When food joins in

Interactions between foods and medicines are well known, but in everyday practice they are regularly underestimated — by customers and at times in the counselling conversation too. Yet the pharmacy is the ideal place to catch them: with a new prescription in particular, a brief note on what goes with the tablet and what does not is worthwhile.[3] This article sorts the practically relevant interactions by mechanism and translates them into concrete counselling rules.

Four ways in which food influences active substances

The countless individual cases can be traced back to a few mechanisms. First, the inhibition or induction of drug-metabolising enzymes — above all CYP3A4 — which makes plasma levels rise or fall (grapefruit). Second, complex or chelate formation with polyvalent cations from milk, minerals or antacids, which reduces the absorption of whole drug groups. Third, pharmacodynamic interactions, in which a food component directly enhances or counteracts the drug effect (vitamin K against anticoagulants, tyramine under MAO inhibitors). Fourth, the influence on absorption and transporters — food can increase or decrease uptake depending on the substance.

Grapefruit & co.: the most prominent case

Grapefruit is the classic — and more dangerous than many think. The furanocoumarins it contains (bergamottin, dihydroxybergamottin) and the flavonoid naringin inhibit the enzyme CYP3A4 above all in the gut. A single glass of grapefruit juice inhibits metabolism for around 24 hours; because the inhibition is irreversible and the enzyme has to be newly formed, the effect lasts several days.[1] [2]

The consequence: for substances metabolised via CYP3A4, bioavailability rises — at times into toxic ranges. Affected are, among others, statins (simvastatin, atorvastatin — but not rosuvastatin, pravastatin or fluvastatin), calcium antagonists (e.g. felodipine), immunosuppressants (ciclosporin, tacrolimus, everolimus), certain benzodiazepines, individual antiarrhythmics and certain oral anticoagulants.[2] [1] With an affected statin, muscle complaints up to rhabdomyolysis threaten.[2]

Two subtleties for counselling: pomelo and bitter oranges act similarly, and in rare cases grapefruit conversely lowers uptake (inhibition of the OATP transporter). The clear message at the counter is: anyone taking an affected substance consistently avoids grapefruit products — separating them in time is not enough because of the long duration of inhibition.[1]

Milk, calcium and iron: the complex formers

Polyvalent cations — calcium from dairy products and fortified mineral water, iron from preparations, aluminium and magnesium from antacids — form poorly soluble complexes with certain active substances. The substance is then absorbed less well and, in extreme cases, the therapy is rendered ineffective.[5]

Particularly relevant are tetracyclines (e.g. doxycycline) and fluoroquinolones (e.g. ciprofloxacin): here an interval of at least two hours before to six hours after calcium-containing foods or preparations is recommended.[4] Bisphosphonates have very low bioavailability anyway and must be taken on an empty stomach, with tap water and in an upright position — not with calcium-rich mineral water.[9] Levothyroxine belongs here too: in the morning on an empty stomach, 30 to 60 minutes before breakfast and separated from calcium, iron or aluminium sources.[5] [9]

Vitamin K and anticoagulants: consistency instead of avoidance

Vitamin K antagonists — in Switzerland phenprocoumon (Marcoumar) and acenocoumarol (Sintrom) — inhibit the formation of vitamin K-dependent clotting factors.[6] Foods rich in vitamin K such as spinach, broccoli or Brussels sprouts can therefore weaken the effect. The decisive counselling point: these vegetables need not be avoided, but should be eaten in as constant a quantity as possible — large fluctuations destabilise the INR.[7]

Useful to know for the distinction: the direct oral anticoagulants (DOACs) do not act via vitamin K and are in this respect independent of diet — here other aspects are more to the fore (e.g. taking certain preparations with a meal, caution with grapefruit for CYP3A4/P-gp substrates).[1]

The cheese effect: tyramine and MAO inhibitors

One of the best-known — and most dangerous — interactions concerns tyramine-rich foods under MAO inhibitors. Mature cheese, smoked and cured products, sauerkraut or red wine contain a great deal of tyramine; if this biogenic amine is no longer broken down because of the enzyme inhibition, a life-threatening rise in blood pressure can result — the cheese effect.[8] Warning signs are sudden severe headache, neck stiffness or chest pain; in that case immediate medical help is needed.[10]

The distinction is important: under non-selective MAO inhibitors such as tranylcypromine a strict low-tyramine diet is mandatory. Under selective inhibitors (moclobemide, selegiline, rasagiline) the interaction is largely uncritical.[8] If a non-selective MAO inhibitor is newly dispensed, dietary counselling is an obligatory part of it.

Alcohol, liquorice and others

Alcohol has broad interaction potential. Clinically particularly relevant is the disulfiram-like reaction with metronidazole (nausea, vomiting, flushing, palpitations); alcohol also increases the risk of gastrointestinal ulcers with NSAIDs and enhances the sedative effect of many centrally acting medicines.[9]

Liquorice (glycyrrhizin) promotes sodium and water retention and potassium loss in larger quantities — with the risk of raised blood pressure and hypokalaemia. Caution is required in hypertension, cardiovascular disease, diabetes and pregnancy, likewise in combination with diuretics or digoxin.[4] Pharmacodynamically, a potassium-rich diet also acts towards hyperkalaemia (in combination with ACE inhibitors, sartans or potassium-sparing diuretics) — a point that counts above all with salt substitute products.

The most important interactions at a glance