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ONLINE SUPPLEMENTAL MATERIAL

ONLINE SUPPLEMENTAL TEXT

Materials:

Ach and SNP were purchased from Sigma-Aldrich (Poole, UK). 5-caffeoylquinic acid, p-

coumaric acid, 3-phenylpropionic acid, cinnamic acid, 4- methoxycinnamic acid, 3-(4-

methoxyphenyl)propionic acid, di-methoxycaffeic acid (methylferulic acid) and di-

methoxydihydrocaffeic acid (methyldihydroferulic acid) were purchased from Sigma-Aldrich

Chemie GmbH (Buchs, Switzerland). Glacial acetic acid, acetonitrile for LC-MS, water for

LC-MS where purchased by Biosolve (Valkenswaard, Netherlands), and ethanol p.a. was

obtained from Merck KGaA (Darmstadt, Germany). Caffeic acid, ferulic acid,

dihydrocaffeic acid, m-coumaric acid, o-coumaric acid and isoferulic acid were purchased

from Extrasynthese (Lyon, France). Dihydroferulic acid was obtained from Fluka (Buchs,

Switzerland). 3-caffeoylquinic acid, 4-caffeoylquinic acid were obtained from Chengdu

Biopurify Phytochemicals Ltd (Chengdu,Sichuan, China). 3-Feruloylquinic acid, 4-

feruloylquinic acid and 5-feruloylquinic acid, dihydroisoferulic acid, m-dihydrocoumaric

acid, o-dihydrocoumaric acid, p-dihydrocoumaric acid, 4-caffeoylquinic-1,5-lactone, 3-

caffeoylquinic-1,5-lactone, 3-feruloylquinic-1,5-lactone, 4-feruloylquinic-1,5-lactone,

dihydroferulic-4´-O-sulfate, ferulic-4´-O-sulfate, caffeic-4´-O-sulfate, dihydrocaffeic-4´-O-

sulfate, dihydrocaffeic-3´-O-sulfate, caffeic-3´-O-sulfate, isoferulic-3´-O-sulfate,

dihydroisoferulic-3´-O-sulfate, 5-caffeoylquinic-4´-O-sulfate, 5-caffeoylquinic-3´-O-sulfate,

5-feruloylquinic-4´-O-sulfate, p-coumaric acid-4´-O-sulfate, m-coumaric acid-3´-O-sulfate,

dihydro-m-coumaric-3´-O-sulfate, dihydro-p-coumaric-4´-O-sulfate, caffeic-4´-O-

glucuronide, dihydrocaffeic-4´-O-glucuronide, dihydroferulic-4´-O-glucuronide, caffeic-3´-

O-glucuronide, ferulic-4´-O-glucuronide, dihydrocaffeic-3´-O-glucuronide, isoferulic-3´-O-

glucuronide, dihydroisoferulic-3´-O-glucuronide, 5-feruloylquinic-4´-O-glucuronide,

dihydro-m-coumaric-3´-O-glucuronide, dihydro-p-coumaric-4´-O-glucuronide, p-coumaric-4

´-O-glucuronide and m-coumaric-3´-O-glucuronide were synthesized at Nestlé Research

Centre, Switzerland. Stable isotope labeled d13C2-caffeic acid standard used as internal

standard was purchased from Orphachem S.A., France. Labeled dihydroisoferulic-d2-3´-O-

sulfate disodium salt and labeled dihydroisoferulic-d2-3´-O-glucuronide were used as internal

standards for the sulfated and glucuronidated metabolites, respectively were purchased by

Toronto Research Chemicals, Canada.

ONLINE SUPPLEMENTAL TABLES

Supplementary Table 1. MS/MS transitions of CGA obtained in negative mode and used to

quantify phenolic and chlorogenic acids in human plasma

CompoundRete

n-

tion

time

(min)

MS1 MS2 (m/z)

DP1

(V)

CE

1(V

)

CE

2

(V)

CX

P1

(V)

CX

P2

(V)

Pare

nt

ion

Base

peak

Secon

dary

peak

3-Caffeoylquinic acid 5.0 353.0 190.9 179.0 -70 -22 -20 -9 -9



3-Caffeoylquinic-1,5-lactone 10.9 335.0 161.0 133.0 -95 -28 -54 -9 -9

4-Caffeoylquinic-1,5-lactone 11.7 335.0 161.0 133.0 -105 -30 -56 -9 -13

Caffeic acid 7.8 179.1 135.0 134.1 -85 -22 -30 -7 -5

Dihydrocaffeic acid 7.5 181.1 137.0 109.0 -65 -16 -20 -7 -7

Caffeic-3´-O-glucuronide 7.1 354.9 178.8 134.8 -25 -24 -52 -11 -7

Caffeic-4´-O-glucuronide 4.7 354.9 178.9 134.8 -25 -24 -52 -11 -7

Dihydrocaffeic-3´-O-glucuronide 7.2 356.9 112.8 180.9 -90 -22 -24 -7 -11

Dihydrocaffeic-4´-O-glucuronide 6.7 356.9 113.0 181.0 -80 -22 -26 -7 -11

5-Caffeoylquinic-3´-O-sulfate 7.2 432.9 190.8 353.0 -25 -32 -24 -9 -15

5-Caffeoylquinic-4´-O-sulfate 6.1 432.9 191.0 179.0 -100 -38 -32 -9 -7

Caffeic-3´-O-sulfate 7.2 259.0 179.1 134.9 -70 -22 -32 -9 -9

Caffeic-4´-O-sulfate 6.4 259.0 178.9 135.0 -60 -22 -40 -9 -9

Dihydrocaffeic-3´-O-sulfate 6.6 261.0 137.0 180.8 -5 -36 -32 -7 -47

Dihydrocaffeic-4´-O-sulfate 6.3 261.0 136.8 180.8 -50 -30 -24 -9 -11

3-Feruloylquinic acid 8.1 367.0 192.9 133.9 -5 -22 -40 -9 -9

4-Ferulloylquinic acid 10.9 367.0 173.0 NA -80 -20 NA -9 NA

5-Ferulloylquinic acid 10.8 367.0 190.8 172.9 -25 -20 -24 -9 -11

3-Feruloylquinic-1,5-lactone 14.2 349.0 174.9 160.0 -115 -26 -42 -9 -9

4-Feruloylquinic-1,5-lactone 14.7 349.0 174.8 160.0 -70 -24 -50 -7 -9

Ferulic acid 12.1 193.1 134.0 177.8 -65 -20 -14 -7 -9

Isoferulic acid 13.0 193.1 178.0 133.9 -90 -16 -22 -9 -9

Methylferulic acid 17.0 207.2 103.0 163.1 -80 -18 -12 -7 -9

Dihydroferulic acid 11.6 195.1 136.1 120.9 -105 -20 -36 -7 -11

Dihydroisoferulic acid 12.8 195.1 135.9 150.9 -70 -18 -14 -19 -7

Methyldihydroferulic acid 16.0 209.0 150.0 165.1 -120 -16 -16 -11 -9

5-Feruloylquinic-4´-O-glucuronide 5.9 543.1 191.0 366.9 -120 -38 -24 -5 -17

Ferulic-4´-O-glucuronide 6.5 368.9 113.0 193.0 -85 -16 -18 -5 -11

Isoferulic-3´-O-glucuronide 9.3 369.0 112.8 193.0 -20 -20 -22 -7 -11

Dihydroferulic-4´-O-glucuronide 8.3 370.9 112.9 175.0 -25 -22 -18 -17 -9

Dihydroisoferulic-3´-O-glucuronide 9.9 371.0 112.9 195.0 -35 -24 -26 -7 -9

5-Feruloylquinic-4´-O-sulfate 7.5 446.9 190.8 193.1 -30 -32 -30 -11 -9

Ferulic-4´-O-sulfate 8.1 273.0 193.0 133.9 -70 -20 -38 -9 -9

Isoferulic-3´-O-sulfate 9.6 273.0 177.9 134.0 -70 -26 -48 -9 -9

Dihydroferulic-4´-O-sulfate 8.1 275.0 195.0 79.9 -75 -22 -58 -11 -11

Dihydroisoferulic-3´-O-sulfate 9.1 275.0 195.1 135.8 -70 -24 -32 -9 -11

m-Coumaric acid 12.7 163.1 118.9 90.8 -60 -20 -30 -9 -13

o-Coumaric acid 14.6 163.1 119.1 116.9 -55 -16 -30 -7 -11

p-Coumaric acid 10.5 163.1 118.9 93.0 -55 -20 -38 -9 -11

m-Dihydrocoumaric acid 11.6 165.0 121.0 105.9 -70 -16 -30 -7 -5

o-Dihydrocoumaric acid 13.1 165.0 121.0 106.1 -30 -18 -30 -9 -5

p-Dihydrocoumaric acid 10.1 165.0 121.0 59.0 -80 -14 -16 -9 -9

m-Coumaric-3´-O-glucuronide 8.2 339.0 112.9 119.0 -55 -22 -56 -13 -11

p-Coumaric-4´-O-glucuronide 4.8 339.0 113.0 118.9 -80 -18 -54 -5 -15

Dihydro-m-coumaric-3´-O-

glucuronide 8.5 341.0 113.0 121.0 -45 -24 -42 -5 -5

Dihydro-p-coumaric-4´-O-

glucuronide 6.9 341.0 113.0 59.0 -75 -22 -54 -5 -7

m-Coumaric acid-3´-O-sulfate 9.0 242.9 163.0 119.0 -50 -24 -42 -7 -9

p-Coumaric acid-4´-O-sulfate 7.3 242.9 119.0 163.0 -55 -38 -20 -7 -7

Dihydro-m-coumaric-3´-O-sulfate 8.2 244.9 165.0 121.0 -90 -24 -32 -5 -9

Dihydro-p-coumaric-4´-O-sulfate 7.4 244.9 165.0 58.9 -65 -24 -36 -7 -9

Cinnamic acid 19.4 147.0 103.0 NA -20 -14 NA -9 NA

4-Methoxycinnamic acid 19.9 176.9 133.0 117.0 -60 -14 -42 -9 -7

3-Phenylpropionic acid 18.5 149.0 105.0 NA -65 -14 NA -7 NA

3-(4-Methoxyphenyl)propionic acid 18.7 179.0 135.2 NA -80 14 NA -9 NA

Internal standards

Labeled d13C2-caffeic acid 7.8 182.1 137.0 136.0 -30 -20 -34 -9 -11

Labeled dihydroisoferulic-3´-O-

sulfate disodium salt9.8 374.0 113.0 198.0 -60 -24 -28 -7 -13

Labeled dihydroisoferulic-3´-O-

glucuronide9.1 277.8 198.1 136.2 -15 -24 -36 -5 -9

DP, declustering potential; CE, collision cell entrance potential; CXP, collision cell exit

potential

Supplementary Table 2. Quantification of plasma chlorogenic acid metabolites after

consumption of high polyphenol coffee containing 310 mg chlorogenic acid by healthy

volunteers1

Compound High polyphenol coffee2

0h 1h 3h 5h

3-Caffeoylquinic acid 0.63 ± 0.39 5.23 ± 0.61c, e 3.09 ± 0.33b, d 2.38 ± 0.28

4-Caffeoylquinic acid 1.31 ± 0.49 7.68 ± 0.78c, e 4.17 ± 0.41c, e 2.91 ± 0.32

5-Caffeoylquinic acid 5.80 ± 1.25 19.02 ± 1.57c 12.72 ± 1.72b, e 8.19 ± 1.25f

3-Caffeoylquinic-1,5-lactone 0.04 ± 0.41 0.78 ± 0.43 ND ND

4-Caffeoylquinic-1,5-lactone 0.37 ± 0.40 0.92 ± 0.42 0.63 ± 0.34 0.27 ± 0.37

Caffeic acid 4.58 ± 2.82 5.62 ± 2.45 3.88 ± 1.74 3.77 ± 1.85

Dihydrocaffeic acid 2.34 ± 0.90 6.41 ± 0.68 8.81 ± 2.88 64.88 ± 31.78c, e

Caffeic-3´-O-glucuronide 0.71 ± 0.65 1.27 ± 0.66 0.71 ± 0.36 0.54 ± 0.64


Dihydrocaffeic-3´-O-glucuronide 0.93 ± 0.41 0.88 ± 0.32 0.66 ± 0.26 7.96 ± 4.94


5-Caffeoylquinic-3´-O-sulfate 0.74 ± 0.47 2.72 ± 0.66a, d 2.23 ± 0.33 1.69 ± 0.29

5-Caffeoylquinic-4´-O-sulfate 1.04 ± 0.37 1.50 ± 0.81 0.9 ± 0.35 1.08 ± 0.47

Caffeic-3´-O-sulfate 1.58 ± 0.58 68.75 ± 6.23c, e 42.8 ± 3.39c, e 36.46 ± 5.00c, e

Caffeic-4´-O-sulfate 1.85 ± 0.48 7.82 ± 0.85c, e 3.47 ± 0.47 3.66 ± 0.63

Dihydrocaffeic-3´-O-sulfate 7.64 ± 1.87 26.47 ± 2.76 32.51 ± 8.35 167.98 ± 61.59c, e

Dihydrocaffeic-4´-O-sulfate 0.44 ± 0.26 1.53 ± 0.29 0.94 ± 0.4 6.87 ± 3.62a, d

3-Feruloylquinic acid 1.06 ± 0.38 10.79 ± 0.93c, e 5.1 ± 0.44c, e 2.61 ± 0.45

4-Feruloylquinic acid 0.26 ± 0.36 8.40 ± 0.81c, e 4.83 ± 0.41c, e 2.29 ± 0.26

5-Feruloylquinic acid 0.77 ± 0.32 17.90 ± 1.44c, e 9.7 ± 0.68c, e 4.75 ± 0.44c, d

3-Feruloylquinic-1,5-lactone 0.32 ± 0.33 0.72 ± 0.31 0.2 ± 0.23 0.06 ± 0.25


Ferulic acid 1.46 ± 0.17 8.57 ± 0.80 c, e 4.59 ±0.52 9.42 ± 3.09c, e

Isoferulic acid 1.38 ± 0.56 14.74 ± 1.47c, e 6.67 ± 0.91b, d 6.77 ± 1.41c, d

Methylferulic acid 14.35 ± 5.18 96.41 ± 6.82c, e 72.25 ± 6.40c, e 60.26 ± 6.33c, e

Dihydroferulic acid 32.97 ± 6.83 45.74 ± 8.16 64.32 ± 2.19c 247.87 ± 62.64f

Dihydroisoferulic acid 52.33 ± 36.31 64.08 ± 28.70 64.42 ± 20.04 189.09 ± 66.96

Methyldihydroferulic acid 22.64 ± 8.35 25.42 ± 7.47 27.91 ± 7.51 25.81 ± 5.91

5-Feruloylquinic-4´-O-glucuronide ND 16.87 ± 3.88c, e 15.19 ± 3.67a, d 12.09 ± 3.13a

Ferulic-4´-O-glucuronide 7.19 ± 1.70 25.78 ± 2.13c, e 18.81 ± 1.65a 17.2 ± 1.74

Isoferulic-3´-O-glucuronide 8.17 ± 3.13 53.39 ± 6.85c, e 40.57 ± 5.15c, e 41.64 ± 6.10c, e

Dihydroferulic-4´-O-glucuronide 11.50 ± 2.54 13.01 ± 2.09 16.07 ± 4.20 60.54 ± 19.9a

Dihydroisoferulic-3´-O-glucuronide 14.48 ± 11.03 18.69 ± 10.70 16.86 ± 7.79 30.34 ± 9.87

5-Feruloylquinic-4´-O-sulfate 1.12 ± 0.33 3.90 ± 0.72c, d 2.84 ± 0.49 1.57 ± 0.36

Ferulic-4´-O-sulfate 3.69 ± 0.70 43.26 ± 3.70c, e 18.94 ± 1.36c, e 20.79 ± 2.75c, e

Isoferulic-3´-O-sulfate 0.67 ± 0.38 9.62 ± 0.99c, e 4.88 ± 0.4c, e 4.44 ± 0.58c, e

Dihydroferulic-4´-O-sulfate 4.45 ± 1.10 10.54 ± 2.21 10.73 ± 3.3 31.28 ± 9.46c, e

Dihydroisoferulic-3´-O-sulfate 8.38 ± 5.58 14.46 ± 4.58 11.54 ± 3.40 20.8 ± 5.24

m-Coumaric acid 1.17 ± 0.47 1.00 ± 0.46 1.75 ± 0.73 2.23 ± 0.73

o-Coumaric acid 2.29 ± 0.42 2.57 ± 0.42 2.89 ± 0.34 2.42 ± 0.42

p-Coumaric acid 1.13 ± 0.34 2.27 ± 0.30 1.4 ± 0.36 1.34 ± 0.35

m-Dihydrocoumaric acid 157.28 ± 64.47 125.59 ± 49.52

173.47 ±

78.88 335.86 ± 117.14

o-Dihydrocoumaric acid 6.64 ± 2.18 9.24 ± 2.48 8.48 ± 1.67 7.72 ± 1.57

p-Dihydrocoumaric acid 4.60 ± 2.84 7.42 ± 4.33 6.63 ± 2.86 6.57 ± 2.58

m-Coumaric-3´-O-glucuronide 0.68 ± 0.38 3.12 ± 0.46a 2.39 ± 0.59 2.3 ± 0.59

p-Coumaric-4´-O-glucuronide 0.41 ± 0.72 0.45 ± 0.66 0.96 ± 0.28 0.3 ± 0.66

Dihydro-m-coumaric-3´-O-glucuronide 10.17 ± 6.66 4.89 ± 1.32 6.17 ± 2.38 36.97 ± 27.38

Dihydro-p-coumaric-4´-O-glucuronide 0.51 ± 0.38 1.89 ± 0.45 0.56 ± 0.28 0.88 ± 0.53

m-Coumaric acid-3´-O-sulfate 1.15 ± 0.60 1.29 ±0.68 0.94 ± 0.66 2.06 ± 0.93

p-Coumaric acid-4´-O-sulfate 1.02 ± 0.38 1.07 ± 0.34 0.73 ± 0.27 0.43 ± 0.30

Dihydro-m-coumaric-3´-O-sulfate 7.75 ± 2.54 10.55 ± 2.13 8.95 ± 3.27 12.5 ± 5.24

Dihydro-p-coumaric-4´-O-sulfate 2.21 ± 0.59 3.00 ± 0.45 2.36 ± 0.56 1.9 ± 0.54

Cinnamic acid 3.93 ± 0.96 4.06 ± 1.24 3.77 ± 0.9 4.58 ± 1.3

4-Methoxycinnamic acid 23.57 ± 10.09 6.61 ± 3.31 7.71 ± 2.39 7.13 ± 2.17

3-Phenylpropionic acid 394.3 ± 74.93 394.10 ± 60.65

349.58 ±

45.52 386.76 ± 65.41

3-(4-Methoxyphenyl)propionic acid 12.41 ± 9.63 13.93 ± 8.00 13.05 ± 7.26 8.85 ± 3.66

1 Results are expressed as mean ± SEM (n=15).

2 Concentration of plasma chlorogenic acid metabolites (nM).

a Significant difference by ttest between baseline and post intervention (1, 3, or 5h), p<0.05; b

Significant difference between baseline and post intervention (1, 3, or 5h), p<0.01; c

Significant difference between baseline and post intervention (1, 3, or 5h), p<0.001.

d Significant difference by ttest between control and intervention drink, p<0.05; e Significant

difference between control and intervention drink, p<0.01; e Significant difference between

control and intervention drink, p<0.001.


consumption of low polyphenol coffee containing 89 mg chlorogenic acid by healthy

volunteers1.

Compound Low polyphenol coffee2

0h 1h 3h 5h

3-Caffeoylquinic acid 0.62 ± 0.39 4.14 ± 0.52c, e 2.36 ± 0.39 1.69 ± 0.41

4-Caffeoylquinic acid 0.56 ± 0.39 5.35 ± 0.50c, e 3.26 ± 0.49b 2.33 ± 0.48

5-Caffeoylquinic acid 5.33 ± 0.91 9.86 ± 0.90 8.68 ± 1.02 6.98 ± 0.98



Caffeic acid 6.7 ± 3.66 6.86 ± 2.77 5.79 ± 2.52 6.14 ± 2.94

Dihydrocaffeic acid 2.45 ± 0.59 7.76 ± 0.82 6.6 ± 1.93

19.89 ±

7.26

Caffeic-3´-O-glucuronide 1.77 ± 0.63 52.97 ± 4.28

34.57 ±

4.54

22.21 ±

4.29



Dihydrocaffeic-4´-O-glucuronide

10.06 ±

3.55 9.91 ± 2.68

10.44 ±

2.58

17.42 ±

5.59



Caffeic-3´-O-sulfate 0.06 ± 0.65 1.11 ± 0.54f 0.71 ± 0.33g 0.16 ± 0.67e

Caffeic-4´-O-sulfate 1.66 ± 0.50 6.43 ± 0.98c, e 3.91 ± 0.62 2.54 ± 0.52

Dihydrocaffeic-3´-O-sulfate 9.84 ± 2.72 31.59 ± 3.58

22.80 ±

3.16

70.32 ±

19.83

Dihydrocaffeic-4´-O-sulfate 0.91 ± 0.61 2.86 ± 0.75 2.05 ± 1.00 3.55 ± 1.76

3-Feruloylquinic acid 0.98 ± 0.34

11.61 ±

1.03c, e

4.56 ± 0.68b,

e 2.03 ± 0.44

4-Feruloylquinic acid 0.11 ± 0.36 8.24 ± 0.82c, e

4.17 ± 0.61c,

e 1.79 ± 0.42

5-Feruloylquinic acid 0.77 ± 0.29 7.34 ± 0.80c, e 4.29 ± 0.69b 2.32 ± 0.48



Ferulic acid 1.37 ± 0.16

7.00 ± 0.37b,

d 2.96 ± 0.27 3.06 ± 0.36

Isoferulic acid 1.87 ± 0.43

12.77 ±

0.84c, e 5.29 ± 0.73 4.24 ± 0.78

Methylferulic acid

19.11 ±

6.64

113.81 ±

4.91c, e

66.98 ±

5.99c, e

55.02 ± 6.5c,

e

Dihydroferulic acid

37.98 ±

10.17 40.34 ± 5.64

39.11 ±

10.94

103.55 ±

26.96

Dihydroisoferulic acid

47.35 ±

19.75

55.09 ±

11.35

47.69 ±

16.99

93.91 ±

27.9

Methyldihydroferulic acid

16.11 ±

5.52 19.33 ± 4.55

19.04 ±

4.10

20.72 ±

4.06

5-Feruloylquinic-4´-O-

glucuronide ND 3.88 ± 2.01 6.46 ± 2.40 3.23 ± 2.25

Ferulic-4´-O-glucuronide 6.17 ± 1.53

23.05 ±

2.51c, e

20.33 ±

4.51b

11.61 ±

1.89

Isoferulic-3´-O-glucuronide 7.81 ± 1.98

47.33 ±

3.57c, e

35.13 ±

3.89b, e

28.70 ±

3.32d

Dihydroferulic-4´-O-glucuronide 13.7 ± 4.03 15.97 ± 3.42

15.21 ±

3.27

32.24 ±

7.33

Dihydroisoferulic-3´-O-

glucuronide

10.13 ±

4.94 11.11 ± 4.02

10.30 ±

2.76

14.17 ±

3.92

5-Feruloylquinic-4´-O-sulfate 1.04 ± 0.33 1.70 ± 0.54 1.99 ± 0.55 1.37 ± 0.44

Ferulic-4´-O-sulfate 3.26 ± 0.78

38.19 ±

2.47c, e

15.91 ±

1.39c, e

11.49 ±

1.39a, e

Isoferulic-3´-O-sulfate 0.69 ± 0.35 7.73 ± 0.49c, e

4.24 ± 0.50c,

e 2.71 ± 0.37

Dihydroferulic-4´-O-sulfate 4.61 ± 1.17 7.53 ± 0.81 6.39 ± 1.35

14.48 ±

3.79

Dihydroisoferulic-3´-O-sulfate 6.88 ± 3.12 12.46 ± 2.33 8.26 ± 1.61

11.59 ±

2.32

m-Coumaric acid 1.84 ± 0.45 1.39 ± 0.45 1.58 ± 0.45 2.56 ± 0.46

o-Coumaric acid 2.68 ± 0.41 2.12 ± 0.38 2.60 ± 0.36 2.92 ± 0.47

p-Coumaric acid 1.21 ± 0.40 1.63 ± 0.38 1.28 ± 0.34 1.18 ± 0.38

m-Dihydrocoumaric acid

171.2 ±

53.77

105.98 ±

27.8

118.47 ±

34.53

380.3 ±

158.43

o-Dihydrocoumaric acid 9.98 ± 3.64 11.5 ± 3.68

10.59 ±

3.32 9.92 ± 3.14


m-Coumaric-3´-O-glucuronide 0.81 ± 0.42 3.42 ± 0.49a 2.48 ± 0.62 2.14 ± 0.53



glucuronide 4.69 ± 1.20 5.89 ± 1.15 7.33 ± 3.88

27.64 ±

23.75


glucuronide 0.94 ± 0.53 2.37 ± 0.61 1.45 ± 0.57 0.84 ± 0.56

m-Coumaric acid-3´-O-sulfate 1.49 ± 0.62 1.56 ± 0.39 0.96 ± 0.66 2.20 ± 0.92



sulfate

10.96 ±

2.45 14.83 ± 2.13 7.69 ± 1.45 9.93 ± 1.16


Cinnamic acid 4.67 ± 1.07 2.98 ± 0.91 2.64 ± 0.77 2.93 ± 0.67

4-Methoxycinnamic acid

32.94 ±

12.19 10.45 ± 3.98 9.45 ± 3.70 6.55 ± 3.34

3-Phenylpropionic acid

491.11 ±

97.01

397.02 ±

80.54

311.62 ±

51.22

324.47 ±

46.51

3-(4-Methoxyphenyl)propionic

acid

18.55 ±

14.2 3.75 ± 1.95 4.35 ± 2.79 2.39 ± 2.72

1Results are expressed as mean ± SEM (n=15).

2Concentration of plasma chlorogenic acid metabolites (nM).

a Significant difference between baseline and post intervention (1, 3, or 5h), p<0.05; b



d Significant difference by ttest between control and intervention drink, p<0.05; e Significant

difference between control and intervention drink, p<0.01; f Significant difference between

control and intervention drink, p<0.001.


consumption of control drink containing 0 mg chlorogenic acid by healthy volunteers1

Compound Control

0h 1h 3h 5h






Caffeic acid 6.16 ± 3.41 3.69 ± 2.12 3.28 ± 1.92 2.66 ± 1.64

Dihydrocaffeic acid 3.09 ± 0.77 2.41 ± 0.98 2.56 ± 0.59 1.64 ± 0.73




Dihydrocaffeic-4´-O-glucuronide 15.52 ± 5.49 12.61 ± 4.43 10 ± 3.45 8.74 ± 3.04



Caffeic-3´-O-sulfate 0.74 ± 0.76 0.72 ± 0.71 0.55 ± 0.52 0.55 ± 0.74

Caffeic-4´-O-sulfate 1.64 ± 0.36 1.7 ± 0.47 1.38 ± 0.39 1.33 ± 0.36

Dihydrocaffeic-3´-O-sulfate 10.93 ± 2.45 9.88 ± 2.63 7.18 ± 2 6.02 ± 2

Dihydrocaffeic-4´-O-sulfate 0.31 ± 0.25 0.31 ± 0.28 0.12 ± 0.24 0.13 ± 0.23

3-Feruloylquinic acid 0.79 ± 0.36 1.5 ± 0.67 1.18 ± 0.41 1.05 ± 0.35





Ferulic acid 1.56 ± 0.17 1.51 ± 0.45 1.12 ± 0.28 0.99 ± 0.31

Isoferulic acid 2.07 ± 0.65 2.11 ± 0.85 1.7 ± 0.54 1.53 ± 0.46

Methylferulic acid 13.05 ± 3.35 17.1 ± 6.3

15.23 ±

4.84 13.63 ± 4.01

Dihydroferulic acid 33.3 ± 8.2 25.3 ± 7.29 15.96 ± 4 12.83 ± 3.78

Dihydroisoferulic acid

115.99 ±

76.93

91.02 ±

63.13

56.35 ±

34.69

35.45 ±

17.76

Methyldihydroferulic acid 18.22 ± 3.66 16.52 ± 3.16

16.28 ±

3.23 14.51 ± 2.94

5-Feruloylquinic-4´-O-glucuronide -0.5 ± 1.92 -0.14 ± 1.91 -0.06 ± 1.94 -0.17 ± 1.95

Ferulic-4´-O-glucuronide 7.12 ± 1.92 8.18 ± 2.62 7.53 ± 2.54 4.81 ± 1.98

Isoferulic-3´-O-glucuronide 14.93 ± 5.78 11.62 ± 5.4 8.43 ± 3.42 6.12 ± 2.58

Dihydroferulic-4´-O-glucuronide 19.23 ± 6.61 14.77 ± 4.82

27.87 ±

18.99

21.52 ±

14.31

Dihydroisoferulic-3´-O-

glucuronide 27.89 ± 22.95

25.61 ±

21.12

17.69 ±

14.64 12.41 ± 9.51

5-Feruloylquinic-4´-O-sulfate 1.26 ± 0.33 1.26 ± 0.34 1.38 ± 0.33 1.3 ± 0.34

Ferulic-4´-O-sulfate 4.21 ± 1.15 2.35 ± 0.74 1.45 ± 0.55 0.77 ± 0.44

Isoferulic-3´-O-sulfate 1.01 ± 0.46 1.06 ± 0.68 0.63 ± 0.46 0.58 ± 0.47

Dihydroferulic-4´-O-sulfate 6.11 ± 1.56 6.28 ± 2.21 7.8 ± 4.43 6.12 ± 3.83

Dihydroisoferulic-3´-O-sulfate 14.72 ± 10.08 12.25 ± 8.62 7.75 ± 5.51 5.18 ± 3.54

m-Coumaric acid 1.31 ± 0.41 1.24 ± 0.46 0.86 ± 0.37 0.83 ± 0.33

o-Coumaric acid 2.48 ± 0.52 2.29 ± 0.49 2.74 ± 0.65 2.94 ± 0.77

p-Coumaric acid 1.24 ± 0.38 1.24 ± 0.35 1.45 ± 0.38 1.26 ± 0.36

m-Dihydrocoumaric acid

147.97 ±

45.66

108.18 ±

41.8

69.25 ±

23.92

49.88 ±

16.08

o-Dihydrocoumaric acid 7.46 ± 2.31 6.43 ± 1.99 7.61 ± 2.49 7.5 ± 2.64


m-Coumaric-3´-O-glucuronide 0.83 ± 0.4 2.32 ± 0.5 2.32 ± 0.55 1.81 ± 0.51



glucuronide 4.84 ± 1.58 3.83 ± 1.25 4.6 ± 2.36 3.96 ± 1.89


glucuronide 2.76 ± 2.33 2.29 ± 2.02

22.76 ±

22.51

18.85 ±

18.67

m-Coumaric acid-3´-O-sulfate 1.48 ± 0.67 1.13 ± 0.67 0.68 ± 0.61 0.38 ± 0.54


Dihydro-m-coumaric-3´-O-sulfate 11.65 ± 3.27 9.09 ± 2.45 7.72 ± 1.92 5.42 ± 1.21


Cinnamic acid 7.54 ± 4.92 4.61 ± 2.25 3.53 ± 1.61 3.54 ± 1.35

4-Methoxycinnamic acid 24.2 ± 9.62 12.01 ± 6.47 8.61 ± 4.16 11.56 ± 6.04

3-Phenylpropionic acid

461.94 ±

100.44

345.47 ±

64.19 349 ± 76.82

305.09 ±

64.46

3-(4-Methoxyphenyl)propionic

acid 14.94 ± 9.99 9.32 ± 4.76 8.25 ± 3.01 7.49 ± 3.48

1Concentration of plasma chlorogenic acid metabolites (nM). Results are expressed as mean

± SEM (n=15).

a Significant difference by ttest between baseline and post intervention (1, 3, or 5h), p<0.05; b



Supplementary Table 5. Pearson’s correlation between plasma chlorogenic acid metabolites

and flow mediated dilatation after the consumption of high polyphenol coffee (310 mg

chlorogenic acid) and low polyphenol coffee (89 mg chlorogenic acid) measured at baseline,

1, 3 and 5h.

Correlation FMD vs [plasma metabolites]

0-1h 3-5h

r p r p

3-Caffeoylquinic acid 0.28 0.0165 -0.15 0.1286

4-Caffeoylquinic acid 0.25 0.025 -0.38 0.0012

5-Caffeoylquinic acid 0.08 0.2703 0.04 0.3782

3-Caffeoylquinic-1,5-lactone 0.11 0.2024 -0.21 0.0547

4-Caffeoylquinic-1,5-lactone 0.07 0.3006 0.38 0.0015

Caffeic acid 0.04 0.3767 -0.23 0.0388

Dihydrocaffeic acid 0.14 0.1500 0.06 0.3112

Caffeic-3´-O-glucuronide -0.09 0.2485 -0.01 0.4639

Caffeic-4´-O-glucuronide 0.13 0.1522 0.09 0.2454

Dihydrocaffeic-3´-O-glucuronide -0.10 0.2250 0.02 0.4314

Dihydrocaffeic-4´-O-glucuronide -0.12 0.1824 0.15 0.1235

5-Caffeoylquinic-3´-O-sulfate 0.01 0.4797 0.07 0.3099

5-Caffeoylquinic-4´-O-sulfate -0.26 0.0243 0.10 0.2316

Caffeic-3´-O-sulfate 0.28 0.0158 0.04 0.3742

Caffeic-4´-O-sulfate 0.09 0.2477 0.26 0.022

Dihydrocaffeic-3´-O-sulfate 0.17 0.0942 0.11 0.2115

Dihydrocaffeic-4´-O-sulfate 0.01 0.4581 0.14 0.1430

3-Feruloylquinic acid 0.14 0.1372 -0.16 0.1102



3-Feruloylquinic-1,5-lactone 0.07 0.3037 0.03 0.4061

4-Feruloylquinic-1,5-lactone 0.06 0.3201 0.15 0.1205

Ferulic acid 0.18 0.0884 0.16 0.106

Isoferulic acid 0.18 0.0830 0.08 0.2794

Methylferulic acid 0.10 0.2205 -0.01 0.4667

Dihydroferulic acid -0.10 0.2279 0.12 0.1907

Dihydroisoferulic acid 0.13 0.1612 0.09 0.2365

Methyldihydroferulic acid -0.01 0.4723 -0.10 0.2319

5-Feruloylquinic-4´-O-glucuronide -0.18 0.0819 -0.32 0.006

Ferulic-4´-O-glucuronide 0.00 0.4997 -0.21 0.056

Isoferulic-3´-O-glucuronide 0.21 0.0577 0.21 0.0542

Dihydroferulic-4´-O-glucuronide -0.07 0.2972 0.09 0.2365

Dihydroisoferulic-3´-O-glucuronide 0.10 0.2307 0.17 0.0943

5-Feruloylquinic-4´-O-sulfate -0.04 0.3796 -0.09 0.2425

Ferulic-4´-O-sulfate 0.21 0.0543 0.22 0.0474

Isoferulic-3´-O-sulfate 0.19 0.0688 0.01 0.4682

Dihydroisoferulic-3´-O-sulfate 0.10 0.2137 0.17 0.0908

Dihydroferulic-4´-O-sulfate -0.02 0.4311 0.08 0.2715

m-Coumaric acid 0.05 0.3609 0.16 0.1066

o-Coumaric acid -0.25 0.0279 -0.33 0.0051

p-Coumaric acid -0.02 0.4519 -0.05 0.3435

m-Dihydrocoumaric acid -0.08 0.2786 0.03 0.4181

o-Dihydrocoumaric acid -0.02 0.4253 -0.22 0.0422

p-Dihydrocoumaric acid 0.11 0.2021 0.16 0.1124

m-Coumaric-3´-O-glucuronide 0.20 0.0595 0.11 0.2025

p-Coumaric-4´-O-glucuronide -0.26 0.0214 -0.22 0.0430

Dihydro-m-coumaric-3´-O-glucuronide -0.11 0.2068 0.11 0.2101

Dihydro-p-coumaric-4´-O-glucuronide -0.13 0.1592 -0.31 0.0072

m-Coumaric acid-3´-O-sulfate 0.06 0.3268 0.26 0.0228

p-Coumaric acid-4´-O-sulfate -0.25 0.0254 0.03 0.3976

Dihydro-m-coumaric-3´-O-sulfate 0.00 0.4881 0.07 0.3055

Dihydro-p-coumaric-4´-O-sulfate -0.01 0.4658 0.06 0.3116

Cinnamic acid -0.17 0.0959 0.17 0.0971

4-Methoxycinnamic acid -0.22 0.0489 0.28 0.0150

3-Phenylpropionic acid 0.12 0.1715 0.12 0.1800

3-(4-Methoxyphenyl)propionic acid 0.10 0.2293 -0.04 0.3672

FMD, flow mediated dilatation; r, correlation

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