41 replies to this topic

[health_nutty]

I wish we could more conclusively establish whether the quercetin benefits of making resveratrol bioavailable outweigh it's sirt1 gene inhibiting effects. I've been holding off of quercetin but feel like I'm missin something.

Yes, I have the same feelings. AOR coming out with a formulation with quercetin makes it hard to ignore. AOR, LEF, and Longivenx (plus others) all include quercetin in their formulations. In addition Bill Sardi is taking large doses of quercetin.

http://www.imminst.o...hl=quercetin&s=

Edit: It was Bill Sardi's routine that had tons of quercetin not Dr. Sinclair

Edited by health_nutty, 26 April 2007 - 08:35 PM.

[malbecman]

Me too! [:o]

Anyone have an idea of what Dr. Sinclair is taking in terms of quercetin dosages? I"ve seen doses here ranging from 50mg to 1gram daily.....

I wish we could more conclusively establish whether the quercetin benefits of making resveratrol bioavailable outweigh it's sirt1 gene inhibiting effects. I've been holding off of quercetin but feel like I'm missin something.

Yes, I have the same feelings. AOR coming out with a formulation with quercetin makes it hard to ignore. AOR, LEF, and Longivenx (plus others) all include quercetin in their formulations. In addition Dr. Sinclair is taking large doses of quercetin.

[edward]

I haven't seen many people remark on the vit. C mixed with quercetin issue. Apparently quercetin in the presence of vit. c activates the SIRTs where as without it or a similar antioxidant it inhibits the SIRTs (hence AOR adding vit. c to their formula, I think their formula is fairly well thought out accept for the bioperine). Personally though I think 50mg of quercetin per 100mg of resveratrol if one is taking as much resveratrol as I and others on here are is a little much as I couldn't guarantee that there would be vit. c at the right place and time to cause quercetin to SIRT rather than inhibit it and therefore taking a lot of quercetin might defeat the purpose of resveratrol in the first place. For the time being I am only consuming quercetin indirectly as it is already in many of the flavonoid containing products I take along with every time I eat fruit. I am waiting for more data. At this point I would consider just taking more resveratrol rather than adding in a bunch of quercetin.

[proteomist]

Can you point me to the reference on quercetin inhibiting Sirt2? I can remember seeing papers/patents where it was a decent Sirt agonist (~4 fold, in vitro) but I can't remember the evidence for inhibition. I know it's out there somewhere, just not where.

I haven't seen many people remark on the vit. C mixed with quercetin issue. Apparently quercetin in the presence of vit. c activates the SIRTs where as without it or a similar antioxidant it inhibits the SIRTs (hence AOR adding vit. c to their formula, I think their formula is fairly well thought out accept for the bioperine). Personally though I think 50mg of quercetin per 100mg of resveratrol if one is taking as much resveratrol as I and others on here are is a little much as I couldn't guarantee that there would be vit. c at the right place and time to cause quercetin to SIRT rather than inhibit it and therefore taking a lot of quercetin might defeat the purpose of resveratrol in the first place. For the time being I am only consuming quercetin indirectly as it is already in many of the flavonoid containing products I take along with every time I eat fruit. I am waiting for more data. At this point I would consider just taking more resveratrol rather than adding in a bunch of quercetin.

[edward]

Here is one article, there are many more though.

http://www.sciencedi...fa9bea381ae658c


SIRT1 stimulation by polyphenols is affected by their stability and metabolism
Vincent C.J. de Boer, Marcus C. de Goffau, Ilja C.W. Arts, Peter C.H. Hollman and Jaap KeijerCorresponding Author Contact Information, E-mail The Corresponding Author
RIKILT – Institute of Food Safety, Wageningen University and Research Centre, Wageningen, The Netherlands

Received 7 December 2005; revised 6 February 2006; accepted 23 February 2006. Available online 17 April 2006.

Abstract

Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to stimulate the deacetylase activity of recombinant SIRT1 protein and could therefore be potential regulators of aging associated processes. However, inconsistent data between effects of polyphenols on the recombinant SIRT1 and on in vivo SIRT1, led us to investigate the influence of (1) stability of polyphenols under experimental conditions and (2) metabolism of polyphenols in human HT29 cells, on stimulation of SIRT1. With an improved SIRT1 deacetylation assay we found three new polyphenolic stimulators. Epigallocatechin galate (EGCg, 1.76-fold), epicatechin galate (ECg, 1.85-fold) and myricetin (3.19-fold) stimulated SIRT1 under stabilizing conditions, whereas without stabilization, these polyphenols strongly inhibited SIRT1, probably due to H2O2 formation. Using metabolically active HT29 cells we were able to show that quercetin (a stimulator of recombinant SIRT1) could not stimulate intracellular SIRT1. The major quercetin metabolite in humans, quercetin 3-O-glucuronide, slightly inhibited the recombinant SIRT1 activity which explains the lack of stimulatory action of quercetin in HT29 cells. This study shows that the stimulation of SIRT1 is strongly affected by polyphenol stability and metabolism, therefore extrapolation of in vitro SIRT1 stimulation results to physiological effects should be done with caution.

[proteomist]

Excellent, thanks a lot! They make it sound like inhibition by the quercetin glucuronidate is very minor.

[wydell]

I mix my resveratrol in less than an ounce of wine. To this wine mix, I also add powdered grape seed extract and powdered pomegranate extract. I then swish it along my inner cheek and lower and upper lip, which become somewhat numb for a couple of minutes.

I understand that it may be possible absorb certain substances into the bloodstream either under the tounge or through the inner cheek tissue. If numbness is any indicator of efficacy of my regimen, then maybe it works.

[health_nutty]

I mix my resveratrol in  less than an ounce of wine.  To this wine mix, I also add powdered grape seed extract and powdered pomegranate extract.  I then swish it along my inner cheek  and lower and upper lip, which  become somewhat numb for a couple of minutes.

I understand that it may be possible absorb certain substances into the bloodstream either under the tounge or through the inner cheek tissue. If numbness is any indicator of efficacy of my regimen, then maybe it works.

Have you always done it this way? If not did you notice any other differences (albeit subjective) with this method?

[shadowrun]

What about just eating an apple or some onions with your resveratrol?

[woly]

Here is one article, there are many more though.

http://www.sciencedi...fa9bea381ae658c


SIRT1 stimulation by polyphenols is affected by their stability and metabolism
Vincent C.J. de Boer, Marcus C. de Goffau, Ilja C.W. Arts, Peter C.H. Hollman and Jaap KeijerCorresponding Author Contact Information, E-mail The Corresponding Author
RIKILT – Institute of Food Safety, Wageningen University and Research Centre, Wageningen, The Netherlands

Received 7 December 2005;  revised 6 February 2006;  accepted 23 February 2006.  Available online 17 April 2006.

Abstract

Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to stimulate the deacetylase activity of recombinant SIRT1 protein and could therefore be potential regulators of aging associated processes. However, inconsistent data between effects of polyphenols on the recombinant SIRT1 and on in vivo SIRT1, led us to investigate the influence of (1) stability of polyphenols under experimental conditions and (2) metabolism of polyphenols in human HT29 cells, on stimulation of SIRT1. With an improved SIRT1 deacetylation assay we found three new polyphenolic stimulators. Epigallocatechin galate (EGCg, 1.76-fold), epicatechin galate (ECg, 1.85-fold) and myricetin (3.19-fold) stimulated SIRT1 under stabilizing conditions, whereas without stabilization, these polyphenols strongly inhibited SIRT1, probably due to H2O2 formation. Using metabolically active HT29 cells we were able to show that quercetin (a stimulator of recombinant SIRT1) could not stimulate intracellular SIRT1. The major quercetin metabolite in humans, quercetin 3-O-glucuronide, slightly inhibited the recombinant SIRT1 activity which explains the lack of stimulatory action of quercetin in HT29 cells. This study shows that the stimulation of SIRT1 is strongly affected by polyphenol stability and metabolism, therefore extrapolation of in vitro SIRT1 stimulation results to physiological effects should be done with caution.

sorry but what do they mean by "stabilizing conditions"?

[krillin]

sorry but what do they mean by "stabilizing conditions"?

I don't have access to the fulltext, but they might have added SOD like these fellows did.

Cancer Res. 2005 Sep 1;65(17):8049-56.
Mechanism of action of (-)-epigallocatechin-3-gallate: auto-oxidation-dependent inactivation of epidermal growth factor receptor and direct effects on growth inhibition in human esophageal cancer KYSE 150 cells.
Hou Z, Sang S, You H, Lee MJ, Hong J, Chin KV, Yang CS.

Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854-8020, USA.

(-)-Epigallocatechin-3-gallate (EGCG), the principal polyphenol in green tea, has been shown to inhibit the growth of many cancer cell lines and to suppress the phosphorylation of epidermal growth factor receptor (EGFR). We observed similar effects of EGCG in esophageal squamous cell carcinoma KYSE 150 cells and epidermoid squamous cell carcinoma A431 cells. Pretreatment of KYSE 150 cells with EGCG (20 micromol/L) for 0.5 to 24 hours in HAM's F12 and RPMI 1640 mixed medium at 37 degrees C, before the addition of EGF, resulted in a decreased level of phosphorylated EGFR (by 32-85%). Prolonged treatment with EGCG (8 or 24 hours) also decreased EGFR protein level (both by 80%). EGCG treatment for 24 hours also caused decreased signals of HER-2/neu in esophageal adenocarcinoma OE19 cells. These effects of EGCG were prevented or diminished by the addition of superoxide dismutase (SOD, 5 units/mL), or SOD plus catalase (30 units/mL), to the cell culture medium. A similar phenomenon on inactivation of EGFR was observed in A431 cells as well. Under culture conditions for KYSE 150 cells, EGCG was unstable, with a half-life of approximately 30 minutes; EGCG dimers and other oxidative products were formed. The presence of SOD in the culture medium stabilized EGCG and increased its half-life to longer than 24 hours and some EGCG epimerized to (+)-gallocatechin-3-gallate. A mechanism of superoxide radical-mediated dimerization of EGCG and H2O2 formation is proposed. The stabilization of EGCG by SOD in the culture medium potentiated the activity of EGCG in inhibiting KYSE 150 cell growth. The results suggest that in cell culture conditions, the auto-oxidation of EGCG leads to EGFR inactivation, but the inhibition of cell growth is due to other mechanisms. It remains to be determined whether the presently observed auto-oxidation of EGCG occurs in vivo. In future studies of EGCG and other polyphenolic compounds in cell culture, SOD may be added to stabilize EGCG and to avoid possible artifacts.

PMID: 16140980

[wydell]

I mix my resveratrol in  less than an ounce of wine.  To this wine mix, I also add powdered grape seed extract and powdered pomegranate extract.  I then swish it along my inner cheek  and lower and upper lip, which  become somewhat numb for a couple of minutes.

I understand that it may be possible absorb certain substances into the bloodstream either under the tounge or through the inner cheek tissue. If numbness is any indicator of efficacy of my regimen, then maybe it works.

Have you always done it this way? If not did you notice any other differences (albeit subjective) with this method?

I just started this method this week. So far, the only thing that I have noticed is the anesthetic effect on my inner cheek and upper and lower inner lip. It lasts for a couple minutes after swishing it around.