---
title: "Glabridin in liquorice pastilles and short-term metabolic effects in young adults"
id: "plos-one-17-glabridin-content-and-metabolic-effects-of-liquorice-confectionaries-a"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-17-glabridin-content-and-metabolic-effects-of-liquorice-confectionaries-a"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0358710"
published_at: "2026-09-22T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Glabridin in liquorice pastilles and short-term metabolic effects in young adults
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-17-glabridin-content-and-metabolic-effects-of-liquorice-confectionaries-a
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0358710)
- **Published At:** 2026-09-22T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This secondary analysis evaluated whether daily intake of 3.3 g of whole liquorice pastilles (from Glycyrrhiza glabra) alters markers of glucose metabolism, blood lipids, systemic inflammation, or calcium metabolism in healthy young adults. - Study design: a randomized, non-blinded 2x2 crossover trial in 28 volunteers aged 18–30 years, with two 2-week intervention periods (liquorice vs control) separated by 2-week washouts. - Intervention product: liquorice pastilles (manufacturer-specified 4% sugars) at 3.3 g/day. Control: sugar-free salty liquorice-flavoured confectionary without declared raw liquorice at 2.9 g/day. Energy contents were similar. - Liquorice pastilles were analysed by LC-MSMS and contained **glabridin** at 0.25 ± 0.14 µg per mg of product. - Primary metabolic endpoints measured after fasting included HbA1c, plasma glucose, insulin, lipid profile (including LDL), high-sensitivity C-reactive protein (**hsCRP**), serum ionized calcium, and plasma parathyroid hormone (PTH). - Laboratory assays were performed at an ISO/IEC 17025-accredited clinical laboratory using standard enzymatic, ECLIA, ion-selective electrode, and immunoturbidimetric methods; samples collected between 08:00–09:00 after overnight fast. - Result summary: No significant changes were observed in markers of dysglycemia, blood lipids, ionized calcium, or PTH attributable to liquorice intake. - hsCRP findings: hsCRP increased by 32.5% (95% CI −9.7 to 74.6) during the liquorice intervention versus a 311.5% increase (95% CI −40.8 to 663.7) during control; between-period difference reached statistical significance (P = 0.045), suggesting liquorice intake attenuated hsCRP elevation relative to control. - Prior work cited by the authors found that 100 mg glycyrrhizic acid (≈3.3 g whole liquorice) raised systolic blood pressure by 3.1 mmHg; the authors conclude potential metabolic/anti-inflammatory effects of glabridin in whole liquorice are unlikely to outweigh known hypertensive risks. - The source excerpt does not report full statistical tables, participant flow details, adverse events, or longer-term outcomes; further methodological and numerical details were not included in the provided text.
## Clinical Analysis & Structured Key Points
Glabridin content and metabolic effects of liquorice confectionaries: A secondary analysis of a randomized crossover trial in young adults | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Background Liquorice, a popular confectionary product, contains several bioactive compounds. Amongst them, glycyrrhizic acid is associated with increased blood pressure, and glabridin is associated with anti-inflammatory and glucose-lowering effects. The aim was to assess the association between short term liquorice intake at a dose known to elevate blood pressure, and markers of dysglycemia, blood lipids, high-sensitivity C-reactive protein (hsCRP), and calcium metabolism. Methods In a 2x2 crossover study, 28 healthy adults were randomized to consume liquorice or a control product in alternating 2-week periods, with measurements of blood glycated haemoglobin A 1c as well as plasma glucose, calcium ion, parathyroid hormone, and lipids at the end of each period. Liquorice glabridin content was determined via LC-MSMS analysis. Results The liquorice contained 0.25 ± 0.14 µg glabridin per mg. The plasma hsCRP value increased by 32.5% (95% CI −9.7 to 74.6) during the intervention period vs 311.5% (95% CI −40.8 to 663.7) during the control period, P = .045. No effects on the other markers were observed. Conclusion Liquorice intake did not improve metabolic markers but attenuated hsCRP elevation. The potential metabolic benefits of glabridin are unlikely to outweigh the hypertensive effects when consumed as whole liquorice. Citation: Åstrand A, Joelsson A, Rådholm K, Nyström FH, af Geijerstam P (2026) Glabridin content and metabolic effects of liquorice confectionaries: A secondary analysis of a randomized crossover trial in young adults. PLoS One 21(9): e0358710. https://doi.org/10.1371/journal.pone.0358710 Editor: Cheorl-Ho Kim, Sungkyunkwan University - Suwon Campus: Sungkyunkwan University - Natural Sciences Campus, KOREA, REPUBLIC OF Received: January 28, 2026; Accepted: August 27, 2026; Published: September 22, 2026 Copyright: © 2026 Åstrand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The individual participant data underlying this study cannot be made publicly available because the dataset contains sensitive health information and, given the small sample size, public sharing would entail a risk of participant re-identification under Swedish legal and ethical requirements. Researchers seeking additional information may contact the Data Protection Officer at Linköping University ( dataskyddsombud@liu.se ), which serves as the institutional point of contact for matters relating to data protection and access to research data. Limited individual-level data may still be shared on a case-by-case basis, subject to applicable legal, ethical, and data protection requirements. Funding: The work was funded by the Strategic Research Network in Circulation and Metabolism at Linköping University (LiU-CircM), King Gustaf V and Queen Victoria Freemason Foundation, The Swedish Heart Lung Foundation and Primary Health Care Centres research fund, Region Östergötland, Sweden (Grant RÖ 2022/13418). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: None of the authors have any conflict of interest to declare. Abbreviations: BP, blood pressure; HbA 1c , glycated haemoglobin A 1c ; hsCRP, high-sensitivity C-reactive protein; LDL, low-density lipoprotein; LC-MSMS, liquid chromatography tandem mass spectrometry; PTH, parathyroid hormone. Introduction Liquorice, produced from the root of the Glycyrrhiza species, is globally used as a flavouring, phytomedicine and confectionaries [ 1 , 2 ]. The main bioactive component of liquorice, glycyrrhizic acid, is known to raise blood pressure (BP) in humans. Previously we found that even a daily intake of 100 mg glycyrrhizic acid, found in 3.3 grams of whole liquorice, raised systolic BP by 3.1 mmHg [ 3 ]. However, liquorice contains several other active substances. An example is the antioxidant isoflavonoid glabridin, first characterized in 1976 and unique to Glycyrrhiza glabra [ 4 , 5 ]. Glabridin has been suggested to possess health-beneficial properties. Interestingly, there are studies showing that glabridin has potential cardiovascular protective effects, including inhibition of low-density lipoprotein (LDL) oxidation and anti-inflammatory properties [ 6 – 8 ]. In mice, glabridin has also shown a comparable glucose-lowering effect to that of common antidiabetic medications [ 9 ]. In vitro, glabridin has been associated with antitumor effects [ 10 – 13 ], increased estrogenic activity [ 14 ], as well as reduced platelet aggregation [ 15 ], oxidative stress [ 16 , 17 ], and myofibroblast activity [ 18 ]. Glabridin may also affect bone metabolism, as liquorice has been shown to increase levels of parathyroid hormone (PTH) [ 19 ]. Despite these suggested effects, few in vivo studies have examined the effects of glabridin, and these have primarily reported reductions in cholesterol levels and LDL oxidation, S1 Table [ 20 – 22 ]. Furthermore, no randomized controlled trial has examined the effect of liquorice on these markers at the low dose evaluated in our study [ 3 ]. Liquorice confectionaries are a dietary source of glabridin, but whether the hypertensive effects of whole liquorice intake can be outweighed by potential beneficial effects on metabolism, blood lipids, and systemic inflammation remains unknown. The aim of this study was therefore to assess the association between a daily intake of 3.3 g of liquorice and markers of dysglycemia, blood lipids, systemic inflammation, and calcium metabolism. Also, given the reported link between glabridin and these markers, we aimed to quantify the glabridin content in the administered liquorice using liquid-chromatography tandem mass spectrometry (LC-MSMS). Methods and materials The metabolic effects of glabridin in young adults This study was a secondary analysis of a crossover study. The methodology has been previously described in detail [ 3 ]. In brief, 28 volunteers aged 18–30 years were recruited from 3 January until 11 April 2023 in Östergötland County, Sweden. Exclusion criteria included known kidney, liver, or endocrine disease, as well as treatment with hormones (including oral contraceptives but not including intrauterine devices). The study had a non-blinded, 2-treatment, 2-period, 2-sequence (2x2) crossover design. After a run-in period, participants were randomized using drawing ballots to alternate between liquorice and a control product in 2-week periods, separated by 2-week wash-out periods. Intervention and control products Liquorice pastilles (from Nature Med S.r.l., Cosenza, Italy), produced from Glycyrrhiza glabra only and with a manufacturer specified content of 4% sugars was used as intervention product. Sugar-free salty liquorice flavoured confectionaries (manufactured by Troll-Gott Konfektyr AB, Årjäng, Sweden) without any declared content of raw liquorice were used as control [ 23 , 24 ]. The energy content of the products was similar ( S2 Table ), and the products have previously been described in detail [ 1 ]. During the intervention period, each participant was instructed to consume 3.3 g of liquorice pastilles daily. During the control period, each participant was asked to consume 2.9 g of the control product daily. Anthropometric measurements and questionnaires All visits took place at a study centre in Norrköping, Östergötland County, Sweden, during 2023. Participants were asked to not use any liquorice for at least 4 weeks before inclusion. Baseline measurements included height, weight, and a questionnaire assessing age, sex, tobacco and alcohol use, and physical activity habits. At the end of each study period, weight measurements were repeated. Blood samples were drawn at baseline and at the end of the control and intervention periods, between 8 and 9 am after an over-night fast, with participants in the seated position after at least 5 minutes of rest. Lipid profile and high-sensitivity C-reactive protein (hsCRP) were analysed from 3 mL plasma tubes with lithium heparin and gel. Calcium ion and insulin were analysed from plasma tubes with serum gel and clot activator of 4 and 3.5 mL respectively. Glycated haemoglobin A 1c (HbA 1c ) was analysed from 3 mL blood tubes with K 2 EDTA; and glucose was analysed from 3 mL FC Mixture tubes containing citrate, natrium fluoride and Na 2 EDTA. Plasma glucose was measured using a hexokinase-based enzymatic photometric method on Cobas c303/c503 (Roche Diagnostics, Mannheim, Germany). Serum insulin was determined by electrochemiluminescence immunoassay (ECLIA) on Cobas e801 (Roche Diagnostics, Mannheim, Germany). Plasma lipids were analysed using an enzymatic colorimetric photometric method on Cobas c503 (Roche Diagnostics, Mannheim, Germany) or a Trinder-reaction photometric method on Indiko (Thermo Fisher Scientific, Waltham, MA, USA). High-sensitivity CRP in plasma was analysed by immunoturbidimetric photometry on Cobas c503 (Roche Diagnostics, Mannheim, Germany). Calcium ion in serum was measured using ion-selective electrode potentiometry on ABL 825 Flex, ABL 90, or ABL 800 (Radiometer, Copenhagen, Denmark). Parathyroid hormone in plasma was quantified using ECLIA on Cobas e801 (Roche Diagnostics, Mannheim, Germany). All blood sample were analysed by validated methods at the ISO/IEC 17025-accredited laboratory Diagnostikcentrum i Östergötland, Linköping, Sweden. Statistical analyses Normality of distributions was assessed using the Shapiro-Wilk test. Continuous variables were shown as the mean and standard deviation, and differences between groups were tested using a 2-sided Wilcoxon rank-sum test. Categorical variables were shown as the frequency and percentage, and differences between groups were tested using a Chi-squared test. Results were evaluated by comparing the mean differences between the run-in period and the intervention and control periods respectively and tested using a 2-sided paired t test for variables with a normal distribution and a 2-sided paired Wilcoxon signed-rank test for variables with a skewed distribution. Individual hsCRP values were further visualized in a sex-stratified paired dot-and-line plot to facilitate interpretation. Data were collected using the REDCap 13.1.35 digital platform (Vanderbilt University, Nashville, TN, USA) and analyses were made using R version 4.3.3 (R Core Team, Vienna, Austria) and R Studio version 2023.12.1 + 402 (Posit Software, Boston, MA, USA). All statistical tests were 2-tailed, with P < .05 considered statistically significant. This study was a secondary analysis of a previously published dataset [ 3 ], and the sample size was therefore not derived from a power calculation for the outcomes of this study. Quantification of glabridin in liquorice confectionaries Chemicals and reagents. A certified reference standard (≥98% pure) of Glabridin was purchased from Sigma-Aldrich (St Louis, MO, USA). LC–MS grade acetonitrile and methanol were obtained from Merck (Darmstadt, Germany). Formic acid was procured from Honeywell Fluka (Brussels, Belgium) and 99.5% ethanol was purchased from Solveco (Rosersberg, Sweden). Ultra-pure water was produced in-house using a Milli-Q Q-POD unit from Merck Millipore (Billerica, MA, USA). Liquid chromatography tandem mass spectrometry analysis. For LC-MSMS analysis a Waters TQ-Absolute instrument (Waters, Solna, Sweden) was used. Mobile phases were 0.01% formic acid in MQ water (A) and 0.01% formic acid in acetonitrile (B). As stationary phase a Waters ACQUITY UPLC BEH C18 Column (50 mm x 2.1 mm, 1.7 μm) was used in combination with a Waters ACQUITY UPLC BEH C18 VanGuard Pre-column (5 mm x 2.1 mm, 1.7 μm). The mobile-phase gradient used was as follows: 40% mobile-phase B was ramped up to 60% within 4 minutes, a 1-minute wash at 90% mobile-phase B and 2-minutes equilibration at 40% B follows. The flowrate was set to 500 μL/min. The column temperature was maintained at 40°C, and the injection volume was set to 1 μL. The samples were extracted and analysed together with a freshly prepared standard curve each day of analysis. Mass detection was performed by a Waters Xevo TQ Absolute (Waters, Stockholm, Sweden) mass spectrometer using electrospray ionization (ESI) interface in negative (ES-) mode. Multiple reaction monitoring method parameters were as follows: dwell time 25 ms, cone voltage 30 V, collision energy 20 eV. The target transition, m/z 323.1 → 201.3, was monitored for 8 minutes. Validation was performed according to the validation scheme by Peters et al. for new analytical methods to be used for analysis of rare analytes [ 25 ]. The calibration function was tested on 5 levels with duplicate standards at: 1, 2, 5, 10, 20 ng/mL and found to be linear ( ) with an R 2 = 0.9988. The repeatability was tested on 2 levels (1 and 10 ng/mL) with 5 repeats each and found to be 3.78% at 1 ng/mL and 3.8% 10 ng/mL respectively. The accuracy was 103% ± 3% at 1 ng/mL and 104% ± 4% at 10 ng/mL. Signal to noise at 1 ng/mL was determined to be 36 and is considered the limit of quantification (LOQ) of the method. Sample preparation and data analysis. One sample of each of the confectionaries were randomly selected for analysis. The pastille (liquorice) was grinded whereafter 10 mg, in triplicates, were weighted and transferred to glass vials for extraction. The control product was cut in small pieces from the middle of the candy and 10 mg in triplicates were weighted and transferred to glass vials. To avoid cross-contamination, the 2 types of confectionaries were handled separately. All samples were extracted in 500 µL 30:70% ethanol: Milli-Q Water for 1 hour at 50°C thereafter they were transferred to injection vials. Prior to LC-MSMS analysis, the liquorice samples were diluted 200 times. The described extraction method was previously published by Tian et al and reported 72.5% recovery for glabridin [ 26 ]. The results were calculated using a freshly prepared standard curve, assumed 72.5% glabridin extraction and expressed as µg glabridin/mg liquorice. Ethical considerations The study complied with the declaration of Helsinki and was approved by the Swedish Ethical Review Authority (Dnr 2022-06163-01). All participants gave written, informed consent prior to participation. For this secondary analysis no extra sampling was performed. The original study was registered at ClinicalTrials.gov before initiation (registration number NCT05661721). Results All 28 participants completed the study, Fig 1 . Of participants, 14 (50%) were men. The mean age was 24.6 (standard deviation, SD 2.9) years, and the mean body mass index was 24.2 (SD 4.7) kg/m 2 . Laboratory results were similar between the 2 groups (intervention then control and control then intervention) at baseline except for plasma PTH, which was 4.3 (Q1-Q3 3.7–4.8) vs 3.2 (Q1-Q3 2.8–4.1) pmol/L, P = .029 ( Table 1 ). Download: PNG larger image TIFF original image Fig 1. Study flow chart. https://doi.org/10.1371/journal.pone.0358710.g001 Download: PNG larger image TIFF original image Table 1. Baseline characteristics of 28 healthy adults according to group. https://doi.org/10.1371/journal.pone.0358710.t001 Comparing plasma hsCRP values between the intervention and control period, it increase by 32.5% (95% CI −9.7 to 74.6) vs 311.5% (95% CI −40.8 to 663.7), P = .045 ( Fig 2 ). However, no significant differences between groups in changes in plasma glucose, blood glycated haemoglobin, serum insulin, plasma lipids, plasma parathyroid hormone and serum calcium ion levels were detected ( Table 2 ). Individual hsCRP trajectories showed substantial variability and no clear sex-specific pattern ( S1 Fig ). Download: PNG larger image TIFF original image Fig 2. Plasma high-sensitivity C-reactive protein during the intervention and control periods. (A) Box plot of the mean change in high-sensitivity C-reactive protein between the run-in and the end of the intervention and control periods, respectively. (B) Line graph of high-sensitivity C-reactive protein during the intervention then control and control then intervention group during each 2-week period. The difference between the control vs intervention period consisted mainly of higher values during the control period of the control-then-intervention group. For the control period, outliers at 4.4 and 8.0 mg/L are not visualized. Abbreviations: C-I, control then intervention; I-C, intervention then control; I/C, intervention/control; WO, wash-out. No missing values were recorded for any measurement, except for 1 (3.6%) missing plasma insulin value during the intervention period. https://doi.org/10.1371/journal.pone.0358710.g002 Download: PNG larger image TIFF original image Table 2. Mean percentage difference in blood sample values between the run-in period and the end of the intervention and control periods, respectively, and the difference between those, in 28 healthy adults. https://doi.org/10.1371/journal.pone.0358710.t002 The measured concentration of glabridin for the intervention product was 1.80 ± 1.01 µg/mL, corresponding to 0.25 ± 0.14 µg glabridin per mg liquorice after accounting for the extraction. Thus, the 3.3-gram dose of the intervention product contained 0.82 ± 0.46 mg of glabridin. In contrast, only trace levels of glabridin, below the lowest calibrator at 1 ng/ml, were detected but could not be quantified in the control product ( Fig 3 ). Download: PNG larger image TIFF original image Fig 3. Quantification of glabridin. A confectionary each from the control and intervention products were cut in small pieces or grinded. The confectionary samples (in triplicates) were mixed with 30% ethanol and incubated for 1h at 50°C. The samples were then analysed by LC-MSMS. The quantification result for the intervention product is shown in a bar chart whereas overlayed chromatograms (representative sample of the control product and the lowest calibrator [1 ng/mL]) are presented to show a qualitative presence of glabridin in the sample chemical structure of glabridin is also visualized. Illustration created with BioRender.com. Abbreviations: EtOH, ethanol; LC-MSMS, liquid chromatography tandem mass spectrometry; Std, calibration standard. https://doi.org/10.1371/journal.pone.0358710.g003 Discussion In this secondary analysis of a cross-over study investigating the effects of short-term low-dose liquorice ingestion, an attenuation of an increase in hsCRP was observed, but no change in glycaemic, lipid values, or calcium metabolism was noted. The metabolic effects of liquorice in young adults The study showed that a daily consumption of 3.3 grams of liquorice attenuated an observed increase in plasma hsCRP but did not alter glycaemic levels, lipid levels, or calcium metabolism despite glabridin presence at a concentration of 0.82 mg. Our study is the first reporting on the effects of whole liquorice intake on glucose or HbA 1c levels in vivo in humans. We showed that a daily liquorice intake during a 2-week period did not affect glycaemic or blood lipid levels when compared to the control product. Although plasma hsCRP increased more during the control vs intervention period, it did not change in absolute terms during either period, indicating that this may reflect normal intra-individual variability rather than a true intervention effect. Further, we did not observe any effect on glycaemic markers. However, this may rela
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