Table 2.
Recent advances in bioavailability and metabolism studies carried out in human models.
| Matrix | Bioactive Compounds | Model (Nº/Volunteers) |
Biological Samples | Collection Times |
Technique (Column) |
Relevant Results (Metabolites, Reactions, etc.) | Reference |
|---|---|---|---|---|---|---|---|
| Rosemary tea | Phenolic acids, flavonoids, | Healthy human volunteers (n = 12) |
Plasma | 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 9, 10 h | HPLC–ESI–QTOF-MS(RP-C18) | Phase II metabolites bioavailables. Metabolism by colonic microbiota. |
[86] |
| Urine | (−2,0), (0–2), (2–5), (5–8), (8–12), (12–24) h | ||||||
| Two cocoa products | Flavanols | Healthy human volunteers (n = 13) |
Plasma | 0, 0.5, 1, 2, 3, 4, 6, 8 h | HPLC–ESI–QTOF-MS(RP-C18) | Phase II derivatives of epicatechin, phenyl-valerolactone and phenylvaleric acid. Importance of colonic reactions. | [43] |
| Urine | (−2,0), (0–4), (4-8), (8–12), (1–-24) h |
||||||
| Cocoa products | Phenolics, flavanols | Healthy human volunteers (n = 13) | Urine | 0, 6, 9, 12, 24, 30, 36, 48 h | UHPLC–ESI–QTOF-MS (RP-C18) | Use of multivariate analyses (PCA and PLS-DA) to identify bioavailable compounds Phenyl-valerolactone metabolites. Phase II conjugated metabolites. |
[96] |
| Bilberry pomace extract | Anthocyanins | Healthy women and women with Crohn’s disease (n = 10) |
Plasma | 0, 1, 2, 4, 8 h | HPLC–ESI–QQQ-MS/MS (RP-C18) |
Glucuronides and sulfated metabolites were detected in plasma and urine samples. Higher bioavailability in presence of an intact gut, revealing its potential site of action. |
[45] |
| Urine | (−24–0), (0–2), (2-–4), (4–8), (8-–24) h |
||||||
| Ileostomy fluid | (−12–0), (0–1), (1–2), (2–4), (4–6), (6–8) h |
||||||
| Cranberry juice cocktail | Flavonoids, phenolic acids and proanthocyanidins | Healthy men and postmenopausal women (n = 10) | Plasma | 0, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 10 h | HPLC–ESI–QQQ-MS (RP-C18, RP-C12) | Presence of PAC-A2 dimers in urine. Rapid phase II transformation and excretion of anthocyanins. |
[70] |
| Urine | 0, 2, 4, 6, 8, 10, 24 h | ||||||
| Instant green/ roasted coffee |
Hydroxy-cinnamates | Healthy human volunteers (n = 12) |
Plasma | 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 9, 10, 12 h | HPLC–ESI–QTOF-MS (RP-C18) |
Sulfate, methyl and glucuronides metabolites were detected. Dihydrohydroxycinnamate esters have been identified for the first time in both plasma and urine. |
[57] |
| Urine | (−2–0), (0–2), (2–5), (5–8), (8–12), (12–24) h | ||||||
| Yerba mate infusion | Caffeoylquinic acids, ferulic acids and hydroxyl-cinnamic acids | Healthy human volunteers (n = 12) |
Plasma | 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 9, 10, 12 h | HPLC–ESI–QTOF-MS (RP-C18) | Sulfated conjugates of caffeic and ferulic/isoferulic acids. Phase II flavanol and phenolic acids metabolites. |
[46] |
| Urine | (−2–0), (0–2), (2–5), (5–8), (8–12), (12–24) h | ||||||
| Mixed berry fruit pureé | Caffeoylquinic acids and anthocyanins | Healthy human volunteers (n = 13) |
Plasma | 0, 0.5, 1, 2, 4, 6 h | HPLC-ESI-QQQ-MS/MS (RP-C18) |
Presence of methylated, sulfated and some dual conjugated compounds. Importance of catabolism in the colon. |
[56] |
| Beverage enriched with grape pomace extract | Procyanidins, phenolic acids and flavanols | Healthy human volunteers (n = 12) |
Urine | 0, 24 h | HPLC–ESI–Q-Orbitrap-MS (RP-C18) | Methylation, sulfation, glucuronidation, hydroxylation, dehydrogenation and glycine conjugation reactions. Seventy metabolites identified. |
[50] |
| Red wine enriched with a grape pomace extract | Phenolic acids, flavanols, stilbenes, anthocyanins and phenyl alcohols. | Healthy human volunteers (n = 12) |
Plasma | 0, 0.5, 1, 2, 4, 6 h | UHPLC–ESI–QQQ-MS (RP-C18) | Intense phase II metabolism. Sulfated form predominated over the glucuronidated one. Novel endogenous production pathway of hydroxytyrosol metabolites. |
[47] |
| Urine | (0–6), (6–12), (12–24) h | ||||||
| Orange juice | Flavanones, flavones and phenolic acids | Healthy human volunteers (n = 9) |
Plasma | 0, 1, 2, 3, 4, 5, 6, 8 h | UHPLC–ESI–QQQ-MS (RP-C18) | Phase II sulfate, glucuronide, and methyl metabolites. Dehydroxylation and demethoxylation mediated by the gut microflora. |
[79] |
| Urine | (0–2), (2–5), (5–10), (10–15), (15–24) h | ||||||
| Cocoa rich in polyphenols | Epicatechin, valerolactones and flavonols | Healthy human volunteers (n = 15) |
Urine | 0, 3, 6, 9, 12, 24, 30, 36, 48 h | UHPLC–ESI–QTOF-MS (RP-C18) | Phase II conjugation into sulfated and glucuronide derivatives. Bacterial metabolism of cocoa major flavanols. | [49] |
| Cranberry extract | Phenolic acids, anthocyanins | Healthy human volunteers (n = 13) |
Urine | Day 1: 0 h Day 7: 1, 2, 4, 6, 8, 10, 12, 24 h |
HPLC–ESI–Q-Orbitrap-MS (RP-C18). |
Identification of 42 analytes highlighting the detection of six valerolactones/valeric acid derivatives | [48] |
| Common beans (Phaseolus vulgaris L.) | Flavanols, phenolic acids, catechols and pyrogallols. | Healthy human volunteers (n = 7) |
Plasma | 0, 1, 2, 4, 6, 8 h | UHPLC–ESI–QTOF-MS (RP-C18) | Glucuronidation and sulfation reactions. Colonic bacterial metabolism of the phenolic compounds was detected. Hippuric acids was the most abundant class of metabolites in urine |
[58] |
| Urine | 0, (0–2), (2–4), (4–6), (6–8), (8–24) h | ||||||
| Orange juice | Phenolic acids | Healthy human volunteers (n = 3) |
Urine | 0–24 h | GC–MS and HPLC–ESI-Q-Orbitrap-MS (RP-C18) | Free phenolics and glucuronide and sulfate conjugates were detected. GC–MS was not suitable for the analysis of phenolic sulfate and glucuronide metabolites. |
[59] |
| Maqui berry extract | Anthocyanins (>35%) and delphinidins (>25%) | Healthy human volunteers (n = 12) |
Plasma | 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 h | UHPLC–DAD–ESI–QQQ-MS/MS (RP-C18) | Extensive and fast first-pass metabolism. Phenolic acids as breakdown products of anthocyanins were observed. |
[28] |
| Brown seaweed extract | Phlorotannin metabolites | Overweight and obese volunteers (n = 80) | Plasma | Weeks 0, 8, 16, 24 | UHPLC–ESI–Q-Orbitrap-MS (RP-C18) | Phase II sulfated and glucuronidated metabolites. | [99] |
| Urine | 24 h | ||||||
| Red grape pomace | Anthocyanins, flavan-3-ol monomers, procyanidins | Healthy human volunteers (n = 10) |
Plasma | 0, 8, 16, 24 h | UHPLC–ESI–QQQ-MS (RP-C18) |
Glucuronide and sulfate forms. High inter-individual variability (importance of gut microbiota). |
[87] |
| Urine | (0–3), (3–6), (6–10), (10–24), (24–36), (36–48) h | ||||||
| Green tea | Phenyl-γ-valerolactones | Healthy human volunteers (n = 16) |
Urine | Day 0, day 8 | UHPLC–ESI–QQQ-MS (RP-C18) | Large inter-individual variability due to differences in microbiota patterns. Colonic catabolism of (–)-epigallocatechin and (–)-epigallocatechin-3-gallate. |
[89] |
| Wild blueberry drinks | Anthocyanins, proanthocyanidins, flavonols and chlorogenic acids. | Healthy human volunteers (n = 9) |
Plasma | 0, 1, 2, 4, 6 h | UHPLC–ESI–QTOF-MS (RP-C18) |
23 phenolic acid metabolites were quantified in plasma. Interindividual variability was high (age, dose-dependent effects, gender, gut microbiota and genetic polymorphisms). |
[44] |
| Cranberry juice | Proanthocyanidins, anthocyanins, flavonols and phenolic acids | Healthy human volunteers (n = 10) |
Plasma | 0, 1, 2, 4, 6, 8, 24 h | UHPLC–ESI–QTOF-MS (RP-C18) | Conjugated and non-conjugated phenolic acid derivatives were detected. Sulfated and glucuronidated metabolites. Phase I and phase II metabolism. |
[29] |
| Urine | (0–8), (8–24) h | ||||||
| Seed/fruit extract (fraxinus angustifolia vahl) | Secoiridoid glucosides | Healthy human volunteers (n = 9) |
Plasma | 0, 1, 2, 4, 8, 24 h | UHPLC–ESI–QTOF-MS (RP-C18) | Metabolic conversion by esterases, glycosidases, and phase II sulfo- and glucuronosyl transferases to form smaller conjugated derivatives. Metabolism by phase I and (or) microbial enzymes. | [84] |
| Urine | 0, (0–8), (8–24) h | ||||||
| Hard gelatine capsule containing phenolic compounds | Flavan-3-ols (epicatechin, procyanidin B1, and polymeric procyanidins) | Healthy human volunteers (n = 7) | Plasma | 0, 1, 2, 4, 8, 24, 48 h | GC–EI-QQQ-MS (DB-5MS) HPLC–DAD–ESI-Q-MS (RP-C18) |
Glucuronidated, sulfated and methylated (-)-epicatechin and 5-(3′,4′-dihydroxyphenyl)-valerolactone were the dominant metabolites in blood and urine. High importance of the gut microbiota in flavan-3-ol metabolism. |
[63] |
| Urine | (0–4), (4–8), (8–24) h | ||||||
| Feces | (0–24) h |
DAD, diode-array detection; EI, electronic impact; ESI, electrospray ionization; GC, gas chromatography; HPLC, high-performance liquid chromatography; IT, ion trap; MS, mass spectrometry; PCA, principal component analyses; PLS-DA, partial-least-squares discriminant analysis; Q, quadrupole; QQQ, triple quadrupole; QTOF, quadrupole time of flight; RP, reversed phase; UHPLC, ultrahigh performance liquid chromatography.