ABSTRACT
BACKGROUND: Licorice, through the effects of glycyrrhizic acid (GA), raises blood pressure (BP). The World Health Organization has suggested that 100 mg GA/d would be unlikely to cause adverse effects, but of 13 previously published studies none have been randomized and controlled and independently quantified the GA content. OBJECTIVE: Our aim was to analyze the effects on home BP of a daily licorice intake containing 100 mg GA. METHODS: Healthy volunteers were randomly assigned to start with either licorice or a control product in a nonblinded, 2 × 2 crossover study. Home BP was measured daily, and blood samples were collected at the end of each 2-wk period. RESULTS: There were 28 participants and no dropouts. The median age was 24.0 y (interquartile range 22.8-27.0 y). During the licorice compared with control intake period, the systolic home BP increased [mean difference: 3.1 mm Hg (95% confidence interval [CI]: 0.8, 5.4 mm Hg) compared with -0.3 mm Hg (95% CI: -1.8, 1.3 mm Hg); P = 0.018] and renin and aldosterone were suppressed [mean change: -30.0% (95% CI: -56.7%, -3.3%) compared with 15.8% (95% CI: -12.8%, 44.4%); P = 0.003; and -45.1% (95% CI: -61.5%, -28.7%) compared with 8.2% (95% CI: -14.7%, 31.1%); P <0.001, respectively]. In the quartile of participants with the most pronounced suppression of renin and aldosterone, N-terminal prohormone of brain natriuretic peptide concentration increased during the licorice compared with control period [mean change: 204.1% (95% CI: -11.6%, 419.7%) compared with 72.4% (95% CI: -52.2%, 197.1%); P = 0.016]. CONCLUSIONS: We found licorice to be more potent than previously known, with significant increases in BP, after a daily intake of only 100 mg GA. Thus, the safe limit of intake of this substance might need to be reconsidered. This trial was registered at clinicaltrials.gov as NCT05661721 (https://clinicaltrials.gov/study/NCT05661721).