Table 1 List of reported candidate liquorice biomarkers of intake, including information about dosage, study design, number of subjects, method used, sample type and the primary references
From: Biomarkers of food intake for cocoa and liquorice (products): a systematic review
Dietary factor | Dose of intervention | Comparable to no. of grams of liquorice containing 0.17% GLa | Study design | Number of subjects (no. of men) | Age range (years) | BMI rangeb (kg/m2) | Analytical method | Approach | Sample type and time | Candidate biomarkers of food intake | HMDB ID* | Primary ref. | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Liquorice (products) | |||||||||||||
Solid | Katzen Kinder by Katjes (0.05% GL) | 200 g | 135 | Acute single-dose study | 4 (1) | 26–29 | 18.6–28.6 | LC-MS/MS (LC-ESI-MS) | Targeted | Blood (0, 0:05, 1, 2, 3, 5 and 7 h) Urine (regularly) | Blood, 18-GA (highest after 6 h; 150–434 ng/ml) Urine − | HMDB0011628 | [53] |
|  | Solid liquorice (0.23% GL) | 50, 100 and 200 g daily for 5 days 500 g within 4 h | 68, 135 and 271 676 | Parallel intervention study (5 days) Acute single-dose study | 3 (0) 1 (1) | 19–23 22 | U U | GC-MS | Targeted | Urine (all up to 5 days) | Urine, 18-GA |  | [52] |
Isolated compounds | Glycyrrhizin (GL) | 600 mg in 2 dl water (excretion study) | 353 | Acute single-dose study | 6 (5) | 24–40 | U | HPLC-UV | Targeted | Urine (all up to 4 days) | 18-GA 3-MGA (Cmax 0.49–2.69 μg/ml) | HMDB0037827 | [99] |
Glycyrrhetinic acid (GA) | 500 mg | 509c | Acute single-dose study | 10 (10) | 24–38 | U | LC analyser | Targeted | Serum (0, 2, 4, 7, 10 and 24 h) Urine (0, 2, 4, 7, 10 and 24 h) | Serum, 18-GA (max after 2–4 h 13.4 μmol/l) Urine − |  | [54] | |
Liquorice extract (LE) vs. glycyrrhizin | 21Â g LE vs. 1600Â mg GL | 941 | Acute crossover study | 16 (8) | U | U | HPLC-UV | Targeted | Plasma (up to 36Â h) | 18-GA (both after LE and GL consumption) | Â | [55] | |
Glycyrrhetinic acid | 500, 1000 and 1500 mg with water | 294, 588 and 882 | Parallel single-dose study | 6 (6) | 27–31 | H, 176–180 cm W, 65–73 kg | HPLC | Targeted | Plasma (− 0.5 h, every 30 min up to 8, 9, 10 and 12 h; 1000 mg additionally at 14 and 24 h; 1500 mg additionally at 48 h) Urine (24 h) | Plasma, 18-GA (Cmax; 500, 4.5 mg/l; 1000, 7 mg/l; 1500, 9 mg/l, tmax 3-4 h) Urine, 18-GA, and 18-GA glucuronides (only at 1500 mg dose) | 18-GA glucuronides: not in HMDB | [51] | |
Liquid | Liquorice flavonoid oil (LFO, 90% MCT, 8% polyphenols, 1% glabridin) | 300, 600 and 1200 mg of LFO vs. placebo | – | Parallel single-dose study Parallel placebo-controlled intervention study (1 week) Parallel placebo-controlled intervention study (4 weeks) | 15 (15) 42 (21) 60 (30) | 20–60 | BW > 50-kg men > 40-kg women | SPE-LC-MS/MS | Targeted | Plasma (0, 2, 4, 6, 8 and 24 h) Plasma (0, 4 and 24 h on day 1 and day 7) Plasma (0 h on days 1, 14 and 28) | Glabridin (Cmax at 4 h, around 0.8–2.1 ng/ml depending on the dose) | HMDB0034188 | [56] |
Mixture | Glycyrrhetic acid, glycyrrhizin and solid liquorice (0.15% GL) | 130 mg 18-GAc in water-propyleneglycol 225 mg GL in water 150-g sweet liquorice 150-g salted liquorice | 132 | 4-way random acute crossover study | 16 (8) | U | U | HPLC | Targeted | Plasma (− 1, 2, 2.5, 4, 5.5, 7, 8.5, 10, 11.5, 13, 14.5, 18, 22, 32, 48 and 56 h) | 18-GA (Cmax about 1000 μg/l, same after salty or sweet-tasting liquorice) |  | [50] |