New Zealand Journal of Botany, 2004, Vol. 42: 815–832 0028–825X/04/4205–0815 © The Royal Society of New Zealand 2004 Diversity of Brassica (Brassicaceae) species naturalised in Canterbury, New Zealand hybridisation. One plant has a ﬂ ow cytometry proﬁ le and a high percentage of malformed pollen that are consistent with being the putative interspeciﬁ c F1
Aecosan.msssi.gob.esReport of the Scientific Committee of the Spanish Agency for
Consumer Affairs, Food Safety and Nutrition (AECOSAN) on the
risk of using Tribulus terrestris in food supplements
Section of Food Safety and Nutrition
Reference number: AECOSAN-2015-003
Elena Alonso Lebrero, José Manuel Barat Baviera, María Report approved by the Section of Food Safety and
Pilar Conchello Moreno, Ramón Estruch Riba, María Antonia Nutrition of the Scientific Committee on plenary session
Ferrús Pérez, Guillermina Font Pérez, Susana Guix Arnau, May 20th, 2015
Arturo Hardisson de la Torre, Ángeles Jos Gallego, Ascensión Marcos Sánchez, Amelia Marti del Moral, Olga Martín Belloso, revista del comité científico nº María Aránzazu Martínez Caballero, Alfredo Palop Gómez, José Luis Ríos Cañavate (Coordinator) Gaspar Pérez Martínez, José Luis Ríos Cañavate, Gaspar Ros Ángeles Jos Gallego Berruezo, Jesús Ángel Santos Buelga, Jesús Simal Gándara, Josep Antoni Tur Marí Technical Secretary
Vicente Calderón Pascual
Tribulus terrestris L. is a plant from the Zygophyllaceae family whose use in food supplements
is authorised in various countries of the European Union. In its natural form, it contains various
active substances, the most notable of which are steroidal saponins, b-carboline alkaloids,
flavonoids and lignanamides.
Tribulus terrestris' toxicity to animals has been widely documented throughout its history as a medicinal plant and it has been reported to have negative neuronal, muscular, hepatic and renal effects.
Some countries consider using parts of the Tribulus terrestris plant to produce food supplements to be unsafe, so they do not allow such supplements to be sold. This is reported through the European Rapid Alert System for Food and Feed (RASFF).
The Scientific Committee has conducted a risk assessment with the aim of determining whether consuming fruit, plant shoots and extracts from Tribulus terrestris in food supplements is safe, concluding that there is insufficient toxicological data to assess how safe using parts from the Tribulus terrestris plant in food supplements is.
In any case, the maximum daily quantity of Tribulus terrestris in food supplements should not exceed the dose used for pharmacological purposes. The part of the plant used, whether it was extracted or prepared in some other way, as well as its saponin content, should all be made clear on the supplement itself.
Tribulus terrestris, food supplements, saponins.
Translated from the original published in the journal: Revista del Comité Científico de la AECOSAN, 21, pp: 37-44 AECOSAN Scientific Committee: Risk of using Tribulus terrestris in food supplements 1. Introduction
Tribulus terrestris L. (common names: caltrop, goathead, rosette and tribule) is a plant from the
Zygophyllaceae family whose use in food supplements is authorised in various European Union
It is an herbaceous perennial plant, which is found naturally in the Mediterranean region although it can be found all around the world. This plant naturally contains various active substances (b-carboline alkaloids and steroidal saponins). Its fruits, leaves and young sprouts are utilised.
revista del comité científico nº Its use in food supplements is authorised in some European Union member states, such as Italy, without any comments or restrictions. However, certain restrictions do exist in other countries. For instance, its use is authorised in Belgium as long as no toxicity is found in regards to the daily recommended dose (Belgium, 2001). In Germany, reference is made to the dose established by the WHO (World Health Organisation) (BVL, 2014), and in France it is required that the parts of the plant be boiled (France, 2014). In a recent assessment of food supplements containing this plant conducted by Denmark Technical University (DTU), it was concluded that Tribulus terrestris can cause serious toxic effects on animals' livers and central nervous systems and that, after having assessed several supplements containing different doses of the plant (2 000-2 250 mg/day), a safe limit intake level cannot be determined. Thus, in Denmark it is considered that, according to available information, it is not possible to establish a threshold below which use of Tribulus terrestris plant parts in food supplements is considered safe for health. Supplements containing said plant are thus classified as non-authorised products, thereby prohibiting its placing on the market. This is reported to the European Rapid Alert System for Food and Feed (RASFF).
In view of the possible side effects attributed to this plant, the Management Board of the Spanish Agency for Consumer Affairs, Food Safety and Nutrition (AECOSAN) has requested that the Section of Food Safety and Nutrition of the Scientific Committee conduct a risk assessment in order to determine whether or not the consumption of fruits, aerial parts and the extracts of Tribulus terrestris in food supplements is safe.
2. Characteristics and composition
Tribulus terrestris L. (Zygophyllaceae) is an herbaceous perennial plant found naturally in the
Mediterranean region, although nowadays it can be found all over the world. The aerial parts are
what are primarily used: fruits, leaves and young plant sprouts.
In its natural form, this plant contains various active substances among which stand out: • Steroidal saponins (protodioscin, prototribestine, pseudo-protodioscine, dioscine, tribulosaponins A and B, tribestine, tribulosin and terrestrosins A-K): between 2.9 % and 0.0015 % (Kostova and Dinchev, 2005) (DTU, 2014).
• b-Carboline alkaloids (harman, norharman and others): 40-80 mg/kg dry weight (0.004-0.008 %) (EFSA, 2012).
AECOSAN Scientific Committee: Risk of using Tribulus terrestris in food supplements • Flavonoids (kaempferol, quercetin and rutin). • Lignanamides (tribulusamide A and B). The content of some of these substances (for example saponins and flavonoids) varies depending on where they originated, the part of the plant and their degree of development (Dinchev et al., 2008).
3. Previous knowledge regarding pharmacological activity and current uses
There are different scientific experimental studies regarding the possible pharmacological revista del comité científico nº activities of Tribulus terrestris (WHO, 2009).
In Chinese medicine, it has been used as a treatment for coronary heart disease and was originally used as a diuretic. Nowadays it has fallen into disuse due to different clinical observations associating Tribulus terrestris intake with cases of neuronal, hepatic and renal toxicity. It is especially contraindicated for pregnant and breastfeeding women, children and patients with liver or kidney diseases. Its recent comeback is due to a supposed aphrodisiac effect, which has won it the name ‘'herbal viagra''. In the Framework of the Regulation (EC) No 1924/2006 of 20 December 2006 concerning nutrition and health claims made on foods, twelve statements about the health properties associated with Tribulus terrestris' fruits and fruit extracts were presented to the European Food Safety Authority (EFSA) for evaluation. The EFSA (2010a,b) has already evaluated and rejected three of these statements and the rest are still pending evaluation. The applications for evaluation attempted to attribute the different beneficial effects to doses between 0.03 and 0.6 g/powder per day, 0.015 and 0.3 g/day of the aqueous powder extract, 0.5 and 3 g/fruit per day and between 200 and 280 mg of the fruit extract (used as a part of multibotanical combination) (EFSA, 2010a,b). Its use in food supplements is authorised in some European Union member states, such as Italy, without any comments or restrictions. In this country, it is indicated as a tonic and metabolic support (for mental and physical fatigue) as well as for improved digestive and urinary functioning (Italy, 2014). However, certain restrictions do exist in other countries. For instance, its use is authorised in Belgium as long as no toxicity is found in the daily recommended dose (Belgium, 2001) and in Germany reference is made to the dose defined by the WHO (BVL, 2014). In turn, in France it is required that the parts of the plant be boiled (France, 2014). 4. Toxicity
The EFSA (2012) considers Tribulus terrestris to be among the plants whose natural compounds
may be of concern for human health when used in foods or food supplements. The German gov-
ernment has included it on the B list - a list containing substances requiring restrictions on use
in foods (BVL, 2014).
Tribulus terrestris' toxicity to animals has been widely documented throughout its history as a medicinal plant (McDonough et al., 1994) (Aslani et al., 2003) (Bourke, 2006) (Schmidt et al., 2011) AECOSAN Scientific Committee: Risk of using Tribulus terrestris in food supplements (Bourke, 2012), and has been reported to have negative neuronal, muscular, hepatic and renal effects such as neuromuscular ataxia, motor impairments, cholestasis, bile duct degradation and inflammation among other effects. When used as feed in small ruminants (especially in herds of sheep) its use was attributed to • "Geeldikkop", tribulosis ovis or "Yellow big head" (with cases primarily in South Africa, Iran, Australia and the United States). It is a photosensitivity characterised by an accumulation of phylloerythrin (a porphyrin derived from the breakdown of chlorophyll in the rumen) due revista del comité científico nº to a bile duct blockage caused by the crystalline material resulting from the calcium salts of epismilagenin and episarsasapogenin glucuronides. These compounds are diosgenin and yamogenin metabolites, Tribulus terrestris steroidal saponins Furthermore, the content and composition of Tribulus terrestris saponins can be different based on previous identification of both lithogenic and non-lithogenic groups (Aslani et al., 2003).
• A motor neuron disease causing lower limb weakness which gives rise to tremors, postural asymmetry (bent posture), atrophy in extensor muscles, etc. (Bourke, 2006). The levels of dopamine in the striatum decrease (Bourke, 1987). These effects have been associated with b-carboline alkaloids found in Tribulus terrestris, harman and norharman (Bourke et al., 1992). Although their presence is apparently trivial for an acute toxicity, it has been proven that they both accumulate in the central nervous system, irreversibly interacting with specific genes. The doses established as toxic are those equivalents to 54 mg/kg for isolated alkaloids and 44.0 mg/kg for alkaloid-enriched fractions. Other studies indicate that the combination of xanthosine intake (a neuromodulator present in Tribulus terrestris) with a molydbenum deficiency could be the cause of this disorder (Bourke, 2012).
In regards to the doses tested during the animal toxicity studies, there is a wide variety with an average of 50 mg/kg (hydroethanol extract) for 8 weeks. In rats, Paula-Lopes et al. (2006) observed toxic effects to the liver and kidney as well as a decrease in body weight following a daily intake of 5 mg of Tribulus terrestris (seeds and fruits) for 60 days. Heidari et al. (2007) indicated unspecified toxic effects in mice following intraperitoneal administration of 400 and 800 mg/kg of a dry methanolic extract obtained from 50 g of the plant.
Jameel et al. (2004) described a case of gynecomastia in a young person, which resulted from the ingestion of a Tribulus terrestris preparation used as an alternative to anabolic steroids. Talasaz et al. (2010) described several toxic effects in a young adult resulting from the intake of Tribulus terrestris infusions for 2 days. Of particular relevance was the hepatotoxicity, nephrotoxicity and neurotoxicity, although fortunately the effects were reversible once intake was discontinued. Recently, Ryan et al. (2015) confirmed the nephrotoxicity secondary to cholestasis and hyperbilirubinemia from Tribulus terrestris in a young patient who took two tablets daily for several months (exact dose and length of time are not indicated). Other recent in vitro studies have also indicated cytotoxicity as well as genotoxic and estrogenic activity from Tribulus terrestris extracts (Abudayyak et al., 2015).
AECOSAN Scientific Committee: Risk of using Tribulus terrestris in food supplements In a recent assessment of food supplements containing Tribulus terrestris that was conducted by Denmark Technical University (DTU), it was reported that Tribulus terrestris can cause serious toxic effects on animals' livers and central nervous system. After having assessed several supplements containing different doses of the plant (2 000-2 250 mg/day), a safe limit intake level cannot be determined (DTU, 2014). Monographs from the Spanish Society of Phytotherapy (SEFIT, 2015) and the World Health Organisation (WHO, 2009) warn against the potential dangers of this plant species.
revista del comité científico nº In a sampling of the Tribulus terrestris food supplements notified in Spain, it was observed that the content of the Tribulus terrestris extract oscillated between 250 and 1 500 mg. The study was performed by selecting food supplements, which referred to the presence of Tribulus terrestris in its commercial name and corresponded to its extracts (without specifying the part of the plant). Considering the recommended maximum daily intake of the plant, its consumption would range from 250 to 9 000 mg.
In their monograph discussing Tribulus terrestris as a medicinal product, the WHO (2009) established a dosage ranging between 3 and 6 g of the dry powdered fruit (single dose with decoction) or an intake ranging between 6 and 9 g spread out over several doses (with decoction) over the course of the day. In addition, the WHO does not recommend intake in children under 12 years of age given the lack of safety information regarding said plant.
Conclusions of the Scientific Committee
The Scientific Committee concludes that there is not enough toxicological data available to as-
sess the safety of the use of Tribulus terrestris plant parts in food supplements.
In any case, the maximum daily quantity of Tribulus terrestris in food supplements should not exceed the dose used for pharmacological purposes. The part of the plant used, whether it was extracted or prepared in some other way, as well as its saponin content should all be made clear on the supplement itself.
Abudayyak, M., Jannuzzi, A.T., Ózhan, G. and Alpertunga, B. (2015). Investigation on the toxic potential of
Tribulus terrestris in vitro. Pharmaceutical Biology, 53, pp: 469-476.
Aslani, M.R., Movassaghi, A.R., Mohri, M., Pedram, M. and Abavisani, A. (2003). Experimental Tribulus terrestris poisoning in sheep: clinical, laboratory and pathological findings. Veterinary Research Communication, 27, pp: 53-62.
Bélgica (2001). Arreté ministériel modifiant l'annexe de l'arreté royal du 29 aout 1997 relatif á la fabrication et au commerce de denrées alimentaires composées ou contenant des plantes ou préparations de plantes.
Bourke, C.A. (1987). A novel nigrostriatal dopaminergic disorder in sheep affected by Tribulus terrestris staggers. Research in Veterinary Science, 43, pp: 347-350.
Bourke, C.A. (2006). Abnormal turning behaviour, GABAergic inhibition and the degeneration of astrocytes in ovine Tribulus terrestris motor neuron disease. Australian Veterinary Journal, 84, pp: 53-58.
AECOSAN Scientific Committee: Risk of using Tribulus terrestris in food supplements Bourke, C.A. (2012). Motor neurone disease in molybdenum-deficient sheep fed the endogenous purine xanthosine: possible mechanism for Tribulus staggers. Australian Veterinary Journal, 90, pp: 272-274. Bourke, C.A., Stevens, G.R. and Carrigan, M.J. (1992). Locomotor effects in sheep of alkaloids identified in Australian Tribulus terrestris. Australian Veterinary Journal, 69, pp: 163-165.
BVL (2014). Bundeseamt für Verbraucherschutz und Lebensmittelsicherheit. BVL report 8.8. List of Substances of the Competent Federal Government and Federal State Authorities Category "Plants and plant parts". Dinchev, D., Janda, B., Evstatieva, L., Oleszek, W., Aslani, M.R. and Kostova, I. (2008). Distribution of steroidal saponins in Tribulus terrestris from different geographical regions. Phytochemistry, 69, pp: 176-186.
DTU (2014). Technical University of Denmark. Risikovurdering af Tribulus terrestris i fire kosttilskud fra revista del comité científico nº EFSA (2010a). European Food Safety Authority. Scientific Opinion on the substantiation of health claims related to various food(s)/food constituent(s) and "energy and vitality" (ID 18, 26, 62, 105, 122, 145, 165, 3962, 4054, 4440), "invigoration of the body" (ID 2383, 2386, 2391, 2393, 2409, 2441, 2463, 2488, 3834, 3883), "general health" (ID 1313, 3348, 4182, 4613), "rejuvenation" (ID 3981, 4023), "tonic" (ID 1703, 3462, 3581, 4418), "stimulant" (ID 3190, 3506) and "metabolic benefits" (ID 4438) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. The EFSA Journal, 8 (10): 1738, pp: 1-21.
EFSA (2010b). European Food Safety Authority. Scientific Opinion on the substantiation of health claims related to various food(s)/food constituent(s) claiming an increase in renal water elimination, "kidneys health", "urinary health", "bladder health", "health of lower urinary tract", "blood health", "elimination", "urinary system benefits" and/or "supports/promotes the excretory function of the kidney", and treatment/prevention of renal gravel/kidney stones and urinary tract infections pursuant to Article 13(1) of Regulation (EC) No 1924/2006. The EFSA Journal, 8 (10): 1742, pp: 1-49.
EFSA (2012). European Food Safety Authority. Scientific report: Compendium of botanicals reported to contain naturally occurring substances of possible concern for human health when used in food and food supplements. The EFSA Journal, 10: 2663.
Francia (2014). Arreté du 24 juin 2014 établissant la liste des plantes, autres que les champignons, autorisées dans les compléments alimentaires et les conditions de leur emploi.
Gandhi, S., Srinivasan, B.P. and Akarte, A.S. (2013). Potential nephrotoxic effects produced by steroidal saponins from hydro alcoholic extract of Tribulus terrestris in STZ-induced diabetic rats. Toxicology Mechanisms and Methods, 23, pp: 548-557. Heidari, M.R., Mehrabani, M., Pardakhty, A., Khazaeli, P., Zahedi, M.J., Yakhchali, M. and Vahedian, M. (2007).
The analgesic effect of Tribulus terrestris extract and comparison of gastric ulcerogenicity of the extract with indomethacine in animal experiments. Annals of the New York Academy of Sciences, 1095, pp: 418-427.
Italia (2014). Decreto de 27 marzo 2014 que modifica al Decreto de 9 de Julio de 2012 Disciplina dell' impiego negli integratori alimentari di sostanze e preparati vegetali.
Jameel, J.K., Kneeshaw, P.J., Rao, V.S. and Drew, P.J. (2004). Gynaecomastia and the plant product "Tribulis terrestris". Breast, 13, pp: 428-430.
Kostova, I. and Dinchev, D. (2005). Saponins in Tribulus terrestris-chemistry and bioactivity. Phytochemistry Reviews, 4, pp: 111-137.
McDonough, S.P., Woodbury, A.H., Galey, F.D., Wilson, D.W., East, N. and Bracken, E. (1994). Hepatogenous photosensitization of sheep in California associated with ingestion of Tribulus terrestris (puncture vine). Journal of Veterinary Diagnostic Investigation, 6, pp: 392-395. Paula-Lopes, T.R.V., Souza, M.A., Paz, K., Lopes, R.A., Sala, M.A., Regalo, S.C.H. and Rodrigues, E.R. (2006). Hepatotoxicity of medicinal plants. XXXIII. Action of Tribulus terrestris L. in rats. A Revista Brasileira de Plantas Medicinais, 8, pp: 150-156.
AECOSAN Scientific Committee: Risk of using Tribulus terrestris in food supplements Ryan, M., Lazar, I., Nadasdy, G.M., Nadasdy, T. and Satoskarm, A.A. (2015). Acute kidney injury and hyperbilirubinemia in a young male after ingestion of Tribulus terrestris. Clinical Nephrology, 83, pp: 177-183. Schmidt, M., Thomsen, M. and Bone, K. (2011). Tribulus terrestis-induced nephrotoxicity? Nephrology Dialysis Transplantation, 26, pp: 3065-3066.
SEFIT (2015). Spanish Society of Phytotherapy. Vademécum de prescripción. Available at: http://www.
Talasaz, A.H., Abbasi, M.R., Abkhizm, S. and Dashti-Khavidaki, S. (2010). Tribulus terrestris-induced severe nephrotoxicity in a young healthy male. Nephrology Dialysis Transplantation, 25, pp: 3792-3793.
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WHO (2009). World Health Organisation. Monographs on Selected Medicinal Plants. vol 4. Genève. pp: 323-
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