1708 replies to this topic

[maxwatt]

This study indicates that an increased concentration of resveratrol overcomes glucuronidation of resveratrol, and that intra-cellular resveratrol, which isn't present in the plasma, may account for as much as 61% of the applied dose.

I still see no strong reason to mix quercetin in the dose.

Pharm Res. 2006 Sep;23(9):2107-15. Epub 2006 Aug 9. Links
Increased transport of resveratrol across monolayers of the human intestinal Caco-2 cells is mediated by inhibition and saturation of metabolites.Maier-Salamon A, Hagenauer B, Wirth M, Gabor F, Szekeres T, Jager W.
Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090, Vienna, Austria.

PURPOSE: The study's aim was to investigate the dose-dependent effect of sulfation and glucuronidation on intestinal absorption of resveratrol, a dietary constituent found in grapes and various medical plants. MATERIALS AND METHODS: The intestinal epithelial membrane transport kinetics and metabolism of resveratrol (10-200 microM) was studied using Caco-2 monolayers cultured in Transwells. RESULTS: Along with resveratrol it was possible to identify three metabolites, namely, resveratrol-4'-O-glucuronide (M1), resveratrol 3-O-gucuronide (M2), and resveratrol-3-O-sulfate (M3) by LC/MS and NMR. Efflux of the glucuronides M1 and M2 followed Michaelis-Menten kinetics significantly favouring basolateral efflux. The predominant metabolite was the monosulfate M3, however, its formation was strongly inhibited at higher resveratrol concentrations. As biotransformation was either inhibited or saturated, total amount of resveratrol transported across the Caco-2 monolayers increased as much as 3.5-fold at 200 microM resveratrol. This value might be even higher when taking into account the high intracellular concentration of resveratrol, which accounted for up to 61% of the applied dose. CONCLUSIONS: Our data demonstrate a concentration-dependent biotransformation of resveratrol in Caco-2 cells, which may also apply to human enterocytes affecting oral bioavailability.

PMID: 16952002

[health_nutty]

After having added 300mg of activin GSE to my regimine I've noticed an increase in the resveratrol effect. I'm noticing better mood, more energy, and appetite suppression. Interesting...

[ageless]

After having added 300mg of activin GSE to my regimine I've noticed an increase in the resveratrol effect.  I'm noticing better mood, more energy, and appetite suppression.  Interesting...

Cool... I've been using the Activin 200mg GSE from NSI along with my resv.

[niner]

The predominant metabolite was the monosulfate M3, however, its formation was strongly inhibited at higher resveratrol concentrations. As biotransformation was either inhibited or saturated, total amount of resveratrol transported across the Caco-2 monolayers increased as much as 3.5-fold at 200 microM resveratrol. This value might be even higher when taking into account the high intracellular concentration of resveratrol, which accounted for up to 61% of the applied dose. CONCLUSIONS: Our data demonstrate a concentration-dependent biotransformation of resveratrol in Caco-2 cells, which may also apply to human enterocytes affecting oral bioavailability.

Nice find, maxwatt! Bear in mind, though, that this is an in vitro experiment, with no liver around to cloud the picture. It's most directly related to resveratrol's passage through the intestinal epithelia, but not as much to resveratrol's fate in the rest of the system. My takehome from this is that resveratrol has a good chance of being intestinally absorbed, but it still faces first pass metabolism.

If quercetin is really a picomolar inhibitor of resveratrol sulfation, and it does that without inhibiting sulfation of everything else, that is a rather huge result... I guess that before wolfing a bunch of quercetin, I would want to know that I was not trashing a significant part of xenobiotic metabolism.

[tintinet]

That's the ticket! Just eat rat chow!!! Yeah!!! [tung]

[edward]

Interesting find Maxwatt. I remember reading somewhere that high single doses of resveratrol were important in overcoming such issues. I think also biotest, in their RES-V write up (yes its marketing but they had to have gotten the idea from somewhere)

"Our recommended dosage of REZ-V is three tablets once per day. It's best to take one large dose of resveratrol, instead of several smaller doses, because of the way it's metabolized. In essence, you want to overwhelm the body's ability to inactivate and excrete resveratrol, which is done through sulfation and glucuronidation (adding sulfate and beta-glucuronide groups).

This "overwhelming" process is accomplished at about 200 mg taken in one shot. A three-tablet dose contains 300 mg of pure resveratrol, which is also the dose we believe delivers the greatest benefit for the least cost."

[edward]

I went through biotest's 48 references for their article but couldn't find where they got the above information but maybe with more digging.

[health_nutty]

I went through biotest's 48 references for their article but couldn't find where they got the above information but maybe with more digging.

Let just say I'm not surprised.

[valjean]

Any idea what other substances are undergoing the same glucoronidation/sulfatation process as resveratrol ? And if these
substances are harmless (even better beneficial) they sould be
cheap and easy to obtain. For thoses who know my question is:
Is glucoronidation/sulfatation a standard procedure of the body
to process substances other than resveratrol?

Currently I'm opening my RESV caps and put the content into ~200ml
red vine and then I add 5000mg of grap seed powder after this I let
this mix alone for half an hour to give ETHO time to dissolve as much
as possible of the flavonoids/OPCs/RESV. Maybe it's a good idea to
give it a moderate microwave treatment. I'm not sure if this is reasonable, any suggestions ?

[valjean]

Any idea what other substances are undergoing the same glucoronidation/sulfatation process as resveratrol ? And if these
substances are harmless (even better beneficial) they sould be
cheap and easy to obtain. For thoses who know my question is:
Is glucoronidation/sulfatation a standard procedure of the body
to process substances other than resveratrol?

Currently I'm opening my RESV caps and put the content into ~200ml
red vine and then I add 5000mg of grap seed powder after this I let
this mix alone for half an hour to give ETHO time to dissolve as much
as possible of the flavonoids/OPCs/RESV. Maybe it's a good idea to
give it a moderate microwave treatment. I'm not sure if this is reasonable, any suggestions ?

[sablystone]

Does anyone know of a particular brand & type of wine that qualifies as RSV rich comparatively, relatively cheap, and tastes good?  The later being the most important to me.  (I'm no wine connoisseur obviously.)

Thanks!
Trance

Hi Trance, a french Pinot Noir has the most TRES. Try to stay away from blush reds, like Sangria, chianti etc. The bolder the flavor, likely the more polyphenols you're getting. In general, Pinot Noir's have the highest TRES levels. Red wine drinking is a habit/taste that takes time for some.

[markymark]

could everybody of you out there, who is doing before-and-after TRES blood work also provide testosterone, DHEAS and TSH before-and-after-values in addition to the other parameters of interest..?!

[health_nutty]

I'll have DHEAS and TSH for you, no testosterone.

Looking forward to some blood test results!

[malbecman]

The predominant metabolite was the monosulfate M3, however, its formation was strongly inhibited at higher resveratrol concentrations. As biotransformation was either inhibited or saturated, total amount of resveratrol transported across the Caco-2 monolayers increased as much as 3.5-fold at 200 microM resveratrol. This value might be even higher when taking into account the high intracellular concentration of resveratrol, which accounted for up to 61% of the applied dose. CONCLUSIONS: Our data demonstrate a concentration-dependent biotransformation of resveratrol in Caco-2 cells, which may also apply to human enterocytes affecting oral bioavailability.

Nice find, maxwatt! Bear in mind, though, that this is an in vitro experiment, with no liver around to cloud the picture. It's most directly related to resveratrol's passage through the intestinal epithelia, but not as much to resveratrol's fate in the rest of the system. My takehome from this is that resveratrol has a good chance of being intestinally absorbed, but it still faces first pass metabolism.

If quercetin is really a picomolar inhibitor of resveratrol sulfation, and it does that without inhibiting sulfation of everything else, that is a rather huge result... I guess that before wolfing a bunch of quercetin, I would want to know that I was not trashing a significant part of xenobiotic metabolism.

I totally agree, you are not going to overcome first pass metabolism in the liver with ingestion of your trans-Resv. The only way to do that would be with an IV injection or snorting your resveratrol. (Not recommended, obviously) I don't think we'll truly know the mechanistic effects of ingesting your trans-resv. with quercetin, at least for awhile. For now, we're all just basically guestimating, right, based on the scantily available evidence. I take resveratrol but I also think I'm being a bit premature. However, I also see no real downside to what I am doing, other than some $ and making my urine expensive.

[maxwatt]

That's the ticket! Just eat rat chow!!! Yeah!!!  [tung]

I can give you a link to buy Zoopreem large-primate chow. I was thinking of buying it for my rather-large and hungry teenage son.....

[wayside]

I came across an interesting link today. If anyone wants to buy resveratrol in bulk, here's a list of 40+ companies in China that are offering to sell it. It looks like you can go from 20% up to 98-99% pure. Some of them claim to have GMP facilities, some say they will provide it in capsules. No prices were listed that I saw ( I didn't look at all 40+ though).

I didn't notice any restrictions listed on who could buy it or where they would ship to...I guess that would be up to the individual company.

http://www.made-in-c...p=999&x=29&y=17

[tintinet]

That's the ticket! Just eat rat chow!!! Yeah!!!  [tung]

I can give you a link to buy Zoopreem large-primate chow. I was thinking of buying it for my rather-large and hungry teenage son.....

Ya, I got one o' them too! Too dang lazy to even heat up a frozen pizza!

[Futurist1000]

Hi i,m fairly new to this forum so forgive me if am repeating something that has already been said earlier. I've been reading these posts and am interested in the reported mental effects that people are getting. Apparently SIRT1 in the brain is found in high levels in the striatum and cortex. Daitoku et al. (2) found that CREB-binding protein binds and acetylates FKHR and that Sir2 binds and deacetylates residues acetylated by CREB-binding protein. So it would be interesting if SIRT1 did the same thing. I would surmise that deacetyating those things that are acetylated by CREB might reduce its effect. CREB in the nucleus accumbens (pleasure center of the brain) is pro-depressive and is increased by drugs of abuse and stress. Increased CREB encodes for dynorphin, BDNF and several other genes which dampen the reward signal. Could this be the mechanism for resveratrol's antidepressant action? It seems like it could in theory help cravings associated with addiction. Another thing is that increasing CREB in the hippocampus is a good thing, just the opposite as the nucleus accumbens. Decreasing CREB's activity in the hippocampus i would think might impair memory, but it seems that resveratrol improves peoples memory. So i am not too sure what this means. Does anybody have any thoughts on any of this?

[Futurist1000]

A few more things i've found. Exposure to cocaine increases H4 (histone) and H3 acetylation. BDNF and Cdk5 promoters are genes that are induced by this acetylation and subsequent increase in gene transcription. (http://linkinghub.el...i/S0896-6273(05)00790-7)
I think resveratrol deacetylates these histones, but i am not sure if this is true in neurons. Decreasing transcription of these genes would probably lead to an antidepressant effect and an anticraving effect. I can only speculate that it might be a way to avoid tolerance to drugs. Still if anyone has any input that might disprove this that would be great. Thanks.

[niner]

Is glucoronidation/sulfatation a standard procedure of the body
to process substances other than resveratrol?

Currently I'm opening my RESV caps and put the content into ~200ml
red vine and then I add 5000mg of grap seed powder after this I let
this mix alone for half an hour to give ETHO time to dissolve as much
as possible of the flavonoids/OPCs/RESV. Maybe it's a good idea to
give it a moderate microwave treatment. I'm not sure if this is reasonable, any suggestions ?

Yes, glucuronidation and sulfation are common ways in which the body increases the water solubility and excretion of xenobiotics (any foreign chemical). I don't think that resveratrol needs a lot of help in order to be absorbed. The wine and other flavonoids may help to reduce the amount of conjugation of the resveratrol, thus increasing the level of of free resveratrol in your system. I would not microwave the mixture, as this may induce unwanted chemical reactions. Resveratrol in solution is not super stable, I think it only lasts for a few days in solution, maybe less.

[rwoodin]

OK, been taking about 300mg for last 5 days. Not as much 'hypomanic' feeling now. Hardly any at all really, although my mood level is OK by me. I did want to mention that along with the antidepressant, bouyant mood lift I experienced when first starting the RESV there was a bit of a 'stuttery' kind of distracted feeling along with the antidepressant effect that seemed to be produced by the resveratrol over the last few days. Like I would get confused in which sequence to carry out a few simple tasks. For example, go to the kitchen, refill the glass of water, throw the paper plate in the garbage, throw an empty beverage can in the recycle bin. Like I would really have to concentrate to do one, then the next, then the next in sequential order or risk standing in the middle of the kitchen in a mental quandry. I know I'm leaving myself wide open to string of jokes ... but I figure I should not just mention beneficial effects while leaving out any negative ones. I do also seem to have come down with a bit of a minor sore throat/upper respiratory type of thing today. Who knows, maybe allergies, maybe a 'bug' going around work. I'm in Greensboro NC and this is the start of allergy season here. These effects could be partly or wholly due to that.
I finally received my order of Bio-Forte 250mg RESV caplsules and have taken one so far today. I'm going to take about another 100-150mg today. I guess I think it will be of help to all, the more information we can provide about any of our experiences, subjective or objective

[fearfrost]

Its weird you mention the sore throat rwoodin. About 1 week after starting resveratrol I got one of the nastiest sore throats of my life. Then it went away a few days later. I am guessing it has NOTHING to do with resveratrol, but who knows.

[tintinet]

Anecdotal symptoms: When I first started to take "low dose" (one Longevinex/day) resveratrol, several years ago, I shortly thereafter developed chronic serous otitis in one ear. Resolved now (s/p myringotomy), but I wondered, at the time, if the 2 were related. Hasn't returned despite now "high dose" (~1 gm/day resveratrol, various sources).

Also, have recently exacerbated apparent rosacea, possibly due to increased NO production due to resveratrol..... probably gonna need pulsed dye laser, IMO.

[rwoodin]

hmmm...I started experiencing what I think is rosacea as well. I started about a year ago and roughly coincided with when I started resveratrol....Seems to come and go, sometimes very noticable red circles due to dilated veins under eyes. Might be gettin pulsed myself...

[markymark]

arrrggghhh, anybody else with rosacea-like symptoms?

[health_nutty]

arrrggghhh, anybody else with rosacea-like symptoms?

Not me.

[shadowrun]

I have (for the past 3 days) what feels like...A minor ear infection in the right ear - Sore throat on the right Tonsil and a little pain in my lower jaw
...Its prob relational to a bitchy Wisdom tooth or perhaps I have an infection...

Most likely it has nothing to do with the Resveratrol...I hope its that easy!

[shadowrun]

No rosacea symptoms to report...

BTW - I think someone posted earlier that Resveratrol in fact diminished their rosacea

[tintinet]

Hmmmm....well, might just be a contact reaction to some el cheapo skin cream, but, at times, I could pass for Rudolf the Reindeer's brother!

[saxiephon]

So what's wrong with a ruddy complexion?