Accurate measurements of dietary exposures are required in order to evaluate compliance in dietary intervention studies, to find associations with disease outcomes, or to monitor dietary changes in populations. Traditionally, dietary exposure has been measured with self-reported methods, usually dietary recalls or food frequency questionnaires (). However, random and systematic errors such as recall bias and difficulty in assessing portion sizes are inherent in such methods and often result in inconsistencies (, ). As a result, efforts have been directed towards the application of dietary biomarkers as more objective measures of dietary exposure (). These biomarkers have been used to measure nutritional status and exposure to bioactive molecules in foods, as surrogate indicators of food intake, and also to validate measures of dietary intake (). Biomarkers are also useful when little or no data exist on food composition, as is often the case for bioactive molecules such as glucosinolates or food contaminants such as aflatoxins (, ).
Epidemiological studies have measured a variety of dietary biomarkers in plasma/serum (carotenoids, fatty acids, vitamins, polyphenols, food contaminants, and enzymes), red blood cells (fatty acids, carotenoids and haemoglobin adducts) and to a lesser extent in urine (polyphenols, vitamins, inorganic compounds and amino acids) (Table 1). Some of these biomarkers correspond to nutrients and bioactive compounds and have been utilized as surrogate biomarkers of food intake (Table 2): polyphenols, carotenoids and vitamin C for fruits and vegetables (, ), alkylresorcinols for wholegrain cereals (, ), isoflavones for soy (), amino acids and fatty acids for meat (, ), fatty acids for dairy products and fish (, ) and polyphenols for tea and wine (, ). Dietary biomarkers not only include natural food constituents but also certain food additives like iodine in milk () or food contaminants like polychlorinated biphenyls in fatty fish (), which are often specific of certain exposed populations. Other biomarkers are directly derived from the digestion and gut absorption of food constituents, or are endogenous metabolites that have been altered by exposure to specific nutrients.
Dietary biomarkers are not without their limitations, as they may be altered due to possible interactions with genetic factors, physiological or health status (i.e. age or obesity) (), dietary factors such as fats for lipophilic biomarkers (), and lifestyle factors such as alcohol intake or smoking (). Their levels also vary over time according to their pharmacokinetic properties and some have very short half-lives, thus are only useful in populations where their dietary sources are regularly and frequently consumed. Important qualities of dietary biomarkers include sufficient sensitivity to measure exposures within ranges commonly found in the populations of interest, and specificity for a particular food or food group.
Traditionally, single biomarkers have been utilised to characterize complex dietary exposures such as consumption of a whole food group or intake of a group of compounds with related biological activities. However, analytical approaches based on estimation of combinations of dietary constituents may provide more accurate measurements of dietary exposure. Metabolomics constitutes a comprehensive approach to identify new panels of biomarkers, specific or common to particular foods or food groups (Table 3). This should greatly improve the assessment of exposure to classes of food bioactive compounds, food groups or dietary patterns.
|Amino acids||1-Methylhistidine, 3-methylhistidine|
|Aliphatic acyclic compounds||Urea|
|Chemical elements||Nitrogen, 15N/14N|
|Fatty acids||9-cis-Linoelaidic acid, α-linolenic acid, arachidonic acid, cis-docosapentaenoic acid, cis-octadecenoic acid, cis-palmitoleic acid, DHA, DPA, eicosadienoic acid, eicosenoic acid, elaidic acid, EPA, lauric acid, linoelaidic acid, linoleic acid, linolenic acid, myristic acid, myristoleic acid, oleic acid, ω-3 PUFAs, ω-6-PUFA, palmitic acid, petroselaidic acid, phytanic acid, phytanic acid, rumenic acid, stearic acid, tetradecenoic acid, trans-hexadecenoic acids, trans-octadecadienoic acid, trans-octadecenoic acid, vaccenic acid|
|Vitamins||Vitamins B1, B2, B5, B6, B12, C, D, E, K1, folic acid, nicotinamide|
|Inorganic compounds||Iodine, phosphorus, potassium, selenium, sodium, zinc, iron|
|Carotenoids||α-Carotene, β-carotene, β-cryptoxantin, lutein, lycopene, zeaxanthin|
|Polyphenols||4-O-Methylgallic acid, 5-heneicosylresorcinol, 5-heptadecylresorcinol, 5-nonadecylresorcinol, 5-tricosylresorcinol, apigenin, caffeicacid, chlorogenicacid, daidzein, DHBA, DHPPA, dihydrodaidzein, dihydrogenistein, enterodiol, enterolactone, equol, eriodictyol, gallic acid, genistein, glycitein, hesperetin, isorhamnetin, kaempferol, luteolin, m-coumaricacid, naringenin, ODMA, phloretin, quercetin, resveratrol, tamarixetin|
|Food contaminants||Aflatoxins, mercury, PCBs|
|Cooking products||Acrylamide, 1-hydroxypyrene glucuronide|
|Endogenous metabolites and enzymes||5-Hydroxytryptophol / 5-Hydroxyindole-3-acetic acid, ALAT, ASAT, GGT|
|Fruits||Apple||Kaempferol, isorhamnetin, m-coumaric acid, phloretin|
|Orange||Caffeic acid, hesperetin, proline betaine|
|Citrus fruits||Ascorbic acid, β-cryptoxanthin, hesperetin, naringenin, proline betaine, vitamin A, zeaxanthin|
|Fruits (total)||4-O-Methylgallic acid, β-cryptoxanthin, carotenoids (mix), flavonoids (mix), gallic acid, hesperetin, isorhamnetin, kaempferol, lutein, lycopene, naringenin, phloretin, vitamin A, vitamin C, zeaxanthin|
|Tomato||Carotenoids (mix), lycopene, lutein|
|Vegetables, leafy||Ascorbic acid, beta-carotene, carotenoid (mix)|
|Vegetables, root||Ascorbic acid, α-Carotene, β-carotene|
|Vegetables (total)||Ascorbic acid, α-carotene, β-carotene, β-cryptoxanthin, carotenoids (mix), enterolactone, lutein, lycopene|
|Fruit & vegetables||Fruit & vegetables (total)||α-Carotene, apigenin, ascorbic acid, β-carotene, β-cryptoxanthin, carotenoids (mix), eriodictyol, flavonoids(mix), hesperetin, hippuric acid, lutein, lycopene, naringenin, phloretin, phytoene, zeaxanthin|
|Cereal products||Wholegrain rye||5-Heptadecylresorcinol, 5-pentacosylresorcinol, 5-tricosylresorcinol|
|Wholegrain wheat||5-Heneicosylresorcinol, 5-tricosylresorcinol, alkylresorcinols (mix)|
|Wholegrain cereals (total)||5-Heneicosylresorcinol, 3,5-dihydroxybenzoic acid, 3-(3,5-dihydroxyphenyl)-1-propanoic acid), 5-pentacosylresorcinol, 5-tricosylresorcinol, alkylresorcinols (mix)|
|Seeds||Soy products||Daidzein, genistein, isoflavones (mix), O-desmethylangolensin|
|Meats||Meat||1-Hydroxypyrene glucuronide, 1-methylhistidine,|
|Meat, beef||Pentadecylic acid|
|Animal products||Animal products (total)||1-Methylhistidine, 3-methylhistidine, margaric acid, pentadecylic acid, phytanic acid|
|Dairy products||Milk, dairy products||Iodine, margaric acid, pentadecylic acid, phytanic acid|
|Fish||Fish, fatty||DHA, EPA, long chain ω-3 PUFAs, PCB toxic equivalents, pentachlorodibenzofuran, polychlorinated biphenyl 126, polychlorinated biphenyl 153, ω-3 PUFAs|
|Fish, lean||Long chain ω-3 PUFAs|
|Beverages (non-alcoholic)||Tea||4-O-Methylgallic acid, gallic acid, kaempferol|
|Beverages (alcoholic)||Wine||4-O-Methylgallic acid, caffeic acid, gallic acid, resveratrol metabolites|
|Beverages (alcoholic) (total)||5-Hydroxytryptophol / 5-hydroxyindole-3-acetic acid, carbohydrate-deficient transferrin, ethyl glucuronide, γ-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase|
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