Published research on the plants we sell

A sclerotium-forming mushroom native to Southeast Asia, with a long history of use in Malaysian and indigenous folk practice.

3 published studies, 1 in people — 1 systematic review; 1 human study (uncontrolled); 1 animal study.

• Asthma across animal and human studies

  Systematic reviewPaneerselvam et al., BMC Pulmonary Medicine 2026 Limitation: The review's own stated conclusion is that the evidence base is largely preclinical — the great majority of included…

  What it looked atThe authors set out to systematically review the published research on Lignosus rhinocerus in relation to asthma, covering animal, in vitro and human studies, together with the mushroom's reported bioactive constituents.

  What the authors reportedThe review reported that animal studies described suppression of eosinophil infiltration, Th2 cytokines (IL-4, IL-5 and IL-13) and IgE levels, alongside attenuated airway remodelling; that in vitro work described bronchorelaxation effects mediated through calcium channel modulation; and that a single human study reported decreases in IL-1β, IL-8 and malondialdehyde together with changes in lung function and quality-of-life measures. The review concluded that the current evidence is largely preclinical and limited in scope, and that further high-quality, larger-scale trials are needed to validate efficacy and safety in humans.

  LimitationsThe review's own stated conclusion is that the evidence base is largely preclinical — the great majority of included data comes from animal and in vitro work, with only one human study, and that human study was uncontrolled. Extract types, preparations, doses and routes of administration (including intranasal dosing in animal models) varied widely across the included studies and frequently bear little resemblance to an orally taken food supplement. No meta-analysis was performed, so no pooled effect size is quantified, and heterogeneity between studies was not statistically assessed.

  Effectiveness of tiger milk mushroom (Lignosus rhinocerus) on asthma: a systematic review — Paneerselvam et al., BMC Pulmonary Medicine 2026. PMID 41877083. Read the full paper on PubMed → (opens in a new tab)

• Respiratory, immune and antioxidant markers

  Human study (uncontrolled)n=50Tan et al., Scientific Reports 2021 Limitation: This was an open-label, single-arm study with no placebo or control group, no randomisation and no blinding, so the…

  What it looked atThe researchers set out to examine whether three months of tiger milk mushroom supplementation was associated with changes in a panel of inflammatory, immune and oxidative-stress markers (IL-1β, IL-8, IgA, total antioxidant capacity, malondialdehyde, 3-nitrotyrosine and 8-hydroxydeoxyguanosine), in pulmonary function measures, and in self-reported respiratory symptoms.

  What the authors reportedThe authors reported statistically significant (p<0.05) reductions in IL-1β, IL-8 and malondialdehyde, and in reported respiratory symptom scores, over the three-month period, together with statistically significant increases in immunoglobulin A, total antioxidant capacity and pulmonary function measures. They also reported that gender and BMI appeared to influence the antioxidant-status outcomes.

  LimitationsThis was an open-label, single-arm study with no placebo or control group, no randomisation and no blinding, so the reported before-and-after changes cannot be attributed to the supplement rather than to participant expectation, seasonal variation in respiratory symptoms, or regression to the mean. The sample was small (n=50) and drawn from a single country. One of the three authors was affiliated with the research and development department of a commercial company (Nexus Wise Sdn Bhd), representing a potential commercial interest. Follow-up was limited to three months.

  Effect of tiger milk mushroom (Lignosus rhinocerus) supplementation on respiratory health, immunity and antioxidant status: an open-label prospective study — Tan et al., Scientific Reports 2021. PMID 34083710. Read the full paper on PubMed → (opens in a new tab)

• Subchronic oral toxicity in rats

  Animal studyn=96 rats (12 male + 12 female per group across four groups); compositional analysis not applicableLi et al., International Journal of Environmental Research and Public Health 2021 Limitation: This is an animal toxicology and compositional study, not a study of any effect in people; animal NOAEL values do…

  What it looked atThe researchers set out to characterise the nutritional composition of Lignosus rhinocerotis mycelium produced by submerged liquid fermentation, and to assess its safety profile in a 13-week repeated-dose oral toxicity study in rats.

  What the authors reportedThe authors reported the mycelium powder's composition as approximately 9.0% moisture, 1.9% ash, 1.6% crude lipid, 8.4% crude protein and 79.3% carbohydrate, with an energy value of 364 kcal/100 g, total free amino acids ranging from 349 to 5636 mg/100 g and an umami index of 0.37. In the 13-week toxicology arm they reported that all animals survived, with no abnormal changes in clinical signs, body weight or ophthalmological examination, no test-article-related differences in urinalysis, haematology or serum biochemistry, and no treatment-related changes on necropsy or histopathology. They identified a no-observed-adverse-effect level greater than 3400 mg/kg body weight per day.

  LimitationsThis is an animal toxicology and compositional study, not a study of any effect in people; animal NOAEL values do not translate directly into human intake guidance. It examined mycelium grown by submerged liquid fermentation, which is compositionally distinct from the wild or cultivated sclerotium from which most tiger milk mushroom supplements are made, so the composition figures should not be read as describing any particular retail product. All five authors were affiliated with a commercial biotechnology company (Grape King Bio Ltd.), and the 13-week duration does not address longer-term or lifetime intake.

  Nutritional and 13-Week Subchronic Toxicological Evaluation of Lignosus rhinocerotis Mycelium in Sprague-Dawley Rats — Li et al., International Journal of Environmental Research and Public Health 2021. PMID 33572641. Read the full paper on PubMed → (opens in a new tab)

The research above concerns the plant, not this product, and does not describe what this product does. ProBotanics products are food supplements, not medicines.

Bark of the African cherry tree, used for generations in traditional African herbal practice.

4 published studies, 4 in people — 2 systematic reviews; 1 meta-analysis; 1 randomised controlled trial.

• Benign prostatic hyperplasia in men

  Systematic review18 randomised controlled trials, n=1,562 menWilt et al., The Cochrane Database of Systematic Reviews 2002 Limitation: The reviewers themselves flagged substantial weaknesses: only 1 of the 18 trials reported a method of treatment…

  What it looked atThe reviewers set out to assess, by systematic review of randomised trials, whether extracts of Pygeum africanum differed from placebo in men with benign prostatic hyperplasia, whether they were comparable to standard pharmacological treatments for that condition, and how reported side effects compared. Trials were sought in MEDLINE (1966–2000), EMBASE, the Cochrane Library and Phytodok, with bibliography checking and contact with manufacturers and researchers.

  What the authors reportedThe reviewers reported that 18 randomised trials involving 1,562 men met their inclusion criteria. Across the 6 trials that could be pooled, they reported an effect size of -0.8 SD (95% CI -1.4 to -0.3) for the combined outcome of urologic symptom scores and flow measures compared with placebo, and a risk ratio of 2.1 (95% CI 1.4 to 3.1) for participants reporting an improvement in overall symptoms. They also reported nocturia reduced by 19%, residual urine volume by 24%, and peak urine flow increased by 23%. On tolerability, the reviewers reported that adverse effects were mild and comparable to placebo, with an overall dropout rate of 12% (13% Pygeum, 11% placebo).

  LimitationsThe reviewers themselves flagged substantial weaknesses: only 1 of the 18 trials reported a method of treatment allocation concealment; the mean study duration was just 64 days, so nothing is established beyond about four months; many trials did not report data in a form permitting meta-analysis, so the headline effect size rests on only 6 studies; doses and preparations varied widely; and standardised validated efficacy measures were rarely used. No trial compared Pygeum africanum with alpha-blockers or 5-alpha reductase inhibitors. The literature search ends in 2000 and the review has not since been updated. Critically for a food-supplement context, the trials used standardised pharmaceutical lipophilic bark extracts at defined doses, which are not interchangeable with generic powdered bark supplements. The population was men with a diagnosed medical condition, not general consumers.

  Pygeum africanum for benign prostatic hyperplasia — Wilt et al., The Cochrane Database of Systematic Reviews 2002. PMID 11869585. Read the full paper on PubMed → (opens in a new tab)

• Urinary symptoms in benign prostatic hyperplasia

  Meta-analysis18 randomised controlled trials, n=1,562 menIshani et al., The American Journal of Medicine 2000 Limitation: This analysis draws on the same 18 trials and the same 1,562 participants as the Cochrane review above, and shares…

  What it looked atThe authors set out to conduct a systematic review and quantitative meta-analysis of the therapeutic efficacy and tolerability of Pygeum africanum in men with symptomatic benign prostatic hyperplasia, searching Medline (1966–2000), Embase, Phytodok, the Cochrane Library, trial bibliographies, and contacting authors and drug companies. Randomised trials were eligible where the intervention was a P. africanum preparation alone or combined with other phytotherapeutic agents and the control group received placebo or another pharmacological therapy.

  What the authors reportedThe authors reported that 18 randomised trials involving 1,562 men met inclusion criteria. Pooling 6 placebo-controlled studies, they reported an effect size of -0.8 SD (95% CI -1.4 to -0.3) on the combined outcome of urologic symptoms and flow measures, a risk ratio of 2.1 (95% CI 1.40 to 3.1) for participants reporting improvement in overall symptoms, nocturia reduced by 19%, residual urine volume reduced by 24%, and peak urine flow increased by 23%. They reported adverse effects as mild and similar to placebo, with dropout rates of 13% (P. africanum), 11% (placebo) and 8% (other controls). Their stated conclusion was that the literature is limited by short study duration and variability in design, preparation and reported outcomes, and that further research using standardised preparations is needed to determine long-term effectiveness.

  LimitationsThis analysis draws on the same 18 trials and the same 1,562 participants as the Cochrane review above, and shares authors (Wilt, Rutks, MacDonald) with it — it is therefore not independent corroboration and the two should be counted as one body of evidence, not two. The authors noted only 1 of 18 trials reported allocation concealment and that many trials could not be pooled. Trials permitted combination products, so not every included trial isolates Pygeum africanum. Mean duration was 64 days. Contact with drug companies formed part of the search strategy and funding of the underlying trials is not characterised in the abstract. The evidence base is now more than 25 years old.

  Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis — Ishani et al., The American Journal of Medicine 2000. PMID 11099686. Read the full paper on PubMed → (opens in a new tab)

• Once versus twice daily dosing schedules

  Randomised controlled trialn=209 completed the 2-month randomised comparative phase; n=174 continued into the 10-month open-label extensionChatelain et al., Urology 1999 Limitation: This trial had no placebo arm — both randomised groups received Pygeum africanum — so it can only compare two dosing…

  What it looked atThe investigators set out to compare the efficacy and safety of two dosage schedules of the same Pygeum africanum extract — 50 mg twice daily versus 100 mg once daily — over a 2-month randomised, parallel-group, double-blind phase, followed by a 10-month open-label phase at 100 mg once daily. Assessment parameters were the International Prostate Symptom Score (IPSS), a quality-of-life measure, and maximum urinary flow rate.

  What the authors reportedThe authors reported that the two dosage schedules performed similarly over the 2-month randomised phase: IPSS (baseline 17 in both groups) changed by 38% in the twice-daily group and 35% in the once-daily group, the quality-of-life measure changed by 28% in both, and maximum urinary flow rate rose by 1.63 mL/s in one group and 2.02 mL/s in the other. After 12 months they reported IPSS falling from 16 at baseline to 9. They reported the safety profile as similar between the two groups and across both study phases, and concluded the two schedules were equally effective and safe at 2 months.

  LimitationsThis trial had no placebo arm — both randomised groups received Pygeum africanum — so it can only compare two dosing schedules and cannot show that either differs from placebo or from no treatment. The changes reported over time therefore cannot be separated from placebo response, natural fluctuation, or regression to the mean. The 10-month extension was open-label and uncontrolled, which is the weakest design for the long-term figures quoted. It tested a specific standardised pharmaceutical bark extract at 100 mg/day, not a generic powdered-bark food supplement. The abstract does not disclose funding, and one author's involvement is consistent with a commercial dosage-form study. Participants were men with a diagnosed medical condition.

  Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension — Chatelain et al., Urology 1999. PMID 10475357. Read the full paper on PubMed → (opens in a new tab)

• Dietary supplements and lower urinary tract symptoms

  Systematic review6 systematic reviews covering 195 articlesKim et al., Maturitas 2012 Limitation: The Pygeum africanum finding here is inherited from a single underlying review — the same 2000-era Wilt/Ishani…

  What it looked atThe authors set out to summarise, at overview-of-systematic-reviews level, the existing evidence on the efficacy and adverse effects of dietary supplements used in benign prostatic hyperplasia with lower urinary tract symptoms, searching five electronic databases without language or publication-status limits.

  What the authors reportedThe authors reported including 6 systematic reviews covering 195 articles. They reported that Serenoa repens was covered by 3 reviews with no specific effect observed on symptom and urinary flow measures, whereas beta-sitosterol, Pygeum africanum and Cernilton were each covered by a single review reporting significant improvement. They reported that all the compounds included had mild and infrequent adverse effects. They explicitly noted that the reviews covering beta-sitosterol, Pygeum africanum and Cernilton had not been updated since 2000 and that updates would be necessary.

  LimitationsThe Pygeum africanum finding here is inherited from a single underlying review — the same 2000-era Wilt/Ishani analysis cited above — rather than from new or independent data, so it adds no fresh evidence and must not be counted as a second positive result. The authors themselves identified the currency problem, flagging that the Pygeum evidence had not been updated since 2000; it remains un-updated today. This is an overview of secondary literature with no primary data, no new pooling, and no assessment of individual trial quality beyond what the source reviews reported. As with the source reviews, it concerns men with a diagnosed medical condition and pharmaceutical-grade standardised extracts.

  Dietary supplements for benign prostatic hyperplasia: an overview of systematic reviews — Kim et al., Maturitas 2012. PMID 22883375. Read the full paper on PubMed → (opens in a new tab)

The research above concerns the plant, not this product, and does not describe what this product does. ProBotanics products are food supplements, not medicines.

The root of a climbing vine used in East Asian herbal tradition, commonly standardised for its isoflavone content.

4 published studies, 4 in people — 3 randomised controlled trials; 1 human study (uncontrolled).

• Alcohol intake in heavy drinkers

  Randomised controlled trialn=17Lukas et al., Psychopharmacology 2013 Limitation: Very small sample (17 men only), short four-week treatment period, single centre, and a narrow population of young…

  What it looked atThe researchers set out to assess the safety and the effects of four weeks of a standardised kudzu root extract, compared with a matched placebo, on self-reported alcohol consumption and desire to use alcohol in an outpatient setting, using a randomised, double-blind, between-subjects design with a two-week baseline and two-week follow-up.

  What the authors reportedThe authors reported no effect on alcohol craving, but reported that kudzu extract reduced the number of drinks consumed each week by 34-57%, reduced the number of heavy drinking days and increased the number of consecutive days of abstinence compared with placebo — which they described as a modest reduction in young, non-treatment-seeking heavy drinkers.

  LimitationsVery small sample (17 men only), short four-week treatment period, single centre, and a narrow population of young non-treatment-seeking heavy drinkers, so the findings do not generalise to women, older adults, or the general population. Alcohol intake was self-reported via an actigraphy device rather than biochemically verified. The extract was a specific standardised research preparation (NPI-031) at 750 mg isoflavones per day, which is not equivalent to an arbitrary retail kudzu supplement.

  A standardized kudzu extract (NPI-031) reduces alcohol consumption in nontreatment-seeking male heavy drinkers — Lukas et al., Psychopharmacology 2013. PMID 23070022. Read the full paper on PubMed → (opens in a new tab)

• Alcohol intake in a laboratory drinking session

  Randomised controlled trialn=20 (10 per group)Penetar et al., Drug and Alcohol Dependence 2015 Limitation: Very small sample (20 men, 10 per arm), single acute laboratory session rather than real-world drinking over time,…

  What it looked atThe researchers set out to test whether a single 2 g dose of kudzu extract (520 mg isoflavones), given 2.5 hours before an afternoon drinking session, would alter how much alcohol participants chose to drink, compared with placebo, in a double-blind, placebo-controlled, between-subjects laboratory experiment. Water and juice were available as alternative beverages throughout.

  What the authors reportedThe authors reported that the placebo group's consumption rose from 2.7 to 3.4 beers between the baseline and post-treatment sessions, while the kudzu group's fell from 3.0 to 1.9 beers. They also reported that kudzu-treated participants drank more slowly. They described this as the first demonstration that a single dose of kudzu extract altered consumption in a binge-drinking paradigm, and framed the wider body of work as clinical evidence relevant to alcohol abuse and dependence.

  LimitationsVery small sample (20 men, 10 per arm), single acute laboratory session rather than real-world drinking over time, men only, and baseline consumption differed slightly between arms. Outcomes were measured in beers consumed in an artificial setting. The dose (2 g extract standardised to 520 mg isoflavones) is a specific research preparation. One co-author is affiliated with the company supplying the extract, which is a potential conflict of interest.

  A single dose of kudzu extract reduces alcohol consumption in a binge drinking paradigm — Penetar et al., Drug and Alcohol Dependence 2015. PMID 26048637. Read the full paper on PubMed → (opens in a new tab)

• Menopausal symptoms, lipids and hormone levels

  Randomised controlled trialn=127Woo et al., Menopause 2003 Limitation: Largely a null result for the primary cardiometabolic and hormonal outcomes, which the authors themselves state

  What it looked atThe researchers set out to compare Pueraria lobata (equivalent to 100 mg isoflavones) with hormone replacement therapy and with no treatment over three months, measuring lipid profile, sex hormone levels (oestradiol, FSH, LH), a urinary bone turnover marker, menopausal symptom questionnaires, quality of life, and a battery of neuropsychological tests covering memory, attention, motor speed and word-finding.

  What the authors reportedThe authors reported that only the hormone replacement group showed a reduction in total and LDL cholesterol that differed significantly from the control group, and that they observed no significant changes in lipid profile, FSH or LH in the Pueraria lobata group compared with controls. They reported that both the hormone replacement and Pueraria lobata groups showed higher Mini-Mental State Examination scores and attention span than the untreated group, with different patterns between the two. The authors concluded that the study was unable to demonstrate a scientific basis for the use of Pueraria lobata for improving the health of postmenopausal women in general, and said the effect on cognitive function deserved further study.

  LimitationsLargely a null result for the primary cardiometabolic and hormonal outcomes, which the authors themselves state. The comparator arm was untreated rather than placebo, so expectation effects cannot be excluded for the questionnaire and cognitive measures; multiple outcomes were tested, raising the chance of incidental findings. Short three-month duration, a single Hong Kong Chinese population with a background dietary phytoestrogen intake that may not match a UK population, and a specific 100 mg isoflavone-equivalent preparation.

  Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause — Woo et al., Menopause 2003. PMID 12851519. Read the full paper on PubMed → (opens in a new tab)

• Bone turnover markers and menopausal symptoms

  Human study (uncontrolled)n=50Bihlet et al., Frontiers in Pharmacology 2021 Limitation: This was an open-label dose-ranging study in which participants were randomised across five active dose groups with…

  What it looked atThe researchers set out to explore, over four weeks, how five different dose regimens of kudzu root extract affected biochemical markers of bone and cartilage turnover (serum and urinary CTX-I and urinary CTX-II) and Menopause Rating Scale scores, and to record safety endpoints including adverse events, haematology, safety chemistry, vital signs and electrocardiogram. The design was an open-label, parallel-group, single-centre exploratory study with participants allocated equally across the five regimens.

  What the authors reportedThe authors reported that, after four weeks, markers of bone resorption and cartilage degradation fell from baseline in the group taking two capsules three times daily (serum CTX-I -18.4%, urinary CTX-I -34.2%, urinary CTX-II -17.4%), with effects they described as consistent across groups but appearing to favour three-times-daily dosing. They reported statistically significant reductions from baseline in Menopause Rating Scale total score in four of the five groups. They reported the extract was well tolerated at all doses and frequencies with no serious adverse events, and framed their own findings as indicative and exploratory rather than confirmatory.

  LimitationsThis was an open-label dose-ranging study in which participants were randomised across five active dose groups with no placebo arm, so there is no untreated comparison. Open-label with no placebo or control arm — every comparison is against the participants' own baseline, so improvement in a subjective symptom scale cannot be separated from placebo response or regression to the mean. Small sample of 50 spread across five dose groups (about 10 each), short four-week duration, single centre, and surrogate biochemical markers rather than clinical outcomes such as fracture. The study was conducted by a contract research organisation with commercial ties in the field, and the doses were multi-capsule regimens of a specific extract.

  The Efficacy and Safety of Multiple Dose Regimens of Kudzu (Pueraria lobata) Root Extract on Bone and Cartilage Turnover and Menopausal Symptoms — Bihlet et al., Frontiers in Pharmacology 2021. PMID 34744740. Read the full paper on PubMed → (opens in a new tab)

The research above concerns the plant, not this product, and does not describe what this product does. ProBotanics products are food supplements, not medicines.

A six-botanical liquid blend. Because it is a blend, each study below is labelled with the single ingredient it actually concerns — none of them tested this product.

4 published studies, 4 in people — 1 systematic review; 2 meta-analyses; 1 human study (uncontrolled).

• Blood pressure in adults

  Meta-analysisn=254 across 16 randomised crossover trials (7-30 participants per study)Ingredient: Beetroot (dietary/inorganic nitrate)Siervo et al., The Journal of Nutrition 2013 Limitation: Every included trial was a small crossover study (7-30 participants; 254 in total) and intervention periods ranged…

  What it looked atThe researchers set out to systematically assess randomised clinical trials comparing inorganic nitrate or beetroot juice supplementation against placebo, and to pool what those trials measured for systolic and diastolic blood pressure in adults.

  What the authors reportedThe authors reported a pooled difference in systolic blood pressure of -4.4 mm Hg (95% CI: -5.9, -2.8) and a smaller pooled difference in diastolic blood pressure of -1.1 mm Hg (95% CI: -2.2, 0.1) that did not reach conventional statistical significance. Their meta-regression indicated an association between daily inorganic nitrate dose and the change in systolic blood pressure. The authors concluded that these findings need to be tested in long-term trials and in individuals at greater cardiovascular risk.

  LimitationsEvery included trial was a small crossover study (7-30 participants; 254 in total) and intervention periods ranged from as little as two hours to fifteen days, so the review says nothing about sustained or long-term use. The authors themselves flagged that the findings require testing in long-term trials. Nitrate was delivered as beetroot juice or as inorganic nitrate salts at defined doses, which is not the same delivery form or dose as beetroot in a multi-ingredient liquid supplement.

  Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis — Siervo et al., The Journal of Nutrition 2013. PMID 23596162. Read the full paper on PubMed → (opens in a new tab)

• Curcumin absorption with piperine

  Human study (uncontrolled)Not stated in the retrieved PubMed record — healthy human volunteers plus Wistar ratsIngredient: Curcuma longa (curcumin) with Piper nigrum (piperine)Shoba et al., Planta Medica 1998 Limitation: This is a small, short, single-dose pharmacokinetic study from 1998, not a trial of any health outcome — it measures…

  What it looked atThe researchers set out to measure whether giving piperine, a constituent of black pepper and a known inhibitor of hepatic and intestinal glucuronidation, alongside curcumin changed curcumin's pharmacokinetics — its serum concentration, extent of absorption and bioavailability — in rats and in healthy human volunteers.

  What the authors reportedThe authors reported that when 2 g of curcumin was given alone to humans, serum levels were either undetectable or very low, whereas concomitant administration of 20 mg piperine produced much higher serum concentrations from 0.25 to 1 hour after dosing, which they calculated as a 2000% increase in bioavailability. In rats they reported a 154% increase. The authors reported no adverse effects at the doses used.

  LimitationsThis is a small, short, single-dose pharmacokinetic study from 1998, not a trial of any health outcome — it measures only how much curcumin reaches the bloodstream, not what that concentration does. The retrieved PubMed record does not state how many human volunteers took part, and funding and independence are not stated in that record. The doses studied were single boluses of isolated compounds (2 g curcumin, 20 mg piperine) which may not correspond to the quantities present in a multi-ingredient food supplement.

  Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers — Shoba et al., Planta Medica 1998. PMID 9619120. Read the full paper on PubMed → (opens in a new tab)

• Hawthorn extract in chronic heart failure

  Systematic review14 trials included; n=855 patients across the 10 trials providing poolable dataIngredient: Crataegus (hawthorn) leaf-and-flower extractPittler et al., The Cochrane Database of Systematic Reviews 2008 Limitation: This review concerns patients with a diagnosed cardiac condition taking a standardised pharmaceutical-grade extract,…

  What it looked atThe reviewers set out to assess the benefits and harms reported in double-blind, placebo-controlled randomised trials of hawthorn leaf-and-flower extract monopreparations in patients being treated for chronic heart failure.

  What the authors reportedThe review reported that, pooling the available trials, hawthorn extract was associated with a greater maximal workload than placebo (weighted mean difference 5.35 Watt, 95% CI 0.71 to 10.00, n=380), an increase in exercise tolerance (122.76 Watt x min, 95% CI 32.74 to 212.78, n=98), a decrease in the pressure-heart rate product — an index of cardiac oxygen consumption — of -19.22 mmHg/min (95% CI -30.46 to -7.98, n=264), and greater improvement in reported symptoms such as shortness of breath and fatigue. The reviewers noted that no relevant mortality or morbidity data such as cardiac events were reported, and that reported adverse events were infrequent, mild and transient.

  LimitationsThis review concerns patients with a diagnosed cardiac condition taking a standardised pharmaceutical-grade extract, in most trials alongside prescription heart medication — a population, product form and clinical context entirely unlike a general-sale food supplement taken by a healthy adult. The literature searches ran only to June 2006, so the review is not current. No mortality or cardiac-event outcomes were available, and the pooled effects rest on modest participant numbers for several outcomes (n=98 for exercise tolerance).

  Hawthorn extract for treating chronic heart failure — Pittler et al., The Cochrane Database of Systematic Reviews 2008. PMID 18254076. Read the full paper on PubMed → (opens in a new tab)

• Thermogenesis and resting metabolic rate

  Meta-analysis13 placebo-controlled trials included in the meta-analysis (participant total not stated in the retrieved record)Ingredient: Capsicum annuum (capsaicinoids / capsinoids from red pepper)Irandoost et al., Phytotherapy Research 2021 Limitation: The pooled difference in resting metabolic rate is roughly 34 kcal per day, a very small quantity against typical…

  What it looked atThe researchers set out to resolve conflicting earlier trial results by pooling placebo-controlled clinical trials measuring what effect capsaicinoids or capsinoids from red pepper had on thermogenesis indices — resting metabolic rate and respiratory quotient — in healthy adults.

  What the authors reportedThe authors reported that, compared with placebo, capsaicinoids/capsinoids were associated with a higher resting metabolic rate (weighted mean difference 33.99 kcal/day, 95% CI: 15.95, 52.03) and a lower respiratory quotient (-0.01, 95% CI: -0.02, -0.01), together with reported differences in energy expenditure and substrate oxidation. They characterised the observed changes as moderate and stated that further high-quality studies are required to clarify the thermogenic properties of these compounds.

  LimitationsThe pooled difference in resting metabolic rate is roughly 34 kcal per day, a very small quantity against typical daily energy intake, and the authors themselves called the improvement moderate and asked for further high-quality studies. Included trials were short-term and used isolated capsaicinoid or capsinoid preparations, frequently in capsule form, at doses that will not necessarily correspond to a liquid culinary-pepper preparation. The authors noted that the earlier trial literature was conflicting, which was the reason for undertaking the review.

  The effect of Capsaicinoids or Capsinoids in red pepper on thermogenesis in healthy adults: A systematic review and meta-analysis — Irandoost et al., Phytotherapy Research 2021. PMID 33063385. Read the full paper on PubMed → (opens in a new tab)

The research above concerns the plant, not this product, and does not describe what this product does. ProBotanics products are food supplements, not medicines.

A tropical herb known traditionally as “stone breaker” — a folk name reflecting its history of use, not an effect of this product.

4 published studies, 4 in people — 1 systematic review; 1 meta-analysis; 1 randomised controlled trial; 1 human study (uncontrolled).

• Urinary stone size and number

  Meta-analysis2 controlled human studies met the inclusion criteria (pooled participant total not stated in the abstract)Dhawan et al., The Canadian Journal of Urology 2020 Limitation: Only two studies met inclusion criteria, so the pooled estimate rests on a very small and narrow evidence base; the…

  What it looked atThe authors set out to pool the available controlled human studies to examine what effect Phyllanthus niruri had on measured urinary stone size and stone number, and separately to quantify public search interest in the plant relative to conventional stone procedures using Google Trends.

  What the authors reportedThe authors reported that only two studies met their inclusion criteria, and that in the pooled analysis of those two studies mean stone size showed a standardised mean difference of -0.39 cm (95% CI -0.68 to -0.09, p = 0.01) and stone number a standardised mean difference of -0.38 (95% CI -0.68 to -0.09, p = 0.01). The review concluded that limited clinical evidence supports modest efficacy in reducing stone burden, pending further study. They also reported that public search interest in the plant in the United States rose over 2014-2018.

  LimitationsOnly two studies met inclusion criteria, so the pooled estimate rests on a very small and narrow evidence base; the authors themselves describe the clinical evidence as limited and explicitly flag that further study is needed. A fixed-effects model was used despite the tiny number of studies, the pooled participant total is not stated in the abstract, and the Google Trends component measures public interest rather than any clinical outcome. Extract type and dose were not standardised across the included studies, so the findings cannot be mapped onto any particular food supplement preparation.

  Phyllanthus niruri (stone breaker) herbal therapy for kidney stones; a systematic review and meta-analysis of clinical efficacy, and Google Trends analysis of public interest — Dhawan et al., The Canadian Journal of Urology 2020. PMID 32333735. Read the full paper on PubMed → (opens in a new tab)

• Stone clearance after shock wave lithotripsy

  Randomised controlled trialn=150 (78 in the Phyllanthus niruri group, 72 controls)Micali et al., The Journal of Urology 2006 Limitation: The overall stone-free difference was not statistically significant; only a subgroup (lower caliceal stones, n=56)…

  What it looked atThe researchers set out to examine whether taking a Phyllanthus niruri extract for at least three months after extracorporeal shock wave lithotripsy was associated with any difference in stone clearance compared with no such treatment, assessed by abdominal x-ray and ultrasound at 30, 60, 90 and 180 days.

  What the authors reportedThe authors reported that at 180 days the stone-free rate was 93.5% in the group taking the extract and 83.3% in the control group, a difference that did not reach statistical significance (p = 0.48). In the subgroup with lower caliceal stones (56 patients) they reported rates of 93.7% and 70.8% respectively (p = 0.01). They reported no significant difference in re-treatment need (39.7% versus 43.3%, p = 0.2), and stated that no side effects were recorded with either the lithotripsy or the Phyllanthus niruri therapy.

  LimitationsThe overall stone-free difference was not statistically significant; only a subgroup (lower caliceal stones, n=56) reached significance, and subgroup findings from a single trial of this size are exploratory rather than confirmatory. The study was open-label with no placebo control, and allocation was uneven (78 versus 72) in a way not fully explained. Critically, every participant had already undergone lithotripsy, a hospital procedure — the study cannot say anything about the plant taken on its own. The dose (2 g daily of a specific commercial extract) may differ from a typical food supplement, and the study dates from 2006.

  Can Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study — Micali et al., The Journal of Urology 2006. PMID 16890682. Read the full paper on PubMed → (opens in a new tab)

• Urinary metabolic measures in stone formers

  Human study (uncontrolled)n=56Pucci et al., International Braz J Urol 2018 Limitation: This was a small, single-arm before-and-after study with no control or placebo group and no randomisation, so…

  What it looked atThe researchers set out to examine prospectively what happened to a range of blood and 24-hour urinary metabolic measurements, and to ultrasound-assessed stone counts, across a 12-week period of taking a Phyllanthus niruri infusion and a subsequent 12-week wash-out period.

  What the authors reportedThe authors reported no significant changes across the periods in anthropometric measures or in several serum measurements including full blood count, creatinine, uric acid, sodium, potassium, calcium, urine volume and pH. From baseline to wash-out they reported increases in urinary potassium (50.5 ± 20.4 to 56.2 ± 21.8 mg/24h, p = 0.017), magnesium/creatinine ratio (p = 0.013) and potassium/creatinine ratio (p = 0.008), and a fall in mean stone count per patient from 3.2 ± 2 to 2.0 ± 2 (p < 0.001). Within subgroups they reported reduced urinary oxalate in those with hyperoxaluria (p = 0.0002) and reduced urinary uric acid in those with hyperuricosuria (p = 0.0057). The authors concluded that intake was safe and did not cause significant adverse effects on serum metabolic parameters.

  LimitationsThis was a small, single-arm before-and-after study with no control or placebo group and no randomisation, so observed changes cannot be separated from natural stone passage, regression to the mean, changes in fluid intake, or the effect of being observed in a clinic. Several of the reported findings come from small subgroups (hyperoxaluria, hyperuricosuria), which increases the chance of spurious results. The intervention was a home-prepared infusion rather than a standardised capsule or extract, so the dose is not quantified and does not map onto a commercial food supplement.

  Effect of phyllanthus niruri on metabolic parameters of patients with kidney stone: a perspective for disease prevention — Pucci et al., International Braz J Urol 2018. PMID 29617079. Read the full paper on PubMed → (opens in a new tab)

• Chronic hepatitis B virus infection

  Systematic review16 randomised trials, n=1326 participantsXia et al., The Cochrane Database of Systematic Reviews 2011 Limitation: This is genus-level evidence: the included trials used various Phyllanthus species and the review authors explicitly…

  What it looked atThe Cochrane review set out to evaluate the benefits and harms of Phyllanthus species in people with chronic hepatitis B virus infection, by systematically searching international and Chinese databases for randomised trials comparing Phyllanthus with placebo, no intervention, or an antiviral drug alone.

  What the authors reportedThe review concluded that there is no convincing evidence that Phyllanthus, compared with placebo, benefits patients with chronic hepatitis B virus infection. The authors reported that only one trial (42 participants) compared Phyllanthus with placebo and found no significant difference in HBeAg seroconversion. In fifteen trials comparing Phyllanthus plus an antiviral drug against the antiviral drug alone, they reported differences in serum markers but noted substantial heterogeneity, and stated that the result for serum HBV DNA was not supported by trial sequential analysis. The authors reported that heterogeneity, systematic errors and random errors question the validity of the results, and called for large, low-risk-of-bias trials.

  LimitationsThis is genus-level evidence: the included trials used various Phyllanthus species and the review authors explicitly recommend that future trials report which species is used, so the findings cannot be attributed to Phyllanthus niruri specifically. Almost all trials were conducted in one country and gave the herb alongside prescription antiviral drugs in a hospital setting, at doses and durations unrelated to a food supplement. The authors judged heterogeneity substantial and the overall conclusion is essentially null. Only two of the sixteen trials reported adverse events at all.

  Phyllanthus species for chronic hepatitis B virus infection — Xia et al., The Cochrane Database of Systematic Reviews 2011. PMID 21491412. Read the full paper on PubMed → (opens in a new tab)

The research above concerns the plant, not this product, and does not describe what this product does. ProBotanics products are food supplements, not medicines.

A tall, woolly-leaved plant with centuries of use in traditional European herbalism. The research base here is small and mostly laboratory work — we have said so plainly.

3 published studies, 1 in people — 1 randomised controlled trial; 1 laboratory study; 1 literature review.

• Phytochemistry and traditional uses of mullein

  Literature reviewGupta et al., Phytotherapy Research 2022 Limitation: This is a narrative review, not a systematic review or meta-analysis — there is no stated search protocol, no…

  What it looked atThe authors set out to compile and critically appraise the published phytochemistry and reported pharmacological activities of Verbascum thapsus, and to summarise its documented traditional uses across Europe, Asia, north Africa and Indian traditional medicine.

  What the authors reportedThe review authors reported that V. thapsus contains a range of phytoconstituents including flavonoids, iridoid, phenylethanoid and phenylpropanoid glycosides, saponins, vitamin C and minerals. They reported that the emerging literature, which they described as based on experimental studies, has described antiviral, antioxidant, analgesic, sedative, anti-inflammatory, hypnotic, antibacterial, antifungal activities. The authors characterised the plant's standing as resting on a long history of traditional use.

  LimitationsThis is a narrative review, not a systematic review or meta-analysis — there is no stated search protocol, no risk-of-bias appraisal and no quantitative synthesis. Critically, the underlying evidence it summarises is overwhelmingly in vitro and animal work; the review does not identify a body of human clinical trials on oral mullein. Activities observed in cell or animal models at laboratory concentrations cannot be extrapolated to a person taking a food supplement.

  Health-promoting and disease-mitigating potential of Verbascum thapsus L. (common mullein): A review — Gupta et al., Phytotherapy Research 2022. PMID 35088467. Read the full paper on PubMed → (opens in a new tab)

• Episiotomy wound scores in first-time mothers

  Randomised controlled trialn=93Taleb et al., BMC Complementary Medicine and Therapies 2021 Limitation: Route of administration is entirely different from a food supplement: this was a cream applied to the skin, not an…

  What it looked atThe researchers set out to test, in a double-blind randomised placebo-controlled design, whether a topical Verbascum thapsus cream applied to an episiotomy site altered wound-repair scores compared with placebo, assessed on the REEDA scale before treatment and on days 1, 3 and 10.

  What the authors reportedThe authors reported that mean REEDA scores on days 1 and 3 were better in the Verbascum group than the control group but that these differences were not statistically significant. They reported that on day 10 mean REEDA scores were significantly better in the Verbascum group than in the placebo group (p=0.01).

  LimitationsRoute of administration is entirely different from a food supplement: this was a cream applied to the skin, not an ingested preparation, so the findings say nothing about oral intake. Small single-centre trial (n=93) in one narrow population (post-episiotomy first-time mothers) in one country, so generalisability is very limited. Only one of the three assessment time-points reached statistical significance. The cream's extract concentration and standardisation are not comparable to a dried-leaf or capsule supplement, and no independent replication was identified.

  The effect of the Verbascum Thapsus on episiotomy wound healing in nulliparous women: a randomized controlled trial — Taleb et al., BMC Complementary Medicine and Therapies 2021. PMID 34103042. Read the full paper on PubMed → (opens in a new tab)

• Antiviral activity in cultured cells

  Laboratory studyEscobar et al., Natural Product Research 2012 Limitation: This is laboratory cell-culture work only — there are no people, no animals and no ingestion involved, so no…

  What it looked atThe researchers set out to measure whether a methanolic extract of Verbascum thapsus inhibited pseudorabies virus plaque formation in cultured cells, to determine the extract's cytotoxicity to those cells, and to establish at which stage of the viral replication cycle any inhibition occurred.

  What the authors reportedThe authors reported a 50% inhibitory concentration for plaque formation of 35 µg/mL, and cytotoxic concentration (CC50) values of 1100 µg/mL by neutral red uptake and 1426 µg/mL by MTT assay, giving selectivity indices of 31.4 and 40.7. They reported approximately 99% inhibition when the virus was incubated with the extract or when the extract was added during the adsorption phase, 70% inhibition when cells were pre-treated before infection, and no inhibitory effect when the extract was added after adsorption. The authors concluded that the extract may contain compounds acting mainly at the adsorption phase.

  LimitationsThis is laboratory cell-culture work only — there are no people, no animals and no ingestion involved, so no inference about what happens in a person can be drawn. The virus studied (pseudorabies, a pig herpesvirus) is not a human pathogen and was used as a model. A methanolic solvent extract applied directly to cells at defined microgram-per-millilitre concentrations bears no relationship to the dose, form or absorption of a mullein leaf food supplement taken by mouth. Single laboratory, no replication identified.

  Antiviral effect and mode of action of methanolic extract of Verbascum thapsus L. on pseudorabies virus (strain RC/79) — Escobar et al., Natural Product Research 2012. PMID 21999656. Read the full paper on PubMed → (opens in a new tab)

The research above concerns the plant, not this product, and does not describe what this product does. ProBotanics products are food supplements, not medicines.

Three botanicals combined in traditional herbal practice. Each study below concerns one of the three, not the blend.

4 published studies, 3 in people — 2 systematic reviews; 1 randomised controlled trial; 1 literature review.

• Symptom scores in Crohn's disease

  Randomised controlled trialn=40 (20 active, 20 placebo)Ingredient: Wormwood (Artemisia absinthium)Omer et al., Phytomedicine 2007 Limitation: Small (n=40) and, critically, the intervention was a multi-herb blend containing wormwood, not wormwood alone, so…

  What it looked atWhether a herbal blend containing wormwood herb, given at 3 x 500 mg/day for 10 weeks alongside existing medication, was associated with different symptom scores compared with placebo while corticosteroids were tapered to zero on a defined schedule.

  What the authors reportedThe authors reported that scores on the Crohn's Disease Activity Index, the Inflammatory Bowel Disease Questionnaire, the Hamilton Depression Scale and a visual analogue scale changed over the study period in 18 of the 20 participants receiving the wormwood-containing blend despite steroid tapering, and they characterised this as a steroid-sparing effect. They reported that corticosteroids had to be restarted after week 10 in 16 of 20 placebo participants compared with 2 of 20 in the wormwood group, and that scores on the depression scale also differed between groups.

  LimitationsSmall (n=40) and, critically, the intervention was a multi-herb blend containing wormwood, not wormwood alone, so nothing can be attributed to wormwood as a single ingredient. Every participant remained on concomitant corticosteroids and/or immunosuppressants throughout, so the preparation was never tested in isolation. The population was people with diagnosed Crohn's disease under specialist supervision, not general supplement users. Treatment lasted only 10 weeks, giving no information on longer-term use. The same investigator group produced the only other wormwood-in-Crohn's trial, so there is no independent replication.

  Steroid-sparing effect of wormwood (Artemisia absinthium) in Crohn's disease: a double-blind placebo-controlled study — Omer et al., Phytomedicine 2007. PMID 17240130. Read the full paper on PubMed → (opens in a new tab)

• Herbal therapies in inflammatory bowel disease

  Systematic review21 randomised controlled trials, 1484 participants in total (14 ulcerative colitis, 7 Crohn's disease)Ingredient: Wormwood (Artemisia absinthium)Ng et al., Alimentary Pharmacology & Therapeutics 2013 Limitation: This is a synthesis of a small and heterogeneous literature rather than new evidence: the wormwood signal rests on…

  What it looked atA systematic review of English and non-English controlled clinical studies from 1947 to 2013 across MEDLINE, EMBASE, EBM Reviews, AMED and Global Health, examining herbal therapies used in inflammatory bowel disease, with response and remission rates as outcome measures.

  What the authors reportedThe review reported that, in the Crohn's disease trials available at the time, Artemisia absinthium was described as superior to placebo for inducing remission. The authors concluded overall that trials of herbal therapy in inflammatory bowel disease show "encouraging results but studies remain limited and heterogenous", and called for larger controlled studies with stricter endpoints and better-defined patient groups before firmer conclusions could be drawn.

  LimitationsThis is a synthesis of a small and heterogeneous literature rather than new evidence: the wormwood signal rests on the same two small German trials, so the review inherits their limitations instead of resolving them. Included trials varied widely in preparation, dose, duration and endpoints, and the authors themselves described the evidence base as limited. It concerns medically diagnosed inflammatory bowel disease populations, not healthy adults taking a food supplement, and the search ends in 2013.

  Systematic review: the efficacy of herbal therapy in inflammatory bowel disease — Ng et al., Alimentary Pharmacology & Therapeutics 2013. PMID 23981095. Read the full paper on PubMed → (opens in a new tab)

• Thujone safety limits in foods and medicines

  Literature reviewIngredient: Wormwood (Artemisia absinthium) — thujone constituentLachenmeier et al., Regulatory Toxicology and Pharmacology 2010 Limitation: A modelling exercise built on rodent toxicity data, not a human study — the seizure endpoint driving the derived…

  What it looked atA re-evaluation of the toxicological evidence underpinning regulatory limits for thujone, the monoterpene ketone found in wormwood and sage, using the benchmark dose approach rather than the older no-observed-effect-level approach, and incorporating long-term chronic toxicity data for the first time.

  What the authors reportedThe authors reported a benchmark dose lower confidence limit (BMDL10) of 11 mg/kg body weight/day for clonic seizures in male rats, and on that basis proposed an acceptable daily intake for thujone of 0.11 mg/kg body weight/day. They reported that this figure would not be reached even by high-level consumers of thujone-containing foods including absinthe, estimated that between 2 and 20 cups of wormwood or sage tea would be required to reach it, and concluded that short-term medicinal use of these herbs can be regarded as safe and that existing regulatory limits are sufficiently protective for consumers.

  LimitationsA modelling exercise built on rodent toxicity data, not a human study — the seizure endpoint driving the derived intake figure was observed in rats. The reassurance is explicitly framed around short-term use and around wormwood and sage consumed as foods, beverages and teas; it does not establish the safety of concentrated wormwood extracts taken daily over extended periods, which is the situation relevant to a food supplement. The paper is a regulatory assessment and reflects the data and European limits current in 2010.

  Risk assessment of thujone in foods and medicines containing sage and wormwood--evidence for a need of regulatory changes? — Lachenmeier et al., Regulatory Toxicology and Pharmacology 2010. PMID 20727933. Read the full paper on PubMed → (opens in a new tab)

• Plant-derived analgesics in dental pain

  Systematic review21 studies met inclusion criteria (randomised controlled trials, clinical trials and systematic reviews)Ingredient: Clove (Syzygium aromaticum / eugenol)Reddy et al., International Journal of Dentistry 2025 Limitation: This concerns clove oil and eugenol applied topically in and around the mouth in a clinical dental context — the…

  What it looked atA systematic review of PubMed, Cochrane Library, Scopus and Web of Science covering January 2015 to March 2025, examining the efficacy, safety and clinical applications of plant-derived analgesic compounds used in dentistry, with quality of evidence assessed using the GRADE approach.

  What the authors reportedThe review reported that clove oil (eugenol) was among the phytotherapeutic agents described as having the strongest analgesic properties in dental applications, alongside turmeric (curcumin) and capsaicin, and described mechanisms in the included literature ranging from inhibition of prostaglandin synthesis to modulation of inflammatory pathways and direct effects on nociceptors. The authors concluded that standardisation of preparations and larger randomised controlled trials are needed to establish optimal dosing regimens and long-term safety profiles.

  LimitationsThis concerns clove oil and eugenol applied topically in and around the mouth in a clinical dental context — the route of administration, the dose and the purpose are all different from swallowing a clove-containing food supplement, and the review says nothing about oral ingestion of clove capsules. It is a narrative-leaning systematic review without meta-analysis, so effect sizes are not pooled. The authors noted that preparations were not standardised across the included studies and that long-term safety is not established.

  Analgesic Efficacy of Phytotherapeutic Agents in Dental Pain Management: A Systematic Review — Reddy et al., International Journal of Dentistry 2025. PMID 41322706. Read the full paper on PubMed → (opens in a new tab)

The research above concerns the plant, not this product, and does not describe what this product does. ProBotanics products are food supplements, not medicines.

One of the most heavily studied plants in the herbal literature — and the one with the best-documented interactions with prescription medicines. Please read the interactions section below before considering this botanical.

3 published studies, 3 in people — 3 systematic reviews.

• Interactions with prescribed medicines

  Systematic reviewHenderson et al., British Journal of Clinical Pharmacology 2002 Limitation: This is a 2002 review and much of its interaction evidence rests on spontaneous case reports rather than controlled…

  What it looked atThe authors set out to identify which prescribed medicines interact with St John's wort preparations, and to determine the pharmacological mechanisms responsible, by systematically reviewing the published literature together with spontaneous adverse-reaction reports held by European regulators.

  What the authors reportedThe authors reported that they identified a number of clinically significant interactions with prescribed medicines — including warfarin, phenprocoumon, ciclosporin, HIV protease inhibitors, theophylline, digoxin and oral contraceptives — resulting in a decrease in the concentration or effect of those medicines. They attributed this to induction of the cytochrome P450 isoenzymes CYP3A4, CYP2C9 and CYP1A2 and of the transport protein P-glycoprotein by constituents of St John's wort, and noted that the degree of induction is unpredictable because the quality and quantity of constituents varies between preparations. The authors additionally reported possible pharmacodynamic interactions with selective serotonin re-uptake inhibitors and with serotonin (5-HT1d) receptor agonists such as triptans, which they associated with an increased risk of adverse reactions. They stated that in Sweden and the UK the potential risks to patients were judged significant, that product information for the licensed medicines involved was amended, and that St John's wort preparations were voluntarily labelled with warnings.

  LimitationsThis is a 2002 review and much of its interaction evidence rests on spontaneous case reports rather than controlled trials, so causality in individual cases cannot be established and the true frequency of interactions is unknown. The authors themselves noted that induction is unpredictable because constituent content varies between St John's wort preparations, meaning findings cannot be transferred reliably to any one product or dose. The review concerns pharmaceutical-grade Hypericum extracts used at medicinal doses, which may differ from a food-supplement presentation.

  St John's wort (Hypericum perforatum): drug interactions and clinical outcomes — Henderson et al., British Journal of Clinical Pharmacology 2002. PMID 12392581. Read the full paper on PubMed → (opens in a new tab)

• Herb-drug interactions with prescription medicines

  Systematic reviewIzzo et al., Drugs 2009 Limitation: The review pools heterogeneous evidence of very uneven quality, mixing controlled clinical trials with uncontrolled…

  What it looked atThe authors set out to review the literature to determine the possible interactions between seven widely used herbal medicines — ginkgo, St John's wort, ginseng, garlic, echinacea, saw palmetto and kava — and conventional prescribed drugs, searching MEDLINE, the Cochrane Library and EMBASE.

  What the authors reportedThe authors reported that clinical trials indicate St John's wort, via cytochrome P450 and/or P-glycoprotein induction, reduces the plasma concentrations of, and/or increases the clearance of, an extensive list of medicines including alprazolam, amitriptyline, atorvastatin, ciclosporin, digoxin, erythromycin, fexofenadine, imatinib, indinavir, irinotecan, methadone, midazolam, nifedipine, omeprazole, oral contraceptives, simvastatin, tacrolimus, verapamil, voriconazole and warfarin. They further reported that case reports or case series suggest interactions with additional agents including bupropion, nevirapine, paroxetine, sertraline, venlafaxine, prednisone and theophylline. The review concluded that while the significance of many herb–drug interactions is uncertain, several interactions — particularly those involving St John's wort — may have serious clinical consequences.

  LimitationsThe review pools heterogeneous evidence of very uneven quality, mixing controlled clinical trials with uncontrolled case reports from which causality cannot be established. Extract type, hyperforin content, dose and duration varied across the included studies and are not standardised in the summary, so the findings cannot be mapped onto any particular commercial preparation. The review dates from 2009 and covers seven herbs rather than examining St John's wort in isolation.

  Interactions between herbal medicines and prescribed drugs: an updated systematic review — Izzo et al., Drugs 2009. PMID 19719333. Read the full paper on PubMed → (opens in a new tab)

• Use alongside hormonal contraceptives

  Systematic reviewBerry-Bibee et al., Contraception 2016 Limitation: Only four studies met the inclusion criteria and each was small, so the evidence base is thin and the review's own…

  What it looked atThe authors set out to examine, by systematic review of PubMed and the Cochrane Library, whether co-administration of St John's wort with hormonal contraceptives leads to significant safety or efficacy concerns, given that St John's wort is a known strong inducer of CYP3A4 and that both the ethinyl estradiol and progestin components of hormonal contraceptives are CYP3A4 substrates.

  What the authors reportedThe authors reported that of the four included studies, two showed no change in markers of ovulation but one demonstrated increased follicular growth and probable ovulation when combined oral contraceptives were co-administered with St John's wort, and three demonstrated an increased risk of breakthrough bleeding. They reported that three studies showed changes in at least one pharmacokinetic parameter suggesting significantly decreased exposure to hormone concentrations, and that the single study finding no significant pharmacokinetic difference had examined a St John's wort product containing a low amount of hypericin. The review concluded that the limited evidence showing increased risk of ovulation and breakthrough bleeding raises concern for decreased contraceptive efficacy, and that the pharmacokinetic evidence is mixed but suggests St John's wort administration may be associated with weak to moderate induction of the metabolism of combined oral contraceptives.

  LimitationsOnly four studies met the inclusion criteria and each was small, so the evidence base is thin and the review's own conclusions are hedged. Findings were inconsistent between studies, and the authors noted that the product's hypericin content appeared to influence whether an effect was seen — meaning results may not generalise across differently standardised preparations. No study measured pregnancy as an outcome, so the clinical consequence for contraceptive failure is inferred from surrogate markers rather than directly demonstrated.

  Co-administration of St. John's wort and hormonal contraceptives: a systematic review — Berry-Bibee et al., Contraception 2016. PMID 27444983. Read the full paper on PubMed → (opens in a new tab)

The research above concerns the plant, not this product, and does not describe what this product does. ProBotanics products are food supplements, not medicines.

A blend of fourteen plant extracts, the largest being horse chestnut seed at 200 mg per serving. The research below concerns some of those individual plants. It does not concern this blend.

9 published studies, all of them in people — 2 systematic reviews, 3 meta-analyses and 4 randomised controlled trials. None tested this blend, and none measured lymphatic function.

• Horse chestnut seed extract for chronic venous insufficiency

  Systematic reviewPittler and Ernst, Cochrane Database of Systematic Reviews 2012 Limitation: Every trial in the review used extract standardised to a declared escin content. Our extract states no…

  What it looked atA Cochrane systematic review and meta-analysis of 17 randomised controlled trials of oral horse chestnut seed extract in people with chronic venous insufficiency, a condition of the leg veins. Trials ran from 2 to 16 weeks. Combination products were deliberately excluded — only single-herb preparations were included.

  What the authors reportedPooling six trials in 502 people, leg volume fell by a weighted mean difference of 32.1 mL (95% CI 13.49 to 50.72) compared with placebo. Leg pain was reduced in six of seven placebo-controlled trials. The extract performed comparably to rutosides in four trials and to compression stockings in two, and was less effective than pycnogenol for oedema. Adverse events were reported as mild and infrequent. The authors' own conclusion was cautious: they wrote that several caveats exist and that larger, definitive trials are required.

  LimitationsEvery trial in the review used horse chestnut seed extract standardised to a declared escin (aescin) content, typically 600 mg of extract a day delivering 100 mg of aescin. Our product provides 200 mg of horse chestnut extract and states no aescin standardisation, so the material is not established as comparable and the finding cannot be transferred to it. The trials are old, mostly German, and many were linked to manufacturers. The longest ran 16 weeks, so there is no long-term data. Leg volume is a surrogate measure whose meaning to an individual is uncertain. And the condition studied is a vein disorder, not a lymphatic one.

  Horse chestnut seed extract for chronic venous insufficiency — Pittler and Ernst, Cochrane Database of Systematic Reviews 2012. PMID 23152216. Read the full paper on PubMed → (opens in a new tab)

• Horse chestnut extract compared with compression stockings

  Randomised controlled trialDiehm et al., The Lancet 1996 Limitation: The trial used 100 mg of aescin a day — a standardised dose this product does not state and…

  What it looked atA randomised, partially blinded, placebo-controlled trial in 240 people with chronic venous insufficiency, run over 12 weeks. Three arms: horse chestnut seed extract standardised to 50 mg of aescin taken twice daily, class II compression stockings, or placebo.

  What the authors reportedLower leg volume fell by 43.8 mL with the extract and 46.7 mL with compression stockings, and rose by 9.8 mL on placebo. The extract beat placebo (p=0.005), and the two active treatments were statistically equivalent to one another.

  LimitationsThe trial used 100 mg of aescin a day, from extract standardised to deliver it. Our product provides 200 mg of horse chestnut extract with no stated aescin content, so the dose actually delivered is unknown and cannot be assumed equivalent. Blinding was only partial, because a compression stocking cannot be disguised, and expectations affect self-reported symptoms. There was manufacturer involvement. It is a single trial that has not been replicated at this scale, and the endpoint is leg volume in a vein condition.

  Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency — Diehm et al., The Lancet 1996. PMID 8569363. Read the full paper on PubMed → (opens in a new tab)

• Phlebotonics, including rutosides, for oedema in venous insufficiency

  Systematic reviewMartinez-Zapata et al., Cochrane Database of Systematic Reviews 2020 Limitation: The rutoside trials used purified troxerutin, a chemically modified compound, not Japanese pagoda…

  What it looked atA Cochrane systematic review and meta-analysis of oral phlebotonics — a drug and supplement category used for vein problems — covering 69 randomised trials, 56 with usable data, in 7,690 people of mean age 50. Twenty-eight of the included trials were of rutosides, the largest single block of evidence in the review. Two trials of Centella asiatica (gotu kola) were also included.

  What the authors reportedAll findings were graded for certainty. For oedema, moderate-certainty evidence of a risk ratio of 0.70 (95% CI 0.63 to 0.78) across 13 studies in 1,245 people — which Cochrane described as reducing oedema "slightly". Ankle circumference fell by a mean of 4.27 mm. For quality of life there was moderate-certainty evidence of little or no difference. For ulcer healing, low-certainty evidence of no effect. And there was moderate-certainty evidence of more adverse events than placebo, mostly gastrointestinal, with a risk ratio of 1.14 (95% CI 1.02 to 1.27).

  LimitationsThe rutoside trials used purified troxerutin and related hydroxyethylrutosides — chemically modified compounds given at roughly 1 to 2 grams a day — not Japanese pagoda tree extract. Rutin is industrially sourced from that plant, but the trialled substance is not the same material, and we found no trial of the whole-herb extract itself. Our product contains 100 mg of pagoda tree flower bud extract with no stated rutin content. Certainty was downgraded from high for risk of bias and imprecision. Only short-term safety could be assessed. The two gotu kola trials are far too few to draw any conclusion about that ingredient.

  Phlebotonics for venous insufficiency — Martinez-Zapata et al., Cochrane Database of Systematic Reviews 2020. PMID 33141449. Read the full paper on PubMed → (opens in a new tab)

• A seven-component supplement containing gotu kola after breast surgery

  Randomised controlled trialSgaramella et al., Scientific Reports 2025 Limitation: Gotu kola was one of seven components, and the arm without it also beat placebo — which points…

  What it looked atA double-blind randomised placebo-controlled trial in 114 people who had undergone breast-conserving surgery, over 30 days, with three arms. One group received a supplement containing Boswellia phytosome and bromelain together with alpha-lipoic acid, superoxide dismutase, B and D vitamins and Centella asiatica. A second received Boswellia and bromelain without the Centella. A third received placebo.

  What the authors reportedThe seven-component group had less oedema (p=0.002 at one month) and less seroma (p<0.001 at one month) than placebo. This is the closest study we found to a lymphatic-adjacent outcome anywhere in the literature on these plants.

  LimitationsGotu kola was one of seven components, so the design cannot show what it contributed. Decisively, the second group — the same formula without gotu kola — also outperformed placebo, which points the effect towards the bromelain and Boswellia rather than the Centella. The population is post-surgical, not general. Single centre. Neither bromelain nor Boswellia is in our product.

  Efficacy of a nutraceutical supplement in reducing postoperative complications after breast-conserving surgery — Sgaramella et al., Scientific Reports 2025. PMID 39929877. Read the full paper on PubMed → (opens in a new tab)

• Olive leaf extract and cholesterol — a null result

  Randomised controlled trialStevens et al., European Journal of Nutrition 2020 Limitation: None needed for the headline — the trial found nothing, at five times our dose. We include it…

  What it looked atA randomised, double-blind, placebo-controlled trial in 77 overweight or obese adults with mildly raised cholesterol, taking 500 mg of olive leaf extract daily for 8 weeks. The trial was pre-registered.

  What the authors reportedNothing. There was no significant effect on blood lipids at either 4 or 8 weeks, and none on oxidised LDL, blood pressure, glucose, insulin or liver function. All comparisons returned p greater than 0.05.

  LimitationsWe include this because it is the best-designed olive leaf trial we found and because it is negative — and a negative result at 500 mg is directly relevant to a product containing 100 mg. One author was affiliated with a supplement company, which makes an industry-linked null finding more credible rather than less. The population was specific (overweight adults with raised cholesterol) and the endpoints were metabolic, so this does not speak to other possible effects. It does, however, undercut any assumption that olive leaf extract does something detectable at these doses.

  The effect of olive leaf extract on cardiovascular health markers: a randomized placebo-controlled clinical trial — Stevens et al., European Journal of Nutrition 2020. PMID 33034707. Read the full paper on PubMed → (opens in a new tab)

• Astragalus alongside prescribed treatment in diabetic kidney disease

  Meta-analysisLin et al., Renal Failure 2024 Limitation: Publication bias was detected, and the trials used decoctions or injections at doses orders of…

  What it looked atA systematic review and meta-analysis of 32 randomised trials in 2,462 people with stage III diabetic nephropathy, testing astragalus added to a prescribed medicine class used in kidney disease, compared with that medicine alone.

  What the authors reportedThe astragalus add-on groups showed reductions in urinary protein excretion, serum creatinine, blood urea nitrogen and HbA1c relative to the medicine alone.

  LimitationsThe authors detected publication bias for several outcomes, including total effective rate, serum creatinine and 24-hour urinary protein — meaning negative trials are likely missing from the literature. All trials came from one region. "Total effective rate" is a soft composite measure. Astragalus preparation, dose and route were not harmonised across trials, and much of this literature uses injectable preparations or decoctions of 15 to 30 grams of raw herb per day. Our product contains 100 mg of extract, two to three orders of magnitude below a decoction. The participants were patients with diagnosed kidney disease taking prescription medicines; nothing here applies to a healthy adult, and nothing relates to lymphatic function. The authors themselves called for rigorous large-scale double-blind trials, which these were not.

  Astragalus for diabetic nephropathy: a systematic review and meta-analysis — Lin et al., Renal Failure 2024. PMID 38836372. Read the full paper on PubMed → (opens in a new tab)

• Ginger preparations for nausea and vomiting after surgery

  Meta-analysisZhao et al., Journal of Ethnopharmacology 2023 Limitation: Trials used 1,000 to 3,000 mg of ginger a day. This product contains 25 mg — between a fortieth…

  What it looked atA Bayesian network meta-analysis of 18 randomised controlled trials in 2,199 people, comparing ginger preparations for nausea and vomiting after surgery, with the evidence graded for certainty.

  What the authors reportedGinger oil ranked best for reducing vomiting after surgery, with a risk ratio of 0.39 (95% CI 0.16 to 0.96) and high-to-moderate confidence. For nausea, no ginger preparation outperformed placebo, at moderate-to-low certainty.

  LimitationsThe effect was specific to ginger oil rather than dried rhizome powder, and concentrated in particular subgroups — Asian populations, older patients, higher doses and preoperative timing. The dose gap is the decisive point: the ginger literature uses roughly 1,000 to 3,000 mg a day for anti-inflammatory effects and 500 to 1,500 mg for nausea. This product contains 25 mg, between a fortieth and a hundred-and-twentieth of the amounts trialled. No trial has tested 25 mg of ginger, and there is no basis to expect a ginger effect at that amount.

  Efficacy of ginger for postoperative nausea and vomiting: a network meta-analysis — Zhao et al., Journal of Ethnopharmacology 2023. PMID 37379959. Read the full paper on PubMed → (opens in a new tab)

• Red clover isoflavones and blood lipids in menopausal women

  Meta-analysisLuís et al., Climacteric 2018 Limitation: Studied only in peri- and postmenopausal women, using standardised isoflavone doses this product…

  What it looked atA systematic review and meta-analysis of 12 randomised controlled trials in 1,284 peri- and postmenopausal women, with treatment periods running from 4 weeks to 18 months, examining red clover isoflavones and blood lipids.

  What the authors reportedTotal cholesterol fell by 12.34 mg/dL (95% CI −18.21 to −6.48), LDL cholesterol by 10.61 mg/dL and triglycerides by 10.18 mg/dL, while HDL rose by 1.60 mg/dL.

  LimitationsThe population is narrow — peri- and postmenopausal women — and the results do not generalise to adults in general. Trials used 40 to 85 mg a day of standardised isoflavones; our product contains 100 mg of flower-head extract with no stated isoflavone content, which could plausibly deliver anywhere from roughly 8 to 40 mg, and cannot be verified from the label. Durations from 4 weeks to 18 months were pooled together. The endpoints are blood markers, not cardiovascular events. Effect sizes are modest in absolute terms. A separate two-year trial of 50 mg a day found no effect on bone density at any site.

  Effects of red clover on total cholesterol, LDL, HDL and triglycerides: a systematic review and meta-analysis — Luís et al., Climacteric 2018. PMID 30269660. Read the full paper on PubMed → (opens in a new tab)

• Red clover and bone density over two years — no effect

  Randomised controlled trialClifton-Bligh et al., European Journal of Clinical Nutrition 2014 Limitation: Included as a documented failure of a commonly repeated claim, not as evidence about this product…

  What it looked atA randomised controlled trial of red clover isoflavones at 50 mg a day, run over two years, measuring bone mineral density and blood lipids.

  What the authors reportedNo effect on bone density at any measured site. LDL cholesterol fell by around 12%, consistent with the lipid findings above.

  LimitationsWe include this as a documented failure of a claim that is frequently repeated about red clover, not as evidence about our product. It is a single trial. The dose, 50 mg of standardised isoflavones, is again a standardised figure our label does not state. As with all the red clover work, the population is menopausal women.

  Red clover isoflavones enriched with formononetin lower serum LDL cholesterol — a randomized, double-blind, placebo-controlled study — Clifton-Bligh et al., European Journal of Clinical Nutrition 2014. PMID 25369831. Read the full paper on PubMed → (opens in a new tab)

The research above concerns individual plants, not this product, and does not describe what this product does. Several ingredients in this blend — dandelion, cleavers, burdock, yerba mate and grapefruit seed — have no meaningful human clinical evidence at all for anything relevant here, and we would rather say so than leave the gap unmentioned. ProBotanics products are food supplements, not medicines.

A children's supplement providing four nutrients, alongside a small botanical blend, collagen and three amino acids. The research below is on those nutrients in children generally. It is not research on this product.

9 published studies, all of them in people — 5 systematic reviews, 2 meta-analyses, 2 randomised controlled trials. The honest summary is that the benefit in a well-nourished UK child is small at best, and for two of the ingredients there is no paediatric evidence at all.

• Calcium supplementation for bone density in healthy children

  Systematic reviewWinzenberg et al., Cochrane Database of Systematic Reviews 2006 Limitation: The authors' stated conclusion is that the results do not support calcium supplementation in…

  What it looked atA Cochrane systematic review of 19 randomised trials in 2,859 healthy children, examining whether calcium supplementation increases bone mineral density.

  What the authors reportedNo effect on bone mineral density at the femoral neck, and none at the lumbar spine. Small effects on total body bone mineral content (standardised mean difference 0.14, 95% CI 0.01 to 0.27) and upper limb density (0.14, 95% CI 0.04 to 0.24). After supplementation stopped, only the upper limb effect persisted, and its confidence interval very nearly crossed zero. The authors modelled this as roughly a 1.7% greater increase in bone density, which they wrote would at best reduce absolute fracture risk in children by 0.1 to 0.2% a year. Their stated conclusion was that the results do not support the use of calcium supplementation in healthy children as a public health intervention.

  LimitationsThe effects were not modified by the child's baseline calcium intake, sex, ethnicity, physical activity or pubertal stage — so there was no identifiable subgroup that benefited more. This review remains at its 2006 version and has not been updated, so the definitive synthesis on this question is now twenty years old. A separate trial found that children supplemented with calcium gained bone mineral content during supplementation and then lost the difference entirely within twelve months of stopping, which the authors attributed to a transient reduction in bone turnover rather than durable bone gain.

  Calcium supplementation for improving bone mineral density in children — Winzenberg et al., Cochrane Database of Systematic Reviews 2006. PMID 16625624. Read the full paper on PubMed → (opens in a new tab)

• What happens when calcium supplementation stops

  Randomised controlled trialLee et al., Acta Paediatrica 1997 Limitation: The gain seen during supplementation disappeared within a year of stopping, which is the point…

  What it looked atA trial in 159 children whose habitual calcium intake was around 300 mg a day — well below typical UK intakes — measuring radial bone mineral content during calcium supplementation and for twelve months after it stopped.

  What the authors reportedDuring supplementation the children gained 17.9% more radial bone mineral content than controls. In the twelve months after withdrawal they gained 16.1% less. The difference between the groups disappeared. The authors described this as a transient reduction in bone turnover rate.

  LimitationsA single trial in children with unusually low habitual calcium intake, so it is not directly transferable to a well-fed UK child. Radial bone mineral content is one site and a surrogate measure. We include it because it illustrates something the headline figures obscure: a measured gain during supplementation is not the same as a lasting one, and this trial is the clearest published demonstration of the catch-down effect.

  Bone mineral acquisition in low calcium intake children following the withdrawal of calcium supplement — Lee et al., Acta Paediatrica 1997. PMID 9202789. Read the full paper on PubMed → (opens in a new tab)

• Vitamin D and bone density in children — pooled individual participant data

  Meta-analysisWu et al., American Journal of Clinical Nutrition 2023 Limitation: Generalises mainly to White postpubertal girls, and does not apply to symptomatic deficiency…

  What it looked atAn individual participant data meta-analysis — the strongest form of pooling, using each participant's own data rather than published summaries — of 9 randomised trials in 1,439 children and adolescents aged 1 to 19. Mean baseline vitamin D status was 36.3 nmol/L, which is genuinely low. Bone outcomes were measured at one year, and the certainty of evidence was rated high.

  What the authors reportedA small increase in total hip bone density of 6.8 mg/cm² (95% CI 0.7 to 12.9). No effect on total body bone mineral content, femoral neck, lumbar spine, or either forearm site. Critically, there was no interaction between baseline vitamin D status and the treatment effect — the results were similar whether children started below or above the thresholds tested. The authors' stated conclusion was that clinically important benefits for bone density from one year of vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely.

  LimitationsThe pooled population generalises mainly to White postpubertal girls. It does not apply to symptomatic vitamin D deficiency or rickets, which remain genuine clinical conditions requiring treatment — this is about supplementation in children who are not clinically deficient. One year is a meaningful but not lifelong window. The finding supersedes an earlier 2010 Cochrane review which had hinted that deficient children might benefit; that hypothesis did not survive individual participant analysis.

  Effect of vitamin D supplementation on bone density in healthy children and adolescents: an individual participant data meta-analysis — Wu et al., American Journal of Clinical Nutrition 2023. PMID 37661104. Read the full paper on PubMed → (opens in a new tab)

• The earlier Cochrane review of vitamin D and children's bones

  Systematic reviewWinzenberg et al., Cochrane Database of Systematic Reviews 2010 Limitation: Its suggestion that deficient children might benefit was not confirmed by the later and…

  What it looked atA Cochrane systematic review of 6 randomised trials in 884 children, examining vitamin D supplementation and bone density.

  What the authors reportedNo significant effect on total body bone mineral content, hip or forearm bone density. At the lumbar spine there was a trend only, which did not reach significance (standardised mean difference 0.15, 95% CI −0.01 to 0.31, p=0.07). The authors suggested that children who were vitamin D deficient at baseline might benefit.

  LimitationsWe include this because it is widely cited and because its central suggestion — that deficient children are the group who benefit — was tested directly by the later individual participant data meta-analysis above and was not confirmed. Six trials in 884 children is a small evidence base. Where an older review and a newer, higher-certainty analysis disagree, the newer one should carry the weight.

  Vitamin D supplementation for improving bone mineral density in children — Winzenberg et al., Cochrane Database of Systematic Reviews 2010. PMID 20927753. Read the full paper on PubMed → (opens in a new tab)

• Vitamin D fortification and children's growth

  Systematic reviewHuey et al., Cochrane Database of Systematic Reviews 2020 Limitation: Low certainty, and the confidence interval for height crosses zero — this is a null result…

  What it looked atA Cochrane review of vitamin D fortification of foods, with 64 studies contributing to meta-analysis, examining growth outcomes in children.

  What the authors reportedFor height, a mean difference of 0.66 cm (95% CI −0.37 to 1.68) — a confidence interval that crosses zero, at low certainty, which the review characterised as little to no difference. For stunting, a risk ratio of 0.90 (95% CI 0.80 to 1.01), again crossing the line of no effect.

  LimitationsLow certainty of evidence throughout. This concerns fortified foods rather than supplements specifically, and the studies span very different populations and baseline vitamin D status. We include it because growth is what a parent buying a product with "growing up" in its name is likely thinking about, and this is the largest synthesis addressing that question directly. It does not show a height benefit.

  Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five — Huey et al., Cochrane Database of Systematic Reviews 2020. PMID 33305842. Read the full paper on PubMed → (opens in a new tab)

• Zinc supplementation and growth in children

  Systematic reviewImdad et al., Cochrane Database of Systematic Reviews 2023 Limitation: 87 of the 96 trials were in low- or middle-income countries, and the authors' conclusion is…

  What it looked atThe current Cochrane review of preventive zinc supplementation in children aged 6 months to 12 years, covering 96 randomised trials in 219,584 children, with most trials using 10 to 15 mg a day.

  What the authors reportedFor height, a standardised mean difference of 0.12 (95% CI 0.09 to 0.14) at moderate certainty, which the review described as a slight increase. No difference in mortality and none in lower respiratory tract infection, both at high certainty. Increased vomiting, at high certainty. The authors' conclusion was explicitly conditional: that the benefits of preventive zinc supplementation may outweigh the harms in regions where the risk of zinc deficiency is relatively high.

  LimitationsEighty-seven of the ninety-six trials were carried out in low- or middle-income countries, where zinc deficiency is common. The conclusion is conditional on that context and does not transfer to a well-nourished child in the UK. A separate meta-analysis of 33 trials found that growth responses were greater in children with low initial weight-for-age, and in those with low initial height-for-age — that is, the effect concentrates in children who were already faltering. In absolute terms, 10 mg of zinc a day for 24 weeks produced a net height gain of about 0.37 cm in developing-country settings. No meta-analysis demonstrates a growth benefit in well-nourished, zinc-replete children in a high-income country.

  Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years — Imdad et al., Cochrane Database of Systematic Reviews 2023. PMID 36994923. Read the full paper on PubMed → (opens in a new tab)

• Which children respond to zinc, and which do not

  Meta-analysisBrown et al., American Journal of Clinical Nutrition 2002 Limitation: The response concentrates in children who were underweight or short for their age to begin…

  What it looked atA meta-analysis of 33 randomised controlled trials of zinc supplementation in children, examining not just whether zinc affects growth but which children respond.

  What the authors reportedA positive effect on height (effect size 0.350, 95% CI 0.189 to 0.511) and on weight (0.309, 95% CI 0.178 to 0.439), but none on weight-for-height (−0.018). The authors reported that growth responses were greater in children with low initial weight-for-age scores, and in those aged over 6 months with low initial height-for-age scores.

  LimitationsThis is the clearest statement in the literature of the point that matters for a UK parent: the zinc growth response concentrates in children who were underweight or short for their age to begin with. It is an older analysis, superseded in size by the 2023 Cochrane review, and it does not include a well-nourished high-income comparison group because such trials are largely not done. Separately, iron given alongside zinc has been reported to reduce zinc's benefit, which is relevant to any multi-ingredient formula.

  Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials — Brown et al., American Journal of Clinical Nutrition 2002. PMID 12036814. Read the full paper on PubMed → (opens in a new tab)

• Vitamin K2 in healthy children — the only trial, and it measured a marker

  Randomised controlled trialvan Summeren et al., British Journal of Nutrition 2009 Limitation: It measured osteocalcin carboxylation, not bone. No bone density, no bone mineral content, no…

  What it looked atA randomised trial in 55 healthy prepubertal children given 45 µg of vitamin K2 as MK-7 daily for 8 weeks. The outcome measured was the carboxylation status of osteocalcin, a protein involved in bone metabolism.

  What the authors reportedUndercarboxylated osteocalcin fell and the ratio of undercarboxylated to carboxylated osteocalcin improved. The authors also reported that bone markers and coagulation parameters remained constant over the study period.

  LimitationsThis is, as far as we can establish, the only randomised trial of vitamin K in healthy children — and it did not measure bone. There is no bone density outcome, no bone mineral content, and no fracture data; eight weeks could not detect a change in bone density in any case. Osteocalcin carboxylation is a biochemical marker, and an improvement in a marker is not the same as a benefit to a child's skeleton. Everything else in this area is either observational, carried out in children with specific diseases, or extrapolated from trials in postmenopausal women — whose authors have themselves written that whether their results extend to children needs further investigation. One randomised paediatric comparison, in children on long-term steroid treatment, found bone density scores fell in the vitamin K group. There is no authorised health claim for vitamin K in children, and no evidence base that would support one.

  The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children — van Summeren et al., British Journal of Nutrition 2009. PMID 19450370. Read the full paper on PubMed → (opens in a new tab)

• Ginkgo in children — the only paediatric trials, and the verdict

  Literature reviewSarris et al., Complementary Therapies in Medicine 2011 Limitation: There are no trials of ginkgo in healthy children at all, and no long-term paediatric safety…

  What it looked atA review of herbal medicines studied in attention deficit hyperactivity disorder, which is the only context in which ginkgo has been trialled in children at all.

  What the authors reportedThe review's stated conclusion was that current data suggest ginkgo biloba is ineffective in treating ADHD. The individual paediatric trials are small, single-centre, and studied ginkgo added to existing prescribed medication rather than on its own.

  LimitationsWe include this to make an absence visible. There are no trials of ginkgo in healthy children for any purpose, and no long-term paediatric safety data of any kind. The European Medicines Agency's herbal monograph on ginkgo leaf states that use under 18 is not recommended, because use in that group has not been established due to a lack of adequate data. Where the only paediatric evidence that exists is negative, in a clinical population, and a European regulator has separately declined to endorse the ingredient for anyone under 18, the honest summary is that this ingredient has nothing behind it for children.

  Herbal medicines in the treatment of psychiatric disorders: a systematic review — Sarris et al., Complementary Therapies in Medicine 2011. PMID 21827936. Read the full paper on PubMed → (opens in a new tab)

The research above concerns these nutrients in children generally, not this product, and does not describe what this product does. There is no paediatric evidence for the collagen hydrolysate, the three amino acids, or five of the six botanicals in this formula, and we would rather say so than leave the gap unmentioned. ProBotanics products are food supplements, not medicines.