Connor, W.E., M.P. Cerqueria, R.W. Connor, R.B. Wallace, M.R. Malinow, and H.R. Casdorph. 1978. The plasma lipids, lipoproteins and diet of the Tarahumara Indians of Mexico. Am. J. Clin. Nutr. 31:1131-1142.
Coulston, A.M., C.B. Hollenbeck, A.L.M. Swislocki, Y.D.I. Chen, and G.M. Reaven. 1987. Deleterious metabolic effect of high carbohydrate, sucrose-containing diets in patients with non-insulin-dependent diabetes mellitus. Am. J. Med. 82:213-220.
Coulston, A.M., C.B. Hollenbeck, A.L.M. Swislocki, and G.M. Reaven. 1989. Persistence of hypertriglyceridemic effect of high-carbohydrate low-fat diets in NIDDM patients. Diabetes Care 12:94-101.
Crane, S.C., and P.A. Ladene. 1983. Effects of sucrose, glucose and fructose on spontaneous activity and brain monamines in rat pups. Nutr. Rep. Int. 28:991-997.
Dallaglio, E., F. Chang, H. Chang, J. Stem, and G.M. Reaven. 1983. Effect of exercise and diet on triglyceride metabolism in rats with moderate insulin deficiency. Diabetes 32:46-50.
de Bont, A.J., I.A. Baker, A.S. St. Leger, P.M. Sweetnam, K.G. Wragg, S.M. Stephens, and T.M. Hayes. 1981. A randomised controlled trial of the effect of low fat diet advice on dietary response in insulin dependent diabetic young women. Diabetologia 21:529-533.
Drewnowski, A., J.B. Brunzell, K. Sande, P.H. Iverius, and M.R.C. Greenwood. 1985. Sweet tooth reconsidered: taste responsiveness in human obesity. Physiol. Behav. 35:617-622.
Dunnigan, M.G., T. Fyfe, M.T. McKiddie, and S.M. Crosbie. 1970. The effects of isocaloric exchange of dietary starch and sucrose on glucose tolerance, plasma insulin and serum lipids in man. Clin. Sci. 38:1-9.
Edgar, W.M. 1981. Effect of sequence in food intake on plaque pH. Pp. 279-287 in J.J. Hefferren and H.M. Koehler, eds. Foods, Nutrition and Dental Health, Vol. 1. Pathotox Publishing, Park Forest South, Ill.
Edgar, W.M., B.G. Bibby, S. Mundorff, and J. Rowley. 1975. Acid production in plaques after eating snacks: modifying factors in foods. J. Am. Dent. Assoc. 90:418-425.
Edgar, W.M., W.H. Bowen, S. Amsbaugh, E. Monell-Torrens, and J. Brunelle. 1982. Effects of different eating patterns on dental caries in the rat. Caries Res. 16:384-389.
Emanuele, M.A., C. Abraira, W.S. Jellish, and M. De Bartlo. 1986. A crossover trial of high and low sucrose carbohydrate diets in Type II diabetics with hypertriglyceridemia. J. Am. Coll. Nutr. 5:429-437.
Fernstrom, J.D., and R.J. Wurtman. 1971. Brain serotonin content: increase following ingestion of carbohydrate diet. Science 174:1023-1025.
Finn, S.B., and H.C. Jamison. 1980. The relative effects of three dietary supplements on dental caries. ASDC J. Dent. Child. 47:109-113.
Firestone, A.R., R. Schmid, and H.R. Muhlemann. 1982. Cariogenic effects of cooked wheat starch alone or with sucrose and frequency controlled feedings in rats. Arch. Oral Biol. 27:759-763.
Garcia-Palmieri, M.R., P. Sorlie, J: Tillotson, R. Costas, Jr., E. Cordero, and M. Rodriguez. 1980. Relationship of dietary intake to subsequent coronary heart disease incidence: the Puerto Rico Heart Health Program. Am. J. Clin. Nutr. 33:1818-1827.
Garg, A., A. Bonanome, S.M. Grundy, Z.J. Zhang, and R.H. Unger. 1988. Comparison of a high-carbohydrate diet with a high-monounsaturated-fat diet in patients with non-insulin-dependent diabetes mellitus. N. Engl. J. Med. 319:829-834.
Geddes, D.A.M., W.M. Edgar, G.N. Jenkins, and A.J. Rugg-Gunn. 1977. Apples, salted peanuts and plaque pH. Br. Dent. J. 142:317-319.
Geddes, D.A.M., J.A. Cooke, W.M. Edgar, and G.N. Jenkins. 1978. The effect of frequent sucrose mouthrinsing on the induction in vivo of caries-like changes in human dental enamel. Arch. Oral Biol. 23:663-665.
Glass, R.L., and S. Fleisch. 1974. Diet and dental caries: dental caries incidence and the consumption of ready-to-eat cereals. J. Am. Dent. Assoc. 88:807-813.
Glinsmann, W.H., H. Irausquin, and Y.K. Park. 1986. Evaluation of health aspects of sugars contained in carbohydrate sweeteners: report of Sugars Task Force, 1986. J. Nutr. 116:S1-S216.
Goda, T., K. Yamada, M. Sugiyama, S. Moriuchi, and N. Hosoya. 1982. Effect of sucrose and acarbose feeding on the development of streprozotocin-induced diabetes in the rat. J. Nutr. Sci. Vitaminol. 78:41-56.
Gonen, B., W. Patsch, I. Kvisk, and G. Schoenfeld. 1981. The effect of short-term feeding of a high carbohydrate diet on HDL subclasses in normal subjects. Metabolism 30: 1125-1129.
Gonnermann, B., R. Schafer-Spiegel, H. Laube, and H. Schatz. 1982. The effect of a saccharose-rich diet on carbohydrate and lipid metabolism of streptozotocin-diabetic rats and genetically determined "diabetic" mice (gg-diab). Int. J. Obesity 6 suppl. 1:41-48.
Gordon, T., A. Kagan, M. Garcia-Palmieri, W.B. Kannel, W.J. Tukel, J. Tillotson, P. Sorlie, and M. Hjortland. 1981. Diet and its relation to coronary heart disease and death in three populations. Circulation 63:500-515.
Gray, G.E. 1987. Crime and diet: is there a relationship? World Rev. Nutr. Diet. 49:66-86.
Gray, G.E., and L.K. Gray. 1983. Diet and juvenile delinquency. Nutr. Today 18:14-22.
Gray, G.M. 1983. Intestinal disaccharidose deficiencies and glucose-galactose malabsorption. Pp. 1729-1742 in J.B. Stanbury, J.B. Wyngaarden, D.S. Fredrickson, J.L. Goldstein, and M.S. Brown, eds. The Metabolic Basis of Inherited Disease. McGraw-Hill, New York.
Gray, R.S., and J.M. Olefsky. 1982. Effect of a glucosidase inhibitor on the metabolic response of diabetic rats to a high carbohydrate diet, consisting of starch and sucrose, or glucose. Metabolism 31:88-92.
Greenwood, M.R.C., R. Kava, D.B. West, and V.A. Lukasik. 1988. Wistar fatty rat: a sexually dimorphic model of human noninsulin-dependent diabetes. Pp. 316-318 in E. Shafrir and A.E. Renold, eds. Frontiers in Diabetes Research: Lessons from Animal Diabetes II. John Libbey, London.
Gridley, D.S., J.D. Kettering, J.M. Slater, and R.L. Nutter. 1983. Modification of spontaneous mammary tumors in mice fed different sources of protein, fat and carbohydrate. Cancer Lett. 19:133-146.
Grinker, J.A. 1978. Obesity and sweet taste. Am. J. Clin. Nutr. 31:1078-1087.
Grundy, S.M., L. Florentin, D. Nix, and M.F. Whelan.1988. Comparison of monounsaturated fatty acids and carbohydrates for reducing raised levels of plasma cholesterol in man. Am. J. Clin. Nutr. 47:965-969.
Gustafsson, B.E., C.E. Quensel, L.S. Lanke, C. Lundquist, H. Grahnen, B.E. Bonow, and B. Krasse. 1954. The Vipeholm Dental Caries Study. The effect of different levels of carbohydrate intake on caries activity in 436 individuals observed for five years. Acta Ondontol. Scand. 11:232-364.
Hakama, M., and E.A. Saxen. 1967. Cereal consumption and gastric cancer. Int. J. Cancer 2:265-268
Hallfrisch, J., F. Lazar, and S. Reiser. 1979. Effect of feeding sucrose or starch to rats made diabetic with streptozotocin. J. Nutr. 109:1909-1915.
Harper, A.E., and D.A. Gans. 1986. Claims of antisocial behavior from consumption of sugar: an assessment. Food Technol. 40:142-149.
Harper, D.S., J.C. Osborn, R. Clayton, and J.J. Hefferren. 1987. Modification of food cariogenicity in rats by mineral-rich concentrates from milk. J. Dent. Res. 66:42-45.
Heath, H., and Y.C. Hamlett. 1976. The sorbitol pathway: effect of streptozotocin-induced diabetes and the feeding of a sucrose-rich diet on glucose, sorbitol and fructose in the retina, blood and liver of rats. Diabetes 12:43-46.
Heath, H., S.S. Kang, and D. Philippou. 1975. Glucose, glucose-6-phosphate, lactate and pyruvate content of the retina, blood and liver of streptozotocin-diabetic rats fed sucrose- or starch-rich diets. Diabetes 11:57-62.
Hefti, A., and R. Schmid. 1979. Effect on caries incidence in rats of increasing dietary sucrose levels. Caries Res. 13:298-300.
Hei, T.K., and O. Sudilovsky. 1985. Effects of a high-sucrose diet on the development of enzyme-altered foci in chemical hepatocarcinogenesis in rats. Cancer Res. 45:2700-2705.
Hems, G. 1978. The contributions of diet and childbearing breast-cancer rates. Br. J. Cancer 37:974-982.
Hems, G., and A. Stuart. 1975. Breast cancer rate in populations of single women. Br. J. Cancer 31:118-123.
Hill, W., T.W. Castonguary, and G.H. Collier. 1980. Taste or diet balancing? Physiol. Behav. 24:765-767.
Himsworth, H.P. 1935-1936. Diet and the incidence of diabetes mellitus. Clin. Sci. Mol. Med. 2:117-148.
Hoehn, S.K., and K.K. Carroll. 1978. Effects of dietary carbohydrate on the incidence of mammary tumors induced by rats by 7,12-dimethylbenz(a)anthracene. Nutr. Cancer 1: 27-30.
Hollenbeck, C.B., W.E. Connor, U.C. Riddle, P. Alaupovic, and J.E. Leklem. 1985. The effects of a high-CHO, low-fat cholesterol-restricted diet on plasma lipid, lipoprotein, and apoprotein concentrations in insulin-dependent (Type I) diabetes mellitus. Metabolism 34:559-566.
Horton, W.A., A.E. Jacobs, R.M. Green, V.F. Hillier, and D.B. Drucker. 1985. The cariogenicity of sucrose, glucose, and maize starch in gnotobiotic rats mono-infected with strains of the bacteria Streptococcus mutans, Streptococcus salivarius, and Streptococcus milleri. Arch. Oral Biol. 30:777-780.
Ikeda, H., A. Shino, T. Matsuo, H. Iwatsuka, and Z. Suzuoki. 1981. A new genetically obese-hyperglycemic rat (Wistar fatty). Diabetes 30:1045-1050.
Imfeld, T., R.S. Hirsch, and H.R. Muhlemann. 1978. Telemetric recordings of interdental plaque pH during different meal patterns. Br. Dent. J. 144:40-45.
Jellish, W.S., M.A. Emanuele, and C. Abraira. 1984. High sucrose carbohydrate diets vs sucrose restricted diets in overt diabetics. Am. J. Med. 77:1015-1022.
Jensen, M.E., and C.F. Schachtele. 1983. The acidogenic potential of reference foods and snack at interproximal sites in the human dentition. J. Dent. Res. 62:889-892.
Johnson, M.L., B.S. Burke, and J. Mayer. 1956. Relative importance of inactivity and overeating in the energy balance of obese high school girls. Am. J. Clin. Nutr. 4:37-44.
Jukes, T.H. 1986. Sugar and Health. World Rev. Nutr. Diet. 48:137-194.
Kalderon, B., A. Gutman, E. Levy, E. Shafrir, and J. Adler. 1986. Characterization of stages in development of obesity-diabetes syndrome in sand rat (Psammomys obesus). Diabetes 35:717-724.
Kanarek, R.B., and E. Hirsch. 1977. Dietary-induced overeating in experimental animals. Fed. Proc. 36:154-158.
Kanarek, R.B., and N. Orthen-Gambill. 1982. Differential effects of sucrose, fructose and glucose on carbohydrate-induced obesity in rats. J. Nutr. 112:1546-1554.
Kang, S.S., R. Fears, S. Noirot, J.N. Mbanya, and J. Yudkin. 1982. Changes in metabolism of rat kidney and liver caused by experimental diabetes and by dietary sucrose. Diabetes 22:285-288.
Katan, M.J. 1984. Diet and HDL. Pp. 103-131 in N.E. Miller and G.J. Miller, eds. Metabolic Aspects of Cardiovascular Disease, Vol. 3. Clinical and Metabolic Aspects of HDL. Elsevier, Oxford.
Kawate, R., M. Yamakido, Y. Nishimoto, P.H. Bennett, R.F. Hamman, and W.C. Knowler. 1979. Diabetes mellitus and its vascular complications in Japanese migrants on the island of Hawaii. Diabetes Care 2:161-170.
Keen, J., B.J. Thomas, R.J. Jarrett, and J.H. Fuller. 1979. Nutrient intake, adiposity, and diabetes. Br. Med. J. 1:655-658.
Keys, A., C. Aravanis, H. Blackburn, F.S.P. Van Buchem, K. Buzina, B.S. Djordjevic, A.S. Dontas, F. Fidanz, M.J. Karvonen, N. Kimura, D. Lekos, M. Monti, V. Puddu, and H.L. Taylor. 1967. Epidemiologic studies related to coronary heart disease: characteristics of men aged 40-59 in seven countries. Acta Med. Scand., Suppl. 460:1-392.
Kiehm, G., J.W. Anderson, and K. Ward. 1976. Beneficial effects of a high carbohydrate, high fiber diet on hyperglycemic diabetic men. Am. J. Clin. Nutr. 29:895-899.
Klurfeld, D.M., M.M. Webber, and D. Kritchevsky. 1984. Comparison of dietary carbohydrates for promotion of DMBA-induced mammary tumorigenesis in rats. Carcinogenesis 5:423-425.
Knuiman, J.T., C.E. West, M.J. Katan, and J.G.A.J. Houtvast. 1987. Total cholesterol levels in populations differing in fat and carbohydrate intake. Arteriosclerosis 7: 612-619.
Kolterman, O.G., M. Greenfield, G.M. Reaven, M. Saekow, and J.M. Olefsky. 1979. Effect of a high carbohydrate diet on insulin binding to adipocytes and on insulin action in vivo in man. Diabetes 28:731-736.
Krasse, B. 1985. The cariogenic potential of foodsa critical review of current methods. Int. Dent. J. 35:36-42.
Kreitzman, S.N., and R.M. Klein. 1976. Non-linear relationship between dietary sucrose and dental caries. J. Dent. Res. (sp. iss.) 55:B175.
Kromhout, D. 1983a. Changes in energy and macronutrients in 871 middle-aged men during 10 years of follow-up (the Zutphen Study). Am. J. Clin. Nutr. 37:287-294.
Kromhout, D. 1983b. Energy and macronutrient intake in lean and obese middle-aged men (the Zutphen Study). Am. J. Clin. Nutr. 37:295-299.
Kruesi, M.J.P., and J.L. Rapoport. 1986. Diet and human behavior: how much do they affect each other? Annu. Rev. Nutr. 6:113-130.
Leach, S.A., and R.M. Green. 1981. Reversal of fissure caries in the albino rat by sweetening agents. Caries Res. 15:508-511.
Leach, S.A., R. Connell, J.A. Speechley, and R.M. Green. 1984. Reversal of dental caries by the sugar substitute lycasin in vivo. J. Dent. Res. (sp. iss.) 63:334.
Leiter, E.H., D.L. Coleman, D.K. Ingram, and M.A. Reynolds. 1983. Influence of dietary carbohydrate on the induction of diabetes in C57BL/KsJ-db/db diabetes mice. J. Nutr. 113:184-195.
Lin, W.J., and J.W. Anderson. 1977. Effects of high sucrose or starch-bran diets on glucose and lipid metabolism of normal and diabetic rats. J. Nutr. 107:584-595.
Lincoln, J.E. 1972. Calorie intake, obesity, and physical activity. Am. J. Clin. Nutr. 25:390-394.
Linke, H.A.B. 1980. Inhibition of dental caries in the inbred hamster by saccharin. Ann. Dent. 39:71-74.
Liu, G.C., A.M. Coulston, and G.M. Reaven. 1983. Effects of high-carbohydrate low-fat diets on plasma glucose, insulin, and lipid responses in hypertriglyceridemic humans. Metabolism 32:750-753.
Macquart-Moulin, G., E. Riboli, J. Correa, B. Charnay, P. Berthezene, and N. Day. 1986. Case-control study on colorectal cancer and diet in Marseilles. Int. J. Cancer 38:183-191.
Malcolm, R., P.M. O'Neil, A.A. Hirsch, H.S. Currey, and G. Moskowitz. 1980. Taste hedonics and thresholds in obesity. Int. J. Obesity 4:203-212.
Mann, J.I., and A.S. Truswell. 1970. Effects of isocaloric exchange of dietary sucrose and starch of fasting serum lipids, post-prandial insulin secretion and alimentary lipaemia in human subjects. Br. J. Nutr. 27:295.
Marston, R., and N. Raper. 1987. Nutrient content of the U.S. food supply. National Food Review, Winter-Spring, NFR-36:18-23.
Maxfield, E., and F. Konishi. 1966. Patterns of food intake and physical activity in obesity. J. Am. Diet. Assoc. 49: 406-408.
McCarthy, M.C. 1966. Dietary and activity patterns of obese women in Trinidad. J. Am. Diet. Assoc. 48:33-37.
McDonald, I. 1972. Relationship between dietary carbohydrates and fats in their influence on serum lipid concentrations. Clin. Sci. 43:265-274.
McDonald, J.L., Jr. 1985. Cariogenicity of foods. Pp. 320-345 in R.L. Pollack and E. Kravitz, eds. Nutrition in Oral Health and Disease. Lea & Febiger, Philadelphia.
McDonald, J.L., Jr., and J.K. Stookey. 1977. Animal studies concerning the cariogenicity of dry breakfast cereals. . Dent. Res. 56:1001-1006.
Medalie, J.H., C. Papier, J.B. Herman, U. Goldbourt, S. Tamir, H.N. Neufeld, and E. Riss. 1974. Diabetes mellitus among 10,000 adult men. I. Five-year incidence and associated variables. Isr. J. Med. Sci. 10:681-697.
Michaelis, O.E., IV, K.C. Ellwood, J.M. Judge, N.W. Schoene, and C.T. Hansen. 1984. Effect of dietary sucrose on the SHR/N-corpulent rat: a new model for insulin-
independent diabetes. Am. J. Clin. Nutr. 39:612-618.
Michalek, S.M., J.R. McGhee, T. Shiota, and D. Devenyns. 1977. Low sucrose levels promote extensive Streptococcus mutans-induced dental caries. Infect. Immun. 16:712-714.
Milich, R. 1986. Sugar and hyperactivity: a critical review of empirical findings. Clin. Psychol. Rev. 6:493-513.
Modan, B.W., V. Barrell, F. Lubin, R.A. Greenberg, M. Modan, and S. Graham. 1974. The role of starches in the etiology of gastric cancer. Cancer 34:2087-2092.
Mormann, J.E., and H.R. Muhlemann. 1981. Oral starch degradation and its influence on acid production in human dental plaque. Caries Res. 15:166-175.
Morris, J.N., J.W. Marr, and D.G. Clayton. 1977. Diet and heart: a post-script. Br. Med. J. 2:1307-1314.
Nestel, P.J., M. Reardon, and N.H. Fidge. 1979. Sucrose- induced changes in VLDL- and LDL-B apoprotein removal rates. Metabolism 28:531-535.
Nikkilä, W.A., and M. Kekki. 1972. Effects of dietary fructose and sucrose on plasma triglyceride metabolism in patients with endogenous hypertriglyceridemia. Acta Med. Scand., Suppl. 542:221-227.
Nizel, A.E., and R.S. Harris. 1964. The effects of phosphates on experimental dental caries: a literature review. J. Dent. Res. 43:1123-1136.
NRC (National Research Council). 1982. Diet, Nutrition, and Cancer. Report of the Committee on Diet, Nutrition, and Cancer, Assembly of Life Sciences. National Academy Press, Washington, D.C. 478 pp.
Obell, A.E 1974. Recent advances in mechanism of causation of diabetes mellitus in man and Acomy cahirinus. East Afr. Med. J. 51:425-428.
Olefsky, J.M., and M. Saekow. 1978. The effects of dietary carbohydrate content on insulin binding and glucose metabolism by isolated rat adipocytes. Endocrinology 103:2252-2263.
Ornoy, A., and A.M. Cohen. 1980. Teratogenic effects of sucrose diet in diabetic and nondiabetic rats. Isr. J. Med. Sci. 16:789-791.
Pan, X.R., C.E. Walden, G.R. Warnick, S.X. Hue, J.J. Albers, M. Cheung, and E.L. Bierman. 1986. A comparison of plasma lipoproteins and apoproteins in Chinese and American non-insulin dependent diabetics and controls. Diabetes Care 9:395-400.
Paolino, V. 1982. Anti-plaque activity of cocoa. Pp. 43-58 in J.J. Hefferren and H.M. Koehler, eds. Foods, Nutrition and Dental Health, Vol. 2: Third Annual Conference. American Dental Association, Chicago.
Papachristodoulou, D., H. Heath, and S.S. Kang. 1976. The development of retinopathy in sucrose fed and streptozotocin-diabetic rats. Diabetes 12:367-374.
Pearce, E.I.F., and I.H.C. Gallagher. 1979. The behavior of sucrose and xylitol in an intra-oral caries test. N.Z. Dent. J. 75:8-14.
Perlow, W., E. Baraona, and C.S. Lieber. 1977. Symptomatic intestinal disaccharidase deficiency in alcoholics. Gastroenterology 72:680-684.
Peterson, D.B., J. Lambert, S. Geiring, P. Darling, RD. Carter, R. Jelfs, and J.I. Mann. 1986. Sucrose in the diet of diabetic patientsjust another carbohydrate? Diabetologia 29:216-220.
Phillips, R.W., N. Westmoreland, L. Panepinto, and G.L. Case. 1982. Dietary effects on metabolism of Yucatan miniature swine selected for low and high glucose utilization. J. Nutr. 112:104-111.
Porte, D., Jr., E.L. Bierman, and J.D. Bagdade. 1966. Substitution of dietary starch for dextrose in hyperlipemic subjects. Proc. Soc. Exp. Biol. Med. 123:84-86.
Prinz, R.J., W.A. Roberts, and E. Hantman. 1980. Dietary correlates of hyperactive behavior in children. J. Consult. Clin. Psychol. 48:760-769.
Rattigan, S., and M.G. Clark. 1984. Effect of sucrose solution drinking option on the development of obesity in rats. J. Nutr. 114:1971-1977.
Reaven, G.R. 1986. Effect of dietary carbohydrate on the metabolism of patients with non-insulin dependent diabetes mellitus. Nutr. Rev. 44:65-73.
Reaven, G.R. 1988. Dietary therapy for non-insulin dependent diabetes mellitus. N. Engl. J. Med. 319:862-864.
Reiser, S., M.C. Bickard, J. Hallfrisch, O.E. Michaelis IV, and E.S. Prather. 1981a. Blood lipids and their distribution in lipoproteins in hyperinsulinemic subjects fed three different levels of sucrose. J. Nutr. 111:1045-1057.
Reiser, S., E. Bohn, J. Hallfrisch, O.E. Michaelis IV, M. Keeney, and E.S. Prather. 1981b. Serum insulin and glucose in hyperinsulinemic subjects fed three different levels of sucrose. Am. J. Clin. Nutr. 34:2348-2358.
Riccardi, G., A. Rivellese, D. Pocioni, S. Genovese, P. Mastranzo, and M. Mancini. 1984. Separate influence of dietary carbohydrate and fibre on the metabolic control in diabetes. Diabetologia 26:116-121.
Rice, M.G., and R.P. Robertson. 1980. Reevaluation of the sand rat as a model for diabetes mellitus. Am. J. Physiol. 239E:340-345.
Risch, H.A., M. Jain, N.W. Choi, J.G. Fodor, C.J. Pfeiffer, G.R. Howe, L.W. Harrison, K.J. Craib, and A.B. Miller. 1985. Dietary factors and the incidence of cancer of the stomach. Am. J. Epidemiol. 122:947-959.
Rosen, S., D.B. Min, D.S. Harper, W.J. Harper, W.X. Beck, and F.M. Beck. 1984. Effect of cheese, with and without sucrose, on dental caries and recovery of Streptococcus mutans in rats. J. Dent. Res. 63:894-896.
Rosenmann, E., Z. Palti, A. Teitelbaum, and A.M. Cohen. 1974. Testicular degeneration in genetically selected sucrose-fed diabetic rats. Metabolism 23:343-348.
Sato, A.T., Y. Nakagima, T. Koyama, T. Shirai, and N. Ito. 1984. Dietary carbohydrate level as a modifying factor on 3'-methyl-4-dimethylaminoazobenzene liver carcinogenesis in rats. Gann 75:665-671.
Schachtele, C.F., and M.E Jensen. 1983. Can foods be ranked according to their cariogenic potential? Pp. 136-146 in B. Guggenheim, ed. Cariology Today. S. Karger, Basel.
Schauss, A.G. 1980. Diet, Crime and Delinquency. Parker House, Berkeley, Calif. 108 pp.
Scheinin, A. 1976. Caries control through the use of sugar substitutes. Int. Dent. J. 26:4-13.
Scheinin, A., K.K. Makinen, and K. Ylitalo. 1975. Turku sugar studies. I. An intermediate report on the effect of sucrose, fructose, and xylitol diets on the caries incidence in man. Acta Ondontol. Scand. 33 suppl. 70:5-34.
Schlierf, G., and E. Dorow. 1973. Diurnal patterns of triglycerides, free fatty acids, blood sugar, and insulin during carbohydrate-induction in man and their modification by nocturnal suppression of lipolysis. J. Clin. Invest. 42:732-746.
Schlierf, G., V. Stossberg, and W. Reinheimer. 1971. Diurnal patterns of plasma triglycerides and free fatty acids in normal subjects and in patients with endogenous (type IV) hyperlipoproteinemia. Nutr. Metabol. 13:80.
Schoenthaler, S.J. 1982. The effect of sugar on the treatment and control of antisocial behavior: a double-blind study of an incarcerated juvenile population. Int. J. Biosocial Res. 3:1-9.
Sclafani, A., and S. Xenakis. 1984. Sucrose and polysaccharide induced obesity in the rat. Physiol. Behav. 32:169-174.
Shaw, J.H. 1987. Causes and Control of Dental Caries. N. Engl. J. Med. 317:996-1004.
Shrestha, B.M., and P.A. Kreutler. 1983. A comparative rat caries study on cariogenicity of foods using the intubation and gel methods. J. Dent. Res. 62:685.
Shyu, K.W., and M.Y. Hsu. 1980. The cariogenicity of xylitol, mannitol, sorbitol, and sucrose. Proc. Natl. Sci. Council Rep. China 4:21-26.
Silva, M.F., R.C. Burgess, H.J. Sandham, and G.N. Jenkins. 1987. Effects of water-soluble components of cheese on experimental caries in humans. J. Dent. Res. 66:38-41.
Simpson, R.W., J.I. Mann, J. Eaton, R.D. Carter, and T.D.R. Hockaday. 1979a. High-carbohydrate diets and insulin-dependent diabetes. Br. Med. J. 2:523-525.
Simpson, R.W., J.I. Mann, J. Eaton, R.A. Moore, R. Carter, and T.D.R. Hockaday. 1979b. Improved glucose control in maturity-onset diabetes treated with high-carbohydrate-modified fat diet. Br. Med. J. 1:1753-1756.
Skinner, A., P. Connolly, and M.N. Naylor. 1982. Influence of the replacement of dietary sucrose by maltose in solid and in solution on rat caries. Caries Res. 16:443-452.
Sognnaes, R.F. 1948. Analysis of war time reduction of dental caries in European children. Am. J. Dis. Child. 75:792-821.
Sopko, G., D.R. Jacobs, Jr., and H.L. Taylor. 1984. Dietary measures of physical activity. Am. J. Epidemiol. 120:900-911.
Sreebny, L.M. 1982. Sugar availability, sugar consumption, and dental caries. Community Dent. Oral Epidemiol. 10:1-7.
Steams, S.B., and P.H. Smith. 1985. Sucrose-feeding does not alter triglyceride secretion rates or insulin release in female rats. Nutr. Int. 1:26-29.
Stefanik, P.A., F.P. Heald, and J. Mayer. 1959. Caloric intake in relation to energy output of obese and non-obese adolescent boys. Am. J. Clin. Nutr. 7:55-62.
Stone, D.B., and W.E. Connor. 1963. The prolonged effects of a low cholesterol, high carbohydrate diet upon the serum lipids in diabetic patients. Diabetes 12:127-132.
Story, L., J.W. Anderson, W.J. Chen, D. Karounos, and B. Jefferson. 1985. Adherence to high-carbohydrate, high-fiber diets: long-term studies of non-obese diabetic men. J. Am. Diet. Assoc. 85:1105-1110.
Takeuchi, M. 1961. Epidemiological study on dental caries in Japanese children before, during, and after World War II. Int. Dent. J. 11:443-457.
Taylor, S.A., R.G. Price, S.S. Kang, and J. Yudkin. 1980. Modification of the glomerular basement membrane in sucrose-fed and streptozotocin-diabetic rats. Diabetes 19: 364-378.
Tehrani, A., F. Brudevold, F. Attarzadeh, J. Van Houte, and J. Russo. 1983. Enamel demineralization by mouth rinses containing different concentrations of sucrose. J. Dent. Res. 62:1216-1217.
Tenovuo, J., K.K. Makinen, and K. Paunio. 1984. Effects on oral health of mouth rinses containing xylitol, sodium cyclamate, and sucrose sweeteners in the absence of oral hygiene. IV. Analysis of whole saliva. Proc. Finn. Dent. Soc. 80:28-34.
Thornber, J.M., and C.D. Eckhert. 1984. Protection against sucrose induced retinol capillary damage at the Wistar rat. J. Nutr. 114:1070-1075.
Toverud, G. 1957. The influence of war and post-war conditions on the teeth of Norwegian school children. III. Discussion of food supply and dental condition in Norway and other European countries. Milbank Mem. Fund Quart. 35:373-459.
Turner, J.L., E.L. Bierman, J.D. Brunzell, and A. Chait. 1979. Effect of dietary fructose on triglyceride transport and glucoregulatory hormones in hypertriglyceridemic man. Am. J. Clin. Nutr. 32:1043-1050.
Tuyns, A.J., M. Haelterman, and R. Kaaks. 1987. Colorectal cancer and the intake of nutrients: oligosaccharides are a risk factor, fats are not. A case control study in Belgium. Nutr. Cancer 10:181-196.
USDA (U.S. Department of Agriculture). 1984. Nationwide Food Consumption Survey. Nutrient Intakes: Individuals in 48 States, Year 1977-78. Report No. 1-2. Consumer Nutrition Division, Human Nutrition Information Service, Hyattsville, Md. 439 pp.
USDA (U.S. Department of Agriculture). 1986. Nationwide Food Consumption Survey. Continuing Survey of Food Intakes by Individuals. Men 19-50 Years, 1 Day, 1985. Report No. 85-3. Nutrition Monitoring Division, Human Nutrition Information Service, Hyattsville, Md. 94 pp.
USDA (U.S. Department of Agriculture). 1987. Nationwide Food Consumption Survey. Continuing Survey of Food Intakes by Individuals. Women 19-50 Years and Their Children 1-5 Years, 4 Days, 1985. Report No. 85-4. Nutrition Monitoring Division, Human Nutrition Information Service, Hyattsville, Md. 182 pp.
USDA (U.S. Department of Agriculture). 1988. Nationwide Food Consumption Survey. Continuing Survey of Food Intakes by Individuals. Low-Income Women 19-50 Years and Their Children 1-5 Years, 4 Days, 1985. Report No. 85-5. Nutrition Monitoring Division, Human Nutrition Information Service, Hyattsville, Md. 220 pp.
Virkunen, M. 1982. Reactive hypoglycemic tendency among habitually violent offenders. Neuropsychobiology 8:35-40.
Virkunen, M., and M.O. Huttunen. 1982. Evidence for abnormal glucose tolerance test among violent offenders. Neuropsychobiology 8:30-34.
Walker, A.R.P. 1977. Sugar intake and diabetes mellitus. S. Afr. Med. J. 51:842-851.
Weinsier, R.L., A. Seeman, M.G. Herrera, J.P. Assal, J.S. Soeldner, and R.E. Gleason. 1974. High- and low-carbohydrate diets in diabetes mellitus. Ann. Intern. Med. 80: 332-341.
Welsh, S.O., and R.M. Marston. 1982. Review of trends in food use in the United States, 1909 to 1980. J. Am. Diet. Assoc. 81:120-125.
West, K.M. 1978. Epidemiology of Diabetes and Its Vascular Lesions. Elsevier, New York. 579 pp.
West, K.M., M.E. Sanders, E.L. McCulloch, R.P. Robinson, and J.A. Stober. 1976. Does sugar consumption increase risk of diabetes and obesity? Diabetes 25 suppl. 1:342.
WHO (World Health Organization) Multinational Study of Vascular Disease in Diabetics. 1985. Prevalence of small vessel and large vessel disease in diabetic patients from 14 centres. Diabetologia 28:615-640.
Wilkinson, P.W., J.M. Parkin, G. Pearlson, M. Strong, and P. Sykes. 1977. Energy intake and physical activity in obese children. Br. Med. J. 1:756.
Wolraich, M., R. Milich, P. Stumbo, and F. Schultz. 1985. Effects of sucrose ingestion on the behavior of hyperactive boys. J. Pediatr. 106:675-682.
Yager, J., and R.T. Young. 1974. Non-hypoglycemia is an epidemic condition. N. Engl. J. Med. 291:907-908.
Yano, K., G.G. Rhoads, A. Kagan, and J. Tillotson. 1978. Dietary intake and risk of coronary heart disease in Japanese men living in Hawaii. Am. J. Clin. Nutr. 31: 1270-1279.
Yudkin, J. 1964. Dietary fat and dietary sugar in relation to ischemic heart disease and diabetes. Lancet 2:4-5.