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Table 1 Studies reporting candidate biomarkers for cereal food intake

From: Biomarkers of 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]

  1. 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