Many people like the bittersweet taste of grapefruit. The trendy pomelo, on the other hand, is appreciated for its fruity aroma. Both citrus fruits contain certain ingredients that interact with a large number of medicines and can lead to a serious health risk.
They look like giant grapefruits and yet they are different. The pomelo is a cross between a shaddock and a grapefruit. They are grown in Israel and China and have been enjoying increasing popularity in Europe for some time. Their peel is pale yellow to greenish, very thick and – unlike other citrus fruits – inedible. Before eating, the peel of the pomelo must be removed, as well as the white layer inside the fruit. Once peeled, the pomelo can be eaten raw.
Potentially dangerous ingredients
Grapefruits also block certain proteins in the body that are actually there to transport active substances into the cells. As a result, eating grapefruit and pomelo means that the active substances cannot be adequately absorbed by the body and some medicines work much more weakly than usual.
Which ingredients are responsible for the interactions?
The ingredients of grapefruit and pomelo that cause these undesirable effects include naringenin, naringin and dihydroxybergamottin. Other citrus fruits also show similar effects, namely shaddocks and bitter oranges (Seville oranges). Eating oranges (and drinking orange juice) is unproblematic – they do not contain these substances.
The ingredient of greatest relevance for possible interactions is the flavonoid naringin, which is enzymatically cleaved in the gastrointestinal tract into naringin glucuronides and the aglycone naringenin. In addition to the metabolite naringenin, the furanocoumarins bergamottin and 6′,7′-dihydroxybergamottin are also formed. These metabolic products of naringin all inhibit the cytochrome P450 isoenzyme CYP3A4 (CYP3A4 for short) and thus influence the metabolism of certain drugs.
However, the inhibition of CYP3A4 is limited to gastrointestinal CYP3A4. Interactions are therefore only relevant for orally administered drugs, not for other routes of administration.
The effects of the interaction with medicines are particularly evident with active substances that have low oral bioavailability. Bioavailability is a measure of how quickly and to what extent a medicine is absorbed and becomes available at its site of action. If grapefruit switches off the enzyme CYP3A4, it reduces the intestinal “first-pass effect” and the bioavailability of the medicine is increased. This can lead to serious complications, because the previously low bioavailability was taken into account when the medicine was dosed.
What advice is given to patients?
Grapefruit and pomelo lead to interactions in combination with orally taken medicines. Fruit, juice and other preparations of grapefruit and pomelo are equally affected. There is no safe minimum amount of grapefruit products. Pomelos and grapefruit are natural products – the amounts of bitter compounds they contain can vary greatly.
Leaving a time interval after eating the fruit does not prevent the undesirable effect either, as the plant compounds bind the enzymes permanently. Apart from that, the CYP3A4 enzyme is active to different degrees in each person, which makes the effects of grapefruit unpredictable. While the CYP3A4 enzyme in the intestinal wall is naturally rather weakly active in some people, in others it is up to eight times as active. And the more active the enzyme is, the stronger the effect of grapefruit and pomelo. Pomelos and grapefruit or their juice should therefore be avoided completely when taking active substances with known interactions.
Interactions
Active substances whose effect is increased by grapefruit/pomelo include, for example:
- Simvastatin (cholesterol-lowering drug)
- Ciclosporin (immunosuppressant)
- Carbamazepine (anti-epileptic drug)
- Amiodarone (anti-arrhythmic drug)
- Lovastatin (HMG-CoA reductase inhibitor)
- Verapamil, nifedipine, amlodipine, felodipine, nisoldipine, nitrendipine (calcium antagonists)
- Terfenadine, ciclosporin (anti-allergy drugs)
- Zolpidem (sleeping drug)
- Tolvaptan (drug for kidney disease)
- Fentanyl (painkiller)
- Sildenafil (drug for erectile dysfunction)
- Midazolam (sedative).
When taken at the same time as the anticoagulant phenprocoumon (e.g. Marcumar), naringin can increase the tendency to bleed.
The active substances cyclophosphamide (anti-cancer drug) and aliskiren/bilastine (drugs for high blood pressure) work less strongly in combination with grapefruit.
The effect of grapefruit (fruit or juice) can last throughout the day. Patients should be made aware of this. The interaction is not avoided merely by not taking the two at the same time. Grapefruit and pomelos cause an irreversible inhibition of CYP3A4 that can last from 24 hours to several days. Staggering intake achieves nothing; pomelos and grapefruit must be completely removed from the diet.
Ask your doctor or pharmacist
Many people are not aware that eating healthy fruit can have undesirable consequences, especially in connection with taking medicines, and that various interactions can occur. The number of medicines for which interactions with grapefruit/pomelo are found is constantly growing because a great deal of research is being done. To be completely sure, it is therefore best to ask your doctor or pharmacist whether interactions with grapefruit (or other foods) are possible when taking your medicine. In particular, advice at the pharmacy about the corresponding effects of various types of fruit – especially during the “citrus season” – is extremely important.
Sources:
– Vorsicht Wechselwirkungen – Was Apotheker zur Trendfrucht Pomelo wissen sollten. DAZ online, 02.01.2019
