Scientific Opinion on safety evaluation of Ephedra species for use in food

Abstract

The ANS Panel provides a scientific opinion evaluating the safety in use of Ephedra herb and its preparations originating from Ephedra species when used in food, e.g. in food supplements. Ephedra species contain alkaloids of biological relevance: ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine (cathine), methylephedrine and methylpseudoephedrine. They have sympathomimetic activity and some of them are also used as active ingredients in medicinal products for which adverse effects are described. The use of Ephedra herb in food supplements is prohibited in several European countries, however food supplements containing Ephedra herb, also in combination with caffeine, are offered for sale via the internet. The Panel reviewed the available scientific data on a possible association between the intake of Ephedra herb, its preparations or its alkaloids and potential harmful effects on health. There is wide variation in the concentration of the individual ephedra alkaloids in different Ephedra species and in their preparations for use in food. No adequately specified individual preparations of Ephedra herb are known for which sufficient toxicological data for hazard characterisation exist. Due to the absence of adequate data on genotoxicity, short-term, long-term and reproductive and developmental toxicity the Panel could not provide advice on a daily intake of Ephedra herb and its preparations that do not give rise to concerns about harmful effects to health. Ephedra herb and its preparations in food supplements may result in exposure to total ephedra alkaloids or ephedrine which falls within or may exceed the therapeutic dose ranges for the individual ephedra alkaloids or ephedrine, respectively, in medicinal products. Such an exposure could lead to severe adverse effects, which may be enhanced by the combination with caffeine. The Panel concluded that Ephedra herb and its preparations containing ephedra alkaloids used as food supplements were of significant safety concern at the estimated use levels.

COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy?

“…The presence of a few medicinal plants such as Ephedra in the suggested guidance for COVID-19 is a subject of major concerns. Although Ephedra, listed in the WHO monographs (WHO, 1999), has been used for the treatment of asthma, cough, cold as well as in the management of weight loss (its primary use as a supplement in the USA), globally regulatory agencies have banned food supplements and medicines containing the ephedra alkaloid ephedrine, due to the serious adverse effects especially on the cardiovascular and nervous system and reported deaths (FDA, 2008;EFSA, 2013;EMA, 2015b).…”

Taken to heart—arrhythmic potential of heart-leaf sida, a banned ephedrine alkaloid: a case report

“…was imposed by the European Commission in 2015. 4 , 5 Ephedrine alkaloids were previously sold widely for weight loss, energy, and athletic performance and still used in traditional Asian medicine. Common botanical sources include Ephedra species and Sida cordifolia , otherwise known as ‘heart-leaf sida’ due to the plant’s heart-shaped leaves.…”

“…Thus, existing bans within the E.U., USA, Canada, Australia, and New Zealand do not provide full reassurance about the availability of Ephedra and ephedrine alkaloids. 4 Physicians should actively engage with patients about their use of herbal supplements and encourage more comprehensive regulation for patient safety.…”

The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis

“…Since the use of ephedrine in food supplements has become prohibited in several European countries and in the USA, p -synephrine has gained considerable interest as the main substitute of ephedrine in weight loss products [ 12 , 19 , 20 , 21 ]. Synephrine is similar to ephedrine with regard to its structure and mechanism of action; however, it is less lipophilic, resulting in decreased transport through the blood–brain barrier [ 7 , 22 , 23 , 24 ].…”