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unit 3.
assessing exposure to the environment
chapter 11.
Dietary intake
and nutritional status
Jiyoung Ahn, Christian C. Abnet, Amanda J. Cross, and Rashmi Sinha
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U te
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Summary a
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damage and tissue concentrations metabolism, as food is a complex
Though dietary factors are
implicated in chronic disease risk, are also discussed. mixture; thus, the absorption and
assessment of dietary intake has metabolism of any single nutrient is
limitations, including problems affected by the presence of another.
Biomarkers of nutritional
with recall of complex food intake exposure and nutritional For example, iron taken with vitamin
patterns over a long period of status: An overview C is absorbed more efficiently than
time. Diet and nutrient biomarkers by itself, but phytate can bind iron
may provide objective measures and make it unavailable. Cooking
Food frequency questionnaires
of dietary intake and nutritional (FFQ), multiple food records, and 24- is another important factor that can
status, as well as an integrated hour recalls are the most common change concentrations of nutrients
measure of intake, absorption and methods to assess dietary intake or can form compounds not normally
metabolism. Thus, the search for in nutritional epidemiologic studies present in foods. Obtaining this level
an unbiased biomarker of dietary (1). The strengths and limitations of of detail using dietary assessment
intake and nutritional status is an dietary assessment methods, as well instruments is generally not feasible.
important aspect of nutritional as nutritional status biomarkers, are Furthermore, food composition
epidemiology. This chapter reviews summarized in Table 11.1. Generally, tables are not available for all
types of biomarkers related to the accuracy of the information nutrients, limiting the assessment
dietary intake and nutritional status, collected depends on the ability to of many of them. Finally, there
such as exposure biomarkers of diet integrate complex eating patterns are numerous nutrients, such as
and nutritional status, intermediate concisely and the subject’s memory. selenium and vitamin D, that cannot
endpoints, and susceptibility. Novel be measured adequately in the food
Current dietary assessment
biomarkers, such as biomarkers source.
methods may not completely
of physical fitness, oxidative DNA capture nutrient interactions and
Unit 3 • Chapter 11. Dietary intake and nutritional status 189
Table 11.1. Strengths and limitations of intake assessment methods and nutritional status biomarkers
Assess by Limitations Strengths
Estimate of dietary intake Questionnaire - Prone to different types of bias - Easier to administer in
FFQ - Dependent on memory population-based
Food records - May not capture variability in studies
24-hour recall eating pattern - Long-term intake
Diet history - does not account for absorption estimate
Food composition table or bioavailability when foods
are cooked or eaten as complex
mixtures
- Not comprehensive especially
for diaries and recalls
- Focused on specific nutrient
- Many newer dietary compounds
of interest not covered
Nutritional status Biomarker of: - Collection - Objective measure
- absolute intake - Storage - Error structure
- correlated intake - Sensitivity different than
- Specificity questionnaire-based
- Laboratory variability information
- Single measure may not be - Integrated measure
representative of usual
Diet and nutrient exposure biomarker (> 0.8) (2). The two well- the methods used to measure the
biomarkers may be independent studied recovery biomarkers are recovered products are technically
of the subject’s memory or urinary nitrogen and doubly-labelled challenging (4).
the capacity to describe foods water. Urinary nitrogen is an example Urinary nitrogen and doubly-
consumed. Biomarkers may provide of a recovery biomarker of protein labelled water are the only validated
an integrated measure of intake, intake. A 24-hour urine collection is recovery biomarkers, but it must
absorption and metabolism, which required, and subjects should take still be assumed that the testing
may improve the accuracy of para-aminobenzoic acid (PABA) period is representative of the
the estimation of the association tablets with the three main meals of subjects’ usual habits. The relative
between the nutrient and disease, the day to validate the completeness complexity and high cost of these
but limit the direct interpretation of of the collection (3). The amount of methods prevents these biomarkers
the connection between intake and nitrogen recovered in a 24-hour from being applied to large cohort
disease. However, since biomarkers urine collection can be converted studies. Thus, these biomarkers
may be affected by biospecimen to protein intake using estimates of are often used as gold standards
the percent of nitrogen excreted in for validating dietary questionnaires
collection methods, storage
conditions and laboratory variations, urine (~81%). Doubly-labelled water or developing correction factors to
these factors must be carefully is another example of a recovery estimate measurement attenuation.
considered in the study design. biomarker for energy expenditure,
in which the average metabolic Biomarkers of correlated intake:
Types of biomarkers rate of a human is measured over Concentration biomarkers
a period of time. A dose of doubly-
Exposure biomarkers labelled water, in which both the Biomarkers of correlated intake are
hydrogen and the oxygen have based on concentrations in the body
Biomarkers of absolute intake: been partly or completely replaced (i.e. in blood, urine, saliva, hair, nails
Recovery biomarkers for tracking purposes (i.e. labelled) or tissue), reflecting current intake
with an uncommon isotope of these status. Concentration biomarkers
Biomarkers of absolute intake, elements, is administered to the are correlated with intake, such
or recovery biomarkers, reflect individual. The loss of deuterium and that higher concentrations of these
a balance between intake and O-18 is then measured over time by biomarkers result from higher
output over a defined period, with regular sampling of heavy isotope intake. The measured concentration
relatively high correlation between concentrations in the body water is a consideration of intake, uptake,
the absolute dietary intake and the (by sampling saliva, urine or blood); and metabolism. Concentration
190
biomarkers can enhance dietary For example, in the EPIC study, useful estimate of true exposure.
assessment, or in some cases be high serum concentrations of In addition, because menstruation
the primary method of assessment α-tocopherol were associated with can lead to very different amounts
of nutrient exposure. significantly lower risks of gastric of iron loss in women, the estimation
cancer, but estimated dietary intake of intake may not be biologically
Nutrients of vitamin E was not (11). relevant. There are several
Biomarkers as the primary biomarkers for iron, including
This type of biomarker may be method of assessment. This type of serum iron and serum ferritin; both
used to enhance assessment and biomarker may be used to measure are subject to homeostatic control
measurement of dietary components intake for dietary components that and influenced by inflammation,
that are currently captured by dietary are not currently captured by dietary respectively.
questionnaires. Vitamin C is thought questionnaires. The selenium Vitamin D is a third example of
to protect against oxidative stress, but content of foods is highly dependent a nutrient that is not well measured
by intake estimates. Liver, fatty
assessment of intake is complicated on local soil concentrations,
by the varying concentration in foods which range over several orders fish, ergocalciferol in mushrooms,
and fortified milk are major dietary
and the widespread and episodic of magnitude. Wheat is an
use of vitamin C supplements. important selenium source in many sources of vitamin D; however, for
Vitamin C is water soluble and populations, but the selenium content most people, the primary source of
responsive to short-term changes of wheat can vary considerably; vitamin D is produced internally upon
in intake; any single measure of therefore, wheat used to produce exposure of the skin to ultraviolet B
vitamin C may not accurately rank flour, bread, pasta and other noodles (UVB). This production depends
subjects’ typical exposure. Because from different geographic areas can on the melanin content of the skin
the serum or plasma must be stored result in variable levels of selenium. and the amount of UVB exposure.
using metaphosphoric acid or other Several well-established biomarkers Estimating sun exposure is complex,
preservatives, few epidemiologic of selenium have been developed, because of differences in time spent 1
t 3 1
outside, amount of exposed skin, i
studies use vitamin C biomarkers including serum and toenail n r
(5). selenium, which provide a valid weather conditions and sunscreen U te
use. Thus, circulating 25-hydroxy p
estimate of selenium status. More a
Vitamin E, especially
α-tocopherol, has been the focus of than 20 studies have examined the vitamin D is considered a more Ch
a great deal of scrutiny because of association between serum, plasma reliable indicator of vitamin D status,
its potential benefits in reducing the or nail selenium and risk of prostate capturing both dietary intake and
risk of cancers and cardiovascular cancer; a meta-analysis concluded endogenous production. 25-hydroxy
diseases (6,7). The correlation that serum and plasma selenium vitamin D has been used in several
of estimates of vitamin E intake were consistently lower in cases prospective epidemiologic studies
from questionnaires with serum compared with controls (12). Serum to assess the role of vitamin D in
concentrations is highly variable, and toenail selenium are common chronic disease prevention (13).
since most dietary vitamin E is validated biomarkers of selenium
obtained from vegetable oils used in status (9). Non-nutritional components
cooking (8) and intake of such oils is Iron is another example of a
not estimated well by food frequency concentration biomarker than may An important aspect of the
better reflect exposure and provide
questionnaires (FFQs)(9). For connection between diet and
example, the correlation between a more informative assessment of chronic disease is the assessment
the FFQ-estimated vitamin E intake the association between iron and of potentially hazardous dietary
and serum α-tocopherol ranged from disease than intake estimates. components. The human diet may
0.47 in Dutch men to −0.08 in Italian Dietary iron is acquired from plant contain inadvertent contaminants
men in the European Prospective and animal sources, as well as that are formed during food
Investigation into Cancer and fortified grain in some countries. processing or cooking. Examples of
Nutrition (EPIC) (10). Many studies There are large differences in contaminants formed during cooking
have found an association between the bioavailability and absorption are heterocyclic amines (HCAs) and
serum α-tocopherol levels and pathways of heme and non-heme polycyclic aromatic hydrocarbons
chronic disease risk, but not with iron, suggesting that estimating (PAHs). Some developing countries
dietary estimates of vitamin E. total iron intake will not give a lack an integrated food delivery
Unit 3 • Chapter 11. Dietary intake and nutritional status 191
system that affords the chance to Figure 11.1. Potential heterocyclic amines (HCAs) biomarkers (71)
regulate some undesirable food
contaminants, such as mycotoxins
or by-products of processing
(e.g. silica from grinding grain or
nitrosamines in salted fish).
Food-cooking by-products.
HCAs and PAHs, both known
carcinogens in animal models, are
formed in the highest concentrations
in meat cooked well-done using
high-temperature cooking methods,
such as pan-frying or grilling. The
assessment of exposure to these
compounds can be estimated
using questionnaires, but may
benefit from the use of biomarkers With a large sample size, though, Mycotoxins. Fungal carcinogens
of exposure. Moreover, there is urinary HCAs could still be used to are another example of a food
no national database available for validate intake of HCAs as estimated contaminant whose study may
food by cooking methods. A limited by questionnaires. benefit from the use of an exposure
database, CHARRED, has been HCA-DNA adducts can be biomarker. Aflatoxin (AFB1) is
created that is based on the type measured in lymphocytes and HCA produced by Aspergillus flavus and
of meat, cooking method and the metabolites bound to circulating other related species, and plays an
degree of doneness (http://charred. blood proteins, such as haemoglobin important role in the high rates of
cancer.gov/). (Hb) or serum albumin (SA). The hepatocellular carcinoma seen in
HCAs are formed from the measurement of these biomarkers southern China and parts of Africa
reaction at high temperatures can provide an estimate of exposure (20). Assessment of AFB1 exposure
between creatine or creatinine and the biologically effective dose, by questionnaire is very limited,
(found in muscle meats), amino but they do not provide a measure of as the amount of infection in grain
acids, and sugars (14–17). HCAs genetic damage directly in the target and the amount of toxin produced
undergo extensive metabolism by tissue. DNA and protein adducts varies by locality, crop and storage
phase I and II enzymes. Various of HCAs have been detected in conditions. In communities where
biomarkers of HCAs have been experimental animal models by most food is grown and stored at
investigated in urine, blood and hair, 32P-postlabelling. There is a paucity home, the ability to develop general
with each having advantages and of data on HCA biomarkers in exposure metrics applicable to
limitations. humans, however, as their detection questionnaire data is minimal.
Urine is a useful biological fluid Therefore, the development of
and quantification remains a
for the measurement of exposure to challenging analytical problem: the biomarkers of exposure to these
various classes of carcinogens, since concentration of HCAs in the diet is dietary contaminants is critical.
large quantities may be obtained at the parts-per-billion level, and the Extensive work on the
non-invasively. HCAs are rapidly quantity of HCA biomarkers formed metabolism of AFB1 led to the
absorbed from the gastrointestinal in humans occurs at very low levels. identification of AFB1 adducts
tract and eliminated in urine as Accumulation of HCAs in human with DNA and albumin, including
multiple metabolites, with several hair, which may serve as a potential AFB1-DNA adducts in urine (21),
percent of the dose present as the long-term biomarker to assess as correlates of the effective dose
unmetabolized parent compound chronic exposure of HCAs, has of AFB1. Using urinary AFB1-DNA
within 24 hours of consuming grilled been suggested but not yet validated adducts as a biomarker, a nested
meats. HCAs in urine have short (18,19). Similar, but larger, issues case–control study demonstrated a
half-lives, however, and may not be exist for PAHs, as these compounds 5-fold increased risk of liver cancer
ideal measures of “usual” intake in are even more ubiquitous in the food in subjects who had measurable
etiologic studies, especially if there source and environment. levels of these adducts (22). In the
is substantial day-to-day variability. same study, dietary aflatoxin intake
192
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