Table 6.

Metabolites analyzed in urine after acute cocoa interventions and studied with targeted methodologies.

Chemical Category	Metabolite	Treatment 1			Treatment 2			Reference
		Type of Matrix	Concentration	Sampling Period (h)	Type of Matrix	Concentration	Sampling Period (h)
Flavonoids and conjugates	(-)-catechin	N.R.	N.R.	N.R.	Dairy cocoa drink	4.0 ± 0.4 µmol	0–24	[79]
	(-)-epicatechin	N.R.	N.R.	N.R.	Dairy cocoa drink	13 ± 2 µmol	0–24	[79]
		N.R.	N.R.	N.R.	Non dairy cocoa drink	N.R.	0–24	[76]
		N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	0.6 ± 0.2 ng/mg creatintine	0–4	[60]
	(-)-epicatechin glucuronide	Non-dairy cocoa drink	194.95 µg/g creatinine	0–6	Dairy cocoa drink	112.79 µg/g creatinine	0–6	[75]
	(-)-epicatechin sulfate (isomer 1)	Non-dairy cocoa drink	48.83 µg/g creatinine	0–6	Dairy cocoa drink	30.86 µg/g creatinine	0–6	[72,75]
	(-)-epicatechin sulfate (isomer 2)	No- dairy cocoa drink	195.29 µg/g creatinine	6–12	Dairy cocoa drink	128.47 µg/g creatinine	6–12	[72,75]
	(-)-epicatechin sulfate (isomer 3)	Non-dairy cocoa drink	5.07 µg/g creatinine	0–6	Dairy cocoa drink	72.45 µg/g creatinine	0–6	[72,75]
	(-)-epicatechin-3´-sulfate	N.R.	N.R.	N.R.	Dark chocolate	5.80 ± 1.78 µmol	5–10	[66]
	(-)-epicatechin-3´-β-D-glucuronide	N.R.	N.R.	N.R.	Dark chocolate	8.74 ± 2.92 µmol	5–10	[66]
	(-)-epicatechin-4´-sulfate	N.R.	N.R.	N.R.	Dark chocolate	0.37 ± 0.13 µmol	5–10	[66]
	(-)-epicatechin-4´-β-D-glucuronide	N.R.	N.R.	N.R.	Dark chocolate	0.56 ± 0.14 µmol	5–10	[66]
	(-)-epicatechin-5-sulfate	N.R.	N.R.	N.R.	Dark chocolate	0.72 ± 0.36 µmol	5–10	[66]
	(-)-epicatechin-7-β-D-glucuronide	N.R.	N.R.	N.R.	Dark chocolate	4.59 ± 0.74 µmol	10–24	[66]
Flavonoids and conjugates	(-)-epicatechin-O-glucuronide	Cocoa powder with water	405 ± 44 µmol/L	0–2	Cocoa powder with milk	136 ± 24 µmol/L	2–5	[77]
	(-)-epicatechin-O-sulfate (isomer 2)	Cocoa powder with water	1127 ± 196 µmol/L	0–2	Cocoa powder with milk	737 ± 118 µmol/L	2–5	[77]
	(+)-catechin	N.R.	N.R.	N.R.	Dairy cocoa drink	9.8 ± 1.4 µmol	0–24	[79]
	(+)-epicatechin	N.R.	N.R.	N.R.	Dairy cocoa drink	10 ± 1 µmol	0–24	[79]
	Epicatechin	Hot water	N.D.	0–24	Cocoa powder with water	4.3 ± 4.2 µmol	0–24	[69]
	(epi) catechin-O-sulfate (isomer 1)	Cocoa powder with water	928 ± 110 µmol/L	0–2	Cocoa powder with milk	476 ± 75 µmol/L	0–2	[77]
	3´-O-methyl-(-)-epicatechin	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	0.2 ± 0.3 ng/mg creatinine	0–4	[60]
	3´-O-methyl-(-)-epicatechin 4´-sulfate	N.R.	N.R.	N.R.	Dark chocolate	1.27 ± 0.39 µmol	5–10	[66]
	3´-O-methyl-(-)-epicatechin 5-sulfate	N.R.	N.R.	N.R.	Dark chocolate	8.87 ± 3.05 µmol	5–10	[66]
	3´-O-methyl-(-)-epicatechin 7-sulfate	N.R.	N.R.	N.R.	Dark chocolate	1.55 ± 0.55 µmol	5–10	[66]
	3´-O-methyl-(-)-epicatechin-3´-β-D-glucuronide	N.R.	N.R.	N.R.	Dark chocolate	0.69 ± 0.12 µmol	5–10	[66]
	4´-O-methyl-(-)-epicatechin 5-sulfate	N.R.	N.R.	N.R.	Dark chocolate	0.92 ± 0.34 µmol	5–10	[66]
	4´-O-methyl-(-)-epicatechin 7-sulfate	N.R.	N.R.	N.R.	Dark chocolate	0.55 ± 0.29 µmol	5–10	[66]
	O-methyl-(epi)-catechin-O-sulfate	Cocoa powder with water	1146 ± 231 µmol/L	0–2	Cocoa powder with milk	823 ± 131 µmol/L	0–2	[77]
Flavonoids and conjugates	Naringenin	Hot water	0.1 ± 0.2 µmol	0–24	Cocoa powder with water	0.3 ± 0.4 µmol	0–24	[69]
	Procyanidin B2	N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
Lignans	Enterodiol	N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
		Hot water	0.5 ± 1.1 µmol	0–24	Cocoa powder with water	0.2 ± 0.3 µmol	0–24	[69]
	Enterolactone	N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
		Hot water	3.8 ± 2.8 µmol	0–24	Cocoa powder with water	3.6 ± 2.9 µmol	0–24	[69]
Methylxanthines	1,3,7-trimethyluric acid	Cocoa powder with milk	0.7 ± 0.3 µmol/L	0–2	Cocoa powder with milk, enriched with methylxanthines	1.8 ± 0.6 µmol/L	9.7 ± 6.9	[81]
	1,3-dimethyluric acid	Cocoa powder with milk	1.3 ± 1.1 µmol/L	21.5 ± 6.0	Cocoa powder with milk, enriched with methylxanthines	3.4 ± 1.9 µmol/L	18.0 ± 7.5	[81]
	1,7-dimethyluric acid	Cocoa powder with milk	3.9 ± 2.7 µmol/L	20.0 ± 7.7	Cocoa powder with milk, enriched with methylxanthines	13.5 ± 7.8 µmol/L	12.7 ± 8.7	[81]
	1-methyluric acid	Cocoa powder with milk	9.2 ± 4.1 µmol/L	19.7 ± 8.2	Cocoa powder with milk, enriched with methylxanthines	45.2 ± 16.4 µmol/L	12.4 ± 7.5	[81]
	1-methylxanthine	Cocoa powder with milk	5.5 ± 2.7 µmol/L	21.2 ± 6.8	Cocoa powder with milk, enriched with methylxanthines	15.3 ± 7.3 µmol/L	13.7 ± 7.7	[81]
Methylxanthines	3,7-dimethyluric acid	Cocoa powder with milk	2.7 ± 1.1 µmol/L	21.2 ± 6.8	Cocoa powder with milk, enriched with methylxanthines	7.3 ± 2.9 µmol/L	14.3 ± 8.6	[81]
	3-methylxanthine	Cocoa powder with milk	34.8 ± 8.9 µmol/L	14.8 ± 9.1	Cocoa powder with milk, enriched with methylxanthines	98.1 ± 21.9 µmol/L	12.0 ± 7.4	[81]
	7-methylxanthine	Cocoa powder with milk	110.1 ± 40.1 µmol/L	16.3 ± 8.7	Cocoa powder with milk, enriched with methylxanthines	187.4 ± 82.1 µmol/L	12.0 ± 7.2	[81]
	Caffeine	Cocoa powder with milk	2.1 ± 0.7 µmol/L	14.5 ± 9.3	Cocoa powder with milk, enriched with methylxanthines	9.9 ± 3.5 µmol/L	7.7 ± 5.5	[81]
		Baseline	<2.5–23.4 µmol/L	0	Dark chocolate	4.2–24.7 µmol/L	1.5	[59]
	Paraxanthine	Cocoa powder with milk	3.5 ± 1.8 µmol/L	15.1 ± 9.0	Cocoa powder with milk, enriched with methylxanthines	10.7 ± 5.8 µmol/L	11.7 ± 7.5	[81]
	Theobromine	Cocoa powder with milk	50.4 ± 18.4 µmol/L	14.2 ± 9.6	Cocoa powder with milk, enriched with methylxanthines	177.4 ± 45.0 µmol/L	7.7 ± 5.5	[81]
		Baseline	2.5–94.9 µmol/L	0	Dark chocolate	131.9–449.4 µmol/L	1.5	[59]
	Theophylline	Baseline	1.0 ± 1.4 µmol/L	14.9 ± 8.9	Dark chocolate	2.5 ± 1.3 µmol/L	7.6 ± 5.8	[81]
N-phenylpropenoyl-L-amino acids	N-[3´,4´-dihydroxy-(E)-cinnamoyl]-L-aspartic acid	Baseline	N.D.	0	Non-dairy cocoa drink	4.76 ± 4.01 µg	2	[20]
	N-[3´,4´-dihydroxy-(E)-cinnamoyl]-L-dopa	Baseline	N.D.	0	Non-dairy cocoa drink	1.25 ± 1.19 µg	2	[20]
	N-[3´,4´-dihydroxy-(E)-cinnamoyl]-L-glutamic acid	Baseline	N.D.	0	Non-dairy cocoa drink	N.D.	N.D.	[20]
	N-[3´,4´-dihydroxy-(E)-cinnamoyl]-L-tyrosine	Baseline	N.D.	0	Non-dairy cocoa drink	0.30 ± 0.39 µg	2	[20]
	N-[4´-hydroxy-(E)-cinnamoyl]-L-aspartic acid	Baseline	N.D.	0	Non-dairy cocoa drink	64.37 ± 20.22 µg	2	[20]
	N-[4´-hydroxy-(E)-cinnamoyl]-L-dopa	Baseline	N.D.	0	Non-dairy cocoa drink	0.85 ± 0.96 µg	2	[20]
N-phenylpropenoyl-L-amino acids	N-[4´-hydroxy-(E)-cinnamoyl]-L-glutamic acid	Baseline	N.D.	0	Non-dairy cocoa drink	22.17 ± 12.57 µg	2	[20]
	N-[4´-hydroxy-(E)-cinnamoyl]-L-tryptophane	Baseline	N.D.	0	Non-dairy cocoa drink	<0.1 µg	1–4	[20]
	N-[4´-hydroxy-(E)-cinnamoyl]-L-tyrosine	Baseline	N.D.	0	Non-dairy cocoa drink	18.91 ± 5.53 µg	2	[20]
	N-[4´-hydroxy-3´-methoxy-(E)-cinnamoyl]-L-aspartic acid	Baseline	N.D.	0	Non-dairy cocoa drink	9.70 ± 2.93 µg	2	[20]
	N-[4´-hydroxy-3´-methoxy -(E)-cinnamoyl]-L-tyrosine	Baseline	N.D.	0	Non-dairy cocoa drink	1.91 ± 0.59 µg	2	[20]
	N-[cinnamoyl]-L-aspartic acid	Baseline	N.D.	0	Non-dairy cocoa drink	0.43 ± 0.33 µg	2	[20]
Phenolic acids and others	3-hydroxybenzoic acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	1 ± 1 ng/mg creatinine	0–4	[66]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
	3,4-dihydroxyphenyl acetic acid	Baseline	15.8 ± 4.4 nmol/mg creatinine	−24–0	Chocolate	38.8 ± 12.3 nmol/mg creatinine	0–24	[65]
		Cocoa powder with water	1.60 ± 0.37 nmol/mg creatinine	6–12	Cocoa powder with milk	0.45 ± 0.10 nmol/mg creatinine	12–24	[78]
		N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	10 ± 10 ng/mg creatinine	0–4	[60]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
Phenolic acids and others	3,4-dihydroxyphenyl propionic acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	6 ± 5 ng/mg creatinine	0–4	[60]
		Baseline	3.1 ± 0.7 nmol/mg creatinine	−24–0	Chocolate	2.6 ± 0.6 nmol/mg creatinine	0–24	[65]
		Cocoa powder with water	16.84 ± 2.81 nmol/mg creatinine	0–6	Cocoa powder with milk	16.9 ± 4.0 nmol/mg creatinine	0–6	[78]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
	3-hydroxyphenyl acetic acid	Cocoa powder with water	10.1 ± 3.42 nmol/mg creatinine	12–24	Cocoa powder with milk	7.36 ± 1.61 nmol/mg creatinine	12–24	[78]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
		N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	30 ± 20 ng/mg creatinine	0–4	[60]
	3-hydroxyphenyl propanoic acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	10 ± 7 ng/mg creatinine	0–4	[60]
	3-methoxy-4-hydroxy-phenylacetic acid	Cocoa powder with water	11.30 ± 1.63 nmol/mg creatinine	6–12	Cocoa powder with milk	9.30 ± 0.74 nmol/mg creatinine	6–12	[78]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
	4-hydroxy-5-(3´,4´-dihydroxyphenyl) valeric acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	0.2 ± 0.3 ng/mg creatinine	0–4	[60]
	4-hydroxybenzoic acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	16 ± 6 ng/mg creatinine	0–4	[60]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
	4-hydroxyphenyl acetic acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	210 ± 50 ng/mg creatinine	0–4	[60]
Phenolic acids and others	4-hydroxyphenyl propanoic acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	0.02 ± 0.04 ng/mg creatinine	0–4	[60]
	4-O-methylgallic acid	N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
		Hot water	N.D.	0–24	Cocoa powder with water	0.6 ± 1.1 µmol	0–24	[69]
	5-(3´,4´-dihydroxyphenyl) valerolactone	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	2 ± 4 ng/mg creatinine	48	[60]
	Caffeic acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	1.2 ± 0.5 ng/mg creatinine	0–4	[60]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
		Hot water	0.1 ± 0.2 µmol	0–24	Cocoa powder with water	0.4 ± 0.4 µmol	0–24	[69]
	Dihydroxyphenyl valeric acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	0.01 ng/mg creatintine	-	[60]
	Ferulic acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	21 ± 4 ng/mg creatinine	0–4	[60]
		Baseline	131 ± 59 nmol/mg creatinine	−24–0	Chocolate	321 ± 99 nmol/mg creatinine	24–48	[65]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
	Hippuric acid	Cocoa powder with water	193.16 ± 27.89 nmol/mg creatinine	0–6	Cocoa powder with milk	122.82 ± 18.83 nmol/mg creatinine	12–24	[78]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
		Baseline	2943 ± 1923 nmol/mg creatinine	−24–0	Chocolate	974± 115 nmol/mg creatinine	0–24	[65]
	m-coumaric acid	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	1 ± 1 ng/mg creatinine	0–4	[60]
		Hot water	0.5 ± 0.9 µmol	0–24	Cocoa powder with water	1.4 ± 1.4 µmol	0–24	[69]
Phenolic acids and others	m-coumaric acid	N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
	Methyl-5-(3´, 4´-dihydroxyphenyl)-valerolactone	N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	0.5 ± 0.8 ng/mg creatinine	48	[60]
	m-hydroxybenzoic acid	Baseline	Non detected	−24–0	Chocolate	8.93 ± 3.9 nmol/mg creatinine	24–48	[65]
		Cocoa powder with water	0.56 ± 24 nmol/mg creatinine	6–12	Cocoa powder with milk	0.60 ± 0.28 nmol/mg creatinine	12–24	[78]
	m-hydroxyphenyl acetic acid	Baseline	21.2 ± 3.5 nmol/mg creatinine	−24–0	Chocolate	156 ± 54 nmol/mg creatinine	24–48	[65]
	m-hydroxyphenyl propionic acid	Baseline	5.4 ± 2.4 nmol/mg creatinine	−24–0	Chocolate	13.4 ± 4.1 nmol/mg creatinine	24–48	[65]
	p-coumaric acid	N.R.	N.R.	N.R.	Cocoa procyanidin concentrate	1 ± 1 ng/mg creatinine	48	[60]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
	Phenylacetic acid	Cocoa powder with water	163.77 ± 22.10 nmol/mg creatinine	0–6	Cocoa powder with milk	167.72 ± 23.80 nmol/mg creatinine	0–6	[78]
		Baseline	70.1 ± 11.3 nmol/mg creatinine	−24–0	Chocolate	36.8 ± 8.1 nmol/mg creatinine	24–48	[65]
	p-hydroxybenzoic acid	Baseline	54.2 ± 8.1 nmol/mg creatinine	−24–0	Chocolate	41.2 ± 10.4 nmol/mg creatinine	24–48	[65]
		Cocoa powder with water	6.39 ± 0.66 nmol/mg creatinine	0–6	Cocoa powder with milk	3.01 ± 0.97 nmol/mg creatinine	12–24	[78]
Phenolic acids and others	p-hydroxyhippuric acid	Cocoa powder with water	3.13 ± 0.60 nmol/mg creatinine	0–6	Cocoa powder with milk	1.76 ± 0.30 nmol/mg creatinine	6–12	[78]
		Baseline	71.1 ± 13.6 nmol/mg creatinine	−24–0	Chocolate	90.5 ± 21.3 nmol/mg creatinine	24–48	[65]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
	Protocatechuic acid	Cocoa powder with water	11.07 ± 1.19 nmol/mg creatinine	0–6	Cocoa powder with milk	8.8 ± 2.2 nmol/mg creatinine	0–6	[78]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
		N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	40 ± 20 ng/mg creatinine	8–24	[60]
	Vanillic acid	Cocoa powder with water	5.96 ± 1.15 nmol/mg creatinine	0–6	Cocoa powder with milk	9.85 ± 1.27 nmol/mg creatinine	0–6	[78]
		Baseline	64.6 ± 25.5 nmol/mg creatinine	−24–0	Chocolate	228 ± 33 nmol/mg creatinine	0–24	[65]
		N.R.	N.R.	N.R.	Non-dairy cocoa drink	N.R.	0–24	[76]
		N.R.	N.R.	N.R.	Cocoa polymeric procyanidin concentrate	14 ± 4 ng/mg creatinine	0–4	[60]

Notes: N.R. refers to non-reported or non-cocoa matrix was used, and N.D. to non-detected.