Sambucus – Elderberry (Sambuci fructus)
|Latin name of the genus:||Sambucus|
|Latin name of herbal substance:||Sambuci fructus|
|Botanical name of plant:||Sambucus nigra l.|
|English common name of herbal substance:||Elderberry|
Latin name of the genus: Sambucus
Latin name of herbal substance: Sambuci fructus
Botanical name of plant: Sambucus nigra L.
English common name of herbal substance: Elderberry
- 1. Introduction
- 2. Historical data on medicinal use
- 3. Non-Clinical Data
- 3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
- 3.4. Overall conclusions on non-clinical data
- 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
- 4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
- 4.2. Clinical Efficacy
- 4.2.1. Dose response studies
- 4.2.2. Clinical studies (case studies and clinical trials)
- 4.3. Clinical studies in special populations (e.g. elderly and children)
- 4.4. Overall conclusions on clinical pharmacology and efficacy
- 5. Clinical Safety/Pharmacovigilance
- 6. Overall conclusions
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
The herbal substance consists of the dried, ripe berries of Sambucus nigra L. (elderberry). The wrinkled, more or less spherical drupes are dark
The unripe berries contain toxic constituents such as cyanogenic glycosides and should be avoided in elderberry preparation (Pogorzelski 1982, Kunitz et al. 1984, Batz et al. 2005).
Fresh fruit is more or less spherical/round. Dried elderberry fruits are used as well as fresh fruit. The dried fruits and fresh fruit of elderberry in various herbal preparations were considered for inclusion during the assessment work in support of the establishment of a draft Community herbal monograph.
• Herbal preparation(s)
Comminuted herbal substance
The available information on herbal preparations is described in section 2.2. ‘Information on traditional/current indications and specified substances/preparations’.
•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.
The fruit of Sambucus nigra L. contains several components that may contribute to pharmacological activity. Large amounts of anthocyanins are present in fresh fruits, the main constituents have been identified as
Table 1: Constituents from the fruits of Sambucus nigra L. (elderberries)
*Note* These references were not available.
**Note** Total amount of anthocyanins have been identified in different varieties of the elderberry and increasing with ripeness of the berries.
1.2. Information about products on the market in the Member States
Regulatory status overview
MA: Marketing Authorisation TRAD: Traditional Use Registration
Other TRAD: Other national Traditional systems of registration Other: If known, it should be specified or otherwise add ’Not Known’
This regulatory overview is not legally binding and does not necessarily reflect the legal status of the products in the MSs concerned.
Sambuci fructus is widely used across Europe in various food supplements, but no product containing Sambuci fructus as a single herbal substance/herbal preparation is authorised/registered as medicine according to the available information. Only combination products are reported to be on the market.
In the Czech Republic, a fixed combination (herbal tea for oral use) has been on the market since 1972.
This tea contains Fucus, Frangulae cortex, Sambuci nigrae flos, Sennae folium, Foeniculi fructus, Petroselini radix, Sambuci fructus, Betulae folium and Liquiritiae radix. This tea is used as a supplement in dieting regimens and in obesity complicated with constipation and fluids retention.
In Poland, two fixed combinations have been on the market for 21 years.
1. Herbal tea
The herbal tea in bags contains Frangulae cortex, Sennae folium, Carvi fructus, Sambuci fructus and Menthae piperitae folium.
Oral use: 0.9 – 1.4 g (168 – 252 mg of Sambuci fructus) once daily
The tea is used as a laxative in constipations.
The following adverse drug effects are listed: rarely itch, urticaria, rash in hypersensitive persons; rarely spastic pains abdominal cavity, watery stool; electrolyte and water balance disorders, potassium loss, Pseudomelanosis coli, albuminuria and hematuria in prolonged use.
Extractum compositum (1:2) ex: Helichrysi inflorescentia, Matricariae flore, Coriandri fructus, Sambuci fructus (24:15.5:7.5:3), extraction solvent: ethanol 60% (v/v) + Taraxaci intractum (1:1), extraction solvent: ethanol 96% (v/v).
This extract is traditionally used as a cholagogue in symptoms of dyspepsia.
1.3. Search and assessment methodology
The following electronic databases were searched on various dates from August 2011 to September 2012 with the search terms “Sambucus nigra fructus, Elderberry, and European elderberry”.
PubMed: (No case report of safety concern)
Sambucus nigra fructus: 38 references
Elderberry: 766 references
European elderberry: 18 references
Sambucus nigra fructus: 24 references
Elderberry: 204 references
European elderberry: 101 references
Scifinder: (Both chemical abstracts and Medline)
Sambucus nigra fructus: 13 references
Elderberry: 632 references
European elderberry: 5 references
The Cochrane Library:
Sambucus nigra fructus: No references are obtained
Elderberry: 9 references
European elderberry: 1 reference
Each database was searched from its start to the search dates. All languages were included.
Key text books were also searched for relevant studies. All references from the extracted papers were searched for citations not retrieved in the literature search.
2. Historical data on medicinal use
2.1. Information on period of medicinal use in the Community
The traditional use of the elderberry goes back to ancient times. The traditional medicinal uses of elderberry against cold, as laxative, as diaphoretic and as a diuretic have been documented in scientific literature and several handbooks such as Madaus (1938), Grieve (1931), Bisset and Wichtl (2001) and Wichtl (2004).
Elder is native to Europe, west and central Asia and North Africa. The material of commerce is imported from Russia, Poland, Hungary, Portugal and Bulgaria (Wichtl 2004). Historically elder was a highly valued plant, because almost all the different parts of the plant were used, for various purposes, both as food and in folk medicine in Europe (Blochwich 1677, Vallès 2004). In Europe, the tradition has been to use both the fruits and flowers in folk medicine (Madaus 1938, Grieve 1931).
According to Madaus (1938), a decoction of dried elderberries was used as a laxative in Germany and a tea made from fresh elderberries has been used for the same purpose in Ukraine, Poland and Czechoslovakia since 1887. Elderberry syrup (Roob Sambuci) was also used as a laxative according to Grieve (1931) with reference to the British Pharmacopoeia 1788.
In his reference to the British Pharmacopoeia 1788, Grieve (1931) mentioned that elderberry syrup (Roob Sambuci) has traditionally been used against cold in parts of Europe, including England and Holland. According to Bisset and Wichtl, the drug is used as a diaphoretic in catarrhal complaints (Bisset and Wichtl 2001).
According to Madaus (1938) both fresh elderberries and elderberry juice were used as a diaphoretic in Europe and elderberry syrup (Roob Sambuci) was used to the same purpose according to information mentioned in Wichtl 2004 with reference to the Swiss Pharmacopoeia 1953.
A herbal tea made from dried elderberry fruit has also been used as a diuretic (Bisset and Wichtl 2001, Wichtl 2004).
Elderberry juice has also been used to treat sciatica, headache, dental pain, heart pain, nerve pain, especially in nerve pain and has been mentioned in handbooks such as Wichtl (2004) and Grieve (1931).
Elderberry is still commonly used for various purposes according to published studies and from what is seen in health food stores as food supplements and marketed on various Internet webshops within EU.
2.2. Information on traditional/current indications and specified substances/preparations
Table 2: Evidence regarding the traditional use and posology from handbooks
Other uses mentioned:
Mild diuretic effect is reported in some handbooks such as Grieve 1931, Bisset and Wichtl 2001, Ebadi 2001 and Wichtl 2004. Mild diuretic effect is also mentioned in Karmazín et al. 1984.
Laxative use is also mentioned in the British Pharmacopoeia 1788, Madaus 1938, Grieve 1931, Czech National Norm 1958, Bisset and Wichtl 2001, Wichtl 2004 and in Karmazín et al. 1984.
Elderberry has also been traditionally used against catarrhal conditions, especially in the upper respiratory tract such as cough, fever and colds and has been reported in Bisset and Wichtl 2001, Wichtl 2004 and Greive 1931 with reference to the British Pharmacopoeia 1788.
2.3. Specified strength/posology/route of administration/duration of use for relevant preparations and indications
Elderberry has been used as herbal tea for many years in European countries like Germany, England, Czech Republic and Poland for various complaints. Only a single dose is described in the available sources of information for the herbal tea. A specified daily posology for this herbal preparation is needed to fulfill the criteria for evidence of a traditional medicinal use for a specified posology.
The pharmaceutical dosage form and indication, freshly prepared juice in combination with port wine for use in neuralgia as described by Karl 1970, is not defined as required for a herbal preparation for inclusion in a Community monograph.
Hagers Handbuch (List & Hörhammer 1979) refers to juice pressed from the fresh berries used by Epstein as Spezificum against genuine neuralgia, and it is written that addition of 20% alcohol improves the effects.
Neuralgia is associated with a variety of pain conditions, and is therefore considered to be an indication not suitable to prevent treatment of more serious pathologies. Traditional herbal medicinal products
are intended and designed for use without the supervision of a medical practitioner for diagnostic purposes or for prescription or monitoring of treatment.
The traditional use of elderberry syrup (Roob Sambuci) as a laxative according to the information cited in Wichtl 2004 with reference to the Swiss Pharmacopoeia and Grieve 1931 with reference to the British Pharmacopoeia 1788, is related to use of high doses and without specified posology.
This syrup is also used according to Grieve 1931 to promote perspiration and to be demulcent to the chest. For this use the defined posology is one or two tablespoonsful mixed with a tumblerful of hot water, taken at night. It is described that the syrup should have a thickness as honey according to Grieve 1931. The description on how the syrup is prepared from berries does not provide the necessary information needed in order to calculate a defined strength that can be used to prepare a herbal preparation with an acceptable level of reproducibility from batch to batch.
The listed herbal preparations do not fulfill the requirements for inclusion in a monograph.
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
In vitro experiments
Elderberry extracts (see Table 3) have been tested for immunomodulatory activity on monocytes from healthy individuals, and an increase in their cytokine production was observed in vitro following stimulation. The production of inflammatory cytokines was tested using blood derived monocytes from 12 healthy human donors in vitro. Elderberry extracts and lipopolysaccharid (as a positive control for monocyte activation) were added to the monocytes and incubated. The results show an increase in secretion of proinflammatory cytokines (tumour necrosis
Table 3: Elderberry preparations studied for
the immune response, as demonstrated in human monocyte cultures, to Th1 (inflammation- associated) responses. Treatment of
It has been reported that lectins are able to promote the release of histamine from basophils and mast cells. Sambucus nigra agglutinin (unknown which) can cause allergic reactions because it is able to release interleukins
Barsett et al. (2012) studied the immunomodulatory effects in order to clarify the pharmacology of substances from Sambucus nigra L. They wanted to investigate if the immunomodulating activity of compounds present in berries and flowers of Sambucus nigra were of the same order, or different, and also if the most active components were of high or low molecular weight nature. Defatted material of berries and flowers of Sambucus nigra were extracted with 50% ethanol and with water of 50° C and 100° C. High molecular weight fractions were obtained after gel filtration on BioGelP6DG. The different fractions were investigated for their monosaccharide contents and carbohydrate structures. The immunomodulating effects were investigated using a complement fixing assay as well as a system for measuring the production of NO after stimulation of macrophages with the different fractions. All fractions contained substantial amounts of carbohydrates. Removal of low molecular weight material revealed polysaccharide fractions containing monosaccharides typical for pectins and showed enhanced bioactivity. High molecular weight fractions from elderflowers showed higher bioactivity than the equally extracted fractions from elderberries. The 100°C water flower fraction gave after gel filtration the fraction with the highest activity and with the longest backbone of rhamnogalacturonan I.
Antiviral activity (influenza virus)
The inhibitory activity of a standardised elderberry extract has been studied in cell cultures infected with multiple strains of human influenza A and B type and animal influenza strain of this virus. Darby canine kidney cells were incubated with the standardised elderberry extract. It was shown that the standardised elderberry extract prevented virus to bind to host cell. This inhibition was attributed to the presence of novel flavonoids such as methylated flavonoid
Roschek et al. (2009) studied the
extractions using ethanol diluted with water (4:1, v/v). The major contributors to the
Elderberries contains anthocyanin flavonoids known to possess significant antioxidant properties. Low concentrations (4 µg/ml) of
A fruit juice concentrate made from fresh berries of Aronia (Aronia melanocarpa), elderberry (Sambucus nigra) and macqui (Aristotelia chilensis), was tested for antioxidant activity in vitro. H2O2- induced DNA damage as well as oxidised DNA bases were determined in human tumour HT29 clone 19a cells. Two test methods were used, the micro gel electrophoresis assay (Comet test) which is a sensitive method to measurement of genotoxic effects and DNA damage, and ferric reducing ability assay (FRA assay) to examine intracellular oxidative/antioxidative effects of the samples. The results indicated that intracellular oxidative stress was little affected by natural plant ingredients such as anthocyanins and anthocyanidins. The mechanism behind these antioxidative effects are, however, not clear. In this FRA test, the antioxidative capacity may be a reflection of the compounds’ potential to chelate FeCl3 as well as to scavenge free radicals. Among anthocyanin concentrates, elderberry exhibited the strongest antioxidant activity followed by Aronia and macqui
Extracts of raspberry, cranberry, elderberry, strawberry, bilberry, blueberry and a combination of these extracts were examined for their antibacterial activities against Helicobacter pylori with and without addition of clarithromycin. Antibacterial effects were observed of the various extracts at different concentrations (0.25%, 0.5% and 1%). The results indicated that inhibition of Helicobacter pylori is
Hearst et al. (2010) investigated some Irish traditional herbal medicines for antibacterial activity against
Krawitz et al. (2011) analysed a standardised elderberry extract for its antimicrobial and antiviral activity using the microtitre broth
group C and G Streptococci, and the
Plant lectins are a heterogeneous group of proteins or glycoproteins that have a common unique ability to recognise specific sugar or
Nigrin f which is a
Citores et al. (1996) examined the various activities of the lectins from crude extract (unripe/scratch) on rat in vitro. They analysed the effects of nigrin f on protein synthesis and translation. Protein synthesis was carried out in cell free translation systems derived from rabbit reticulocyte lysates, rat liver, wheat germ, Vicia sativa germ, and Cucumis sativus bacterium. The result showed that nigrin f had an inhibitory effect on protein synthesis performed by rabbit reticulocyte lysates and rat liver cell- free systems, while it had no effect on plant
In vivo experiments
Bobek et al. (2001) also studied antioxidative activity. Rats with acute colitis were fed for a month with a diet containing 4% black elderberry extract (extraction solvent 70% ethanol, concentrated to the 50- 60% content of dry matter.) Colitis was induced by intraluminal instillation of 4% acetic acid. Long- term feeding with a diet containing black elderberry extract showed increased resistance to experimentally induced colitis. Lower levels of oxidative stress in the experimental group compared with the control group who received laboratory control diet (without black elderberry extract) was observed. In addition, neutrophil infiltration caused by myeloperoxidase activity was significantly lower, while higher activity of lysosomal enzymes (acid phosphatase and cathepsin D) that are released during inflammation was observed in colonic tissue in the experimental group. Both macroscopic damage to the colon and myeloperoxidase activity was 50% lower in the treatment group compared with the control diet group. The results suggest that a diet containing black elderberry extract can increase the level of antioxidative defense of the organism and thus lead to increased resistance to induction of colitis. Rats with acetic
Chimpanzees (n=4) given a syrup containing a standardised elderberry extract, either as a prophylactic treatment or as a
10 ml elderberry syrup daily, while five chimpanzees constituting a control group received sugar syrup. When chimpanzees in the experimental group exhibited
There is not enough scientific information available to conclude on an immunomodulatory effect or on an antibacterial effect of any of these elderberry extracts. Although some information on immunomodulatory and antibacterial effects is available, the tested herbal preparations are not fulfilling the requirements for inclusion in a monograph.
The antioxidative capacity of an elderberry extract has also been shown, but the mechanism is not clear. The major constituents, cyanidin
In vitro studies have shown that the ripening process leads to a significant reduction of the amount of lectin, and this is confirmed by the fact that ripe fruits are not toxic to humans.
Elderberry ethanol extract has been shown to protect rats against induced colitis.
A syrup containing a standardised elderberry extract has been shown to have symptomatic and prophylactic effects on
No information available.
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
No data available.
Pharmacokinetic interactions with other medicinal products
In a study on rats, an aqueous extract of elderberries (decoction 1:10) administered orally (2 ml/kg) caused a reduction of the sleep induction time of pentobarbitone and a very modest increased sleeping time when compared with rats administered pentobarbitone only. No significant effect was observed on the analgesic activity of morphine taken in combination with elderberries. These preliminary experiments indicate an interaction between the elderberry and the centrally acting drug pentobarbitone (Jakovljevic et al. 2001). Evidence for an interaction between the extracts of elderberry and pentobarbitone appears to be limited to this study on rats which found only a very modest increase in sleep time. It is not known whether this effect will occur in humans, but even if it does, it is unlikely to be clinically relevant.
A combination product, sold as a food supplement containing Echinacea purpurea and Sambucus nigra, was evaluated for the inhibitory potential of isolated human CYP3A4 with testosterone as substrate in vitro. The product performed relatively weak inhibition of CYP3A4 activity with an IC50 value (half maximal inhibitory concentration) of 1.192 mg / ml. The inhibitory potency seems to be exercised by E. purpurea whereas Sambucus nigra showed an insignificant inhibitory effect on CYP3A4 (Schrøder- Aasen et al. 2012).
There is not enough data available to draw conclusions about the potential effect of elderberry on centrally acting drugs such as morphine and phenobarbital. Elderberry did not show inhibitory effect on CYP3A4 in vitro.
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
Cyanogen glycosides and lectins
Cyanogenic glycosides can be found in edible parts of some plants. When such plant parts are consumed,
Dewick (2009) also provides information about the crushing of the plant containing cyanogenic glycosides. The author indicated that the crushing leads to glycosides come in contact with glycosidase present in the plant and then release of HCN.
Several sources, summarised in the systematic review by Vlachojannis et al. (2010), warn that all plant parts of elder containing cyanogenic glycosides including unripe/uncooked fruits, fresh leaves, bark and roots can cause nausea, vomiting or severe diarrhoea when consumed and should be avoided in elderberry preparations (Duke et al. 1985, Bisset and Wichtl 2001, Lewis and
According to Battelli et al. (1997), bark lectins, mainly nigrin b, are toxic because of their ability to bind to eukaryotic cells and terminate protein synthesis. Nigrin b has structural and activity similarities to ricin but has been shown to be less toxic. Gayoso et al. (2005) also reported that nigrin b is less toxic to animal cells cultures than ricin.
In May 2012, the European Food Safety Authority (EFSA) published a new version of the compendium of plants reported to contain toxic, addictive, psychotropic or other substances from 2009, “Compendium of botanicals reported to contain naturally occurring substances of possible concern for human health” (http://www.efsa.europa.eu/en/efsajournal/pub/2663.htm). Sambucus nigra L. has been listed with the following information:
Table 4: Information about Sambucus nigra L. in EFSA Compendium of botanicals 2012
Reproductive and developmental toxicity studies
No reproductive and developmental toxicity studies have been found.
There are no data on genotoxicity available on elderberry.
3.4. Overall conclusions on
Pharmacology – Pharmacodynamics
In vitro experiments showed that elderberry extract inhibited the replication of common human and animal influenza A and B strains as well as prevention of viral adhesion of two cell receptors. The studies showed that methylated and esterified flavonoids may contribute to the antiviral activity. There is not enough evidence to suggest an
beneficial effects related to lectins. A small in vivo experiment with four chimpanzees indicated that
There is not enough data available to draw conclusions about elderberry potential effect on the pharmacokinetic parameters of the centrally acting drugs morphine and pentobarbitone.
Toxicological data on elderberry is limited. Nonetheless, neither the chemical composition nor the long- term widespread use as food in the European Union (see section 5.2.) suggests that there is a high risk associated with the use of elderberry preparations prepared from ripe fruits.
4. Clinical Data
4.1. Clinical Pharmacology
No data available.
4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
No data available.
4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
Mülleder et al. (2002) recruited 16 healthy volunteers (8 men, 8 women) to a pharmacokinetic study of elderberry
4 hours after intake. The addition of sugar to elderberry juice resulted in a delay of excretion suggesting that intestinal sugar carriers may play a role in flavonoid absorption. The anthocyanins can be absorbed into the enterocyte by its glucose moiety, which is bound by a glucose transporter. It is possible that consumption of sugar leads to a saturation of the glucose transporter and inhibiting the uptake of anthocyanins. Possible metabolites were observed in this study but not identified (Mülleder et al. 2002).
Four women (age: 67 ± 4 years) were recruited to a pharmacokinetic study. Subjects were fasted overnight before the day of baseline blood sampling. Each subject was then given 12 g elderberry extract containing 720 mg anthocyanins, mainly
glycosides) seems to be hydrolysed in the gut so that only the aglycones (anthocyanidins) were absorbed within 72 minutes and metabolised in the liver by glycosylation to increase the solubility prior to excretion via the kidneys. The elimination of plasma anthocyanins appeared to follow
One male subject 35 years of age consumed 25 g of elderberry extract as one dose, containing 1.5 g anthocyanins after fasting overnight. Blood samples were collected before and 30 and 60 minutes after anthocyanin consumption.
Absorption and metabolism of anthocyanins of elderberries were studied in four healthy women, 60- 70 years. They consumed 12 g elderberry extract that contained a total of 720 mg of anthocyanins mixed in 500 ml water after overnight fasting. Urine samples were collected before and after the consumption of elderberry extract. Two major anthocyanins
4 hours after ingestion. This study suggests low rates of absorption and excretion of anthocyanins compared with other flavonoids (Wu et al. 2002).
The bioavailability seems to be very low in the above mentioned studies.
Table 5: Bioavailability studies on elderberry (Sambucus nigra L.)
KEY:CO – crossover, n – number of patients, O – open
4.2. Clinical Efficacy
4.2.1. Dose response studies
There are no dose response studies available
4.2.2. Clinical studies (case studies and clinical trials)
Two clinical studies have been conducted by
The first study was conducted on 27 people (15 receiving treatment and 12 receiving an undefined placebo preparation). Improvement of flu symptoms including fever was obtained in 93.3% of the patients within 2 days after initial dosing, while 91.7% in the placebo group (P<0.001) showed signs of improvement after 6 days. Immunological tests found a higher level of influenza virus antibodies in patients who received elderberry than those who received the placebo, suggesting an enhanced immune activity. None of the patients reported any adverse reactions related to the medication
The second study was conducted in 60 people (30 were treated with an oral elderberry syrup and 30 were given an undefined placebo preparation) with early symptoms of flu. The treatment effect (15 ml four times a day) was evaluated by assessing symptoms and general wellbeing and the result was determined by visual analog score (VAS)
frequency, sleep quality, nasal congestion, and mucous discharge) and
None of the patients reported any adverse reactions related to the medication
extract group compared to baseline. Total cholesterol was 199 mg/dl at baseline versus 190 mg/dl at the end of the
Table 6: Clinical Studies on elderberry (Sambucus nigra L.)
KEY: n – number of patients, O – open, R – randomised, DB – double blind, PC – placebo controlled
4.3. Clinical studies in special populations (e.g. elderly and children)
No information available.
4.4. Overall conclusions on clinical pharmacology and efficacy
Three controlled clinical studies have been conducted to determine the effectiveness of herbal preparations of elderberry, with very small numbers of patients. Two of the clinical trials studied the effectiveness of elderberry on flu treatment and the third one on blood lipids reduction. Results from two clinical studies indicate possible effectiveness of elderberry aqueous extract for treatment of influenza suggesting a faster recovery. More studies are needed to confirm this effect.
Effect of powdered elderberry juice on blood lipids showed insignificant reduction of blood lipids which may be due to the low dose of elderberry extract. It could be possible that higher doses may cause more significant effect on lipid reduction. Further studies are needed.
There are no clinical investigations available on elderberry laxative activity. Overall the existing data cannot be considered to meet the criteria for
5. Clinical Safety/Pharmacovigilance
5.1.Overview of toxicological/safety data from clinical trials in humans
A considerable patient/consumer exposure must be anticipated as elderberry is widely used as a natural source of food flavouring and in food supplements on the market in Europe. The regulatory status implies that no systematic pharmacovigilance activities have been performed.
5.3. Adverse events and serious adverse events and deaths
The World Health Organization Uppsala Monitoring Centre
Andrographis paniculata, Salix alba and Sambucus nigra. Among those 26 adverse events, 22 were described as various allergic reactions.
Acute poisoning was reported after ingestion of juice made from berries crushed with their leaves and branches of Sambucus mexicana, the elder tree indigenous to the western United States. Within
15 minutes after drinking the juice, 11 people experienced nausea and vomiting. One report of severe illness following the ingestion of juice prepared from elderberries has been recorded by the Centres for Disease Control in 1984. People attending a picnic, who ingested several glasses of juice made from berries, picked the day before, reported nausea, vomiting, weakness, dizziness, numbness, and stupor. Eleven people experienced nausea and vomiting, eight of whom had acute GI and neurologic symptoms after ingesting an elderberry juice made from raw elderberries, leaves, and branches. One person who consumed 5 glasses of juice was hospitalised for stupor. All recovered. The poisoning was attributed to the content of a bitter alkaloid and cyanogen glycosides in leaves, bark and buds that were crushed together with the fruits in the production of the juice. The toxic glycosides may under certain circumstances liberate hydrogen cyanide (Kunitz et al. 1984).
Table 7: Adverse events
5.4. Laboratory findings
No information available.
5.5. Safety in special populations and situations
Use in children and adolescents
The use is not recommended in adolescents and children below 18 years due to insufficient data on safety and efficacy.
Theoretically, elderberry might interfere with immunosuppressant therapy because of possible immunostimulating activity. Elderberry may stimulate the production of cytokines from human monocytes even though this must be confirmed in studies of higher quality. Immunostimulating herbal remedies may interfere with immunosuppressant drugs and corticosteroids (Barak et al. 2001).
Use in 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 because of potential risk of toxicity.
Withdrawal and rebound
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.
5.6. Overall conclusions on clinical safety
Plant parts other than the flowers and ripe berries are reported to be poisonous and should not be ingested nor be present in herbal preparations with elderberry. Hence, inclusion of other parts of the plant should be avoided. Bark lectins are considered to be toxic and should be avoided in elderberry preparations. In addition, the leaves and stems should not be crushed, since crushing leads to the liberation of hydrocyanic acid.
Heat treatment of fruit/juice will also reduce the small amount of hydrogen cyanide that can be liberated from the seeds and is therefore recommended. The fruits are safe to consume when ripe, cooked or dried. The safety of elderberry during pregnancy and lactation has not been established.
Elderberry cannot be recommended during pregnancy or lactation and in children and adolescents under 18 years of age due to insufficient data on safety and efficacy.
6. Overall conclusions
Elderberry preparations have been studied in clinical trials, but the published clinical studies cannot be considered to fulfill the criteria required for
For elderberry preparations, complete information on traditional use with a specified posology and the necessary information on a specified strength are missing in order to establish a monograph that fulfills the requirements of medicinal use for at least 30 years (including at least 15 years within the European Union) according to Directive 2004/24/EC.
Based on the available information, a Community herbal monograph on Sambucus nigra L., fructus cannot be established at present.