3 replies to this topic

[InquilineKea]

This is something I've thought a while about.

As many of us know, grapefruit juice is a potent inhibitor of some Cytochrome P450 enzymes responsible for the breakdown of many drug compounds. This can lead to complications when it comes to certain drugs/supplements that become toxic in high doses. However, in the case of other drugs/supplements, it could be the case that grapefruit juice could then be beneficial (as it allows such drugs/supplements to act for longer periods of time before breaking down - this might be most useful for drugs/supplements that are expensive/limited but yet are relatively innocuous at higher-than-recommended doses). Has anyone thought about this?

[niner]

This is something I've thought a while about.

As many of us know, grapefruit juice is a potent inhibitor of some Cytochrome P450 enzymes responsible for the breakdown of many drug compounds. This can lead to complications when it comes to certain drugs/supplements that become toxic in high doses. However, in the case of other drugs/supplements, it could be the case that grapefruit juice could then be beneficial (as it allows such drugs/supplements to act for longer periods of time before breaking down - this might be most useful for drugs/supplements that are expensive/limited but yet are relatively innocuous at higher-than-recommended doses). Has anyone thought about this?

Sure, this comes up a lot. Grapefruit is a fairly potent inhibitor of CYP3A4, primarily in the gut. Other fruit juices have similar effects, though generally not as potent as grapefruit. 3A4 tends to oxidize hydrophobic compounds, particularly if they are large. Most supplements are natural products, and tend to be more on the hydrophilic side. As such, there aren't going to be many supplements for which 3A4 is on the critical metabolic path. The metabolic enzymes that seem to cause the most trouble around here are phase 2 conjugative enzymes responsible for glucuronidation and sulfation. These are the bane of resveratrol and curcumin users, for example. There are some compounds that inhibit these, e.g. quercetin for sulfation and piperine for glucuronidation.

Juices can be a real problem with some common drugs, like statins.

[krillin]

Br J Cancer. 2007 Jul 31;97(3):440-5.
Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study.
Monroe KR, Murphy SP, Kolonel LN, Pike MC.
1Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9175, USA.

In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii-Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06-1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (P(trend)=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.

PMID: 17622247

[InquilineKea]

Interesting

Little curcumin, when eaten, is absorbed-- 2 grams of curcumin alone resulted in undetectable to very low serum levels.[8] Much of it is excreted through glucuronidation. Co-supplementation with 20 mg of piperine (extracted from black pepper) significantly increased the absorption of curcumin by 2000%[8]. However, due to its effects on drug metabolism, piperine should be taken cautiously (if at all) by individuals taking other medications. Some benefits of curcumin, such as the potential protection from colon cancer, may not require systemic absorption. Alternatively, dissolving curcumin in hot water prior to ingestion, or in warm oily liquids, appears to increase bioavailability.