What is a food and what is a medicinal product in the European Union? Use of the benchmark dose (BMD) methodology to define a threshold for “pharmacological action”

The decision criterion for the demarcation between foods and medicinal products in the EU is the significant “pharmacological action”. Based on six examples of substances with ambivalent status, the benchmark dose (BMD) method is evaluated to provide a threshold for pharmacological action. Using significant dose–response models from literature clinical trial data or epidemiology, the BMD values were 63 mg/day for caffeine, 5 g/day for alcohol, 6 mg/day for lovastatin, 769 mg/day for glucosamine sulfate, 151 mg/day for Ginkgo biloba extract, and 0.4 mg/day for melatonin. The examples for caffeine and alcohol validate the approach because intake above BMD clearly exhibits pharmacological action. Nevertheless, due to uncertainties in dose–response modelling as well as the need for additional uncertainty factors to consider differences in sensitivity within the human population, a “borderline range” on the dose–response curve remains. “Pharmacological action” has proven to be not very well suited as binary decision criterion between foods and medicinal product. The European legislator should rethink the definition of medicinal products, as the current situation based on complicated case-by-case decisions on pharmacological action leads to an unregulated market flooded with potentially illegal food supplements.

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► The benchmark dose (BMD) is introduced to define a threshold for pharmacological action.
► Six examples include caffeine, alcohol, lovastatin, glucosamine, Ginkgo biloba, melatonin.
► Several products currently sold as food supplement are medicinal products.
► The definition of medicinal products in EU law needs revision to avoid complicated case-by-case decisions.