Barberry (Berberis vulgaris)

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15. Safety

Adverse effects in trials. In the one trial of a root preparation, 12 of the barberry group and 6 of the placebo group left for non-compliance or side effects; the side effects were not listed, and the protocol excluded anyone who developed one, so the trial cannot tell us how often harms occur [14]. In berberine trials the common effects are gastrointestinal: constipation, flatulence and abdominal discomfort; in two trials reported together (one against metformin, one open add-on) 34.5 per cent had gastrointestinal effects, mostly in the first four weeks [3]. Commission E listed dizziness, nosebleeds, breathlessness, skin and eye irritation, gastrointestinal irritation, nausea, diarrhoea, nephritis and urinary disorders at berberine doses above 500 mg [3].

Case reports. Bone and Mills found no adverse reaction documented for barberry itself [3]. A Swiss case of acquired long QT and torsades de pointes involved a 56-year-old woman who had taken hemp oil (cannabidiol and cannabigerol) for 4 months, at up to six times the recommended dose, and had added a 250 mg berberine supplement for about 6 weeks; the QT normalised within 5 days of stopping all supplements [44]. Causality for berberine alone is possible at most, because the cannabinoids were taken in excess at the same time.

Toxicology. Oral LD50 of powdered B. vulgaris root in mice, 2600 mg/kg; of a barberry root extract fraction, 520 mg/kg in mice and 1280 mg/kg in rats; of berberine in mice, 329 mg/kg orally and 23 mg/kg intraperitoneally [45]. A hydro-ethanolic root bark extract, prepared as a homoeopathic mother tincture, caused no deaths at 2000 µL/kg and no adverse change over 28 days at up to 1000 µL/kg/day in rats, but caused malformations in zebrafish embryos at high concentration [46]; doses were given by volume of a tincture whose strength is not stated as a drug ratio, so they cannot be converted to bark. Berberine hydrochloride was weakly mutagenic in Salmonella TA98 without metabolic activation and inactive with it [3]. A 2026 European review of the wider literature found in vitro evidence of gene mutation and chromosomal damage by berberine, not yet tested in vivo, and found no eligible genotoxicity or mammalian toxicity study of B. vulgaris root or bark itself [60]. Under UVA, berberine damaged keratinocytes and lens epithelial cells in vitro, and eyewashes containing berberine are best used out of bright sunlight [3].

Contraindications.

• Pregnancy. Contraindicated by MediHerb [4]; "best avoided" (Bone and Mills) [3]; contraindicated in early pregnancy by the BHP 1983 [3]. The basis is berberine’s displacement of bilirubin from albumin [3,5], a review naming barberry and its protoberberine alkaloids as uterine stimulants [5], uterine contraction with berberine in experimental models, and increased contractility of isolated uterus with an alcohol extract of Berberis branch and stem bark [3]. Bone and Mills note that ten berberine-containing extracts stimulated or relaxed isolated uterus without relation to their berberine content [3]. In rats fed berberine chloride dihydrate from gestational day 6 to 20, the maternal no-observed-adverse-effect level was 282 mg/kg a day, and the developmental no-observed-adverse-effect level 531 mg/kg a day with the lowest effect level at 1313 mg/kg a day; a gavage follow-up suggested the developmental level could be raised to about 1100 mg/kg a day [3]. Mills and colleagues rate the kernicterus concern evidence level 3 and the uterine-stimulant concern level 4 on their scale [5]. Grade: animal and in vitro; no human pregnancy data.
• Breastfeeding and neonatal jaundice. Contraindicated by MediHerb [4]. Berberine displaced bilirubin from albumin about ten times more strongly than phenylbutazone in vitro and lowered bilirubin protein binding in rats given it by injection [3,5]; kernicterus in premature Chinese infants has been linked with Coptis, directly, across the placenta or through breast milk, although later animal data dispute the link [3]. Whether berberine passes into human milk has not been measured in the sources read. Grade: animal, in vitro and contested observational.
• G6PD deficiency in newborns. Singapore banned Coptis and berberine in 1978 after cases of neonatal jaundice and kernicterus in G6PD-deficient babies; they stayed under the Poisons Act until 2013, when the Health Sciences Authority lifted the prohibition after reviewing the evidence [47]. Grade: observational, contested.
• Gallstones. Caution, because of the possibility of impacted stones and obstructed bile ducts with a cholagogue [4]. Grade: theoretical.
• General anaesthesia. MediHerb advises stopping 7 days before [4]. Grade: precautionary.
• Diarrhoea. The BHP 1983 listed diarrhoea as a contraindication; Bone and Mills judge this "probably not valid", since berberine is used to treat diarrhoea [3].

Interactions.

AIP comment (Medicine): every clinical interaction above was shown with isolated berberine at 300 to 900 mg a day. Bark at 1.5 to 3 g a day supplies an estimated 37 to 180 mg (section 12). The interactions are probably weaker with the herb. Nobody has tested the herb, and the low end of the ciclosporin data (300 mg a day) is within about two- to fourfold of the 73 to 180 mg estimated for the top practitioner dose, so the cautions stand. Ciclosporin and other narrow-therapeutic-index drugs cleared by CYP3A4, CYP2D6 or CYP2C9 (for example tacrolimus, warfarin and phenytoin) are the combinations to avoid without drug-level monitoring; for other substrates, monitoring is enough. Patients who take a berberine supplement as well as the herb should be treated as taking berberine at trial doses.

Children and older people. Berberine has been given to children with diarrhoea and giardiasis in trials, and Bone and Mills advise avoiding use in neonates and very young children [3]. Older people are more likely to take the interacting drugs listed above [43].

Overdose. A teaspoonful of powdered root bark acts as a purgative [18]. Commission E knew of no poisoning with barberry, and of possible deaths from berberine [3].

Regulatory safety notices. The Permissible Ingredients Determination sets no warning statement for B. vulgaris, although the entry for B. aristata requires the pregnancy warning "Not recommended for use by pregnant and lactating women" [8]. AIP comment: this is inconsistent, since the two barks carry the same alkaloid; practitioners should apply the pregnancy and lactation contraindication to both. A search of the TGA website in September 2026 for "berberine" (59 results), "Berberis" (125) and "Berberis vulgaris" (48) found ARTG entries, sponsor cancellations and one ingredient-name notice, and no safety alert, safety advisory or Medicines Safety Update item [56].

Australian adverse-event reports. The TGA Database of Adverse Event Notifications (DAEN – medicines), data to 15/09/2026, was searched in September 2026 [57]. "Barberry" matched no medicine. "Berberis vulgaris" matched 21 medicines, all multi-ingredient listed products, with 45 reports (36 naming a single suspected medicine) and no reported death; the commonest terms were nausea (9), vomiting (7), diarrhoea (6), abdominal pain (5), headache (5) and urticaria (4). "Berberine" matched 7 medicines (mostly B. aristata products) with 20 reports and no death: vomiting (6), diarrhoea (5), nausea (3), liver injury (3, none with a single suspected medicine), constipation (2) and drug interaction (2). Spontaneous reports cannot establish cause or frequency, and none of these products is barberry bark alone. Grade: spontaneous reports; the pattern matches the gastrointestinal effects seen in berberine trials.

Overseas regulatory review (European Union; no standing in Australia). At the European Commission’s request, the European Food Safety Authority’s Panel on Nutrition, Novel Foods and Food Allergens endorsed a draft opinion on 29/01/2026 on the safety of berberine-containing plant preparations used in food supplements; B. vulgaris root and bark is one of the 13 plant materials it covers, and the draft was released for public consultation in 2026 [60]. The Panel found in vitro evidence of gene mutation and chromosomal damage by berberine, with confirmation in vivo lacking, and no adequate repeated-dose toxicity study of berberine alone. For B. vulgaris it retrieved no eligible genotoxicity study and no eligible mammalian toxicity study. It attributed carcinogenic activity in rodents to goldenseal (Hydrastis canadensis) rhizome and root, and idiosyncratic liver injury to greater celandine (Chelidonium majus) herb; neither finding concerns barberry. It also noted transient gastrointestinal effects of berberine supplements and a risk of interactions through CYP3A4. Its overall conclusion was that the available data do not allow a safe intake to be set for any of the preparations assessed [60]. No final opinion had been published when this was checked in October 2026, and the opinion concerns food supplements in the European Union. A web search the same day found no TGA safety alert or advisory on berberine or barberry. AIP comment (Medicine): for barberry the draft records gaps in the data and reports no harm observed with the herb itself. It supports the cautions already given for pregnancy, interacting drugs and high-dose berberine products, and it makes in vivo genotoxicity and repeated-dose studies of a characterised bark extract a research priority. Grade: regulatory review of in vitro, animal and human data; draft.

Referral. Anyone who is pregnant, breastfeeding, caring for a jaundiced newborn, taking ciclosporin or other prescription medicines, or managing diabetes should consult a degree-qualified herbalist with competencies and adequate training in pharmacognosy before using barberry bark. Fainting, palpitations or a racing heart while taking a berberine product, or yellowing of the skin or eyes in a baby, needs urgent medical assessment.