Re: Resveratrol +/0s

[Guest guest]

In post # 24571 procyanidins are identified as the key ingredient in red wine, not resveratrol. I’ve reproduced the post below. Moral: don’t try to fool (or extract from) mother nature. Get your goodies from the food (or in this case “drink”), or from the skins of grapes to be sure.

Re: [ ] procyanidins and not resveratrol is the key ingredient in red wine

Red wine procyanidins, not resveratrol 4 health

Hi All,

The below paper is pdf-availed and may support the

Subject of this post to which this is a reply.

Oenology: Red wine procyanidins and vascular health

R. Corder, W. Mullen, N. Q. Khan, S. C. Marks, E. G.

Wood, M. J. r and A. Crozier

Nature 444, 566 (30 November 2006)

Regular, moderate consumption of red wine is linked to

a reduced risk of coronary heart disease and to lower

overall mortality1, but the relative contribution of

wine's alcohol and polyphenol components to these

effects is unclear2. Here we identify procyanidins as

the principal vasoactive polyphenols in red wine and

show that they are present at higher concentrations in

wines from areas of southwestern France and Sardinia,

where traditional production methods ensure that these

compounds are efficiently extracted during

vinification. These regions also happen to be

associated with increased longevity in the population.

High consumption of polyphenols inhibits

atherosclerosis in experimental models3, 4. Red-wine

polyphenols induce endothelium-dependent dilatation of

blood vessels and suppress the synthesis of

endothelin-1 (ET-1), a peptide that has a

vasoconstricting effect5, 6, 7, and this may account

for their anti-atherosclerotic activity. However,

there is a lack of consensus on the protective effects

of red wine, which may be due to variability in

vasoactive constituents in different wines.

Red-wine polyphenols are a complex mixture of

flavonoids (mainly anthocyanins and flavan-3-ols) and

non-flavonoids (such as resveratrol and gallic acid).

Flavan-3-ols are the most abundant, with oligomeric

and polymeric procyanidins (condensed tannins) often

representing 25–50% of the total phenolic

constituents8.

We used cultured endothelial cells to identify the

most potent vasoactive polyphenols in red wine (for

methods, see supplementary information). These were

shown by high-performance liquid chromatography with

mass spectrometry2 to be straight-chain B-type

oligomeric procyanidins (OPCs) (tetra-epicatechin

gallate, m/z = 1,305; procyanidin trimer-gallate, m/z

= 1,017; procyanidin tetramer, m/z = 1,153; and

pentamer-gallate, m/z = 1,593; see supplementary

information).

Total polyphenols and OPC content of each wine

correlated with the suppression of ET-1 synthesis

(Fig. 1a, . However, the linear regression plot for

total polyphenols intercepted the y-axis at about 5

mM, which is consistent with most polyphenols

(anthocyanins, catechins and resveratrol) lacking

vasoactivity at the concentrations found in wine5, 7.

Figure 1: Relationship between procyanidin content and

vasoactive properties of red wine.

a, b, Total polyphenol (a) and oligomeric procyanidin

(OPC) ( content correlate with the inhibition of

synthesis of endothelin-1, expressed as ED50 (dilution

inhibiting by 50%; see supplementary information); R =

0.84 for both, n = 165. c, d, Comparison of inhibition

of endothelin-1 synthesis © with OPC concentration

(d) of wines from different geographical regions. Au,

Australia; EU, France, Greece, Italy or Spain; SA,

South America; US, United States; Sd, Sardinia; Nu,

Nuoro province, Sardinia; swF, southwest France. CE,

catechin equivalents (see supplementary information).

***P < 0.001 compared with all the other wines; *P <

0.01 compared with the United States [Nu,

polyphenolds], and P < 0.001 swF for polyphenols and

log OPC] compared with the other wines; **P < 0.02

compared with the United States and South America [Nu,

log OPC], and P < 0.001 compared with the other wines

[Nu, log OPC].

To investigate how the OPC content of red wines from a

particular region might relate to mortality in that

region, we compared wines produced in areas of

increased longevity (as an index of overall good

health) with a broad selection of wines from different

countries. People living in Nuoro province, Sardinia,

have high longevity, particularly men9. In France,

there are marked regional variations in mortality from

coronary heart disease. We used the 1999 census data

to identify unusual patterns of ageing in France (see

supplementary information) and found that there are

relatively more men aged 75 or over in the département

of Gers in the Midi-Pyrenees in southwest France.

Wines from Nuoro and the Gers area have 2–4-fold more

biological activity and OPC content than other wines

(Fig. 1c, d). This difference remains (P < 0.001) when

OPC measurements are extended to a wider selection of

wines from the Gers area (2.9 0.1 mM, n = 58), from

France (1.8 0.1 mM, n = 61) and from other parts of

the world (1.5 0.04 mM, n = 227).

Grape seeds are the main source of OPCs but poor

solubility, combined with oenological and viticultural

factors, influence the amount of OPCs in wine8. The

higher OPC concentration in wines from southwest

France is due to traditional wine-making, which

ensures that high amounts of OPCs are extracted, and

to the flavonoid-rich grape Tannat, which makes up a

large proportion of grapes used to produce local wines

in the Gers area but is rarely grown elsewhere.

Absorption of OPCs and their identification in plasma

has been demonstrated in vivo10, but little is known

about their biological availability and metabolism.

Further investigation of OPC-rich wines and foods

should provide insight into how vascular function

might be optimally maintained.

From: Al Pater <old542000@...>

Reply-< >

Date: Thu, 3 Jul 2008 12:35:47 -0700 (PDT)

< >

Subject: [ ] Resveratrol +/0s

Resveratrol has plus and zeros. It counters aging conditions, but not aging. I am pleased to not have invested $ in resveratrol. The below paper is pdf-availed.

http://www.sciencedaily.com:80/releases/2008/07/080703120402.htm <http://www.sciencedaily.com/releases/2008/07/080703120402.htm>

http://tinyurl.com/6oq4jj

http://www.cbc.ca/health/story/2008/07/03/wine-aging.html

http://health.usnews.com:80/articles/health/healthday/2008/07/03/compound-in-red-wine-fights-ravages-of-age.html <http://health.usnews.com/articles/health/healthday/2008/07/03/compound-in-red-wine-fights-ravages-of-age.html>

http://tinyurl.com/5m75o3

http://www.sciencenews.org:80/view/generic/id/33832/title/Fountain_of_Youth,_with_caveats <http://www.sciencenews.org/view/generic/id/33832/title/Fountain_of_Youth,_with_caveats>

http://tinyurl.com/6qwd7e

http://ukpress.google.com/article/ALeqM5gqiZpHm3v9fsdam_0H6-iyhGW0Yg

http://tinyurl.com/5z5r29

Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span

J. Pearson, ph A. Baur, Kaitlyn N. , Leonid Peshkin, L. Price, Nazar Labinskyy, R. Swindell, a Kamara, Robin K. Minor, , Hamish A. son, Yongqing Zhang, R. Dunn, Kumar Sharma, Pleshko, A. Woollett, Csiszar, Yuji Ikeno, Le Couteur, J. Elliott, G. Becker, Placido Navas, K. Ingram, Norman S. Wolf, Zoltan Ungvari, A. Sinclair, and de Cabo

Summary

A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms.

In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice show a marked reduction in signs of aging, including reduced albuminuria, decreased inflammation, and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age.

Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.

....

Acknowledgments

A. Sinclair declares he is a consultant to Sirtris, a GSK sirtuin company, and a board member/shareholder of Genocea Biosciences, a vaccine company. J. Elliott declares he is a full-time employee and shareholder of GSK/Sirtris. ...

-- Al Pater, alpater@...

[Guest guest]

I agree- it's best to get good things from one's food and drink, but the fact that procyanidins may be responsible for beneficial health aspects of red wine does not discount the powerful effects resveratrol has been proven to possess.

On Thu, Jul 3, 2008 at 4:27 PM, Francesca Skelton <fskelton@...> wrote:

In post # 24571 procyanidins are identified as the key ingredient in red wine, not resveratrol. I've reproduced the post below. Moral: don't try to fool (or extract from) mother nature. Get your goodies from the food (or in this case "drink"), or from the skins of grapes to be sure.

Re: [ ] procyanidins and not resveratrol is the key ingredient in red wine

Red wine procyanidins, not resveratrol 4 health

Hi All,

The below paper is pdf-availed and may support the

Subject of this post to which this is a reply.

Oenology: Red wine procyanidins and vascular health

R. Corder, W. Mullen, N. Q. Khan, S. C. Marks, E. G.

Wood, M. J. r and A. Crozier

Nature 444, 566 (30 November 2006)

Regular, moderate consumption of red wine is linked to

a reduced risk of coronary heart disease and to lower

overall mortality1, but the relative contribution of

wine's alcohol and polyphenol components to these

effects is unclear2. Here we identify procyanidins as

the principal vasoactive polyphenols in red wine and

show that they are present at higher concentrations in

wines from areas of southwestern France and Sardinia,

where traditional production methods ensure that these

compounds are efficiently extracted during

vinification. These regions also happen to be

associated with increased longevity in the population.

High consumption of polyphenols inhibits

atherosclerosis in experimental models3, 4. Red-wine

polyphenols induce endothelium-dependent dilatation of

blood vessels and suppress the synthesis of

endothelin-1 (ET-1), a peptide that has a

vasoconstricting effect5, 6, 7, and this may account

for their anti-atherosclerotic activity. However,

there is a lack of consensus on the protective effects

of red wine, which may be due to variability in

vasoactive constituents in different wines.

Red-wine polyphenols are a complex mixture of

flavonoids (mainly anthocyanins and flavan-3-ols) and

non-flavonoids (such as resveratrol and gallic acid).

Flavan-3-ols are the most abundant, with oligomeric

and polymeric procyanidins (condensed tannins) often

representing 25–50% of the total phenolic

constituents8.

We used cultured endothelial cells to identify the

most potent vasoactive polyphenols in red wine (for

methods, see supplementary information). These were

shown by high-performance liquid chromatography with

mass spectrometry2 to be straight-chain B-type

oligomeric procyanidins (OPCs) (tetra-epicatechin

gallate, m/z = 1,305; procyanidin trimer-gallate, m/z

= 1,017; procyanidin tetramer, m/z = 1,153; and

pentamer-gallate, m/z = 1,593; see supplementary

information).

Total polyphenols and OPC content of each wine

correlated with the suppression of ET-1 synthesis

(Fig. 1a, . However, the linear regression plot for

total polyphenols intercepted the y-axis at about 5

mM, which is consistent with most polyphenols

(anthocyanins, catechins and resveratrol) lacking

vasoactivity at the concentrations found in wine5, 7.

Figure 1: Relationship between procyanidin content and

vasoactive properties of red wine.

a, b, Total polyphenol (a) and oligomeric procyanidin

(OPC) ( content correlate with the inhibition of

synthesis of endothelin-1, expressed as ED50 (dilution

inhibiting by 50%; see supplementary information); R =

0.84 for both, n = 165. c, d, Comparison of inhibition

of endothelin-1 synthesis © with OPC concentration

(d) of wines from different geographical regions. Au,

Australia; EU, France, Greece, Italy or Spain; SA,

South America; US, United States; Sd, Sardinia; Nu,

Nuoro province, Sardinia; swF, southwest France. CE,

catechin equivalents (see supplementary information).

***P < 0.001 compared with all the other wines; *P <

0.01 compared with the United States [Nu,

polyphenolds], and P < 0.001 swF for polyphenols and

log OPC] compared with the other wines; **P < 0.02

compared with the United States and South America [Nu,

log OPC], and P < 0.001 compared with the other wines

[Nu, log OPC].

To investigate how the OPC content of red wines from a

particular region might relate to mortality in that

region, we compared wines produced in areas of

increased longevity (as an index of overall good

health) with a broad selection of wines from different

countries. People living in Nuoro province, Sardinia,

have high longevity, particularly men9. In France,

there are marked regional variations in mortality from

coronary heart disease. We used the 1999 census data

to identify unusual patterns of ageing in France (see

supplementary information) and found that there are

relatively more men aged 75 or over in the département

of Gers in the Midi-Pyrenees in southwest France.

Wines from Nuoro and the Gers area have 2–4-fold more

biological activity and OPC content than other wines

(Fig. 1c, d). This difference remains (P < 0.001) when

OPC measurements are extended to a wider selection of

wines from the Gers area (2.9 0.1 mM, n = 58), from

France (1.8 0.1 mM, n = 61) and from other parts of

the world (1.5 0.04 mM, n = 227).

Grape seeds are the main source of OPCs but poor

solubility, combined with oenological and viticultural

factors, influence the amount of OPCs in wine8. The

higher OPC concentration in wines from southwest

France is due to traditional wine-making, which

ensures that high amounts of OPCs are extracted, and

to the flavonoid-rich grape Tannat, which makes up a

large proportion of grapes used to produce local wines

in the Gers area but is rarely grown elsewhere.

Absorption of OPCs and their identification in plasma

has been demonstrated in vivo10, but little is known

about their biological availability and metabolism.

Further investigation of OPC-rich wines and foods

should provide insight into how vascular function

might be optimally maintained.

From: Al Pater <old542000@...>

Reply-< >

Date: Thu, 3 Jul 2008 12:35:47 -0700 (PDT)

< >

Subject: [ ] Resveratrol +/0s

Resveratrol has plus and zeros. It counters aging conditions, but not aging. I am pleased to not have invested $ in resveratrol. The below paper is pdf-availed.

http://www.sciencedaily.com:80/releases/2008/07/080703120402.htm <http://www.sciencedaily.com/releases/2008/07/080703120402.htm>

http://tinyurl.com/6oq4jj

http://www.cbc.ca/health/story/2008/07/03/wine-aging.html

http://health.usnews.com:80/articles/health/healthday/2008/07/03/compound-in-red-wine-fights-ravages-of-age.html <http://health.usnews.com/articles/health/healthday/2008/07/03/compound-in-red-wine-fights-ravages-of-age.html>

http://tinyurl.com/5m75o3

http://www.sciencenews.org:80/view/generic/id/33832/title/Fountain_of_Youth,_with_caveats <http://www.sciencenews.org/view/generic/id/33832/title/Fountain_of_Youth,_with_caveats>

http://tinyurl.com/6qwd7e

http://ukpress.google.com/article/ALeqM5gqiZpHm3v9fsdam_0H6-iyhGW0Yg

http://tinyurl.com/5z5r29

Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span

J. Pearson, ph A. Baur, Kaitlyn N. , Leonid Peshkin, L. Price, Nazar Labinskyy, R. Swindell, a Kamara, Robin K. Minor, , Hamish A. son, Yongqing Zhang, R. Dunn, Kumar Sharma, Pleshko, A. Woollett, Csiszar, Yuji Ikeno, Le Couteur, J. Elliott, G. Becker, Placido Navas, K. Ingram, Norman S. Wolf, Zoltan Ungvari, A. Sinclair, and de Cabo

Summary

A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms.

In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice show a marked reduction in signs of aging, including reduced albuminuria, decreased inflammation, and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age.

Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.

....

Acknowledgments

A. Sinclair declares he is a consultant to Sirtris, a GSK sirtuin company, and a board member/shareholder of Genocea Biosciences, a vaccine company. J. Elliott declares he is a full-time employee and shareholder of GSK/Sirtris. ...

-- Al Pater, alpater@...

-- Diogenes - " What I like to drink most is wine that belongs to others. "

[Guest guest]

Actually, I think it may be for mice and humans- not sure about rats!On Sat, Jul 5, 2008 at 1:37 PM, Dowling <christopher.a.dowling@...> wrote:

Both.On Sat, Jul 5, 2008 at 2:20 PM, jwwright <jwwright@...> wrote:

Proved in rats or humans?

Re: [ ] Resveratrol +/0s

I agree- it's best to get good things from one's food and drink, but the fact that procyanidins may be responsible for beneficial health aspects of red wine does not discount the powerful effects resveratrol has been proven to possess.

On Thu, Jul 3, 2008 at 4:27 PM, Francesca Skelton <fskelton@...> wrote:

In post # 24571 procyanidins are identified as the key ingredient in red wine, not resveratrol. I've reproduced the post below. Moral: don't try to fool (or extract from) mother nature. Get your goodies from the food (or in this case " drink " ), or from the skins of grapes to be sure. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.

..

-- Rita Rudner - " When I eventually met Mr. Right I had no idea that his first name was Always. "

-- Bob Hope - " Middle age is when your age starts to show around your middle. "

[Guest guest]

Both.On Sat, Jul 5, 2008 at 2:20 PM, jwwright <jwwright@...> wrote:

Proved in rats or humans?

Re: [ ] Resveratrol +/0s

I agree- it's best to get good things from one's food and drink, but the fact that procyanidins may be responsible for beneficial health aspects of red wine does not discount the powerful effects resveratrol has been proven to possess.

On Thu, Jul 3, 2008 at 4:27 PM, Francesca Skelton <fskelton@...> wrote:

In post # 24571 procyanidins are identified as the key ingredient in red wine, not resveratrol. I've reproduced the post below. Moral: don't try to fool (or extract from) mother nature. Get your goodies from the food (or in this case " drink " ), or from the skins of grapes to be sure. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.

..

-- Rita Rudner - " When I eventually met Mr. Right I had no idea that his first name was Always. "

[Guest guest]

Proved in rats or humans?

Re: [ ] Resveratrol +/0s

I agree- it's best to get good things from one's food and drink, but the fact that procyanidins may be responsible for beneficial health aspects of red wine does not discount the powerful effects resveratrol has been proven to possess.

On Thu, Jul 3, 2008 at 4:27 PM, Francesca Skelton <fskeltonerols> wrote:

In post # 24571 procyanidins are identified as the key ingredient in red wine, not resveratrol. I've reproduced the post below. Moral: don't try to fool (or extract from) mother nature. Get your goodies from the food (or in this case "drink"), or from the skins of grapes to be sure. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.

..

[Guest guest]

Dr Dowling,

I was wondering about Alan's post which had the comment:

"Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife."

Surely that applies to humans?

And I don't see how I can infer the use of resveratrol from animal studies, nor inference from red wine studies. We have centenarians who have used resveratrol supps?

Regards

Re: [ ] Resveratrol +/0s

Actually, I think it may be for mice and humans- not sure about rats!

On Sat, Jul 5, 2008 at 1:37 PM, Dowling <christopher.a.dowlinggmail> wrote:

Both.

..

[Guest guest]

The first statement applies to mice. Mice's health concerns are slightly different from those of humans, so the results are not absolutely predictive of effects for humans.WRT humans, it is true only short term study results are available, but all indications are that resveratrol and related compounds can confer significant health benefits, if not extension of maximum life span. There aren't any control studies attesting to CR's ability to increase max human lifespan either, BTW.

On Sat, Jul 5, 2008 at 5:37 PM, jwwright <jwwright@...> wrote:

Dr Dowling,

I was wondering about Alan's post which had the comment:

" Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife. "

Surely that applies to humans?

And I don't see how I can infer the use of resveratrol from animal studies, nor inference from red wine studies. We have centenarians who have used resveratrol supps?

Regards

Re: [ ] Resveratrol +/0s

Actually, I think it may be for mice and humans- not sure about rats!

On Sat, Jul 5, 2008 at 1:37 PM, Dowling <christopher.a.dowling@...> wrote:

Both.

..

-- Lynde - " I sang in the choir for years, even though my family belonged to another church. "

[Guest guest]

Thanks very much,

The next thing I wonder about is the possible mode of action.

I know more or less that CR probably lowers oxidation products and that seems logical to me.

I have read that

Resveratrol Suppresses the Angiogenesis and Tumor Growth of Gliomas in Rats

http://clincancerres.aacrjournals.org/cgi/content/full/10/6/2190

Also, Oregon state has an overview that might be helpful:

http://lpi.oregonstate.edu/infocenter/phytochemicals/resveratrol/

The thing that bothered me was the Cytochrome P450 activity.

That I avoid because it interferes with my medication.

"Drugs known to be metabolized by CYP3A4 include but are not limited to HMG-CoA reductase inhibitors (atorvastatin, lovastatin, and simvastatin), calcium channel antagonists (felodipine, nicardipine, nifedipine, nisoldipine, nitrendipine, nimodipine, and verapamil), anti-arrhythmic agents (amiodarone), HIV protease inhibitors (saquinivir), immunosuppressants (cyclosporine and tacrolimus), antihistamines (terfenadine), benzodiazepines (midazolam and triazolam), and drugs used to treat erectile dysfunction (sildenafil)."

To me that is one major difference between CR and resveratrol.

Regards

Re: [ ] Resveratrol +/0s

Actually, I think it may be for mice and humans- not sure about rats!

On Sat, Jul 5, 2008 at 1:37 PM, Dowling <christopher.a.dowlinggmail> wrote:

Both.

.. -- Lynde - "I sang in the choir for years, even though my family belonged to another church."

[Guest guest]

This is an in vivo theoretical and, in vitro analysis, weak effect of resveratrol. Don't know that it's been established as a real human interaction or effect.On Sun, Jul 6, 2008 at 7:48 AM, jwwright <jwwright@...> wrote:

Thanks very much,

The next thing I wonder about is the possible mode of action.

I know more or less that CR probably lowers oxidation products and that seems logical to me.

I have read that

Resveratrol Suppresses the Angiogenesis and Tumor Growth of Gliomas in Rats

http://clincancerres.aacrjournals.org/cgi/content/full/10/6/2190

Also, Oregon state has an overview that might be helpful:

http://lpi.oregonstate.edu/infocenter/phytochemicals/resveratrol/

The thing that bothered me was the Cytochrome P450 activity.

That I avoid because it interferes with my medication.

" Drugs known to be metabolized by CYP3A4 include but are not limited to HMG-CoA reductase inhibitors (atorvastatin, lovastatin, and simvastatin), calcium channel antagonists (felodipine, nicardipine, nifedipine, nisoldipine, nitrendipine, nimodipine, and verapamil), anti-arrhythmic agents (amiodarone), HIV protease inhibitors (saquinivir), immunosuppressants (cyclosporine and tacrolimus), antihistamines (terfenadine), benzodiazepines (midazolam and triazolam), and drugs used to treat erectile dysfunction (sildenafil). "

To me that is one major difference between CR and resveratrol.

Regards

Re: [ ] Resveratrol +/0s

Actually, I think it may be for mice and humans- not sure about rats!

On Sat, Jul 5, 2008 at 1:37 PM, Dowling <christopher.a.dowling@...> wrote:

Both.

..

-- Lynde - " I sang in the choir for years, even though my family belonged to another church. "

-- Simone de Beauvoir - " To catch a husband is an art; to hold him is a job. "