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
| 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 | 21 g LE vs. 1600 mg GL | 941 | Acute crossover study | 16 (8) | U | U | HPLC-UV | Targeted | Plasma (up to 36 h) | 18-GA (both after LE and GL consumption) | [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] | |
aCalculated based on the report of the European Scientific Committee on Food, reporting a mean glycyrrhizin content in liquorice confectionery of 0.17% [96]. This is not calculated for LE and LFO, as it is unclear what the exact percentages of these compounds are in liquorice itself
bIf BMI was reported in the article, only height and/or weight were reported. If nothing was reported at all, we have written down U
cAmount GA was first converted to amount GL, as 130 mg GA is equivalent to 225 mg GL, according to [50]
*HMDB-ID is only reported once for the same candidate biomarker of food intake
18-GA 18(β)-glycyrrhetic acid or 18(β)-glycyrrhetinic acid, 3-MGA 3β-monoglucuronyl-18β-glycyrrhetinic acid, BW body weight, GC-MS gas chromatography-mass spectrometry, GL glycyrrhizin, H height, HPLC high-performance liquid chromatography, LC-ESI-MS liquid chromatography-electrospray ionization-tandem mass spectrometry, LC-MS/MS liquid chromatography-tandem mass spectrometry, LE liquorice extract, LFO liquorice flavonoid oil, Ref. reference, SPE-LC-MS/MS solid phase extraction liquid chromatography tandem mass spectrometry, U unknown: values not reported in the article, UV ultraviolet, W weight