8 replies to this topic

[a.maier]

A week or so earlier there was a thread on this topic but I found it got locked.
Since I myself take resveratrol+curcumin+quercetin combo as recommended by Imminst.org, I think the potential danger of mixing a number of P450 inhibitors deserves a serious discussion so here I am strating a new thread.


Resveratrol
http://www.google.co...r...q=&gs_rfai=
http://www.google.co...R...q=&gs_rfai=

Curcumin
http://www.google.co...C...q=&gs_rfai=
http://www.google.co...C...q=&gs_rfai=

Quercetin
http://www.google.co...q...q=&gs_rfai=
http://www.google.co...Q...q=&gs_rfai=

Piperine(=Bioperine)
http://www.google.co...p...q=&gs_rfai=
http://www.google.co...b...q=&gs_rfai=


I did a through homework by reading at least first 3 pages of articles for each search result. All studies seem to agree that resveratrol, curcumin, quercetin and bioperine are potent inhibitors of P450.

Now I have always thought P450 is only involved in drug metabolism but it turned out not so simple. P450 is a family of the most powerful detox enzymes in our system, it breaks down all kinds of harmful chemicals we inhale and ingest everyday, e.g. air pollutants, food additives and pesticides to name a few. As such, it comes as no surprise that most detox programs rely on supplements that induce(amplify) P450 activity and unfortunately resveratrol, curcumin, quercetin and bioperine are doing exactly the opposite.

Then I came across this article. It appears to be a press release by one resveratrol vender.
http://www.prwebdire...prweb469646.php

A couple of points caught my eyes:

"Claims that resveratrol is not "biologically available" are mistaken. Resveratrol is linked (conjugated) to a molecule called glucuronate in the liver, which extends its life in the blood circulation up to 9 hours. The delivery of resveratrol to tissues is then facilitated by an enzyme called glucuronidase that releases resveratrol."

It appears that resveratrol is inherently bioavailable and there is no need to tweak it for better absorption.

"Resveratrol is not suggested for growing children or pregnant females."

I did more research on this one and learned that Resveratrol retards growth of fetus and children by suppressing new blood vessel formation. I would think that it may be wise for bodybuilders and muscle bulking athletes too, not to supplement resveratrol.

"Prescription medications should not be taken at the same time as resveratrol pills. Resveratrol and quercetin inhibit detox (cytochrome p450) enzymes in the liver which protectively dull the effects of medications. If these enzymes are inhibited, medications may work too well, for example, causing blood pressure to drop a bit too far if taking blood pressure pills, or causing liver problems if taking statin cholesterol-lowering drugs. Since resveratrol is rapidly metabolized, these effects are usually transitory. This is similar to the problem of drinking grapefruit juice prior to taking medications. If in need of more information, ask your pharmacist about cytochrome p450 reactions."

Then it hit me. I take statin and remember that I was cautioned not to take more than a cup of grapefruit juice a day and now I understand why: grapefruit juice inhibits P450 and it is this exact P450 inhibiting side effect that resveratrol, curcumin, quercetin and bioperine share. I dialed my doctor right away only to hear him barking at me to immediately quit taking the combo. According to him resveratrol, curcumin, quercetin and bioperine's P450 inhibition are orders of magnitude higher than that of grapefruit juice. He also disagrees with the statement "these effects are usually transitory".
"Don't go wild with curry either" and he hung up/

Will see him in his office next week and meanwhile I further searched the net and found that it is not just statins but myriad of drugs including popular NSAIDs, antibiotics, antifungals, contraceptives, benzos, SSRIs, arthritis and cardiovascular/heart/BP medications that should not be mixed with P450 inhibitor. I would guess red yeast rice is no exception either.

My bottom line:
If you are on prescription medications, you should not take any of resveratrol, curcumin, quercetin and bioperine without first consulting your doctor. If you are not on prescription medications, you should still be cautious on mixing these four since no matter how beneficial they are thought to be, they share one undeniable adverse effect that they all potently inhibit our body's natural detox system, P450, which IMO should be working in overdrive mode 24/7 as we breathe and eat plenty of harmful pollutants and chemicals every day. I definitely wouldn't go for triple/quadruple combo whammy, maybe not even mixing any two of the four. I would go for just one in small dose. But as for me for now, I have no choice but quitting them all at once as strongly advised by my doctor.

Lesson I learned:
There is no panacea. Not surprising albeit disappointing. Supplementing, like anything else in life, is all about compromise and don't let anyone tell you otherwise.

[maxwatt]

Wirgentlich spricht ihr deutsch? Ich weiss nicht.

Full-circle, you are extremely transparent in your creation of another alias.

And by the way, links google searches do not have the weight of evidence that references to scientific journals have.
And for the record: Imminst does NOT recommend Curcumin or Quercetin or ioperine either individually or in combination. Individual posters have done so, or recommended not to take them.

Knock yourself out.

[bobdrake12]

And for the record: Imminst does NOT recommend Curcumin or Quercetin or ioperine either individually or in combination.

I've been taking Resveratrol and Curcumin from Life Extension for about 4 years and found them beneficial.

I don't mix the two but take them at different times of the day.

I take Curcumin with freshly squeezed grapefruit juice.

I don't use Big Pharma products.

Other than Big Pharma, is there a reason Imminst does not recommend using then?

Edited by bobdrake12, 17 April 2010 - 12:36 PM.

[maxwatt]

And for the record: Imminst does NOT recommend Curcumin or Quercetin or ioperine either individually or in combination.

I've been taking Resveratrol and Curcumin from Life Extension for about 4 years and found them beneficial.

I don't mix the two but take them at different times of the day.

I take Curcumin with freshly squeezed grapefruit juice.

I don't use Big Pharma products.

Other than Big Pharma, is there a reason Imminst does not recommend using then?

Imminst is agnostic. Not recommending is not the same as recommending not to. Some members such as Michael Rae recommend against taking any phyto-chemical for life extension purposes, including resveratrol. Others here believe it can be beneficial and post about it, referencing studies on the effects pf various substances. A recent study showing a synergy between resveratrol and curcumin against cancer prompted some discussion on that. Theoretically, quercetin would inhibit sulfonation enzymes, making more resveratrol available in the blood. I believe this has been measured. Bioperine inhibits various CYP (P450) enzymes that gluoronate various phyto-chemicals. However, glucoronidation is not the major metabolic pathway that eliminates resveratrol, so it would robably not have much effect on resveratrol blood serum levels. Someone sells a combination curcumin/bioperine pill which is said to be more effective than curcumin alone. Maybe, maybe not. Many members recommend against taking any bioperine at all.

[joe57777]

Wirgentlich spricht ihr deutsch? Ich weiss nicht.

Full-circle, you are extremely transparent in your creation of another alias.

And by the way, links google searches do not have the weight of evidence that references to scientific journals have.
And for the record: Imminst does NOT recommend Curcumin or Quercetin or ioperine either individually or in combination. Individual posters have done so, or recommended not to take them.

Knock yourself out.

Max, I did not want to believe maier about Resveratrol's p450 inhibition but here is a pub-med article:

http://www.ncbi.nlm....pubmed/20027150 If indeed it is not a good thing to inhibit p450, then Resveratrol may do more harm than good let alone Curcumin and Quercetin.

Please advise.

[joe57777]

Wirgentlich spricht ihr deutsch? Ich weiss nicht.

Full-circle, you are extremely transparent in your creation of another alias.

And by the way, links google searches do not have the weight of evidence that references to scientific journals have.
And for the record: Imminst does NOT recommend Curcumin or Quercetin or ioperine either individually or in combination. Individual posters have done so, or recommended not to take them.

Knock yourself out.

Max, I did not want to believe maier about Resveratrol's p450 inhibition but here is a pub-med article:

http://www.ncbi.nlm....pubmed/20027150 If indeed it is not a good thing to inhibit p450, then Resveratrol may do more harm than good let alone Curcumin and Quercetin.

Please advise.

I just found in one of maier's Resveratrol articles that Resveratrol has an affect on p450 but here is the conclusion from that study which is surprising and contrary to maier's said conclusion: "9 and 89 μM. These results suggest that resveratrol is a selective human P450 1A1 inhibitor, and may be considered for use as a strong cancer chemopreventive agent in humans."

Therefore, maier, I would consider Resveratrol a good thing with information from your own example article.

Please explain this maier.

[mikeinnaples]

Personally, I take my statin in the AM and my resv/curcumin/resv in the afternoon. This gives me 15 hours after i take the P450 inhibitor before I take a statin ...and 9 hours after I take the statin before I take the P450 inhibitors.

This is my own personal best practice though.

[j87]

 

 

Wirgentlich spricht ihr deutsch? Ich weiss nicht.

Full-circle, you are extremely transparent in your creation of another alias.

And by the way, links google searches do not have the weight of evidence that references to scientific journals have.
And for the record: Imminst does NOT recommend Curcumin or Quercetin or ioperine either individually or in combination. Individual posters have done so, or recommended not to take them.

Knock yourself out.

Max, I did not want to believe maier about Resveratrol's p450 inhibition but here is a pub-med article:

http://www.ncbi.nlm....pubmed/20027150 If indeed it is not a good thing to inhibit p450, then Resveratrol may do more harm than good let alone Curcumin and Quercetin.

Please advise.

 

I just found in one of maier's Resveratrol articles that Resveratrol has an affect on p450 but here is the conclusion from that study which is surprising and contrary to maier's said conclusion: "9 and 89 μM. These results suggest that resveratrol is a selective human P450 1A1 inhibitor, and may be considered for use as a strong cancer chemopreventive agent in humans."

Therefore, maier, I would consider Resveratrol a good thing with information from your own example article.

Please explain this maier.

 

 

Any more info on this?

[hav]

Here's a detailed writeup as well as a another article on statin interaction with P450s .

 

It looks like P450 is a class of enzymes and that specific statins only interact with a very limited number of them.  The stronger interaction P450s  enumerated are CYP3A4 (found in grapefruit) and CYP2C9.  The resveratrol study shows it affects CYP450 2D2 which doesn't look like one of the ones having an impact on any of the statins.  I would expect that the only drugs that antioxidants like resveratrol might interfere with are pro-oxidants, like those used in chemotherapy.  I think there is also some insinuation that antioxidants generally might reduce the effectiveness of supplements like l-arginine or l-cysteine, which promote NO production in blood vessel walls,  so you might want to avoid having antioxidants in your bloodstream at the same time.

 

Howard

 

Edited by hav, 23 June 2014 - 03:50 PM.