Conclusions

This is a paper for discussion. This does not represent the views of the Committee and should not be cited.

108.             Three Echinacea species – E. purpurea, E. angustifolia and E. pallida have been used medicinally to relieve the symptoms and shorten the duration of cold and flu infections. Echinacea preparations can be made from the dried roots of all three species, the fresh or dried aerial parts and the pressed juice from E. purpurea. Ethanolic extracts are also often used in many Echinacea products. The effects of Echinacea are due to the combination of bioactive metabolites including alkylamides, caffeic acid derivatives and polysaccharides. The composition of these compounds varies across the species, the plant parts, season, growing conditions and extraction methods used.

109             There is evidence from in vitro and in vivo studies that Echinacea preparations can inhibit viral entry and modulate immune responses following infection. Herbal products containing E. purpurea, E. angustifolia and E. pallida have herbal medicinal licenses in EU/EEA member states and THR license from the MHRA based on traditional use for the relief of common cold symptoms in adults and children over 12 years of age. Regulatory authorities, including the EMA and MHRA, do not recommend the use of Echinacea containing medicinal products during pregnancy or lactation due to the absence of high‑quality, guideline‑conforming reproductive and developmental toxicity studies and the limited human evidence available. THR licensed Echinacea products in the UK also carry warnings advising against use in these populations. Nevertheless, survey data indicate that up to 10% of pregnant women may use Echinacea for the treatment or prevention of cold and flu symptoms or for immune support.

110.             In addition to products with a THR license, there is a range of foods and food supplements containing Echinacea and its extracts. The most common food supplements are tablets and capsules, and the majority of these products carry a warning against their use in pregnancy/lactation and a recommendation for short term use only. There are also food products such as tea and honey which contain Echinacea. Whilst products with THR are acknowledged in this paper, the focus in the conducted exposure assessment has been the consumption of Echinacea foods and food supplements.

111.             The in vivo toxicological studies on Echinacea suggested that it has low toxicity. Clinical studies reported that Echinacea products are well tolerated with minor and reversible side effects including gastrointestinal disturbances and allergic skin reactions. There are isolated case reports of Echinacea causing erythema nodosum, hyperoesinophilia, leucopenia, thrombocytopenia and hepatotoxicity, but causality has not been confirmed. Pharmacovigilance cases and follow up investigation of selected patients also suggested that Echinacea can trigger allergic reactions, as serious as anaphylaxis in some cases, in patients with pre-existing atopic diseases. EMA (2014) recommends Echinacea preparations should be used with caution in patients with asthma or history of atopy. Due to its potential for immune system modulation, Echinacea is also not recommended for people with autoimmune diseases, immunodeficiencies, immunosuppression and diseases of the white blood cell system.

112.             There is an uncertainty around the potential of Echinacea to interact with prescription medicines during pregnancy. In vitro and in vivo studies demonstrated that Echinacea could affect the activity of CYP enzymes leading to inhibition of CYP1A2 and CYP3A4. However, the clinical relevance of these in vitro and in vivo studies is unknown as there are limited number of human studies investigating the interactions of Echinacea with over the counter or prescription medicines.

113.             Contaminants such as heavy metals, fungi, bacteria, mycotoxins and pesticides are sometimes found in herbal preparations. There is an uncertainty of how much risk the potential contaminants in Echinacea preparations pose to pregnant consumers due to lack of research. Whilst studies have reported that cadmium and lead levels detected in Echinacea preparations have been lower than the WHO limits, the presence of fungal contaminants and mycotoxins found in some Echinacea products can pose an additional risk during pregnancy.

114.             There is a lot of uncertainty around the safety of using Echinacea products during pregnancy or lactation due to limited data from in vitro, in vivo and clinical studies. In vitro and in vivo OECD guideline conforming studies suggested that Echinacea is not genotoxic. There are two studies in mice, one in pigs and two studies in rabbits looking at the effects of Echinacea supplementation during pregnancy. Whilst the two mice studies highlighted potential increase in foetal loss and altered angiogenesis with Echinacea, the sample sizes were small and some of the results reported on foetal angiogenesis were conflicting. The pig and rabbit studies did not report any significant differences in relation to birth weight, pregnancy outcomes and frequency of malformations between Echinacea and control groups. There are human observational studies describing the effects of Echinacea on pregnancy outcomes and they did not highlight any adverse effects associated with gestational use of Echinacea. These studies rely on self-reported use of Echinacea during pregnancy and the dose, preparation or duration of use were not specified.

115.             The doses used in clinical studies on the efficacy of Echinacea are comparable to the estimated exposures to Echinacea in women of child-bearing age, calculated by the FSA Exposure Assessment Team. Echinacea was well-tolerated in these clinical studies, but they did not include pregnant or lactating women. In addition, an exact comparison between different Echinacea products is challenging due to products containing different combinations of the three medicinally used species, their dried plant parts and extracts. Some food products such as tea and honey often lack information on the exact species, plant parts or extracts used.

116.             Overall, Members emphasised that the available information is insufficient to support a robust risk assessment or the derivation of any health‑based guidance values. However, the Committee did not identify any reason to expect adverse effects in humans from the current levels of exposure of Echinacea as part of the maternal diet.