Soya-bean lecithin – Lecithinum ex soya (Glycine max (L.) Merr.)
|Latin name of the genus:||Lecithinum ex soya|
|Latin name of herbal substance:||Glycine max (l.) merr.|
|Botanical name of plant:||Herbalref.com|
|English common name of herbal substance:||Soya-bean lecithin|
Latin name of the genus: Lecithinum ex soya
Botanical name of plant: Glycine max (L.) Merr.
English common name of herbal substance: Soya-bean lecithin
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
•Herbal substance(s) Not applicable
Soya lecithin is phospholipids obtained from seeds of Glycine max (L). Merr. Soya bean is an annual herbaceous plant in the family Fabaceae (legume or bean family) that is cultivated. The fruit contains
The following herbal preparations have been reported as constituents of medicinal products on the market in the EU/EEA Member States (for further information see section 2 “Data on medicinal use”):
For oral use:
Soya lecithin contains
In addition to the herbal preparations reported as constituents of medicinal products, there is a broad range of dietary soya products on the market, including whole soya foods, soya flours, textured soya proteins, soya protein concentrates, soya protein isolates, isoflavone rich soya proteins, isoflavone extracts from the soya seed or soya germ, isolated isoflavone mixtures, pure genistein, lecithin products of varying purity and soya oils. The composition of the bioactive compounds differs markedly between products and is affected by processing methods. Only references where a medicinal use is described or indicated, and where the extracts have been properly described, are taken into account in the assessment report.
•Combinations of herbal substance(s) and/or herbal preparation(s) including a description of vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products assessed, where applicable.
1.2. Search and assessment methodology
Scientific databases: PubMed, Embase, Cochrane Database of Systematic Reviews
A PubMed search on soybean found 38,193 articles in February 2015. Thus, to be able to find relevant articles among this high number of citations, additional database searches were performed combining the following search terms: lecithin, phosphatidylcholine, phospholipid, polyenylphosphatidylcholine, polyunsaturated phosphatidylcholine, Essentiale, Lipostabil, extract, soya, soybeans, glycine max, cholesterol, hypercholesterolemia, lipids, LDL, HDL, hyperlipidemia, liver, hepatic, hepatitis, hepatotoxic, exhaustion, stress, tension, anxiety, hypersensitivity, allergy, immunology, drug interactions, humans. The citations found were manually screened and all English articles deemed relevant were accessed and included in the assessment report. Further references found in lists of references were included, if deemed relevant. An additional search in PubMed was performed in May 2016 combining the following search terms: soy and lecithin; soya and lecithin; soybean and lecithin; soyabean and lecithin.
Books, acts of law and regulations (see list of references in Annex): PDR for Herbal Medicines (LaGow ed. 2004); Martindale The Extra Pharmacopoeia (Reynolds ed., 1989); Hager’s Handbuch der Pharmazeutischen Praxis (Hänsel ed., 1993); Lehrbuch der Pharmakognosie und Phytopharmazie (Steinegger, Hänsel, 1972); Herbal Medicine (Barnes ed. 2007); Expanded Commission E Monographs (Blumenthal ed. 2000); The Review of Natural Products (der Marderosian ed. 2015).
Search engines used: Google
Medical databases: Micromedex, HerbMed, MedlinePlus, ESCOP, WHO
Toxicological databases: TOXLINE, HSDB. LactMed
Data from EU and
2. Data on medicinal use
2.1.Information about products on the market
Information about products on the market in the EU/EEA Member States
Information on medicinal products marketed in the EU/EEA
Table 1: Overview of data on soya lecithin
This overview is not exhaustive. It is provided for information only and reflects the situation at the time when it was established.
Information on relevant combination medicinal products marketed in the EU/EEA
Information on other products marketed in the EU/EEA (where relevant)
2.1.2. Information on products on the market outside the EU/EEA
2.2. Information on documented medicinal use and historical data from literature
Soya lecithin is used in the food and pharmaceutical industry for technical purposes, because it represents an easily digestible emulsifier of natural origin (e.g. margarine production and pharmaceutical emulsions). In medicine, it has been used in general physical weakness and to strengthen the nerves. Lecithin has also been used in certain diseases of the liver and fat metabolism (Steinegger and Hänsel, 1972).
In Hagers Handbuch der Pharmazeutischen Praxis, soya lecithin is reported to have been used in mild dyslipidaemia, in particular mild hypercholesterolemia, if dietary measures alone are not sufficient. Average daily dosage is 3.5 g. Traditionally, it has been used for the relief of physical weakness, concentration difficulties and to strengthen the nerves (Hänsel, 1993).
According to the Commission E, soya lecithin has historically been used in case of poor nutrition, rickets, anaemia, diabetes and tuberculosis. Furthermore, soya lecithin has been used to treat hypercholesterolemia, neurologic disorders, and liver disorders, including fatty liver and toxic liver damage. The Commission E has published two positive monographs on soya lecithin (Blumenthal et al., 2000).
1.Soy lecithin (lecithinum ex soya)
In 1988 the Commission E approved soya lecithin extracted from soya beans and its preparations in effective dosage for moderate disturbances of fat metabolism, especially hypercholesterolemia if dietary measures are not sufficient.
Available dosage recommendations are the following:
Preparations from soya beans for oral intake containing total phospholipids in their natural mixture composition corresponding to 3.5 g
2.Soy phospholipid with
In 1994 the Commission E approved the internal use of soya phospholipid with
–less severe forms of hypercholesterolemia in which diet and other
–improvement of subjective complaints, such as loss of appetite and feeling of pressure in the region of the liver in toxic nutritional liver disease and chronic hepatitis; prerequisite to the therapy of chronic liver disease is the recognition and avoidance of noxious agents – in the case of liver disease, alcohol abstinence. In chronic hepatitis adjuvant therapy with phospholipids of soya beans is only indicated when improvement of symptoms is discernible from other therapy.
Daily dosage is
It is summarised in the Review of Natural Products, that lecithin is used for its emulsifying properties in the food, pharmaceutical, and cosmetic industries. Proposed pharmacological use of lecithin includes treatment for hypercholesterolemia, neurologic disorders, manic disorders, and liver ailments (The Review of Natural Products, 2014).
2.3. Overall conclusions on medicinal use
Based on the information obtained from Member States and literature, medicinal use of soya lecithin has been reported in the EU/EEA at least since 1966. According to the market overview the soya bean preparation in Table 2 fulfils the criteria of medicinal use throughout a period of at least 30 years, including at least 15 years within the EU/EEA.
Table 2: Soya bean preparation that fulfil the criteria of medicinal use throughout a period of at least 30 years, including at least 15 years within the EU/EEA considered acceptable for the EU herbal monograph
Soya lecithin has been used for the relief of temporary fatigue and sensation of weakness since 1966, i.e. traditional medicinal use according to Directive 2004/24/EC is considered fulfilled for this indication.
Soya lecithin as a medicinal product has also been used for more than 30 years in the EU/EEA for the treatment of mild hypercholesterolemia if diet and other
Authorised products with the indication mild hypercholesterolemia can be found on the EU market for more than 10 years. The clinical efficacy of soya lecithin, based on Article 10a of Directive 2001/83/EC
Furthermore, soya lecithin has been used to improve subjective complaints e.g. loss of appetite, feeling of pressure in the right epigastrium due to hepatic damage in the EU/EEA at least since 1976. However, hepatic damage is not considered appropriate for
Authorised products with the indication ‘improvement of subjective complaints e.g. loss of appetite, feeling of pressure in the right epigastrium due to hepatic damage’ can be found on the EU market for more than 10 years. The availability of clinical evidence for soya lecithin to establish recognised
efficacy and an acceptable level of safety based on Article 10a of Directive 2001/83/EC (well- established use), is evaluated in section 4. “Clinical data”.
The amphipathic phospholipids make up the lipid bilayer found in all cell membranes and influence numerous cellular functions (Gundermann et al. 2011). The
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
3.1.1. Primary pharmacodynamics
In decreased performance such as fatigue and sensation of weakness
No data found. However, one experimental study indicates that soybean lecithin may improve memory impairment in aged rats (Suzuki et al., 2001).
In the scientific literature, there are some publications on the hypercholesterolemic properties of dietary soya lecithin in animals. Although this assessment report has focused on soya lecithin used as medicinal product some other publications are also mentioned.
Adding soya lecithin (3.4%) to the diet reduced
Reduction of LDL cholesterol as well as an increase in the level of HDL cholesterol was observed in rats feed a hypercholesterolemic diet in combination with lecithin (2.5 or 0.7%) (Jimenez et al., 1990). However, 6% soya lecithin had no effect on the serum cholesterol level in rats fed on a diet containing 0.5% cholesterol although lecithin compared to corn oil reduced cholesterol absorption (O’Mullane and Hawthorne, 1982).
Soybean lecithin reduced total plasma cholesterol without a decrease in HDLC in guinea pig fed by cholesterol diet (O’Brien and Corrigan, 1988).
Gundermann et al. reviewed in 2011 that cytoprotective properties of lecithin have been corroborated in 25 in vitro studies and in 145 in vivo experiments in 8 different animal species. In these studies, lecithin has primarily been administrated to avoid hepatic toxicity induced by chemicals (e.g. carbon tetrachloride) or drugs (e.g. cyclosporine A) (Gundermann et al., 2011).
Fatty liver with cholangitis with bile duct proliferation, cholestatsis and fibrosis were induced in rabbits by atherogenic diet for 18 months. For rabbits receiving additional feeding of soya lecithin (3%) for an additional 4 months only some cholangitis with minimal fibrosis was observed (Hunt and Duncan, 1985).
Lecithin had both preventive and curative effect on
3.1.2. Secondary pharmacodynamics
No data found.
3.1.3. Safety pharmacology
No data found.
3.1.4. Pharmacodynamic interactions
No data found.
Relevant experimental studies on soya lecithin to support the proposed indication are limited since most experimental studies have poorly described extracts, inadequate posology or lack of relevant control groups. However, none of the reported pharmacological studies constitute any cause for safety concerns.
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
The absorption rate following oral administration within 24 h is higher than 90% in animals (Gundermann et al., 2011). The Commission E describes that phospholipids are degraded to lysophophatidylcholine in the intestine and absorbed primarily in this form (animal data). In the gut wall, the phospholipids are in part
Phospholipids are primarily incorporated into the liver, with minor incorporation into other organs such as the gastrointestinal tract, spleen, lungs, muscles, kidneys and brain (Gundermann et al., 2011).
In plasma, phosphatidylcholine and other phosphoglycerides are tightly bound to lipoproteins or albumin, or to both (Blumenthal et al., 2000).
Phosphatidylcholine and other phosphoglycerides are degraded through a series of
Renal excretion after a single dose in the first eight days was 17.4% of the administered dose in rats and 17.7% in rhesus monkeys. The excretion in the faeces was low, with
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
3.3.1. Single dose toxicity
In the Commission E monograph on lecithin enriched extracts from soya bean, doses of phosphatidylcholine of up to 10 g/kg bw in mice and rats and 4.5 g/kg bw in rabbits given intravenous, intraperitoneally, and orally in a single dose are reported to be
Phosphatidylinositol from soya lecithin at doses of up to 2 g/kg of was administrated once orally to male and female rats. There were no deaths or any clinical sign in any group throughout the observation period (Honda et al., 2009).
3.3.2. Repeat dose toxicity
Phosphatidylinositol from soya lecithin was repeatedly administered orally to male and female rats at daily doses of 100, 300 and 1,000 mg/kg for 13 weeks. Neither death nor any toxicological signs during the administration period and no changes related to the test substance administered were observed in any group with regard to body weight, food consumption, ophthalmoscopy, hematology, blood biochemistry, necropsy, organ weights or histopathology. Based on these results, the
No data have been found for soya lecithin. Genotoxic evaluation of phosphatidylinositol from soya lecithin has been carried out using the bacterial reverse mutation test (Ames test) and in vitro chromosome aberration test in compliance with the OECD guidelines for testing chemicals. In the Ames test, the strains Salmonella typhimurium TA100, TA1535, TA 98 and TA1537 and Escherichia coli WP2uvrA were used. The concentration range tested in Ames test with and without metabolic activation was
No data found.
3.3.5. Reproductive and developmental toxicity
In the Commission E monograph on lecithin enriched extracts from soya bean, doses of up to 3.75 g/kg bw in pregnant animals, animals embryos, and animal neonates showed no pathology of toxicity to reproduction. The lowest teratogenic or
intravenous administration was more than 1 g/kg bw. In rabbits teratogenic dosages were greater than 1 g/kg bw for oral administration and greater than 0.5 g/kg bw in intravenous administration (Blumenthal et al., 2000).
Two reproductive and developmental toxicity studies on dietary soya lecithin in rats have been found in the scientific literature (Bell and Lundberg, 1985; Bell and Slotkin, 1985). In the study by Bell and Lundberg, pregnant rat dams and offspring were exposed to a 5 or 2% soya lecithin preparation or a control diet. The authors report that sensorimotor deficits (reflex righting and swimming development) were seen in the 5% soya lecithin preparation group. Later, animals exposed to lifelong 5 or 2% soya lecithin preparations were hypoactive, had poor postural reflexes, and showed attenuated morphine analgesia. In another study by Bell and Slotkin, rats exposed perinatally to dietary commercial soya lecithin preparation showed alterations in sensorimotor development and brain cell maturation (latencies for righting responses measured on postnatal days
3.3.6. Local tolerance
The allergic potency of soya have been evaluated and presented in the ‘Public statement on the allergenic potency of herbal medicinal products containing soya or peanut protein’ (EMA/HMPC/138139/2005) (see section 5.3 Adverse events, serious adverse events and deaths).
3.3.7. Other special studies
Genotoxicity and carcinogenicity have not been fully evaluated. Since the genotoxic potential of soya lecithin has not been fully evaluated, a European Union list entry cannot be recommended from a
Reproductive and developmental toxicology have not been fully evaluated. In two publications on dietary soya lecithin in rats, the authors report developmental toxicity. Since the composition of soya lecithin might differ between food and medicinal products, the relevance of these studies for soya lecithin as active ingredient in medicinal products on the EEA market is not known. As there is limited information on reproductive and developmental toxicity, the use during pregnancy and lactation cannot be recommended.
3.4. Overall conclusions on
The available documentation (information from literature, products available on the market and valid registrations within the EU) show a
Safety during pregnancy and lactation has not been established. In the absence of sufficient data, the use during pregnancy and lactation is not recommended.
4. Clinical Data
4.1. Clinical pharmacology
4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
Phospholipids make up the lipid bilayer found in all cell membranes and influence numerous cellular functions. Polyunsaturated fatty acids are basic constituents of the phospholipids, influencing membrane fluidity and modulating the activities of
Soya lecithin is claimed to have beneficial effects in hypercholesterolemia by reducing total cholesterol and low density lipoprotein cholesterol
4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
Absorption, distribution, metabolism and elimination of dilinoeylphosphatidylcholine (DLPC) have been reported in a study on five patients after single oral administration of 1 g of DLPC labelled with 3H in choline and 14C in the two linoleic acid residues. Based on data from faecal excretion and renal elimination measured up to 7 days, it was estimated that more than 90% was absorbed, either intact or after intestinal hydrolysis to lysophosphatidylcholine. Peak plasma 3H levels were reached in 6 to 24 hours at about 20% of the total administered dose, whereas 14C maximum was reached in 4 to 12 hours at about 28% of the total administered dose. A large portion of the radioactivity from labelled oral phosphatidylcholine appeared in phosphatidylcholine of plasma lipoproteins and red blood cells (Zierenberg et al., 1982).
4.2. Clinical efficacy
In addition to the herbal preparations reported as constituents of medicinal products, there is a broad range of dietary soya products on the market. The composition of the bioactive compounds differs markedly between products and is affected by processing method. Therefore, only soya lecithin preparations included in medicinal products on the
4.2.1. Dose response studies
No relevant clinical study has been found.
4.2.2. Clinical studies (case studies and clinical trials)
Soya lecithin in decreased performance such as fatigue and sensation of weakness
There are no studies found concerning soya lecithin and effects on performance such as fatigue and sensation of weakness.
Soya lecithin in the treatment of mild hypercholesterolemia
For the data base search on soya lecithin in hypercholesterolemia, all clinical studies found, whether controlled or not, have been included. However, only studies on soya lecithin products as medicinal products on the EEA market were further evaluated. Studies on soya lecithin with unknown composition as well as unclear or irrelevant posology were excluded. Also, studies on healthy volunteers, patients on dialysis, patients with diabetes and patients with alcoholic fatty liver diagnosis were excluded (Kirsten et al., 1989; Kirsten et al., 1994). The included studies are presented in Table 3.
For the assessment on clinical efficacy of soya lecithin in hyperlipidemic treatment, the EMA document ‘Guideline on clinical investigation of medicinal products in the treatment of lipid disorders’ (EMA/CHMP/748108/2013) is considered appropriate to use. The guideline recommends:
•A relative reduction in low density lipoprotein cholesterol
•For medicinal products modifying lipid parameters other than
•Studies for the evaluation of efficacy or safety of a new
•When specifically claimed, patients with familial hypercholesterolemia (heterozygous and homozygous) should normally be studied in separate clinical trials, based on their cholesterol levels and clinical genetic characteristics
•All measurements should be performed under standardised, fasting conditions following a dietary
•Comparative studies with accepted therapy are expected for evaluating the efficacy and safety of newer
•Duration will depend on their expected outcome but should last at least a minimum of 3 months (for known mechanisms of action) and preferably up to 12 months (for others)
The guideline also discusses that blood lipid levels may be affected by other clinical conditions such as diabetes. If included, patients with type 2 diabetes mellitus should be represented in adequate numbers that will permit
Soya lecithin in subjective complaints due to hepatic damage
For the data base search on soya lecithin in hepatic damage, all clinical studies found, whether controlled or not, have been included. However, only studies on soya lecithin products as medicinal products on the EEA market were further evaluated and presented in table 4. The diverse study populations and results are inconclusive and the conditions not relevant for a TU product. The relevance of the studies presented in table 4 is therefore limited.
Table 3: Clinical studies on soya lecithin containing medicinal products on the EEA market in the treatment of hypercholesterolemia
Table 4: Clinical studies on soya lecithin containing medicinal products with hepatic indications on the EEA market
4.3. Clinical studies in special populations (e.g. elderly and children)
No clinically relevant study in special populations has been found.
4.4. Overall conclusions on clinical pharmacology and efficacy
There are several clinical studies on the cholesterol lowering effect of soya lecithin, however, very few studies have been published during the last 20 years. In particular, there are only two studies on soya lecithin medicinal products found in the literature (Kesaniemi et al., 1986; ter Welle et al., 1974). Both studies are small, open and exploratory, and do not support a cholesterol lowering effect of soya lecithin. The current requirements for
The effect of soya lecithin with hepatic indications has been studied in patients with different liver diseases such as chronic hepatitis (Niederau et al., 1998; Jenkins et al., 1982), hepatic failure (Singh and Prasad, 1998), alcoholic fatty liver (Turecky et al., 2003) and alcoholic liver disease (Lieber et al., 2003). Generally, the composition of the products used in these studies are not well described. Furthermore, none of the hepatic indications are relevant for
In the scientific literature, there are no clinical studies on soya lecithin in the improvement of subjective complaints e.g. loss of appetite, feeling of pressure in the right epigastrium due to hepatic damage. Hence, Article 10a of Directive 2001/83/EC
5. Clinical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trials in humans
No data found.
5.2. Patient exposure
Aside from market presence and data from studies, there are no concrete data concerning patient exposure.
Phospholipids are mainly obtained by food consumption
5.3. Adverse events, serious adverse events and deaths
Dietary soya products are known to cause allergic reactions including severe anaphylaxis in persons with soya allergy. Patients with known allergy to peanut protein carry an enhanced risk for severe reactions to soya preparations. The allergic potency of soya and peanut has been evaluated in the ‘Public statement on the allergenic potency of herbal medicinal products containing soya or peanut protein’ (EMA/HMPC/138139/2005).
In addition to allergic reactions, the information obtained from the market overview of medicinal products containing soya lecithin includes reports on gastrointestinal disorders (such as soft stool and diarrhoea) and skin reactions (such as urticaria, exanthema, and pruritus).
5.4. Laboratory findings
No data available.
5.5. Safety in special populations and situations
5.5.1. Use in children and adolescents
According to the information obtained from the market overview, soya lecithin used for the relief of temporary fatigue and sensation of weakness, has not been used in children under 12 years of age.
In the information obtained from the market overview of medicinal products containing soya lecithin, the antiphospholipid syndrome is contraindicated in some products on the market. However, in guidelines on the current treatment of antiphospholipid syndrome there are no recommendations that soya lecithin should be avoided for these patients (Lim, 2013; Tuthill 2009).
5.5.3. Special warnings and precautions for use
If the symptoms worsen during the use of the medicinal product, a doctor or a qualified health care practitioner should be consulted.
5.5.4. Drug interactions and other forms of interaction
No interaction studies have been performed.
5.5.5. Fertility, pregnancy and lactation
Safety during pregnancy and lactation has not been established. In the absence of sufficient data, the use during pregnancy and lactation is not recommended. No fertility data are available.
No case of overdose has been reported.
5.5.7. Effects on ability to drive or operate machinery or impairment of mental ability
No studies on the effect on the ability to drive and use machines have been performed.
5.5.8. Safety in other special situations
5.6. Overall conclusions on clinical safety
Based on limited data from clinical experience, mainly cases of gastrointestinal discomfort and hypersensitivity reactions have been reported. The frequencies of the undesirable effects are not known.
Soya lecithin used for the relief of temporary fatigue and sensation of weakness, has a long standing medicinal use in the EU. If patients with known hypersensitivity to soya bean, peanut or other plants of the Fabaceae (legume) family and to birch pollen are excluded, a traditional use is considered safe if administration follows the instructions as specified in the monograph.
6. Overall conclusions
Soya lecithin as a medicinal product has been used for more than 30 years in the EU/EEA for the treatment of mild hypercholesterolemia if diet and other
There are only two clinical studies on soya lecithin medicinal products found in the literature. Other studies have been excluded and not assessed. The included studies are small, open and do not support a cholesterol lowering effect of soya lecithin. The current requirements for
Furthermore, soya lecithin has been used to improve subjective complaints e.g. loss of appetite and feeling of pressure in the right epigastrium due to hepatic damage, in the EU/EEA at least since 1976. Hepatic damage is not appropriate for
Soya lecithin has been used for the relief of temporary fatigue and sensation of weakness, throughout a period of at least 30 years, including at least 15 years within the EU/EEA, i.e. traditional medicinal use according to Directive 2004/24/EC is considered fulfilled. If patients with known hypersensitivity to soya bean, peanut or other plants of the Fabaceae (legume) family and to birch pollen are excluded, a traditional use is considered safe if administration follows the instructions as specified in the monograph. The use in children under 12 years of age has not been established due to lack of adequate data.
Therapeutic area for browse search: Fatigue and weakness.