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Research Breakdown on Tribulus terrestris
Tribulus terrestris (of the family Zygophyllaceae) is an annual creeping herb widespread in China, eastern Asia, and extends into western Asia and southern Europe. The fruits of this plant have been used in Traditional Chinese Medicine for the treatment of eye trouble, edema, abdominal distention, high blood pressure, and cardiovascular diseases while in India its usage in Ayurveda was for the purpose of impotency, poor appetite, jaundice, urogenital disorders, and cardiovascular diseases. In Ayurvedic medicine, Tribulus terrestris is referred to as Gokshura or Chhota Gokshura for the treatment of lower back pain, sciatica, inflammation of the pelvic and sacral region, dry cough, respiratory disorders; it is known to be interchangeable with pedalium murex for the purpose of gokshura.
Tribulus is a plant used in both traditional chinese medicine and ayurveda for purposes mostly related to cardiovascular health, virility, and urogenital health
The tribulus genera extends to 25 species of which 12 of them are found in the middle east.
There are other species in the tribulus genera that are sometimes used in supplementation, including pentandrus (has more kaempferol in its flavonoid profile whereas terrestris has more quercetin; pentandrus also has tricin-7-diglucoside as a unique componnet) and alatus which also possesses steroidal glycosides such as spirostane, furostane, and cholestane and is implicated in testosterone boosting similar to pedalium murex but not tribulus terrestris.
Tribulus terrestris is one of a few species of the tribulus genera and the most commonly supplemented species
The main components of the tribulus terrestris root extract include:
Protodioscin commonly seen as the main bioactive and can comprise up to 45% of the Tribulus terrestris dry extract (exluding macronutrient and water weight)
Hecogenin-3-O-β-d-glucopyranosyl(1 → 4)-β-d-galactopyranoside
Gitogenin type saponins called Protodibestin and tribestin
di-p-coumaroylquinic acid and 4,5-di-p-cis-coumaroylquinic acid
A 60kDa antilithiatic protein
The fruits of the Tribulus plant (Tribulus terrestris fructi) contain:
Furostanol based steroidal saponins such as terrestroside A,B as well as terrestrinin B, terrestroneoside A, and chloromaloside and glycosides of these molecules including tribufuroside C and I-J
The root contains phenolics at around 178.57mg/g in the water extract (17.8%) and 114.28mg/g in ethanolic (11.4%) with the flavonoid component being 10mg/g and 5mg/g, respectively.
Both the fruits and the plant root itself appear to contain a variety of compounds that are roughly based on a steroid skeleton, steroidal saponins
Protodioscin, seen as the active muscle building compound (Tribulus' most heavily marketed claim), is highest in Turkey (Ankara), Bulgarian (Haskovo hirsut) and Macedonian (Bogdanzi glabr) respectively. These three species have more than double all other species.
The chemical make-up of the plant seems to vary by region of growth, with Vietnamese and Indian tribulus lacking both tribestin and prototribestin (the gitogeninic type)and having higher levels of tribulosin, at around 50-150 times more than the aforementioned species.
Much of the literature focuses on the extracts of Bulgarian, Chinese, and Indian origin; which proves problematic if the tribestin or protodioscin contents are the active components.
Although the region of Tribulus growth appears to influence the components, the major difference is in those grown in middle-eastern Europe and Western Asia having a higher protodioscin content and those grown in Eastern Asia and Oceania tending to have greater tribuloin content and no gitogenic saponins
Beyond the numerical differences of the above 6 compounds, Bulgarian Tribulus is the only extract to possess sulphated spirostanol and furostanol saponins and chinese tribulus seems to be the only compound with cisA/B ring junctures in their saponins.
Technically may interact with acetylcholine metabolism, but this has not yet been shown in a living model and it doesn't seem to be overly potent at the concentrations expected to be seen in the blood and brain In a rat model of chronic manageable stress (induces depression), 750-2,250mg/kg of a tribulus terrestris extract (80% saponins) was able to preserve the reduction in appetite.
There do appear to be increases in appetite in stressed rats and may be some inhernetly; needs more research to properly assess the traditional claims of increasing appetite In this study subjected mice to a chemical and thermal pain test (formalin and tail-flick, respectively) and although it was tested at various doses (50, 100, 200, 400, and 800mg/kg) an injection of 100mg/kg Tribulus extract appeared to be most potent and tended to be less pain-relieving than 2.5mg/kg morphine yet more than 300mg/kg Aspirin; the mechanism of action is not mediated by opioid receptors. In diabetic rats, 100-300mg/kg of a water extract over eight weeks is able to prevent diabetes-induced hyperalgesia (more sensitivity to pain) in heat and chemical testing with a potency comparable to 100mg/kg Pregabalin.
Tribulus terrestris extracts appear to be fairly effective in reducing pain perception in response to chemical and heat pain tests, with a potency comparable to some reference drugs 750mg/kg was as effective as the clinical dose of fluoxetine (1.8mg/kg). Ghana tablets (tribulus, tinospora cordifolia, and emblica officinalis) at 260mg/kg, correlating to a 2g human dose, appears to exert antidepressant and anxiolytic effects although to a degree weaker than the reference drugs diazepam (2mg/kg) and imipramine (5mg/kg).
Tribulus terrestris appears to have antidepressant effects in stressed rats, suggesting that it is an adaptogenic herb. The potency is respectable although it requires very high doses to be so) that usage of tribulus terrestris was associated with improvements in menopausal symptoms in 98% of the research group (49/50) although it had a potential conflict of interest.
The aphrodisiac/adaptogenic effects are supposed to extend to women, but this is not a well researched topic at all which is due to the tribulosin content (decreased infarct size to 20.24-30.32% of control with 1-100nM) in a manner that is abolished by blocking PKCε or ERK signalling at 10nM; as both the PKCε pathway and ERK signalling are involved in cardiomyocyte apoptosis, it is thought that tribulosin exerts a direct anti-apoptotic effect (specifically, by activating ERK which then translocates PKCε). Other saponins may have cardioprotective effects, such as hecogenin-3-O-β-d-glucopyranosyl(1 → 4)-β-d-galactopyranoside (30-100μg/mL) via activating PKCε although they are significantly weaker than tribulosin at doing so.
Due to activating protein kinase C epsilon (PKCε), tribulosin can protect cardiac cells from cell death. This occurs at a remarkably low concentration and is likely relevant to oral supplementation of tribulus terrestris saponinsIn hypertensive humans given 3g of tribulus fruits or a water extract thereof, four weeks supplementation was sufficient to slightly reduced heart rate. In rats (spontaneously hypertensive 2K1C), 10mg/kg of the lyophilized fruit extract appears to reduce blood pressure and correct the higher than normal levels of ACE. In otherwise healthy rats, 2.5-10mg/kg tribulus terrestris appears to increase blood pressure in a dose-dependent manner (6-11%) during erections, although when the rats were not sexually stimulated there were no differences.
Tribulus may reduce blood pressure via either the kidneys (a diuretic and/or protective effect) or via ACE inhibition, and while it shouldn't influence blood pressure in otherwise normal subjects it may increase the erection-induced blood pressure spikeIn humans with hypertension, tribulus terrestris given at 2g of the whole fruit extract of a water extract thereof over four weeks noted significant reductions in systolic blood pressure (4-4.3%) by one week which increased to 9.6-10.7% after four weeks; diastolic blood pressure was reduced by 7.4-8.1% after four weeks. This study should be approached with caution as the intervention group had significantly higher blood pressure at baseline which may have exacerbated the results. As the reduction in blood pressure was associated with an increase in urinary output, it is though that the observed benefits were secondary to the kidneys.
Appears to reduce blood pressure in hypertensive humans, and while the lone study is incredibly promising more research should be put forward to ascertain the potency As the main bioactive for this effect was not delineated, it is unsure if this applies to tribulus terrestris. Tribulus terrestris has been found to inhibit adrenaline-induced platelet aggregation with an IC50 value of 970µg/mL.
Tribulus terrestris has weak and probably not relevant anti-platelet effects, although the species of pterocarpus appears to be quite potent. They were measured on different aggregators, however, and it is not sure if tribulus terrestris has a role in blood clotting or not
Possible reductions in total cholesterol that need to be investigated furtherTurmeric isopropanol extraction (160ng/mL) and acetone extract (7.4µg/mL). Concentrations of 0.1-10mg/mL of the isolated saponins have been noted to inhibit this enzyme activity by 20.83-52.62% in vitro and there appears to be some inhibitory potential against α-glucosidase as well. In rats, 100mg/kg of the saponins from tribulus terrestris is able to approximately half the increase in blood glucose from an oral sucrose tolerance test; it failed to influence glucose absorption.
May inhibit the enzymatic activity of pancreatic amylase and some other enzymes, and while it doesn't seem to be the most potent herb in doing so this may be biologically relevant This may have been secondary to prevention of damage to the liver, as assessed by histological examination. In diabetic rats, 50mg/kg of a hydroalcoholic extract (45.84% saponins) for eight weeks is able to improve insulin levels in serum with a potency comparable to 6mg/kg Olmesartan and slightly less effective than 1mg/kg Glimepiride.
Appears to confer anti-diabetic effects, particularly insulin is increased (normally suppressed in these models of diabetes). Mechanisms are not yet known This inhibitory potential was lesser than other tested plants of tinospora cordifolia (IC50 176µg/mL), holy basil (IC50 280µg/mL), and morinda cetrifolia (IC50 132µg/mL) as well as the standard reference Quercetin (IC50 82µg/mL) on aldose reductase.
Tribulus terrestris appears to have aldose reductase inhibiting potential, which doesn't seem to be too potent when compared to other herbsIn diabetic rats, supplementation of 50mg/kg of an hydroalcoholic extract is able to improve kidney function as assessed by glomerular filtration rate.
May improve kidney function in diabetic rats (diabetic nephropathy)
Does not appear to modify glucose uptake into skeletal muscle, although this is not a well researched topic and supplementation of a standardized extract at 450mg (60% saponins) similarly failed in elite rugby players over five weeks.
The limited human evidence has been conducted in well trained human subjects, and supplementation at the recommended doses for power output (and above the recommended dosages for libido enhancement) has twice failed to improve power output
Possibly relevant anti-inflammatory effects that need to be investigated further There was also a significant increase in neurons expressing NADPH-d by 67%, suggesting that Tribulus can increase Nitric Oxide Synthase (NOS) and subsequent NO production as NADPH-d immunostaining can be a biomarker for NOS activity.
Expression of the androgen receptor may be increased in the brain, possibly related to the libido enhancing effectsWhen testing for androgenic effects of Tribulus independent of serum testosterone levels, a rat study measuring prostate weight of rats subject to 11, 42, and 110mg/kg Tribulus extract (11.42% Protodioscin) with the lowest dose correlating to 750mg Tribulus extract in a 70kg human noted that, over 28 days of feeding, that aside from serum testoterone being unaffected prostatic weight was unaffected at all doses suggesting no intrinsic androgenic activity.
There does not appear to be a direct androgenic effect of tribulus supplementation (independent of increasing testosterone)When tested in vitro, an extract of tribulus terrestris did not appear to significantly inhibit the 5α-reductase enzyme.
May not interact with the 5α-reductase enzymeWhen looking at interventions, currently those that show an increase in circulating testosterone including a non-human primate injection of isolated protodioscin (7.5mg/kg) resulting in a 52% increase acutely which returned to baseline 90-180min after injection. This same study noted that 8 weeks administration of 5-10mg/kg in rabbits and rats led to increases in dihydrotestosterone (DHT) in rabbits (testosterone increases statistically insignificant) and in the castrated rats testosterone increased by 25% and another study exclusively using sexually sluggish rats (those that were previously shown to copulate less with receptive females) noted an increase in testosterone from 2.4+/-0.03ng/mL to 3.12+/-0.06 and 3.72+/-0.06ng/m (30% and 55% increase) with 50mg/kg and 100mg/kg fruit extract, respectively. One other study using otherwise healthy rats has noted, offhand, an increase in testosterone with both the control drug (Viagra at 0.71mg/kg) and Tribulus fruits at 100mg/kg but does not disclose total increases. In humans, tribulus terrestris of Bulgarian origin has been shown to have no influence on total testosterone or luteinizing hormone levels when supplemented to healthy men in 200mg a day with a 60% saponin content. It does not seem to influence testosterone levels in females at 450mg (low powered case studies) and when 450mg Tribulus is adminsitered to weight trained men and rugby players for up to 5 weeks fails to note significant increases in testosterone. It should be noted that based on body surface area conversions an oral dose of 450mg Tribulus equates to 30.94mg/kg in rat studies if we assume a 200lb human. Previous studies with dehydrate fruit extracts of Tribulus note increases in testosterone with 50-100mg/kg bodyweight in rats, which correlates to a 200lb human ingesting 727mg-1.45g Tribulus fruits. Some human studies have shown increased testosterone associated with Tribulus supplementation, however they are confounded with coingestion of other nutrients and one which used 6g of the root extract of tribulus terrestris by itself for 60 days in infertile men noted a trend to increase testosterone (failed to be statistically significant) reaching 16.3%. This is similar to the first study using a formulation known as Tribestan where an increase in testosterone was noted in impotent male rams and suggests that the only role tribulus terrestris may have in increasing testosterone is normalizing testicular damage in impotent subjects.
When looking at animal and human evidence, there is sporadic evidence to suggest an increase in testosterone with this herb in rodents but it has repeatedly failed to increase testosterone in humans. There may be a weak increase in testosterone in infertile men, but this needs to be explored more
Currently no evidence to support alterations in estrogen metabolism with supplementation of tribulus terrestris This protective effect extends to other minerals such as mercury (6mg/kg of the methanolic fruit extract in mice). In an in vitro tacrine induced toxicity model, the fruits of tribulus terrestris with Tribulusimide D (10-20µM; EC50 13.46+/-0.2µM) and Quercetin-3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (20-40µM; EC50 of 7.06+/-0.7 µM) having a potency comparable to Silybin at 100µM; Terrestiamide confirmed inactive and since Tribulusimides A and B have been shown to be hepatoprotective elsewhere it is though this lignanamide class is responsible for hepatoprotection.
Tribulus terrestris appears to have protective effects in the liver, which are more potent than vitamin E when looking at antioxidative changes against mineral toxicity and slightly weaker or comparable when looking at cellular damage and liver enzymesAnti-inflammatory effects have been noted with the aqueous extract of Tribulus in vitro, where suppression of HepG2 tumor cell growth was noted (and no effect on normal cell growth) and thought to be secondary to increasing IκBα content and reducing NF-kB content, the former of which appears to be through inhibiting the IκBα kinase enzyme (although it did not influence binding of the IKK-β subunit, usually implicated with NF-kB).Vitamin E. This protective effect extends to mice, where mercury toxicity with 6mg/kg of a methanolic extract of tribulus terrestris fruits
In studies on rodents given experimental heavy metal toxicity, tribulus appears to be quite protective with a potency exceeding Vitamin E on a weight basis. This occurs at a concentration low enough that it likely applies to supplementation in humansA case study of tribulus terrestris overconsumption (2L of a tribulus water product for the treatment of kidney stones) has resulted in nephrotoxicity which was treated in a clinical setting. Although it has been claimed that the particular product in question could have been contaminated with bacteria (the symptoms were similar) a subsequent study in diabetic rats given a hydroalcoholic extract of tribulus terrestris at 50mg/kg (45.84% saponins) reported histological damage to distal tubules and collecting ducts while glomerular function and the renal cortex seemed unaffected. This study also reported improvemetns in diabetic symptoms and an increase in glomerular filtration rate, so it is unsure if this 'toxicity' is relevant to kidney function.
While possible kidney toxicity cannot yet be ruled out, it seems to not be too much of a concern since the case study failed to place causation on the herb and the lone rat intervention also noted improvements in kidney function alongside the 'altered' histologyA 60kDa protein found in tribulus terrestris appears to be able to dissolve calcium oxalate kidney stones in vitro with a potency comparable to cystone. A basic water extract of tribulus terrestris fruits themselves also show this property, with 25-100µg/mL causing 71% inhibition of calcium oxalate nucleation in vitro while showing dose-dependence in preventing stone growth between 25µg/mL (18%) and 1,000µg/mL (170%) with 50-200µg/mL causing 65-70% inhibition. A part of the benefit from tribulus terrestris is thought to be due to flavonoids that inhibit oxalate synthesis, such as quercetin (Noncompetitive inhibition of glycolate oxidase with an IC50 of 0.5µM) and kaempferol (Competitive with an IC50 of 0.3µM). Beyond reducing stone growth, the cell damage induced by calcium oxalate is significantly reduced by 10-50µg/mL of the fruit water extract and the protein itself. When tribulus terrestris itself is used in rats, it shows dose-dependent protective effects with most potency in the ethanolic extract and when Unex is used (a combination formula of tribulus terrestris and boerhaavia diffusa) in a rat model of ethylene glycol induced kidney stones, 200mg/kg oral ingestion is able to reduce kidney stone formation with a potency comparable to 750mg/kg cystone (400mg/kg Unex appeared to be slightly less potent).
Tribulus terrestris appears to be able to reduce kidney stone formation in vitro (specifically calcium oxalate stones) which may be due to multiple components. It has shown efficacy in rodents, and when paired with another herb known as Boerhaavia diffusa it appears to be quite potentIn a human study giving 3g of the fruit extract of tribulus terrestris or a water extract thereof, both interventions were effective in increasing urinary output by 200mL daily when supplemented for a month.
The water soluble components in tribulus appear to have diuretic properties in humansVitamin E.
Appears to have general antioxidative and mineral chelating effects in the testicles are respectable oral dosages11mg/kg tribulus terrestris in boars (750mg human equivalent at 70kg bodyweight) appears to increase seminal volume, although 42-110mg/kg was not associated with an increase. In rats, 50-100mg/kg of the fruits appears to increase sperm count by 25.8-32.2% over 28 days of supplementation. Testicular weight may be increased with triblus supplementation without any abnormal changes in histological examination. In humans with oligozoospermia (low sperm count), supplementation of tribulus terrestris at 6g of the root extract daily for two months is able to improve sperm count and motility although the degree of increase was not significantly greater than placebo.Stinging Nettle with some efficacy seen with Saw Palmetto. Tribulus has been investigated for its benefits on BPH, although this study used a combination supplement of Tribulus Terrestris and Murraya koenigii. Although only 12 weeks in length, the combination supplement was able to reduce IPSS symptoms from a score of 17 down to 9, which was not significantly different than the efficacy of 400mcg tamsulosin reducing IPSS symptoms from 14 to 8; the herbal combination reduced prostatic volume from 33.5mL to 31.6mL (5.6% reduction) and was statistically significant while the 3.4% reduction seen with tamsulosin did not reach significance. This study was criticized for its usage of generic tamsulosin (and thus no control for active amounts of tamsulosin) paired with a lack of placebo group. Another possible confound to the above research is that IPPS symptoms include urinary flow, as Benign Prostatic Hyperplasia may sometimes reduce flow rate. Tribulus itself appears to possess diuretic properties, although this study used a large dose of Tribulus where 5g/kg in Guinea pigs was as effective as furosemide.
Possibly beneficial for benign prostatic hyperplasia, but evidence is limited and no mechanisms are knownEurycoma Longifolia Jack and Leuzea carthamoides noted that 11mg/kg oral administration (correlating to a 750mg oral dose for a 70kg human) increased mounting behaviour by 20% and increase seminal volume; higher doses (42mg/kg and 110mg/kg) were unaffective. Various other animal models confirm aphrodisiac effects, including the lyophilized extract dried fruits at 50mg/kg and 100mg/kg in sexually sluggish male rats which noted dose-dependent increases in all parameters of sexuality and penile function increasing with prolonged administration. Intake of tribulus at lower doses of 2.5, 5, and 10mg/kg for a period of 8 weeks was associated with decreases in the latency of mounting, intromission, and ejaculation while improving mounting and intromission frequency; with 5mg/kg and 10mg/kg being of equal potency and in castrated rats Tribulus appears to be slightly less effective at 5mg/kg than were biweekly injections of testosterone cypionate at inducing aphrodisia, but both groups were lesser than an uncastrated control while another study comparing Tribulus Terrestris against Sildenafil Citrate (Viagra) in sexually normal rats at doses of 100mg/kg bodyweight and 0.71mg/kg, respectively, found that there were no significant differences between both groups, as both were more effective than control at inducing aphrodisia with similar efficacy. In men with low sperm count, supplementation of 6g tribulus root is associated with a significantly greater improvement in sexual health (assessed by survey) by 49.38% which was greater than placebo (27.80%).nitric oxide metabolism (not inhibited by L-NAME or methylene blue), prostaglandin metabolism (indomethacin ineffective), and independent of potassium channels (4-AP and glibenclamide ineffectve). Changes in cAMP and cGMP could also not explain the observed effects. Elsewhere, a mixture of tribulus terrestris and cornus officinalis (the latter working via nitric oxide metabolism) has noted that tribulus alone was more effective than all mixtures of the two herbs and that the mixture was no more proerectile following oral ingestion than tribulus alone. An increase in erectile properties have been noted in rabbits given 2.5-100mg/kg of a tribulus fruit extract for one month and this dosage range has been noted to enhance the efficacy of pro-erectile signalling molecules (acetylcholine or electrical stimulation) without affecting anti-erectile signalling molecules. Protodioscin by itself in ineffective and this same dosage range in rats appears to enhance the intracavernous pressure (ICP) of the penis by 17-43% (most efficacy at 5mg/kg) during erections.
Tribulus terrestris appears to relax penile tissue in vitro and enhances erections after oral ingestion, but the difference in dosages (quite high in vitro yet low oral doses) suggest differing mechanisms of action. The mechanism by which tribulus increases erections is not known, but may be related to central androgen receptorsIn persons with low sperm count given 6g of tribulus root daily for two months (where almost half of participants reported erectile problems) there was significant improvements in the loss of erection (6.03%), rigidity (9.41%), premature ejaculation (6.12%), and lack of orgasm (9.76%).
Increases in erectile properties and sexual satisfaction in men has been improved with the standard oses of tribulus supplementation A later in vitro study demonstrated that a result of Melanocyte-Stimulating Hormone, the actual proliferation of melanocytes, appears to be concentration dependent with 0.5mg/mL actually inhibiting proliferation and 1.5mg/mL inducing proliferation. These effects on melanocyte differentiation were also correlated with tyrosinase activity, suggesting that high doses of Tribulus may have the ability to induce hair pigmentation.
May have the ability to induce coloration of hair follicles at high concentrations, but results are too preliminary to implicate any practical guides and augmenting the UVB-induced increase in nucleotide excision repair genes (XPA and XPC, two major DNA repair genes) which were not increased in control cells nor in cancerous skin cells (squamous cell carcinoma).
Appears to increase DNA repair in skin cells that are exposed to radiation, and this does not occur in cancerous cells and another LD50 study found that the LD50 of a basic lyophilized extract of Tribulus (aerial parts and root) as assessed by intraperitoneal injections was 813mg/kg and the 95% condfidence interval calculated to be 739-894mg/kg, suggesting that a lethal dose of Tribulus injections in humans would be (based on body surface area conversions) 118-143mg/kg. Due to unknown bioavailability, it cannot be estalished what a toxic oral dose would be.
Doses typically used for supplementation do not appear to be lethal or harmful This study involved a 21-year old man with a history of breast swelling whom used cigarettes (2 daily) and drank alcohol (10 units weekly) who reported development of a benign nodule in the left breast that coincided with consumption of a Tribulus product (unnamed). Causation could not be placed on the product.
Standard assortment of case studies, with little evidence to outright blame Tribulus for the effects caused (which is thought to be confounded with the possibility of microbial contamination as the symptoms were similar) and a subsequent study in diabetic rats given a hydroalcoholic extract of tribulus terrestris at 50mg/kg (45.84% saponins) reported histological damage to distal tubules and collecting ducts while glomerular function and the renal cortex seemed unaffected. Additionally serum creatinine, cystatin c, and beta 2 microglobulin were reduced in these rats and protein/albumin normalized which suggested an increase in glomerular filtration rate (improvement in kidney function). There are well established instances of tribulus terrestris induced neurotoxicity and renal toxicity in ruminant animals (known as Geeldikkop and Staggers) although this does not appear to extend to humans.
There is limited evidence to support an increase in kidney toxicity with tribulus terrestris. While the case study did pretty much note causation to the product it is possible that it was contaminated, and the rat study noting renal toxicity had quite mixed results and it is difficult to reach a conclusion at this point in time
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