To assess the effect of a fixed dose of licorice with a specified amount of glycyrrhizic acid on blood pressure, potassium and sodium levels and cortisol/cortisone balance in normotensive subjects. In order to explore individual genetic influences,…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
bloeddruk, elektrolyten, cortison/cortisol balans
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome will be the difference in 24-hour ambulatory systolic and
diastolic blood pressure after exposure to a fixed dose of licorice
Secondary outcome
Secondary outcome parameters will be the difference in cortisol/cortisone
ratio, potassium, sodium and aldosterone excretion in 24h urine collection.
Furthermore, the difference in concentrations of plasma potassium, sodium,
eGFR, creatinine, aldosterone and plasma renin activity will be measured. In
addition, we will determine the individual weight at the end of the run-in
period (screening) and at the end of the intervention period. Finally, an
exploratory analysis for single nucleotide polymorphisms in the gene encoding
for 11-beta-hydroxysteroiddehydrogenase will be performed in those five
participants with the greatest increase in blood pressure
Background summary
Glycyrrhizic acid is known to induce pseudohyperaldosteronism, which results in
a reduction of the selective conversion of cortisol to cortisone. Cortisol has
a much higher affinity for the mineralocorticoid receptor compared to cortisone
and causes activation of the mineralocorticoid receptors, resulting in
hypertension, increased sodium retention, excessive renal potassium loss, low
renin and reduced aldosterone levels. There is no worldwide consensus of the
legal upper use limit specified for the maximum amount of glycyrrhizic acid
that may be present in foods and supplements. The European Food Safety
Authority (EFSA) determine a maximum level of glycyrrhizic acid in
confectionery of 1500 mg/kg. However, this amount is often exceeded by
manufacturers. A maximal level of 100 mg/person/day glycyrrhizic acid ingestion
in adults is considered to be safe for the majority of the population, but many
individuals exceed the recommended amount. Licorice induced hypertension has
been focus of a few studies, but the individual susceptibility to licorice
exposure and variations in blood pressure and urinary excretion of
cortisol/cortisone ratio has not been systematically assessed.
Study objective
To assess the effect of a fixed dose of licorice with a specified amount of
glycyrrhizic acid on blood pressure, potassium and sodium levels and
cortisol/cortisone balance in normotensive subjects. In order to explore
individual genetic influences, blood samples of participants with significant
changes will be considered by investigating the existence of genetic single
nucleotide polymorphisms.
Study design
Controlled clinical experiment
Study burden and risks
In total, this study will take approximately 3 weeks to complete. During this
period study participants will be asked to visit the Academic Medical Centre on
5 occasions. These visits will take approximately 15 minutes to 30 minutes. The
first visit concerns a screening, which will be conducted two weeks before the
start of the study. Participants will be screened by measuring blood pressure
clinically and completing a standard case record form. Information concerning
the study period will be provided. During the second and fourth visit,
participants will be weighted, blood sampling will be performed and the
participants will be requested to perform 24h urinary collection prior to the
visits. Furthermore, a 24h ambulatory monitoring of the blood pressure will be
performed, starting directly after the visit.
The risks associated with this study consists of the possible side-effects of
liquorice ingestion regarding the mineralocorticoid effect of glycyrrhizic
acid. These risks are considered low. Licorice consumption for 8 weeks at a
dose of 2 mg/kg has been shown to have no significant hazardous effect on serum
potassium and cortisol/cortisone levels. In addition, the exposure period of
our study is very brief further minimizing the risk associated with licorice
exposure. There are no direct health benefits that relate to study
participation. The indirect benefit of participating in this study is the
awareness of the possible individual susceptibility and subsequent safety of
the described effects of glycyrrhizic acid after a short period of daily
licorice ingestion.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Willing and able to participate in the study protocol
- Written informed consent
- Age 18-60 years
- Office diastolic blood pressure maximal 90 mmHg and office systolic blood pressure maximal 140 mmHg
- BMI > 18 or < 35 g/m2
- No use of medication which affects the primary or secondary outcome measurements such as diuretics, antihypertensive drugs and NSAIDs < six weeks before start of the study
- Willing to adhere to the study protocol
- Accessible veins on arm(s) as determined by examination at information meetings
Exclusion criteria
- Allergy to one of the ingredients of licorice
- Office blood pressure >140/90 mm
- Reported alcohol consumption > 28 units/week or recreational drug use
- Existing cardiovascular diseases
- Use of medication which affects the primary or secondary outcome measurements such as diuretics, antihypertensive drugs and NSAIDs < six weeks before start of the study
- Currently on a medically prescribed diet, or slimming diet
- Potassium <3.5 mmol/l
- eGFR <60
- Excessive ingestion of licorice (>200 gr/week) or >3 litre of licorice tea per week
- Pregnancy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL64405.018.17 |
| OMON | NL-OMON26713 |