Chanca Piedra

In Amazonian and South American medicine, chanca piedra is a primary remedy for the urinary tract and the liver. In Brazil it is a folk remedy for urinary stones ^{1,2Reference 1Nishiura et al. · 2004RCTPhyllanthus niruri normalizes elevated urinary calcium levels in calcium stone forming patients — randomized controlled trialView study →Reference 2Micali et al. · 2006RCTCan Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study — RCTView study →}, and in South America it is also taken for excess uric acid ^{19Reference 19Murugaiyah et al. · 2009In vitroMechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents — animal model and in vitroView study →}.

Traditional indications include kidney stones, gallstones, bladder irritation, painful urination, liver congestion, digestive upset, fluid retention and inflammatory pain.

It is also taken during viral illness, and is regarded as cleansing and cooling.

In the Caribbean the root has been used as a diuretic, to clear bladder stones and for jaundice. An infusion of the fresh root was taken for chronic dysentery ^{37Reference 37FernFern, K. (n.d.). Phyllanthus niruri — habit, range, habitat and uses — plant database. Useful Tropical Plants Database. https://tropical.theferns.info/viewtropical.php?id=Phyllanthus+niruriView study →}.

In Ayurvedic medicine, closely related Phyllanthus species are used for liver disorders, jaundice, urinary irritation, digestive inflammation and excess heat.

They are regarded as cooling and detoxifying, particularly for the liver and the urinary system.

Modern Western herbalism uses chanca piedra mainly for preventing kidney stones, for the urinary tract and the liver, and for gentle metabolic support.

It is included in formulas for urinary irritation, gallbladder congestion, raised cholesterol and chronic inflammation.

A randomised, placebo-controlled trial gave 69 calcium-stone formers 450 mg capsules three times daily for three months. Overall there was no change in urinary chemistry, stone passage or pain, but urinary calcium fell in the patients whose calcium had been high ^{1Reference 1Nishiura et al. · 2004RCTPhyllanthus niruri normalizes elevated urinary calcium levels in calcium stone forming patients — randomized controlled trialView study →}.

In 150 patients after shock-wave lithotripsy, 78 took a 2 g daily extract for at least three months and 72 served as controls. The overall stone-free rate did not differ significantly (93.5% vs 83.3%), but for lower-pole stones it was 93.7% vs 70.8% (p=0.01) ^{2Reference 2Micali et al. · 2006RCTCan Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study — RCTView study →}.

In 56 patients with stones under 10 mm, 12 weeks of chanca piedra tea reduced the number of stones from 3.2 to 2.0 per patient. Urinary oxalate fell in those with high oxalate, urinary uric acid fell in those with high uric acid, and magnesium and potassium excretion rose. The study had no control group ^{3Reference 3Pucci et al. · 2018ObservationalEffect of Phyllanthus niruri on metabolic parameters of patients with kidney stone — prospective cohortView study →}.

An uncontrolled study gave 48 patients a standardised extract with magnesium and vitamin B6 for three months. Afterwards 40% of the stones were gone, with the best results for stones of 3 mm or less ^{4Reference 4Cealan et al. · 2019Clinical trialEfficacy of Phyllanthus niruri standardized extract combined with magnesium and vitamin B6 for uncomplicated nephrolithiasis — uncontrolled clinical studyView study →}.

A 2020 meta-analysis of two controlled studies found modest reductions in stone size and number ^{5Reference 5Dhawan et al. · 2020Meta-analysisPhyllanthus niruri herbal therapy for kidney stones — systematic review and meta-analysisView study →}. A meta-analysis of four trials of expulsive therapy after lithotripsy, one of them using a chanca piedra extract, found better stone clearance overall ^{6Reference 6Schuler et al. · 2009Meta-analysisMedical expulsive therapy as an adjunct to improve shockwave lithotripsy outcomes — systematic review and meta-analysisView study →}.

Across these studies the benefit appeared mainly in people with abnormal urinary chemistry, not in stone formers generally.

In the laboratory, a water extract blocked the uptake of calcium-oxalate crystals by kidney cells ^{7Reference 7Campos et al. · 1999In vitroPhyllanthus niruri inhibits calcium oxalate endocytosis by renal tubular cells — in vitroView study →}. In rats with a calcium-oxalate seed placed in the bladder, it inhibited stone growth and reduced the number of satellite stones ^{8Reference 8Freitas et al. · 2002AnimalThe effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization — rat model / in vivoView study →}.

In human urine the extract did not stop crystals from forming, but the crystals were smaller and clumped together less ^{9Reference 9Barros et al. · 2003In vitroEffects of an aqueous extract from Phyllanthus niruri on calcium oxalate crystallization — in vitroView study →}. Given early in the rat model, an extract cut stone number by 75% and stone weight by 65%. Given after a stone had formed, it did not stop the stone growing, but left it smoother ^{10Reference 10Barros et al. · 2006AnimalEffect of extract of Phyllanthus niruri on crystal deposition in experimental urolithiasis — rat model / in vivoView study →}. Ellagic acid from the plant protected kidney cells and mice against oxalate injury ^{11Reference 11Li et al. · 2022In vitroPhyllanthus niruri exerts protective effects against calcium oxalate-induced renal injury via ellagic acid — in vitro and animal modelView study →}.

Gap: no adequately powered trial has shown fewer new stones or fewer recurrences as its main outcome, and no trial has shown an existing stone dissolving. It is not a substitute for medical care of a stone that is causing symptoms.

Liver protection is well studied in animals and cells. In a bioassay-guided study, a water extract of the aerial parts protected liver cells and rats against carbon tetrachloride. It normalised ALT and AST, restored glutathione and superoxide dismutase, and lowered TNF-α, NF-κB, IL-6 and COX-2 ^{12Reference 12Ezzat et al. · 2020In vitroIn-depth hepatoprotective mechanistic study of Phyllanthus niruri — in vitro and in vivoView study →}.

The most active compounds in that study were corilagin, isocorilagin, a kaempferol rhamnoside and brevifolin carboxylic acid, with quercetin and gallic acid moderately active ^{12Reference 12Ezzat et al. · 2020In vitroIn-depth hepatoprotective mechanistic study of Phyllanthus niruri — in vitro and in vivoView study →}.

A protein isolate, injected into mice, protected the liver against the same toxin ^{13Reference 13Bhattacharjee et al. · 2007AnimalProtein isolate from Phyllanthus niruri plays hepatoprotective role against carbon tetrachloride-induced liver damage — mouse / in vivoView study →}.

In rats with fatty liver from a high-fat diet, a 50% methanolic extract reduced liver enlargement, fibrosis, ALT, cholesterol, LDL and insulin resistance, with ellagic acid and phyllanthin as its main compounds ^{14Reference 14Al Zarzour et al. · 2017AnimalPhyllanthus niruri standardized extract alleviates non-alcoholic fatty liver disease progression — rat model / in vivoView study →}.

The effect is attributed to antioxidant activity ^{12Reference 12Ezzat et al. · 2020In vitroIn-depth hepatoprotective mechanistic study of Phyllanthus niruri — in vitro and in vivoView study →}.

No completed human liver trial has been published. Registered fatty-liver and alcoholic-liver-disease studies have not reported.

One human study used the traditional tea. In a randomised crossover study, five healthy men drank either chanca piedra tea (5 g in 750 mL) or water. After the tea, plasma gallic acid rose at one, two and four hours and plasma ascorbic acid at one hour, while red-cell catalase and superoxide dismutase did not change ^{15Reference 15Colpo et al. · 2014RCTAntioxidant effects of Phyllanthus niruri tea on healthy subjects — randomized crossover trialView study →}.

In diabetic rats, a water extract of the leaves prevented the rise in kidney lipid peroxidation and the fall in superoxide dismutase, catalase and glutathione peroxidase ^{16Reference 16Giribabu et al. · 2014In vitroAqueous extract of Phyllanthus niruri leaves displays in vitro antioxidant activity and prevents oxidative stress in diabetic rat kidney — in vitro and animal modelView study →}.

The human study measured blood markers over four hours, not any clinical outcome.

The chloroform fraction of a methanol extract had anti-inflammatory, pain-relieving and fever-reducing effects in rodents. It cut acetic-acid writhing by 56–67% and reduced yeast-induced fever. It raised the pain threshold of inflamed tissue but did not change the response on a hot plate, which points to a peripheral action ^{17Reference 17Obidike et al. · 2010AnimalThe anti-inflammatory and antinociceptive properties of the chloroform fraction from Phyllanthus niruri — rat / animal modelView study →}.

Corilagin restrained NLRP3 inflammasome activation in macrophages and reduced joint swelling in a mouse model of gout ^{18Reference 18Luo et al. · 2022In vitroCorilagin restrains NLRP3 inflammasome activation and pyroptosis through the ROS/TXNIP/NLRP3 pathway — in vitroView study →}.

All of this is in animals or isolated fractions, and the active fraction was not a tea.

P. niruri lowers uric acid mainly by increasing its excretion. In rats with high uric acid, a methanol extract given by injection raised urinary uric acid excretion 1.7-fold, and in vitro it inhibited xanthine oxidase (IC₅₀ ~39 µg/mL) ^{19Reference 19Murugaiyah et al. · 2009In vitroMechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents — animal model and in vitroView study →}.

The lignans phyllanthin, hypophyllanthin and phyltetralin were poor xanthine-oxidase inhibitors but strong promoters of uric acid excretion. Pyrazinamide suppressed phyllanthin’s effect, as it does that of the uricosuric drug benzbromarone ^{19Reference 19Murugaiyah et al. · 2009In vitroMechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents — animal model and in vitroView study →}.

In stone formers with high urinary uric acid, urinary uric acid fell after 12 weeks of the tea ^{3Reference 3Pucci et al. · 2018ObservationalEffect of Phyllanthus niruri on metabolic parameters of patients with kidney stone — prospective cohortView study →}.

No dedicated human gout or high-uric-acid trial exists.

An early uncontrolled study gave a whole-plant preparation of the related P. amarus to nine people with mild high blood pressure, four of whom also had diabetes. Blood glucose fell over 10 days ^{20Reference 20Srividya et al. · 1995Clinical trialDiuretic, hypotensive and hypoglycaemic effect of Phyllanthus amarus — uncontrolled clinical study (n=9)View study →}.

In alloxan-diabetic rats, a methanol extract of the aerial parts lowered blood glucose, suppressed the rise after a glucose meal, reduced haemoglobin glycation and raised liver glycogen. In vitro it inhibited α-amylase and α-glucosidase ^{21Reference 21Okoli et al. · 2011AnimalStudies on the possible mechanisms of antidiabetic activity of extract of aerial parts of Phyllanthus niruri — rat / animal modelView study →}.

Corilagin and repandusinic acid A are potent α-glucosidase inhibitors (IC₅₀ ~0.9 and 1.9 µM) ^{22Reference 22Najari Beidokhti et al. · 2017In vitroInvestigation of antidiabetic potential of Phyllanthus niruri using α-glucosidase, muscle glucose transport, liver glucose production and adipogenesis assays — in vitroView study →}.

The single human study is small, decades old and used a different species. Everything since is in vitro or in rodents, with no controlled trial in people with diabetes.

Chronic hepatitis B is the most-studied indication.

An early systematic review of 22 randomised trials, most of them of low quality, found that Phyllanthus species cleared HBsAg more often than placebo or no treatment, and improved the effect of interferon ^{24Reference 24Liu et al. · 2001Systematic reviewGenus Phyllanthus for chronic hepatitis B virus infection — systematic reviewView study →}.

A Cochrane review then included 16 randomised trials with 1,326 patients. Only one trial, with 42 participants, compared phyllanthus with placebo, and it found no difference. The other trials added phyllanthus to an antiviral drug and showed effects on HBV DNA and HBeAg, but with large differences between trials, and the HBV DNA result did not hold up under trial sequential analysis ^{25Reference 25Xia et al. · 2011Meta-analysisPhyllanthus species for chronic hepatitis B virus infection — Cochrane systematic review and meta-analysisView study →}.

A second Cochrane review, of five trials against antiviral drugs, found insufficient evidence either way ^{26Reference 26Xia et al. · 2013Meta-analysisPhyllanthus species versus antiviral drugs for chronic hepatitis B virus infection — Cochrane systematic review and meta-analysisView study →}.

A 12-month double-blind, placebo-controlled trial enrolled 50 people with chronic hepatitis B. It found no difference in viral load, and no participant cleared HBsAg. Recruitment was stopped after two years because there was no apparent benefit ^{27Reference 27Baiguera et al. · 2018RCTPhyllanthus niruri versus placebo for chronic hepatitis B virus infection — randomized controlled trialView study →}.

Gap: the placebo-controlled studies are null. The positive results come from older trials at high risk of bias and from combinations with antiviral drugs. Chronic hepatitis B has effective antiviral treatment, and this is not a substitute for it.

In rats with raised blood lipids, an oral extract lowered serum lipids and the apoproteins of VLDL and LDL. The effect was attributed to less cholesterol made in the liver, more bile acid excreted and higher lecithin:cholesterol acyltransferase activity ^{23Reference 23Khanna et al. · 2002AnimalLipid lowering activity of Phyllanthus niruri in hyperlipemic rats — animal modelView study →}. In the fatty-liver model, total cholesterol fell by 48% and LDL by 65% ^{14Reference 14Al Zarzour et al. · 2017AnimalPhyllanthus niruri standardized extract alleviates non-alcoholic fatty liver disease progression — rat model / in vivoView study →}.

No human lipid data exist. Both studies are in rodents and used extracts rather than the whole herb.

The human data come from one small study of the related P. amarus. Nine people with mild high blood pressure took a whole-plant preparation for 10 days. Their 24-hour urine volume and their urine and blood sodium rose, and systolic blood pressure fell in the non-diabetic and female participants ^{20Reference 20Srividya et al. · 1995Clinical trialDiuretic, hypotensive and hypoglycaemic effect of Phyllanthus amarus — uncontrolled clinical study (n=9)View study →}.

The study had no control group and no dose-ranging, and it has not been repeated.

A crude methanol extract was active against all the Gram-positive and Gram-negative bacteria tested, which cause common skin, urinary and gut infections ^{28Reference 28Ibrahim et al. · 2013In vitroAntimicrobial activity of crude methanolic extract from Phyllanthus niruri — in vitroView study →}. An alcohol extract of the leaves inhibited five bacteria that cause tooth decay, though less than Solanum nigrum ^{29Reference 29Sunitha et al. · 2017In vitroAntimicrobial effect of leaves of Phyllanthus niruri and Solanum nigrum on caries-causing bacteria — in vitro studyView study →}.

These are test-tube screening results, with no infection model in animals and no clinical data.

These studies used isolated corilagin. It inhibited the growth of ovarian cancer cells, with much lower toxicity to normal ovarian cells, and slowed tumour growth in mice by blocking TGF-β/Smad and ERK/AKT signalling ^{30Reference 30Jia et al. · 2013In vitroCorilagin inhibits ovarian cancer cell growth through blocking TGF-β signaling pathways — in vitro and mouse xenograftView study →}. It also suppressed oesophageal squamous-cell carcinoma by causing DNA damage and lowering the E3 ligase RNF8, and it strengthened the effect of cisplatin ^{31Reference 31Qiu et al. · 2019In vitroCorilagin inhibits esophageal squamous cell carcinoma by inducing DNA damage and down-regulation of RNF8 — in vitro and mouse xenograftView study →}.

Gap: this is purified corilagin at micromolar concentrations. There is no whole-herb or human anticancer data.

Tolerability. No serious adverse events were reported in the kidney-stone or hepatitis B trials ^{2,25,27Reference 2Micali et al. · 2006RCTCan Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study — RCTView study →Reference 25Xia et al. · 2011Meta-analysisPhyllanthus species for chronic hepatitis B virus infection — Cochrane systematic review and meta-analysisView study →Reference 27Baiguera et al. · 2018RCTPhyllanthus niruri versus placebo for chronic hepatitis B virus infection — randomized controlled trialView study →}. Occasional mild stomach upset is the main complaint.

Animal toxicity. In rats, an ethanol extract of the whole plant given for 90 days at 30 or 300 mg/kg caused no liver or kidney toxicity, and it was not genotoxic or cytotoxic ^{32Reference 32Asare et al. · 2012AnimalGenotoxicity, cytotoxicity and toxicological evaluation of whole plant extracts of Phyllanthus niruri — rat / animal modelView study →}. A supercritical-fluid extract showed low toxicity to zebrafish embryos (LD₅₀ ~506 µg/mL) ^{33Reference 33Hassim et al. · 2021Scale-up approach for supercritical fluid extraction of Phyllanthus niruri for safe enriched herbal extracts — zebrafish toxicity evaluationView study →}.

Blood pressure, blood sugar and diuretics. In the one human study, of the related P. amarus in nine people, urine output and sodium excretion rose and blood pressure and blood glucose fell ^{20Reference 20Srividya et al. · 1995Clinical trialDiuretic, hypotensive and hypoglycaemic effect of Phyllanthus amarus — uncontrolled clinical study (n=9)View study →}. Take care alongside antihypertensive, antidiabetic or diuretic medicines, where the effects could add up.

Gout medicines and lithium. The herb increases uric acid excretion in animals ^{19Reference 19Murugaiyah et al. · 2009In vitroMechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents — animal model and in vitroView study →} and changed urinary calcium, oxalate, magnesium and potassium in stone formers ^{1,3Reference 1Nishiura et al. · 2004RCTPhyllanthus niruri normalizes elevated urinary calcium levels in calcium stone forming patients — randomized controlled trialView study →Reference 3Pucci et al. · 2018ObservationalEffect of Phyllanthus niruri on metabolic parameters of patients with kidney stone — prospective cohortView study →}. People taking gout medicines, or lithium, which is cleared by the kidneys, should be monitored.

Drug interactions. No cytochrome P450 or other pharmacokinetic study has been done. The cautions above follow from the herb’s measured effects.