1000
ACNS National Meeting 1996 APJCN 1997; 6(2): 143-151
Volume 6, Number 2: 143-151
Focus
on nutrition, cardiovascular
disease and cancer:
ACNS National Meeting 1996
Prof Madeleine Ball, Deakin University, Geelong,
VIC
The ACNS Meeting was held in Sydney on the 30th September,
1996. It was, in part, a joint meeting with the Nutrition Society of
Australia with common lecture sessions in the morning and an option
of ACNS Symposia in the afternoon and an evening session primarily aimed
at General Practitioners. The Plenary Lecture
in the morning was by Prof Alan Husband from the Dept of Veterinary
Pathology, University of Sydney. His topic was ‘Nutrition, stress
and immune activation1. Professor Husband discussed how the
response to stress (physical, social or microbial) provokes an inte-grated
reaction involving the immune system (via cyto-kines), the cental nervous
system (via nervous output) and the endocrine system (via hormones),
each influencing and influenced by the other physiological responses
to environ-mental change. He explained that in this context there was
a close link between nutrition and immunity, in that nutritional deficiencies
may cause stress or may alter CNS output and thereby impact on immune
function. He also proposed that changes in immune status have a feedback
effect on nutrient intake and utilisation partitioning such that inappropriate
immune activation has deleterious effects on growth and development.
His talk was complemented by examples from animal nutrition, but many
of the issues may have common counterparts in human work. In
the subsequent symposium on Nutrition and Immunity, Dr Michael James
from the Rheumatology Unit at the Royal Adelaide Hospital, spoke on
‘Dietary polyunsaturated fats and inflammation’. Dr James
discussed the influence of n-3 and n-6 fatty acids in our diet and the
biochemical interactions that may effect the immune status. There is
considerable evidence that increasing the amount of dietary n-3 fat
can suppress inflammatory mediator production and thus inflammation.
He suggested mech-anisms for these effects and how high levels of n-6
fats in the diet may reduce the optimal anti-inflammatory effects of
n-3 fats. On a practical level he was keen to explore the interaction
of diets high in n-3 and lower in n-6, together with anti inflammatory
drugs in inflammatory joint disease. Dr Judy Carman
from the Communicable Disease Control Branch, South Australian Health
Commission then spoke on ‘The relationship between anti oxidants
and immune function in healthy men’. She described a study in which
64 healthy men were examined for the relationship between blood concentrations
of the anti oxidants zinc, selenium, b -carotene and vitamins A, C and
E with immune function (as measured by the CD4 number), whilst taking
into account the potential confounders-- smoking, alcohol consumption,
hepatitis and active exercise. They found that only b -carotene showed a relationship with CD4 number, a higher b -carotene being associated with a lower CD4 number. Dr
Ann Swain, from the Allergy Service, Dept of Immunology, Royal Prince
Alfred Hospital in Sydney, spoke on ‘Food allergy’. Anne discussed
food allergy as a common cause of morbidity in children and the importance
of recognition of the condition so that treatment can be effected. She
acknowledged that this is sometimes difficult because the presence of
hidden food allergens in commercially prepared and packaged foods may
not be easy to identify. She also noted that distinguishing clinically
between true allergic reactions and non-immunological intolerances is
important, the latter being the more common cause of adverse reactions
in the community.The ACNS Plenary session consisted
of four talks: ‘Micronutrients and CVD’ by Dr Samir Samman,
‘Micronutrients and Cancer’ by Dr Dorothy Mackerras, ‘Macronutrients
and Cancer’ by Prof Stewart Truswell and ‘Macronutrients and
CVD’ by Prof Madeleine Ball. These reviewed the areas of our knowledge
and also some areas of uncertainty in our appreciation of the inter-relationship
of diet and these two common diseases. The abstracts of these talks
follow. There were a small number of Free Communications and Posters,
on food intake and cardiovascular risk factors in Beijing, presented
by staff from the Monash Medical Centre. Abstracts of these papers and
a couple of posters are included at the end of this report. The ACNS
evening program was entitled ‘Dietary advice in the Nineties- Prudent,
Practical, Preventative?’ After a very pleasant dinner, the session
opened with Dr Ross Walker giving a very amusing and practical description
of sensible lifestyle advice for prevention of cardiovascular disease.
His emphasis was very much on sensible eating and lifestyle, some red
wine and taking time to relax and enjoy life! Associate Prof David Colquhoun
then spoke on ‘Dietary advice in the nineties’ and promoted
the use of the modified fat or Mediterranean diet as a palpable diet
to reduce cardiovascular risk and to improve compliance to the dietary
prescription. Dr David Sullivan discussed how the practical nutritional
advice we are promoting was applicable to both cardiovascular disease
and cancer, in that a reduction in saturated fat and an increase in
fruit and vegetables had very likely benefits for both these disorders.
The ACNS committee was pleased with the results
of the meeting, which allowed some exchange of ideas with members of
the Nutrition Society and interaction with a number of local General
Practitioners. The next meeting will be in conjunction with the Nutrition
Society of Australia, in Brisbane in late November and again will provide
an opportunity in the afternoon/evening for the involvement of local
doctors. We thank the organisers, speakers and everyone who attended
in 1996 for helping to make the meeting a success. Enquiries about the
1997 meeting should be addressed to David Colquhoun.
1.
Nutrition, stress and immune activation.
AJ Husband
and WL Bryden
Nutrition, stress and immune activation
AJ Husband and WL Bryden1
Departments of Veterinary Pathology
and Animal Science1, The University of Sydney,
Sydney
The response to stress (physical, social or microbial)
provokes an integrated reaction involving the immune system (via cytokines),
the central nervous system (via nervous output) and the endocrine
system 1000 (via hormones) each influencing and influenced by the
other physiological responses to environ-mental change. In this context,
the concept of a link between nutrition and immunity is readily appreciated,
in that nutritional deficiencies may cause stress or may alter CNS
output and thereby impact on immune function. However, this paper
addresses some facets of nutrition-immune interactions which are less
obvious. While the selective effects on immunity of individual components
of the diet, and the effect on selective components of the immune
system of nutrient imbalance are addressed, the concept is proposed
that changes in immune status have a feedback effect on nutrient intake
and utilisation partitioning such that inappropriate immune activation
has deleterious effects on growth and development. The potential mediators
by which these effects occur are explored.
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list
Dietary polyunsaturated fats and inflammation
MJ James and LG Cleland
Rheumatology Unit, Royal Adelaide
Hospital
Dietary polyunsaturated fats are classified as n-3
or n-6 according to their double bond chemistry and these chemical
differences confer differential biological effects on fatty acids
from these two classes. In the modern Australian diet, the intake
of n-6 fats exceeds that of n-3 fats by approximately 25-fold. This
relative abundance of n-6 fat intake is reflected in the cell membranes
where the ratio of n-6:n-3 PUFA is approximately 7:1. While this relative
excess of n-6 to n-3 fat has been driven by agricultural and industrial
changes as well as dietary changes aimed at lowering blood cholesterol
levels, there is considerable evidence that increasing the amount
of dietary n-3 fat can suppress inflammatory mediator production and
can suppress inflammation. Animal studies using models of inflammatory
disease have demonstrated that ingestion of fish oil, rich in n-3
fats, can suppress inflammation. In human studies, at least 11 double-blind,
placebo-controlled clinical trials with rheumatoid arthritis patients
have demonstrated that dietary supplements of fish oil can provide
symptomatic benefits. The mechanisms for these clinical responses
lie in the effects which n-3 fats have on the production of inflammatory
mediators. Dietary fish oil which contains 20- and 22-carbon n-3 fatty
acids and flaxseed oil which contains their 18-carbon n-3 progenitor
fatty acid, can inhibit the production of the eicosanoid inflammatory
mediators, prostaglandin E2 (PGE2) and leukotriene
B4 (LTB4) and the cytokine inflammatory mediators,
interleukin-1b (IL-1b ) and tumour necrosis factor-a
(TNFa ).
Because n-6 fats can decrease the levels of n-3 fats in cell membranes,
it is most likely that the optimum anti-inflammatory effects of n-3
fats will be within the context of diets also containing lower levels
of n-6 fats than those in the current Australian diet.
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The relationship
between antioxidants
and immune function in healthy men
J Carman, D Naidoo, P Stewart
Communicable Disease Control Branch,
South Australian Health Commission, SA
Dep 1000 artment of Clinical Chemistry, Prince of Wales Hospital,
Sydney
Department of Clinical Biochemistry, Royal Prince Alfred Hospital,
Sydney
Antioxidant vitamins and minerals have been linked
to immune function, with deficiencies linked to an impaired immune
function and supplementation linked to an improvement in immune function.
However, few studies have either considered this relationship in relatively
healthy individuals in the community or accounted for potential confounders
of the relationship, such as smoking, alcohol consumption, hepatitis
and active exercise. This study explores, in 64 relatively healthy
men, the relationship between the concentration of the antioxidants
zinc, selenium, b-carotene and vitamins A, C and E with immune function (as measured by
the CD4 number), whilst taking into account the potential confounders,
smoking, alcohol consumption, hepatitis and active exercise. The results
indicate that under these conditions, these antioxidants have no relationship
with the CD4 number, except for b-carotene. b-carotene was found to have an inverse relationship with the CD4 number,
so that a higher concentration of b-carotene was associated with a
lower CD4 number.
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Food allergy
A Swain, V Soutter, R Loblay
Allergy Service, Dept of Immunology,
Royal Prince Alfred Hospital, Sydney
In young children food allergy is a common cause of
morbidity due to its association with atopic eczema and gastrointestinal
disorders. Although most children grow out of food allergies before
puberty, highly sensitised individuals can have life-threatening reactions.
Recognition is important since successful avoidance can prevent the
occurrence of morbidity and mortality. However, the presence of hidden
food allergens in commercially prepared and packaged foods can make
this difficult, and mounting evidence of morbidity and mortality from
accidental ingestion is a cause for concern. It is also important
to distinguish clinically between true allergic reactions and non-immunological
intolerances, the latter being more common causes of adverse reactions
in the community. Better understanding of this distinction by the
public as well as health professionals should help to clear up much
of the confusion surrounding food allergy, and should also help to
eradicate many of the misguided testing and treatment methods which
have plagued this area for over half a century.
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Micronutrients
and coronary heart
disease
Samir Samman
Human Nutrition Unit, University of
Sydney
A number of minor dietary constituents have been shown
to affect coronary heart disease (CHD). These include some recognised
nutrients as well as other substances, mostly derived from plants.
A number of different mechanisms are involved including:
- antioxidant (or pro-oxidant) activity which impacts
on the oxidisability of low density lipoprotein (LDL),
- alteration in the lipoprotein profile or
- effects on steroid hormone meta 1000 bolism.
As an example, it has been reported widely that vitamin
E is negatively associated with CHD. Vitamin E, or specifically a -tocopherol, confers its protective activity probably by reducing the
oxidisability of LDL. Vitamin C acts synergistically with a -tocopherol by regenerating it from its major oxidised product, the
tocopheryl quinone. In addition, vitamin C is associated (epidemiologically)
with an elevation in the anti-atherogenic high density lipoprotein
(HDL) which not only promotes reverse cholesterol transport but may
also reduce the oxidisability of LDL. Flavonoids are a family of compounds
found ubiquitously in plants and are considered non-nutritive. They
are potent inhibitors of the oxidative modification of LDL and foods
containing these compounds, such as tea and red wine, have been shown
to be negatively associated with CHD. Flavonoids reduce the formation
of free radicals, protect or regenerate a -tocopherol or alternatively, they
chelate divalent metal ions and prevent them from participating in
the Fenton reaction. Less is known about other minor dietary constituents,
such as boron, which is found in fruits and vegetables.
Boron may have an impact on CHD by inducing small
increases in the concentration of plasma oestrogen and testosterone
but in animals it has been shown to reduce the concentration of HDL.
The regular consumption of fruits and vegetables and moderate consumption
of beverages such as red wine and tea may protect against atherosclerosis
and thrombotic tendency. More research is required to elucidate the
mechanisms by which minor dietary factors are absorbed, metabolised
and interact with other nutrients in vivo.
The presence of a large number of minor dietary factors
that protect against CHD reinforces the recommendation to eat a variety
of foods and to increase the intake of fruits and vegetables rather
than the consumption of high doses of any specific supplement.
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Micronutrients
and cancer
Dorothy Mackerras
Menzies School of Health Research,
Darwin
The way diet-disease relationships are envisaged has
changed over the last 20 years. Formerly, the focus was on diseases
for which the lack of a nutrient was both the necessary and the sufficient
cause of the disease. (Indeed, this is the basis of the definition
of a nutrient.)
Nowadays, much attention is given to the possible
role of a variety of food factors in preventing diseases such as cancer.
These diseases are ‘multi-factorial’ in contrast to the
‘uni-factorial’ nature of the deficiency diseases. This
means that lack or excess of the food factor is neither necessary
for the disease to occur, nor, on its own, sufficient to make the
disease occur. This makes relationships much harder to study - we
have to talk about changes in the probability with which rare events
are occurring. Studies have to be larger, because most study subjects,
even those at high risk, will not get the disease. Studies have to
last longer to deal with latent periods. Hence they are much more
expensive and so there has to be reasonable evidence that a relationship
might exist before it would be sensible to spend money on a trial
to confirm or refute the hypothesis.
A series of case-control studies examining the effect
of diet on lung cancer started with showing an inverse 1000 association
for vitamin A. The hypothesis shifted to b-carotene and later to other nutrients
in food. Other cancers were also studied, although the relationships
found were not as consistent as those involving respiratory cancer.
A number of different foods were examined, but the associations were
not consistent for any one food type although there was a general
pattern for people with high fruit and vegetable consumption having
a lower incidence of cancer. Studies using biochemical data, rather
than reported dietary intake, are not necessarily superior because
the disease may alter the levels of the nutrient. At least one cohort
study has shown that the association between lung cancer incidence
and low serum b -carotene levels declines with time after measurement.
These data show that low dietary intake or serum levels
‘predict’ cancer incidence in a descriptive sense: they
identify individuals at higher risk. They suggest that changing the
level of dietary factors may lead to a change in the incidence of
cancer, but they do not prove it. This hypothesis can only be proved
by a study in which intakes are actually changed - a randomised controlled
trial. Results from trials reported to date indicate that, with few
exceptions, high doses of b-carotene, vitamin C and vitamin E do not alter the incidence of cancers
or precancerous lesions. Indeed, two large studies have found that
smokers or those with a history of asbestos exposure have a higher
incidence of lung cancer if they took b-carotene.
A third study, with only a small proportion of smokers, found no difference
in lung cancer incidence in the active and placebo arms. Hence there
is no evidence to date that taking high doses of these nutrients will
reduce the incidence of cancer. Smokers should be dissuaded from taking
b-carotene (although it should be remembered
that the increase in risk is very small in relation to the risk due
to smoking).
These trials do not answer all possible questions.
For example, the effect of increasing intakes via the diet remains
to be tested. However, the contradictory results from the lung cancer
studies raise interesting questions for regulatory bodies concerning
the type and level of proof that is needed for things such a health
claims and functional foods.
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Macronutrients
and cancer (colo-rectal
and breast)
A Stewart Truswell
Human Nutrition Unit, University of
Sydney
There is more information on colo-rectal cancer and
breast cancer than other cancers. Doll and Peto (1981) considered
that 90% of avoidable colo-rectal cancer deaths were related to diet;
Willett (1995) revised the dietary contribution to 70% because of
clear evidence that physical activity plays an important protective
role. There are strong genetic contributions to colo-rectal cancer
(CRca) with familial adenomatous polyposis and several other syndromes.
CRca usually develops from adenomas. This precancerous condition makes
research on the aetiology easier. The changes in DNA along the sequence
from a tiny adenoma to metastasising carcinoma are better known than
for other cancers. A characteristic change is hypomethylation of DNA.
In half of over 20 case-control studies and in the US Nurses prospective
study dietary fat was a risk factor. In the latter, this was animal,
not vegetabl 1000 e, fat and the incidence of CRca is low in Greece
despite considerable consumption of olive oil. The mechanisms for
the effect of fat might be increased concentration of secondary bile
acids, or free fatty acids in the large intestine or diacylglycerol.
Red meat was a risk factor in 10/22 case-control studies and in the
US Nurses prospective study. The mechanism here may be via heterocyclic
amines (IQ, MeIQ, etc) on the surface of well-done meat, which are
potent mutagens. Plant foods were protective in 15 of Trock’s
23 case-control studies and in the US Nurses prospective. The latter
was not statistically significant but fibre and folate were significantly
protective against adenomas in the male Health Professionals prospective
study. Resistant starch adds to the metabolic effects of fibre (or
NSP) in the colon: dilution, lowered pH, production of butyrate, more
rapid transit. Vegetable foods also may protect via anti-cancer compounds:
glucosinolates in brassicas, sulphur-containing compounds in the onion
family, carotenoids, etc. Alcohol appears to be a risk factor for
rectal cancer, and calcium may protect against CRca by neutralising
fatty acids. The Australian Polyp Prevention Trial (APPT) shows that
low fat diet + wheat bran significantly reduce development of CR adenomas.
At least 7 trials of similar design to the APPT are ongoing, with
calcium or fibre or resistant starch or mixed vitamins or aspirin
alone or in combinations being tested.
Breast cancer (BC) is estimated by Doll, Peto (1981)
and by Willett recently to be 50% avoidable by dietary change-- but
which diet is so far elusive. In communities with high incidences
of BC the majority of cases are post-menopausal. There is no easily
sampled precancerous lesion and the genetic contribution only accounts
for 2 to 5% of the aetiology. Early menarche and/or late menopause
increase the risk, bilateral oophorectomy protects, and endogenous
plasma oestrogens are higher in post-menopausal BC. Prolonged lactation
gives some protection but only against the less common pre-menopausal
BC. Between countries BC mortality correlates very well with national
apparent fat consumption. But less than half of such consumption is
by women (men eat more than half the food) and several other indices
of affluence correlate nearly as well (eg. sugar consumption).
In rodents given chemical carcinogens (eg DMBA) fat
acts as a promoter of mammary tumours. In humans however, plasma cholesterol
does not predict BC in prospective studies and adipose fatty acid
pattern is the same in BC cases as controls. Over 20 case-control
studies have been reported. Overall, eg in a meta-analysis of 16 studies
in 11 countries the summary relative risk (RR) was only 1.12 for fat
and there was wide variability between studies. In the US Nurses study,
however, and in another 6 prospective studies the summary RR for fat
(by quintile) was a non-significant 1.05 and did not change down to
fat intakes of 20% energy. It now seems therefore that fat is unlikely
to be an important risk factor in adults. It may, however, have an
influence in adolescent girls (height seems to be a risk factor for
BC) or even in utero. Plant foods were reported protective in at least
10 case-control studies. A meta analysis of 12 such studies showed
RR of 0.83 for fibre and 0.63 for vitamin C. Either of these may be
surrogates for the active protective component(s). Promising possibilities
include phytoestrogens (soya intake was protective in a Singapore
study) or dietary fibre (interfering with reabsorption of oestrogens).
Alcohol has emerged recently as a possible weak risk factor. The average
RR is only around 1.25 and confounding cannot be excluded but alcohol
showed up in case-control studies in different countries and in the
US Nurses prospective study. Alcohol can raise plasma oestrogens.
No intervention trials are under way with macronutrients except possible
the NCI 20% fat trial, which has 1000 been on, off, on, off and maybe
on again.
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Macronutrients
and cardiovascular
disease risk
Madeleine J Ball
Deakin University, Melbourne, Australia
Food consists of a mixture of macronutrients, micronutrients
and non-nutrients. Differentiating the specific effects of individual
nutrients can be quite difficult; for example, fat contains fat soluble
vitamins and animal protein is rich in iron. There are also interactions
between food intake and genetic predisposition and life style. Our
evidence for the role of diet and its components on cardiovascular
disease comes from a range of sources, including epidemiological and
intervention studies. The end points have sometimes been cardiovascular
disease (CVD) events, but more often have been changes in what we
consider to be cardiovascular disease risk factors. These risk factors
obviously include hyperlipidaemia, lipid oxidation, raised blood pressure,
central obesity, hyper-glycaemia, insulin resistance, diabetes and
thrombotic status. There is also now interest in the role of endothelial
damage, endothelial local hormones, and vascular comp-liance with
emerging evidence that diet may effect these parameters.
The association between saturated fat intake and CVD,
and the different effects of saturated fats and unsaturated fats on
lipid parameters have been known for many years. There is now further
information that the various saturated fatty acids have very different
effects on LDL, HDL cholesterol, and probably also on thrombosis risk,
and that mono and polyunsaturated fatty acids alter the susceptibility
of LDL to oxidation in opposite ways. Our detailed knowledge about
the omega-6 and omega-3 fatty acids is also still evolving, although
the beneficial effects of the omega-3 rich fish oils on triglyceride
levels and haemostasis is well recognised. A few years ago concern
was raised about trans fatty acids in the diet: the relevance for
the overall Australian diet is unclear as intakes are estimated to
be 2.7-4.8g per day, but moves to reduce the trans fatty acid content
in some foods have been encouraged.
Concerning proteins, there have been a number of small
studies published over the last 10 years looking at the possible benefits
of soy protein. A recent meta analysis confirms the lipid lowering
effects of soy compared to animal protein, particularly in hypercholesterolaemic
individuals.
In the area of carbohydrate and carbohydrate rich
foods, consumption of fruit, vegetables and whole grains is being
promoted. The effects of various types of fibres, including soluble
fibres in oat bran and beans, and of resistant starch on lipid and
bile acid metabolism suggest these carbo-hydrates are beneficial.
There is much interest in other forms of plant fibre, the lignans
which can have phyto-estrogen properties and also in other phytoestrogens
present in foods such as soy products.
The relationship of alcohol to cardiovascular risk
remains the topic of ongoing discussion in prime medical journals.
There has been considerable debate about the role of alcohol per se
and of the many other compounds in alcoholic beverages such as wine,
where various flavonoids may contribute to the biochemical effects.
Our detailed knowledge of the influence of the various
nutrients on metabolism and CVD risk factors, and the inter-actions
related to the overall diet, lifestyle and the individual’s genetic
make-up is still increasing. The effect of the ApoE phenotype in determining
fat clearance and LDL levels has 1000 been well reported but there
is ongoing research on the role of genes for other apoproteins and
lipoprotein lipase.
The Dietary Recommendations for Australians are a
practical summary of our current knowledge on dietary measures likely
to reduce the risk of CVD and a number of other chronic diseases.
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Food intake
patterns in Beijing
Chinese
Zhang Hua2, Fu Pingl,
BH-H Hsu-Hage2, Wang Shu Qin1, Mark Wahlqvist2,
Xue Anna1
1 Institute of Nutrition
and Food Hygiene, CAPM, Beijing, China
2 Dept of Medicine, Monash University, Melbourne
Chinese food culture derives from one historical background.
The eating patterns of Chinese people, however, is one that evolves
and develops to interpret the very core food culture by adopting local
and available resources into cooking, thus creating diversity of eating.
Regional differences in cooking and eating have been documented in
both ancient and modern Chinese. In this report, we study food intake
patterns of 430 (men, 196; women, 234) Chinese adults living in Beijing,
China. This study used a 156-item quantitative food frequency questionnaire.
Last 12-month intakes were recalled. Subjects were randomly selected
from the Chunwen district of Beijing.
Men and women differed in food consumed. Men had a
significantly higher intake of wheat and wheat products and red meat,
and drank more tea and beer than did women, while women consumed more
leafy greens, fruits, nuts and seeds and eggs, and drank more milk
than did men. Women also had a high food variety in the diet. Younger
age groups and educated men and women incorporated a wider food variety
in their diet. Household income was positively associated with red
meat intake in men, and the consumption of non-staple wheat products
and wine in women. The consumption of tea decreased with increasing
education level, and increased with increasing age. The consumption
of soft drinks was negatively associated with age. In women, the intake
of legumes and products, leafy greens and cruciferous vegetables was
negatively associated with education level and positively associated
with age.
This cross-sectional study showed emerging evidence
that soft drinks were favoured amongst the young and replace tea as
a main beverage. In the past decades, China underwent major economic
transformation. This begins to reflect in food intake patterns in
sub-groups of the society (eg consumption of wine in women of higher
income family). Education brought about changes in consumption of
key culture marker foods (legumes, leafy greens and cruciferous vegetables)
in women.
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Cardiovascular
risk factor prevalence
in Beijing Chinese
Fu Ping1, BH-H Hsu-Hage2,
Wang Shu Qin1, Xue Anna1, ML Wahlqvist2,
Zhang Hua2
1 Inst. of Nutrition
and Food Hygiene ,CAPM, Beijing
2 Dept of Medicine, Monash University, Melbourne
Degrees of economical development and environmental
exposure have been associated with increased cardiovascular disease
mortality in developed countri 1000 es. Epidemiological evidence began
to show increased cardiovascular disease risk factor prevalence in
the fast growing Asia Pacific Region. ‘People of Chinese ethnicity’
is by far the largest population in the Region. While Chinese people
share similar principles in food culture and perhaps genetic make-up,
they differ in environmental exposure, such as local food supply.
For these reasons, there is a case to study eating habits and cardio-vascular
risk factor prevalence in Chinese people living in different parts
of China and compare with those of overseas Chinese.
In this study, we report cardiovascular risk factor
prevalence study of 433 (199 men and 234 women) Chinese adults living
in Beijing, China. All subjects were randomly selected from Beijing
Chongwen district according to the distribution of occupation reported
in 1990 census.
The mean levels of age, systolic blood pressure (SBP),
diastolic blood pressure (DBP), BMI, waist-to-hip ratio (WHR), CHOL,
TRIG, HDL, LDL and LDL-to-HDL ratio, were 46 years, 121mmHg, 77mmHg,
23.4kg/m2, 0.90, 4.59mmol/l, 1.29mmol/l, 2.77mmol/L, 1.22mmol/L
and 2.44 in men, respectively; 45 years, 117mmHg, 73mmHg, 23.6kg/m2,
0.82, 4.68mmol/l, 1.13mmol/l, 2.83mmol/l, 1.33mmol/l and 2.28 in women,
respectively. The prevalence of overweight/obesity was 33.9% for men
and 36.1% for women. 17% of men and 16% of women had defined hypertension.
The prevalence of combined hyper-lipidaemia was less then 1% for men
and women. 57% of men smoked regularly while 93% of women never smoked.
Compared to the collaborative study arms in Guangdong
Province of China and Melbourne Australia, the Beijing Chinese had
a moderate multiple cardiovascular risk factor (at least one of the
three risk factors present) prevalence (men: Guangdong, 78%; Beijing,
62%; Melbourne, 40%; women: Guangdong, 35%; Beijing, 20%; Melbourne,
16%). Smoking accounted for differences in multiple risk factor prevalence
in these Chinese populations; this is in spite of a high prevalence
of hypertension and overweight in Beijing Chinese.
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Dietary advice
in the nineties - prudent? practical? preventative?
‘Make food thy medicine’ Hippocrates 400 BC
Assoc Prof D Colquhoun
Wesley Medical Centre, Queensland
An elevated plasma cholesterol and specifically low
density lipoprotein cholesterol is the prime cause of coronary atherosclerosis.
The plasma level is determined by genetic predisposition and environmental
factors. The key environmental factor is the absolute amount of saturated
fat (SFA). The most important cholesterol raising SFA are palmitic,
myristic and lauric acids. The 25 year follow up of the Seven Countries
Study has shown that risk factors are universal, but the force of
a risk factor is determined by cultural factors. The 25 year follow
up has shown that a cholesterol of 5.4mmol/l in the south of Europe
is associated with a third of the risk as the same serum cholesterol
in northern Europe.
Kritchevsky, in a number of experiments in the 1970’s,
demonstrated in the animal model that hypercholesterolemia does not
always parallel atherogenicity. The recent Lyon Diet and Heart Study
confirmed the cardioprotective effect of a Mediterranean diet. This
post-infarction study, which compared a Prudent diet and a Mediterranean
diet was to run for 5 years, but it was stopped prematurely due to
the clear benefit of the Mediterranean type diet. There was a significant
70% reduction in total coronary events and a 70% redu 1000 ction in
total death rate. There is no difference in the serum cholesterol
between the treatment groups.
The Seven Countries Study has also demonstrated that
there is no relationship between percent of energy as fat in the diet
and body weight. The NHANES I Study (7,000 subjects) compared body
weight change over an 8-10 year period. Those with the lowest mean
fat intake (27% E) gained weight the same as those with a high fat
intake (47% E). The MONICA data on body weight across eighteen European
countries also showed no evidence of an association between fat intake
and median "BMI" among men and an inverse relationship among
women. Over the last decade %E from fat in the USA has decreased from
36% to 34%. At the same time average adult weight has increased by
3kg. The key factors for obesity are genes and lack of physical exercise.
The dietary guidelines in the Western world almost
universally suggest lowering fat as a percentage of calories to 30%
or less. Recently the World Health Organisation (WHO) revised this
to accept up to 35% of the calories as fat if the predominant fat
is monounsaturated fat. Restriction of total fat is unnecessary on
epidemiological, experimental and thera-peutic grounds. The emphasis
on decreasing total fat was based on the misconception that this would
have the benefit of lowering body weight and was the most effective
for lowering cholesterol.
A low fat diet is associated with poor compliance
and is unnecessarily restrictive. In the only direct comparative trial
using clinical endpoints a high fat Mediterranean type diet was clearly
superior in preventing CHD, and it of course tasted better.
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Practical
nutritional advice
to avoid CVD and cancer
Dr David Sullivan
Dept Clinical Biochemistry, Royal
Prince Alfred Hospital, Sydney
The burden of disease has changed from communicable
to noncommunicable diseases. Clinical nutrition has responded by looking
beyond the problem of single diseases caused by deficiency of individual
nutrients. Instead, it places greater emphasis on the relationship
between the diet, as judged by the nutrient and energy balance of
foods, and a broad group of degenerative disorders. Two of the most
important of these are cancer and cardiovascular disease (CVD).
Diet may play an important role in the aetiology of
a large proportion of cancers, although the proportion which are amenable
to prevention by dietary intervention may not be quite as large. Unfortunately,
others have made unjustified extrapolations concerning the possible
treatment of established cancer resulting in unrealistic expectations
amongst cancer sufferers. A summary of metanalyses of dietary risk
factors for 6 of the most common forms of malignancy will be presented
to demonstrate that the nutritional advice for prevention of CVD should
also lessen the risk of cancer. Intake of plant food, avoidance of
fat (especially of animal origin), and exercise reduce the risk of
several types of cancer. The only inconsistency seems to be alcohol,
which appears to reduce CVD risk, especially in men aged more than
40, whilst in women it mildly increases the risk of breast cancer.
There seems to be greater protection from foods rich
in particular nutrients rather than from single nutrients used in
isolation. Nevertheless, nutrients which may be important as far as
cancer is concerned include antioxidants, phyto-chemicals, carcinogens
and anticarcinogens. Antioxidants such as several vitamins and phytochemicals
may reduce the 1000 oxidative damage to DNA, typified by the hydroxylation
of guanidine to produce 8-OH guanidine.
Cancer appears to be less likely in individuals who
maintain adequate plasma levels of Vitamin C (>50m mol/L) and alpha Tocopherol (>
30m mol/L). There is also evidence to suggest that smoking increases 8-OH-guanidine
and that this can be rectified by consumption of large quantities
of brussel-sprouts. Examples of food sources of several nutrients
which reduce the risk of cancer will be discussed. Genistein will
be discussed as an example of a nutrient which may prevent cancer
by several mechanisms.
These concepts threaten to add to the complexity of
nutritional counselling, so an alternative approach will be described.
It is based on the fact that human genetic make-up has changed little
since our ancestors relied on hunting and gathering for their food
supply. In the meantime, there have been substantial changes in diet
due to agriculture and modern food technology. The two most crucial
elements associated with these changes are the decrease in dietary
diversity and reduction in exercise. Lack of dietary diversity is
associated with hypertension, obesity and diabetes. The simplified
approach to nutritional advice relies on the concepts of the nutrient
density and energy density of individual foods, and stresses the need
for adequate dietary diversity and exercise. The outcome in individual
patients depends on the interaction between genetic and environ-mental
factors where the diet is one of the major environ-mental factors.
We are in the early stages of identifying the interaction between
genetic traits and nutrition, as illus-trated by the increased risk
of carcinoma of the colon in fast acetylators whose diet contains
polycyclic hydrocarbons.
There is good evidence to assume that improved nutrition
can reduce the risk of both cancer and CVD in individuals and the
population at large.
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Energy adjustment- the concepts underlying the debate
Dorothy Mackerras
Menzies School of Health Research,
Darwin
Over the last decade, there has been quite a debate
in the literature about how energy should be controlled in studies
examining the relationship between diet and disease, especially when
macronutrients are the focus of interest. The four methods commonly
referred to-- the standard multi-variate, partition, density and residual
methods-- are said to be mathematically interchangeable. Yet Kushi
et al1 have shown that different relative
risks are obtained when each method is applied to the same data. How
can this be?
The problem often relates more to the way study results
are expressed than to mathematical minutiae. For example, we would
expect the relative risk describing the association for an 80g difference
in fat intake to be larger than the relative risk describing the association
for a 20g difference in intake. However, most studies present the
relative risk for the ‘high’ versus ‘low’ groups
but do not always show what the difference in intake is between the
groups. Once it is realised that the standard multivariate method
calculates relative risk over a larger range than the residual method,
the observation that the standard multivariate method generally gives
larger relative risks than the residual method becomes self-explanatory.
The difference in ranges between the two methods is much greater for
the macronut 1000 rients than the micronutrients. Both results are
correct and mutually consistent. However, if the results are to be
used to estimate likely effects in the community, it is important
to find the relative risk for the likely change and not to quote the
relative risk for an unrealistic amount of difference.
There is a strong correlation- about 0.9- between
fat expressed as a percentage of energy intake (density) and fat expressed
as a residual (in grams). Hence both methods place individuals into
the same groups and yield the same relative risks for ‘high’
versus ‘low’ intakes even though the units are different.
However this may not apply to other nutrients.
This poster illustrates several other examples. In
parti-cular all methods except the partition method give a relative
risk that summarises the effect of a change in all energy sources
of the diet, whereas the partition method does not. Also, the fact
that the micronutrients do not contribute to energy supply, which
is the factor being adjusted for, alters some of the considerations
related to this topic.
References:
- Kushi et al. Dietary fat and postmenopausal
breast cancer. J Natl Cancer Inst 1992;84: 1092-9
- Mackerras D. Energy adjustment - the concepts underlying
the debate. J Clin Epidemiol 1996 (in press)
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Relationship
of serum leptin to
total and truncal body fat
M Solin, MJ Ball, A de Silva, J Pascoe1,
M Kotovitz1, G Collier
School of Nutrition & Public Health,
Deakin University, Melbourne
1 Department of Medicine, Geelong Hospital,
Geelong
Leptin, the 16kDa protein product of the adipose specific
obese (ob) gene, is postulated as being involved in the regulation
of food intake and energy expenditure. Associations between serum
leptin and BMI have been described. In this study the relationship
between fasting serum leptin levels and measures of body fat distribution
was determined in 183 women aged 20-80 years and BMI 17-43 kg/m2.
Body composition was assessed by both anthropometric measures and
by Dual Energy X-ray Absorptiometry (DEXA) scans.
Serum leptin concentration was strongly positively
correlated with most anthropometric and DEXA measures. The relationship
between serum leptin (log transformed) and total grams of body fat
r = 0.68 (p< 0.0001), and % body fat, r=0.76(p<0.0001) were
strongest. The relationship with most parameters, including that with
BMI and waist circumference, ceased to be statistically significant
when the effect of total body fat (measured by DEXA) or % body fat
was adjusted for, using partial correlation analysis.
Truncal body fat, although a strong risk factor for
cardiovascular disease and non insulin dependent diabetes, did not
appear to have a strong relationship with serum leptin levels once
total body fat was accounted for (r fell from 0.66 to 0.05).
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The fate of
postprandial TRL-apo(a) complexes
Maria C Scariot, Christine Contacos1,
David R Sullivan1
Dept of Biochemistry 1000 , University
of Sydney
1Dept of Clinical Biochemistry, Royal Prince
Alfred Hospital, Camperdown, Sydney
The mechanism of clearance or catabolism of Lipoprotein(a)
is not known. A proportion of apolipoprotein(a) appears to become
associated with triglyceride-rich lipoproteins follow-ing fat intake.
It is postulated that TRL-apo(a) may be cleared by receptor mechanisms,
the more favourable being the LDL-receptor-related protein (LRP).
The present study was undertaken to investigate the fate of TRL-apo(a)
complexes following triglyceride (TG) hydrolysis by the enzyme lipoprotein
lipase (LPL), to determine whether TRL-apo(a) remained intact or dissociated.
This process may represent a pathway for Lipoprotein(a) catabolism.
Subjects consumed a fat-rich meal (1.5g fat/kg body
weight) and venous blood was collected 3 h later. TRL of Sf > 400
was isolated by ultracentrifugation and incubated with d > 1.006
g/ml serum fraction (4 h, 37°C) to obtain TRL-apo(a). TRL-apo(a) was
incubated with bovine LPL (67 U/ml mixture; LPL:TG ratio = 67) in
the presence of fatty acid-free albumin (4% (w/v)) at 37°C for 5 h.
The enzymatic reaction was terminated with diethyl p-nitrophenyl phosphate
(2 mmol/l). In addition, negative controls containing heat-inactivated
LPL, or no LPL were included. At each timepoint, aliquots were removed
for measurement of triglycerides (without free glycerol), and quantitation
of apo(a) by sandwich ELISA, and ultracentrifugation. The top and
bottom fractions were recovered for apo(a) Western blot analysis and
ELISA (Lp(a) measurement).
Qualitatively, Western blot analysis showed that TRL-apo(a)
clearly dissociated between 50% to 75% hydrolysis of TRL-triglycerides.
A range of 40% to 60% hydrolysis of TG caused an average of 50% dissociation
of apo(a) from TRL as measured by ELISA. TRL-apo(a) did not dissociate
with both negative controls. In conclusion, lipolysis leads to dissociation
of TRL-apo(a).
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Transport
of lipoprotein(a)
and low density lipoprotein across endothelial cells: effect of triglyceride-rich
lipoproteins
Christine Contacos, Ljubica Vrga, Wendy
Jessup1, David Sullivan
Dept of Clinical Biochemistry, Royal
Prince Alfred Hospital, Sydney
1Cell Biology Group, The Heart Research Institute,
Sydney
We assessed the transendothelial transport of lipoprotein(a)
(Lp(a)) and low density lipoprotein (LDL), in the presence or absence
of triglyceride-rich lipoproteins (TRL). Lp(a) differs from LDL in
that Lp(a) comprises of LDL with the glycoprotein, apolipoprotein(a)
(apo(a)), disulphide-linked to apoB-100. Differences in apo(a) size
(400-900 kDa) result in many apo(a) isoforms and, in general, apo(a)
size is inversely related to plasma Lp(a) concentration. Interestingly,
larger molecular weight apo(a) isoforms preferentially bind TRL both
in vitro and in vivo following a fat-rich meal. 125I-labelled
Lp(a) (affinity-purified by lysine-sepharose chromatography) and 125I-labelled
LDL were supplied to either the intimal or luminal surface (final
125I-lipoprotein total cholesterol = 0.05 mmol/L) of a
cell culture system containing human umbilical vein endothelial cell
(HUVEC) monolayers grown on porous collagen-coated filters. When TRL
were included, 125I-labelled Lp(a) and 125I-labelled
LDL were incubated (4h 37°C) with TRL of Sf<400 (final triglyceride
concentration = 1.5 mmol/L) before being applied to HUVECs. Intact
Lp(a) and LDL were transp 1000 orted in both directions across the
cell monolayers. The rate of luminal Ü intimal Lp(a) transport
was similar to LDL transport (mean % [SD] at 24h; 12.9% [4.1] vs 10.7%
for Lp(a) and LDL, respec-tively). Both lipoproteins were transported
at similar rates from the intimal Ü luminal face of the monolayer.
When 125I-Lp(a) was pre-incubated with TRL, 20% of 125I-label
became associated with TRL. However, Lp(a) transport was similar (in
both directions) with or without TRL (24h luminal Ü intimal; 14.0% [4.0] vs
12.7% [1.9] for Lp(a) and TRL+Lp(a), respectively). LDL, in the presence
of TRL, was transported at a similar rate to Lp(a), with or without
TRL. When lipoproteins of d<l .006 g/mL were isolated after incubation
of 125I-Lp(a) with TRL and applied to the luminal side
of the HUVECs, there was a small (non-significant) reduction in transport
(23.7% [4.6]) compared to Lp(a) transport in the absence of TRL (31.8%
[4.0]). Although retention of 125I-labelled material on
the filters was similar for Lp(a) and LDL, it was significantly increased
for Lp(a), but not LDL, in the presence of TRL (P< 0.01). We conclude
that; i) Lp(a) and LDL are transported at similar rates across the
endothelium, and ii) the rate which Lp(a) is transported across the
endothelium does not appear to be affected by its association with
TRL.
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Effects of
changes in plasma
triglyceride and cholesterol ester transfer protein activity on cholesterol
ester transfer and LDL particle size in hypercholesterolaemic patients
David Sullivan, Christine Contacos, and
Philip Barter1
Dept of Clinical Biochemistry, Royal
Prince Alfred Hospital, Sydney
1 Dept of Medicine, Royal Adelaide Hospital,
Adelaide
We studied the effects of postprandial lipaemia and
pravastatin therapy, which produce opposite effects on plasma triglyceride
(TG) and cholesterol ester transfer protein (CETP) activity, on cholesterol
ester transfer (CET) and low density lipoprotein (LDL) particle size
in 19 patients (12 male, 7 female, ages 30 - 74 years) with primary
hypercholesterolaemia (TC>6.5 mmol/L and LDL-C >4.5 mmol/L).
After 6 weeks’ therapy with placebo or pravastatin 40 mg nocte
according to a double blind randomised cross-over design, samples
were collected fasting and 6h after an oral fat load (0.88g/kg) comprising
skim milk cream and peanut oil (90% fat, 5.2% protein, 4.8% carbohydrate).
Lipids, lipoproteins, CET (modified from Mann’ et al.), CETP
activity (modified from Groener2 et al.) and LDL Stokes’ diameter
(gradient gel electrophoresis on 3-13% Gradipore gels) were assayed
and statistical analysis was performed with BMDP software.
The oral fat load significantly increased TG but did
not alter CETP activity during placebo and pravastatin phases. Pravastatin
significantly reduced TG and CETP activity in both the fasting and
postprandial state compared to the equivalent phases on placebo. CET
increased significantly following the fat load but pravastatin attenuated
both fasting and postprandial levels of CET. LDL Stokes’ diameter
did not change.
CET correlated with TG and high density lipoprotein-cholesterol
(HDL-C), but the relationship with TG was curvilinear. LDL Stokes’
diameter also correlated with TG and HDL-C. Relationships involving
TG were enhanced during the postpr 8d1 andial phase, and LDL size
was most strongly correlated with triglyceride rich lipoproteins (TRL)
(r = -0.54 fasting, r = -0.81 postprandially). CET was only correlated
with LDL Stokes’ diameter during the postprandial phase (r =
-0.62). Pravastatin weakened these correlations. Stepwise regression
suggested that postprandial TRL accounted for 85% of the variance
in CET, with a further 4% attributable to CETP activity. Postprandial
TRL also accounted for 65% of the variability in LDL Stokes’
diameter.
We sought to determine whether there was a threshold
TRL level which would predict the transition between normal and small
dense LDL particles. Even though LDL Stokes’ diameter does not
change acutely following an oral fat load, our results suggest that
postprandial lipaemia exerts a strong cumulative effect on LDL size.
References:
- Mann CJ, Yen FT, Grant AM, and Bihane BE. (1991)
Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia.
J Clin Invest 88:2059- 66.
- Groener JEM, Pelton RW, Kostner GM. (1986) Improved
estimation of cholesteryl ester transfer/exchange activity in serum
or plasma. Clin Chem 32:283-6.
Copyright © 1996 [Asia Pacific Journal of Clinical Nutrition]. All
rights reserved.
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