Table 2 List of studies reporting candidate biomarkers for herb and spice intake
From: Herbs and Spices- Biomarkers of Intake Based on Human Intervention Studies – A Systematic Review
Dietary factor | Study design | Subjects | Analytical method | Sample type | Discriminating metabolites/candidate biomarkers | Primary Ref. |
|---|---|---|---|---|---|---|
Anise (anethole admn.) | Acute human study. [methoxy-14C]-labeled compound | 5 (males) | Radiochemical (14C labeled) and HPLC | Urine (2 h–10 h, 24 h, and 48 h) | 4-methoxybenzoic acid, 4-methoxyhippuric acid, 3 unknown compounds | [36] |
Anise-based alcoholic drink | Dose escalating study (120 ml, 200 ml, 360 ml “Helenas Ouzo” (anethole-containing drink) | 1 | HS-SPME-GC–MS | Serum (1, 2, 4, 8, and 24 h) | Anethole | [37] |
Observational study: drivers under the influence of alcoholic-containing anethole drink | 50 | Serum | ||||
Capsicum sp. Chili pepper (capsule) | Acute crossover study (5 g of capsicum extract) | 12 (males) | HPLC | Plasma | Capsaicin | [41] |
Capsicum sp. CH-19 sweet non-pungent red pepper (capsule) | Double-blind, randomized, placebo-controlled, dose-escalating (15 or 30 mg capsinoids extract) | 24 (males) | LC-MS/MS and HPLC-UV | Plasma (15 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h) | Capsiate, dihydrocapsiate, nordihydrocapsiate, vanillyl alcohol | [150] |
Capsicum sp. Paprika carotenoids | Case study. 200 ml paprika carotenoid beverage | 5 (young, healthy) | HPLC-UV-VIS and Q-TOF-MS/MS | Plasma (0 week, 2 weeks, 4 weeks), erythrocytes | β-cryptoxanthin, cucurbitaxanthin A, cryptocapsin, lutein, zeaxanthin, capsanthin, capsanthone | [42] |
Cinnamon | Four-way crossover study | 24 | HPLC MS/MS | Plasma and urine | 7-hydroxycoumarin | [48] |
Fennel (fennel tea) | Single-dose acute study (500 ml of fennel tea) | 7 | LC-MS/MS and GC-GC-MS | Urine (1.5, 4, 8, 14, 24 h) | Estragole, 1′-hydroxyestragole, trans-Anethole, -Allylphenol-G | [63] |
Dose-escalation study (250, 500, 1000 ml fennel tea). | 1 | Plasma (0.75,1.5, 2, 2.5 h) | ||||
Fennel, basil, and tarragon | 15 mL fennel extract; 15 ml tarragon extract; 15 ml basil brewed | NP | IS-R-DLLME and HPLC | Plasma (2 h, 4 h, and 8 h) and Urine (3 h, 6 h, and 9 h) | Para-anisaldehyde trans-anethole estragole | [38] |
Ginger (extract) | Acute single dose: 2 g ginger extracts | 9 (healthy) | LC-MS/MS | Plasma (0.25 h, 0.5 h, 0.75 h, 1 h, 2 h, 4 h, 6 h, 10 h, 24 h, 48 h, and 72 h) | 10-Gingerol, 6-Shogaol, 6-Gingerol-G, 8-Gingerol-G 10-Gingerol-G, 6-Shogaol-G 6-Gingerol-S, 8-Gingerol-S, 10-Gingerol-S, 6-Shogaol-S | [70] |
Multiple dose: 24-day randomized controlled trial. 250 mg ginger extract | 30 (healthy) | Plasma (0–24 h) and colon (biopsy) | 6-Gingerol-G (plasma), 10-Gingerol-G (plasma), 6-Gingerol-S (plasma), 10-Gingerol-G (colon), 10-Gingerol-S (colon) | |||
Multiple dose: 24-day randomized controlled trial. 250 mg ginger extract | 20 (high-risk colorectal cancer) | Plasma (0-24 h) and colon (biopsy) | 6-Gingerol-G (plasma), 10-Gingerol-G (plasma), 6-Gingerol-S (plasma) 10-Gingerol-G (colon), 10-Gingerol-S (colon) | |||
Ginger | Dose escalation study: 100 mg, 250 mg, 500 mg, 1 g, 1.5 g, 2 g ginger extract (capsule) | 27 (healthy) | HPLC-ECD, HPLC-UV | Plasma (15 min, 30 min, and 45 min, 1 h, 2 h, 4 h, 6 h, 10 h, 24 h, 48 h, and 72 h) | 6-Gingerol-G, 8-Gingerol-G, 10-Gingerol-G, 6-Shogaol-G, 6-Gingerol-S, 10-Gingerol-S | [69] |
Ginger (ginger tea) | Acute study. 2× (18 g/bag) ginger tea (focused on the metabolism of shogaol) | 3 (healthy males) | LC/ESI-MS/MS | Urine (0–2 h, 2–4 h, 4–6 h, 6–9 h, 9–12 h, and 12–24 h) | 5-Cys-6S, 5-NAC-6S, 5-Cys-Gly-6S, 5-Cys-M6, 5-NAC-M6, 5-Cys-Gly-M6, 5-Cys-8S, 5-Cys-M6’, 5-Cys-10S, 5-Cys-M6" | [71] |
Marjoram (extract) | Acute single oral dose (3.75 g) of O. onites extract | 6 (healthy) | HPLC-CEAD | Urine (24 h, 48 h) | Protocatechuic acid, p-hydroxybenzoic acid, caffeic acid, ferulic acid, syringic acid, vanillic acid, p-coumaric acid, 3,4-dihydroxyphenylacetic acid, m-hydroxyphenylacetic acid | [97] |
Nutmeg | Acute oral dose in rats (100 mg/kg body mass) of EL, MY, and SA or a single 500 mg/kg body mass of nutmegs | 2 rats × each substance and dose | GC-MS | Urine (24 h) | O-demethyl elemicin*, O-demethyl dihydroxy elemicin*, demethylenyl myristicin*, dihydroxy myristicin*, demethylenyl safrole* | [73] |
Observational exploratory toxicological study: after nutmeg abuse (~ 5 nutmegs) | 1 | |||||
Oregano (extract) | Oregano extract (25, 75, or 225 mg/kg | 15 mice | HPLC–MS/MS | Plasma and brain tissue | Carvacrol | [95] |
Parsley | Randomized crossover with two 1-week intervention periods in succession, supplemented with parsley 20 g parsley/MJ | 14 (healthy) | HPLC-DAD | Urine (24 h) | Apigenin | |
Parsley | Acute human study. (149.45 ± 35.21 g parsley) | 11 (healthy) | HPLC-ECD | Plasma (4–11 h, 28 h), urine (24 h), and red blood cells | Apigenin | [102] |
Peppermint oil (capsule) | Acute pharmacokinetic study. Intake of 0.4 ml peppermint oil in either colpermin or gelatine capsules (91–97 mg capsule) | 6 (healthy) | NP | Urine (24 h) | Menthol-G | [117] |
6 (ileostomy) | ||||||
Peppermint oil | Acute randomized intake of 0.6 ml peppermint oil in either Colpermin or Mintec preparations | 13 (healthy) | GC-MS | Urine (2 h-interval for 14 h + single overnight (10 h) | Menthol-G | [116] |
Peppermint oil (capsule) | 180 mg peppermint oil enteric-coated capsule (peroral administration) | 4 (males) | GC-FID | Urine (2-h interval up to 14 h) | Menthol-G | [118] |
Peppermint oil (capsule) | Acute (400 mg peppermint oil in enteric-coated capsule) and repeated 4 weeks later | 5 (healthy) | 2H-NMR | Urine (2 h, 4 h, 6 h, and 8 h) | Menthol-G | [120] |
Peppermint oil (capsule) | (1) 400 mg of enteric-coated peppermint oil capsules and 6 g of 99% [U-13C] glucose | 1 (female) | 13C-NMR | Urine (2-4 h) | 13C-menthol-G | [119] |
(2) Primed infusion of [U-13C] glucose + 400 mg enteric-coated peppermint oil capsules | 4 (severe heart failure) | Urine (2 h) | ||||
Peppermint oil (L-menthol preparation) | Escalating-single-dose, randomized, double-blind, placebo-controlled (menthol preparation, 80–320 mg). Intragastric spraying of peppermint oil | 24 (males) | GC-MS | Plasma (5, 10, 30, 60, 120, and 240 min and 8, 12, and 24 h after each dose) | Menthol, menthol-G, M7, M9, M11, M29 | [121] |
Urine (before dosing (−12–0 h) and 0–4 h, 4–8 h, 8–12 h, and 12–24 h after | Menthol-G, M2, M3–11, M12, M13–18, M19–21, M22–28, M29, M30–32. | |||||
Rosemary (extract) | Acute, controlled, randomized study. Rosemary extract enriched in carnosic acid 40% (w/w) | 24 Zucker rats | HPLC/QTOF-MS and HPLC-UV | Gut, liver, plasma, brain, | Carnosic acid-G, carnosol-G, rosmanol-G, carnosic acid 12 methyl ether, 5,6,7,10-tetrahydro-7-hydroxyrosmariquinone, carnosic glutathione oxidized, carnosol-S, rosmanol-S, rosmarinic acid, carnosic cysteine, carnosic glutathione, rosmadial-G, rosmanol, ipirosmanol, epiisorosmanol, rosmadial/rosmanol quinone, rosmanol/epirosmanol methyl ether, carnosol, rosmadial methyl ether, epirosmanol ethyl ether, epiisorosmanol methyl ether, carnosol methyl ether, carnosic acid. | [100] |
Subchronic, controlled, randomized study Rosemary extract enriched in carnosic acid 40% (w/w) (64 days) | ||||||
Saffron (tea) | Single-dose acute study. 200 mg saffron in 150 ml water (saffron tea) | 4 (healthy) | SPE-HPLC-DAD | Plasma (0 h, 2 h, and 24 h) | cis-Crocetin, trans-Crocetin | [126] |
Saffron (purified crocetin) | Open-label, single dose escalation of crocetin (7.5, 15 and 22.5 mg) | 10 (healthy) | HPLC | Plasma (1 , 2 h, 4 h, 6 h, 8 h, 10 h, and 24 h) | Crocetin | [127] |
Sage (tea) | Acute human study (1.02 mg 1,8-cineole) in sage tea | 1 (female) | SPME-GC-MS and LC-MS/MS | Plasma (0.75 h, 1.7 h, 3.25 h, 6.75 h, and 24 h) and urine (2 h, 5 h, 7 h, 10 h, 17 h, 21 h, 28 h, 32 h, 35 h, 44 h, 50 h, 53 h, 60 h, and 69 h) | 1,8-cineole, 2-hydroxy-1,8-cineole, 3-hydroxy-1,8-cineole, 7-hydroxy-1,8-cineole, 9-hydroxy-1,8-cineole. | [130] |
Thyme (tablet) | Acute study. A single dose of a Bronchipret® TP (tablet equivalent to 1.08 mg thymol) | 12 | HS-SPME-GC-MS and LC-MS/MS | Plasma (0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 10 h, 11 h, 12 h, 14 h, 24 h, 31 h, 38 h, 48 h, 55 h, 62 h, and 72 h) | Thymol-S | [151] |
Urine (0 to 3 h, 3 to 6 h, 6 to 9 h, 9 to 14 h, 14 to 24 h, 24 to 31 h, 38 to 48 h, 48 to 55 , 55 to 62 h, and 62 to 72 h) | Thymol-G, thymol-S | |||||
Thyme | Acute intake of 1.5 g of thyme extract | 12 Wistar rats | μSPE-UPLC-MS/MS | Plasma | Thymol-S, thymol-G, luteolin-S, luteolin-G, hydroxyphenylpropionic acid-S, coumaric acid-S, caffeic acid-S, ferulic acid-S, ferulic acid-G, hydroxybenzoic acid, and dihydrophenylpropionic acid-S | [98] |
Thyme (olive oil enriched with thyme polyphenols) | Randomized, double-blind, controlled, cross-over trial. Administration of 25 ml/day (VOO)/VOO + PC/VOO + PC + PC of thyme | 33 (hypercholesterolemic) | μSPE-UPLC-ESI-MS/MS | Plasma | Thymol-S, hydroxyphenylpropionic acid-S, caffeic acid-S | [99] |
Urine (24 h) | Thymol-S, Thymol-G, hydroxyphenylpropionic acid-S, p-cymene-diol-G, caffeic acid-S | |||||
Thyme (olive oil enriched with thyme) | (1) In vitro colonic fermentation (0 to 48 h) | 3 (healthy) | UPLC-ESI-MS/MS and GC-FID | Feces (in vitro fermentation) | Thymol, carvacrol, 2-(3′,4′-dihydroxyphenyl) acetic acid, 2-(4′-hydroxyphenyl) acetic acid, phenylacetic acid, 3-(4′-hydroxyphenyl) propionic acid, phenylpropionic acid. | [96] |
2-(3′,4′-dihydroxyphenyl) acetic acid, 2-(4′-hydroxyphenyl) acetic acid, Phenylacetic acid, 3-(4′-hydroxyphenyl) propionic acid, phenylpropionic acid | ||||||
Caffeic acid, p-coumaric acid, 3-(3′, 4′-dihydroxyphenyl) propionic acid; hydroxyphenylpropionic acid; phenylpropionic acid, 2-(3′,4′-dihydroxyphenyl) acetic acid; 2-(4′-hydroxyphenyl) acetic acid; phenylacetic acid | ||||||
3-(3′, 4′-dihydroxyphenyl) propionic acid; hydroxyphenylpropionic acid; phenylpropionic acid, 2-(3′,4′-dihydroxyphenyl) acetic acid, 2-(4′-hydroxyphenyl) acetic acid; phenylacetic acid | ||||||
(2) Human intervention study: 25 ml/day of a thyme phenol-enriched olive oil for 3 weeks | 10 | Feces (in vivo, (0-3wk) | Carvacrol, 2-(4-hydroxyphenyl) acetic acid, 3-(3′-4′-dihydroxyphenyl) propionic acid, hydroxyphenylpropionic acid, phenylpropionic acid | |||
Turmeric (curcuminoids in capsule) | Randomized double blind placebo (1 g/day, 4 g/day, placebo), 6 months | 31 (elderly) | LC-MS/MS | Plasma (2–2.5 h after 1 month) | Curcumin, DMC BDMC, THC, ferulic acid, vanillic acid | [132] |
Turmeric (curcuminoids in capsule) | Acute study | 2 (healthy) | LC-MS/MS | Plasma | COG | [141] |
Turmeric (curcuminoidsin nanoemulsion) | Acute study (2 g nanoemulsion curcuminoids) | 2 (healthy) | LC-MS/MS | Plasma | Curcumin, COG, COS, DMC, BDMC, and THC | [142] |
Turmeric (curcuminoids in capsule) | Nonrandomized, open-label, phase II trial (starting dose 8 g curcuminoids) 8 weeks | 25 (pancreatic cancer) | LC-MS | Plasma (1 h, 2 h, 6 h, 24 h, 48 h, 72 h, day 8 and after 4 weeks | COG and COS | [140] |
Turmeric (curcuminoids in capsule) | Dose escalation. 450–3600 mg/day 1 week | 12 (hepatic metastasis from colorectal cancer) | HPLC-UV, LC-MS | Plasma and liver tissue | Hexahydrocurcumin (liver), hexahydrocurcuminol (liver), curcumin (plasma), COG (plasma), COS (plasma). | [143] |
Turmeric (curcuminoids in capsule) | Acute study. | 12 (colorectal carcinoma) | HPLC-UV HPLC-MS | Plasma and colorectal tissue | Curcumin (plasma and colorectal tissue), COG and COS (colorectal tissue) | [6] |
Turmeric (curcuminoids-different administration types) | Randomized double blind crossover study with formulated (CP, CTR, CHC) and unformulated (CS) curcumin | 12 (healthy) | LC-MS/MS | Plasma (1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, and 12 h) | Curcumin, DMC, BDMC, THC | [138] |
Turmeric (curcuminoids in capsule) | 14-day intervention (2.35 g capsule) | 24 (colorectal cancer) | UPLC-UV, LC-MS/MS | Plasma, urine and colon tissue | Curcumin, BDMC, DMC, BDMC-S, DMC-S, COS, COG, BDMC-G, DMC-G | [147] |
Turmeric (Theracurmin®) | Acute dose escalation 150 mg and 210 mg | 6 (healthy) | LC-MS/MS | Plasma (0 h, 1 h, 2 , 4 h, 6 , 24 h) | Curcumin | [152] |
Turmeric (Theracurmin®) | Multi-week dose escalation | 16 (pancreatic or biliary tract cancer) | LC-MS/MS | Plasma (2 h) | Curcumin | [153] |
Turmeric (turmeric fresh derived curcuminoids vs. std. curcumin) | Multi-week double crossover study. 250 mg/kg body weight | 18 (mice) | LC-DAD-ESI-MS/MS | Plasma (0 h, 0.5 , 1 h, 3 h, 5 h, 8 h, 12 h) | Curcumin, DMC, BMDC | [149] |
Acute, single-blind crossover study, 100 mg, 250 mg, 1000 mg | 15 (healthy) | |||||
Turmeric (C3 complex) | Acute study. 1 single dose (4 g) | 8 (healthy) | HPLC | Serum | Curcumin | [154] |
3–4-week intervention study. (8 g/day) | 15 (with HNSCC) | |||||
Turmeric (curcuma extract capsule) | Dose escalation: 440 mg–2200 mg/day. 4 months | 15 (colorectal cancer) | HPLC-UV | Blood, urine, feces | COS (only detected in feces) | [25] |
Turmeric (C3 complex) | Dose escalation study. 4-month intervention (450, 900, 1800, 3600 mg). 4 months | 15 (colorectal adenocarcinoma patients) | LC-MS | Plasma, urine, feces | Curcumin (plasma, urine, feces), COG (plasma, urine), DMC (plasma, urine), BDMC (plasma), DMC-G (plasma, urine), DMC-S (plasma) COS (plasma, urine, and feces). | [145] |
Turmeric (C3 complex, 10 or 12 g) | Acute study | 12 (healthy) | HPLC | Plasma | COG and COS | [139] |
Turmeric | 3-month intervention with different doses each group (500, 1000, 2000, 4000, 8000 mg/day) | 25 cancer | HPLC-UV | Serum (0 h, 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 14 h, and 24 h) | Curcumin (only in serum) | [144] |
Urine (0–2 h, 2–4 h, 4–8 h, and 8–24 h) | ||||||
Turmeric (Theracurmin®) | Acute study. Curcumin in powder and Theracurmin® in liquid (30 mg). | 12 Sprague-Dawley rats and 14 humans | LC-MS/MS | Plasma | Theracurmin and curcumin | [148] |
Turmeric (curcumin) | Dose escalation study. C3 complex adm. 500 mg, 1000 mg, 2000 mg, 4000 mg, 6000 mg, 8000 mg, 10,000 mg, and 12,000 mg) | 24 | HPLC | Plasma and serum | Curcumin (just in serum at 10000 and 12,000 mg) | [146] |