A Balanced Risk-Benefit Analysis to Determine Human Risks Associated with Pyrrolizidine Alkaloids (PA)-The Case of Herbal Medicinal Products Containing St. John's Wort Extracts (SJW).

Nutrients. 2018 Jun 22;10(7). pii: E804. doi: 10.3390/nu10070804. Habs M1, Binder K2, Krauss S3, Müller K4, Ernst B5, Valentini L6, Koller M7. Author information 1 Faculty of Medicine, LMU-University of Munich, 80336 Munich, Germany. info@michael-habs.de. 2 Didactics of Mathematics, University of Regensburg, 93053 Regensburg, Germany. karin.binder@mathematik.uni-regensburg.de. 3 Didactics of Mathematics, University of Regensburg, 93053 Regensburg, Germany. stefan.krauss@mathematik.uni-regensburg.de. 4 Center for Clinical Studies, University Hospital Regensburg, 93053 Regensburg, Germany. karolina.mueller@ukr.de. 5 General Medicine Unit, University Hospital Regensburg, 93053 Regensburg, Germany. dr.b.ernst@t-online.de. 6 Institute of Evidence-Based Dietetics, University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany. valentini@hs-nb.de. 7 Center for Clinical Studies, University Hospital Regensburg, 93053 Regensburg, Germany. michael.koller@ukr.de. Abstract OBJECTIVES: Pyrrolizidine alkaloids (PA) exist ubiquitously in our environment. More than 6000 plants, about 3% of the world’s flowering plants, are known to synthesize PA. As a consequence, many herbal ingredients, including St. John’s wort (SJW), are contaminated with PA that can possess acute and subchronic toxic effects as well as mutagenic and genotoxic properties. Therefore, the possible benefits of SJW as an herbal remedy against depression need to be weighed against the possible risks of unwanted PA intake. METHODS: We searched the literature regarding the current knowledge on PA and evaluated the evidence on the antidepressant effects of quantified SJW extract based on a Cochrane Review and the current practice guidelines on depression. Risks are depicted in form of a risk ladder and benefits in form of an icon array. RESULTS: Evidence from clinical studies indicates that quantified SJW extract is an effective treatment option for mild to moderate depression with fewer side effects than conventional antidepressants. Health statistics from different countries do not quantify cases of death caused by PA intake. However, deaths due to suicide, often triggered by depression, are common (11 in 1000 in Germany in 2015) and rank between fatalities due to liver diseases (16 in 1000) and household accidents (10 in 1000). CONCLUSIONS: Quantified SJW extract is a safe and effective treatment option, and its potential of treating depression outweighs the (hypothetical) risk of unwanted PA intake. KEYWORDS: St. John’s wort extract (SJW); pyrrolizidine alkaloids (PA); risk-benefit analysis PMID: 29932143 PMCID: PMC6073194 DOI: 10.3390/nu10070804 Free PMC Article