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Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (2005)

Chapter: 3 Relationship of Macronutrients and Physical Activity to Chronic Disease

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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
×
Page 78
Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
×
Page 79
Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
×
Page 80
Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
×
Page 81
Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
×
Page 82
Suggested Citation:"3 Relationship of Macronutrients and Physical Activity to Chronic Disease." Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. doi: 10.17226/10490.
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3 Relationship of Macronutrients and Physical Activity to Chronic Disease OVERVIEW Over the last 40 years, a growing body of evidence has accumulated regarding the relationships among consumption of dietary fat, carbohydrate, protein, and energy and risk of chronic disease. The fact that diets are usually composed of a variety of foods that include varying amounts of carbohydrate, protein, and various fats imposes some limits on the type of research that can be conducted to ascertain causal relationships. The avail- able data regarding the relationships among major chronic diseases that have been linked with consumption of dietary energy and macronutrients (fats, carbohydrates, fiber, and protein), as well as physical inactivity, are discussed below and are reviewed in greater detail in the specific nutrient chapters (Chapters 5 through 11) and the chapter on physical activity (Chapter 12). CANCER Diet has long been suspected as a cancer-causing agent. Early studies in animals showed that diet could influence carcinogenesis (Tannenbaum, 1942; Tannenbaum and Silverstone, 1957). Cross-cultural studies that com- pare incidence rates of specific cancers across populations have found great differences in cancer incidence, and dietary factors, at least in part, have been implicated as causes of these differences (Armstrong and Doll, 1975; Gray et al., 1979; Rose et al., 1986). In addition, observational studies have found strong correlations among dietary components and incidence and mortality rates of cancer (Armstrong and Doll, 1975). 53

54 DIETARY REFERENCE INTAKES Associations among dietary fat, carbohydrates, and protein and can- cer have been hypothesized. Many of these associations, however, have not been supported by clinical and interventional studies in humans. Increased intakes of energy, total fat, n-6 polyunsaturated fatty acids, cholesterol, sugars, protein, and some amino acids have been thought to increase the risk of various cancers, whereas intakes of n-3 fatty acids, dietary fiber, and physical activity are thought to be protective. The major findings and potential mechanisms for these relationships are discussed below. Energy Animal studies suggest that restriction of energy intake may inhibit cell proliferation (Zhu et al., 1999) and tumor growth (Wang et al., 2000). A risk of mortality from cancer has been associated with increased energy intakes during childhood (Frankel et al., 1998; Must and Lipman, 1999). Excess energy intake is a contributing factor to obesity, which is thought to increase the risk of certain cancers (Carroll, 1998). To support this con- cept, a number of studies have observed a positive association between energy intake during adulthood and risk of cancer (Andersson et al., 1996; Lissner et al., 1992; Lyon et al., 1987), whereas other studies did not find an association (Stemmermann et al., 1985). Dietary Fat High intakes of dietary fat have been implicated in the development of certain cancers. Early cross-cultural and case-control studies reported strong associations between total fat intake and breast cancer (Howe et al., 1991; Miller et al., 1978; van’t Veer et al., 1990), yet a number of epidemio- logical studies, most in the last 15 years, have found little or no association (Hunter et al., 1996; Jones et al., 1987; Kushi et al., 1992; van den Brandt et al., 1993; Velie et al., 2000; Willett et al., 1987, 1992). Evidence from epidemiological studies on the relationship between fat intake and colon cancer has been mixed as well (De Stefani et al., 1997b; Giovannucci et al., 1994; Willett et al., 1990). Howe and colleagues (1997) reported no asso- ciation between fat intake and risk of colorectal cancer from the com- bined analysis of 13 case-control studies. Epidemiological studies tend to suggest that dietary fat intake is not associated with prostate cancer (Ramon et al., 2000; Veierød et al., 1997b). Giovannucci and coworkers (1993), however, reported a positive association between total fat consumption, primarily animal fat, and risk of advanced prostate cancer. Findings on the association between fat intake and lung cancer have been mixed (De Stefani et al., 1997a; Goodman et al., 1988; Veierød et al., 1997a; Wu et al.,

55 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY 1994). Numerous mechanisms for the carcinogenic effect of dietary fat have been proposed, including eiconasanoid metabolism, cellular prolifera- tion, and alteration of gene expression (Birt et al., 1999). Experimental evidence suggests several mechanisms in which n-3 fatty acids may protect against cancer. n-3 Fatty acids, particularly docosahexaenoic acid and eicosapentaenoic acid, have been shown to suppress neoplastic transformation (Takahashi et al., 1992), inhibit cell growth and prolifera- tion (Anti et al., 1992; Calviello et al., 1998; Grammatikos et al., 1994), induce apoptosis (Calviello et al., 1998; Lai et al., 1996), and inhibit angio- genesis (Rose and Connolly, 2000), which may occur by suppressing n-6 fatty acid eicosanoid production. Epidemiological studies have shown an inverse relationship between fish consumption and the risk of breast and colorectal cancer (Caygill and Hill, 1995; Caygill et al., 1996; Kaizer et al., 1989; Sasaki et al., 1993; Willett et al., 1990). Monounsaturated fatty acids have been reported as being protective against breast, colon, and possibly prostate cancer (Bartsch et al., 1999). However, there is also some epidemiological evidence for a positive asso- ciation between these fatty acids and breast cancer risk in women with no history of benign breast disease (Velie et al., 2000) and prostate cancer in men (Schuurman et al., 1999). There may be protective effects associated with olive oil (Rose, 1997; Trichopoulou et al., 1995; Willett, 1997); how- ever, these benefits may reflect constituents other than monounsaturated fatty acids. Dietary Carbohydrate While the data on sugar intake and cancer are limited and insufficient, several case-control studies have shown an increased risk of colorectal cancer among individuals with high intakes of sugar-rich foods (Benito et al., 1990; Macquart-Moulin et al., 1986, 1987; Tuyns et al., 1988). Additionally, high vegetable and fruit consumption and avoidance of foods containing highly refined sugars were shown to be negatively correlated to the risk of colon cancer (Giovannucci and Willett, 1994). Dietary Fiber There is some evidence based on observational and case-control studies that fiber-rich diets are protective against colorectal cancer (Lanza, 1990; Trock et al., 1990). There is also some epidemiological evidence of a pro- tective effect of cereals and cereal fiber against colon carcinogenesis (Hill, 1997). Despite these and other positive findings, a number of important studies (Fuchs et al., 1999; Giovannucci and Willett, 1994) and three recent clinical intervention trials (Alberts et al., 2000; Bonithon-Kopp et al., 2000;

56 DIETARY REFERENCE INTAKES Schatzkin et al., 2000) do not support a protective effect of dietary fiber against colon cancer, and the issue remains to be resolved. High-fiber diets may also be protective against the development of colonic adenomas (Giovannucci et al., 1992; Hoff et al., 1986; Little et al., 1993; Macquart-Moulin et al., 1987; Neugut et al., 1993). However, not all studies have found a significant association between the dietary intake of total, cereal, or vegetable fiber and colorectal adenomas, although a slight reduction in risk was observed with increasing intake of fruit fiber (Platz et al., 1997). There are numerous hypotheses as to how fiber might protect against the development of colon cancer. These include the dilution of carcino- gens, procarcinogens, and tumor promoters in a bulky stool; a more rapid rate of transit through the colon with high-fiber diets; a reduction in the ratio of secondary bile acids to primary bile acids by acidifying colonic contents; the production of butyrate from the fermentation of dietary fiber by the colonic microflora; and the reduction of ammonia, which is known to be toxic to cells (Harris and Ferguson, 1993; Jacobs, 1986; Klurfeld, 1992; Van Munster and Nagengast, 1993; Visek, 1978). Fiber has been shown to lower serum estrogen concentrations (Rose et al., 1991), and therefore may have a protective effect against hormone- related cancers. Recent studies have shown a decreased risk of endome- trial cancer (Barbone et al., 1993; Goodman et al., 1997), ovarian cancer (Risch et al., 1994; Tzonou et al., 1993), and prostate cancer (Andersson et al., 1996) with high fiber intakes. More research is needed before con- clusions can be drawn on these relationships. Although fiber has the ability to decrease blood estrogen concentra- tions by a variety of different mechanisms (Rose et al., 1991), it is not yet known whether this action is sufficient to decrease the risk of breast cancer. Half of the epidemiological studies attempting to link low dietary fiber intake to breast cancer have failed to show this relationship (Gerber, 1998). The data on cereal intake and breast cancer risk are considerably stronger than overall fiber intake (Rohan et al., 1993), suggesting that certain cereal foods are protective or that only certain types and stages of breast cancer respond to these interventions. Physical Activity Regular exercise, as recommended in this report, has been shown to be negatively correlated with the risk of colon cancer (Colbert et al., 2001; White et al., 1996). This is, in part, due to the reduction in obesity, which is positively related to cancer (Carroll, 1998). In men and women who are physically active, the risk of colon cancer is reduced by 30 to 40 percent compared with those who are sedentary. A plausible mechanism for the

57 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY effect of physical activity on colon cancer is the shortening of intestinal transit time, thus reducing contact time between intestinal mucosa and carcinogens and mutagens in the diet that are carried in the fecal stream (Batty and Thune, 2000). Examination of more than 30 epidemiological studies concluded that regular physical activity decreased the risk of breast cancer by 20 to 40 percent (IARC, 2002). However, relatively few studies found a consistent association between physical activity and decreased incidence of endome- trial cancer. For prostate cancer, results of about 20 studies were less consistent, with only moderately strong relationships. As endogenous sex steroids have been implicated in the development of breast, endometrial, and prostrate cancers, a plausible explanation for the inverse relationship among physical activity and reproductive organ cancers may involve the effect of exercise on the binding and turnover of sex steroids and glucoregulatory hormones, as well as the overall effect of exercise on body fat (IARC, 2002; Vainio and Bianchini, 2001). With regard to the possible effect of exercise on other forms of cancer, such as pancreatic cancer (Michaud et al., 2001), exercise may also play a beneficial role by compensating for effects of excess energy intake; by modifying the effects of carcinogens, cocarcinogens, and cancer promoters; or by decreasing body fat and lessening the accumulation of cancer-causing substances in body tissues (Shephard, 1990, 1996). Regular activity may also bolster the immune system (Bruunsgaard et al., 1999; Mazzeo et al., 1998). HEART DISEASE The known risk factors for coronary heart disease (CHD) include high serum low density lipoprotein (LDL) cholesterol concentration, low serum high density lipoprotein (HDL) cholesterol concentration, a family history of CHD, hypertension, diabetes mellitus, cigarette smoking, advancing age, and obesity (Castelli, 1996; Hennekens, 1998; Parmley, 1997). There is a positive linear relationship between serum total cholesterol and LDL cholesterol concentrations and risk of CHD or mortality from CHD (Jousilahti et al., 1998; Neaton and Wentworth, 1992; Sorkin et al., 1992; Stamler et al., 1986). A low concentration of HDL cholesterol is positively correlated with risk of CHD, independent of other risk factors (Austin et al., 2000). High concentrations of serum triacylglycerol may also contribute to CHD (Austin, 1989), but the evidence is less clear. Most studies show a positive relationship between serum triacylglycerol and CHD (Bainton et al., 1992; Carlson and Böttiger, 1972; Gordon et al., 1977; Hulley et al., 1980; Stampfer et al., 1996); however, Gordon and coworkers (1977) found

58 DIETARY REFERENCE INTAKES that the statistical significance of this relationship disappears after control- ling for total cholesterol, LDL cholesterol, or HDL cholesterol. The role of diet in the promotion or prevention of heart disease is the subject of considerable research. New studies investigating dietary energy sources and physical activity for their potential to alter some of the risk factors for heart disease are underway (i.e., plasma cholesterol, hyper- tension, obesity, and diabetes). Dietary Fat Increasing the intake of saturated fat can increase serum total choles- terol and LDL cholesterol concentrations (Clarke et al., 1997; Hegsted et al., 1993; Kasim et al., 1993; Krauss and Dreon, 1995; Mensink and Katan, 1992). Furthermore, a meta-analysis of 37 intervention studies showed that a reduction in plasma total cholesterol and LDL cholesterol concentra- tions was correlated with reductions in percentages of total dietary fat that also included a decrease in saturated fats (Yu-Poth et al., 1999). The corre- lation between total fat and serum cholesterol concentration is due, in part, to the strong positive association between total fat and saturated fat intake and the weak association between total fat and polyunsaturated fat intake (Masironi, 1970; Stamler, 1979). Furthermore, the impact of satu- rated fats in increasing LDL cholesterol concentration is twofold greater than the impact of polyunsaturated fats in reducing LDL cholesterol (Hegsted et al., 1993; Mensink and Katan, 1992). This effect, however, is not seen with all saturated fatty acids. While lauric, myristic, and palmitic acids increase cholesterol concentration (Mensink et al., 1994), stearic acid has been shown to have a neutral effect (Bonanome and Grundy, 1988; Denke, 1994; Yu et al., 1995). Similar to saturated fat, increasing intakes of trans fatty acids and cholesterol increase serum total cholesterol and LDL cholesterol concen- trations (Ascherio et al., 1999; Clarke et al., 1997; Hegsted, 1986; Howell et al., 1997). Epidemiological studies have generally demonstrated a posi- tive association between trans fatty acid intake and increased risk of heart disease (Ascherio et al., 1994, 1996b; Hu et al., 1997; Pietinen et al., 1997; Willett et al., 1993); however, the risk with cholesterol intake has been mixed (Ascherio et al., 1996b; Hu et al., 1997, 1999b; Kushi et al., 1985; Mann et al., 1997; Pietinen et al., 1997). There is wide interindividual variation in serum cholesterol response to dietary cholesterol (Hopkins, 1992), which may be due to genetic factors. Monounsaturated and polyunsaturated fatty acids decrease serum total cholesterol and LDL cholesterol concentrations (Gardner and Kraemer, 1995). The epidemiological data indicate that monounsaturated fats are either not associated or are positively associated with risk of CHD (Hu et

59 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY al., 1997; Kromhout and de Lezenne Coulander, 1984; Pietinen et al., 1997). High intakes of n-6 polyunsaturated fats have been associated with the reduced total cholesterol and LDL cholesterol concentrations that are associated with low risk of CHD (Arntzenius et al., 1985; Becker et al., 1983; Sonnenberg et al., 1996). In general, epidemiological studies have demonstrated an inverse association between n-6 polyunsaturated fatty acid intake and risk of CHD (Arntzenius et al., 1985; Gartside and Glueck, 1993). n-3 Polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) have been shown to reduce the risk of CHD and stroke by a multitude of mechanisms: by preventing arrhythmias (Billman et al., 1999; Kang and Leaf, 1996; McLennan, 1993), reducing atherosclerosis (von Schacky et al., 1999), decreasing platelet aggregation (Harker et al., 1993), lowering plasma triacylglycerol concentrations (Harris, 1989), decreasing proinflammatory eicosanoids (James et al., 2000), modulating endothelial function (De Caterina et al., 2000), and decreasing blood pressure in hypertensive individuals (Morris et al., 1993). Many epidemiological studies have used fish or fish oil intake as a surro- gate for n-3 fatty acid intake because of the high content of EPA and DHA found in fish. A number of these studies have concluded that fish con- sumption reduced the risk of CHD mortality (Daviglus et al., 1997; Dolecek, 1992; Kromhout et al., 1985, 1995), while others found no asso- ciation (Albert et al., 1998; Ascherio et al., 1995). Dietary Carbohydrate High carbohydrate (low fat) intakes tend to increase plasma tri- acylglycerol and decrease plasma HDL cholesterol concentrations (Borkman et al., 1991; Brussaard et al., 1982; Marckmann et al., 2000; West et al., 1990; Yost et al., 1998). This effect has been observed especially for increased sugar intake (Mann et al., 1973; Rath et al., 1974; Reiser et al., 1979; Yudkin et al., 1986). Fructose is a better substrate for de novo lipogenesis than glucose or starches (Cohen and Schall, 1988; Reiser and Hallfrisch, 1987), and Parks and Hellerstein (2000) concluded that hypertriacylglycerolemia is more extreme if the carbohydrate content of the diet consists primarily of monosaccharides, particularly fructose. Dietary Fiber Evidence supports a protective effect of dietary fiber for CHD, particu- larly viscous fibers that occur naturally in foods, which reduce total choles- terol and LDL cholesterol concentrations (see Chapter 7). Reduced rates of CHD were observed in individuals consuming high fiber diets (Jacobs et al., 1998; Kushi et al., 1985; Pietinen et al., 1996). These studies used fiber-

60 DIETARY REFERENCE INTAKES containing foods; fiber supplements may not have the same effects. The type of fiber is important; oat bran (viscous fiber) significantly reduces total cholesterol, but wheat bran (primarily nonviscous fiber) may not (Behall, 1990). Viscous fibers are thought to lower serum cholesterol con- centrations by interfering with absorption and recirculation of bile acids and cholesterol in the intestine and thus decreasing the concentration of circulating cholesterol. These fibers may also work by delaying absorption of fat and carbohydrate, which could result in increased insulin sensitivity (Hallfrisch et al., 1995) and lower triacylglycerol concentrations (Rivellese et al., 1980). Dietary fiber intake has also been shown to be negatively associated with hypertension in men (Ascherio et al., 1992), but not women (Ascherio et al., 1996a). Fiber intake was shown to have an inverse rela- tionship with systolic and diastolic pressures (Ashcerio et al., 1996a). Dietary Protein An inverse relationship between protein intake and risk of CHD has been observed (Hu et al., 1999a). High protein intake has been shown to lower blood pressure (Obarzanek et al., 1996), and substitution of carbo- hydrate with protein resulted in lower LDL cholesterol and triacylglycerol concentrations (Wolfe and Piché, 1999). These results may, however, be confounded by the fact that dietary animal protein and dietary fat tend to be highly correlated. Independent effects of protein on CHD mortality have not been shown (Gordon et al., 1981; Keys et al., 1986). Soy-based protein may reduce serum cholesterol concentrations, but the evidence has been mixed (Anderson et al., 1995; Bakhit et al., 1994; Meinertz et al., 1989; van Raaij et al., 1982). Physical Activity Exercise improves and maintains vessel function. An inverse relation- ship between exercise and CHD mortality has been observed in numerous studies (Arraiz et al., 1992; Kannel et al., 1986; Lindsted et al., 1991; Paffenbarger et al., 1984). Regular exercise increases serum HDL choles- terol, decreases serum triacylglycerol, decreases blood pressure, enhances fibrinolysis, lessens platelet adherence, enhances glucose effectiveness and insulin sensitivity, and decreases risk of cardiac arrhythmias (Araújo-Vilar et al., 1997; Arroll and Beaglehole, 1992; El-Sayed, 1996; Hinkle et al., 1988; Huttunen et al., 1979). The mechanisms by which exercise serves to mitigate progression of cardiovascular disease (CVD) and coronary artery disease (CAD) are numerous. For instance, patients with CAD who participated in exercise training showed improved endothelium-dependent vasodilatation in epi-

61 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY cardial coronary vessels and in resistance vessels (Hambrecht et al., 2000). Thus, exercise serves to maintain conduit function in vessels impacted by CAD. An inverse dose–response relationship between physical activity and physical fitness and CVD mortality has been documented (Arraiz et al., 1992; Blair et al., 1993; Kannel and Sorlie, 1979; Kannel et al., 1986; Lindsted et al., 1991; Paffenbarger et al., 1984). Activity may also influence CVD indirectly via an influence on lipoprotein metabolism. Vigorous physical activity increases plasma HDL cholesterol, HDL2, and apolipoprotein A-I and decreases plasma triacylglycerol, very low density lipoprotein, and atherogenic small, dense LDL concentrations (Williams et al., 1986, 1990, 1992; Wood et al., 1988). Gradient gel electro- phoresis shows that the protective HDL2b subclass is increased while the HDL3b subclass is decreased through exercise (Williams et al., 1992). The distribution of LDL is shifted toward larger and more buoyant particles of lower density that result in a decrease in the prevalence of the small, dense LDL phenotype among vigorously active men (Williams et al., 1990). Cross- sectional comparisons of high mileage and low mileage runners suggest that the benefits of vigorous exercise on the lipoprotein profile increase linearly with exercise dose through at least 40 mi (64 km)/wk for both HDL cholesterol and triacylglycerol (Williams, 1997). Physical activity pre- vents the rise in plasma triacylglycerols in individuals who consume high carbohydrate diets (Koutsari et al., 2001). Many of the exercise-induced changes in lipoproteins may arise from the effects of lipolytic enzymes on lipoprotein size and composition, namely increases in lipoprotein lipase activity and decreases in hepatic lipase activity (Williams et al., 1986). Runners have significantly higher lipoprotein lipase activity in both muscle and adipose tissue (Nikkilä et al., 1978). Weight loss is known to both increase lipoprotein lipase and reduce hepatic lipase (Marniemi et al., 1990; Purnell et al., 2000). This may explain, in part, why increases in HDL cholesterol and HDL2 mass in sed- entary men who begin exercising vigorously are strongly associated with loss of body fat (Williams et al., 1983). Lipoprotein lipase activity may also explain why HDL cholesterol concentrations in sedentary men predict their success at running (Williams et al., 1994). Specifically, the enzyme’s activity is positively correlated with HDL cholesterol concentrations and is higher in slow-twitch red muscle fibers. Thus, high HDL concentrations may be a marker for muscle fiber composition that facilitates endurance exercise. DENTAL CARIES Sugars play an important role in dental caries development (Walker and Cleaton-Jones, 1992). Sugars provide a favorable environment for bac-

62 DIETARY REFERENCE INTAKES teria in the mouth, and the presence of these sugars increases the rate and volume of plaque formation (Depaola et al., 1999). However, because development of caries involves other factors such as fluoride intake, oral hygiene, food composition, and frequency of meals and snacks, sugar intake alone is not the only cause of caries. TYPE 2 DIABETES MELLITUS Type 2 diabetes mellitus is characterized by a genetic predisposition to the disorder, decreased tissue sensitivity to insulin (insulin resistance), and impaired function of pancreatic β-cells, which control the timely release of insulin (Anderson, 1999). Obesity, physical inactivity, and advancing age are primary risk factors for insulin resistance and development of type 2 diabetes (Barrett-Connor, 1989; Colditz et al., 1990; Helmrich et al., 1991; Manson et al., 1991). Dietary factors have also been suggested as playing a major role in the development of insulin resistance and type 2 diabetes. Dietary Fat Intervention studies that have evaluated the effect of the level of fat intake on biochemical risk factors for diabetes have been mixed (Abbott et al., 1989; Borkman et al., 1991; Coulston et al., 1983; Fukagawa et al., 1990; Howard et al., 1991; Jeppesen et al., 1997; Leclerc et al., 1993; Straznicky et al., 1999; Swinburn et al., 1991; Thomsen et al., 1999; Yost et al., 1998). Some epidemiological studies have shown a correlation between higher fat intakes and insulin resistance (Marshall et al., 1991; Mayer-Davis et al., 1997; Parker et al., 1993). It is not clear, however, whether the correlation is due to fat in the diet or to obesity. Obesity, particularly abdominal obesity, is a risk factor for type 2 diabetes (Vessby, 2000). Decreased physical activity is also a significant predictor of higher post- prandial insulin concentrations and may confound some studies (Feskens et al., 1994; Parker et al., 1993). Findings from intervention studies tend to suggest a lack of adverse effect of saturated fat on risk indictors of diabetes in healthy individuals (Fasching et al., 1996; Roche et al., 1998; Thomsen et al., 1999). However, it was recently reported that the consumption of saturated fatty acids can significantly impair insulin sensitivity (Vessby et al., 2001). Because of the favorable effects of n-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on risk indicators of coronary heart dis- ease, they are often used in patients with lipid disorders. There has been concern about the use of these fatty acids for lipid disorders because many of these patients also have type 2 diabetes. A number of studies have sug-

63 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY gested that n-3 polyunsaturated fatty acid intake may have adverse effects in individuals with type 2 diabetes (Glauber et al., 1988; Kasim et al., 1988), requiring increased doses of hypoglycemic agents (Friday et al., 1989; Stacpoole et al., 1989; Zambon et al., 1992). Dietary Carbohydrate There is little evidence that total dietary carbohydrate intake is associ- ated with type 2 diabetes (Colditz et al., 1992; Lundgren et al., 1989). There may be an increased risk, however, when the glycemic index of a meal is considered instead of total carbohydrates (Salmerón et al., 1997a, 1997b). Some studies have found that reducing the glycemic index of a meal can result in short-term improved glucose tolerance and insulin sensi- tivity in healthy individuals (Frost et al., 1998; Jenkins et al., 1988; Liljeberg et al., 1999; Wolever et al., 1988). Additional long-term studies are needed to elucidate the true relationship between glycemic index and the development of type 2 diabetes and to determine its effect on glucose tolerance and insulin. Dietary Fiber Certain dietary fibers may attenuate the insulin response and thus be protective against type 2 diabetes. There is good epidemiological evidence for the protective effect of fiber against type 2 diabetes (Colditz et al., 1992; Meyer et al., 2000; Salmerón et al., 1997a, 1997b). Viscous soluble fibers, such as pectin and guar gum, have been found to produce a signifi- cant reduction in glycemic response in the majority of studies reviewed by Wolever and Jenkins (1993). It is believed that viscous soluble fibers reduce the glycemic response of food by delaying gastric emptying and therefore delaying the absorption of glucose (Jenkins et al., 1978; Wood et al., 1994). Physical Activity Increased levels of physical activity have been found to improve insulin sensitivity in individuals with type 2 diabetes (Horton, 1986; Mayer-Davis et al., 1998; Schneider et al., 1984). Physical inactivity was found to be associ- ated with increased incidence of type 2 diabetes in cross-sectional (King et al., 1984; Taylor et al., 1983), cohort (Helmrich et al., 1991; Manson et al., 1991, 1992), and longitudinal training studies (Tuomilehto et al., 2001). Short- and long-term effects of physical activity on glucose tolerance, insulin action, and muscle glucose uptake show that contracting muscle has an “insulin-like” effect on promoting glucose uptake and metabolism (Bergman et al., 1999; Horton, 1991; Richter et al., 1981). This synergistic

64 DIETARY REFERENCE INTAKES effect of contractions on insulin action is thought to increase insulin action and decrease circulating glucose and insulin concentrations. Further, by increasing muscle mass, decreasing total and abdominal obesity (Björntorp et al., 1979; Després et al., 1988), and diverting dietary carbohydrate to muscle for oxidation and glycogen repletion (Brooks et al., 2000), physical activity reduces the potential for energy intakes exceeding expenditures, leading to fat accumulation. Physical activity can reduce the risk of type 2 diabetes (Diabetes Prevention Program Research Group, 2002; Tuomilehto et al., 2001), and can also reduce total and abdominal obesity, both of which are risk factors for type 2 diabetes (Vessby, 2000). OBESITY Obesity results from an imbalance between energy intake and energy expenditure. The health risks associated with obesity include increased mortality, hypertension, cardiovascular disease, diabetes mellitus, gallbladder disease, some cancers, and changes in endocrine function and metabolism (NHLBI/NIDDK, 1998). The risk factors for becoming obese are not entirely understood but are thought to include genetics, food intake, physi- cal inactivity, and some rare metabolic disorders (NHLBI/NIDDK, 1998). Dietary Fat The available data on whether diets high in total fat increase the risk for obesity are conflicting and are complicated by underreporting of food intake, notably fat intake (Bray and Popkin, 1998; Lissner and Heitmann, 1995; Lissner et al., 2000; Willett, 1998). Intervention studies have shown that high-fat diets, as compared with low-fat diets with equivalent energy intake, are not intrinsically fattening (Davy et al., 2001), whereas cross- cultural, animal, and some human studies have provided support for the theory that diets with a high percentage of fat increase the risk of obesity (Astrup et al., 1997; Lissner and Heitmann, 1995; West and York, 1998). Other studies have shown that as the proportion of fat in the diet increases, so does energy intake (Kendall et al., 1991; Lissner et al., 1987; Stubbs et al., 1995). Because energy density was not kept separate from fat content in these studies, recent investigators have questioned the conclusions of these studies and have found differing results. Further studies have shown that fat content does not affect energy intake (Saltzman et al., 1997; Stubbs et al., 1996; van Stratum et al., 1978), and that energy density has an effect on energy intake independent of the fat content of the diet (Bell et al., 1998).

65 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY Dietary Carbohydrate A negative correlation between total sugars intake and body mass index has been reported in adults (Dreon et al., 1988; Dunnigan et al., 1970; Fehily et al., 1984; Gibson, 1993, 1996b; Miller et al., 1990). Increased added sugars intakes have been shown to result in increased energy intakes of children and adults (see Chapter 6) (Bowman, 1999; Gibson, 1996a, 1997; Lewis et al., 1992). In spite of this, a negative correlation between added sugars intake and body mass index has been observed in children (Bolton-Smith and Woodward, 1994; Gibson, 1996a; Lewis et al., 1992). Published reports disagree about whether a direct link exists between the trend toward higher intakes of sugars and increased rates of obesity. Any association between added sugars intake and body mass index is, in all likelihood, masked by the pervasive and serious problem of underreporting, which is more prevalent and severe among the obese population. In addi- tion, foods and beverages high in added sugars are more likely to be underreported compared to other foods that may be perceived as “healthy” (Johnson, 2000). Dietary Fiber Consumption of soluble fibers, which are low in energy, delays gastric emptying (Roberfroid, 1993), which in turn can cause an extended feeling of fullness and therefore satiety (Bergmann et al., 1992). A number of intervention studies suggest that diets high in fiber may assist in weight loss (Birketvedt et al., 2000; Eliasson et al., 1992; Rigaud et al., 1990; Rössner et al., 1987; Ryttig et al., 1989), although other studies have not found this effect (Astrup et al., 1990; Baron et al., 1986). Thus, the evi- dence to support a role of fiber in the prevention of obesity is unclear at this time. Physical Activity Energy expenditure by physical activity (see Chapters 5 and 12) varies considerably between individuals, affecting the energy balance and the body composition by which energy balance and weight maintenance are achieved (Ballor and Keesey, 1991; Williamson et al., 1993). Indeed, physi- cal inactivity is a major risk factor for development of obesity in children and adults (Astrup, 1999; Goran, 2001). In one study, increasing the level of physical activity in obese individuals appeared to have no effect on food intake, whereas in normal-weight individuals an increase in activity was coupled with an increase in food intake (Pi-Sunyer and Woo, 1985).

66 DIETARY REFERENCE INTAKES SKELETAL HEALTH Physical activity has a beneficial effect on bone health in individuals of all ages (Anderson, 2000; French et al., 2000; Hurley and Roth, 2000; Khan et al., 2000; Layne and Nelson, 1999; Madsen et al., 1998). Physical activity increases bone mass in children and adolescents and maintains bone mass in adults (French et al., 2000; Khan et al., 2000). In elderly individuals, bone mineral density has been found to be higher in those who exercise than in those who do not (Hurley and Roth, 2000). The same is true for young athletes compared to nonathletes (Madsen et al., 1998). Physical activity results in muscle strength, coordination, and flex- ibility that may benefit elderly individuals by preventing falls and fractures. SUMMARY Many causal relationships among over- or underconsumption of macronutrients, physical inactivity, and chronic disease have been pro- posed. When the diet is modified for one energy-yielding nutrient, it invariably changes the intake of other nutrients, which makes it extremely difficult to have adequate substantiating evidence for providing clear and specific nutritional guidance. Acceptable Macronutrient Distribution Ranges can be estimated, however, by considering risk of chronic disease, as well as in the context of consuming adequate amounts of essential macronutrients and micronutrients. This information is provided in detail in Chapter 11. REFERENCES Abbott WGH, Boyce VL, Grundy SM, Howard BV. 1989. Effects of replacing satu- rated fat with complex carbohydrate in diets of subjects with NIDDM. Diabetes Care 12:102–107. Albert CM, Hennekens CH, O’Donnell CJ, Ajani UA, Carey VJ, Willett WC, Ruskin JN, Manson JE. 1998. Fish consumption and risk of sudden cardiac death. J Am Med Assoc 279:23–28. Alberts DS, Martínes ME, Roe DJ, Guillén-Rodríguez JM, Marshall JR, van Leeuwen JB, Reid ME, Ritenbaugh C, Vargas PA, Bhattacharyya AB, Earnest DL, Sampliner RE. 2000. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. N Engl J Med 342:1156–1162. Anderson JJB. 2000. The important role of physical activity in skeletal develop- ment: How exercise may counter low calcium intake. Am J Clin Nutr 71:1384– 1386. Anderson JW. 1999. Nutritional management of diabetes mellitus. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease, 9th ed. Baltimore, MD: Williams and Wilkins. Pp. 1365–1394. Anderson JW, Johnstone BM, Cook-Newell ME. 1995. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 333:276–282.

67 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY Andersson S-O, Wolk A, Bergström R, Giovannucci E, Lindgren C, Baron J, Adami H-O. 1996. Energy, nutrient intake and prostate cancer risk: A population- based case-control study in Sweden. Int J Cancer 68:716–722. Anti M, Marra G, Armelao F, Bartoli GM, Ficarelli R, Percesepe A, De Vitis I, Maria G, Sofo L, Rapaccini GL. 1992. Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer. Gastroenterology 103:883– 891. Araújo-Vilar D, Osifo E, Kirk M, García-Estévez DA, Cabezas-Cerrato J, Hockaday TDR. 1997. Influence of moderate physical exercise on insulin-mediated and non-insulin-mediated glucose uptake in healthy subjects. Metabolism 46:203– 209. Armstrong B, Doll R. 1975. Environmental factors and cancer incidence and mor- tality in different countries, with special reference to dietary practices. Int J Cancer 15:617–631. Arntzenius AC, Kromhout D, Barth JD, Reiber JHC, Bruschke AVG, Buis B, van Gent CM, Kempen-Voogd N, Strikwerda S, van der Velde EA. 1985. Diet, lipo- proteins, and the progression of coronary atherosclerosis. The Leiden Inter- vention Trial. N Engl J Med 312:805–811. Arraiz GA, Wigle DT, Mao Y. 1992. Risk assessment of physical activity and physical fitness in the Canada Health Survey Mortality Follow-up Study. J Clin Epidemiol 45:419–428. Arroll B, Beaglehole R. 1992. Does physical activity lower blood pressure: A review of the clinical trials. J Clin Epidemiol 45:439–447. Ascherio A, Rimm EB, Giovannucci EL, Colditz GA, Rosner B, Willett WC, Sacks F, Stampfer MJ. 1992. A prospective study of nutritional factors and hyperten- sion among US men. Circulation 86:1475–1484. Ascherio A, Hennekens CH, Buring JE, Master C, Stampfer MJ, Willett WC. 1994. Trans-fatty acids intake and risk of myocardial infarction. Circulation 89:94– 101. Ascherio A, Rimm EB, Stampfer MJ, Giovannucci EL, Willett WC. 1995. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 332:977–982. Ascherio A, Hennekens C, Willett WC, Sacks F, Rosner B, Manson J, Witteman J, Stampfer MJ. 1996a. Prospective study of nutritional factors, blood pressure, and hypertension among US women. Hypertension 27:1065–1072. Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer M, Willett WC. 1996b. Dietary fat and risk of coronary heart disease in men: Cohort follow up study in the United States. Br Med J 313:84–90. Ascherio A, Katan MB, Zock PL, Stampfer MJ, Willett WC. 1999. Trans fatty acids and coronary heart disease. N Engl J Med 340:1994–1998. Astrup A. 1999. Macronutrient balances and obesity: The role of diet and physical activity. Public Health Nutr 2:341–347. Astrup A, Vrist E, Quaade F. 1990. Dietary fibre added to very low calorie diet reduces hunger and alleviates constipation. Int J Obes 14:105–112. Astrup A, Toubro S, Raben A, Skov AR. 1997. The role of low-fat diets and fat substitutes in body weight management: What have we learned from clinical studies? J Am Diet Assoc 97:S82–S87. Austin MA. 1989. Plasma triglyceride as a risk factor for coronary heart disease. The epidemiologic evidence and beyond. Am J Epidemiol 129:249–259.

68 DIETARY REFERENCE INTAKES Austin MA, Rodriguez BL, McKnight B, McNeely MJ, Edwards KL, Curb DJ, Sharp DS. 2000. Low-density lipoprotein particle size, triglycerides, and high-density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese-American men. Am J Cardiol 86:412–416. Bainton D, Miller NE, Bolton CH, Yarnell JWG, Sweetnam PM, Baker IA, Lewis B, Elwood PC. 1992. Plasma triglyceride and high density lipoprotein cholesterol as predictors of ischaemic heart disease in British men. The Caerphilly and Speedwell Collaborative Heart Disease Studies. Br Heart J 68:60–66. Bakhit RM, Klein BP, Essex-Sorlie D, Ham JO, Erdman JW, Potter SM. 1994. Intake of 25 g of soybean protein with or without soybean fiber alters plasma lipids in men with elevated cholesterol concentrations. J Nutr 124:213–222. Ballor DL, Keesey RE. 1991. A meta-analysis of the factors affecting exercise-induced changes in body mass, fat mass and fat-free mass in males and females. Int J Obes 15:717–726. Barbone F, Austin H, Partridge EE. 1993. Diet and endometrial cancer: A case- control study. Am J Epidemiol 137:393–403. Baron JA, Schori A, Crow B, Carter R, Mann JI. 1986. A randomized controlled trial of low carbohydrate and low fat/high fiber diets for weight loss. Am J Public Health 76:1293–1296. Barrett-Connor E. 1989. Epidemiology, obesity, and non-insulin-dependent diabetes mellitus. Epidemiol Rev 11:172–181. Bartsch H, Nair J, Owen RW. 1999. Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: Emerging evidence for their role as risk modifiers. Carcinogenesis 20:2209–2218. Batty D, Thune I. 2000. Does physical activity prevent cancer? Evidence suggests protection against colon cancer and probably breast cancer. Br Med J 321:1424– 1425. Becker N, Illingworth R, Alaupovic P, Connor WE, Sundberg EE. 1983. Effects of saturated, monounsaturated, and ω-6 polyunsaturated fatty acids on plasma lipids, lipoproteins, and apoproteins in humans. Am J Clin Nutr 37:355–360. Behall KM. 1990. Effect of soluble fibers on plasma lipids, glucose tolerance and mineral balance. Adv Exp Med Biol 270:7–16. Bell EA, Castellanos VH, Pelkman CL, Thorwart ML, Rolls BJ. 1998. Energy density of foods affects energy intake in normal-weight women. Am J Clin Nutr 67:412– 420. Benito R, Obrador A, Stiggelbout A, Bosch FX, Mulet M, Muñoz N, Kaldor J. 1990. A population-based case-control study of colorectal cancer in Majorca. I. Di- etary factors. Int J Cancer 45:69–76. Bergman BC, Butterfield GE, Wolfel EE, Lopaschuk GD, Casazza GA, Horning MA, Brooks GA. 1999. Muscle net glucose uptake and glucose kinetics after endurance training in men. Am J Physiol 277:E81–E92. Bergmann JF, Chassany O, Petit A, Triki R, Caulin C, Segrestaa JM. 1992. Correla- tion between echographic gastric emptying and appetite: Influence of psyllium. Gut 33:1042–1043. Billman GE, Kang JX, Leaf A. 1999. Prevention of sudden cardiac death by dietary pure ω-3 polyunsaturated fatty acids in dogs. Circulation 99:2452–2457. Birketvedt GS, Aaseth J, Florholmen JR, Ryttig K. 2000. Long term effect of fibre supplement and reduced energy intake on body weight and blood lipids in overweight subjects. Acta Medica (Hradec Králové) 43:129–132.

69 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY Birt DF, Shull JD, Yaktine AL. 1999. Chemoprevention of cancer. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease, 9th ed. Baltimore, MD: Williams and Wilkins. Pp. 1263–1295. Björntorp P, Sjöström L, Sullivan L. 1979. The role of physical exercise in the management of obesity. In: Munro JF, ed. The Treatment of Obesity. Baltimore, MD: University Park Press. Pp. 123–138. Blair SN, Kohl HW, Barlow CE. 1993. Physical activity, physical fitness, and all- cause mortality in women: Do women need to be active? J Am Coll Nutr 12:368– 371. Bolton-Smith C, Woodward M. 1994. Dietary composition and fat to sugar ratios in relation to obesity. Int J Obes Relat Metab Disord 18:820–828. Bonanome A, Grundy SM. 1988. Effect of dietary stearic acid on plasma choles- terol and lipoprotein levels. N Engl J Med 318:1244–1248. Bonithon-Kopp C, Kronborg O, Giacosa A, Räth U, Faivre J. 2000. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: A randomised intervention trial. Lancet 356:1300–1306. Borkman M, Campbell LV, Chisholm DJ, Storlien LH. 1991. Comparison of the effects on insulin sensitivity of high carbohydrate and high fat diets in normal subjects. J Clin Endocrinol Metab 72:432–437. Bowman SA. 1999. Diets of individuals based on energy intakes from added sugars. Fam Econ Nutr Rev 12:31–38. Bray GA, Popkin BM. 1998. Dietary fat intake does affect obesity! Am J Clin Nutr 68:1157–1173. Brooks GA, Fahey TD, White TP, Baldwin KM. 2000. Exercise Physiology: Human Bioenergetics and its Applications, 3rd ed. Mountain View, CA: Mayfield Publishing. Brussaard JH, Katan MB, Groot PHE, Havekes LM, Hautvast JGAJ. 1982. Serum lipoproteins of healthy persons fed a low-fat diet or a polyunsaturated fat diet for three months. A comparison of two cholesterol-lowering diets. Atherosclerosis 42:205–219. Bruunsgaard H, Jensen MS, Schjerling P, Halkjaer-Kristensen J, Ogawa K, Skinhøj P, Pedersen BK. 1999. Exercise induces recruitment of lymphocytes with an activated phenotype and short telomeres in young and elderly humans. Life Sci 65:2623–2633. Calviello G, Palozza P, Piccioni E, Maggiano N, Frattucci A, Franceschelli P, Baroli GM. 1998. Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: Effects on pro- liferation and apoptosis. Int J Cancer 75:699–705. Carlson LA, Böttiger LE. 1972. Ischaemic heart-disease in relation to fasting values of plasma triglycerides and cholesterol. Stockholm Prospective Study. Lancet 1:865–868. Carroll KK. 1998. Obesity as a risk factor for certain types of cancer. Lipids 33:1055– 1059. Castelli WP. 1996. Lipids, risk factors and ischaemic heart disease. Atherosclerosis 124:S1–S9. Caygill CPJ, Hill MJ. 1995. Fish, n-3 fatty acids and human colorectal and breast cancer mortality. Eur J Cancer Prev 4:329–332. Caygill CPJ, Charlett A, Hill MJ. 1996. Fat, fish, fish oil and cancer. Br J Cancer 74:159–164. Clarke R, Frost C, Collins R, Appleby P, Peto R. 1997. Dietary lipids and blood cholesterol: Quantitative meta-analysis of metabolic ward studies. Br Med J 314:112–117.

70 DIETARY REFERENCE INTAKES Cohen JC, Schall R. 1988. Reassessing the effects of simple carbohydrates on the serum triglyceride responses to fat meals. Am J Clin Nutr 48:1031–1034. Colbert LH, Hartman TJ, Malila N, Limburg PJ, Pietinen P, Virtamo J, Taylor PR, Albanes D. 2001. Physical activity in relation to cancer of the colon and rectum in a cohort of male smokers. Cancer Epidemiol Biomarkers Prev 10:265–268. Colditz GA, Willett WC, Stampfer MJ, Manson JE, Hennekens CH, Arky RA, Speizer FE. 1990. Weight as a risk factor for clinical diabetes in women. Am J Epidemiol 132:501–513. Colditz GA, Manson JE, Stampfer MJ, Rosner B, Willett WC, Speizer FE. 1992. Diet and risk of clinical diabetes in women. Am J Clin Nutr 55:1018–1023. Coulston AM, Liu GC, Reaven GM. 1983. Plasma glucose, insulin and lipid responses to high-carbohydrate low-fat diets in normal humans. Metabolism 32:52–56. Daviglus ML, Stamler J, Orencia AJ, Dyer AR, Liu K, Greenland P, Walsh MK, Morris D, Shekelle RB. 1997. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med 336:1046–1053. Davy KP, Horton T, Davy BM, Bessessen D, Hill JO. 2001. Regulation of macro- nutrient balance in healthy young and older men. Int J Obes Relat Metab Disord 25:1497–1502. De Caterina R, Liao JK, Libby P. 2000. Fatty acid modulation of endothelial activa- tion. Am J Clin Nutr 71:213–223. Denke MA. 1994. Effects of cocoa butter on serum lipids in humans: Historical highlights. Am J Clin Nutr 60:1014S–1016S. Depaola DP, Faine MP, Palmer CA. 1999. Nutrition in relation to dental medicine. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease, 9th ed. Baltimore, MD: Williams and Wilkins. Pp. 1099–1124. Després J-P, Tremblay A, Nadeau A, Bouchard C. 1988. Physical training and changes in regional adipose tissue distribution. Acta Med Scand Suppl 723: 205–212. De Stefani E, Deneo-Pellegrini H, Mendilaharsu M, Carzoglio JC, Ronco A. 1997a. Dietary fat and lung cancer: A case-control study in Uruguay. Cancer Causes Control 8:913–921. De Stefani E, Mendilaharsu M, Deneo-Pellegrini H, Ronco A. 1997b. Influence of dietary levels of fat, cholesterol, and calcium on colorectal cancer. Nutr Cancer 29:83–89. Diabetes Prevention Program Research Group. 2002. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403. Dolecek TA. 1992. Epidemiological evidence of relationships between dietary poly- unsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial. Proc Soc Exp Med Biol 200:177–182. Dreon DM, Frey-Hewitt B, Ellsworth N, Williams PT, Terry RB, Wood PD. 1988. Dietary fat:carbohydrate ratio and obesity in middle-aged men. Am J Clin Nutr 47:995–1000. Dunnigan MG, Fyfe T, McKiddie MT, Crosbie SM. 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. Eliasson K, Ryttig KR, Hylander B, Rossner S. 1992. A dietary fibre supplement in the treatment of mild hypertension. A randomized, double-blind, placebo- controlled trial. J Hypertens 10:195–199.

71 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY El-Sayed MS. 1996. Effects of exercise on blood coagulation, fibrinolysis and plate- let aggregation. Sports Med 22:282–298. Fasching P, Ratheiser K, Schneeweiss B, Rohac M, Nowotny P, Waldhausl W. 1996. No effect of short-term dietary supplementation of saturated and poly- and monounsaturated fatty acids on insulin secretion and sensitivity in healthy men. Ann Nutr Metab 40:116–122. Fehily AM, Phillips KM, Yarnell JWG. 1984. Diet, smoking, social class, and body mass index in the Caerphilly Heart Disease Study. Am J Clin Nutr 40:827–833. Feskens EJM, Loeber JG, Kromhout D. 1994. Diet and physical activity as determi- nants of hyperinsulinemia: The Zutphen Elderly Study. Am J Epidemiol 140: 350–360. Frankel S, Gunnell DJ, Peters TJ, Maynard M, Smith GD. 1998. Childhood energy intake and adult mortality from cancer: The Boyd Orr Cohort Study. Br Med J 316:499–504. French SA, Fulkerson JA, Story M. 2000. Increasing weight-bearing physical activity and calcium intake for bone mass growth in children and adolescents: A review of intervention trials. Prev Med 31:722–731. Friday KE, Childs MT, Tsunehara CH, Fujimoto WY, Bierman EL, Ensinck JW. 1989. Elevated plasma glucose and lowered triglyceride levels from omega-3 fatty acid supplementation in type II diabetes. Diabetes Care 12:276–281. Frost G, Leeds A, Trew G, Margara R, Dornhorst A. 1998. Insulin sensitivity in women at risk of coronary heart disease and the effect of a low glycemic diet. Metabolism 47:1245–1251. Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Stampfer MJ, Rosner B, Speizer FE, Willett WC. 1999. Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med 340:169–176. Fukagawa NK, Anderson JW, Hageman G, Young VR, Minaker KL. 1990. High- carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults. Am J Clin Nutr 52:524–528. Gardner CD, Kraemer HC. 1995. Monounsaturated versus polyunsaturated dietary fat and serum lipids. A meta-analysis. Arterioscler Thromb Vasc Biol 15:1917– 1927. Gartside PS, Glueck CJ. 1993. Relationship of dietary intake to hospital admission for coronary heart and vascular disease: The NHANES II National Probability Study. J Am Coll Nutr 6:676–684. Gerber M. 1998. Fibre and breast cancer. Eur J Cancer Prev 7:S63–S67. Gibson SA. 1993. Consumption and sources of sugars in the diets of British school- children: Are high-sugar diets nutritionally inferior? J Hum Nutr Diet 6:355– 371. Gibson SA. 1996a. Are diets high in non-milk extrinsic sugars conducive to obesity? An analysis from the Dietary and Nutritional Survey of British Adults. J Hum Nutr Diet 9:283–292. Gibson SA. 1996b. Are high-fat, high-sugar foods and diets conducive to obesity? Int J Food Sci Nutr 47:405–415. Gibson SA. 1997. Non-milk extrinsic sugars in the diets of pre-school children: Association with intakes of micronutrients, energy, fat and NSP. Br J Nutr 78:367–378. Giovannucci E, Willett WC. 1994. Dietary factors and risk of colon cancer. Ann Med 26:443–452. Giovannucci E, Stampfer MJ, Colditz G, Rimm EB, Willett WC. 1992. Relationship of diet to risk of colorectal adenoma in men. J Natl Cancer Inst 84:91–98.

72 DIETARY REFERENCE INTAKES Giovannucci E, Rimm EB, Colditz GA, Stampfer MJ, Ascherio A, Chute CC, Willett WC. 1993. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst 85:1571–1579. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. 1994. Intake of fat, meat, and fiber in relation to risk of colon cancer in men. Cancer Res 54:2390–2397. Glauber H, Wallace P, Griver K, Brechtel G. 1988. Adverse metabolic effect of omega-3 fatty acids in non-insulin-dependent diabetes mellitus. Ann Intern Med 108:663–668. Goodman MT, Kolonel LN, Yoshizawa CN, Hankin JH. 1988. The effect of dietary cholesterol and fat on the risk of lung cancer in Hawaii. Am J Epidemiol 128:1241–1255. Goodman MT, Wilkens LR, Hankin JH, Lyu L-C, Wu AH, Kolonel LN. 1997. Asso- ciation of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol 146:294–306. Goran MI. 2001. Metabolic precursors and effects of obesity in children: A decade of progress, 1990–1999. Am J Clin Nutr 73:158–171. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. 1977. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 62:707–714. Gordon T, Kagan A, Garcia-Palmieri M, Kannel WB, Zukel WJ, Tillotson J, Sorlie P, Hjortland M. 1981. Diet and its relation to coronary heart disease and death in three populations. Circulation 63:500–515. Grammatikos SI, Subbaiah PV, Victor TA, Miller WM. 1994. n-3 And n-6 fatty acid processing and growth effects in neoplastic and non-cancerous human mam- mary epithelial cell lines. Br J Cancer 70:219–227. Gray GE, Pike MC, Henderson BE. 1979. Breast-cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices. Br J Cancer 39:1–7. Hallfrisch J, Scholfield DJ, Behall KM. 1995. Diets containing soluble oat extracts improve glucose and insulin responses of moderately hypercholesterolemic men and women. Am J Clin Nutr 61:379–384. Hambrecht R, Wolf A, Gielen S, Linke A, Hofer J, Erbs S, Schoene N, Schuler G. 2000. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Eng J Med 342:454–460. Harker LA, Kelly AB, Hanson SR, Krupski W, Bass A, Osterud B, Fitzgerald GA, Goodnight SH, Connor WE. 1993. Interruption of vascular thrombus forma- tion and vascular lesion formation by dietary n-3 fatty acids in fish oil in non- human primates. Circulation 87:1017–1029. Harris PJ, Ferguson LR. 1993. Dietary fibre: Its composition and role in protection against colorectal cancer. Mutat Res 290:97–110. Harris WS. 1989. Fish oils and plasma lipid and lipoprotein metabolism in humans: A critical review. J Lipid Res 30:785–807. Hegsted DM. 1986. Serum-cholesterol response to dietary cholesterol: A re- evaluation. Am J Clin Nutr 44:299–305. Hegsted DM, Ausman LM, Johnson JA, Dallal GE. 1993. Dietary fat and serum lipids: An evaluation of the experimental data. Am J Clin Nutr 57:875–883. Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS. 1991. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 325:147–152.

73 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY Hennekens CH. 1998. Risk factors for coronary heart disease in women. Cardiol Clin 16:1–8. Hill MJ. 1997. Cereals, cereal fibre and colorectal cancer risk: A review of the epidemiological literature. Eur J Cancer Prev 6:219–225. Hinkle LE, Thaler HT, Merke DP, Renier-Berg D, Morton NE. 1988. The risk factors for arrhythmic death in a sample of men followed for 20 years. Am J Epidemiol 127:500–515. Hoff G, Moen IE, Trygg K, Frølich W, Sauar J, Vatn M, Gjone E, Larsen S. 1986. Epidemiology of polyps in the rectum and sigmoid colon. Evaluation of nutri- tional factors. Scand J Gastroenterol 21:199–204. Hopkins PN. 1992. Effects of dietary cholesterol on serum cholesterol: A meta- analysis and review. Am J Clin Nutr 55:1060–1070. Horton ES. 1986. Exercise and physical training: Effects on insulin sensitivity and glucose metabolism. Diabetes Metab Rev 2:1–17. Horton ES. 1991. Exercise and decreased risk of NIDDM. N Engl J Med 325: 196–197. Howard BV, Abbott WGH, Swinburn BA. 1991. Evaluation of metabolic effects of substitution of complex carbohydrates for saturated fat in individuals with obesity and NIDDM. Diabetes Care 14:786–795. Howe GR, Friedenreich CM, Jain M, Miller AB. 1991. A cohort study of fat intake and risk of breast cancer. J Natl Cancer Inst 83:336–340. Howe GR, Aronson KJ, Benito E, Castelleto R, Cornée J, Duffy S, Gallagher RP, Iscovich JM, Deng-ao J, Kaaks R, Kune GA, Kune S, Lee HP, Lee M, Miller AB, Peters RK, Potter JD, Riboli E, Slattery ML, Trichopoulos D, Tuyns A, Tzonou A, Watson LF, Whittemore AS, Wu-Willimas AH, Shu Z. 1997. The relation- ship between dietary fat intake and risk of colorectal cancer: Evidence from the combined analysis of 13 case-control studies. Cancer Causes Control 8:215– 228. Howell WH, McNamara DJ, Tosca MA, Smith BT, Gaines JA. 1997. Plasma lipid and lipoprotein responses to dietary fat and cholesterol: A meta-analysis. Am J Clin Nutr 65:1747–1764. Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Rosner BA, Hennekens CH, Willett WC. 1997. Dietary fat intake and the risk of coronary heart disease in women. N Engl J Med 337:1491–1499. Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Speizer FE, Hennekens CH, Willett WC. 1999a. Dietary protein and risk of ischemic heart disease in women. Am J Clin Nutr 70:221–227. Hu FB, Stampfer MJ, Rimm EB, Manson JE, Ascherio A, Colditz GA, Rosner BA, Spiegelman D, Speizer FE, Sacks FM, Hennekens CH, Willett WC. 1999b. A prospective study of egg consumption and risk of cardiovascular disease in men and women. J Am Med Assoc 281:1387–1394. Hulley SB, Rosenman RH, Bawol RD, Brand RJ. 1980. Epidemiology as a guide to clinical decisions. The association between triglyceride and coronary heart disease. N Engl J Med 302:1383–1389. Hunter DJ, Spiegelman D, Adami H-O, Beeson L, van den Brandt PA, Folsom AR, Fraser GE, Goldbohn A, Graham S, Howe GR, Kushi LH, Marshall JR, McDermott A, Miller AB, Speizer FE, Wolk A, Yaun S-S, Willett W. 1996. Co- hort studies of fat intake and the risk of breast cancer—A pooled analysis. N Engl J Med 334:356–361. Hurley BR, Roth SM. 2000. Strength training in the elderly. Effects on risk factors for age-related diseases. Sports Med 30:249–268.

74 DIETARY REFERENCE INTAKES Huttunen JK, Länsimies E, Voutilainen E, Ehnholm C, Hietanen E, Penttilä I, Siitonen O, Rauranaa R. 1979. Effect of moderate physical exercise on serum lipoproteins. A controlled clinical trial with special reference to serum high- density lipoproteins. Circulation 60:1220–1229. IARC (International Agency for Research on Cancer). 2002. IARC Handbooks of Cancer Prevention. Volume 6: Weight Control and Physical Activity. Lyon, France: IARC Press. Jacobs DR, Meyer KA, Kushi LH, Folsom AR. 1998. Whole-grain intake may reduce the risk of ischemic heart disease death in postmenopausal women: The Iowa Women’s Health Study. Am J Clin Nutr 68:248–257. Jacobs LR. 1986. Relationship between dietary fiber and cancer: Metabolic, physi- ologic, and cellular mechanisms. Proc Soc Exp Biol Med 183:299–310. James MJ, Gibson RA, Cleland LG. 2000. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr 71:343S–348S. Jenkins DJA, Wolever TMS, Leeds AR, Gassull MA, Haisman P, Dilawari J, Goff DV, Metz GL, Alberti KGMM. 1978. Dietary fibres, fibre analogues, and glucose tolerance: Importance of viscosity. Br Med J 1:1392–1394. Jenkins DJA, Wolever TMS, Buckley G, Lam KY, Giudici S, Kalmusky J, Jenkins AL, Patten RL, Bird J, Wong GS, Josse RG. 1988. Low-glycemic-index starchy food in the diabetic diet. Am J Clin Nutr 48:248–254. Jeppesen J, Schaaf P, Jones C, Zhou M-Y, Chen Y-DI, Reaven GM. 1997. Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women. Am J Clin Nutr 65:1027–1033. Johnson RK. 2000. What are people really eating and why does it matter? Nutr Today 35:40–45. Jones DY, Schatzkin A, Green SB, Block G, Brinton LA, Ziegler RG, Hoover R, Taylor PR. 1987. Dietary fat and breast cancer in the National Health and Nutrition Examination Survey I. Epidemiologic follow-up study. J Natl Cancer Inst 79:465–471. Jousilahti P, Vartiainen E, Pekkanen J, Tuomilehto J, Sundvall J, Puska P. 1998. Serum cholesterol distribution and coronary heart disease risk. Observations and predictions among middle-aged population in eastern Finland. Circulation 97:1087–1094. Kaizer L, Boyd NF, Kriukov V, Tritchler D. 1989. Fish consumption and breast cancer risk: An ecologic study. Nutr Cancer 12:61–68. Kang JX, Leaf A. 1996. Antiarrhythmic effects of polyunsaturated fatty acids: Recent studies. Circulation 94:1774–1780. Kannel WB, Sorlie P. 1979. Some health benefits of physical activity. The Framingham Study. Arch Intern Med 139:857–861. Kannel WB, Belanger A, D’Agostino R, Israel I. 1986. Physical activity and physical demand on the job and risk of cardiovascular disease and death: The Framingham Study. Am Heart J 112:820–825. Kasim SE, Stern B, Khilnani S, McLin P, Baciorowski S, Jen K-LC. 1988. Effects of omega-3 fish oils on lipid metabolism, glycemic control, and blood pressure in type II diabetic patients. J Clin Endocrinol Metab 67:1–5. Kasim SE, Martino S, Kim P-N, Khilnani S, Boomer A, Depper J, Reading BA, Heilbrun LK. 1993. Dietary and anthropometric determinants of plasma lipo- proteins during a long-term low-fat diet in healthy women. Am J Clin Nutr 57:146–153.

75 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY Kendall A, Levitsky DA, Strupp BJ, Lissner L. 1991. Weight loss on a low-fat diet: Consequence of the imprecision of the control of food intake in humans. Am J Clin Nutr 53:1124–1129. Keys A, Menotti A, Karvonen MJ, Aravanis C, Blackburn H, Buzina R, Djordjevic BS, Dontas AS, Fidanza F, Keys MH, Kromhout D, Nedeljkovic S, Punsar S, Seccareccia F, Toshima H. 1986. The diet and 15-year death rate in the seven countries study. Am J Epidemiol 124:903–915. Khan K, McKay HA, Haapasalo H, Bennell KL, Forwood MR, Kannus P, Wark JD. 2000. Does childhood and adolescence provide a unique opportunity for exer- cise to strengthen the skeleton? J Sci Med Sport 3:150–164. King H, Taylor R, Zimmet P, Pargeter K, Raper LR, Beriki T, Tekanene J. 1984. Non-insulin-dependent diabetes (NIDDM) in a newly independent Pacific nation: The Republic of Kiribati. Diabetes Care 7:409–415. Klurfeld DM. 1992. Dietary fiber-mediated mechanisms in carcinogenesis. Cancer Res 52:2055S–2059S. Koutsari C, Karpe F, Humphreys SM, Frayn KN, Hardman AE. 2001. Exercise pre- vents the accumulation of triglyceride-rich lipoproteins and their remnants seen when changing to a high-carbohydrate diet. Arterioscler Thromb Vasc Biol 21:1520–1525. Krauss RM, Dreon DM. 1995. Low-density-lipoprotein subclasses and response to a low-fat diet in healthy men. Am J Clin Nutr 62:478S–487S. Kromhout D, de Lezenne Coulander C. 1984. Diet, prevalence and 10-year mortal- ity from coronary heart disease in 871 middle-aged men. Am J Epidemiol 119:733–741. Kromhout D, Bosschieter EB, de Lezenne Coulander C. 1985. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 312:1205–1209. Kromhout D, Feskens EJM, Bowles CH. 1995. The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. Int J Epidemiol 24:340–345. Kushi LH, Lew RA, Stare FJ, Ellison CR, el Lozy M, Bourke G, Daly L, Graham I, Hickey N, Mulcahy R, Kevaney J. 1985. Diet and 20-year mortality from coro- nary heart disease. The Ireland-Boston Diet-Heart Study. N Engl J Med 312:811– 818. Kushi LH, Sellers TA, Potter JD, Nelson CL, Munger RG, Kaye SA, Folsom AR. 1992. Dietary fat and postmenopausal breast cancer. J Natl Cancer Inst 84:1092– 1099. Lai PBS, Ross JA, Fearson KCH, Anderson JD, Carter DC. 1996. Cell cycle arrest and induction of apoptosis in pancreatic cancer cells exposed to eicosapenta- enoic acid in vitro. Br J Cancer 74:1375–1383. Lanza E. 1990. National Cancer Institute Satellite Symposium on Fiber and Colon Cancer. In: Kritchevsky D, Bonfield C, Anderson JW, eds. Dietary Fiber: Chemis- try, Physiology, and Health Effects. New York: Plenum Press. Pp. 383–387. Layne JE, Nelson ME. 1999. The effects of progressive resistance training on bone density: A review. Med Sci Sports Exerc 21:25–30. Leclerc I, Davignon I, Lopez D, Garrel DR. 1993. No change in glucose tolerance and substrate oxidation after a high-carbohydrate, low-fat diet. Metabolism 42:365–370. Lewis CJ, Park YK, Dexter PB, Yetley EA. 1992. Nutrient intakes and body weights of persons consuming high and moderate levels of added sugars. J Am Diet Assoc 92:708–713.

76 DIETARY REFERENCE INTAKES Liljeberg HGM, Åkerberg AKE, Björck IME. 1999. Effect of the glycemic index and content of indigestible carbohydrates of cereal-based breakfast meals on glu- cose tolerance at lunch in healthy subjects. Am J Clin Nutr 69:647–655. Lindsted KD, Tonstad S, Kuzma JW. 1991. Self-report of physical activity and pat- terns of mortality in Seventh-day Adventist men. J Clin Epidemiol 44:355–364. Lissner L, Heitmann BL. 1995. Dietary fat and obesity: Evidence from epidemiol- ogy. Eur J Clin Nutr 49:79–90. Lissner L, Levitsky DA, Strupp BJ, Kalkwarf HJ, Roe DA. 1987. Dietary fat and the regulation of energy intake in human subjects. Am J Clin Nutr 46:886–892. Lissner L, Helgesson Ö, Bengtsson C, Lapidus L, Hultén B, Branehög I, Holmberg E. 1992. Energy and macronutrient intake in relation to cancer incidence among Swedish women. Eur J Clin Nutr 46:501–507. Lissner L, Heitmann BL, Bengtsson C. 2000. Population studies of diet and obesity. Br J Nutr 83:S21–S24. Little J, Logan RFA, Hawtin PG, Hardcastle JD, Turner ID. 1993. Colorectal adenomas and diet: A case-control study of subjects participating in the Nottingham Faecal Occult Blood Screening Programme. Br J Cancer 67:177– 84. Lundgren H, Bengtsson C, Blohmé G, Isaksson B, Lapidus L, Lenner RA, Saaek A, Winther E. 1989. Dietary habits and incidence of noninsulin-dependent dia- betes mellitus in a population study of women in Gothenburg, Sweden. Am J Clin Nutr 49:708–712. Lyon JL, Mahoney AW, West DW, Gardner JW, Smith KR, Sorenson AW, Stanish W. 1987. Energy intake: Its relationship to colon cancer risk. J Natl Cancer Inst 78:853–861. Macquart-Moulin G, Riboli E, Cornée J, Charnay B, Berthezène P, Day N. 1986. Case-control study on colorectal cancer and diet in Marseilles. Int J Cancer 38:183–191. Macquart-Moulin G, Riboli E, Cornée J, Kaaks R, Berthezène P. 1987. Colorectal polyps and diet: A case-control study in Marseilles. Int J Cancer 40:179–188. Madsen KL, Adams WC, Van Loan MD. 1998. Effects of physical activity, body weight and composition, and muscular strength on bone density in young women. Med Sci Sports Exerc 30:114–120. Mann JI, Watermeyer GS, Manning EB, Randles J, Truswell AS. 1973. Effects on serum lipids of different dietary fats associated with a high sucrose diet. Clin Sci 44:601–604. Mann JI, Appleby PN, Key TJ, Thorogood M. 1997. Dietary determinants of ischaemic heart disease in health conscious individuals. Heart 78:450–455. Manson JE, Rimm EB, Stampfer MJ, Colditz GA, Willett WC, Krolewski AS, Rosner B, Hennekens CH, Speizer FE. 1991. Physical activity and incidence of non- insulin-dependent diabetes mellitus in women. Lancet 338:774–778. Manson JE, Nathan DM, Krolewski AS, Stampfer MJ, Willett WC, Hennekens CH. 1992. A prospective study of exercise and incidence of diabetes among US male physicians. J Am Med Assoc 268:63–67. Marckmann P, Raben A, Astrup A. 2000. Ad libitum intake of low-fat diets rich in either starchy foods or sucrose: Effects on blood lipids, factor VII coagulant activity, and fibrinogen. Metabolism 49:731–735. Marniemi J, Seppänen A, Hakala P. 1990. Long-term effects on lipid metabolism of weight reduction on lactovegetarian and mixed diet. Int J Obes 14:113–125.

77 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY Marshall JA, Hamman RF, Baxter J. 1991. High-fat, low-carbohydrate diet and the etiology of non-insulin-dependent diabetes mellitus: The San Luis Valley Dia- betes Study. Am J Epidemiol 134:590–603. Masironi R. 1970. Dietary factors and coronary heart disease. Bull World Health Organ 42:103–114. Mayer-Davis EJ, Monaco JH, Hoen HM, Carmichael S, Vitolins MZ, Rewers MJ, Haffner SM, Ayad MF, Bergman RN, Karter AJ. 1997. Dietary fat and insulin sensitivity in a triethnic population: The role of obesity. The Insulin Resis- tance Arteriosclerosis Study (IRAS). Am J Clin Nutr 65:79–87. Mayer-Davis EJ, D’Agostino R, Karter AJ, Haffner SM, Rewers MJ, Saad M, Bergman RN. 1998. Intensity and amount of physical activity in relation to insulin sensi- tivity. The Insulin Resistance Atherosclerosis Study. J Am Med Assoc 279:669– 674. Mazzeo RS, Rajkumar C, Rolland J, Blaher B, Jennings G, Esler M. 1998. Immune response to a single bout of exercise in young and elderly subjects. Mech Age- ing Dev 100:121–132. McLennan PL. 1993. Relative effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on cardiac arrhythmias in rats. Am J Clin Nutr 57:207–212. Meinertz H, Nilausen K, Faergeman O. 1989. Soy protein and casein in cholesterol- enriched diets: Effects on plasma lipoproteins in normolipidemic subjects. Am J Clin Nutr 50:786–793. Mensink RP, Katan MB. 1992. Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb 12:911–919. Mensink RP, Temme EH, Hornstra G. 1994. Dietary saturated and trans fatty acids and lipoprotein metabolism. Ann Med 26:461–464. Meyer KA, Kushi LH, Jacobs DR, Slavin J, Sellers TA, Folsom AR. 2000. Carbohy- drates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr 71:921–930. Michaud DS, Giovannucci E, Willett WC, Colditz GA, Stampfer MJ, Fuchs CS. 2001. Physical activity, obesity, height, and the risk of pancreatic cancer. J Am Med Assoc 286:921–929. Miller AB, Kelly A, Choi NW, Matthews V, Morgan RW, Munan L, Burch JD, Feather J, Howe GR, Jain M. 1978. A study of diet and breast cancer. Am J Epidemiol 107:499–509. Miller WC, Lindeman AK, Wallace J, Niederpruem M. 1990. Diet composition, energy intake, and exercise in relation to body fat in men and women. Am J Clin Nutr 52:426–430. Morris MC, Sacks F, Rosner B. 1993. Does fish oil lower blood pressure? A meta- analysis of controlled trials. Circulation 88:523–533. Must A, Lipman RD. 1999. Childhood energy intake and cancer mortality in adult- hood. Nutr Rev 57:21–24. Neaton JD, Wentworth D. 1992. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Arch Intern Med 152:56–64. Neugut AI, Garbowski GC, Lee WC, Murray T, Nieves JW, Forde KA, Treat MR, Waye JD, Fenoglio-Preiser C. 1993. Dietary risk factors for the incidence and recurrence of colorectal adenomatous polyps. A case-control study. Ann Intern Med 118:91–95.

78 DIETARY REFERENCE INTAKES NHLBI/NIDDK (National Heart, Lung, and Blood Institute/National Institute of Diabetes and Digestive and Kidney Diseases). 1998. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. The Evidence Report. NIH Publication No. 98-4083. Bethesda, MD: National Insti- tutes of Health. Nikkilä EA, Taskinen M-R, Rehunen S, Härkönen M. 1978. Lipoprotein lipase activity in adipose tissue and skeletal muscle of runners: Relation to serum lipoproteins. Metabolism 27:1661–1671. Obarzanek E, Velletri PA, Cutler JA. 1996. Dietary protein and blood pressure. J Am Med Assoc 275:1598–1603. Paffenbarger RS, Hyde RT, Jung DL, Wing AL. 1984. Epidemiology of exercise and coronary heart disease. Clin Sports Med 3:297–318. Parker DR, Weiss ST, Troisi R, Cassano PA, Vokonas PS, Landsberg L. 1993. Rela- tionship of dietary saturated fatty acids and body habitus to serum insulin concentrations: The Normative Aging Study. Am J Clin Nutr 58:129–136. Parks EJ, Hellerstein MK. 2000. Carbohydrate-induced hypertriacylglycerolemia: Historical perspective and review of biological mechanisms. Am J Clin Nutr 71:412–433. Parmley WW. 1997. Nonlipoprotein risk factors for coronary heart disease: Evalua- tion and management. Am J Med 102:7–14. Pietinen P, Rimm EB, Korhonen P, Hartman AM, Willett WC, Albanes D, Virtamo J. 1996. Intake of dietary fiber and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Circulation 94:2720–2727. Pietinen P, Ascherio A, Korhonen P, Hartman AM, Willett WC, Albanes D, Virtamo J. 1997. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol 145:876–887. Pi-Sunyer FX, Woo R. 1985. Effect of exercise on food intake in human subjects. Am J Clin Nutr 42:983–990. Platz EA, Giovannucci E, Rimm EB, Rickett HRH, Stampfer MJ, Colditz GA, Willett WC. 1997. Dietary fiber and distal colorectal adenoma in men. Cancer Epidemiol Biomarkers Prev 6:661–670. Purnell JQ, Kahn SE, Albers JJ, Nevin DN, Brunzell JD, Schwartz RS. 2000. Effect of weight loss with reduction of intra-abdominal fat on lipid metabolism in older men. J Clin Endocrinol Metab 85:977–982. Ramon JM, Bou R, Romea S, Alkiza ME, Jacas M, Ribes J, Oromi J. 2000. Dietary fat intake and prostate cancer risk: A case-control study in Spain. Cancer Causes Control 11:679–685. Rath R, Massek J, Kujalová V, Slabochová Z. 1974. Effect of a high sugar intake on some metabolic and regulatory indicators in young men. Nahrung 18:343–353. Reiser S, Hallfrisch J. 1987. Lipogenesis and blood lipids. In: Metabolic Effects of Dietary Fructose. Boca Raton, FL: CRC Press. Pp. 83–111. Reiser S, Hallfrisch J, Michaelis OE, Lazar FL, Martin RE, Prather ES. 1979. Isocaloric exchange of dietary starch and sucrose in humans. I. Effects on levels of fast- ing blood lipids. Am J Clin Nutr 32:1659–1669. Richter EA, Ruderman NB, Schneider SH. 1981. Diabetes and exercise. Am J Med 70:201–209. Rigaud D, Ryttig KR, Angel LA, Apfelbaum M. 1990. Overweight treated with energy restriction and a dietary fibre supplement: A 6-month randomized, double-blind, placebo-controlled trial. Int J Obes 14:763–769.

79 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY Risch HA, Jain M, Marrett LD, Howe GR. 1994. Dietary fat intake and risk of epithelial ovarian cancer. J Natl Cancer Inst 86:1409–1415. Rivellese A, Riccardi G, Giacco A, Pacioni D, Genovese S, Mattioli PL, Mancini M. 1980. Effect of dietary fibre on glucose control and serum lipoproteins in diabetic patients. Lancet 2:447–450. Roberfroid M. 1993. Dietary fiber, inulin, and oligofructose: A review comparing their physiological effects. Crit Rev Food Sci Nutr 33:103–148. Roche HM, Zampelas A, Jackson KG, Williams CM, Gibney MJ. 1998. The effect of test meal monounsaturated fatty acid:saturated fatty acid ratio on postprandial lipid metabolism. Br J Nutr 79:419–424. Rohan TE, Howe GR, Friedenreich CM, Jain M, Miller AB. 1993. Dietary fiber, vitamins A, C, and E, and risk of breast cancer: A cohort study. Cancer Causes Control 4:29–37. Rose DP. 1997. Dietary fatty acids and cancer. Am J Clin Nutr 66:998S–1003S. Rose DP, Connolly JM. 2000. Regulation of tumor angiogenesis by dietary fatty acids and eicosanoids. Nutr Cancer 37:119–127. Rose DP, Boyar AP, Wynder EL. 1986. International comparisons of mortality rates for cancer of the breast, ovary, prostate, and colon, and per capita food con- sumption. Cancer 58:2363–2371. Rose DP, Goldman M, Connolly JM, Strong LE. 1991. High-fiber diet reduces serum estrogen concentrations in premenopausal women. Am J Clin Nutr 54:520–525. Rössner S, von Zweigbergk D, Öhlin A, Ryttig K. 1987. Weight reduction with dietary fibre supplements. Results of two double-blind randomized studies. Acta Med Scand 222:83–88. Ryttig KR, Tellnes G, Haegh L, Boe E, Fagerthun H. 1989. A dietary fibre supple- ment and weight maintenance after weight reduction: A randomized, double- blind, placebo-controlled long-term trial. Int J Obes 13:165–171. Salmerón J, Ascherio A, Rimm EB, Colditz GA, Spiegelman D, Jenkins DJ, Stampfer MJ, Wing AL, Willett WC. 1997a. Dietary fiber, glycemic load, and risk of NIDDM in men. Diabetes Care 20:545–550. Salmerón J, Manson JE, Stampfer MJ, Colditz GA, Wing AL, Willett WC. 1997b. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. J Am Med Assoc 277:472–477. Saltzman E, Dallal GE, Roberts SB. 1997. Effect of high-fat and low-fat diets on voluntary energy intake and substrate oxidation: Studies in identical twins consuming diets matched for energy density, fiber, and palatability. Am J Clin Nutr 66:1332–1339. Sasaki S, Horacsek M, Kesteloot H. 1993. An ecological study of the relationship between dietary fat intake and breast cancer mortality. Prev Med 22:187–202. Schatzkin A, Lanza E, Corle D, Lance P, Iber F, Caan B, Shike M, Weissfeld J, Burt R, Cooper MR, Kikendall JW, Cahill J. 2000. Lack of effect of a low-fat, high- fiber diet on the recurrence of colorectal adenomas. N Engl J Med 342:1149– 1155. Schneider SH, Amorosa LF, Khachadurian AK, Ruderman NB. 1984. Studies on the mechanism of improved glucose control during regular exercise in type 2 (non-insulin-dependent) diabetes. Diabetologia 26:355–360. Schuurman AG, van den Brandt PA, Dorant E, Brants HAM, Goldbohm RA. 1999. Association of energy and fat intake with prostate carcinoma risk. Results from the Netherlands Cohort Study. Cancer 86:1019–1027. Shephard RJ. 1990. Physical activity and cancer. Int J Sports Med 11:413–420.

80 DIETARY REFERENCE INTAKES Shephard RJ. 1996. Exercise and cancer: Linkages with obesity? Crit Rev Food Sci Nutr 36:321–339. Sonnenberg LM, Quatromoni PA, Gagnon DR, Cupples LA, Franz MM, Ordovas JM, Wilson PWF, Schaefer EJ, Millen BE. 1996. Diet and plasma lipids in women. II. Macronutrients and plasma triglycerides, high-density lipoprotein, and the ratio of total to high-density lipoprotein cholesterol in women: The Framingham Nutrition Studies. J Clin Epidemiol 49:665–672. Sorkin JD, Andres R, Muller DC, Baldwin HL, Fleg JL. 1992. Cholesterol as a risk factor for coronary heart disease in elderly men. The Baltimore Longitudinal Study of Aging. Ann Epidemiol 2:59–67. Stacpoole PW, Alig J, Ammon L, Crockett SE. 1989. Dose–response effects of dietary marine oil on carbohydrate and lipid metabolism in normal subjects and patients with hypertriglyceridemia. Metabolism 38:946–956. Stamler J. 1979. Population studies. In: Levy R, Rifkind B, Dennis B, Ernst N, eds. Nutrition, Lipids, and Coronary Heart Disease. New York: Raven Press. Pp. 25–88. Stamler J, Wentworth D, Neaton JD. 1986. Is relationship between serum choles- terol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). J Am Med Assoc 256:2823–2828. Stampfer MJ, Krauss RM, Ma J, Blanche PJ, Holl LG, Sacks FM, Hennekens CH. 1996. A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. J Am Med Assoc 276:882–888. Stemmermann GN, Nomura AM, Heilbrun LK. 1985. Cancer risk in relation to fat and energy intake among Hawaii Japanese: A prospective study. Princess Takamatsu Symp 16:265–274. Straznicky NE, O’Callaghan CJ, Barrington VE, Louis WJ. 1999. Hypotensive effect of low-fat, high-carbohydrate diet can be independent of changes in plasma insulin concentrations. Hypertension 34:580–585. Stubbs RJ, Ritz P, Coward WA, Prentice AM. 1995. Covert manipulation of the ratio of dietary fat to carbohydrate and energy density: Effect on food intake and energy balance in free-living men eating ad libitum. Am J Clin Nutr 62:330– 337. Stubbs RJ, Harbron CG, Prentice AM. 1996. Covert manipulation of the dietary fat to carbohydrate ratio of isoenergetically dense diets: Effect on food intake in feeding men ad libitum. Int J Obes Relat Metab Disord 20:651–660. Swinburn BA, Boyce VL, Bergman RN, Howard BV, Bogardus C. 1991. Deteriora- tion in carbohydrate metabolism and lipoprotein changes induced by modern, high fat diet in Pima Indians and Caucasians. J Clin Endocrinol Metab 73:156–165. Takahashi M, Przetakiewicz M, Ong A, Borek C, Lowenstein JM. 1992. Effect of omega 3 and omega 6 fatty acids on transformation of cultured cells by irra- diation and transfection. Cancer Res 52:154–162. Tannenbaum A. 1942. The genesis and growth of tumors. II. Effects of caloric restriction per se. Cancer Res 2:460–467. Tannenbaum A, Silverstone H. 1957. Nutrition and the genesis of tumours. In: Raven RW, ed. Cancer, Vol. 1. London: Butterworth. Pp. 306–334. Taylor RJ, Bennett PH, LeGonidec G, Lacoste J, Combe D, Joffres M, Uili R, Charpin M, Zimmet PZ. 1983. The prevalence of diabetes mellitus in a traditional-living Polynesian population: The Wallis Island Survey. Diabetes Care 6:334–340.

81 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY Thomsen C, Rasmussen O, Christiansen C, Pedersen E, Vesterlund M, Storm H, Ingerslev J, Hermansen K. 1999. Comparison of the effects of a mono- unsaturated fat diet and a high carbohydrate diet on cardiovascular risk factors in first degree relatives to type-2 diabetic subjects. Eur J Clin Nutr 52:818–823. Trichopoulou A, Katsouyanni K, Stuver S, Tzala L, Gnardellis C, Rimm E, Trichopoulos D. 1995. Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece. J Natl Cancer Inst 87:110–116. Trock B, Lanza E, Greenwald P. 1990. Dietary fiber, vegetables, and colon cancer: Critical review and meta-analyses of the epidemiologic evidence. J Natl Cancer Inst 82:650–661. Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. 2001. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350. Tuyns AJ, Kaaks R, Haelterman M. 1988. Colorectal cancer and the consumption of foods: A case-control study in Belgium. Nutr Cancer 11:189–204. Tzonou A, Hsieh C-C, Polychronopoulou A, Kaprinis G, Toupadaki N, Trichopoulou A, Karakatsani A, Trichopoulos D. 1993. Diet and ovarian cancer: A case-control study in Greece. Int J Cancer 55:411–414. Vainio H, Bianchini F. 2001. Physical activity and cancer prevention—Is ‘no pain, no gain’ passé? Eur J Cancer Prev 10:301–302. van den Brandt PA, van’t Veer P, Goldbohm RA, Dorant E, Volovics A, Hermus RJJ, Sturmans F. 1993. A prospective cohort study on dietary fat and the risk of postmenopausal breast cancer. Cancer Res 53:75–82. Van Munster IP, Nagengast FM. 1993. The role of carbohydrate fermentation in colon cancer prevention. Scand J Gastroenterol 200:80–86. van Raaij JMA, Katan MB, West CE, Hautvast JGAJ. 1982. Influence of diets con- taining casein, soy isolate, and soy concentrate on serum cholesterol and lipo- proteins in middle-aged volunteers. Am J Clin Nutr 35:925–934. van Stratum P, Lussenburg RN, van Wezel LA, Vergroesen AJ, Cremer HD. 1978. The effect of dietary carbohydrate:fat ratio on energy intake by adult women. Am J Clin Nutr 31:206–212. van’t Veer P, Kok FJ, Brants HAM, Ockhuizen T, Sturmans F, Hermus RJJ. 1990. Dietary fat and the risk of breast cancer. Int J Epidemiol 19:12–18. Veierød MB, Laake P, Thelle DS. 1997a. Dietary fat intake and risk of lung cancer: A prospective study of 51,452 Norwegian men and women. Eur J Cancer Prev 6:540–549. Veierød MB, Laake P, Thelle DS. 1997b. Dietary fat intake and risk of prostate cancer: A prospective study of 25,708 Norwegian men. Int J Cancer 73:634–638. Velie E, Kulldorff M, Schairer C, Block G, Albanes D, Schatzkin A. 2000. Dietary fat, fat subtypes, and breast cancer in postmenopausal women: A prospective cohort study. J Natl Cancer Inst 92:833–839. Vessby B. 2000. Dietary fat and insulin action in humans. Br J Nutr 83:S91–S96. Vessby B, Uusitupa M, Hermansen K, Riccardi G, Rivellese AA, Tapsell LC, Nälsén C, Berglund L, Louheranta A, Rasmussen BM, Calvert GD, Maffetone A, Pedersen E, Gustafsson I-B, Storlien LH. 2001. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study. Diabetologia 44:312–319. Visek WJ. 1978. Diet and cell growth modulation by ammonia. Am J Clin Nutr 31:S216–S220.

82 DIETARY REFERENCE INTAKES von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. 1999. The effect of dietary ω-3 fatty acids on coronary atherosclerosis. A randomized, double- blind, placebo-controlled trial. Ann Intern Med 130:554–562. Walker ARP, Cleaton-Jones PE. 1992. Sugar intake and dental caries. Br Dent J 172:7. Wang G-S, Olsson JM, Eriksson LC, Stål P. 2000. Diet restriction increases ubiquinone contents and inhibits progression of hepatocellular carcinoma in the rat. Scand J Gastroenterol 35:83–89. West CE, Sullivan DR, Katan MB, Halferkamps IL, van der Torre HW. 1990. Boys from populations with high-carbohydrate intake have higher fasting tri- glyceride levels than boys from populations with high-fat intake. Am J Epidemiol 131:271–282. West DB, York B. 1998. Dietary fat, genetic predisposition, and obesity: Lessons from animal models. Am J Clin Nutr 67:505S–512S. White E, Jacobs EJ, Daling JR. 1996. Physical activity in relation to colon cancer in middle-aged men and women. Am J Epidemiol 144:42–50. Willett WC. 1997. Specific fatty acids and risks of breast and prostate cancer: Dietary intake. Am J Clin Nutr 66:1557S–1563S. Willett WC. 1998. Is dietary fat a major determinant of body fat? Am J Clin Nutr 67:556S–562S. Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Hennekens CH, Speizer FE. 1987. Dietary fat and the risk of breast cancer. N Engl J Med 316:22–28. Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Speizer FE. 1990. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N Engl J Med 323:1664–1672. Willett WC, Hunter DJ, Stampfer MJ, Colditz G, Manson JE, Spiegelman D, Rosner B, Hennekens CH, Speizer FE. 1992. Dietary fat and fiber in relation to risk of breast cancer. An 8-year follow-up. J Am Med Assoc 268:2037–2044. Willett WC, Stampfer MJ, Mason JE, Colditz GA, Speizer FE, Rosner BA, Sampson LA, Hennekens CH. 1993. Intake of trans fatty acids and risk of coronary heart disease among women. Lancet 341:581–585. Williams PT. 1997. Relationship of distance run per week to coronary heart disease risk factors in 8283 male runners. The National Runners’ Health Study. Arch Intern Med 157:191–198. Williams PT, Wood PD, Krauss RM, Haskell WL, Vranizan KM, Blair SN, Terry R, Farquhar JW. 1983. Does weight loss cause the exercise-induced increase in plasma high density lipoproteins? Atherosclerosis 47:173–185. Williams PT, Krauss RM, Wood PD, Lindgren FT, Giotas C, Vranizan KM. 1986. Lipoprotein subfractions of runners and sedentary men. Metabolism 35:45–52. Williams PT, Krauss RM, Vranizan KM, Wood PDS. 1990. Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moder- ately overweight men. Circulation 81:1293–1304. Williams PT, Krauss RM, Vranizan KM, Albers JJ, Wood PDS. 1992. Effects of weight- loss by exercise and by diet on apolipoproteins A-I and A-II and the particle- size distribution of high-density lipoproteins in men. Metabolism 41:441–449. Williams PT, Stefanick ML, Vranizan KM, Wood PD. 1994. The effects of weight loss by exercise or by dieting on plasma high-density lipoprotein (HDL) levels in men with low, intermediate, and normal-to-high HDL at baseline. Metabo- lism 43:917–924. Williamson DF, Madans J, Anda RF, Kleinman JC, Kahn HS, Byers T. 1993. Recre- ational physical activity and ten-year weight change in a US national cohort. Int J Obes Relat Metab Disord 17:279–286.

83 R ELATIONSHIP OF MACRONUTRIENTS AND PHYSICAL ACTIVITY Wolever TMS, Jenkins DJA. 1993. Effect of dietary fiber and foods on carbohydrate metabolism. In: Spiller G, ed. CRC Handbook of Dietary Fiber in Human Nutrition. Boca Raton, FL: CRC Press. Pp. 111–162. Wolever TMS, Jenkins DJA, Ocana AM, Rao VA, Collier GR. 1988. Second-meal effect: Low-glycemic-index foods eaten at dinner improve subsequent break- fast glycemic response. Am J Clin Nutr 48:1041–1047. Wolfe BMJ, Piché LA. 1999. Replacement of carbohydrate by protein in a conven- tional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects. Clin Invest Med 22:140–148. Wood PD, Stefanick ML, Dreon DM, Frey-Hewitt B, Garay SC, Williams PT, Superko HR, Fortmann SP, Albers JJ, Vranizan KM, Ellsworth NM, Terry RB, Haskell WL. 1988. Changes in plasma lipids and lipoproteins in overweight men dur- ing weight loss through dieting as compared with exercise. N Engl J Med 319:1173–1179. Wood PJ, Braaten JT, Scott FW, Riedel KD, Wolynetz MS, Collins MW. 1994. Effect of dose and modification of viscous properties of oat gum on plasma glucose and insulin following an oral glucose load. Br J Nutr 72:731–743. Wu Y, Zheng W, Sellars TA, Kushi LH, Bostick RM, Potter JD. 1994. Dietary choles- terol, fat, and lung cancer incidence among older women: The Iowa Women’s Health Study (United States). Cancer Causes Control 5:395–400. Yost TJ, Jensen DR, Haugen BR, Eckel RH. 1998. Effect of dietary macronutrient composition on tissue-specific lipoprotein lipase activity and insulin action in normal-weight subjects. Am J Clin Nutr 68:296–302. Yu S, Derr J, Etherton TD, Kris-Etherton PM. 1995. Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic. Am J Clin Nutr 61:1129–1139. Yudkin J, Eisa O, Kang SS, Meraji S, Bruckdorfer KR. 1986. Dietary sucrose affects plasma HDL cholesterol concentration in young men. Ann Nutr Metab 30: 261–266. Yu-Poth S, Zhao G, Etherton T, Naglak M, Jonnalagadda S, Kris-Etherton PM. 1999. Effects of the National Cholesterol Education Program’s Step I and Step II dietary intervention programs on cardiovascular disease risk factors: A meta- analysis. Am J Clin Nutr 69:632–646. Zambon S, Friday KE, Childs MT, Fujimoto WY, Bierman EL, Ensinck JW. 1992. Effect of glyburide and ω3 fatty acid dietary supplements on glucose and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Am J Clin Nutr 56:447–454. Zhu Z, Jiang W, Thompson HJ. 1999. Effect of energy restriction on tissue size regulation during chemically induced mammary carcinogenesis. Carcinogenesis 20:1721–1726.

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Responding to the expansion of scientific knowledge about the roles of nutrients in human health, the Institute of Medicine has developed a new approach to establish Recommended Dietary Allowances (RDAs) and other nutrient reference values. The new title for these values Dietary Reference Intakes (DRIs), is the inclusive name being given to this new approach. These are quantitative estimates of nutrient intakes applicable to healthy individuals in the United States and Canada. This new book is part of a series of books presenting dietary reference values for the intakes of nutrients. It establishes recommendations for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. This book presents new approaches and findings which include the following:

  • The establishment of Estimated Energy Requirements at four levels of energy expenditure
  • Recommendations for levels of physical activity to decrease risk of chronic disease
  • The establishment of RDAs for dietary carbohydrate and protein
  • The development of the definitions of Dietary Fiber, Functional Fiber, and Total Fiber
  • The establishment of Adequate Intakes (AI) for Total Fiber
  • The establishment of AIs for linolenic and a-linolenic acids
  • Acceptable Macronutrient Distribution Ranges as a percent of energy intake for fat, carbohydrate, linolenic and a-linolenic acids, and protein
  • Research recommendations for information needed to advance understanding of macronutrient requirements and the adverse effects associated with intake of higher amounts

Also detailed are recommendations for both physical activity and energy expenditure to maintain health and decrease the risk of disease.

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