Licorice and Home Blood Pressure

Licorice and Home Blood Pressure: a Randomized Crossover Trial

Out-of-office blood pressure is more strongly associated with cardiovascular risk than office blood pressure. Licorice is known to raise blood pressure, but no previous studies have measured the effects on home blood pressure. The aim of this study is to analyze the association between licorice intake and home blood pressure.

Study Overview

• Status: Completed
• Conditions: Hypertension,Essential
• Intervention / Treatment: Other: Sweet licorice; Other: Salty licorice

Detailed Description

Healthy volunteers will be invited to participate in a randomized, non-blinded, cross-over study. Participants will be randomized to either of two groups with a 1:1 allocation ratio, stratified by sex. Intervention will be sweet licorice and control will be salty licorice. A run-in period of 1 week will be followed by a 2-week intervention/control, a 2-week washout period, another 2-week control/intervention period and again a 2-week washout period. Home blood pressure will be measured continuously, and blood samples (including potassium and aldosterone) will be collected every two weeks. Analyses will be made comparing baseline characteristics of the two groups, intervention/control and washout period results of the two groups to look for potential carry-over effects, and finally comparing intervention and washout period results respectively to the baseline data to look for the effects of licorice.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Östergötland
    • Norrköping, Östergötland, Sweden, 60239
      • Cityhälsan Centrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18 to 30 years

Exclusion Criteria:

• known hypertension, cardiovascular disease, kidney disease, liver disease, hormonal disease, peanut allergy, eating disorder or headache disease (including tension headache and migraine)
• known alcohol abuse or drug abuse (including cannabis and anabolic steroids)
• treatment with hormonal drugs (including oral contraceptives
• known intolerance to licorice intake

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Intervention first, control after ("Sweet then salty"); This arm will be divided into the following periods: Run-in period: 7 days without any licorice intake Intervention period: 14 days with sweet licorice intake First wash-out period: 14 days without any licorice intake Control period: 14 days with salty licorice intake Second wash-out period: 14 days without any licorice intake.	Other: Sweet licorice; Ecologic, vegan and gluten free, low-sodium sweet licorice pastilles made from Glycyrrhiza glabra, with a manufacturer specified content of 4% sugars, 2% glycyrrhizin and 0.03% salt, will be used as intervention. The exact glycyrrhizin content will be determined before the study begins, and participants will be instructed to consume a daily licorice dose that is equivalent to 100 mg of glycyrrhizin.; Other Names: Glycyrrhiza glabra; Other: Salty licorice; A vegan and gluten free salty licorice without glycyrrhizin, flavored with ammonium chloride, with a manufacturer specified content of 0% sugars and 0.05% salt, will be used as control. The amount of salty licorice will be the same as for sweet licorice, and thus determined after the glycyrrhizin content analysis of the sweet licorice.
Other: Control first, intervention after ("Salty then sweet"); This arm will be divided into the following periods: Run-in period: 7 days without any licorice intake Control period: 14 days with salty licorice intake First wash-out period: 14 days without any licorice intake Intervention period: 14 days with sweet licorice intake Second wash-out period: 14 days without any licorice intake.	Other: Sweet licorice; Ecologic, vegan and gluten free, low-sodium sweet licorice pastilles made from Glycyrrhiza glabra, with a manufacturer specified content of 4% sugars, 2% glycyrrhizin and 0.03% salt, will be used as intervention. The exact glycyrrhizin content will be determined before the study begins, and participants will be instructed to consume a daily licorice dose that is equivalent to 100 mg of glycyrrhizin.; Other Names: Glycyrrhiza glabra; Other: Salty licorice; A vegan and gluten free salty licorice without glycyrrhizin, flavored with ammonium chloride, with a manufacturer specified content of 0% sugars and 0.05% salt, will be used as control. The amount of salty licorice will be the same as for sweet licorice, and thus determined after the glycyrrhizin content analysis of the sweet licorice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic home blood pressure (mmHg)	Systolic home blood pressure (mmHg)	Mean at the end of 14 days of intervention compared with mean during run-in period
Diastolic home blood pressure (mmHg)	Diastolic home blood pressure (mmHg)	Mean at the end of 14 days of intervention compared with mean during run-in period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight (kg)	Body weight (kg)	Mean at the end of 14 days of intervention compared with mean during run-in period
Plasma potassium (mmol/L)	Plasma potassium (mmol/L)	Mean at the end of 14 days of intervention compared with mean during run-in period
Plasma sodium (mmol/L)	Plasma sodium (mmol/L)	Mean at the end of 14 days of intervention compared with mean during run-in period
Plasma renin (mIU/L)	Plasma renin (mIU/L)	Mean at the end of 14 days of intervention compared with mean during run-in period
Serum aldosterone (μmol/L)	Serum aldosterone (μmol/L)	Mean at the end of 14 days of intervention compared with mean during run-in period

Collaborators and Investigators

• Sponsor: Linkoeping University
• Investigators: Study Director: Fredrik H Nyström, MD, PhD, Linkoeping University

Publications and helpful links

General Publications

• Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; Authors/Task Force Members:. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018 Oct;36(10):1953-2041. doi: 10.1097/HJH.0000000000001940. Erratum In: J Hypertens. 2019 Jan;37(1):226.
• Deutch MR, Grimm D, Wehland M, Infanger M, Kruger M. Bioactive Candy: Effects of Licorice on the Cardiovascular System. Foods. 2019 Oct 14;8(10):495. doi: 10.3390/foods8100495.
• Parati G, Stergiou GS, Bilo G, Kollias A, Pengo M, Ochoa JE, Agarwal R, Asayama K, Asmar R, Burnier M, De La Sierra A, Giannattasio C, Gosse P, Head G, Hoshide S, Imai Y, Kario K, Li Y, Manios E, Mant J, McManus RJ, Mengden T, Mihailidou AS, Muntner P, Myers M, Niiranen T, Ntineri A, O'Brien E, Octavio JA, Ohkubo T, Omboni S, Padfield P, Palatini P, Pellegrini D, Postel-Vinay N, Ramirez AJ, Sharman JE, Shennan A, Silva E, Topouchian J, Torlasco C, Wang JG, Weber MA, Whelton PK, White WB, Mancia G; Working Group on Blood Pressure Monitoring and Cardiovascular Variability of the European Society of Hypertension. Home blood pressure monitoring: methodology, clinical relevance and practical application: a 2021 position paper by the Working Group on Blood Pressure Monitoring and Cardiovascular Variability of the European Society of Hypertension. J Hypertens. 2021 Sep 1;39(9):1742-1767. doi: 10.1097/HJH.0000000000002922.
• Spinks EA, Fenwick GR. The determination of glycyrrhizin in selected UK liquorice products. Food Addit Contam. 1990 Nov-Dec;7(6):769-78. doi: 10.1080/02652039009373939.
• Rizzato G, Scalabrin E, Radaelli M, Capodaglio G, Piccolo O. A new exploration of licorice metabolome. Food Chem. 2017 Apr 15;221:959-968. doi: 10.1016/j.foodchem.2016.11.068. Epub 2016 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): December 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: licorice2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: As specified below.
• IPD Sharing Time Frame: After publication in a peer-reviewed journal and for the period of time for which local archive regulations stipulate.
• IPD Sharing Access Criteria: To be determined on a case by case basis.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No