Huge energy today with Grapefruit and Ubiquinol (Coenzyme Q10). We'll see about tomorrow.

[researcher]

BTW, I just checked. The Nature Made brand doesn't use Ubiquinol right? Why not change to this form?

thanks

@BeautifulDay Did you see this message?

Thanks

 

[BeautifulDay]

Thanks @researcher

The studies point to Ubiquinol being the best form for absorption. That's the one recommended by my Mito doctor. However, each one of these by different vendors has different quality and fillers. My doctor said many have tested to be poor quality and not matching quantity.

In addition, to Ubiquinol, I've also had some improvement on Kaneka CoQ10. But it depends on the manufacturer. I go by how any of them makes me feel.

Right now I'm relying on the ubiquinol prescribed by my Mitochondrial Clinic (contained in Mito Cocktail made for me) and filled by the compounding pharmacy recommended by the Mito Clinic. I figure if I can't rely on them for quality, then there is a real issue. Sometimes, my prescription refill arrives a day or two late and then I use whatever form of CoQ10 is in the house.

 

[researcher]

Thanks @researcher

The studies point to Ubiquinol being the best form for absorption. That's the one recommended by my Mito doctor. However, each one of these by different vendors has different quality and fillers. My doctor said many have tested to be poor quality and not matching quantity.

In addition, to Ubiquinol, I've also had some improvement on Kaneka CoQ10. But it depends on the manufacturer. I go by how any of them makes me feel.

Right now I'm relying on the ubiquinol prescribed by my Mitochondrial Clinic (contained in Mito Cocktail made for me) and filled by the compounding pharmacy recommended by the Mito Clinic. I figure if I can't rely on them for quality, then there is a real issue. Sometimes, my prescription refill arrives a day or two late and then I use whatever form of CoQ10 is in the house.

Gotcha.

I don't have the time to read the entire thread. Could you tell me whether you're still having the same results?

Basically what you found out is that CoQ10 (whatever form) is highly absorbed if you take grapefruit seed extract. Correct?

 

[blueberry]

I've been trying it......definite improvement in stamina. Worked today, came home very fatigued, but after a rest I did some crafting......haven't done that in over a year (i.e. since the relapse) Dosage +quality seems crucial. I've wasted money on so many brands of CoQ10 that had no effect. Drs Best Kaneka at 400mg seems good to me. I've had to be careful to still take my 5-10 min meditation breaks at work. Good energy levels all afternoon. The drive home killed me, as usual. But recovered quicker. So far, so good!!

 

[BeautifulDay]

I've been trying it......definite improvement in stamina. Worked today, came home very fatigued, but after a rest I did some crafting......haven't done that in over a year (i.e. since the relapse) Dosage +quality seems crucial. I've wasted money on so many brands of CoQ10 that had no effect. Drs Best Kaneka at 400mg seems good to me. I've had to be careful to still take my 5-10 min meditation breaks at work. Good energy levels all afternoon. The drive home killed me, as usual. But recovered quicker. So far, so good!!

Good morning @blueberry

Thank you for the update. Please keep updating with your progress (good, bad, obstacles). It's all very helpful and informative.

 

[BeautifulDay]

I don't have the time to read the entire thread. Could you tell me whether you're still having the same results?

Basically what you found out is that CoQ10 (whatever form) is highly absorbed if you take grapefruit seed extract. Correct?

Hi @researcher

Nope, it's not grapefruit seed extract. That is something completely different from grapefruit and grapefruit juice.

I'm hoping at some point to have time to add to my first post with a summary for those who don't want to read the entire thread. I'll post when I've gotten to that.

In the mean time, I'll keep updating with progress.

 

[BeautifulDay]

Update - report from first day with red grapefruit juice instead of grapefruit

Yesterday, I had the first normal day in decades (no laydowns, and I even went to a school board meeting until 9:00 p.m.).
It was also the day that I switched over from 1/2 grapefruit twice a day (with 300 mg of ubiquinol) to 100% ruby red grapefruit juice (3/4 cup twice a day).

The day started with me realizing I was out of coffee. Yikes. So I had two cups of black tea during the day instead. I made breakfast, kids lunches, did a load of dishes and a load of laundry, got them out the door to school, and got on the treadmill for 30 minutes of walking.

After 30 minutes, I was feeling tired and decided I wouldn't shoot for the other 30 minutes of my walk. But then I got a huge burst of energy and started to clean our bedroom. It's the messiest room in the house with the largest piles. It will take me a full week to clean, but I made unbelievable progress. Moving from upstairs to downstairs as needed putting away kids items from crayons, markers, colored pencils, balls, projects, and games. I threw away items that were stained or had holes or were out of style. I put clothes that no longer fit into two bags for goodwill.

It was similar to the energy that I had the day I cleaned my daughters room, but I didn't need any lay downs (not even later in the day). At 4:00 I realized I had yet to lie down. I was able to just keep going throughout the day.

A friend then reminded me that there was a school meeting of parents and the school board from 7:00 - 9:00 p.m. I hadn't made one of those in a decade. She offered to pick me up. My energy was starting to dip, and I thought there is not a chance I'll be awake or have any energy to attend that meeting. But then I thought, what if I add in a small amount of ubiquinol with another glass of grapefruit juice (this was at 4:30 p.m.). Would I be able to make it through the meeting?

I then took 120 mg of ubiquinol (not my prescription, just an over the counter pill) with another 3/4 cup of grapefruit juice. By the time my husband came home, I was talking a bit too fast and was bouncy and perky. A little too bouncy and perky. Had I been stopped by a police officer, he might have thought I was on speed. I wasn't jittery like with too much coffee. That overshooting the energy probably lasted for 30 minutes. My friend picked me up for the school meeting and I lasted and was fully awake the entire time. Sitting in this meeting did remind me how ADHD I have become. I really needed a figit toy. Looking at my phone would have appeared rude.

One thought. I read an article that suggested coffee shouldn't be taken with CoQ10 because it rushes things through the system too fast, reducing the time for absorption. I believe it was more of a theory. So maybe my lack of coffee yesterday had an impact too. Since I need coffee for BM, this morning I did add back in my coffee.

I decided today to have my morning coffee an hour after my 300 mg ubiquinol and 3/4 cup of red grapefruit juice. I'm feeling really energetic today. Kids are off to school. I've already gotten in 30 minutes of my walk. I'm hoping to do the other 30 minutes later today. I never get back to doing walking in the afternoon because I'm too tired - so we'll see if it actually happens. And I'm excited to go back and tackle another corner of our bedroom. I'll let you know how it goes.

 

[andyguitar]

I am so pleased for you @BeautifulDay and now your improvement has gone on so long we can say it is certainly not the placebo effect. Just one word of caution. Dont forget that although you have more energy it will take a while before your body- in particular your muscles- gets back to normal strength.

 

[BeautifulDay]

I am so pleased for you @BeautifulDay and now your improvement has gone on so long we can say it is certainly not the placebo effect. Just one word of caution. Dont forget that although you have more energy it will take a while before your body- in particular your muscles- gets back to normal strength.

@andyguitar I wish I had thought of that yesterday. Today my thighs are hurting from all the knee bends spent picking things up off the floor yesterday. Today, I've been trying to work on items higher off the ground (piles on bureaus, etc...) that involve less knee bends. But despite the thighs, I have an abundance of energy. I did take a half hour lay down at 1:00. It's another great day so far.

 

[andyguitar]

Yeah you will get pain here and there as a result of more activity and hopefully thats all you get. But i knew 2 sufferers who had a diagnosis of ME who both got a lot better very quickly, did to much, and ended up with something called 'shin splints'. This is something that those who work out get and can be pretty painful. They recovered ok but it's not much fun and is easy to avoid.

 

[BeautifulDay]

Yesterday, I cut my mid-afternoon Ubiquinol dose in half to see if it would get rid of that 30 minute speed like episode I had the day before while still keeping up energy into later in the day.

This is what I ended up taking yesterday. 300 mg of Ubiquinol with 3/4 cup of ruby red grapefruit juice with breakfast. I didn't have my coffee until an hour later. I had another 300 mg of Ubiquinol with 3/4 cup of ruby red grapefruit juice with lunch. I then had my second cup of coffee an hour later. I had another 60 mg Ubiquinol with 3/4 cup grapefruit juice mid-afternoon.

After the above doses, last night I was vacuuming the steps going down into the basement at 7:00 p.m., and then I swept the kitchen floor. I then thought about going on the treadmill for those last 30 minutes of my walk. I decided not to do it, worrying that exercising so late might impact my sleep. But other than the 30 minute lay down yesterday, it was an exceptional day of energy.

I'm not having trouble getting to sleep. I always wake (and have always woken up) in the middle of night for a few hours. This has not changed. I was told that for people with ATP or CoQ10 issues, that not having enough ATP in the sleep center of the brain can cause that night time wakefulness. I might try taking another low dose at dinner to see if it helps or hurts sleep.

I’m also wondering if it’s the combination mid-afternoon that is extending my energy into much later in the day, or is it just the grapefruit juice or just the Ubiquinol? Another thing to self-test.

I do hope the pharmaceutical companies figure this all out and develop an extended release medication. I’d love to see the little ups and downs during the day evened out. I’m getting spoiled having energy and the little dips (while nothing like dips in the past) are not fun.

Until they do, I’ll probably also self-test breaking up those 300 mg doses to two 150’s each and spreading them out to see if that creates a more even rhythm to the energy flow during the day.

Since I also take my B12, D3, and B2 (Ribofalvin) supplements with breakfast, I’m also wondering if any of the slight boost is also from possible increased absorption of those items due to the grapefruit juice.

In the meantime, our college daughter comes home soon for 48 hours during Easter Break. That’s when I’ll have a better idea if it’s just me, or if other family members with Mitochondrial Disease in our family also respond positively to the combination. There's not a chance she'll buy grapefruit juice in college, unless she sees the positive results first at home. The Mito Doctor already has her on the Ubiquinol, so it’s just a matter of adding in the ruby red grapefruit juice. If she does respond positively, then it will be onto the other two kids.

Not everything has disappeared. This morning I was stuck standing at a counter waiting for a clerk. I had to keep moving so that the low pulse pressure wouldn't drop me (faint). I had plenty of energy to move and bring the blood that gets stuck in my legs when standing, back up to my brain. But most people don't have to keep moving in order not to drop.

Some things are damaged in the womb from lack of enough ATP (for example some with MitoD have chiari malformations). It would be nice if the increased ATP would fix such things when given later in life, but it's probably highly doubtful. But then again, maybe it will stop damage that would otherwise occur.

 

[E.man]

"Red grapefruit juice " !

Bloody hell. I still haven't found any type of juice. (End of the world here........apparently ).

 

[Hip]

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.

 

[blueberry]

My ability to report back is being hampered by this really annoying on again off again viral infection that I've had for weeks. It's making it really hard for me to see what's going on with my energy levels. I'm working on clearing it out on a number of fronts. What I will say is that I'm not dosing in the mid afternoon anymore, as I ended up "overdoing" in the evening......giddy on the sweet taste of having some energy in the evening, I ignored my body's request for rest. I'm doing 400mg in the am and 200 at lunchtime.

 

[BeautifulDay]

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.

@Hip this is very interesting. Thank you for finding it and following up.

And this paper says that the flavonoids quercetin and rutin among others are P-glycoprotein inhibitors.

It looks like both quercetin and rutin are found in capers. Maybe a few more spices in tonight's dinner.
But then again, it looks like they are poorly absorbed.

According to Oregon State University:
"Quercetin
Oral supplementation with quercetin glycosides at doses ranging between 3 mg/day-1,000 mg/day for up to three months has not resulted in significant adverse effects in clinical studies (reviewed in 154). A randomized, placebo-controlled study in 30 patients with chronic prostatitis reported one case of headache and another of tingling of the extremities associated with supplemental quercetin (1,000 mg/day for one month); both issues resolved after the study ended (155). In a phase I clinical trial in cancer patients unresponsive to standard treatments, administration of quercetin via intravenous infusion resulted in symptoms of nausea, vomiting, sweating, flushing, and dyspnea (difficulty breathing) at doses ≥10.5 mg/kg body weight (~756 mg of quercetin for a 70 kg individual) (156). Higher doses up to 51.3 mg/kg body weight (~3,591 mg of quercetin) were associated with renal (kidney) toxicity, yet without evidence of nephritis, infection, or obstructive uropathy (reviewed in 154)."
http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids

The few capers I ever use probably wouldn't do much.

If you find out more, I'd love to hear. Also, please let me know how your self-test goes.

 

[BeautifulDay]

My ability to report back is being hampered by this really annoying on again off again viral infection that I've had for weeks. It's making it really hard for me to see what's going on with my energy levels. I'm working on clearing it out on a number of fronts. What I will say is that I'm not dosing in the mid afternoon anymore, as I ended up "overdoing" in the evening......giddy on the sweet taste of having some energy in the evening, I ignored my body's request for rest. I'm doing 400mg in the am and 200 at lunchtime.

@blueberry I'm sorry to hear you have been fighting a viral infection. Please keep posting your experience. My experience with a virus was similar. The things that normally impact my energy (such as a virus), still have an impact even when I'm on the grapefruit juice and Ubiquinol.

@blueberry I love the way you describe "Giddy on the sweet taste of having some energy in the evening." That's a perfect way of describing it. There are times I am giddy because I now have energy. To go from debilitating fatigue to having some energy is like a choir of angels coming down and singing. People who don't have debilitating fatigue could never understand the impact and joy that comes with energy.

 

[Hip]

It looks like both quercetin and rutin are found in capers. Maybe a few more spices in tonight's dinner.
But then again, it looks like they are poorly absorbed.

That's a good point, quercetin is poorly absorbed, with a bioavailability of about 4%. Rutin bioavailability may be higher, but I am not sure.

Though even with the poor bioavailability, I have found quercetin 500 mg overstimulating, and don't like it (quercetin acts on the same adenosine receptors as caffeine, which is why I think it produces overstimulation). I am fine with rutin 500 mg though.

Itraconazole I find makes me sleep more deeply, for some reason, which is nice. So I think I will use grapefruit juice and itraconazole to inhibit P-glycoprotein.

 

[sissypop]

I was so excited to stumble on this thread! Thank you @BeautifulDay . Unfortunately my first try of this this morning sent me back to bed for a 4 hour sleep.
This is usually the case for me, I read something that works for someone and I get so excited. Then it does absolutely nothing for me or makes me worse.
The bright side is that I may have found something for my insomnia.
But I'm going to try it again tomorrow.

 

[Alvin2]

Quercetin is one i know a lot about, Its bioavailability is low (a few percent), there is a bioactive form called EMIQ that is very bioavailaible (and much more pricey). It has a half life in the body (what gets in) of about 2 hours (iirc). All that said if all its doing is increasing absorption in the gut it may not matter that it has low bioavailability, it may not need to get into the bloodstream at all, and of the agents mentioned its probably the safest to consume regularly and has many actions in the body (it helps eliminate senescent cells for one) an its found in many vegetables and even coffee in small amounts. It may also reduce the risk of Parkinsons (or even treat it).

 

[pattismith]

Quercetin is one i know a lot about, Its bioavailability is low (a few percent), there is a bioactive form called EMIQ that is very bioavailaible (and much more pricey). It has a half life in the body (what gets in) of about 2 hours (iirc). All that said if all its doing is increasing absorption in the gut it may not matter that it has low bioavailability, it may not need to get into the bloodstream at all, and of the agents mentioned its probably the safest to consume regularly and has many actions in the body (it helps eliminate senescent cells for one) an its found in many vegetables and even coffee in small amounts. It may also reduce the risk of Parkinsons (or even treat it).

This surprises me, because Low fT3 is linked to disease severity in Parkinson and Quercitin (like most flavonoids) inhibits Deiodinase type 1, which means lower T3 (and higher rT3), so it looks contradictory...