Table 1.
Studies reporting candidate biomarkers for cereal food intake
| Discriminating metabolites/candidate biomarkers | Dietary factor | Study design | Number of subjects | Analytical method | Sample type | Primary reference(s) |
|---|---|---|---|---|---|---|
| Biomarkers of total whole grain (WG) intake | ||||||
| Total ARs |
WG products RG products |
Intervention study, crossover, randomized (6 weeks) | 30 | GC-MS | Plasma | [30] |
| ARs | WG cereal | Observational study | 33 | GC-MS | Plasma | [55] |
| ARs |
WG products RG products |
Intervention study, parallel, randomized (12 weeks) | 50 | LC-MS/MS | Plasma | [56] |
| ARs |
WG diet RG diet |
Intervention study, crossover, randomized (6 weeks) | 33 | LC-MS/MS | Plasma | [57] |
| AR |
WG products WG rye WG bread |
Observational study | 522 | GC-MS | Plasma | [58] |
|
ARs Betaine |
WG diet RG diet |
Intervention study, crossover, randomized (2 weeks) | 17 |
GC-MS/MS (ARs) LC-MS/MS (betaine) |
Plasma | [59] |
| Total ARs (C17:0, C19:0, C21:0, C23:0, C25:0) |
WG products Habitual diet |
Intervention study, parallel, randomized (16 weeks) | 316 | GC-MS | Plasma | [31] |
|
Total AR AR (C17:0-C25:0) |
WG products | Observational study | 360 | GC-MS | Plasma | [60] |
| AR (C17:0, C19:0, C21:0, C23:0, C25:0) | WG products | Observational study | 407 | LC-MS | Plasma | [61] |
| AR (C17:0-C25:0) | WG products | Observational study | 20 | GC–MS | Adipose tissue | [62] |
|
DHBA DHPPA DHBA+DHPPA |
WG products Cereal fiber |
Observational study | 104 | GC-MS | Urine | [63] |
|
DHBA DHPPA Total metabolites |
WG foods Cereal fiber |
Observational study | 66 | GC-MS | Urine | [64] |
|
DHBA DHPPA |
WG products Fiber |
Observational study | 2833 | HPLC | Plasma | [65] |
| DHPPA |
WG products WG rye and wheat |
Observational study | 100 | HPLC-CEAD | Urine | [66] |
|
2-Aminophenol-Slf HPAA-GlcA HHPAA HMBOA-GlcA HBOA glycoside HPPA HMBOA DHPPA-GlcA 3,5-Dihydroxyphenylethanol-Slf DHPPTA-Slf Hydroxybenzoic acid-Slf Dihydroferulic acid-Slf Enterolactone-GlcA Pyrraline 3-Indolecarboxylic acid-GlcA Riboflavin N-α-Acetylcitrulline 2,8-Dihydroxyquinoline-GlcA |
White bread WG bread |
Observational study | 155 | HPLC-q-TOF-MS | Urine | [67] |
|
5-Nonadecyl-1,3-benzenediol-GlcA (AR) 5-(16-Heneicosenyl)-1,3-benzenediol-GlcA |
WG products, fatty fish and bilberries diet WG diet Refined wheat bread diet |
Intervention study, parallel, randomized (12 weeks) | 106 | UHPLC-q-TOF-MS | Plasma | [53] |
|
Proline Ornithine Arginine |
Grain protein-based diet (wheat, bran, rice, and maize) Dairy protein-based diet (milk and milk products, yogurt and cheese) Meat protein-based diet (pork, beef, and chicken) |
Intervention study, crossover, randomized (1 week) | 100 | LC-tripleQ-MS | Plasma | [68] |
| Biomarkers of whole-grain wheat and rye intake | ||||||
| Total ARs |
WG rye bread and WG wheat bread Gluten-free diet |
Intervention study, parallel (2 weeks) | 9 | GC-MS | Plasma and erythrocyte membranes | [69] |
| Total ARs |
WG rye and wheat Cereal fiber |
Observational study | 51 | GC-MS | Plasma | [70] |
|
Total ARs AR C17:0, C19:0, C21:0, C23:0, C25:0 Enterolactone |
Rye bread Wheat bread |
Intervention study, crossover, randomized (8 weeks) | 39 | GC-MS | Plasma | [71] |
|
Total AR (C17:0, C19:0, C21:0, C23:0, C25:0) AR C17:0/C21:0 Enterolactone |
WG wheat WG rye crisp bread |
Intervention study, crossover, randomized (1 week) | 15 | GC-MS |
Plasma (AR) erythrocyete membrane (AR) Lipoproteins (AR) Serum (enterolactone) |
[69] |
|
Total ARs (C17:0–C25:0) AR C17:0/C21:0 |
Nordic diet (rich in WG rye and wheat) Control diet |
Intervention study, parallel, randomized (18–24 weeks) | 158 | GC-MS | Plasma | [32] |
|
Total ARs AR C17:0/C21:0 |
WG wheat RG wheat |
Intervention study, parallel, randomized (12 weeks) | 72 | LC-MS/MS | Plasma | [72] |
|
DHBA DHPPA |
Rye bread Bread fiber |
Observational study | 122 | HPLC-CEAD |
Urine Plasma |
[73] |
|
DHBA DHPPA |
Rye bread with plant sterols Rye bread |
Intervention study, parallel, randomized (4 weeks) | 68 | HPLC-CEAD | Plasma | [74] |
|
DHBA DHPPA |
Rye bread | Intervention study (postprandial trial) | 15 | HPLC-CEAD | Urine | [75] |
|
DHBA DHPPA |
Rye bread | Intervention study (postprandial trial) | 15 | HPLC-CEAD | Plasma | [76] |
|
DHBA DHPPA |
Rye | Observational study | 60 | HPLC-CEAD |
Urine Plasma |
[77] |
|
DHBA DHPPA |
WG rye and wheat | Observational study | 52 | GC-MS | Urine | [78] |
|
DHBA DHBA glycine DHPPA DHPPTA |
RG wheat bread, WG wheat bread | Intervention study (postprandial trial) | 12 |
LC-MS HPLC-CEAD |
Urine | [79] |
|
HHPAA-GlcA HHPAA-Slf HPAA-Slf HBOA-GlcA Phenylacetylglutamine derivative Creatinine N-feruloylglycine-Slf |
WG rye foods | Intervention study (8 weeks) | 33 | FIE-MS | Urine | [80] |
|
DHFA Ferulic acid |
WG wheat products Refined wheat products |
Intervention study, parallel, randomized (8 weeks) | 80 | HPLC-MS/MS |
Urine Serum Feces |
[81] |
|
3,5-Dihydroxyhydrocinamic acid sulfate Ascorbic acid 2-Aminophenol-Slf Nonanedioic acid DHPPA-GlcA Indolylacryloylglycine Enterolactone-GlcA DHPPA-Slf Ferulic acid-4-Slf 2,4-Dihydroxy-1,4-benzoxazin-3-one-Slf 3,5-Dihydroxyphenylethanol-Slf 1,3,4,5-Tetrahydroxycyclohexane-1-carboxylic acid Others non-identified metabolites |
WG rye bread Refined wheat bread |
Intervention study, crossover, randomized (4 weeks) | 20 | UPLC-q-TOF-MS | Urine | [50] |
| Biomarkers of specific fractions of foods of wheat and rye intake | ||||||
|
Total ARs AR (C17:0, C19:0, C21:0, C23:0, C25:0) |
WG grains Cereal fiber Bran Total fiber Legume fiber |
Observational study | 165 | GC-MS | Plasma | [82] |
|
Total ARs AR C17:0/C21:0 |
Cereal fiber | Observational study | 2845 | GC-MS | Plasma | [83] |
|
Total ARs AR C17:0/C21:0 |
Cereal fiber | Observational study | 2744 | GC-MS | Plasma | [84] |
|
Total AR AR C17:0/C21:0 |
Rye WG/bran Refined wheat |
Intervention study, crossover, randomized (6 weeks) | 17 | GC-MS | Plasma | [85] |
|
AR C23:0 AR C25:0 AR C17:0/C21:0 |
Rye bran flakes | Intervention study (postprandial trial) | 6 | GC-MS | Plasma | [86] |
|
ARs (plasma) DHBA (urine) DHPPA (urine) |
Cereal fiber | Observational study | 56 | HPLC-CEAD |
Urine Plasma |
[87] |
|
DHBA DHPPA |
Cereal fiber | Observational study | 56 | HPLC-CEAD | Plasma | [88] |
|
HPAA-Slf HHPAA-Slf |
WG sourdough rye bread White bread with native unprocessed rye bran White bread with bioprocessed rye bran White bread |
Intervention study, crossover, randomized (postprandial trial) | 12 | LC-q-TOF-MS | Plasma | [52] |
|
2,6-dihydroxybenzoic acid 2-aminophenol-Slf |
High fiber diet Low fiber diet |
Intervention study, crossover, randomized (5 weeks) | 25 | UPLC-q-TOF-MS | Plasma | [89] |
| Ferulic acid |
Rye bran bread Inert wheat bran |
Intervention study, crossover, randomized (6 weeks) | 18 | HPLC | Urine | [90] |
|
Ferulic acid Vanillic acid Sinapic acid 3,4-Dimethoxybenzoic acid Phenylpropionic acid 3-Hydroxyphenylpropionic acid |
Whole wheat bread with bioprocessed bran Whole wheat bread with native bran |
Intervention study, crossover, randomized (postprandial trial) | 8 | GCxGC-q-TOF-MS |
Urine Plasma |
[91] |
|
Ferulic acid Sinapic acid |
White wheat bread with bioprocessed rye bran White wheat bread with native rye bran |
Intervention study, crossover, randomized (postprandial trial) | 15 | GC-MS | Urine | [92] |
|
Indole-2-carboxylic acid Hydrocinnamic acid α-tocopherol Benzoic acid Cycloartenol Pantothenic acid Phenylacetic acid β-sitosterol |
Heat-stabilized rice bran | Intervention study, parallel, randomized (4 weeks) | 7 | GC-MS | Feces | [93] |
| Biomarkers of quinoa | ||||||
| Even-numbered AR | Quinoa | Intervention study | NS |
LC-MS/MS GC-MS/MS |
Plasma | [94] |
| Biomarkers dependent on gut microbiota | ||||||
| Enterolactone |
High-fiber bread Fiber Fruits and berries |
Observational study | 1099 | TRFIA | Plasma | [95] |
| Enterolactone | WG products | Observational study | 1889 | TRFIA | Plasma | [95] |
| Enterolactone |
High-fiber rye High-fiber wheat Low-fiber foods |
Intervention study, crossover, randomized (4 weeks) | 28 | TRFIA | Plasma | [96] |
| Enterodiol |
WG diet RG diet |
Intervention study, crossover, randomized (12 weeks) | 13 | HPLC-CEAD) | Urine | [97] |
|
Enterolactone Enterodiol |
Quinoa flakes Corn flakes |
Intervention study, parallel, randomized (4 weeks) | 35 | HPLC |
Urine Serum |
[98] |
|
Enterodiol (serum) Enterolactone (serum & urine) |
Flaxseed Rice |
Intervention study, parallel (6 weeks) | 27 | HPLC |
Urine Serum |
[99] |
Abbreviations: AR alkylresorcinols, CEAD coulometric electrode array detection, DHBA 3,5-dihydroxy-benzoic acid, DHBA glycine 2-(3,5-dihydroxybenzamido)acetic acid, DHFA dihydroferulic acid, DHPPA 3-(3,5-dihydroxyphenyl)-1-propanoic acid, DHPPTA 5-(3,5-dihydroxyphenyl)pentanoic acid, FIE flow infusion electrospray-ionization, GC gas chromatography, GCxGC two-dimensional GC, GlcA glucuronide, HBOA 2-Hydroxy-1,4-benzoxazin-3-one, HHPAA 2-hydroxy-N-(2-hydroxyphenyl) acetamide, HPAA N-(2-hydroxyphenyl) acetamide, HPLC high-performance liquid chromatography, LC liquid chromatography, MS mass spectrometry, MS/MS tandem mass spectrometry, NS not specified, q-TOF quadrupole time-of-flight, RG refined-grain, Slf sulfate, TRFIA time-resolved fluoroimmunoassay, WG whole-grain