Title:Association of flavonoid-rich foods and statins in the management of hypercholesterolemia: a dangerous or helpful combination?
Volume: 16
Issue: 9
Author(s): Ilaria Peluso, Maura Palmery and Mauro Serafini
Affiliation:
Keywords:
Cytochrome P450, esterases, flavonoids, food-drug interactions, phase III transporters, statins, uridine diphosphate glucuronosyltransferases.
Abstract: Statins and dietary modifications are the cornerstone of hypercholesterolemia management. Although it
is well known that possible adverse effect of statins can occur due to drug-drug interactions, food-drug interactions
are a commonly overlooked aspect. In particular, flavonoids could interfere with statins’ bioavailability through
different mechanisms, such as competition with cytochrome P450 (CYP) enzymes, esterases, uridine diphosphate
glucuronosyltransferases and transporters (P-glycoprotein, multi-drug resistance-associated proteins, organic anion
transporting polypeptides, breast cancer-resistance protein and monocarboxylate transporters). Transporters are
characterized by low substrate specificity and flavonoid- rich foods could interfere with the bioavailability of all statins at this level. On
the other hand, in addition to being substrates of drug metabolism/ transport systems, flavonoids are also able to modulate gene expression
of enzymes and transporters. Therefore, long-term transcriptional induction may increase the clearance of statins, despite flavonoids
act as competitive inhibitors after bolus consumption. In humans, major interactions were observed between grapefruit juice and statins
that are substrates of P-glycoprotein/CYP3A, but other fruit juices also affect the bioavailability of statins that are not metabolised by
CYP. Even if flavonoids could play a role in the prevention of hypercholesterolemia, the question whether there’s a helpful or dangerous
association between flavonoid-rich foods and statins, due to the interactions between flavonoid-rich foods and statins and the potential
associated adverse effects of statins, remain unanswered. Therefore, the anamnesis of patients must include detailed information about
their eating habits and the present review suggests monitoring and reporting any possible case of interaction between a prescribed statin
and food.
