Tribulus terrestris

• How It Works

  Tribulus has not been shown to treat or prevent cancer in humans.

  Tribulus is an herb that grows in the subtropical regions of eastern and western Asia, southern Europe, and Africa. It is used in traditional medicine for chest pain, heart problems, dizziness, skin and eye disorders, to expel kidney stones, and as a diuretic and tonic. Tribulus is also marketed as a dietary supplement to improve sexual function and for body building due to the belief that it acts like testosterone in the body. However, this effect has not been confirmed. There are two small studies that suggest that it may help female sexual dysfunction, but large-scale studies are needed.

  Test tube and animal studies show that tribulus has medicinal effects against high blood pressure, diabetes, inflammation, infection, and cancer.

  The use of tribulus has been linked to adverse effects in both animals and humans. Due to its potential hormonal activities, prostate cancer patients should avoid this herb until more is known about its safety.

• Purported Uses
  • To treat cancer
    Tribulus showed anticancer activities in lab studies. It has not been tested in humans as a cancer treatment.
  • To lower blood pressure
    Tribulus extract can relax blood vessels and may help to lower blood pressure.
  • To enhance sexual function
    Tribulus increases sperm production in animal models, but human studies of its effects on testosterone levels gave mixed results. The current evidence suggests that it is not effective for increasing testosterone levels or treating erectile dysfunction. However, two small studies suggest that it may help female sexual dysfunction. Large-scale studies are needed to confirm this.
  • To improve muscle strength and muscle mass
    A clinical study did not find any significant changes in muscle strength or mass with use of tribulus.
  • To treat infections
    Tribulus has antifungal activities in lab studies. Human data are lacking.
  • To reduce pain
    Tribulus extract reduced inflammation in lab studies, but human studies have not been done.
  • To treat kidney stones
    Tribulus can promote urination and stop calcium compounds that cause kidney stones from forming. However, these effects have not been studied in humans.
• Do Not Take If
  • You are taking diruetics: Tribulus may increase the effects of diuretic drugs.
  • You are taking antihypertensive drugs: Tribulus may have an additional blood pressure lowering effect.
  • You are taking antidiabetics: Tribulus may have additive blood sugar lowering effects.
  • You are taking clopidogrel: Tribulus may increase the risk of blood clots.
• Side Effects
  • Gastrointestinal irritations
  • Case reports of severe liver, kidney, and neurological toxicities
• Scientific Name

  Tribulus terrestris

• Clinical Summary

  Tribulus is a perennial herb that grows in the subtropical regions of eastern and western Asia, southern Europe, and Africa. It is used in traditional Chinese and Indian medicine systems for chest pain, heart-related problems, dizziness, skin and eye disorders, to expel kidney stones, and as a diuretic and tonic. It is also marketed as a dietary supplement to enhance sexual function ⁽²⁵⁾ and for body building ^(26) (27).

  Preliminary studies indicate that tribulus has analgesic ⁽¹⁾, antihypertensive ^(2) (3), anti-inflammatory ^(4) (28), antiedematous ⁽²⁸⁾, antioxidant ^(5) (6), diuretic ⁽⁷⁾, hypoglycemic ⁽⁸⁾, antibacterial ⁽⁹⁾, antifungal ^(9) (10), cardioprotective ⁽²⁹⁾, and anticancer properties ^{(11) (12) (15)}.

  In vitro studies found that saponins in tribulus inhibit platelet aggregation ⁽³⁰⁾. In animal models of chronic mild stress tribulus saponins produced antidepressive effects ⁽³¹⁾. In diabetic neuropathic pain models, a standardized tribulus extract was found to be comparable to the drug Pregabalin, with significant increases in pain threshold responses ⁽³²⁾.

  Tribulus has been shown to increase sperm production ⁽¹³⁾, but its effects on testosterone levels are mixed ^(14) (16). In human studies, testosterone increases only occurred when tribulus was part of a combined supplement therapy, making it difficult to determine its contribution to this effect ⁽²⁵⁾. In a randomized double-blind study to evaluate effects on erectile dysfunction and serum total testosterone, tribulus was not more effective than placebo ⁽³³⁾. A pilot study evaluating tribulus in men with partial androgen deficiency showed significant differences in testosterone levels and erectile function, but no significant differences in levels of luteinizing hormone ⁽³⁴⁾. In women, however, two small studies indicate improvements in sexual dysfunction ^(35) (36). Larger randomized controlled trials are needed to confirm these results. A tribulus extract used alone did not not improve androgenic status or physical performance among athletes ^(26) (37).

  Saponins in tribulus have shown activity against in breast ⁽³⁸⁾ and prostate cancer cells ⁽³⁹⁾, and may protect against UVB-induced carcinogenesis ⁽⁴⁰⁾. In animal models, tribulus resulted in a significant reduction in tumor incidence, tumor burden, and cumulative number of papillomas ⁽¹⁹⁾, and relieved cisplatin-induced renal toxicity ⁽⁴¹⁾.

  Due to its purported hormonal activities, prostate cancer patients should avoid this product.

• Purported Uses
  • Cancer treatment
  • Hypertension
  • Infertility in both sexes
  • Impotency
  • Infections
  • Rheumatic pain
  • Kidney stones
• Mechanism of Action

  In vitro, cinnamic amides in tribulus fruits inhibit papain-like protease (PLpro), an essential proteolytic enzyme which plays a critical role in virus-mediated RNA replication ⁽⁴²⁾. Di-p-coumaroylquinic acid derivatives in tribulus are associated with its antioxidant effects ⁽⁴³⁾.

  Aphrodisiac effects may be associated with the constituent protodioscin, which leads to an increase in some sex hormones ⁽⁴⁴⁾. Erectogenic effects may also occur via conversion of protodioscin to DHEA ⁽³⁶⁾ or by concentration-dependent relaxation of the corpus cavernosum (CC) via reactions in the nitric oxide (NO)/NO synthase pathway and CC endothelium ^(45) (25). The NO release effect may explain observed physiological responses to tribulus supplementation, independent of testosterone level ⁽²⁵⁾. In a study conducted in rats with ovarian cysts, tribulus extract showed a luteinizing effect related to gonadotropin-like activity ⁽²⁰⁾.

  Saponins exhibit cytotoxic and antihyperlipidemic effects ⁽⁴²⁾. They may protect against atherosclerosis by suppressing angiotensin II-induced vascular smooth muscle cell proliferation via inhibition of intracellular ROS production, calcium ion mobilization, pkc-α expression, ERK1/2 phosphorylation, and proto-oncogene expression ⁽⁴⁶⁾. In ischemic cells, polyphenol-mediated antioxidant activity with tribulus extract resulted in significant suppression of LDH release, ROS generation, and superoxide production ⁽²⁹⁾.

  In animal models, tribulus exerts a protective effect in diabetic rats by inhibiting oxidative stress ⁽⁶⁾ and lowering levels of glycosylated hemoglobin and cholesterols ⁽⁸⁾. In diabetic neuropathic pain models, tribulus modulates oxidative stress and inflammatory cytokine release in a dose-dependent manner via increases in superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione and lipid peroxide levels ⁽³²⁾. In chronic mild stress models, the attenuation of serum corticotropin-releasing factor and cortisol levels by tribulus saponins suggest normalization of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity ⁽³¹⁾. Antihypertensive effects occur via arterial smooth muscle relaxation, NO release, and membrane hyperpolarization ⁽³⁾. An aqueous extract also demonstrated angiotensin converting enzyme (ACE)-inhibition activity ⁽²⁾ that may help lower blood pressure. Phenolic acids such as chlorogenic acid, caffeic acid and 4-hydroxybenzoic acid may be responsible for reputed cardioprotective properties ⁽²⁹⁾.

  Tribulus extracts induce apoptosis and suppress cancer cell proliferation by activating caspase 3, dephosphorylating extracellular signal-related kinase (ERK) 1 and 2 ⁽¹⁵⁾, and by inhibiting nuclear factor (NF-kappa B) signaling ⁽¹²⁾. Saponins from tribulus inhibit multiple-drug resistance of cancer cells ⁽¹¹⁾. In breast carcinoma cell lines, a saponin extract changed mRNA levels of CXCR4, CCR7 and BCL2 genes ⁽³⁸⁾. In models of human prostate cancer, antitumor and antiangiogenic activities are attributed to cell-cycle arrest and apoptotic induction not involving the caspase pathway ⁽³⁹⁾. Saponins also act as a modulator of apoptosis: in normal human keratinocytes, saponins attenuate UVB-induced programmed cell death through inhibition of intrinsic apoptotic pathway, but enhance apoptotic response in squamous cell carcinomas ⁽⁴⁰⁾. The photoprotective effect of saponins is attributed to enhanced NER gene expression and inhibition of UVB-mediated NF-kappaB activation ⁽⁴⁰⁾. In animal models, a hydroalcoholic extract of tribulus relieved cisplatin-induced renal toxicity, perhaps via diuretic effects that increase drug excretion, scavenging free radicals via increase in antioxidant enzymes, suppressing inflammatory agents, and acting on organic cation transporter 2 (OCT2) proteins ⁽⁴¹⁾.

  Tribulus extract was shown to limit formation of calcium oxalate and calcium hydrogen phosphate dihydrate crystals ^(21) (22), mineral compounds that can cause kidney stones.

  Consumption of tribulus causes motor neuron adverse effects in animals by affecting the gamma-aminobutyric acid (GABA) receptors ⁽¹⁸⁾. The steroidal saponin diosgenin is thought to be responsible for hepatotoxic effects associated with tribulus ⁽²⁷⁾.

• Adverse Reactions

  Transient GI problems including irritation of gastric mucosa and gastric reflux ⁽³⁶⁾.

  Case Reports

  • Severe hyperbilirubinemia: In a healthy 30-year-old male body-builder, followed by acute renal failure and bile-containing casts in the tubules associated with the ingestion of tribulus extract tablets, once daily for “a few months” ⁽²⁷⁾.
  • Neuro-, hepatic, and renal toxicity suggestive of acute tubular necrosis (ATN): In a 28-year-old man who consumed large quantities of tribulus extract for its antiurolithiatic properties. Additionally, he developed hypertension, seizures, and markedly elevated serum aminotransferases (>40x ULN) ⁽¹⁷⁾.
• Herb-Drug Interactions
  • Diruetics: Tribulus may increase the effects of other diuretic drugs ⁽⁷⁾.
  • Antihypertensive drugs: Tribulus has angiotensin converting enzyme (ACE)-inhibition activity and therefore, may have an additional hypotensive effect ^(2) (3).
  • Antidiabetics: Tribulus may have additive hypoglycemic effects ⁽⁸⁾.
  • Clopidogrel: May increase the risk of blood clots. Stent thrombosis has been reported in patients following concurrent use of clopidogrel and an herbal formula containing tribulus ⁽²³⁾.
  • P-glycoprotein (P-gp) substrate drugs: In vitro, saponins and phenolic compounds from Tribulus terrestris has been shown to inhibit P-gp activity. This may increase the risks of adverse effect of substrate drugs ⁽⁴⁸⁾.
• Herb Lab Interactions
  • Case reports of significant elevations in serum aminotransferases and creatinine ⁽⁴⁷⁾, and mildly elevated alkaline phosphatase as well as aspartate and alanine aminotransferases ⁽²⁷⁾.
• References

  1. Heidari MR, Mehrabani M, Pardakhty A, et al. The analgesic effect of Tribulus terrestris extract and comparison of gastric ulcerogenicity of the extract with indomethacine in animal experiments. Ann N Y Acad Sci. Jan 2007;1095:418-427.

  2. Sharifi AM, Darabi R, Akbarloo N. Study of antihypertensive mechanism of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE activity. Life Sci. Oct 24 2003;73(23):2963-2971.

  3. Phillips OA, Mathew KT, Oriowo MA. Antihypertensive and vasodilator effects of methanolic and aqueous extracts of Tribulus terrestris in rats. J Ethnopharmacol. Apr 6 2006;104(3):351-355.

  4. Hong CH, Hur SK, Oh OJ, et al. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J Ethnopharmacol. Nov 2002;83(1-2):153-159.

  5. Kamboj P, Aggarwal M, Puri S, et al. Effect of aqueous extract of Tribulus terrestris on oxalate-induced oxidative stress in rats. Indian J Nephrol. Jul 2011;21(3):154-159.

  6. Amin A, Lotfy M, Shafiullah M, et al. The protective effect of Tribulus terrestris in diabetes. Ann N Y Acad Sci. Nov 2006;1084:391-401.

  7. Al-Ali M, Wahbi S, Twaij H, et al. Tribulus terrestris: preliminary study of its diuretic and contractile effects and comparison with Zea mays. J Ethnopharmacol. Apr 2003;85(2-3):257-260.

  8. El-Tantawy WH, Hassanin LA. Hypoglycemic and hypolipidemic effects of alcoholic extract of Tribulus alatus in streptozotocin-induced diabetic rats: a comparative study with T. terrestris (Caltrop). Indian J Exp Biol. Sep 2007;45(9):785-790.

  9. Al-Bayati FA, Al-Mola HF. Antibacterial and antifungal activities of different parts of Tribulus terrestris L. growing in Iraq. J Zhejiang Univ Sci B. Feb 2008;9(2):154-159.

  10. Zhang JD, Cao YB, Xu Z, et al. In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens. Biol Pharm Bull. Dec 2005;28(12):2211-2215.

  11. Ivanova A, Serly J, Dinchev D, et al. Screening of some saponins and phenolic components of Tribulus terrestris and Smilax excelsa as MDR modulators. In Vivo. Jul-Aug 2009;23(4):545-550.

  12. Kim HJ, Kim JC, Min JS, et al. Aqueous extract of Tribulus terrestris Linn induces cell growth arrest and apoptosis by down-regulating NF-kappaB signaling in liver cancer cells. J Ethnopharmacol. Jun 14 2011;136(1):197-203.

  13. Martino-Andrade AJ, Morais RN, Spercoski KM, et al. Effects of Tribulus terrestris on endocrine sensitive organs in male and female Wistar rats. J Ethnopharmacol. Jan 8 2010;127(1):165-170.

  14. Singh S, Nair V, Gupta YK. Evaluation of the aphrodisiac activity of Tribulus terrestris Linn. in sexually sluggish male albino rats. J Pharmacol Pharmacother. Jan 2012;3(1):43-47.

  15. Neychev VK, Nikolova E, Zhelev N, et al. Saponins from Tribulus terrestris L are less toxic for normal human fibroblasts than for many cancer lines: influence on apoptosis and proliferation. Exp Biol Med (Maywood). Jan 2007;232(1):126-133.

  16. Saudan C, Baume N, Emery C, et al. Short term impact of Tribulus terrestris intake on doping control analysis of endogenous steroids. Forensic Sci Int. Jun 10 2008;178(1):e7-10.

  17. Talasaz AH, Abbasi MR, Abkhiz S, et al. Tribulus terrestris-induced severe nephrotoxicity in a young healthy male. Nephrol Dial Transplant.Nov 2010;25(11):3792-3793.

  18. Bourke CA. Abnormal turning behaviour, GABAergic inhibition and the degeneration of astrocytes in ovine Tribulus terrestris motor neuron disease. Aust Vet J. Jan-Feb 2006;84(1-2):53-58.

  19. Kumar M, Soni AK, Shukla S, et al. Chemopreventive potential of Tribulus terrestris against 7,12- dimethylbenz (a) anthracene induced skin papillomagenesis in mice. Asian Pac J Cancer Prev. Apr-Jun 2006;7(2):289-294.

  20. Dehghan A, Esfandiari A, Bigdeli SM. Alternative treatment of ovarian cysts with Tribulus terrestris extract: a rat model. Reprod Domest Anim. Feb 2012;47(1):e12-15.

  21. Joshi VS, Parekh BB, Joshi MJ, et al. Inhibition of the growth of urinary calcium hydrogen phosphate dihydrate crystals with aqueous extracts of Tribulus terrestris and Bergenia ligulata. Urol Res. May 2005;33(2):80-86.

  22. Aggarwal A, Tandon S, Singla SK, et al. Diminution of oxalate induced renal tubular epithelial cell injury and inhibition of calcium oxalate crystallization in vitro by aqueous extract of Tribulus terrestris. Int Braz J Urol. Jul-Aug 2010;36(4):480-488; discussion 488, 489.

  23. Vatankulu MA, Tasal A, Erdogan E, et al. [Three case reports of the use of herbal combinations resulted in stent thrombosis: herbal combinations; friend or foe?]. Turk Kardiyol Dern Ars. Apr 2012;40(3):265-268.

  24. Rogerson S, Riches CJ, Jennings C, et al. The effect of five weeks of Tribulus terrestris supplementation on muscle strength and body composition during preseason training in elite rugby league players. J Strength Cond Res. May 2007;21(2):348-353.

  25. Qureshi A, Naughton DP, Petroczi A. A systematic review on the herbal extract Tribulus terrestris and the roots of its putative aphrodisiac and performance enhancing effect. J Diet Suppl. Mar 2014;11(1):64-79.

  26. Pokrywka A, Obminski Z, Malczewska-Lenczowska J, et al. Insights into Supplements with Tribulus Terrestris used by Athletes. J Hum Kinet. Jun 28 2014;41:99-105.

  27. Ryan M, Lazar I, Nadasdy GM, et al. Acute kidney injury and hyperbilirubinemia in a young male after ingestion of Tribulus terrestris. Clin Nephrol. Mar 2015;83(3):177-183.

  28. Mohammed MS, Alajmi MF, Alam P, et al. Chromatographic finger print analysis of anti-inflammatory active extract fractions of aerial parts of Tribulus terrestris by HPTLC technique. Asian Pac J Trop Biomed. Mar 2014;4(3):203-208.

  29. Reshma PL, Lekshmi VS, Sankar V, et al. Tribulus terrestris (Linn.) Attenuates Cellular Alterations Induced by Ischemia in H9c2 Cells Via Antioxidant Potential. Phytother Res. Jun 2015;29(6):933-943.

  30. Kang LP, Wu KL, Yu HS, et al. Steroidal saponins from Tribulus terrestris. Phytochemistry. Nov 2014;107:182-189.

  31. Wang Z, Zhang D, Hui S, et al. Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats. J Tradit Chin Med. Apr 2013;33(2):228-232.

  32. Ranjithkumar R, Prathab Balaji S, Balaji B, et al. Standardized Aqueous Tribulus terristris (nerunjil) extract attenuates hyperalgesia in experimentally induced diabetic neuropathic pain model: role of oxidative stress and inflammatory mediators. Phytother Res. Nov 2013;27(11):1646-1657.

  33. Santos CA, Jr., Reis LO, Destro-Saade R, et al. Tribulus terrestris versus placebo in the treatment of erectile dysfunction: A prospective, randomized, double blind study. Actas Urol Esp. May 2014;38(4):244-248.

  34. Roaiah MF, El Khayat YI, GamalEl Din SF, et al. Pilot Study on the Effect of Botanical Medicine (Tribulus terrestris) on Serum Testosterone Level and Erectile Function in Aging Males With Partial Androgen Deficiency (PADAM). J Sex Marital Ther. Apr 7 2015:1-5.

  35. Akhtari E, Raisi F, Keshavarz M, et al. Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo-controlled study. Daru. 2014;22:40.

  36. Gama CR, Lasmar R, Gama GF, et al. Clinical Assessment of Tribulus terrestris Extract in the Treatment of Female Sexual Dysfunction. Clin Med Insights Womens Health. 2014;7:45-50.

  37. Neychev VK, Mitev VI. The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men. J Ethnopharmacol. Oct 3 2005;101(1-3):319-323.

  38. Goranova TE, Bozhanov SS, Lozanov VS, et al. Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris. Neoplasma. 2015;62(1):27-33.

  39. Wei S, Fukuhara H, Chen G, et al. Terrestrosin D, a steroidal saponin from Tribulus terrestris L., inhibits growth and angiogenesis of human prostate cancer in vitro and in vivo. Pathobiology. 2014;81(3):123-132.

  40. Sisto M, Lisi S, D’Amore M, et al. Saponins from Tribulus terrestris L. protect human keratinocytes from UVB-induced damage. J Photochem Photobiol B. Dec 5 2012;117:193-201.

  41. Raoofi A, Khazaei M, Ghanbari A. Protective effect of hydroalcoholic extract of tribulus terrestris on Cisplatin induced renal tissue damage in male mice. Int J Prev Med. 2015;6:11.

  42. Song YH, Kim DW, Curtis-Long MJ, et al. Papain-like protease (PLpro) inhibitory effects of cinnamic amides from Tribulus terrestris fruits. Biol Pharm Bull. 2014;37(6):1021-1028.

  43. Hammoda HM, Ghazy NM, Harraz FM, et al. Chemical constituents from Tribulus terrestris and screening of their antioxidant activity. Phytochemistry. Aug 2013;92:153-159.

  44. Gauthaman K, Ganesan AP. The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction—an evaluation using primates, rabbit and rat. Phytomedicine. Jan 2008;15(1-2):44-54.

  45. Do J, Choi S, Choi J, et al. Effects and Mechanism of Action of a Tribulus terrestris Extract on Penile Erection. Korean J Urol. Mar 2013;54(3):183-188.

  46. Li M, Guan Y, Liu J, et al. Cellular and molecular mechanisms in vascular smooth muscle cells by which total saponin extracted from Tribulus terrestris protects against artherosclerosis. Cell Physiol Biochem. 2013;32(5):1299-1308.

  47. Talasaz AH, Abbasi MR, Abkhiz S, et al. Tribulus terrestris-induced severe nephrotoxicity in a young healthy male. Nephrol Dial Transplant. Nov 2010;25(11):3792-3793.

  48. Ivanova A, Serly J, Dinchev D, et al. Screening of some saponins and phenolic components of Tribulus terrestris and Smilax excelsa as MDR modulators. In Vivo. 2009 Jul-Aug;23(4):545-50.