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Is Quercetin a problem with Resveratrol?


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#1 ianlib

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Posted 20 March 2011 - 06:11 PM


Biotivia says Quercetin prevents Resveratrol from working properly and should not be taken with it. Yet other companies say the two are synergistic. Does anyone know which is true?

#2 maxwatt

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Posted 20 March 2011 - 06:27 PM

In this case Biotivia are correct in that quercetin inhibits Sirt1. The reference is given in this topic: HERE

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#3 ianlib

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Posted 21 March 2011 - 01:11 PM

In this case Biotivia are correct in that quercetin inhibits Sirt1. The reference is given in this topic: HERE


Could not find it in the reference.

#4 maxwatt

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Posted 21 March 2011 - 01:26 PM

In this case Biotivia are correct in that quercetin inhibits Sirt1. The reference is given in this topic: HERE


Could not find it in the reference.


THIS topic was linked to in the one above, and makes it a little clearer. Compound 30 in the tables that accompany the paper cited, was ah effective inhibitor of SIRT1.

#5 peteo

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Posted 21 March 2011 - 09:14 PM

In this case Biotivia are correct in that quercetin inhibits Sirt1. The reference is given in this topic: HERE


Could not find it in the reference.


THIS topic was linked to in the one above, and makes it a little clearer. Compound 30 in the tables that accompany the paper cited, was ah effective inhibitor of SIRT1.


so if we take Resveratrol, you shouldn't take quercetin at all or can we take it 12 hours later?

#6 niner

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Posted 21 March 2011 - 09:22 PM

Concern over quercetin as a Sirt1 inhibitor would hinge on resveratrol's actions being significantly a function of Sirt1 activation. While that was the early thinking on it, I thought that had changed. Where are we at on the importance of the resveratrol-Sirt1 connection now?

Quercetin is supposed to be a potent inhibitor of one of the key resveratrol metabolizing enzymes, which was an early driver for combining them.

#7 maxwatt

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Posted 21 March 2011 - 09:30 PM

In this case Biotivia are correct in that quercetin inhibits Sirt1. The reference is given in this topic: HERE


Could not find it in the reference.


THIS topic was linked to in the one above, and makes it a little clearer. Compound 30 in the tables that accompany the paper cited, was ah effective inhibitor of SIRT1.


so if we take Resveratrol, you shouldn't take quercetin at all or can we take it 12 hours later?

Perhaps. Why do you want to take quercetin? what benefits that cannot be derived from resveratrol are you looking for? Does quercein actually induce those effects? Would other polyphenols be beneficial, in addition or in place of resveratrol?

According to the paper referenced in the link I cited above, luteolin, which is chemically and structurally very similar to quercetin, activates SIRT1 even more potently than resveratrol. Perhaps that would be an alternative to quercetin? The fact is there are no studies that address these questions directly, and I don't know why you want to take quercetin.

Some people recommend cycling resveratrol, and I am self-experimenting with that: no resveratrol on weekends, approximately 500 mg in the morning during the week. So far so good. A major marketer of resveratrol pills, who also sells a putative telomerase activator, recommends cycling two weeks on resverarol, then two weeks on his telomerase activator. Then there are other polyphenols: curcumin, whose actions seem to overlap with resveratrol in some respects, though it is not an SIRT1 activator, and myricetin which apparently inhibits SIRT1, but is more effective than reseratrol at lowering fasting blood sugar. I'm sorry I cannot give you more definite answers, but we barely know what single polyphenols do, or the best way to use them, much less combinations of substances.

So let's back off a minute. Yes, about 12 hours later, I would not expect quercetin to interfere with SIRT1 activation. But why do you want to take quercetin? If it's for PDE4 inhibition, you might do better with luteolin.
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#8 Tithonus

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Posted 23 March 2011 - 04:06 PM

Quercetin is also an enhancer of mitochondria biogenesis in muscle and brain. I know that's one of the key reasons I'm taking it.
source found HERE

#9 hamishm00

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Posted 24 March 2011 - 02:47 AM

Agreed, that's one of the main reasons why i take it too, except I don't take it at the same time as resveratrol.

#10 maxwatt

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Posted 24 March 2011 - 04:35 AM

Quercetin is also an enhancer of mitochondria biogenesis in muscle and brain. I know that's one of the key reasons I'm taking it.
source found HERE

good find. resveratrol also induces mitochondrial biogenesis, as we know from Auwerx paper, and the cycling coach who posted here over a year ago who measured his and his athletes perormance. however, Q. inhibits Sirt1 activation, so I wouldn't take lt the same time as resveratrol. resveratrol is best taken in the a.m., as it resets circadian rhythms (great for jet lag) so quercetin at night is a strategy.

fwiw, luteolin also activates sirt1, as does fisetin. Myricetin inhibits srt1, like quercetin. not yet sure what we can do with this information, but it's adding up.

Am J Clin Nutr. 2002 Sep;76(3):560-8.
Flavonoid intake and risk of chronic diseases.
Knekt P, Kumpulainen J, Järvinen R, Rissanen H, Heliövaara M, Reunanen A, Hakulinen T, Aromaa A.

National Public Health Institute, Helsinki, Finland. paul.knekt@ktl.fi
Abstract
BACKGROUND: Flavonoids are effective antioxidants and may protect against several chronic diseases.

OBJECTIVE: The association between flavonoid intake and risk of several chronic diseases was studied.

DESIGN: The total dietary intakes of 10 054 men and women during the year preceding the baseline examination were determined with a dietary history method. Flavonoid intakes were estimated, mainly on the basis of the flavonoid concentrations in Finnish foods. The incident cases of the diseases considered were identified from different national public health registers.

RESULTS: Persons with higher quercetin intakes had lower mortality from ischemic heart disease. The relative risk (RR) between the highest and lowest quartiles was 0.79 (95% CI: 0.63, 0.99: P for trend = 0.02). The incidence of cerebrovascular disease was lower at higher kaempferol (0.70; 0.56, 0.86; P = 0.003), naringenin (0.79; 0.64, 0.98; P = 0.06), and hesperetin (0.80; 0.64, 0.99; P = 0.008) intakes. Men with higher quercetin intakes had a lower lung cancer incidence (0.42; 0.25, 0.72; P = 0.001), and men with higher myricetin intakes had a lower prostate cancer risk (0.43; 0.22, 0.86; P = 0.002). Asthma incidence was lower at higher quercetin (0.76; 0.56, 1.01; P = 0.005), naringenin (0.69; 0.50, 0.94; P = 0.06), and hesperetin (0.64; 0.46, 0.88; P = 0.03) intakes. A trend toward a reduction in risk of type 2 diabetes was associated with higher quercetin (0.81; 0.64, 1.02; P = 0.07) and myricetin (0.79; 0.62, 1.00; P = 0.07) intakes.

CONCLUSION: The risk of some chronic diseases may be lower at higher dietary flavonoid intakes.

PMID: 12198000



#11 markymark

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Posted 24 March 2011 - 05:24 PM

snip

Quercetin actually induced SIRT1(mRNA) and PCG1 alpha transcription in the paper mentioned above:
J. Mark Davis, et al.: Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance.
Quote from the abstract:

"Quercetin increased mRNA expression of PGC-1 and
SIRT1 (P  0.05), mtDNA (P  0.05) and cytochrome c concentration
(P  0.05). These changes in markers of mitochondrial
biogenesis were associated with an increase in both maximal
endurance capacity (P  0.05) and voluntary wheel-running activity
(P  0.05). These benefits of querectin on fitness without
exercise training may have important implications for enhancement
of athletic and military performance and may also extend to
prevention and/or treatment of chronic diseases."

So, @niner,
quercetin induced mRNA of SIRT1... what might be the net effect of induction of mRNA and inhibition of an enzyme... I know, we cannot say at the moment. maybe, as you said, taking quercetin in the evening and the resv. in the morning is a good approach...

MM

#12 maxwatt

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Posted 24 March 2011 - 06:22 PM

snip

Quercetin actually induced SIRT1(mRNA) and PCG1 alpha transcription in the paper mentioned above:
J. Mark Davis, et al.: Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance.
Quote from the abstract:

"Quercetin increased mRNA expression of PGC-1 and
SIRT1 (P  0.05), mtDNA (P  0.05) and cytochrome c concentration
(P  0.05). These changes in markers of mitochondrial
biogenesis were associated with an increase in both maximal
endurance capacity (P  0.05) and voluntary wheel-running activity
(P  0.05). These benefits of querectin on fitness without
exercise training may have important implications for enhancement
of athletic and military performance and may also extend to
prevention and/or treatment of chronic diseases."

So, @niner,
quercetin induced mRNA of SIRT1... what might be the net effect of induction of mRNA and inhibition of an enzyme... I know, we cannot say at the moment. maybe, as you said, taking quercetin in the evening and the resv. in the morning is a good approach...

MM

that was using the Biomol assay, where the fluorophore used for the assay activated sirt1, which gave inaccurate results as to sirt1 activation. A newer, more accurate assay mentioned in this thread discusses the paperwhere researchers developed a more accurate assay, where they found quercetin and myricetin actually inhibit SIRT1, and other polyphenols such as luteolin and piceatannol are stronger activators than is resveratrol.

The effect on PGC1-a is probably responsible for mitochondrial biogenesis.


The paper is well worth studying:


J Pharmacol Sci. 2008 Nov;108(3):364-71. Epub 2008 Nov 13.

A novel chalcone polyphenol inhibits the deacetylase activity of SIRT1 and cell growth in HEK293T cells.
Kahyo T, Ichikawa S, Hatanaka T, Yamada MK, Setou M.

Mitsubishi Kagaku Institute of Life Sciences (MITILS), Machida, Tokyo, Japan.

Abstract
SIRT1 is one of seven mammalian orthologs of yeast silent information regulator 2 (Sir2), and it functions as a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase. Recently, resveratrol and its analogues, which are polyphenols, have been reported to activate the deacetylase activity of SIRT1 in an in vitro assay and to expand the life-span of several species through Sir2 and the orthologs. To find activators or inhibitors to SIRT1, we examined thirty-six polyphenols, including stilbenes, chalcones, flavanones, and flavonols, with the SIRT1 deacetylase activity assay using the acetylated peptide of p53 as a substrate. The results showed that 3,2',3',4'-tetrahydroxychalcone, a newly synthesized compound, inhibited the SIRT1-mediated deacetylation of a p53 acetylated peptide and recombinant protein in vitro. In addition, this agent induced the hyperacetylation of endogenous p53, increased the endogenous p21CIP1/WAF1 in intact cells, and suppressed the cell growth. These results indicated that 3,2',3',4'-tetrahydroxychalcone had a stronger inhibitory effect on the SIRT1-pathway than sirtinol, a known SIRT1-inhibitor. Our results mean that 3,2',3',4'-tetrahydroxychalcone is a novel inhibitor of SIRT1 and produces physiological effects on organisms probably through inhibiting the deacetylation by SIRT1.

PMID: 19008647


The paper is available free through Pubmed, and the results for SIRT1 activation are discussed in the thread I linked to above. However, the advantage of SIRT1 activation is theoretical, not likely the whole story. We may want to activate it and deactivate cyclically, but this is speculation.

Also, resveratrol affects the CLK genes, which resets circadian rhythms, which is why we've been recommending using resverarol in the morning. As far as I know quercetin does not do this, so evening use would be a logical conclusion if using resveratrol concurently. Using both this way might induce mitochondrial biogenesis more strongly than either alone, though it is too is speculative at this point,

Edited by maxwatt, 24 March 2011 - 06:23 PM.


#13 markymark

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Posted 24 March 2011 - 08:55 PM

snip

first of all sorry to both mawatt and niner, for mixing up your names....

but if you look at the paper, they were measuring transcription = mRNA of the SIRT1 and PCG1a genes, not enzyme activity
see the legend of Fig. 1.: "Short-term feedings of the dietary flavonoid quercetin increase expression of genes associated with mitochondrial biogenesis. Peroxisome proliferator-activated receptor-􏰀 coactivator (PGC-1􏰁) and sirtuin 1 (SIRT1) expression were measured in skeletal muscle and brain using RT-PCR following 7 days of quercetin feedings (n 􏰅 15/group). Values are means 􏰋 SE. *Significantly different from placebo (P 􏰂 0.05).

hm, increasing expression of genes (upregulating mRNA) is not the same as increasing enzyme activity. And the Biomol assay was on enzyme activity, if I am not wrong here.

mtDNA content of PCG1a and SIRT1 were also increased in muscle and brain upon quercetin treatment in those rodents...so the likelihood that quercetin does something is high...
regs
MM

#14 maxwatt

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Posted 24 March 2011 - 10:41 PM

snip

first of all sorry to both mawatt and niner, for mixing up your names....

but if you look at the paper, they were measuring transcription = mRNA of the SIRT1 and PCG1a genes, not enzyme activity
see the legend of Fig. 1.: "Short-term feedings of the dietary flavonoid quercetin increase expression of genes associated with mitochondrial biogenesis. Peroxisome proliferator-activated receptor-􏰀 coactivator (PGC-1􏰁) and sirtuin 1 (SIRT1) expression were measured in skeletal muscle and brain using RT-PCR following 7 days of quercetin feedings (n 􏰅 15/group). Values are means 􏰋 SE. *Significantly different from placebo (P 􏰂 0.05).

hm, increasing expression of genes (upregulating mRNA) is not the same as increasing enzyme activity. And the Biomol assay was on enzyme activity, if I am not wrong here.

mtDNA content of PCG1a and SIRT1 were also increased in muscle and brain upon quercetin treatment in those rodents...so the likelihood that quercetin does something is high...
regs
MM


Quite correct, they were not using Biomol. It seems the action on SIRT1 is indirect.
The more we learn, the less we know. :blink:

#15 Tithonus

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Posted 26 March 2011 - 06:00 AM

snip

first of all sorry to both mawatt and niner, for mixing up your names....

but if you look at the paper, they were measuring transcription = mRNA of the SIRT1 and PCG1a genes, not enzyme activity
see the legend of Fig. 1.: "Short-term feedings of the dietary flavonoid quercetin increase expression of genes associated with mitochondrial biogenesis. Peroxisome proliferator-activated receptor-􏰀 coactivator (PGC-1􏰁) and sirtuin 1 (SIRT1) expression were measured in skeletal muscle and brain using RT-PCR following 7 days of quercetin feedings (n 􏰅 15/group). Values are means 􏰋 SE. *Significantly different from placebo (P 􏰂 0.05).

hm, increasing expression of genes (upregulating mRNA) is not the same as increasing enzyme activity. And the Biomol assay was on enzyme activity, if I am not wrong here.

mtDNA content of PCG1a and SIRT1 were also increased in muscle and brain upon quercetin treatment in those rodents...so the likelihood that quercetin does something is high...
regs
MM


Quite correct, they were not using Biomol. It seems the action on SIRT1 is indirect.
The more we learn, the less we know. :blink:



So, based on this study and the expression of the SIRT1 gene, a case could be made that quercetin DOES boost SIRT1, however slightly

#16 maxwatt

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Posted 26 March 2011 - 12:01 PM

snip

first of all sorry to both mawatt and niner, for mixing up your names....

but if you look at the paper, they were measuring transcription = mRNA of the SIRT1 and PCG1a genes, not enzyme activity
see the legend of Fig. 1.: "Short-term feedings of the dietary flavonoid quercetin increase expression of genes associated with mitochondrial biogenesis. Peroxisome proliferator-activated receptor-􏰀 coactivator (PGC-1􏰁) and sirtuin 1 (SIRT1) expression were measured in skeletal muscle and brain using RT-PCR following 7 days of quercetin feedings (n 􏰅 15/group). Values are means 􏰋 SE. *Significantly different from placebo (P 􏰂 0.05).

hm, increasing expression of genes (upregulating mRNA) is not the same as increasing enzyme activity. And the Biomol assay was on enzyme activity, if I am not wrong here.

mtDNA content of PCG1a and SIRT1 were also increased in muscle and brain upon quercetin treatment in those rodents...so the likelihood that quercetin does something is high...
regs
MM


Quite correct, they were not using Biomol. It seems the action on SIRT1 is indirect.
The more we learn, the less we know. :blink:



So, based on this study and the expression of the SIRT1 gene, a case could be made that quercetin DOES boost SIRT1, however slightly

Yes, but apparently it is a downstream effect from one of the other genes or enzymes it is affecting, as the initial cellular effect is to inhibit Sirt1. The effect on mitochondrial biogenesis may be why Lance Armstrong included quercetin in his FRS brand energy drink, though after an initial flurry of sales seems to have declined in popularity.

Quercetin also inhibits angiogenesis, and to such a strong degree that it has been a lab standard for blocking angiogenesis in tissue for over 50 years. Resveratrol, luteolin and other such compounds also inhibit angiogenis via VEGf inhibition, but I speculate the effect is weaker than with quercetin, after a quick scan of the literature. This would make quercetin a good candidate for treating vascular tumors, but not necessarily a good choice for athletes who want to increase vascularization of muscle tissue -- that requires angiogenesis.

I'm particularly interested in looking into the effects of luteolin; it's structure is very similar to quercetin, differing in but one ring attachment (it's a flavanone rather than a flavanol), but it was found to be a strong inducer of Sirt1 (Kahyo T, Ichikawa S, Hatanaka T, Yamada MK, Setou M., PMID: 19008647) In fact, stronger than resveratrol.

#17 markymark

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Posted 26 March 2011 - 12:30 PM

hm, here are some human data on quercetin (seee the abstract at the end of this posting)... after such a shord period quite an effect! OK smal sample size but cross over design.
Is quercetin anti angiogenetic in every tissue?
What migh be the net effect of transcrptional activation of the gene and inhibition of the protein?
Increasing transcription of a gene (SIRT1) must ne necessarily be a downstream effect, as maxwatt said.
What about the other effects in sirtuins of quercetin? Sirt7?

OK there is no sense in playing quercetin against luteolin.... however, a head to head study resv vs. resv/quercetin (humans, animals, cells) will give some clues as to the quercetin yes or no with resv-issue....

And OK there are also null findings on quercetin and ergogenic response: PMID: 19679747
But this trial showed a positive effect. Why didn't they use a resv/quercetin combination arm?...

Int J Sport Nutr Exerc Metab. 2010 Feb;20(1):56-62.
The dietary flavonoid quercetin increases VO(2max) and endurance capacity.

Davis JM, Carlstedt CJ, Chen S, Carmichael MD, Murphy EA.

Div. of Applied Physiology, Dept. of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
Abstract

Quercetin, a natural polyphenolic flavonoid substance present in a variety of food plants, has been shown in vitro and in animal studies to have widespread health and performance benefits resulting from a combination of biological properties, including antioxidant and anti-inflammatory activity, as well as the ability to increase mitochondrial biogenesis. Little is known about these effects in humans, however, especially with respect to exercise performance. The authors determined whether quercetin ingestion would enhance maximal aerobic capacity and delay fatigue during prolonged exercise in healthy but untrained participants. Twelve volunteers were randomly assigned to 1 of 2 treatments: (a) 500 mg of quercetin twice daily dissolved in vitamin-enriched Tang or (b) a nondistinguishable placebo (Tang). Baseline VO2max and bike-ride times to fatigue were established. Treatments were administered for a period of 7 days using a randomized, double-blind, placebo-controlled, crossover study design. After treatment both VO2max and ride time to fatigue were determined. Seven days of quercetin feedings were associated with a modest increase in VO2max (3.9% vs. placebo; p < .05) along with a substantial (13.2%) increase in ride time to fatigue (p < .05). These data suggest that as little as 7 days of quercetin supplementation can increase endurance without exercise training in untrained participants. These benefits of quercetin may have important implications for enhancement of athletic and military performance. This apparent increase in fitness without exercise training may have implications beyond that of performance enhancement to health promotion and disease prevention.

PMID: 20190352 [PubMed - indexed for MEDLINE]

Edited by markymark, 26 March 2011 - 12:31 PM.


#18 maxwatt

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Posted 26 March 2011 - 02:15 PM

One reason for combining quercetin with resveratrol was to attempt to increase resveratrol bioavailability. However the study below shows did not increase blood serum levels. The reasoning was that quercetin inhibits sulfotransferase, which is the major enzyme that eliminates resveratrol, which makes the results below somewhat surprising. So, no benefit vis a vis resveratrol blood serum levels to taking the combination.


Clin Pharmacokinet. 2010 Jul 1;49(7):449-54. doi: 10.2165/11531820-000000000-00000.
Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects.
la Porte C, Voduc N, Zhang G, Seguin I, Tardiff D, Singhal N, Cameron DW.

Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada. claporte@ohri.ca
Abstract
BACKGROUND AND OBJECTIVE: Trans-resveratrol is a polyphenol, which is found in red wine and has cancer chemo-preventive properties and disease-preventive properties. The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages. The present study aimed to investigate the steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol).

METHODS: This was a two-period, open-label, single-arm, within-subject control study in eight healthy subjects. The steady-state 12-hour pharmacokinetics of trans-resveratrol 2000 mg twice daily were studied with a standard breakfast, a high-fat breakfast, quercetin 500 mg twice daily and 5% alcohol 100 mL. Trans-resveratrol plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.

RESULTS: The mean (SD) area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) and maximum plasma concentration (C(max)) of trans-resveratrol were 3558 (2195) ng * h/mL and 1274 (790) ng/mL, respectively, after the standard breakfast. The high-fat breakfast significantly decreased the AUC(12) and C(max) by 45% and 46%, respectively, when compared with the standard breakfast. Quercetin 500 mg twice daily or 5% alcohol 100 mL did not influence trans-resveratrol pharmacokinetics. Diarrhoea was reported in six of the eight subjects. Significant but not clinically relevant changes from baseline were observed in serum potassium and total bilirubin levels.

CONCLUSION: Trans-resveratrol 2000 mg twice daily resulted in adequate exposure and was well tolerated by healthy subjects, although diarrhoea was frequently observed. In order to maximize trans-resveratrol exposure, it should be taken with a standard breakfast and not with a high-fat meal. Furthermore, combined intake with quercetin or alcohol did not influence trans-resveratrol exposure.

PMID: 20528005


Luteolin is an even more potent sulfotransferase inhibitor than quercetin, and some manufacturers have included it with resveratrol for that reason. I am trying to recall if hedgehog included resveratrol-luteolin in his unpublished tests on blood serum levels; it would be an interesting data point. However, two years ago I tried including luteolin with resveratrol in my own regimen, which led to experiencing joint/tendon pain which only began to resolve on discontinuing luteolin and reducing the resveratrol dose. You may recall I found resveratol had eliminated arthritic pain and swelling in my toes and fingers, which has been the main reason I continue to take it. Since then, however, finger-joint pain has recurred despite resveratrol use, but at a greatly reduced level than before I first took resveratrol. I then tried cycling resveratrol, taking it in the morning on weekdays (approximately 500 mg, powder, sublingual and bucal). Slight improvement.

I then learned a few months ago that luteolin activates SIRT1 even more effectively than resveratrol, and also inhibits nf-Kappa beta like resveratrol (which is probably why it is so effective an anti-inflammatory.) I have a some available, having supplied it to two different university labs that requested it. So I substituted an equivalent amount of luteolin for resveratrol for the past week in my regimen. So far so good, but I also note the same feeling of well-being I noted when first taking resveratrol, and feel leaner, as if I am losing weight. Resveratrol undoubtedly has had a mitochondrial biogenesis effect, as I have needed fewer workouts for an equivalent level of fitness for the past three years since taking resveratrol. I believe luteolin (and perhaps quercetin?) will do the same, because mitochondrial biogenesis seems to be an effect of Sirt1 activation, which leads to higher NAD levels, in turn improving mitochondrial respiration and inducing replication of functional mitochondrial- something that seems to be an effect of many polyphenols, some maybe better than others. It's complicated for me by also taking myricetin in the evening - it inhibits SIRT1, I thought it a good idea to cycle SIRT1, and the glucose lowering effect of myricetin seems desireable. I will be reintroducing resveratrol into my mix, I have a lot of that too, and I want to compare it post-luteolin supplementation. It may be these polyphenols have to be cycled to maintain their effectiveness. As for quercetin - I've tried it several times, most recently in 2007; it did not have the effect that resveratrol does for arthritis, at least for me, and like luteolin did not complement resveratrol I am surprised that luteolin by itself seems to work as well as or better than resveratrol for my joints.

I know, I've too many variables to sort out, but so far I feel great, finger pain almost gone and continuing to subside.

It is like the old saying, "the deeper you dig, the deeper it gets." There is a lot we don't understand about polyphenols. They are beneficial, but we do not understand completely their individual effects, or the effects of combinations , or what downsides if any there are. Much of the benefit seems to come by shared characteristics of inhibiting nf-Kappa beta, P53 deacetylase, in some cases via SIRT1 activation. These appear to work for life extension and mitochondrial biogenesis via improving the NAD/NADH ratio, which is something caloric restriction does, and purportedly the supplement Benagene that Mr. Cash is selling on the web. And methylene blue, at least in low doses of around 60 micrograms.

Another thing luteolin does, which is not shared AFAIK by other polyphenols, is its relatively selective PDE4 inhibition. Inhibition of PDE4 repairs deficits in memory that are cause by sleep deprivation, and possibly protects the hippocampus from degenerative changes. I think resveratrol has similar cAMP signalling effects in the brain, but maybe not as strong as luteolin? This is possibly why I feel so good supplementing with luteolin.

Nature 461, 1122-1125 (22 October 2009) | doi:10.1038/nature08488; Received 27 May 2009; Accepted 1 September 2009

Sleep deprivation impairs cAMP signalling in the hippocampus
Christopher G. Vecsey1,2, George S. Baillie3, Devan Jaganath2, Robbert Havekes2, Andrew Daniels2, Mathieu Wimmer1,2, Ted Huang1,2, Kim M. Brown3, Xiang-Yao Li4, Giannina Descalzi4, Susan S. Kim4, Tao Chen4, Yu-Ze Shang4, Min Zhuo4, Miles D. Houslay3 & Ted Abel2

Abstract
Millions of people regularly obtain insufficient sleep1. Given the effect of sleep deprivation on our lives, understanding the cellular and molecular pathways affected by sleep deprivation is clearly of social and clinical importance. One of the major effects of sleep deprivation on the brain is to produce memory deficits in learning models that are dependent on the hippocampus2, 3, 4, 5. Here we have identified a molecular mechanism by which brief sleep deprivation alters hippocampal function. Sleep deprivation selectively impaired 3′, 5′-cyclic AMP (cAMP)- and protein kinase A (PKA)-dependent forms of synaptic plasticity6 in the mouse hippocampus, reduced cAMP signalling, and increased activity and protein levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP. Treatment of mice with phosphodiesterase inhibitors rescued the sleep-deprivation-induced deficits in cAMP signalling, synaptic plasticity and hippocampus-dependent memory. These findings demonstrate that brief sleep deprivation disrupts hippocampal function by interfering with cAMP signalling through increased PDE4 activity. Thus, drugs that enhance cAMP signalling may provide a new therapeutic approach to counteract the cognitive effects of sleep deprivation.


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#19 markymark

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Posted 30 March 2011 - 07:34 AM

Thx for posting the above study
But this is not the type of study I have in my mind in order to gain ground as to the quercetin-with-resv.-yes-or-no-Q.
I would do the following trial(s):

Placebo vs. Resv (500 mg or more). mono vs. Resv/Quercetin (500mg twice / day) for, say, 12 weeks. (Ok for me to do it one year or longer)
baseline, end wks 4, 8 and 12: complete blood work with all biomarkers possible (insulin/gucose metabolism, cytokines, hormones etc. mRNA profile in peripheral blood mononuclear cells etc.) plus muscle/fat biopsy (expression of: PCG1a, Sirtuins, AMPkinase, Adiponectin, etc...).

Study populations:
prediabetic oder type-2 diabetics without an exercise regimen
prediabetic oder type-2 diabetics on an exercise regimen
healthy persons, (no athletes)
well trained athletes

anybody out there to spend the money for these trials? ;-) I would like to conduct them...
regs MM

#20 Tithonus

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Posted 30 March 2011 - 05:45 PM

Thx for posting the above study
But this is not the type of study I have in my mind in order to gain ground as to the quercetin-with-resv.-yes-or-no-Q.
I would do the following trial(s):

Placebo vs. Resv (500 mg or more). mono vs. Resv/Quercetin (500mg twice / day) for, say, 12 weeks. (Ok for me to do it one year or longer)
baseline, end wks 4, 8 and 12: complete blood work with all biomarkers possible (insulin/gucose metabolism, cytokines, hormones etc. mRNA profile in peripheral blood mononuclear cells etc.) plus muscle/fat biopsy (expression of: PCG1a, Sirtuins, AMPkinase, Adiponectin, etc...).

Study populations:
prediabetic oder type-2 diabetics without an exercise regimen
prediabetic oder type-2 diabetics on an exercise regimen
healthy persons, (no athletes)
well trained athletes

anybody out there to spend the money for these trials? ;-) I would like to conduct them...
regs MM


If you also happen to be in the market for a PDE5 inhibitor (selectively) epimedium does the trick. Also stimulates osteoblasts, resulting in increased bone density. And forskolin works to raise cAMP

Sorry, meant to quote maxwatt's post...

Edited by HerbalDoc, 30 March 2011 - 05:46 PM.


#21 APBT

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Posted 30 March 2011 - 06:46 PM

I then learned a few months ago that luteolin activates SIRT1 even more effectively than resveratrol, and also inhibits nf-Kappa beta like resveratrol (which is probably why it is so effective an anti-inflammatory.) I have a some available, having supplied it to two different university labs that requested it. So I substituted an equivalent amount of luteolin for resveratrol for the past week in my regimen. So far so good, but I also note the same feeling of well-being I noted when first taking resveratrol, and feel leaner, as if I am losing weight. Resveratrol undoubtedly has had a mitochondrial biogenesis effect, as I have needed fewer workouts for an equivalent level of fitness for the past three years since taking resveratrol. I believe luteolin (and perhaps quercetin?) will do the same, because mitochondrial biogenesis seems to be an effect of Sirt1 activation, which leads to higher NAD levels, in turn improving mitochondrial respiration and inducing replication of functional mitochondrial- something that seems to be an effect of many polyphenols, some maybe better than others. It's complicated for me by also taking myricetin in the evening - it inhibits SIRT1, I thought it a good idea to cycle SIRT1, and the glucose lowering effect of myricetin seems desireable. I will be reintroducing resveratrol into my mix, I have a lot of that too, and I want to compare it post-luteolin supplementation. It may be these polyphenols have to be cycled to maintain their effectiveness. As for quercetin - I've tried it several times, most recently in 2007; it did not have the effect that resveratrol does for arthritis, at least for me, and like luteolin did not complement resveratrol I am surprised that luteolin by itself seems to work as well as or better than resveratrol for my joints.

.


Max

Regarding your recent incorporation of luteolin:

How much are you using?
How frequently are you dosing?
Taking with or without food?
Taken at the same time as other supps, or solo?
Are you using powder, lozenges, pills?

#22 maxwatt

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Posted 30 March 2011 - 07:16 PM

I then learned a few months ago that luteolin activates SIRT1 even more effectively than resveratrol, and also inhibits nf-Kappa beta like resveratrol (which is probably why it is so effective an anti-inflammatory.) I have a some available, having supplied it to two different university labs that requested it. So I substituted an equivalent amount of luteolin for resveratrol for the past week in my regimen. So far so good, but I also note the same feeling of well-being I noted when first taking resveratrol, and feel leaner, as if I am losing weight. Resveratrol undoubtedly has had a mitochondrial biogenesis effect, as I have needed fewer workouts for an equivalent level of fitness for the past three years since taking resveratrol. I believe luteolin (and perhaps quercetin?) will do the same, because mitochondrial biogenesis seems to be an effect of Sirt1 activation, which leads to higher NAD levels, in turn improving mitochondrial respiration and inducing replication of functional mitochondrial- something that seems to be an effect of many polyphenols, some maybe better than others. It's complicated for me by also taking myricetin in the evening - it inhibits SIRT1, I thought it a good idea to cycle SIRT1, and the glucose lowering effect of myricetin seems desireable. I will be reintroducing resveratrol into my mix, I have a lot of that too, and I want to compare it post-luteolin supplementation. It may be these polyphenols have to be cycled to maintain their effectiveness. As for quercetin - I've tried it several times, most recently in 2007; it did not have the effect that resveratrol does for arthritis, at least for me, and like luteolin did not complement resveratrol I am surprised that luteolin by itself seems to work as well as or better than resveratrol for my joints.

.


Max

Regarding your recent incorporation of luteolin:

How much are you using?
How frequently are you dosing?
Taking with or without food?
Taken at the same time as other supps, or solo?
Are you using powder, lozenges, pills?


Powder; Approximately 350 mg of an 80% extract from peanut shells for 280 mg. The rest is other polyphenols, flavonoids and their glucosides.
In the morning, before other supplements and breakfast.
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#23 saxiephon

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Posted 09 March 2013 - 07:02 PM

Hi Max,

Regarding Luteolin Powder; Approximately 350 mg of an 80% extract from peanut shells for 280 mg. The rest is other polyphenols, flavonoids and their glucosides.

What is your source and how much and how do you take it? Can I purchase it online?

Thanks,
Sax

#24 Jean-François Savouret

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Posted 10 March 2013 - 03:38 PM

Quercetin is a pro-oxidant, pro-apoptotic and an AhR-inducer. Concerning Resv interactions, quercetin is the closest you can get to shoot yourself in the foot with your clothes on. Quercetin is the reason why fresh oak casks use for wine making is not only useless to wine but damageable for health.
The only good additive to Resv is curcumin.

JFS

#25 Kevnzworld

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Posted 10 March 2013 - 05:25 PM

Quercetin is a pro-oxidant, pro-apoptotic and an AhR-inducer. Concerning Resv interactions, quercetin is the closest you can get to shoot yourself in the foot with your clothes on. Quercetin is the reason why fresh oak casks use for wine making is not only useless to wine but damageable for health.
The only good additive to Resv is curcumin.

JFS


Quercetin is an anti oxidant , that can have pro oxidant , pro apoptotic properties at higher doses, doses that might only be achievable in vitro.
Quote " Finally, the antioxidant activity of quercetin was confirmed using a cell-free system of radical generation "
http://www.sciencedi...014482703004105
Quote : " Our data suggest that QN exerts its protective effect by modulating the extent of lipid peroxidation and augmenting antioxidant defense system and thus protects the DNA in experimental animals."
http://www.sciencedi...300483X07007007
Quote: " In conclusion, pre-treatment of quercetin may protect against ethanol-induced oxidative stress by directly quenching lipid peroxides and indirectly by enhancing the production of the endogenous antioxidant GSH."
https://www.jstage.j...0_1398/_article
Re: cytotoxicity, and as a pro oxidant
Quote: " In the last ten years, there has been an important increase in interest in quercetin action as a unique antioxidant, but its putative role in numerous prooxidant effects is also being continually updated. The results are indicative of the intracellular metabolic activation of quercetin to o-quinone, the process which can be partially associated with the observed concentration-dependent cytotoxic effect of quercetin."
http://www.sciencedi...891584998001671
Quote: " Although the activity of quercetin is believed to be due to its antioxidative properties, it has recently been suggested that quercetin also has prooxidant activities, which might effect cytotoxicity directly.
Our findings suggest that quercetin protects mouse thymocytes from oxidative stress-mediated apoptosis and modulates the intracellular redox state through its antioxidant activity"
http://www.sciencedi...014482703004105

Edited by Kevnzworld, 10 March 2013 - 05:32 PM.


#26 Jean-François Savouret

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Posted 10 March 2013 - 05:41 PM

Two points:

Quercetin is a Janus molecule with a dual +/- activity re-oxidation.
Most data are OK, but "in-vitro". This is far from in-vivo. I dropped the matter when I observed its AhR activating effect.

JFS

#27 Daisy Neptune

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Posted 31 July 2013 - 06:16 AM

I can't understand anything that is written within this thread, can some just answer the question, is it ok to take quercetin with resveratrol. I thought quercetin helps the curcumin--my doc said to take curcumin, resveratrol and theaflavin--and I thought I would add in vit d drops and quercetin. So, does the quercetin affect the reservatrol, and is it better to take it separate at nightime? thanks for some clear answers, that aren't full of science jargon.
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#28 blood

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Posted 31 July 2013 - 12:10 PM

I can't understand anything that is written within this thread, can some just answer the question, is it ok to take quercetin with resveratrol. I thought quercetin helps the curcumin--my doc said to take curcumin, resveratrol and theaflavin--and I thought I would add in vit d drops and quercetin. So, does the quercetin affect the reservatrol, and is it better to take it separate at nightime? thanks for some clear answers, that aren't full of science jargon.


It's an "open question" as to whether they should be taken together or separately.

The answers to your questions have not yet been established by science.

(The concern over taking resveratrol and quercetin together is a hypothetical concern - it has never been demonstrated that the two supplements should not be taken together.)

If you do intend to take resveratrol and quercetin (and theaflavin) together, Life Extension has an excellent product containing those three factors (and some other beneficial compounds):

http://www.iherb.com...ggie-Caps/24377

Life Extension, CR Mimetic Longevity Formula, 60 Veggie Caps
Supplement Facts Serving Size: 2 Vegetarian Capsules Servings Per Container: 30 Amount Per Serving %DV Trans-Resveratrol [from Polygonum cuspidatum extract (root)] 250 mg ** Trans-Pterostilbene (as pure Pterospan and SMART^ pterostilbene) 3 mg ** Quercetin (as quercetin dihydrate) 150 mg ** Masquelier's Original OPC's [single and condensed (2-5) units of flavanols & polyphenols from Vitis vinifera (grape) seeds] 50 mg ** Black tea decaffeinated (Camellia sinensis) extract (leaf) [standardized to 12% TF2a theaflavin fraction (36 mg), along with TF1, TF2b and TF3 theaflavin fractions] 300 mg ** Fisetin [from (Rhus succedanea L.) extract (stem)] 48 mg **
**Daily Value not established.
^Same material as research trials


Edited by blood, 31 July 2013 - 12:15 PM.


#29 balance

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Posted 31 July 2013 - 01:08 PM

The problem I have with LEF's CR mimetic is that the dosages are way too low: Pterostilbene you'd ideally want 250mg, Quercetin 500-1500mg, Fisetin 100-300mg, Grapeseed 100-600mg (OPC's only 50mg in the product) so really you are paying for a resveratrol and theaflavin supplement. I'd take LEF's black theaflavin product separately and then take Biotivia 250mg Pterostilbene, Doctor's Best 100mg Fisetin, Jarrow Quercetin or LEF's "optimized" quercetin, Biotivia's 500mg Resveratrol. Guaranteed that would be way more potent.

Edited by piet3r, 31 July 2013 - 01:09 PM.


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#30 maxwatt

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Posted 31 July 2013 - 01:22 PM

The original Fluor de Lys assay found Quercetin activated SIRT1, but a more advanced assay found it did not. Moreover, a metabolite of Quercetin blocks SIRT1. So it may be counterproductive to combine the two. But SIRT1 is not the whole story: resveratrol also activates PPAR-alpha and PPAR-gamma, responsible for the exercise-mimetic effect some users have observed. Blood is correct in that no one knows from actual studies what the combination would do. My own approach is to add or remove supplements one at a time and observe the effects before deciding to keep or discard, and then try a combination. But even so longer term effects will not show up.

Quercetin according to some studies increases mitochondrial biogenesis, hence exercise endurance, enough so it was included in an Energy Drink endorsed by Lance Armstrong. But resveratrol also has this effect according to studies. If anything is likely to increase the effect of resveratrol it would be luteolin, which blocks the elimination of resveratrol so it stays in the blood longer. At least in theory.




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