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The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis

Journal of Human Hypertension volume 31, pages 699–707 (2017)Cite this article

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Abstract

There have been numerous case reports of severe adverse events including deaths following chronic licorice ingestion. The aim of the present study was to evaluate the effect of chronic ingestion of licorice on blood pressure, plasma potassium, plasma renin activity and plasma aldosterone. A search of MEDLINE, PubMed, EMBASE, CENTRAL, DARE, CINAHL and Current Contents Connect was performed from inception through to 26 April 2017. Trials that included a treatment group ingesting a product containing at least 100 mg of glycyrrhizic acid daily were selected. Pooled mean changes from baseline with 95% confidence intervals were calculated for diastolic blood pressure, systolic blood pressure, plasma potassium, plasma renin activity and plasma aldosterone using a random effects model. An assessment of dose–response was also undertaken. A total of 18 studies (n=337) were included in the meta-analysis. There was a statistically significant increase in mean systolic blood pressure (5.45 mm Hg, 95% CI 3.51–7.39) and diastolic blood pressure (3.19 mm Hg, 95% CI 0.10–6.29) after chronic ingestion of a product containing glycyrrhizic acid. Plasma potassium (−0.33 mmol l−1, 95% CI −0.42 to 0.23), plasma renin activity (−0.82 ngml−1 per hour, 95% CI −1.27 to −0.37) and plasma aldosterone (−173.24 pmol l−1, 95% CI −231.65 to −114.83) were all significantly decreased. A significant correlation was noted between daily dose of glycyrrhizic acid and systolic blood pressure (r2=0.55) and diastolic blood pressure (r2=0.65), but not for the other outcome measures. Hence, chronic licorice ingestion is associated with an increase in blood pressure and a drop in plasma potassium, even at modest doses. This is of particular relevance for individuals with existing cardiovascular disease.

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References

  1. Sontia B, Mooney J, Gaudet L, Touyz RM . Pseudohyperaldosteronism, liquorice, and hypertension. J Clin Hypertens 2008; 10: 153–157.

    Article  Google Scholar 

  2. Robles BJ, Sandoval AR, Dardon JD, Blas CA . Lethal liquorice lollies (liquorice abuse causing pseudohyperaldosteronism). BMJ Case Rep 2013; 2013, http://casereports.bmj.com/content/2013/bcr-2013-201007.long.

  3. Chubachi A, Wakui H, Asakura K-I, Nishimura S, Nakamoto Y, Miura AB . Acute renal failure following hypokalemic rhabdomyolysis due to chronic glycyrrhizic acid administration. Intern Med 1992; 31: 708–711.

    Article  CAS  Google Scholar 

  4. Shintani S, Murase H, Tsukagoshi H, Shiigai T . Glycyrrhizin (licorice)-induced hypokalemic myopathy. Report of 2 cases and review of the literature. Eur Neurol 1992; 32: 44–51.

    Article  CAS  Google Scholar 

  5. Achar KN, Abduo TJ, Menon NK . Severe hypokalemic rhabdomyolysis due to ingestion of liquorice during Ramadan. Aust N Z J Med 1989; 19: 365–367.

    Article  CAS  Google Scholar 

  6. Elinav E, Chajek-Shaul T . Licorice consumption causing severe hypokalemic paralysis. Mayo Clin Proc 2003; 78: 767–768.

    Article  Google Scholar 

  7. Heikens J, Fliers E, Endert E, Ackermans M, van Montfrans G . Liquorice-induced hypertension—a new understanding of an old disease: case report and brief review. Neth J Med 1995; 47: 230–234.

    Article  CAS  Google Scholar 

  8. van Beers EJ, Stam J, van den Bergh WM . Licorice consumption as a cause of posterior reversible encephalopathy syndrome: a case report. Crit Care 2011; 15: R64.

    Article  Google Scholar 

  9. van der Zwan A . Hypertension encephalopathy after liquorice ingestion. Clin Neurol Neurosur 1993; 95: 35–37.

    Article  CAS  Google Scholar 

  10. Crean AM, Abdel-Rahman S-E-DT, Greenwood JP . A sweet tooth as the root cause of cardiac arrest. Can J Cardiol 2009; 25: e357–e358.

    Article  Google Scholar 

  11. Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CHL, Edwards CRW . Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. Lancet 1987; 2: 821–824.

    Article  CAS  Google Scholar 

  12. Epstein MT, Espiner EA, Donald RA, Hughes H, Cowles RJ, Lun S . Licorice raises urinary cortisol in man. J Clin Endocrinol Metab 1978; 47: 397–400.

    Article  CAS  Google Scholar 

  13. Armanini D, Lewicka S, Pratesi C, Scali M, Zennaro MC, Zovato S et al. Further studies on the mechanism of the mineralocorticoid action of licorice in humans. J Endocrinol Invest 1996; 19: 624–629.

    Article  CAS  Google Scholar 

  14. Palermo M, Shackleton CH, Mantero F, Stewart PM . Urinary free cortisone and the assessment of 11 beta-hydroxysteroid dehydrogenase activity in man. Clin Endocrinol 1996; 45: 605–611.

    Article  CAS  Google Scholar 

  15. MacKenzie MA, Hoefnagels HL, Jansen RWMM, Benraad TJ, Kloppenborg PWC . The influence of glycyrrhetinic acid on plasma cortisol and cortisone in healthy young volunteers. J Clin Endocrinol Metab 1990; 70: 1637–1643.

    Article  CAS  Google Scholar 

  16. Olukoga A, Donaldson D . Liquorice and its health implications. J R Soc Promot Health 2000; 120: 83–89.

    Article  CAS  Google Scholar 

  17. Størmer FC, Reistad R, Alexander J . Glycyrrhizic acid in liquorice - evaluation of health hazard. Fd Chem Toxic 1993; 31: 303–312.

    Article  Google Scholar 

  18. Simpson FO, Currie IJ . Licorice consumption among high school students. N Z Med J 1982; 95: 31–33.

    CAS  PubMed  Google Scholar 

  19. Spinks EA, Fenwick GR . The determination of glycyrrhizin in selected UK liquorice products. Food Addit Contam 1990; 7: 769–778.

    Article  CAS  Google Scholar 

  20. US Food and Drug Administration. Black licorice: trick or treat? https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm277152.htm (2011).

  21. US Food and Drug Administration. Consumer advisory: black licorice can be a dangerous treat for some. https://www.fda.gov/food/resourcesforyou/consumers/ucm231078.htm (2014).

  22. National Health Service. Can eating too much black liquorice be bad for you? NHS Choices. http://www.nhs.uk/chq/Pages/Can-eating-black-liquorice-be-bad-for-you.aspx?CategoryID=51&SubCategoryID=215 (2015).

  23. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010; 8: 336–341.

    Article  Google Scholar 

  24. National Heart Lung, and Blood Institute. Quality Assessment Tool for before-after (pre-post) studies with no control group. National Institutes of Health. Study Quality Assessment Tools. https://www.nhlbi.nih.gov/health-pro/guidelines/in-develop/cardiovascular-risk-reduction/tools/before-after (2014).

  25. Sigurjónsdóttir HÁ, Ragnarsson J, Franzson L, Sigurdsson G . Is blood pressure commonly raised by moderate consumption of liquorice? J Hum Hypertens 1995; 9: 345–348.

    PubMed  Google Scholar 

  26. DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.

    Article  CAS  Google Scholar 

  27. Higgins JPT, Thompson SG, Deeks JJ, Altman DG . Measuring inconsistency in meta-analyses. Brit Med J 2003; 327: 557–560.

    Article  Google Scholar 

  28. Egger M, Smith GD, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. Brit Med J 1997; 315: 629–634.

    Article  CAS  Google Scholar 

  29. Orwin R . A fail-safe N for effect size in meta-analysis. J Educ Stat 1983; 8: 157–159.

    Google Scholar 

  30. Bernardi M, D'Intino PE, Trevisani F, Cantelli-Forti G, Raggi MA, Turchetto E et al. Effects of prolonged ingestion of graded doses of licorice by healthy volunteers. Life Sci 1994; 55: 863–872.

    Article  CAS  Google Scholar 

  31. Armanini D, De Palo CB, Mattarello MJ, Spinella P, Zaccaria M, Ermolao A et al. Effect of licorice on the reduction of body fat mass in healthy subjects. J Endocrinol Invest 2003; 26: 646–650.

    Article  CAS  Google Scholar 

  32. Armanini D, Mattarello MJ, Fiore C, Bonanni G, Scaroni C, Sartorato P et al. Licorice reduces serum testosterone in healthy women. Steroids 2004; 69: 763–766.

    Article  CAS  Google Scholar 

  33. Ploeger B, Mensinga T, Sips A, Seinen W, Meulenbelt J, DeJongh J . The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic model. Drug Metab Rev 2001; 33: 125–147.

    Article  CAS  Google Scholar 

  34. Kjeldsen K . Hypokalemia and sudden cardiac death. Exp Clin Cardiol 2010; 15: e96–e99.

    PubMed  PubMed Central  Google Scholar 

  35. Bowling CBB, Pitt B, Ahmed MI, Aban IB, Sanders PW, Mujib M et al. Hypokalemia and outcomes in patients with chronic heart failure and chronic kidney disease: findings from propensity-matched studies. Circulation 2010; 3: 253–260.

    PubMed  Google Scholar 

  36. Prospective Studies Collaboration, Lewington S Prospective Studies Collaboration, Clarke R Prospective Studies Collaboration, Qizilbash N Prospective Studies Collaboration, Peto R Prospective Studies Collaboration, Collins R Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–1913.

    Article  Google Scholar 

  37. van Uum SHM, Walker BR, Hermus ARMM, Sweep CGJ, Smits P, de Leeuw PW et al. Effect of glycyrrhetinic acid on 11beta-hydroxysteroid dehydrogenase activity in normotensive and hypertensive subjects. Clin Sci 2002; 102: 203–211.

    Article  CAS  Google Scholar 

  38. Sigurjónsdóttir HÁ, Manhem K, Axelson M, Wallerstedt S . Subjects with essential hypertension are more sensitive to the inhibition of 11 beta-HSD by liquorice. J Hum Hypertens 2003; 17: 125–131.

    Article  Google Scholar 

  39. Leskinen MH, Hautaniemi EJ, Tahvanainen AM, Koskela JK, Paallysaho M, Tikkakoski AJ et al. Daily liquorice consumption for two weeks increases augmentation index and central systolic and diastolic blood pressure. PLoS ONE 2014; 9: e105607.

    Article  Google Scholar 

  40. Epstein MT, Espiner EA, Donald RA, Hughes H . Effect of eating liquorice on the renin-angiotensin aldosterone axis in normal subjects. Brit Med J 1977; 1: 488–490.

    Article  CAS  Google Scholar 

  41. Ferrari P, Sansonnens A, Dick B, Frey FJ . In vivo 11beta-HSD-2 activity: variability, salt-sensitivity, and effect of licorice. Hypertension 2001; 38: 1330–1336.

    Article  CAS  Google Scholar 

  42. Forslund T, Fyhrquist F, Frøseth B, Tikkanen I . Effects of licorice on plasma atrial natriuretic peptide in healthy volunteers. J Intern Med 1989; 225: 95–99.

    Article  CAS  Google Scholar 

  43. Kageyama Y, Suzuki H, Saruta T . Glycyrrhizin induces mineralocorticoid activity through alterations in cortisol metabolism in the human kidney. J Endocrinol 1992; 135: 147–152.

    Article  CAS  Google Scholar 

  44. MacKenzie MA, Hoefnagels HL, Jansen RWMM, Benraad TJ, Kloppenborg PWC . The influence of glycyrrhetinic acid on plasma cortisol and cortisone in healthy young volunteers. J Clin Endocrinol Metab 1990; 70: 1637–1643.

    Article  CAS  Google Scholar 

  45. Sigurjónsdóttir HÁ, Franzson L, Manhem K, Ragnarsson J, Sigurdsson G, Wallerstedt S . Liquorice-induced rise in blood pressure: a linear dose-response relationship. J Hum Hyperten 2001; 15: 549–552.

    Article  Google Scholar 

  46. Sigurjónsdóttir HÁ, Axelson M, Johannsson G, Manhem K, Nystrom E, Wallerstedt S . The liquorice effect on the RAAS differs between the genders. Blood Press 2006; 15: 169–172.

    Article  Google Scholar 

  47. Sobieszczyk P, Borlaug BA, Gornik HL, Knauft WD, Beckman JA . Glycyrrhetinic acid attenuates vascular smooth muscle vasodilatory function in healthy humans. Clin Sci 2010; 119: 437–442.

    Article  CAS  Google Scholar 

  48. Tu JH, He YJ, Chen Y, Fan L, Zhang W, Tan ZR et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol 2010; 66: 805–810.

    Article  CAS  Google Scholar 

  49. van Gelderen CEM, Bijlsma JA, van Dokkum W, Savelkoul TJF . Glycyrrhizic acid: the assessment of a no effect level. Hum Exp Toxicol 2000; 19: 434–439.

    Article  CAS  Google Scholar 

  50. Yan M, Fang PF, Li HD, Xu P, Liu YP, Wang F et al. Lack of effect of continuous glycyrrhizin administration on the pharmacokinetics of the P-glycoprotein substrate talinolol in healthy volunteers. Eur J Clin Pharmacol 2013; 69: 515–521.

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to acknowledge the generous Summer Research Scholarship provided by the University of Sydney that funded the costs of retrieving the medical records for this study.

Author contributions

Study concept and design: EME and GDE. Acquisition of data: RP. Analysis and interpretation of data: GDE and RP. Drafting of the manuscript: RP. Critical revision of the manuscript for important intellectual content: GDE. Statistical analysis: GDE. Study supervision: GDE.

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  1. The Whiteley-Martin Research Centre, Discipline of Surgery, The University of Sydney, Nepean Hospital, Sydney, New South Wales, Australia

    R Penninkilampi, E M Eslick & G D Eslick

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Correspondence to G D Eslick.

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Penninkilampi, R., Eslick, E. & Eslick, G. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. J Hum Hypertens 31, 699–707 (2017). https://doi.org/10.1038/jhh.2017.45

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