Berberine is an isoquinoline alkaloid found in various plants used in food supplements. These supplements are usually taken to regulate blood glucose and/or cholesterol levels, but no health claims are currently authorised in the European regulations for berberine-containing plants or for substances in the group of isoquinoline alkaloids. ANSES was called on by the Directorate General for Competition, Consumer Affairs and Fraud Control (DGCCRF) to establish safe conditions of use for food supplements made with plants or plant preparations containing berberine in France.
Regulations on berberine in food supplements
The Agency studied the regulatory status of berberine in various countries of the European Union and also analysed the data from the literature to assess its toxicity.
In Europe, the regulations on the use of berberine in food supplements vary depending on the country: this substance is authorised in some countries and prohibited or subject to restrictions in others, such as in Belgium, where a maximum daily dose of 10 mg has been set.
In France, several berberine-containing plants are marketed as food supplements. No maximum daily dose of berberine has been defined for these plants, but labels must include a warning advising pregnant women not to use these products.
A regulatory situation needing clarification
The clinical data in the literature show berberine to have pharmacological effects from 400 mg/day in adults, on the cardiovascular (effects on blood pressure and heart rate), nervous (anticonvulsant, antidepressant and analgesic effects) and immune (anti-inflammatory and immunosuppressive effects) systems, as well as on metabolism (hypoglycaemic and hypolipidaemic effects). This means that berberine acts as a drug and not as a food at this dose.
However, the review of the data did not rule out the possibility of pharmacological effects occurring at lower doses, including below the daily dose of 10 mg of isoquinoline alkaloids set in Belgium for food supplements.
Therefore, ANSES recommends undertaking further studies to identify the minimum dose associated with pharmacological effects, to provide a basis for defining the regulatory status of berberine-containing products.
Conditions of use that do not guarantee consumer safety
Because no robust toxicological studies were available, the experts were unable to establish a toxicity reference value (TRV) for berberine. They were only able to define an indicative toxicity value (iTV) of 1.7 μg/kg bw/day, which can be used temporarily, pending the determination of a TRV based on good-quality toxicological studies. This iTV corresponds to a dose of 0.1 mg/day for a 60 kg individual and is likely exceeded for a large number of food supplements currently on the market in France. Thus, in the absence of new data, their safety of use cannot be guaranteed. ANSES recommends that toxicological studies on berberine, undertaken according to the guidelines of the Organisation for Economic Co-operation and Development (OECD), be undertaken in order to establish a toxicity reference value.
ANSES also stresses that the consumption of food supplements made with plants or plant preparations containing berberine can pose risks including gastrointestinal disorders, hypoglycaemia and hypotension. As the risk is higher for children and adolescents, pregnant and breastfeeding women, diabetic individuals and individuals with liver or heart disorders, the Agency advises these population groups to refrain from consuming berberine-containing food supplements.
Moreover, in light of the numerous drug interactions identified by the experts, ANSES calls for extreme vigilance by healthcare professionals, since consuming berberine-containing food supplements in combination with a drug treatment can inhibit its effects or lead to adverse effects.