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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).
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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.,
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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;
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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
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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
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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
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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-
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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-
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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-
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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-
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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
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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.
OCR for page 74
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.
OCR for page 75
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.
OCR for page 76
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.
OCR for page 77
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.
OCR for page 78
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.
OCR for page 79
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.
OCR for page 80
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.
OCR for page 81
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.
OCR for page 82
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.
OCR for page 83
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.
Representative terms from entire chapter:
physical activity
