Twelve Inhibitors of CYP3A & Related Information

Of the senolytic activators fisetin, apigenin, and quercetin, apigenin and quercetin appear to be the most potent inhibitors of CYP3A. Neither is assimilated well. Chrysin is thought to be among the most potent inhibitors but it is very poorly assimilated. Other inhibitors include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal, and of course grapefruit. Berberine is also a CYP3A inhibitor but the effect is strongly dose dependent with a large dose likely required for effect. Other than grapefruit (below) I have not yet determined the time required for each to reach peak inhibition in humans.

Consensus in the literature suggests drinking grapefruit four hours before taking rapamycin, where it peaks at 47% CYP3A inhibition. The half-life of grapefruit juice’s inhibition of CYP3A enzymes is said to be about 24 hours; 72 hours is required to lose all effect. Drinking grapefruit one hour in advance, which is often suggested, does not produce the same effect. However, I have not seen the inhibition curves that would tell us what degree of inhibition could be expected at one hour.

Given that any one of several of these substances will inhibit CYP3A at the ~50% level, and that we know very little about the effect of stacking them, caution would be prudent if combining more than one inhibitor.


The availability of inhibition curves would certainly be useful.

Another factor in this is that when considering the effect of CYP3a4 inhibitors, the distinction between reversible and irreversible inhibition can be very significant.

For example, I use the inhibitor dasatinib in my senolytic cocktail on the day before my sirolimus dose. It is my understanding that dasatinib is reversibly bound to the enzyme so I don’t expect it to have much lingering effect the following day.

Watch the effects on HDAC.