Castor oil – Ricini oleum (Ricinus communis L.)
|Latin name of the genus:||Ricini oleum|
|Latin name of herbal substance:||Ricinus communis l.|
|Botanical name of plant:||Herbalref.com|
|English common name of herbal substance:||Castor oil|
Latin name of the genus: Ricini oleum
Botanical name of plant: Ricinus communis L.
English common name of herbal substance: Castor oil
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
The HMPC has established a European Union herbal monograph on the oil obtained from the seeds of Ricinus communis L., fam. Euphorbiaceae. The monograph does not cover the herbal substance itself, i.e. the seeds.
Ricini oleum virginale (virgin castor oil) is the fatty oil obtained by cold expression of the seeds of the plant Ricinus communis L. (Euphorbiaceae family), in accordance with the European Pharmacopoeia (01/2013:0051). The addition of a suitable antioxidant is accepted. As specific requirements, during the expression step, the temperature of the oil must not exceed 500C.
The European Pharmacopoeia includes another two monographs: Ricini oleum raffinatum (01/2013:2367) that represents refined castor oil which may contain a suitable antioxidant and Ricini oleum hydrogenatum (01/2008:1497) that represent fatty oil obtained by hydrogenation of virgin castor oil.
Definitions, production and labelling requirements for vegetable fatty oils are given in the general monograph in the European Pharmacopoeia.
Castor oil is extracted from the seeds from Ricinus communis (that contain
Chemically, castor oil is a mixture of triglyceride characterised by a high content of ricinolein
(a glyceride of
Beside ricinoleic acid, other fatty acids are present in castor oil, like linoleic acid
According to the European Pharmacopeia, castor oil should contain max. 2% palmitic acid, max. 2.5% stearic acid,
Other sources mention that castor oil also contains 2.4% lauric acid lipase, vitamin E, and
A lectin called ricin is present in the seeds and pods and is considered as one of the most toxic natural poisons. It is a glycoprotein composed of two polypeptide chains, the
bean pulp therefore castor oil is not considered to contain ricin (Worbs et al., 2011). Also Cosmetic Ingredient Review Expert Panel (2007) published a safety assessment that stipulates that castor oil does not contain ricin.
Castor oil, virgin and refined
According to the monographs from European Pharmacopoeia the composition of the
Comparing the monographs, the appearance, the specific absorbance, the acid and peroxide values are different. The other parameters are identical (Table 1).
Table 1: Comparative parameters castor oil virgin vs. refined
The Quality Drafting Group of the HMPC is of the opinion that virgin castor oil and refined castor oil are comparable because the refining process affects impurities only, which means that active ingredients are not changed by the process. The difference in impurity content has no implications to safety and efficacy. Consequently the European Union herbal monograph covers both oils and no distinction is made between the virgin and refined castor oil in this 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
Databases and other sources used to research available pharmaceutical,
•Relevant articles and references retrieved from databases: PubMed and Toxline. Search term: [Ricini oleum], [Castor oil], [Ricinus communis] and [Ricinus communis oil]. Publication year: up to April 2014. In summary 1800 publications were listed.
•Textbooks, pharmacopoeias and monographs.
Additionally, the European Commission´s databases on cosmetic ingredients (CosIng) was searched in April 2014 for information on [castor oil].
Data was also provided by the EMA on behalf of interested parties.
The EudraVigilance database and VigiLyze database of the World Health Organisation’s were searched in August 2014 using the term [Ricini oleum].
The abstracts of the references found were screened manually and all articles identified that could have a possible impact on the assessment report and monograph were included. This assessment report is based on the summary of the most relevant scientific literature.
2. Data on medicinal use
2.1. Information about products on the market
2.1.1. Information about products on the market in the EU/EEA Member States
Information on medicinal products marketed in the EU/EEA
Table 2: Overview of data obtained from marketed medicinal products.
**Additional data on other products marketed in Poland: In Poland castor oil was used with a similar indication in 24.06.1938 (Regulation of Minister of Health and Social Welfare). After the World War II it was mentioned by management of the Minister of Health and Social Welfare in 24.02.1958 (in forms of oral liquid and capsules). In 28.01.1960 it was accepted for distribution in drugstores and herbalistic shops. In 14.09.1993 it was exempted from registration (a category similar to magistral drugs) and all products started to be certified by the Drug Institute. According to available databases the Certificates of Registration were given for 9 products. Eight products are now on the pharmaceutical market in Poland, one as TUR.
***Additional information provided by Latvia demonstrated that castor oil was on the market in the former Soviet Union since 1967
****Data collected from MHRA site. Additional data from UK indicate that the product has been authorised before 1968 as WEU, but the license was withdrawn in 2013, taking into account that castor oil is considered obsolete as laxative in the UK.
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
The castor oil plant Ricinus communis, also known as Palma(e) Christi or wonder tree, is a perennial scrub of the spurge family Euphorbiaceae. Ricinus communis is probably native to eastern Africa and was used in ancient Egypt and by the Romans and Greeks (Williamson, 2003). Nowadays the plant grows wild in many tropical and subtropical regions and is found as an ornamental plant virtually all around the world.
A companion to the British Pharmacopoeia 3rd edition, published in 1866 describes castor oil properties as “a mild and speedy cathartic. Particularly applicable to constipation from indurate faeces, or after swallowing acrid substances, or on the accumulation of acrid secretions. Used in diseases attended with irritation or inflammation of the bowels, as colic, diarrhoea, dysentery, and enteritis“. According to the author, the dose administered corresponds 1/2 to 1 oz. for adults, 1 to 3 drms. (meaning ml) for infants. The oil is administered floating on some aromatic water, or mixed in a cup of hot sweetened coffee (Squire, 1866).
According to Potter’s Herbal Cyclopaedia, castor oil has been used since ancient times as a laxative and purgative. The authors do not recommend regular use and for long periods because the oil is believed to cause histological abnormalities in the intestine. Castor oil is reported also as an emollient and soothing to the skin and eye and is an ingredient of many cosmetic and ophthalmic preparations. The dosage indicated for oral intake corresponds to
Some old medical journals described castor oil as a very potent agent producing catharsis by irritation. Because of this property, the author recommended not to use the oil for the treatment of functional constipation (McKenna, 1964). Other journal (California and Western medicine, 1934) described the use of castor oil for the induction of labor (Holmes, 1934)
In ‘Précis de Matière Médicale’, castor seeds and also four castor oil types (huile de prémière pression; huile pharmaceutique; huile de la deuxième pression; huile sulfurée) are described. As therapeutic indications, the internal use of
In the Handbuch der Pharmacognosie a short history of castor oil and the description of method of preparation of medicinal and technical castor oil are included (Tschirch, 1923).
Ożarowski et al. (1978) included castor oil in a textbook (Lekiroslinne informator), indicating its use in constipations or due to various reasons (including food poisoning, intestinal infections, after use of anthelmintics, before radiological examinations).
British Pharmaceutical Codex 1979 includes 5 preparations based on castor oil, of which 3 used internal as purgative: Emulsio Olei Ricini Aromatici, that contains 30% (V/V) of aromatic castor oil and is administered in dose of 30 to 60 ml; Mistura Olei Ricini, that contains castor oil emulsified with acacia in triple
The Extra Pharmacopoeia (Martindale, 1982) indicates that castor oil is a purgative, acting on the small intestines, the latency until the effect varies between 2 and 8 hours. It is also given at a dose of 15 ml to empty the bowel before
Dobrescu (1989) mentions that virgin castor oil is apurgative that is administered in acute constipation in a single dose of
Also the Romanian Pharmacopoea (Farmacopeea Romana X, 1998) and the Polish Pharmacopoea (Farmakopea Polska IV, 1970) include the monograph of “Ricini oleum” with the indication as a purgative drug. The single dose in adults corresponds to
WHO monograph describes for Oleum Ricini traditional medicinal uses as emenagogue, to induce labor, for the treatment of burns, haemorrhoids, pneumonia, rheumatism and sprains and
PDR for Herbal Medicine also included castor oil as a drug used internally in folk medicine for acute constipation, in intestinal inflammation, for removal of worms, and as a form of birth control. The oil is used externally for inflammatory skin disorders, furuncles, carbuncles, abscesses, inflammation of the middle ear and headaches (poultice). Recommended oral daily dose for acute constipation or as laxative against worms is, at least 10 grams divided into 1 or 5 doses, while for external use, a paste made of grounded seeds is applied to the affected skin areas twice daily, up to 15 days (Gruenwald et al., 2004).
Table 3: Overview of historical data
2.3. Overall conclusions on medicinal use
From market overview (section 2.1) the following indications and respective herbal preparations were identified:
In UK (WEU): As laxative – since 1968
In Germany (WEU):
In Estonia (WEU): Functional constipation not corrected by diet – since 2001
In Latvia (WEU): Used in functional constipation. Clearing of bowels before radiological examination, surgery, labour – since 1998 (and since 1967 in former Soviet Union)
In Poland: Traditionally used in constipations since 2011 as TUR and since 1938 with certificate of registration.
In France: Traditionally used as a purgative since 1959
Based on available clinical literature, information provided by Member States and taking into account HMPC opinion, the following indication is recommended for
Based on clinical trails performed the following posology is proposed:
In adults and elderly:
Duration of use: 7 days
The medicinal use of castor oil (virgin and refined) is documented in several medicinal handbooks throughout a period of at least 30 years, including at least 15 years within the EU.
Castor oil is authorised in the European Union for cleaning of the bowels since 1959 and as a laxative since 1968. Based on this longstanding use and available clinical data just one
The use of castor oil in children and adolescents under 18 years of age is not recommended due to lack of adequate efficacy and safety data.
Table 4: Overview of evidence on period of medicinal use.
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
3.1.1. Primary pharmacodynamics
Castor oil is an anionic surfactant laxative. Orally ingested castor oil is hydrolysed in the small intestine by pancreatic lipases to yield glycerol and ricinoleic acid. Ricinoleic acid acts as a local irritant resulting in electrolyte secretion in the small intestine by reducing net absorption of fluid and electrolytes and stimulates intestinal peristalsis (Brunton, 1990). Gross morphological damage to the intestinal mucosa arising from the potency of this surfactant action may explain, in part, the altered permeability caused by castor oil (Cline et al., 1976).
Because ricinoleate acts in the small intestine, accumulation of fluid and evacuation takes place within
There are several
In vitro experiments
Castor oil and isolated compounds
Mathias et al. (1978) examined the myoelectric effects of castor oil, ricinoleic acid (cis isomer) and ricinelaidic acid (trans isomer) in the small intestine of New Zealand white rabbits. Ricinoleic acid, 2 μg/kg/min (6 mM), was directly perfused into a distal 12 cm ileal loop.
An abnormal myoelectric pattern developed that was similar to the alteration in the electrical activity that has previously been reported for cholera enterotoxin. Castor oil at 0.85 ml/kg, had a similar effect, while ricinelaidic acid had no activity. A second preparation consisted of an intraluminal perfusion of ricinoleic acid, 2 μg/kg/min into the first section of the duodenum. The abnormal myoelectric pattern was observed in the jejunum and the ileum but not the duodenum. The mean onset time for the development of this altered myoelectric state for all experiments was 3.5 h. According to the authors these results suggest that an active motility component in addition to the secretory state exists throughout the small intestine that is exposed to castor oil or ricinoleic acid. The biopsy of the ileal loops at the end of each experiment revealed no alteration in intestinal structure.
Stewart et al. (1975) investigated the effects of ricinoleic acid and several structurally related compounds on the smooth muscle contractions of the coaxially stimulated
Racusen and Binder (1979) investigated the effect of sodium ricinoleate on isolated rat colonic mucosa. 0.5 mM Na ricinoleate perfusion produced significant fluid accumulation, a significant decrease in net Na absorption from 4.7+0.8 to 0.1+0.7 µeq/h cm2 and reversed net Cl transport from absorption (+4.5±0.9) to secretion
Gadacz et al. (1976) investigated on perfused isolated segments (jejunal and ileal
compared with the control solution. Perfusion of one loop with ricinoleic acid produced no changes in fluid absorption from the loop perfused with the control solution.
Gaginella et al. (1977a) investigated the morphology of the rabbit colon after perfusion of the organ with 2.5, 5.0, 7.5, and 10 mM sodium ricinoleate. Colons perfused with ricinoleate produced desquamation of surface epithelial cells. Surface changes in the colon were comparable with those reported after similar treatment of the rabbit ileum. Concomitant with these histological changes was loss of DNA into the lumen of the colon.
JECFA monograph cites a study where sodium ricinoleate at 2 mM concentration caused a 48% reduction in net water absorption in vitro by isolated segments of hamster jejunum. The substance also caused a significant decrease in sodium and chloride absorption, but not potassium absorption
In vivo experiments
NTP cites a gavage study on rhesus monkeys (1 ml/kg castor oil, daily for 4 days) that caused mild morphological changes in the small intestine, characterised by lipid droplets along the mucosal epithelium and in the underlying lamina propria (Irwin, 1992).
Atchison et al. (1978) investigated the effects of castor oil and ricinoleic acid on small bowel electrical activity in the fasted conscious dog and were compared to the effects elicited by two
Stewart and Bass (1976) administered intraduodenally oleic and ricinoleic acids or their trans isomers, elaidic and ricinelaidic acids, and evaluated their effects on the digestive motor activity of the canine small and large bowel. Administration of each cis fatty acid produced an initial stimulation in jejunal areas of about a
small bowel motor activity. The authors classified the laxative effect of both cathartics as mild. Digestive motor patterns returned to control approximately 45 min after oleic acid. There was no indication at any time of an initiation of continuous contractile activity after ricinoleic acid or castor oil which could justify the use of the terms irritant of stimulant to describe their actions.
Cline et al. (1976) investigated in vivo, in perfused hamster small intestine the effect of sodium ricinoleate. A concentration of ricinoleate (2 mM) did not affect water transport, however, did not alter intestinal permeability. Eight mM ricinoleate induced intestinal secretion (effect on water and sodium), which was accompanied by substantial architectural mucosal changes: mucosal cell exfoliation, villi were shortened and villus tip epithelial cells were vacuolated with disintegrating brush borders.
Beubler and Juan et al. (1979) observed that ricinoleic acid, oleic acid, sennoside A + B and mannitol reduced or reversed water flux from lumen to blood in rat colon in situ. Ricinoleic acid, oleic acid and sennoside A + B stimulated release of
In a study by Morehouse et al. (1986), a single 0.1 ml dose of ricinoleic acid (100 mg/ml) administered intragastrically to fasted
Table 5: Overview of the main
Mechanism of action
Gaginella et al. (1977c) used electron microscopy to investigate the effect of sodium ricinoleate
(10 mM) on mucosal structure of the small intestine of rabbit. Sodium ricinoleate produced deep clefts or holes at the tips of villi and at the bases of these clefts unusual cells could be resolved. The microvillus surface of the intestine was also altered at the tips and sides of villi. Microvilli were clumped into “tufts” with numerous intervening “cracks” appearing on the surface. The appearances after ricinoleate were reversed in part during perfusion with control buffer for 2 hours. The authors concluded that these changes may be related to the
Gaginella et al. (1977b) investigated in vitro on isolated epithelial cells from hamster small intestine the cytotoxicity of castor oil and other intestinal secretagogues. Cytotoxicity was assessed by: 1) exclusion of trypan blue; 2) release of intracellular (prelabeled) 51Cr; and 3) inhibition of cellular uptake of
Capasso et al. (1984) studied the effect of ricinoleic acid on prostaglandin E2
increased the amplitude of the
Tavares et al. (1996) compared the effect of rhein and
The effects of
Later published articles (Mascolo et al., 1994, Capasso et al., 1994) confirmed that castor oil (2 ml/rat, orally) induced diarrhea in rats and that this effects involves the
7 hours after challenge. No injury was observed at 0.5 hour or at 9 hours after castor oil administration and the tissue appeared normal by visual examination (Mascolo et al., 1994).
Recently, Tunaru et al. (2012) identified prostaglandin E2 receptors as targets of ricinoleic acid and show that the EP3 receptor mediates in vivo the effects of castor oil on the motility of the uterus and the intestine in genetic mouse models.
3.1.2. Secondary pharmacodynamics
No relevant data available.
3.1.3. Safety pharmacology
No data available.
3.1.4. Pharmacodynamic interactions
No data available.
The scientific literature contains numerous
effects are relevant for the laxative effect of castor oil. It is important to underline that the intestinal mucosal damage was reversible in vitro after 2 hours (Gaginella et al., 1977) and in vivo, the repair being complete after 6 hours (Morehouse et al., 1986), or even longer, up to 9 hours post dosing (Mascolo et al., 1994).
Conflicting data have been published with regard to the ability of ricinoleic acid to induce procontractile effects on intestinal smooth muscle and to alter intestinal ion transport and water flux. Although some researchers observed an inhibition of water and electrolyte absorption, others found an activation of ion secretory processes by ricinoleid acid. In addition to effects on intestinal ion transport and waterflux, evidence has been provided that ricinoleic acid can directly affect intestinal motility. Results from studies with NO synthase inhibitors in rats suggest that NO may play a role in the ‘‘diarrhoea effect’’ of castor oil. Recently, EP3 receptors have been identified as targets of ricinoleic acid. This could explain, at least partially the in vivo effects of castor oil on the motility of the uterus and the intestine in transgenic models.
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
Watson and Gordon (1962) investigated the absorption of a dose of castor oil (1 ml) administered by stomach tube in rats. Castor oil used was of medicinal grade having the following fatty acid composition: ricinoleic 90%, linoleic 4.7%, oleic 3.2%, stearic 1%, palmitic 1% and palmitoleic 0.1%. Approximately 7% of the Ricinoleic acid was absorbed within the first 24 hours when is administered in fasted rats via stomach tube, whereas approximately 24% acid was absorbed when the oil was administered to nonfasted animals. Weanling rats fed a diet containing 20% castor oil for eight weeks were found to have 9.7% ricinoleic acid in their fat pads, whereas the level was only 2% in those animals switched at four weeks from the castor oil diet to an olive oil diet for an additional two weeks.
In a study conducted by Hagenfeldt et al. (1986), castor oil was administered intragastrically to
In a study cited by Cosmetic Ingredient Review Expert Panel, (2007), two groups of five male Wistar rats received 10% castor oil in the diet
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 a study conducted by Capasso et al. (1994), castor oil (2 ml) was administered orally to ten male Wistar rats. The animals were killed and two segments from standardised regions of the duodenum
and jejunum were visibly evaluated for macroscopic damage. Copious diarrhea was reported for all animals on days 3, 5, and 7 post dosing. Macroscopic damage, characterised mainly by vasocongestion, was observed throughout the duodenum and jejunum. The injury observed ranged from mild (at 1 hour) to severe (at 5 hours), and was less severe at 7 hours. Injury was not observed at 0.5 or 9 hours after dosing. Castor
Severe diarrhea, loss of appetite, colic, and fever were reported within 24 hours of oral administration of castor oil (2.5 ml/kg) to ponies (Cosmetic Ingredient Review Expert Panel CIR, 2007). At 24 hours post dose, the mucosa of the cecum and ventral colon had extensive superficial epithelial erosion and neutrophil infiltration. In the ileum, the epithelium of the villous tips was separated from the lamina propria and scanning electron microscopy of the cecal mucosa revealed exposed basement membranes. Ultrastructurally, there was a loss of microvilli, distortion of the cytoplasmic terminal web and other changes. Initiation of regeneration of the intestinal mucosa was evident by 24 hours after dosing; at 48 hours, denuded basement membranes were covered by cuboidal epithelium and; regeneration was complete by 72 hours.
3.3.2. Repeat dose toxicity
Castor oil (Ph.Eur.)
No information available
Castor oil (USP)
Castor oil (Ph.Eur.)
No information available
Castor oil (USP)
In a study, castor oil
5000 µg/ml with and without S9.
No induction of micronuclei was observed in peripheral blood erythrocytes of B6C3F1 mice sampled at the termination of the NTP
Because the USP monograph does not include specifications for the fatty acid compositions, it is unclear if the result of this study can be extrapolated to oils that comply with European Pharmacopoeia monograph.
Castor oil (Ph.Eur.)
No information available
Castor oil (USP)
Both NTP, on its website
No other data was found.
3.3.5. Reproductive and developmental toxicity
Castor oil (Ph.Eur.)
No information available
Castor oil (USP)
Castor oil (quality unknown)
Gao et al. (1998) investigated the effect of castor oil (2 ml/daily) administered by gavage on days 18, 19 and 20 of gestation on the initiation of labour of pregnant rat. The castor oil induced the initiation of labour and shorter the course of the delivery in pregnant rats. Ricinoleic acid was the active component of castor
Later, the same researchers (Gao et al., 1999) evaluated in a similar study the effect of castor oil (2 ml/daily) administered by gavage on days 18, 19 and 20 of gestation on the synthesis of prostaglandin E2 (PGE2) and the induction of labor in pregnant Wistar rats. Compared to the control group, a significant increase in concentrations of PGE2 in tissues of the intestinal mucosa, placenta, amnion, and amniotic cells was noted in test animals.
3.3.6. Local tolerance
In the Final Report on the Safety Assessment of Ricinus Communis (Castor) Seed Oil (Cosmetic Ingredient Review Expert Panel CIR, 2007) significant data regarding local tolerance of castor oil on different species were included. For example the instillation of undiluted castor oil (0.5 ml) into the
rabbit eye resulted in a slight congestion of the iris and conjunctiva in the rabbit eye, but the instillation of castor oil (10 drops daily for 3 weeks) into the eyes of ten rabbits did not produced damage to the corneal epithelium or endothelium. Undiluted castor oil that was applied for 24 hours to two areas on the dorsal surface of six albino angora rabbits produced severe skin irritation, while applied to the dorsal skin of male Hartley guinea pigs, male Wistar rats, and miniature swine produced mild skin irritation in guinea pigs and rats, but not in miniature swine.
3.3.7. Other special studies
No data available.
The majority of the available toxicological data were obtained with USP grade castor oil. Because the USP monograph does not include specifications for the fatty acid compositions, it is unclear if the toxicological data can be extrapolated to oils that comply with European Pharmacopoeia monograph.
Single dose toxicity tests with castor oil induced severe diarrhea with mucosal histological damage (loss of microvilli). The effect was reversible after 72 hours.
The oral administration of castor oil in a
Castor oil in AMES assay test with S. typhimurium strains TA 1535, TA 98, TA 97, and TA 100 showed a negative outcome. Castor oil did not induce
Reproductive toxicity data revealed no toxic effect, while developmental studies in pregnant rats suggested that castor oil may have an influence on the initiation of labour. These data are correlated with the recently identification of EP3 receptor as the in vivo mediator of the castor oil effects on the motility of the uterus and the intestine (Tunaru et al., 2012)
No carcinogenicity data were available.
3.4. Overall conclusions on
Results from the in vitro and in vivo studies support the proposed indication. Studies were performed with castor oil and with ricinoleic acid, the active metabolite of castor oil.
Limited data on pharmacokinetics are available on castor oil after oral administration. Some metabolites (as
Almost all toxicological data were obtained with USP castor oil. Its specifications are different from Ph. Eur grade oil. Acute toxicity revealed, as the main outcome, severe diarrhoea accompanied by histological changes on the microvilli, while
without metabolic activation, did not induce
Tests on carcinogenicity have not been performed, while developmental toxicity revealed that castor oil could induce the initiation of labour and shorter the course of the delivery in pregnant rats.
Based on information on developmental toxicity, the use during pregnancy cannot be recommended.
During the longstanding use as a medicinal product in the European Union no serious side effects have been reported. Therefore, the oral administration of castor oil can be regarded as safe under conditions of use that are described in the monograph.
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
The effects of oleic and ricinoleic acids on jejunal absorption have been studied in six healthy volunteers using
Bretagne et al. (1981) tested two conjugated bile salts (10 mmol/l sodium glycocholate and 10 mmol/l sodium taurodeoxycholate) and three laxatives (30 mmol/l magnesium sulphate, 10 mmol/l ricinoleic acid, 2 mmol/l dioctyl sodium sulphosuccinate DOSS) on seven subjects with no intestinal lesions in 14 experiments by intestinal perfusion of the jejunum. A 25 cm segment was studied. Each solution was perfused at the rate of 10 ml/min. Water and electrolyte fluxes, losses of deoxyribonucleic acid (DNA), and intestinal cell enzyme activity were measured in the fluids collected. All the laxatives and bile salts tested (except sodium glycocholate) induced water and electrolyte secretion, a rise in intraluminal DNA loss, and enzyme activity. It was possible to establish a significant correlation
(P < 0.001) between the amounts of water fluxes and DNA loss under the effect of dioctyl sodium sulphosuccinate and ricinoleic acid. The results confirm the secretory effect on the human jejunum of MgSO4, DOSS and ricinoleic acid.
Sogni et al. (1992) comparared the effects of ricinoleic acid and senna on orocecal and oroanal transit time in 12 healthy subjects, using salacylazosulfapyridine method. The 12 healthy volunteers were: a) under resting conditions; b) 2 weeks later with ricinoleic acid 40 ml (n=6) or senna 19 mg (X- Prep=1.2 g; n=6) administration. In each step, Salazopyrin (2 g) and 20 radiopaque markers were ingested with a 200 kcal meal (Polydiet TCM=200 ml). The following parameters were determined: a) plasmatic level of sulphapyridine (spectrophotometry) at 30 minutes intervals during 12 hours; b) 2- day stool frequency and weight; c)
5.8+ 1.8 to 2.2 + 0.7 hours (P < 0.01) and
6.8hours (P < 0.05).
4.1.2.Overview of pharmacokinetic data regarding the herbal
substance(s)/preparation(s) including data on relevant constituents
Watson et al. (1963) studied the absorption and excretion of castor oil labeled with 131I in five hypertensive subjects (ages and weights not stated). The composition of the castor oil was as follows: palmitic acid (1%), palmitoleic acid (0.1%), stearic acid (1%), oleic acid (3.2%), linoleic acid (4.7%), and ricinoleic acid (90%). The doses administered ranged from 4 to 60 g (approximately 6µCi of radioactivity per dose). Small doses of oil were also administered to the three normal volunteers, and free diet was allowed. Stool collections were made during the first 24 hours after dosing and during the subsequent 72 hours. Urine was collected in
The ingested castor oil is hydrolysed in the small intestine in humans by pancreatic enzymes, leading to the release of glycerol and ricinoleic acid which, like other anionic surfactants, reduces net absorption of fluid and electrolytes, and stimulates intestinal peristalsis (Brunton, 1990). Ricinoleic acid is metabolised systemically and the metabolites are excreted.
Hagenfeldt et al. (1986) found three epoxydicarboxylic acids in the urine of an anorexic woman after the ingestion of castor oil:
The absorption on jejunal mucosa of oleic and ricinoleic acids have been studied in six healthy volunteers using
4.2. Clinical efficacy
4.2.1. Dose response studies
No data available.
4.2.2. Clinical studies (case studies and clinical trials)
Two clinical trials (one double blind positive controlled and one observational) that investigated the laxative effect of castor oil in constipated patients were found in literature. Both studies are also cited by Buechi (2000).
The double blind positive controlled trial was conducted on 60 constipated patients. They were randomly allocated to took either refined castor oil capsules(corresponding to 1.2 g, 2.4 g or 3.6 g, daily; n=30) or two senna capsules (300 mg extract equivalent to 50 mg of total sennosides; n=30) each for 1 week. The initial dose administered corresponds to 1.2 g refined castor oil but could be increased up to 3.6 g, according to response. The main outcome was to obtain 5 stools/week. This
frequency was obtained after 1 week in 15 patients (50%) at dose of 1.2 g/day castor oil, while 2.4 g castor oil produced this frequency in 13 patients (43.3%), and only 2 patients needed the maximum dosage (3.6 g/day). The authors concluded that 4 capsules of castor oil (2.4 g) induced the same effect as 300 mg senna extract capsules (Pawlik et al., 2000).
The observational study was conducted on 168 constipated patients that took castor oil capsules (each containing 1 g oil) for 14 days. The dosage varied from 1 to 12 capsules/day, the mean dose corresponding to 2.5 g castor oil. The main outcomes were: the stools frequency, the stools consistence, duration of effect, incapacity to work. The assessment was done between Day
Assessors comments: The described positive effects are in line with the approved
Bowel cleaning effect
Slanger, (1979) conducted a comparative study of a standardised senna liquid preparation and castor oil in preparing patients for radiographic examination of the colon. The study included 100 patients scheduled for barium enema, 44 men and 56 women, 19 to 86 years old, the average age being 60 years. The patients were randomly divided into four treatment groups, which, on subsequent analysis, were found to be approximately matched in sex and age.
The primary outcome was quality of radiographic visualisation which was rated as excellent, good, fair, or poor. The quantities of faecal residue and of gas present at the time of the barium enema, reflected in these ratings, were individually evaluated and graded by means of a numerical scale ranging from 0 through 3 + (0=none, 1+=small, 2+=moderate, and 3+=large quantity). The verbal inquiries concerned side effects most commonly associated with purgation; specifically, nausea, griping, cramping, and abdominal pain. The senna preparation was highly superior to the
The side effects induced by the single castor oil were: nausea (2 patients/25 total patients), griping (11/25), cramps (12/25) and abdominal pain (11/25). For the divided dose the incidence was almost similar, but the severity was lower.
Novetsky et al. (1981) tested different modes of colon cleansing regimes prior to
night for 3 consecutive nights before scintigram; (4) 79 patients did not undertake any preparation. Patient compliance rates for the 4 regimes were 17%, 32%, 36%, and 46%, respectively.
Gould and Williams (1982) compared the effects of castor oil and senna preparation in colonoscopy in patients with inactive chronic ulcerative colitis. A prospective trial was conducted on 46 patients (26- 71 years old) that were randomly allocated to bowel preparation with either castor oil (30 ml, orally; n=23; 13 men:10 women); or five
Present et al. (1982) evaluated 12
4 packages of “CE”) Protocol 7 (one bottle SEP, containing 2.5 ounces of senna extract+ 2 L water enema); Protocol 8 (one bottle SEP +2 L enema containing 4 packages of “CE” ) Protocol 9 (bisacodyl 20 mg, orally+ 2 L water enema); Protocol 10 (bisacodyl 20 mg, orally+ 2 L enema containing
4 packages of “CE” ); Protocol 11 (bisacodyl 20 mg orally + bisacodyl 10 mg suppositories); Protocol 12 (a bottle of magnesium citrate +3 x 20 mg bisacodyl, orally + 10 mg bisacodyl suppositories). The radiologists judged the acceptability of the final results on the basis of the presence or absence of particulate matter in each part of the colon (1=no particulate matter; 2=particulate matter between 0 and 5 mm in diameter; 3=particulate matter greater than 5 mm but less than 1 cm in diameter; 4=particulate matter more than 1 cm in diameter; 5=Grossly inadequate preparation (e.g., excessive foreign matter, gas, fluid).
Protocols 9, 5, 7, and 12, in this order, are best overall,
1 2 ounces=56.7 grams
The side effects induced by the Protocol 5 (56.7 g castor oil + 2 L water enema) were: nausea (29%), interference with sleep (31%), severe cramp (35%), faintness (16%), bleeding (8%).
Strates and Hofmann (1987) investigated in a randomised study carried out in 195
Yang and Woo (1990) compared the effectiveness of six cleansing methods used in colonoscopy: (1) normal saline enema, (2) castor oil with normal saline enema, (3) castor oil with soapsuds enema, (4) magnesium citrate with normal saline, (5) magnesium citrate with soapsuds enema and (6) ingestion of Golyetly solution. The total number of patients was 247, age distribution was 43 ±15 years old, and sex distribution was 133 males and 114 females. The authors have compared and determined the degree of cleanliness by an experienced endoscopist. The grade I and II represented no difficulties at performing the fiber optic colonoscopy, but grade III and IV had some difficulties, even unable to perform the fiber optic colonoscopy. The effectiveness the cleansing agents, represented with grade I and II was 95.9% (47/49) in method 6, 93.2% (54/58) in method 2, 83.3% (30/33) in method 3, 70.0% (28/40) in method 5, 66.7% (16/24) in method 1, and 45.7% (18/40) in method 4. Method 2 and 6 were the most effective in normal bowel habit patients. In constipated patients, method 6 was the most effective and all methods except method 4 were effective in diarrhoea patients. The degrees of less mucosal irritation by various bowel cleansing method were in the order of method 6 (100%), 1 (100%), 5 (74%), 2 (69%). In subjective symptoms and cleansing groups, abdominal distension, pain, nausea and vomiting were complained, and that’s subject symptoms were in the order of method 3 (88.9%), 6 (79.6%), 1 (75%), 5 (72.5%), 2 (72.4%), 4 (67.5%).
Mundinger et al. (1990) investigated in a controlled study the efficiency of cleansing out the colon and the best contrast medium of two different regimens (total n=237) for preparing the colon for
Kolts et al. (1993) compared the effectiveness and patient tolerance of oral sodium phosphate, castor oil, and standard electrolyte lavage for colonoscopy or sigmoidoscopy preparation. One hundren thirteen patients were randomised to receive either 90 ml sodium phosphate oral (n=34), lemon-
flavored castor oil 60 ml (that contains 95% castor oil), orally (n=41), or 4 L standard polyethylene
Chen et al. (1999) compared colon cleansing efficacy, patient acceptance and side effects in patients given either a magnesium
Table 6: Comparative cleanliness scores magnesium citrate+bisacodyl vs. castor oil
Results are mean + SD. Figures in parentheses are the number of the patients. NS: not significant
Regarding the side effects observed, abdominal pain (38 vs. 11, P < 0.01) and nausea (29 vs. 8, P < 0.05) were significantly more common in patients receiving the castor oil preparation than in patients administered with the magnesium
complained of poor acceptance with the castor oil regimen than with the magnesium
Table 7: Side effects of magnesium citrate+ bisacodyl and castor oil regimens for colonoscopy
Hsieh et al. (2000) used two different cathartics to evaluate the efficacy of bowel cleansing in improving the quality of abdominal gallium imaging. One hundred and fifty patients underwent gallium scintigraphy and were randomly divided into three groups. Group A received no bowel preparation, Group B received 30 ml of castor oil the night before imaging, and Group C received bisacodyl 10 mg the night before imaging. Gallium activity in the intestine was rated on a
Yang et al. (2005) compared the efficacy of castor oil and bisacodyl, in the routine bowel preparation of outpatients for intravenous urography (IVU). They used castor oil in patients undergoing IVU for
1 month, and then used bisacodyl in patients undergoing IVU for another month. Two uroradiologists, unaware of the method of bowel preparation, reviewed the standard radiographs and graded the residue in the large bowel and the clearness of the opacified urinary collecting system. In total,
71 consecutive outpatients received castor oil (80 ml as an emulsion) and 84 received bisacodyl (15 mg), on the evening before IVU. To evaluate the degree of faecal residue on plain abdominal images, the following grading system was created: if there was residue in more than
specific film area the score was 0; if residue was seen in less than two thirds, but more than
Apisarnthanarak et al. (2009) compared efficacy for colon cleanness and side effects of castor oil and sodium phosphate preparation. One hundred patients included in the study were 39 males, 61 females with age range between
Regarding side effects (dizziness, nausea, vomiting, abdominal cramping, rectal pain, incontinence, thirst, palpitation, fatigue, and fainting), only the nausea symptom score tended to be higher in the sodium phosphate group (P=0.067). The incidence of castor’s oil side effects was: dizziness (15%), nausea (44%), vomiting (6%), abdominal cramping (38%), fatigue (32%), fainting (6%), palpitation (6%), incontinence (30%).
Sani et al. (2010) compared the efficacy, adverse effects and patient compliance of two bowel preparation regimens with castor oil and a syrup containing senna (ScS) in of outpatients for Intravenous Urography (IVU). One hundred and fourteen consecutive outpatients were randomised to receive either the standard bowel preparation with 60 ml of castor oil (n=57) or the test method with 60 ml of ScS (n=57) before IVU examination. Two radiologists scored the bowel cleansing on a
The incidence and severity of some of the adverse effects was significantly higher in the castor oil group: nausea (56.1%), vomiting (54.4%), abdominal pain (63.2%), thirst (56.1%), abdominal fullness (68.4%) and insomnia (50.8%). However, the incidence and severity of anal irritation was higher in ScS group. Although the incidence of diarrhoea was higher in ScS (100% vs. 91.2% for castor oil) but its severity was higher in castor oil group.
Dadkhah et al. (2012) assessed whether bowel preparation prior to
Table 8: Clinical studies on humans
RCT=randomised control trial; RPT=randomised positive control trial; IVU=intravenous urography
Table 9: Comparative results of bowel cleaning effect of castor oil (enema vs. without enema)
In the trials, the treatments with castor oil were performed with or without a supplement treatment with an enema.
With enema were found 4 studies: in two studies there was no difference between the efficacy of the preparations used (castor oil vs. senna and castor oil vs. mixture of magnesium citrate, phenolphthalein and bisacodyl), while in one study PEG exhibited a better bowel cleaning effect and in another one the combination of bisacodyl and phosphate was more efficient compared with castor oil.
Without enema were found 10 studies. Only one study had irrelevant results (not significantly different from the control, due to the poor compliance rate) while all other 9 studies proved the cathartic effect of castor oil; in 4 studies castor oil have similar efficacy with other preparations (such as bisacodyl or sodium phosphate); the minimum efficacy dose corresponds to 30 ml (Hsieh et al., 2000; Apisarnthanarak et al., 2009).
4.3. Clinical studies in special populations (e.g. elderly and children)
No data available.
Assessor comments: There are no studies on the potential benefits in children and adolescents. In Estonia and Latvia laxative or ‘clearing the bowels’ products with castor oil are on the market which include a posology for children. However, due to the mechanism of action (anionic surfactant) and the lack of clinical data for children and adolescents, the use in children and adolescents under 18 years of age is not recommended in the monograph.
4.4. Overall conclusions on clinical pharmacology and efficacy
The efficacy of castor oil has been evaluated in clinical trials in the treatment of constipation and for bowel cleansing before radiological investigations or colonoscopy. The use as a laxative (at low dose) and cathartic at higher dose is also described in
Another textbook (Ersparmer, 1982) mentioned that
Regarding the laxative effect of castor oil in constipated patients a review described two trials (one double blind positive controlled and one observational), the results supporting an
In the monograph, a single dose of
5 g/day. The assessment report includes 14 clinical studies that investigated the efficacy of castor oil as bowel cleansing. Eleven of them were conducted in adult patients with normal bowel habits and just three included constipated patients (Strates and Hofmann, 1987; Kolts et al., 1993; Dadkhah et al., 2012). Just one study (Dadkhah et al., 2012) used a valid scale (Rome III criteria) to identify the constipated patients.
In order to assess the efficacy of castor oil, the 14 clinical studies were divided in two categories: studies where the treatment was combined with an enema treatment (4 studies) and studies performed without an additional enema treatment (10 studies). The results from the studies conducted without enema revealed that one study had irrelevant results (not significantly different from the control, due to the poor compliance rate) while in all other nine studies castor oil proved its cathartic effect. In 4 studies castor oil have similar efficacy with other preparations (such as bisacodyl or sodium phosphate).
HMPC is of the opinion that the clinical data are not sufficient to support a purgative indication. Posology used in the trails is too heterogeneous (from 30 ml to 80 ml, as a single or divided dose). Moreover, trial sample sizes are also too heterogeneous; in some trials less than 12 patients are included, while in other trials the groups are larger (hundreds). Also, the
Because there are no publications that investigated the potential benefits in adolescents and children and as a general precaution taking into account the mechanism of action (anionic surfactant), the use is not recommended in children and adolescents under 18 years of age.
5. Clinical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trials in humans
Table 10: Clinical safety data from clinical trials
5.2. Patient exposure
Aside from its market presence and data from clinical studies in humans, castor oil can be found also in food as a flavoring substance and/or adjuvant (21 CFR 172.510). The joint Food and Agriculture Organisation (FAO)/World Health Organisation (WHO) expert committee on food additives (JECFA) has evaluated the castor oil and approved it as safe for use in food as a carrier solvent and/or release agent. FAO/WHO established an acceptable daily intake (for man) of 0 to 0.7 mg/kg body weight for castor oil. The Flavor and Extract Manufacturers Association (FEMA) has also evaluated the food- flavoring uses of castor oil and determined that it is GRAS (Generally Recognised As Safe, FEMA No. 2263; Burdock et al., 2006).
5.3. Adverse events, serious adverse events and deaths
See section 5.1.
In the VigiLyze database of the World Health Organisation’s Uppsala Monitoring Centre for the period up to August 2014, there were 23 spontaneous reports of suspected adverse drug reactions associated with the
Hagenfeldt et al. (1986) reported epoxydicarboxylic aciduria (large amounts of
In a case report by Steingrub et al. (1988), a
Adverse events were also mentioned from Member States. Federal Institute for Drugs and Medical devices (BfArM) reported the following adverse reactions: gastric irritation, nausea, vomiting, painful intestinal cramps and severe diarrhoea that may occur with increasing dose. In such cases dose reduction is necessary.
Chronic use (abuse) may lead to increased loss of water and electrolytes. Especially loss of potassium may occur which can cause disturbance of heart function and muscle weakness.
Hypersensitivity reactions of the skin were reported.
On the basis of the available data the frequency is not assessable. So the frequency is not known.
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 Toxnet system (http://toxnet.nlm.nih.gov), the oral use of castor oil in infants during the first 2 to 3 days of life can induce paralytic ileus and aspiration pneumonia. The same database reported severe hypoalbuminemia, diarrhea and malnutrition in a
There are no studies on the potential benefits or safety in children and adolescents. Therefore, as a general precaution taking into account the mechanism of action (as anionic surfactant), the use is not recommended in children and adolescents under 18 years of age.
Castor oil is contraindicated in patients with known hypersensitivity to castor oil, intestinal obstruction and stenosis, atony, appendicitis, inflammatory colon diseases (e.g. Crohn’s disease, ulcerative colitis), abdominal pain of unknown origin, severe dehydration state with water and electrolyte depletion (Gruenwald et al., 2004 )
According to the WHO monograph, the use of high doses of castor oil during pregnancy and lactation is contraindicated (WHO, 2009).
5.5.3. Special Warnings and precautions for use
In general, if stimulant laxatives are taken for longer than a brief period, this may lead to impaired function of the intestine. The altered intestinal permeability caused by castor oil may reflect grosser morphological damage to the intestinal epithelium. The strong purgative action can cause colic as well as dehydration with electrolyte imbalance. For these reasons and because of possible reduction of the absorption of nutrients,
Castor oil should only be used if a therapeutic effect cannot be achieved by a change of diet or the administration of bulk forming agents.
Patients taking medicinal products mentioned in chapter “interactions” have to consult a doctor before taking castor oil.
5.5.4. Drug interactions and other forms of interaction
Hypokalaemia (resulting from
These interactions are included in the product information of products that authorised in Germany.
5.5.5. Fertility, pregnancy and lactation
Castor oil has been widely used as a method of initiating labour in midwifery practice. Its role in the initiation of labour is poorly understood but this effect was studied in several trails.
Davis (1984) investigated the use of castor oil to stimulate labor in 196 patients with premature rupture of membranes (PROM), who were between 37 and 42 weeks of gestation. Of the 196 patients,
107 (mean age=28.6 years) were dosed orally with castor oil (2 oz=56.7 g) and 89 (mean age=27.6 years) were not. Castor oil was administered only to PROM patients who had a latency period of at least 4 hours. Of the 107 patients dosed with castor oil, 80 (75%) had labour onset. Spontaneous labour occurred in 52 (58%) of the 89 control patients. This difference between patients dosed with castor oil and controls was statistically significant (P < 0.05). The interval between castor oil administration and the onset of labor ranged from 1 to 13 hours (mean=4 hours). Labour outcomes were also evaluated for type of delivery, incidence of oxytocin stimulation, and infant
Garry et al. (2000) evaluated the use of castor oil to induce labour in 52 pregnant women (mean age=24.8±6.7 years). The untreated control group consisted of 48 pregnant women (mean age=24.4 ±4.9 years). Castor oil was administered as a
These data suggest that castor oil at high doses
The use during lactation is not recommended, because ricinoleic acid is absorbed orally and excreted into human breast milk. According to the WHO, a purgative effect was observed in breastfed infants when the mother had used castor oil (WHO, 2009)
Overdosage can lead to gastric irritation with nausea, vomiting, colic and severe diarrhoea, loss of electrolytes and water (Gruenwald et al., 2004)
Treatment should be supportive with generous amount of fluid and correction of electrolytes. A specific antidote is not available.
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
No data available.
5.6. Overall conclusions on clinical safety
Based on the clinical safety data, and the number of and nature of side effects reported in Member States, the oral administration of castor oil can be regarded as safe. Given the history of
From clinical trials, spontaneous reports and information from the Member States the most frequently reported adverse events were: gastric irritation, nausea, vomiting, cramps and severe diarrhoea. The frequencies are not known.
The use of castor oil for a longer period may lead to morphological damage to the intestinal epithelium, this inducing impaired function of the small intestine, as dehydration with electrolyte imbalance. Especially the loss of potassium may occur which can cause disturbance of heart function and muscle weakness. Therefore
The duration of use proposed for 1 week, which is less than the duration of the observational study (Buechi, 2000) but in agreement with the double blind randomised positive control trial (Buechi, 2000) and other European Union monographs for the same therapeutic indication.
Castor oil cannot be recommended for oral use in children and adolescents under 18 years of age due to lack of adequate safety data and taking into account its mechanism of action, as anionic surfactant. Nonclinical and clinical data are suggesting that high doses of castor oil
6. Overall conclusions
Products containing castor oil (virgin and refined) have been registered as traditional herbal medicinal products or
Several experimental findings demonstrate that castor oil has laxative properties. Orally ingested ricinolein, the main constituent of castor oil, is hydrolysed in the small intestine to ricinoleic acid that acts as a local irritant resulting in extensive electrolyte secretion in the small intestine by reducing net absorption of fluid and electrolytes.
Several studies in vitro and in vivo have shown that relatively high concentrations of ricinoleic acid can cause ultrastructural alterations in the villous tips of the intestinal mucosa, but the effects are reversible in all species investigated
The available clinical studies are supporting the use of castor oil as a
The laxative effect of castor oil observed in the clinical results is in line with the
In conclusion, based on well established use in the EU and available clinical evidence one indication is proposed under well established use:
The available clinical data is considered insufficient to support the use as a purgative.
Benefit – risk assessment
Herbal preparations with castor oil have a general positive benefit – risk balance.
The benefit of the medicinal use in the specified well established indication is adequately demonstrated.
In some Member States the use of castor oil is considered obsolete. No safety concerns could be retrieved from literature and pharmacovigilance data which justifies this classification. Moreover, products containing castor oil are authorised medicinal products for the proposed indication in several EU Member States.
The use during pregnancy and lactation is not recommended, taking into account
Castor oil cannot be recommended for oral use in children and adolescents under 18 years of age due to lack of adequate efficacy and safety data.
From clinical trials, spontaneous reports and information from the Member States the most frequently reported adverse events were: gastric irritation, nausea, vomiting, cramps and severe diarrhoea. These reactions should be listed as undesirable effects in section 4.8 of the monograph. The frequencies are not known.
Adequete tests on genotoxicity and carcinogenicity for Ph. Eur. grade castor oil haven not been performed.
ATC code: A06 AB 05 Contact laxative