The only difference being that instead of cutting up an orange and eating the pieces with breakfast and lunch, today I cut up a grapefruit instead of an orange. I also take my prescription for MitoMix with 300 mg of Ubiquinol at breakfast and also lunch.
A half hour before lunch I had so much energy, I had to Google to see if there was any study that showed a relationship between grapefruit and ubiquinol (coenzyme Q10). To my surprise there was. A study out of Japan and published in Food Chemistry in 2010 found that "We have demonstrated that a higher cellular uptake of CoQ10 was achieved in the presence of grapefruit juice." The uptake was increased by almost 50%.
Nice bit of observational science, BeautifulDay.
This paper says it is the
psoralen in grapefruit juice that inhibits the P-glycoprotein in the membrane of cells, which in turn leads to an increased absorption of Q10 into the cells, as found in the Japanese
study.
It is thought that P-glycoprotein acts as a transmembrane pump which removes drugs from the cell membrane and cytoplasm. Ref:
1 So by inhibiting this pump, you can get more drugs or supplements into the cell.
The paper also points out that the way grapefruit juice affects the pharmacokinetics of drugs may be due to P-glycoprotein inhibition rather than, or in addition, to CYP3A4 inhibition (it is the
bergamottin in grapefruit juice that inhibits CYP3A4, which then slows down elimination of drugs from the body, thus potentiating drug effects).
In other words, when it comes to drugs, grapefruit juice may have a dual effect: bergamottin increasing blood levels of the drug by inhibition of the liver enzyme CYP3A4, and then psoralen increasing the intracellular uptake of the drug by inhibiting P-glycoprotein.
There also appear to be several drugs and supplements which inhibit P-glycoprotein, some potently, which may be more effective than grapefruit juice. For example, the antifungal drug itraconazole is a potent inhibitor of P-glycoprotein. Ref:
1
Other P-glycoprotein inhibitors include: clarithromycin, erythromycin, ritonavir and verapamil. Whereas P-glycoprotein inducers include rifampicin and St John’s wort. Ref:
1
Intriguingly, all these P-glycoprotein inhibitors are also CYP3A4 inhibitors. It says
here:
As many P-glycoprotein substrates are also substrates of CYP3A4 and because P-glycoprotein inhibitors are also inhibitors of CYP3A4, many drug-drug interactions are related to inhibition or induction of both P-glycoprotein and CYP3A4.
So with quite a few of these drugs, you get a dual effect on both P-glycoprotein and CYP3A4. In the case of Q10 though, as was pointed out earlier, CYP3A4 has no effect on this.
Some other P-glycoprotein inhibitors are listed in
Table 1 of
this paper.
And
this paper says that the flavonoids quercetin and rutin among others are P-glycoprotein inhibitors.
I am going to try this grapefruit juice + Q10 protocol tomorrow (and I might also add some itraconazole, since I have some of this drug in stock, and perhaps some rutin too).
However, just how effective this grapefruit juice + Q10 protocol will be for ME/CFS patients in general is hard to say. In
this post that you mention that you suffer from a mitochondrial disease, so perhaps that might explain why the increased levels of intracellular Q10 work so well for you.