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European Journal of Clinical Nutrition (2007) 61 (Suppl 1), S100–S111
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Dietary carbohydrate: relationship to cardiovascular
disease and disorders of carbohydrate metabolism
J Mann
Department of Human Nutrition, Edgar National Centre for Diabetes Research, University of Otago, Dunedin, New Zealand
The nature of carbohydrate is of considerable importance when recommending diets intended to reduce the risk of type II
diabetes and cardiovascular disease and in the treatment of patients who already have established diseases. Intact fruits,
vegetables, legumes and wholegrains are the most appropriate sources of carbohydrate. Most are rich in nonstarch
polysaccharides (NSPs) (dietary fibre) and other potentially cardioprotective components. Many of these foods, especially those
that are high in dietary fibre, will reduce total and low-density lipoprotein cholesterol and help to improve glycaemic control in
those with diabetes. There is no good long-term evidence of benefit when NSPs or other components of wholegrains, fruits,
vegetables and legumes are added to functional and manufactured foods. Frequent consumption of low glycaemic index foods
has been reported to confer similar benefits, but it is not clear whether such benefits are independent of the dietary fibre content
of these foods or the fact that low glycaemic index foods tend to have intact plant cell walls. Furthermore, it is uncertain whether
functional and manufactured foods with a low glycaemic index confer the same long-term benefits as low glycaemic index
plant-based foods. A wide range of carbohydrate intake is acceptable, provided the nature of carbohydrate is appropriate.
Failure to emphasize the need for carbohydrate to be derived principally from wholegrain cereals, fruits, vegetables and legumes
may result in increased lipoprotein-mediated risk of cardiovascular disease, especially in overweight and obese individuals who
are insulin resistant.
European Journal of Clinical Nutrition (2007) 61 (Suppl 1), S100–S111; doi:10.1038/sj.ejcn.1602940
Keywords: cardiovascular disease; impaired carbohydrate metabolism
Dietary carbohydrate and cardiovascular disease
Traditional dietary patterns, which are high in carbohydrate,
are associated with low rates of coronary heart disease
(CHD). This appears to be the case regardless of the
carbohydrate containing primary staple, for example rice in
most Asian countries and a range of cereals, root crops and
pulses in different parts of Africa. However, cross-cultural
comparisons provide no indication as to whether the
percentage of energy intake derived from total carbohydrate
intake, total quantity of carbohydrate, particular classes of
carbohydrate and other nutrients, which are found in
carbohydrate-containing foods or method of food preparation, account for the cardioprotection afforded by such
traditional carbohydrate-containing diets. Furthermore, it is
possible that cardiovascular risk is reduced simply because
Correspondence: Professor J Mann, Department of Human Nutrition, Edgar
National Centre for Diabetes Research, University of Otago, Dunedin, New
Zealand.
E-mail: [email protected]
traditional high carbohydrate diets are low in fat, especially
saturated fat, or because they promote satiety and thus
protect against overweight and obesity. Indeed, it is
conceivable that high carbohydrate diets simply act as a
marker for some other protective factor. Prospective epidemiological studies and a range of experimental approaches
examining the effects of carbohydrates on cardiovascular risk
factors have attempted to clarify the role of total carbohydrate and carbohydrate classes (sugars, oligosaccharides
and polysaccharides) and subgroups (for example starch,
nonstarch polysaccharide (NSP)) in CHD and stroke.
Prospective epidemiological studies
Several limitations are common to all prospective studies
examining the relationship between foods and nutrients and
disease risk. However, there are issues that are of particular
relevance when considering the role of carbohydrates. The
lack of consistency in the methods used for the measurement of different classes and subgroups of carbohydrate,
Cardiovascular disease and diabetes
J Mann
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especially the NSP, complicates comparisons between the
results of studies and their extrapolation into nutritional
recommendations. The term ‘dietary fibre’ is often incorrectly regarded as being synonymous with NSP. However, in
this paper, the terms will be used as they occur in the
relevant literature, dietary fibre having been measured and
reported in most of the epidemiological studies and much of
the experimental research. In some countries, total carbohydrate is measured ‘by difference’, after water fat, protein
and ash have all been measured. This is a less reliable
measure than that derived from adding the various classes of
carbohydrate measured individually (see accompanying
papers on ‘definition’ and ‘measurement’).
Of equal, or arguably greater, importance is the extent to
which sources of dietary carbohydrate have changed over
time or differ throughout the world. In some developing
countries, a high proportion of total sugars may be derived
from intact fruits and vegetables. The same may have been
true in the past for societies that are now relatively affluent.
However, nowadays, in most countries, sucrose, high
fructose corn syrup and other free sugars contribute a
substantial proportion of total sugars. Foods rich in free
sugars are usually energy dense and are often poor sources of
essential micronutrients (Baghurst et al., 1991), and are thus
likely to be associated with different physiological effects
and clinical consequences when compared with fruits and
vegetables. Thus, knowledge of total sugar content provides
little information relating to physiology. Similarly, until
relatively recently, dietary fibre was likely to be derived
principally from minimally processed cereals, vegetables,
fruits, legumes and ‘wholegrain’ cereal foods likely to
contain at least a reasonable proportion of intact or lightly
processed grains. Now, dietary fibre is often an added
ingredient and the definition of ‘wholegrain’ permits foods
to be described as such if they contain the constituents of the
grain without requiring the structure to be intact. Again,
the physiological effects of dietary fibre, when derived from
intact fruits, vegetables and grains, may differ from that
added to manufactured products. Thus, it may not be
appropriate to extrapolate the findings of epidemiological
studies involving the consumption of conventional foods to
carbohydrate-containing manufactured and functional
foods, which provide a substantial proportion of total energy
in most affluent and many developing counties.
Early prospective studies reporting the cardioprotective
effect of total carbohydrate intakes and intake of dietary fibre
were published in the 1970s and early 1980s (Morris et al.,
1977; Garcia-Palmieri et al., 1980; McGee et al., 1984). They
were relatively underpowered and confounding of results by
a range of factors certainly could not be excluded. During the
past 20 years, results have been published from a substantial
number of prospective studies involving cohorts of sufficient
size to enable examination of potentially confounding
factors. There has been particular emphasis on the cardioprotective role of cereal grains and dietary fibre. Most studies
define wholegrain as either intact or milled grain with bran,
germ and endosperm in the same proportion as the unmilled
grain. Wholegrain foods have generally been arbitrarily
defined as those foods with more than 25% wholegrain or
bran content by weight (Flight and Clifton, 2006). The
studies have been systematically reviewed (for example Liu,
2002; Truswell, 2002; Hu, 2003; Slavin, 2003; Flight and
Clifton, 2006) and meta-analysed (Anderson, 2002, 2003).
Despite the use of different instruments for assessing dietary
intake, the results of the studies show a remarkably
consistent trend. Meta-analysis, involving four of the largest
published studies, suggested a 28% reduction in risk of CHD
when comparing individuals in the highest and lowest
quintiles of intake of wholegrains (relative risk 0.72, 95%
confidence intervals: 0.48, 0.94) (Anderson 2003). The size of
the most recent cohort studies has enabled analyses to
examine the extent to which these findings might be
confounded by other cardioprotective factors. While residual
confounding cannot be excluded with absolute certainty,
such analyses provide reasonable evidence that wholegrains
protect against CHD regardless of the degree of adiposity and
other measured variables associated with healthy lifestyles
and eating habits. However, it is acknowledged that people
who consistently eat wholegrain breads do indeed have
different lifestyles from those who do not, and it may not be
possible in epidemiological studies to measure all attributes
of lifestyle.
The possibility that an association is truly causal is
strengthened by the existence of a dose response effect.
Such an effect has been demonstrated in the Iowa Women’s
Health Study. After adjustment for cardiovascular risk
factors, relative risks for cardiovascular disease were 1.0,
0.96, 0.71, 0.64 and 0.70 in ascending quintiles of wholegrain intake, P for trend ¼ 0.02 (Jacobs et al., 1998). However,
the epidemiological studies do not provide an indication of
whether all grains are equal in this respect. There is no clear
evidence as to which constituent of the grain provides
cardioprotection or as to whether the structure of the grain
needs to be wholly or partially intact.
Relatively few groups have examined the extent to which
wholegrain intakes influence the risk of stroke. Reporting on
the largest of the prospective studies, the Nurses’ Health
Study, Liu et al. (2000a) observed risk reductions of
magnitude similar to those observed for CHD (relative risk
0.69, 95% confidence intervals: 0.50, 0.98 when comparing
highest relative to lowest quintile of intake of wholegrains).
Similar risk reductions have been observed in three other
somewhat smaller cohorts.
Wholegrains differ in a number of respects from highly
refined cereals, and several of the constituents may explain
their cardioprotective effects (Table 1). Dietary fibre has been
studied more than the other constituents. Several groups of
researchers have pooled the results from a number of studies.
For example, Pereira et al. (2004) reported a relative risk of
0.90 (95% confidence intervals: 0.77, 1.07 that is not
statistically significant) for total CHD events for each
10 g/day increase in cereal fibre. When considering CHD
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Table 1 Constituents of wholegrains which may confer cardioprotection
Antioxidant
Dietary fibre (nonstarch polysaccharide)
Unsaturated cis: n–3 and n–6
Folate
Vitamin E
Selenium
Flavenoids
Phytooestrogens
O
O
O
O
O
O
deaths, the relative risk, 0.75 (95% confidence intervals:
0.63, 0.91) was statistically significant, the association being
independent of a number of dietary factors and other
cardiovascular risk factors.
However, other analyses suggest that while cereal fibre is
inversely associated with CHD rates, the relationship is not
as strong as the inverse relationship between CHD and
wholegrain bread (Anderson et al., 2000). Furthermore, the
effect of dietary fibre may be largely explained by fibre
derived from wholewheat, rye or pumpernickel breads
(Mozaffarian et al., 2003). A single study suggested risk
reduction among those with the highest intake of added
bran compared with those who consumed no added bran
(Jensen et al., 2004). The suggestion that reduced cardiovascular risk principally results from consumption of the
wholegrain rather than dietary fibre is supported by findings
from the Iowa Women’s Health Study. CHD rates were
compared in women consuming similar amounts of cereal
fibre from either predominantly refined grain sources or
predominantly wholegrains. After adjustments, all cause
mortality was significantly lower, and CHD appreciably
(though not statistically significantly) reduced among the
latter group (Jacobs et al., 2000). The absence of a universally
adopted definition of ‘wholegrain’, and the even more
inconsistent use of the terms ‘wholemeal’ and ‘wholewheat’
preclude more definitive conclusions and complicate extrapolation into guidelines.
Fruits and vegetables are important sources of carbohydrate and also contain a range of potentially cardioprotective components, including dietary fibre, folate,
potassium, flavonoids and antioxidant vitamins. Pooled
analyses of the Nurses’ Health Study and the Health
Professionals’ Follow-up Study suggested risk reductions of
20 and 30% for CHD and ischaemic stroke, respectively,
when comparing extreme quintiles of fruit and vegetable
intake (Joshipura et al., 2001). Similar findings were reported
in a recent meta-analysis (He et al., 2006). A dose–response
effect was reported with lowest risk for CHD being associated
with eight servings or more per day and for stroke, four or
more servings daily. It is noteworthy that in this, the largest
study reported to date, individual items relatively low in
total carbohydrate appear to have the most striking protective effect—green leafy vegetables in the case of CHD and
cruciferous vegetables, citrus fruits and juices and vitamin C-rich
European Journal of Clinical Nutrition
Lipid-lowering
Enzyme modulator
O
fruits and vegetables in the case of stroke. In the Physicians’
Health Study, Liu et al. (2001) reported an inverse association
between carotenoid rich vegetables and CHD risk, and
Finnish data suggested that flavonoid-rich foods (for example berries, onions, apples) were especially beneficial in this
regard (Knekt et al., 1994). Legume consumption four or
more times per week compared with less than once per week
has also been associated with cardiovascular risk reduction
(Bazzano et al., 2001).
During the 1960s, Yudkin (1964) and co-workers reported
strong associations between high sugar intakes and CHD.
The data were cross-sectional and flawed (Keys, 1971;
Truswell, 1987). The Iowa Women’s Health Study found no
relationship between intake of sweets and desserts and CHD
in over 30 000 women followed for 9 years (Jacobs et al.,
1998). The glycaemic index (GI; and more recently the
glycaemic load, GL) has provided a means of determining
the extent to which carbohydrate-containing foods may
determine cardiovascular risk through their potential to raise
blood glucose. Liu et al. (2000b) reported from the Nurses’
Health Study that women who consumed diets with a highglycaemic load (that is high in rapidly digested starches)
were at increased risk of CHD compared with those with a
lower consumption; a twofold increase in risk over a 10-year
follow-up was observed when comparing those in the
highest and lowest quintiles of intake. The effect appeared
to be independent of total energy intake and other
cardiovascular risk factors.
The potential of dietary patterns, rather than the effect of
individual foods and nutrients on human health, have been
examined in two of the largest cohort studies—the Nurses’
Health Study and the Health Professionals’ Study (Hu et al.,
2000; Fung et al., 2001b). Factor analysis was used to
examine the association between CHD and two major
dietary patterns identified: ‘western’ and ‘prudent’. The
prudent pattern was characterized by higher intakes of
fruits, vegetables, legumes, fish, poultry and wholegrains
and the western pattern, by higher intakes of red and
processed meats, sweets and desserts, French fries
and refined grains. After adjustment for cardiovascular risk
factors, the prudent diet score was associated with relative
risks of 1.0, 0.87, 0.79, 0.75 and 0.70 from the lowest to the
highest quintiles. Conversely, the relative risks across
increasing quintiles of the western pattern score were 1.0,
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J Mann
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1.21, 1.35, 1.40 and 1.64. The patterns were also related to
biochemical markers of CHD. Positive correlations were
noted between the western pattern score and plasminogen
activator antigen, fasting insulin, C-peptide, leptin, C-reactive
protein and homocysteine after adjustment for confounders.
A significant inverse correlation was observed between
plasma folate and the western dietary pattern score. Inverse
correlations were observed between the prudent pattern
score and fasting insulin and homocysteine, and a positive
correlation was observed with folate (Fung et al., 2001a).
In summary, prospective epidemiological studies provide
strong evidence for a protective role of wholegrain cereals,
fruits and vegetables and dietary patterns characterized by
relatively high intakes of such foods. While a high
consumption of dietary fibre derived from cereals is also
associated with a reduced risk of cardiovascular disease, it is
not clear whether the cardioprotection can entirely be
attributed to the polysaccharides per se. The effect seems to
stem largely from dietary fibre in dark breads and may
therefore be at least partially attributable to other constituents of wholegrains. It is not possible to determine the extent
to which other potentially protective constituents of wholegrains are relevant. Epidemiological studies do not permit
separating the effects of different wholegrains. Even the best
prospective studies cannot conclusively eliminate the possibility of residual confounding, so recommendations regarding the intake of carbohydrates in relation to cardiovascular
disease also depend on the intervention studies described
below.
Carbohydrates and cardiovascular risk factors
Lipids and lipoproteins
The effect of carbohydrates on lipids and lipoproteins has
dominated discussions regarding the amounts and classes of
carbohydrate likely to reduce cardiovascular risk. While
there is no doubt that increasing total carbohydrate at the
expense of fat, especially saturated and trans fatty acids in
the Western diet, will result in reduction of total and lowdensity lipoprotein (LDL) cholesterol, concern has been
expressed that other predictors of lipoprotein-mediated
cardiovascular risk may be adversely affected by substantial
increases in total carbohydrate. The potential of
high carbohydrates to increase fasting triglycerides was first
demonstrated in the 1960s (Ahrens et al., 1961) but later
considered to be a transient phenomenon, the hypertriglyceridaemia diminishing with prolonged exposure to a high
carbohydrate intake (Antonis and Bersohn, 1961; Stone and
Connor, 1963). However, more recent and more sophisticated studies suggest that, at least in certain circumstances, a
low-fat, high carbohydrate diet may be associated with
slightly elevated triglyceride levels for as long as 2 years
(Retzlaff et al., 1995). Furthermore, such a diet may result in
the appearance of small dense LDL particles that are
particularly atherogenic and in an adverse ratio of total to
high-density lipoprotein (HDL) cholesterol considered to be
a more specific marker of CHD than total LDL cholesterol
(Kinosian et al., 1995).
The effect of carbohydrate as replacement energy for fatty
acids has been examined in a fairly recent meta-analysis
involving 60 mostly short-term controlled trials (Mensink
et al., 2003). The results appeared to offer a strong message:
regardless of the source of the fat displaced, an increase in
total carbohydrate was associated with an increased ratio of
total to HDL cholesterol. However, although these studies
paid careful attention to ensure that the comparisons were
carried out under isoenergetic conditions and food intake
was thoroughly controlled, there was less consistency with
regard to the source and class of carbohydrate that was used
as fat replacement. A fairly substantial body of evidence
suggests that the type of carbohydrate influences lipid and
lipoprotein levels. The effect of sugars on triglyceride levels
differs from that of polysaccharides. Compared with starches
and NSPs, sugars, especially sucrose and fructose, may be
associated with appreciable increases in triglyceride levels,
especially when the sugars are consumed in the context of a
diet high in total carbohydrate or when dietary fat comprises
principally of saturated fatty acids (Truswell, 1994). The
effect appears to be more marked in insulin resistant
individuals with abdominal obesity (Fried and Rao, 2003).
Unfortunately, few long-term data are available. However,
the CARMEN study suggested that after 6 months, a very
modest weight loss could mitigate the hypertriglyceridaemic
effect of a moderate increase in sucrose (Saris et al., 2000).
This has also been observed for diets high in total
carbohydrate and starches, which might otherwise have
been associated with hypertriglyceridaemia when compared
with diets lower in total carbohydrates (Kasim-Karakas et al.,
2000).
Dietary fibre has a potentially important effect on lipids
and lipoproteins when consumed in plant foods or as
supplements Viscous subgroups, including pectins, b-glucans,
glucomannans, guar and psyllium, which are generally water
soluble, all lower total and LDL cholesterol between 5 and
10 g/day, lowering LDL by about 5% (Truswell, 2002). The
mechanism appears to be by reducing ileal bile acid
absorption (Morgan et al., 1993). These soluble forms of
dietary fibre appear to have a negligible effect on triglyceride
or HDL levels. Insoluble dietary fibre subgroups are derived
largely from cereal sources and have little or no effect on
lipids and lipoproteins (Jenkins et al., 2000). A Cochrane
Review has been undertaken of randomized controlled trials
(RCTs) investigating the effects of wholegrain cereals on
CHD and cardiovascular risk factors. Only 10 studies were
identified that met the strict criteria required for such a
review. None had clinical end points. They compared
wholegrain foods or diets high in wholegrain foods with
other foods or diets with lower levels or no wholegrains.
Eight of the ten studies evaluated wholegrain oats and
clearly demonstrated the potential of such foods to reduce
total LDL cholesterol. Levels were about 0.2 mmol/l lower
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on the diet rich in oats compared with the control diet.
No changes were observed in triglyceride or HDL cholesterol
levels. Lack of appropriate studies precluded conclusions
on wholegrains other than oats (Brunner et al., 2005).
A Cochrane Review has also been undertaken to explore
the extent to which low glycaemic index diets might
influence CHD and risk factors. The average reduction in
total cholesterol when comparing low and high GI diets was
0.17 mmol/l, P ¼ 0.03 (95% CI 0.32 to 0.02). No convincing differences were apparent in LDL cholesterol, HDL
cholesterol or triglyceride levels (Kelly et al., 2004).
In studies of free living individuals in whom fruits,
vegetables and legumes rich in the viscous forms of NSPs
replaced some of the relatively high fat foods typically
consumed in a western diet, total and LDL cholesterol fell as
expected, and the ratio of total (or LDL) cholesterol to HDL
cholesterol improved with no change reported in triglyceride
despite an appreciable increase in total carbohydrate (Turley
et al., 1998). Total carbohydrate provided 59 and 43% total
energy on the high and low carbohydrate diets. While the
aim of these studies was not to achieve weight loss, small
reductions in body weight did occur on the high carbohydrate diets, perhaps as a result of the enhanced satiety
associated with the more bulky, less energy dense foods.
This, together with the effects of dietary fibre, are likely to
have contributed to the less atherogenic lipid profile
observed on the high carbohydrate diet. Such findings
provide a clear indication of the need to consider the nature
of dietary carbohydrate when carbohydrate rich foods are
recommended as replacement for dietary saturated fatty
acids.
Type II diabetes, impaired carbohydrate metabolism and insulin
resistance
See later section, which deals more fully with this topic.
Inflammatory markers
There has been considerable recent interest in the role of
inflammation as a determinant of cardiovascular risk. Much
of the research relating to the role of nutritional determinants has centred around different dietary fats (Basu et al.,
2006). Jenkins et al. (2003) reported reduced C-reactive
protein levels in hyperlipidaemic patients consuming a high
carbohydrate diet rich in viscous fibre-containing foods.
However, the diets were also high in nuts (almonds), plant
sterols and soy proteins, and it is therefore impossible to
disentangle separate effects. A very recent study (KasimKarakas et al., 2006) found that when carbohydrate replaced
a substantial proportion of dietary fat under eucaloric
conditions, the levels of several inflammatory markers
increased along with an increase in triglyceride. However,
when the participants (post-menopausal women) consumed
the 15% fat diet ad libitum under free living conditions, they
European Journal of Clinical Nutrition
lost weight and triglyceride and the levels of inflammatory
markers decreased.
Hypertension
Several ‘high carbohydrate’ dietary approaches have been
shown to be associated with reduced levels of blood pressure.
However, these have invariably involved many dietary
changes. For example, the Dietary Approaches to Stop
Hypertension approaches have involved an increase in
intakes of fruits and vegetables, low fat dairy products and
a reduction in sodium. Thus, it has been impossible to
disentangle individual effects (Appel et al., 1997).
RCT involving clinical end points
A single RCT has examined the effect of altering dietary
carbohydrate intakes on clinical end points. Burr et al. (1989)
randomized 2033 men who had survived a myocardial
infarction to receive one of eight possible combinations of
dietary advice. Those who were advised to increase cereal
fibre had a similar rate of CHD recurrences and deaths as
those who did not receive this advice when considering a
10-year follow-up period. However, the study was underpowered and the degree of compliance is uncertain (Ness
et al., 2002). Other RCTs, which involved an increase in
dietary carbohydrate, from fruits, vegetables, legumes and
wholegrain, as part of a multifactorial dietary approach to
primary and secondary prevention of CHD, demonstrated
reduction in clinical events among those receiving intensive
dietary advice compared with control groups (Hjermann
et al., 1981; de Lorgeril et al., 1994). The Women’s Health
Initiative Randomised Control for Dietary Modification Trial
involved the intervention group being recommended a high
carbohydrate low fat diet. Failure to demonstrate significant
differences in CHD rates in control and intervention groups
contributed little to the understanding of the role of
carbohydrates since long-term compliance with the intervention diet was poor (Howard et al., 2006).
Dietary carbohydrate and cardiovascular disease:
recommendations
The joint WHO/FAO Expert Consultation on Diet, Nutrition
and the Prevention of Chronic Disease (WHO Technical
Report Series 916, 2003) considered that the evidence
suggesting a cardio-protective effect of fruits and vegetables
was ‘convincing’ and that relating to wholegrain cereals and
NSP was ‘probable’. The evidence that high intakes of total
carbohydrate might increase the risk of cardiovascular
diseases was considered to be ‘insufficient’ (Table 10, p88
TRS 916). Difficulties with regard to the definition of
wholegrains and inability to exclude the possibility of
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residual confounding provide the justification for regarding
the protective effect being graded as ‘probable’ rather than
‘convincing’. The Expert Consultation recommended that
total carbohydrate should provide 55–75% total energy and
that free sugars should provide less than 10%. Recommended intake of fruits and vegetables was 400 or more g per
day, excluding tubers (that is potatoes, cassava). Precise
amounts of NSPs or dietary fibre were not recommended.
However, it was considered that appropriate intakes of fruits,
vegetables, legumes and regular consumption of wholegrain
cereals would provide in excess of 20 g/day of NSP and over
25 g of total dietary fibre. There was also no recommendation regarding glycaemic index. These recommendations
would appear to be generally compatible with this update of
the relevant literature with the following caveats:
Many western countries have average intakes of carbohydrate, which are below 55% total energy. There is no
good evidence that total carbohydrate intake for populations or individuals must reach the lower recommended
intake in order to achieve a cardioprotective dietary
pattern provided guidelines relating to dietary fat and
other nutrients are met. Several national guidelines
suggest a lower limit of 50% total energy.
A wide range of carbohydrate intakes is compatible with
cardioprotection. However, it is important to be prescriptive with regard to the nature of carbohydrate, especially
when total carbohydrate intakes are at the upper end of
the recommended range. Failure to emphasize the need
for carbohydrate to be derived principally from wholegrain cereals, fruits, vegetables and legumes may result in
increased lipoprotein-mediated risk of CHD associated
with an increase in the ratio of total (or LDL) cholesterol
to HDL cholesterol and an increase in triglyceride. This
may apply particularly to overweight and obese individuals who are insulin resistant (see separate section on
diabetes and insulin resistance).
While fruits and legumes rich in viscous (soluble) forms of
NSP and dietary fibre are associated with reduced LDL
cholesterol, insoluble forms derived from wholegrain
cereals also appear to confer cardioprotection possibly in
association with other constituents of wholegrains. There
is no convincing evidence that fibre supplements and
manufactured and functional foods containing them
reduce cardiovascular risk.
Dietary carbohydrate and diabetes, impaired
carbohydrate metabolism and the metabolic
syndrome
The escalating rates of type II diabetes worldwide and the
realization that insulin resistance and its associated metabolic
abnormalities contribute increasingly to the global epidemic
of cardiovascular disease (Mann, 2000) have resulted in
renewed interest in the nutritional determinants of these
metabolic derangements. In the 1960s, Yudkin suggested that
sugar (sucrose) was a major determinant of type II diabetes
(then known as ‘maturity onset’ and later as ‘non-insulin
dependent’ diabetes). The conclusions were based largely on
highly selected, within country and cross country, comparisons (Yudkin, 1964; Nuttall and Gannon, 1981) later
acknowledged to be totally inappropriate analyses (Nuttall
et al., 1985). At about the same time, Trowell, then working in
Uganda, suggested that the low rates of diabetes in rural Africa
were likely to result from a protective effect of large intakes of
dietary fibre found in the minimally processed or unprocessed
carbohydrate, which provided a high proportion of total
dietary energy in such societies (Trowell, 1975). Although it
was not possible to know the extent to which these
observations implied true causation or protection or simply
represented confounding, they stimulated much subsequent
epidemiological and experimental research.
Prospective epidemiological studies
A number of limitations apply to all prospective studies that
have examined the association between foods and nutrients
and the risk of various diseases. The issues that are
potentially relevant to dietary carbohydrate have been
considered in the previous section on cardiovascular disease,
and they apply equally when relating various carbohydrates
to risk of developing diabetes. Recent prospective studies
provide some insight.
In the Nurses’ Health Study, there was no association
between total intake of grains and type II diabetes. However,
wholegrain consumption appeared to be protective. When
comparing the highest and lowest quintiles of intake, age
and energy adjusted relative risk was 0.62 (95% CI: 0.53,
0.71). Further adjustment for other risk factors did not
appreciably alter this risk estimate (Liu et al., 2000). A
virtually identical risk reduction was observed among men
participating in the Health Professionals Study (Fung et al.,
2002). A relative risk of 0.63 was reported in association with
three or more servings per day of wholegrains. In the Iowa
Women’s Health Study, postmenopausal women in the
upper quintile of wholegrain consumption (more than 33
servings per week) were 20% less likely to develop type II
diabetes than those in the lowest quintile (fewer than 13
servings per week) (Meyer et al., 2000). Wholegrains have
also been shown to be protective against type II diabetes in
African-Americans (van Dam et al., 2006), Finns (Montonen
et al., 2003) and Iranians (Esmaillzadeh et al., 2005). Cereal
fibre, as distinct from fibre derived from other sources,
appears to be associated with a protective dose–response
effect that is present after controlling for a range of
potentially confounding factors. In the Nurses’ Health Study,
multivariate relative risks for quintiles 1–5 were 1.0, 0.85,
0.87, 0.82 and 0.64, respectively (Salmeron et al., 1997a). The
role of wholegrains and dietary fibre in diabetes has been
reviewed in detail in Venn and Mann (2004).
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In the Nurses’ Health Study and the Health Professionals
Follow-up Study, a statistically significant relative risk of
about 1.4 was observed when comparing diabetes rates in the
highest and lowest quintiles of dietary glycaemic load, after
adjusting for potentially confounding factors (Salmeron
et al., 1997a, b). A high dietary glycaemic index was also
found to be associated with an increased risk of type II
diabetes in the Melbourne Collaboration Cohort Study
(Hodge et al., 2004).
Rapidly digested starches and sugars, especially glucose,
contribute to the glycaemic load of the diet, and thus such
observations provide some evidence for a promotive role
of these carbohydrates in type II diabetes. However,
no association was found between sucrose intake and risk
of diabetes during a 6-year follow-up of the Nurses’ Health
Study (Colditz et al., 1992). Meyer et al. (2000), reporting the
findings from the Iowa Women’s Health Study, found no
relationship between type II diabetes and either glycaemic
index or glycaemic load. However, dietary glucose and
fructose (but not sucrose) were associated with increased risk.
Women who developed gestational diabetes in the Nurses’
Health Study had lower intakes of dietary fibre and higher
dietary glycaemic load than those who did not (Zhang et al.,
2006).
No prospective studies have examined the relationship between dietary carbohydrate and insulin resistance,
considered to be the underlying abnormality in most
cases of type II diabetes. However, two large cross-sectional
studies, using validated food frequency questionnaires
to assess nutrient intake and either the frequently
sampled intravenous glucose tolerance test or homoeostasis
model assessment for insulin resistance, found that
intake of dietary fibre was inversely associated with the
probability of having insulin resistance (Lau et al., 2005;
Liese et al., 2005). In the Insulin Resistance Atheroscelerosis Study (Liese et al., 2005), it was possible to
demonstrate that fibre was associated with increased
insulin sensitivity even after adjustment for body mass
index. Interestingly, neither study found any relationship between insulin sensitivity and glycaemic index or
glycaemic load.
While diets rich in wholegrains and dietary fibre may
protect against diabetes and pre-diabetic states by virtue of
their potential to promote satiety and weight loss in those
who are overweight or obese (excess adiposity being the
major determinant of these metabolic abnormalities),
the epidemiological data do provide evidence for a protective effect independent of that on fat mass. The data do not
permit distinction among different grains nor the extent to
which structure of the grain or its constituents explain the
protective effect. Several studies suggest that diets with a
relatively low glycaemic index or glycaemic load are
protective against disorders of carbohydrate metabolism,
but the data are insufficient to establish with certainty the
extent to which this is independent of other attributes of
carbohydrates.
European Journal of Clinical Nutrition
Experimental studies
Most studies that have compared the effects of carbohydrates
and fats and the effects of different carbohydrates have been
undertaken in people with established diabetes; however,
some information is available concerning people with
insulin resistance and the metabolic syndrome. Insulin
resistance and its associated dyslipidaemia (high triglyceride,
low HDL) have been shown to be more marked on a high
carbohydrate diet when compared with a diet rich in
monounsaturated fatty acids. However, while such studies
may distinguish between sugars and polysaccharides, they
often do not distinguish between starches, many of which
are rapidly digested and absorbed, and NSPs (Mann, 2001).
A study by Pereira et al. (2002) clearly demonstrates the
importance of doing so. In a controlled 6-week study,
overweight hyperinsulinaemic adults consumed diets providing 55% energy from carbohydrate and 30% from fat.
Carbohydrates were derived from predominantly wholegrain
or refined grain cereals, with dietary fibre content of the
wholegrain diet 28 g compared with 17 g on the refined grain
diet. Dietary fibre was predominantly from cereal sources.
Total carbohydrate and fat and fat sources were virtually
identical on the two diets. Insulin sensitivity measured by a
euglycaemic hyperinsulinaemic clamp was appreciably improved on the wholegrain compared with the refined grain
diet. Fasting insulins and area under the 2-h insulin curve
were lower, despite body weight not being significantly
different on the two diets. Rye bread (Juntunen et al., 2003)
and purified cereal fibre (Weickert et al., 2006) have been
shown to improve insulin sensitivity in overweight and
obese women.
Analysis of a subgroup of individuals within the CARMEN
Study, who were diagnosed with the metabolic syndrome,
showed that the reduction in body weight and improvement
in metabolic indices seen when simple carbohydrate (sugars)
were replaced with complex ones were more striking in
people with this disorder than in the general population
(Poppitt et al., 2002). Studies by McAuley et al. (2005; 2006)
have compared different nutritional approaches in overweight insulin-resistant women. Although a low carbohydrate high fat diet resulted in initial weight loss and
improvement in the metabolic derangements associated
with insulin resistance, the improvement was not sustained.
A diet relatively high in protein and unsaturated fat sources
and with moderate amounts of fibre-rich carbohydrate, and
one low in total fat and relatively high in fibre-rich
carbohydrate produced sustained weight loss and improvement in a range of metabolic measurements over a period of
a year. Thus, while weight loss in those who are overweight
or obese is the cornerstone of management aimed at
improving insulin sensitivity, it appears that this can be
achieved by diets relatively high or relatively low in
carbohydrates, provided the carbohydrate sources are
wholegrain and rich in dietary fibre. Other studies that have
compared the effects of diets of varying amounts of
Cardiovascular disease and diabetes
J Mann
S107
carbohydrate have generated broadly similar results (Nordmann
et al., 2006).
The fact that fructose, compared with glucose, is preferentially metabolized to lipid in the liver and that fructose
consumption induces insulin resistance, impaired glucose
tolerance, hyperinsulinaemia, hypertriglyceridaemia and
hypertension in animal models has led to the suggestion
that fructose, sucrose or high fructose corn syrup may have
uniquely untoward effects compared with other carbohydrates in humans when fed in the context of energy balance.
However, while these sugars may contribute to increasing
the risk of overweight and obesity and thus to the
clinical and metabolic disorders (Mann, 2004), the evidence
regarding fructose remains limited and conflicting, and no
conclusions can be drawn (Elliott et al., 2002; Daly, 2003).
A large number of studies have been undertaken to
determine the extent to which total quantity and nature of
dietary carbohydrate influence glycaemic control, insulin
resistance and cardiovascular risk factors in people with type
II diabetes. While such studies apply principally to diabetes
management, it seems reasonable to assume that the data
also have some relevance to disease prevention.
A meta-analysis of nine studies has been undertaken to
compare the effects of high carbohydrate and high monounsaturated fatty acid diets. The overall results provide
evidence of higher fasting triglycerides and VLDL cholesterol, slightly lower HDL cholesterol, slightly higher glucose,
but not glycated haemoglobin on the high carbohydrate
diets, typically providing 55–60% total energy from carbohydrate (Garg, 1998). There was considerable variation in the
results of the individual studies, partly due to the fact that
they were all relatively underpowered and also because the
severity of diabetes may influence response to dietary
carbohydrate. However, equally important is the fact that
the nature of dietary carbohydrate was not clearly specified.
It appears that a range of ‘complex carbohydrates’ provided a
substantial proportion of total carbohydrate on the high
carbohydrate diets. It seems that there may have been a lack
of appreciation regarding the different effects of starches and
NSPs and indeed the different effects of NSPs from different
sources. This is surprising, given that in the late 1980s, it had
been clearly shown that high carbohydrate diets were only
associated with beneficial effects in terms of glycaemic
control and blood lipids when carbohydrate was derived
principally from foods rich in soluble forms of dietary fibre,
notably pulses, legumes and intact fruits and vegetables
(Rivellese et al., 1980; Simpson et al., 1981; Riccardi et al.,
1984; Mann, 2001). Higher intakes of cereal (insoluble) fibre
were associated with less marked or no benefit in glucose or
lipid levels (Simpson et al., 1979; 1982; Riccardi et al., 1984).
The beneficial effects of soluble forms of dietary fibre derived
from fruits and vegetables appear to have been rediscovered
more recently in randomized crossover studies in type II
diabetes (Chandalia et al., 2000). Dietary fibre has also been
shown to be of benefit in type I diabetes (Giacco et al., 2000).
Cross-sectional epidemiological data, based on the
EURODIAB Complications Study, which included over
2000 patients in 31 European centres, showed an inverse
association between dietary fibre intake of HbA1c and LDL
cholesterol (in men only) and a positive association with
HDL cholesterol in men and women (Toeller et al., 1999). An
RCT (parallel design) in type I patients continued for 6
months, confirmed the potential for around 40 g/day dietary
fibre (half of the soluble type from legumes, fruits and
vegetables) to improve glycaemic control (Giacco et al.,
2000). Some studies have shown improved glycaemic control
when soluble fibres have been fed as supplements to patients
with diabetes. However, evidence-based nutritional guidelines of the Nutrition Study Group of the European
Association for the Study of Diabetes offer no recommendations regarding supplements of functional foods providing
increased dietary fibre. Long-term clinical trials are deemed
necessary before recommendations can be considered (Mann
et al., 2004).
In the 1980s, several RCT with crossover designs demonstrated no adverse effects on glycaemic control, lipids and
lipoproteins when diets containing small amounts of sucrose
(usually around 50 g) were compared under eucaloric conditions with virtually sucrose-free diets in type I and type II
diabetes (Slama et al., 1984; Peterson et al., 1986; Mann, 1987).
While there is thus clear evidence for the acceptability of
moderate intakes of sucrose for most people with diabetes,
there are few data from which to derive acceptable upper
limits. For those who are overweight or obese or are markedly
insulin resistant, fairly severe restriction may be appropriate.
For all others, moderate intakes of free sugars (up to 50 g/day)
are acceptable, provided that free sugars do not exceed 10%
total energy. There are suggestions that sugar in beverages
increases body weight to a greater extent than the same
amount of sugar in the solid form (diMeglio and Mattes, 2000).
A number of randomized trials have examined the extent
to which diets with a low glycaemic index can improve
glycaemic control and cardiovascular risk factors. Several
meta-analyses have been published (Brand-Miller et al., 2003;
Opperman et al., 2004) and the results are broadly comparable. For example, Opperman et al. reported a reduction in
HbA1c of 0.27 (95% confidence intervals: 0.5 to 0.03)
when comparing high and low glycaemic index diets. This
issue was examined in a Cochrane Systematic Review, which
suggested some evidence of an effect of low GI diets
compared with high GI diets after 12 weeks. Pooled analysis
of studies with a parallel design demonstrated mean HbA1c
levels 0.45% less than the high GI diets (95% confidence
intervals: 0.82 to 0.09, P ¼ 0.02). It is of importance to
note that the low GI foods utilized in most of the studies
were plant based (for example peas, lentils, beans, pasta,
barley, parboiled rice, oats and cereals) as were the high
GI foods (potatoes, wheatmeal and white bread and high GI
breakfast cereals). The studies did not generally include
many of the now widely available manufactured and
functional foods, which are not necessarily predominantly
plant based.
European Journal of Clinical Nutrition
Cardiovascular disease and diabetes
J Mann
S108
RCT with clinical end points
Two RCTs involving people with impaired glucose tolerance
consuming ‘western’ diets have examined the extent to
which progression of impaired glucose tolerance to type II
diabetes can be reduced by intensive lifestyle modification
(Tuomilehto et al., 2001; Knowler et al., 2002). In both the
Finnish and US intervention studies, advice regarding
frequent consumption of wholegrain products, vegetables
and fruits has been a pivotal component of the advice to
achieve weight loss. Other components included recommendations to use monounsaturated oils, soft margarines and
low fat meat and milk products, as well as to increase
physical activity of moderate intensity. These interventions
achieved a nearly 60% reduction of progression from
impaired glucose tolerance to type II diabetes. While it is
impossible to accurately disentangle the separate contributions of the different components of the intervention
package, and weight loss was clearly the major determinant
of risk reduction, increased intake of dietary fibre appeared
to be independently associated with reduced risk of progression (Lindstrom et al., 2003). A similar study has been
conducted in India (Ramachandran et al., 2006).
Dietary carbohydrate and diabetes:
recommendations
The Joint WHO/FAO Expert Consultation on Diet, Nutrition
and the Prevention of Chronic Disease (WHO Technical
Report Series 916, 2003) describes the protective effect of NSP
as ‘probable’. However, an explanatory note indicates that
the level of evidence is graded as ‘probable’ rather than
‘convincing’ because of the apparent discrepancy between
the experimental studies, in which it appears that soluble
forms of NSP exert benefit in terms of glycaemic control,
lipids and lipoproteins, and the prospective cohort studies,
which suggest that cereal-derived insoluble forms are
protective. The evidence regarding low glycaemic index
foods as protective is graded as ‘possible’. The evidence table
(Table 9, p 77 TRS 916) leads to the disease-specific
recommendation regarding intakes of NSP, which quite
appropriately disregards a clear distinction between soluble
and insoluble forms and suggests that adequate intakes of
NSP or dietary fibre can be achieved through regular
consumption of wholegrain cereals, legumes, fruits
and vegetables. There is no clear evidence on which to
base precise quantities although a minimum intake of 20 g
of NSP is recommended. These recommendations appear
to be compatible with this update of the relevant literature
with two caveats:
There appears to be a reasonable body of evidence to
suggest a protective effect of wholegrains.
The apparently different effects of soluble and insoluble
forms of NSP or dietary fibre may result from difficulty in
accurately distinguishing between the two forms.
European Journal of Clinical Nutrition
Similar approaches to those suggested for reducing disease
risk have been recommended for the management of
diabetes. The European evidence-based nutritional approaches
(Mann et al., 2004) to the treatment of diabetes indicate that
a wide range of intakes of total carbohydrate (45–60% total
energy) is acceptable, provided a high proportion of
carbohydrate energy is derived from vegetables, legumes,
fruits and wholegrain cereals. This should provide the
recommended intake of total dietary fibre (more than
40 g/day or 20 g/1000 kcal/day), about half of which should
be soluble. Cereal-based foods should whenever possible be
wholegrain and high in fibre. Daily consumption of at least
five servings of fibre-rich vegetables or fruits and at least four
servings of legumes per week help to provide the minimum
requirements for fibre. While a choice anywhere within this
range is acceptable for most people, it is acknowledged that
some, especially those with marked hypertriglyceridaemia
and/or severe insulin resistance, may respond more appropriately to an intake at the lower end of the recommended
range. Use of carbohydrate-containing foods with a low
glycaemic index is encouraged. While a moderate amount of
sugar is acceptable in the context of energy balance, those
who are overweight should substantially restrict sugar-containing energy-dense foods. Sugar-containing beverages,
while not energy dense, promote overweight and obesity
and are best avoided. Finally, it is important to emphasize
that the beneficial effects of certain carbohydrate-containing
foods have been based principally on the consumption of
conventional foods. Evidence for the benefit of manufactured and functional foods containing added dietary fibre or
other components of wholegrains, fruits, vegetables and
legumes is limited. This applies also to foods with a low
glycaemic index. Some foods now marketed as having a low
glycaemic index are high in fat and sugar and therefore may
not be suitable for people with diabetes, especially those
who are overweight. The paper describing the European
recommendations (Mann et al., 2004) provides a detailed list
of references justifying the conclusions summarized here.
Conclusions
Nutritional attributes that are likely to protect against
diabetes and cardiovascular diseases are remarkably similar
as are the principles of nutritional management for those
who already have established disease. In summary, they are
as follows:
A wide range of intakes of carbohydrate containing foods
is acceptable.
Nature of carbohydrate rather than quantity is principally
what matters.
Intact fruits, vegetables, legumes and wholegrains are
excellent sources of carbohydrate likely to be rich in NSP
or dietary fibre and other potentially cardioprotective
components.
Cardiovascular disease and diabetes
J Mann
S109
There is no good evidence of benefit when NSP or other
components of wholegrains, fruits, vegetables and
legumes are added to functional and manufactured foods.
Low glycaemic index foods may confer benefits in terms
of lowering total cholesterol and improving glycaemic
control in people with diabetes. However, it is not clear
whether these benefits are independent of the effects of
dietary fibre or the fact that low glycaemic index foods
tend to have intact plant cell walls. Furthermore, it is
uncertain whether functional and manufactured foods
with a low glycaemic index confer the same long-term
benefits as low glycaemic index predominantly plantbased foods.
A low dietary glycaemic load may reduce the risk of type II
diabetes and cardiovascular disease. The same caveats as
those described above for the therapeutic role of low GI
foods apply.
Limitations to the use of the glycaemic index and
glycaemic load concepts in the clinical setting are further
described in the accompanying paper in this series.
Acknowledgements
I thank Professor Kjeld Hermansen, Dr Andrew Neil, Dr
Gabriele Riccardi, Dr Angela Rivellese, Dr Monika Toeller,
Professor A Stewart Truswell, Dr Rob M van Dam and Dr HH
Vorster for the valuable comments they provided on the
earlier paper.
Conflict of interest
During the preparation and peer-review of this paper in
2006, the author and peer-reviewers declared the following
interests.
Author
Professor Jim Mann: none declared.
Peer-reviewers
Professor Kjeld Hermansen: none declared.
Dr Andrew Neil: none declared.
Dr Gabriele Riccardi: none declared.
Dr Angela Rivellese: none declared.
Dr Monika Toeller: none declared.
Professor A Stewart Truswell: none declared.
Dr Rob M van Dam: none declared.
Dr HH Vorster: member and director of the Africa Unit for
Transdisciplinary health Research (AUTHeR), Research grant
from the South African Sugar association.
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