Introduction and Background

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

Introduction

1.             The Scientific Advisory Committee on Nutrition (SACN) last considered the maternal diet and nutrition in relation to offspring health in its reports on ‘The influence of maternal, foetal and child nutrition on the development of chronic disease in later life’ (SACN, 2011) and on ‘Feeding in the first year of life’ (SACN, 2018). In the latter report, the impact of breastfeeding on maternal health was also considered. In 2019, SACN agreed to conduct a risk assessment on nutrition and maternal health, focusing on maternal outcomes during pregnancy, childbirth and up to 24 months after delivery.

2.             SACN agreed that, where appropriate, other expert committees would be consulted and asked to complete relevant risk assessments. A provisional list of chemicals was proposed by SACN Members. However, this was subject to change following discussion by the COT. A scoping paper was presented to the Committee (TOX/2020/45) to define the scope of the work from a toxicological safety perspective and request their input on the selection of candidate chemicals or chemical classes that could be added or removed.

3.             As part of this work, the Committee decided it would be useful to consider the use of dietary supplements during pregnancy. A scoping paper (TOX/2020/51) was presented, reviewing the dietary supplements commonly used during pregnancy. These supplements are not officially recommended by relevant health and regulatory authorities but are promoted by anecdotal evidence and unofficial sources as having various purported benefits.

4.             The review was confined to herbal dietary supplements which would be regulated under food law, as opposed to traditional herbal medicines, which are overseen by the Medicines and Healthcare Products Regulatory Agency (MHRA). Following this review, the COT suggested that Echinacea required further investigation, noting that both human and animal in vitro and in vivo data were available. The main areas of concern included general toxicity to the mother, effects on the development of the foetus or embryo and possible interactions with drugs.

5.             Based on the COT’s recommendations, a more extensive literature search was undertaken to evaluate the safety of Echinacea use during pregnancy and is presented below (for full details of the search method, see Annex A).

Background

Uses

6.    Echinacea is a genus of herbaceous flowering plants, comprised of ten species and originally native to North America (Ahmadi et al., 2024). Three Echinacea species (Echinacea purpurea, Echinacea pallida, and Echinacea angustifolia) are used medicinally for the prevention and treatment of the common cold, influenza, and upper respiratory tract infections (Ardjomand-Woelkart and Bauer, 2015). E. purpurea is the most widely used and extensively studied of the three. Prior to 1968, Echinacea angustifolia and Echinacea pallida were considered to be different varieties of the same species until a revision of the genus described them as two separate species (WHO, 1999). 

7.    Echinacea herbal products are often sold as dietary supplements to boost the immune system and to reduce the symptoms of common cold and upper respiratory tract infections.  These are popular products in North America and Europe, generating more than 300 million USD annually in the U.S. alone (Ahmadi et al., 2024). 

8.    Complementary and alternative medicines (CAM), including herbal and traditional preparations, are often perceived as safer than conventional medicines. Women are the highest consumer of CAM and survey data suggests that their use continues during pregnancy as women may turn to ‘natural alternatives’ due to fear of teratogenicity from conventional medicines (Hall et al., 2011). The most commonly used herbal preparations during pregnancy include raspberry leaf, ginger, chamomile, Echinacea and cranberry (Cuzzolin et al., 2010; Hall et al., 2011; Holst et al., 2011; Nordeng et al., 2011). 

9.    Echinacea extracts are used for respiratory infections (colds and flu, bronchitis, strep throat, toothache), urinary tract infections, skin disorders (Staphylococcus infections, cold sores, ulcers, wounds, burns, insect bites, eczema, allergies) and rheumatoid arthritis (Hudson, 2012). Between 4.3% (Holst et al., 2011) and 9.2% (Cuzzolin et al., 2010) of pregnant women report using Echinacea during pregnancy for the treatment of cold and flu, boosting the immune system and the prevention of common cold (Cuzzolin et al., 2010; Holst et al., 2011). 

Constituents and preparations

10.    The fresh or dried aerial parts and the fresh pressed juice from the flowering tops of E. purpurea, as well as the whole plant, and the dried roots of all three species are used medicinally (Barnes et al., 2010). The composition of bioactive metabolites varies across the three species and their respective plant parts (Table 1). It is generally considered that there is no single constituent or group of constituents responsible for the activity of Echinacea. The combined effects of several groups of bioactive constituents, including the alkylamides, caffeic acid derivatives, polysaccharides and alkenes, contribute to the biological activity of Echinacea (Barnes et al., 2010). It is worth noting that some of the key pharmacological effects of Echinacea such as its antitumor, antioxidant, antimicrobial, antifungal, antiviral, and immunomodulatory activities are mainly attributed to the caffeic acid derivatives and alkylamides (Ahmadi et al., 2024). The chemical structures of some of the most common Echinacea constituents are shown in Figure 1.

Table 1: Major constituents of medicinally used Echinacea species (adapted from (Barnes et al., 2010).

Figure 1 is the chemical structures of the different echinacea components. The are 5 chemical structures shown in black line and text.

Figure 1. Chemical structures of Echinacea constituents. Adapted from Barnes et. al., 2010.

11.    The concentration of the different bioactive constituents in Echinacea preparations is not only affected by the species, plant part, season and growing conditions, but also by the extraction method employed. Different methods of extraction are used for preparing the Echinacea products (Table 2) and the final products can contain powdered plant parts, dry and liquid extracts, pressed and dried pressed juice. There is no consensus of which of the chemical constituent(s) should serve as a standardisation marker (Upton, 2007).

Table 2: Echinacea extraction and preparation methods (Upton, 2007).