resveratrol rumors

I've been told that scientists can't repeat David Sinclair's resveratrol work. A friend in pharma says resveratrol probably doesn't even activate Sirtuins. Does anyone know anything about this? I been taking resveratrol (Longevinex) for awhile so hope this is a false alarm!!!

Here's a link to show that the results were not just from Sinclair who is currently working with mice.

http://www.brown.edu...-05/04-002.html

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

Thanks for the link. What I have been able to find out is that the "controversy" is over how resveratrol is working. My friend says resveratrol is slowing aging in flies because it is an antioxidant and the whole Sirtuin link is bogus. I guess for me it doesn't matter as long as it works.

From a mailing list:

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2004 IN REVIEW
Is the world ready for an anti-aging pill?
Addendum: Update to THE ANTI-AGING PILL, Here & Now Books, 2004
By Bill Sardi

What a discovery. When David Sinclair PhD of Harvard Medical School and colleagues along with Konrad Howitz of Biomol in Plymouth Meeting, Pennsylvania, announced in the August 2003 issue of Nature Magazine that a red wine molecule may be the long sought-after fountain of youth, a ripple was created in the scientific community, but the public seemed to await confirmation. [Nature 425: 191, 2003] Red wine pills may mimic the beneficial health effects of calorie restriction, which has unequivocally been demonstrated to lengthen the life of yeast cells, fruit flies, roundworms, mice and humans. However, there was no mass rush to purchase wine or red wine pills as there was for red wine in 1991 when the Sixty Minutes TV program first announced the French Paradox, the fact the red-wine drinking French live longer and have much lower rates of cardiovascular disease despite their high-calorie, fat-laden diet.

Chris Mooney, writing for SAGE Crossroads, says the race to find an anti-aging pill was underway. "The race is certainly on," says David Sinclair of Harvard. "At this stage, we're just going as fast as we can, and they're going as fast as they can, and down the line we'll see who's got what, when we reveal our cards."

The competitive nature of anti-aging researchers and the "not invented here syndrome" resulted in many investigators downplaying the resveratrol discovery. It had only been shown in yeast cells, the extension of life by 30-50 percent. Humans could live another 35 years in good health, so the experts surmised, but proof of this in humans is a long way off, so they said.

A flurry of research studies on red wine molecules have been reported in the aftermath of the report in Nature, and initially many were not glowing. In fact, one wondered if scientists weren't ready to turn their wine back into water.

In March of 2003 and December 2004, Thomas Walle and colleagues at the University of South Carolina reported that resveratrol is not biologically available. The liver complexes resveratrol with other molecules (called sulphation and glucuronidation) and may render them non bioavailable. [Drug Metabolism Disposition 32:1377-82, 2004]

In late March of 2004 Stephen R. Spindler, of the University of Riverside, reported that late-in-life calorie restriction was also beneficial and could extend the human life span, based upon animal studies he conducted. [Proceedings of the National Academy of Sciences, April 13, 2004] Spindler also said it would be possible to find drugs that have the same effect on life extension as calorie-restricted diets. When asked: "Does this mean that eventually aging could be slowed by taking a pill?" Spindler replied: "I am confident that that day will come." Oddly, Spindler never mentioned resveratrol, which had made headlines months earlier. [Associated Press March 23, 2004] Spindler captains a company called Lifespan Genetics, funded by the Life Extension Foundation of Florida, which is attempting to use "gene chips" to screen for calorie restriction mimics. Resveratrol's life-extending properties were discovered at Harvard without the use of "gene chips." Spindler also founded Biomarker Pharmaceuticals, a company that is searching for calorie restriction mimics.

By May of 2004, Marty Mayo, a researcher at the University of Virginia, reported that resveratrol starves cancer cells, but cautioned that the alcohol component of wine might increase the risk for cancer. Unfortunately, the news press mistakenly quoted Mayo as saying too much resveratrol, rather than alcohol, might increase the risk for cancer. Resveratrol pill users literally spit the pills out of their mouths when they heard this mistaken news report. [Journal of the European Molecular Biology Organization (EMBO), May 20, 2004]

In late May of 2004, WESH-TV reporters in Boston confronted Professor Leonard Guarente of MIT with Longevinex, a new red wine pill that has been shown to exert Sirtuin 1 gene activity. Professor Guarente, who has been searching for an anti-aging elixir for 15 years and started his own pharmaceutical company, Elixir, said resveratrol shows promise but expressed concern over high doses in the Longevinex pill. "Once you start taking it in larger doses in pills, then I think one has to be cautious, and I wouldn't do it until there is experimental data that proves that in humans this does something good and it does not do something bad," said Guarente. [WESH-TV Boston, May 27, 2004]

In July of 2004, Brian Delaney, president of the Calorie Restriction Society, reported that he is currently practicing the calorie restriction regimen, as well as taking resveratrol. If it proves that resveratrol provides the same benefits as a CR diet, he says would "gladly give up the diet and take resveratrol instead." Delaney says he is "optimistic that work by people like David Sinclair and Konrad Howitz will soon give us even more evidence that resveratrol functions in the same way as the diet, but without the need for dietary restriction."

By late October of 2004, Louise Donnelly of the Imperial College in London reported that resveratrol may be helpful for chronic obstructive lung disease, and she repeated the findings of earlier studies that red wine pills are not bioavailable, which was widely aired in the news press. [American Journal of Physiology-Lung Cellular and Molecular Physiology] Donnelly warned that their research group had "looked at the over-the-counter" versions of resveratrol and found that "it's not very pure and probably wouldn't be worth taking." The major problem is bioavailability. The compound dissolves only in certain solvents, including alcohol, "and is cleared very rapidly in the liver," Donnelly said. She suggested a resveratrol mist delivery system for the lung.

In 2004 geneticists at the Wistar Institute in Philadelphia reported resveratrol may optimally bind to a particular site on the SIR2 gene which produces its superior biological effects over other similar-shaped molecules. [Proceedings National Academy of Sciences, May 18, 2004] What Wistar scientists are now attempting to do is re-design resveratrol into a patentable drug.

That's also what researchers at the University of Leicester in England are doing. Professor Will Steward and colleagues have begun an initial study among healthy volunteers with a daily 500 milligram pill of synthetically produced pure resveratrol. The goal of the Cancer Biomarker and Prevention Group at the University of Leicester is "to develop novel drugs which have promise for reducing the risk of developing cancer." The Leicester group is studying a re-arranged resveratrol molecule called 3,4,5,4'-tetramethoxystilbene, or DMU 212. [British Journal of Cancer 90, 736-744, 2004] Professor Steward was quoted to say that synthetic resveratrol is employed in their cancer study since "removal from wine is far too costly and complex." [Wine Spectator Nov. 7, 2002] (Note: resveratrol is widely available as a raw material for dietary supplements and is not costly.) The pure resveratrol pill is also to be tested on colon cancer patients awaiting surgery.

By July of 2004 Harvard researchers demonstrated that the activation of survival genes (Sir2, Sirtuin1) is induced in calorie-restricted rats, as well as in human cells that are treated with serum from calorie-restricted animals. [Science 305:390-2, 2004] The beneficial effects of calorie restriction are inching closer and closer now to being demonstrated in humans.

By August of 2004 the Boston Globe reported that Elixir Pharmaceuticals, the Cambridge, Massachusetts company, pioneered by anti-aging researchers Leonard Guarente and Cynthia Kenyon, "has suddenly seen its own time horizons shortened." With $55 million in venture capital, it hadn't found the fountain of youth and investors were getting impatient. By March of 2004 its chief executive officer had left. Elixir had been trumped by David Sinclair at Harvard with resveratrol. Without a gene target or a novel molecule to slow aging, Elixir's future appears to be clouded. [Boston Globe, August 2, 2004]

Also in August of 2004, Greek researchers reported that the fasting practices of Greek Orthodox Christians living in Crete may be partly responsible for the notable health and longevity in that Greek isle. Previously the Cretan diet of fish, fiber and plant foods had been extolled. [British Journal Nutrition 92:277-84, 2004]

By October 2004, Longevinex reported that the ability of its red wine pill to activate Sirtuin 1 gene enzymes had been confirmed in tests conducted at Biomol and that their airtight capsules had retained biological activity without degradation over a 10-month period. To date, no other resveratrol pill makers have validated the ability of their products to activate the Sirtuin 1 gene, though many websites touting these competing products widely report Sinclair and Howitz' discovery, intimating their products produce the same effect.

In early November, Paul McGlothin made a presentation at annual meeting of the Calorie Restriction Society (CRS), regarding the use of calorie restriction mimics. He reported that Longevinex, a red wine pill, produces profound beneficial effects in controlling blood sugar and lowering both oxidative-stress and cell-proliferation markers. McGlothin hopes to soon show the Sirtuin 1 gene enzymes are upregulated by red wine pills in human blood. If this can be authentically demonstrated, it would be Nobel Prize-type research. Previously anti-aging authorities indicated anyone who shows the beneficial effects of calorie restriction can be transferred from a molecular mimic to humans would win a special Nobel Prize.

Konrad Howitz of Biomol also made a scientific presentation at CRS meeting. Biomol is the developer of a Sirtuin 1 test kit that can measure the activation of Sirtuin 1 enzymes with the use of a fluoremeter. Howitz says University of Illinois researchers have used the Biomol test kit to demonstrate Sirtuin 1 gene enzymes are upregulated even in resveratrol that has been sulfated in the liver. The contention is that resveratrol, though it is readily absorbed from the digestive tract, may not be able to demonstrate any systemic effects if it is quickly complexed with sulfur and glucuronic acid once in the blood circulation. Also, resveratrol appears to have a half life of about 30 minutes, so it doesn't last long in the human body. On the other hand, these biological processes certainly attest to the safety of resveratrol since it is rapidly detoxified and degraded in the human body.

In mid-November 2004, Lifeline Therapeutics, Inc, announced that its Protandim anti-aging dietary supplement would be marketed by the first quarter of 2005. Bill Driscoll, President, stated, "I am very excited. Protandim is ... the first true anti-aging pill." Lifeline Therapeutics claims Protandim decreases oxidation by as much as 60 percent in humans in just the first 30 days of use by inducing the body to produce its own antioxidant enzymes, namely superoxide dismutase (SOD). Lifeline Therapeutics also claims levels of SOD have been directly correlated with aging in 14 different species, including humans. Species with the highest amounts of SOD live the longest, says Lifeline. Protandim is currently undergoing human trials at the Webb-Waring Institute of Cancer, Aging and Antioxidant Research. [PR Newswire Nov. 19, 2004]

But researchers at University College in London believe otherwise. Investigators used SOD mimetics to measure their effects on the life span of roundworms. The researchers first chemically raised levels of the destructive superoxide radical. Then SOD mimetics raised SOD levels by 500% and prolonged the life of the roundworms, but only when they were stressed by the chemicals. SOD mimetics did not prolong the life of roundworms when there was no biological rise in superoxide radicals. Living tissues make SOD on an "as needed" basis, when faced with oxidative stress. The provision of an SOD mimetic may be of no benefit when given regardless of oxidative stress. This research casts doubt into whether oral SOD pills would ever be proven to be an anti-aging strategy. [Free Radical Biology Medicine 37: 239-50, 2004]

In late November of 2004, Stephen R. Spindler won the Methuselah Foundation's first Rejuvenation Prize for "the first experiment to achieve rejuvenation in middle-aged mice, making them biologically younger while extending life spans." But the object of anti-aging research is not to prove pet mice can live longer. Spindler's animal studies, as impressive as they are, appear to be overshadowed by pioneering human research now underway among members of the Calorie Restriction Society.

By December 1, 2004, the Boston Business Journal reported that Sirtris Pharmaceuticals, a Waltham, Massachusetts-based company founded by David Sinclair, has received $13 million of funding from venture firms and intends to launch clinical studies with resveratrol-like molecules for the treatment of diabetes and obesity. With the FDA approval of an anti-aging pill virtually impossible, Sirtris has decided to test anti-aging molecules to treat disease.

The end of such an eventful year in anti-aging research was topped by Aubrey De Grey, geneticist and immortality theorist from Cambridge University, who predicted a 1000-year human life span is within reach and that people who are now living may be able to utilize technology to live that long. [BBC News, Dec. 1, 2004] De Grey didn't describe any particular anti-aging technology.

Copyright 2004 Bill Sardi

Here's the poop and it don't smell pretty...

J Biol Chem. 2005 Jan 31; [Epub ahead of print]

Substrate specific activation fo sirtuins by resveratrol.

Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell S, Napper A,
Curtis R, Distefano PS, Fields S, Bedalov A, Kennedy BK.

Biochemistry Dept., University of Washington, Seattle, WA 98195.

Resveratrol, a small molecule found in red wine, is reported to slow aging in
simple eukaryotes and has been suggested as a potential calorie restriction
mimetic. Resveratrol has also been reported to act as a Sirtuin activator, and
this property has been proposed to account for its anti-aging effects. We show
here that resveratrol is a substrate-specific activator of yeast Sir2 and human
SirT1. In particular, we observe that, in vitro, resveratrol enhances binding
and deacetylation of peptide substrates that contain Fluor de Lys, a
non-physiological fluorescent moiety, but has no effect on binding and
deacetylation of acetylated peptides lacking the fluorophore. Consistent with
these biochemical data, we find that, in three different yeast strain
backgrounds, resveratrol has no detectable effect on Sir2 activity in vivo, as
measured by rDNA recombination, transcriptional silencing near telomeres, and
life span. In light of these findings, the mechanism accounting for putative
longevity effects of resveratrol should be reexamined.

PMID: 15684413 [PubMed - as supplied by publisher]

See also:

The Longevity Gene
Lisa Scanlon October 2004
Technology Review.Com
An MIT Enterprise

http://www2.technolo...lon1004.asp?p=1

Nevertheless, plenty of other research groups at universities and companies around the world are salivating at the thought of SIR2s potential. Indeed, one of Guarentes main competitors is David Sinclair, one of his former postdoctoral fellows. Sinclair, now an associate professor of pathology at Harvard Medical School, disagrees with Guarente about what activates SIR2 in yeast. He believes that a molecule called nicotinamide and a gene called PNC1 control the activity of SIR2. Guarente, on the other hand, believes that the relative concentration of two molecules, NAD and NADH, determines SIR2s activity in yeast cells. In recent years, Sinclair has published several papers that attempt to disprove some of Guarentes theories and support his own. Theres been a big uproar over this, Guarente says. My feeling on this and I told [Sinclair]was, A, I think were right, and B, I dont think its that important. The dispute about yeast is almost a moot point, Guarente says, because the way in which the SIR2 equivalent is activated in mammals, which is more relevant to how it works in humans, is probably different. But nonetheless, I think were right about yeast, Guarente says firmly.

Apart from the public battles in scientific journals, Sinclair is also competing with Guarente on the pharmacological side, having recently formed a company, Sirtris Pharmaceuticals, to create the same kinds of drugs that Elixir is pursuing. Its a race now between the two, says Picard, who left MIT this summer for a position at Laval University in Qubec City. They both have very big labs working hard. They both have companies working hard, too.

See also: http://www.sirtrispharma.com/

Edited by milt_johnson, 23 March 2005 - 10:35 PM.

Here's the poop and it don't smell pretty...

J Biol Chem. 2005 Jan 31; [Epub ahead of print]

Substrate specific activation fo sirtuins by resveratrol.

Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell S, Napper A, Curtis R, Distefano PS, Fields S, Bedalov A, Kennedy BK.

... we observe that, in vitro, resveratrol enhances binding and deacetylation of peptide substrates that contain Fluor de Lys, a non-physiological fluorescent moiety, but has no effect on binding and deacetylation of acetylated peptides lacking the fluorophore. Consistent with these biochemical data, we find that, in three different yeast strain backgrounds, resveratrol has no detectable effect on Sir2 activity in vivo, as measured by rDNA recombination, transcriptional silencing near telomeres, and life span. In light of these findings, the mechanism accounting for putative longevity effects of resveratrol should be reexamined.

PMID: 15684413 [PubMed - as supplied by publisher]

Folks, this study, unless massively flawed or fraudulent, says that the whole rsveratrol-as-sirtuin-activator-&-thus-CR-mimetic thing is a result of laboratory artifacts and that old nemesis of lifespan studies, the short-lived strain!

Here are some details from the paper and commentary. Ad hominem caveat: as Milt noted, “5 of the 12 authors worked for Elixir Pharmaceuticals” – Guarente’s commercialization wing, and the key rivals to Sinclair’s Sirtris (& their collaborators, Biomol) in the time-wasting race to develop sirtuin-based CR-mimetic life extension drugs (although as we’ve seen, both have in fact retreated from such a goal to please the myopia of venture capital). Sinclair’s group are the folks who reported the sirtuin-activating and (apparent) life-extending effects of resveratrol in yeast (2) and supposed life extension in fruit flies & C. elegans roundworms, too (3).

That said, this IS just ad hominem: studies should be evaluated precisely and exclusively on their merits in design and execution, not on their funding source -- even if it's Big Tobacco, the Atkins Foundation, or (shudder) the Canadian Wheat Board. Both Sinclair's and Guarente's labs have produced much interesting work, and "a pox on both of your houses" doesn't get us far.

Now:

Resveratrol, a small molecule found in red wine, is reported to slow aging in simple eukaryotes [yeast, worms, flies] and has been suggested as a potential calorie restriction mimetic. Resveratrol has also been reported to act as a Sirtuin activator [genes implicated in CR in yeast & to a lesser extent rodnts & even  humans] , and this property has been proposed to account for its anti-aging effects.

We show here that resveratrol is a substrate-specific activator of yeast Sir2 and human SirT1. In particular, we observe that, in vitro, resveratrol enhances binding and deacetylation of peptide substrates that contain Fluor de Lys, a non-physiological fluorescent moiety, but has no effect on binding and deacetylation of acetylated peptides lacking the fluorophore.

OK, you’re glazing . Fluor de Lys, described in perhaps too much detail for most by Biomol’s Konrad Howitz at CR Conference III, is in essence a molecular ‘tag’ designed to let researchers monitor via proxy what is thought to be the key molecular action of sirtuins: the removal of acetyl groups – which are gene-silencing when tagged onto DNA, and activity-modulating when attached to proteins. Resveratrol’s claimed ability to enhance sirtuin activity rests on its ability to stimulate deacetylatioin of proteins tagged with FdL. What these folks found was that the presence of the FdL tag ITSELF is central to the ability of sirtuins to deacetylate these proteins: when, as in the real world, FdL is not tagged onto peptides, then whatever structure-function alteration which resveratrol imposes on sirtuins n longer results in enhanced deacetylation. Ie, resveratrol does not, in fact, have the key molecular action PRESUMED to underlie its life-extending effects in lower eukaryotes, & indeed on whose basis Sinclair’s group started working with it in the first place!!

Returning to the paper:

Consistent with these biochemical data, we find that, in three different yeast strain backgrounds, resveratrol has no detectable effect on Sir2 activity in vivo, as measured by rDNA recombination, transcriptional silencing near telomeres, and life span.

This is a bit more readily understood. Some of the functions of sirtuins which are thought or known to be connected to sirtuin-induced lifespan extension in yeast just do not happen in vivo in response to resveratrol. In fact, this was already observed by Sinclair’s group (2) but didn’t raise enough of a flag. I mean, a lifespan extension is a lifespan extension, right?

Yeah – unless there’s no LS extension! In Kaeberlein et al’s hands, “in three different yeast strain backgrounds, resveratrol has no detectable effect on … life span”!

Now what the heck is up with that? Mistake number 2: short-lived strains!

Sir2-independent life span extension by CR has been observed in the long-lived BY4742 strain background; however, the majority of reports examining CR in yeast have used the shorter-lived PSY316 strain background. CR by growth on low glucose, or by several genetic models, reproducibly increases life span in PSY316 by approximately 35%, while growth in the presence of 10-100 µM resveratrol is reported to enhance life span by up to 100% in this strain background ([2]).

We had found that, unlike the case for the BY4742 or W303R strains, overexpression of SIR2 fails to increase life span in PSY316AR [ie, a substrain of PSY316, in which resveratrol was reported to dramatically extend LS -- by more, in fact, than CR apparently does, on a RELATIVE scale (because it's a SHORT-LIVED STRAIN to begin with. So IOW, the strain in which resveratrol dramatically increases LS does NOT enjoy a LS advantagge from increased levels of Sir2 itself -- throwing, if nothing else, a monkey wrench into the CR-mimetic-sirtuin-activation hypothesis].

One possible explanation for this apparent discrepancy is that Sir2 [enzyme] activity is not increased in response to elevated SIR2 [gene] dosage in PSY316. As previously seen for PSY316AR [ie, one substrain of PSY316], overexpression of SIR2 had no effect on life span in PSY316AT [another such substrain]. Sir2-dependent silencing of [two known sirtuin target] genes integrated near telomeres WAS increased, however, indicating that Sir2 activity WAS elevated in these cells. Therefore, increased Sir2 activity, due to overexpression of the protein, failed to increase life span in the PSY316 genetic background [again providing strong evideence against the the CR-mimetic-sirtuin-activation hypothesis].

Since resveratrol is reported to increase life span in PSY316AT, but activation of Sir2 does not increase life span in this strain, we speculated that resveratrol might be acting as a CR-mimetic and enhancing yeast longevity by a Sir2-independent mechanism. We therefore tested the effect of resveratrol on life span in BY4742, a strain background in which the longevity effects of CR and Sir2 are separable. At a final concentration of either 10 µM or 100 µM [previously reported to activate sirtuins & extend LS in teh PSY316 strain], *resveratrol* obtained from Biomol Inc [gotta get that dig in there ] *failed to significantly increase either mean or maximum life span*. Similarly, no effect on life span was observed using a second source of resveratrol obtained from Sigma.

They then document the lack of sirtuin-activating effect absent the artificial Fluor de Lys tag.

Resveratrol was previously reported to increase life span by up to 100% in the short-lived PSY316AT strain [2]. The inability of resveratrol to increase life span in BY4742 suggested that resveratrol might act in a strain-specific manner. In order to determine the generality of resveratrol as a putative CR mimetic, we tested the effects of resveratrol on life span in W303R, another short-lived strain commonly used in yeast aging research. Unlike in PSY316, overexpression of SIR2 is known to increase life span in W303R (4).

However, similar to our results with BY4742, we were unable to detect any significant increase in either mean or maximum life span of W303R mother cells in response to resveratrol. In contrast to the prior report [by Sinclair's group (2)], we also found that resveratrol had no significant effect on rDNA recombination in W303R.

Given that we found no longevity effect from resveratrol treatment in either BY4742 or W303R, we wished to reproduce the previously observed [by Sinclair's group (2)] life span extension by resveratrol in PSY316. We observed a *marginal* increase in life span in response to resveratrol ...; however, the magnitude of the effect was much reduced compared to that seen [by Sinclair's group (2)] (*12%* increase in mean [replicative LS] [which is a dubiously-extrapolable LS measure IAC -- and see now (4), on which I've been planning to post for some time], *versus 60-100% reported* ). Similarly, we observed only a slight effect on life span in the PSY316AT strain (7% increase, p=0.29). Consistent with the prior report (and unlike the case for overexpression of SIR2), we also found that resveratrol has no effect on Sir2- dependent transcriptional silencing in this strain.

This, of course, sounds more like a flat-out contradiction. However, as I mentioned in my presentation at Conf III, the life-extending effects of resveratrol in yeast reported in (2) was surprisingly variable, & the effect on worms & yeast both widely variable & mostly quite piddley (3). Without having directly compared the results, I'm not sure, but it may just be that Sinclair's yeasts were kept even shorter than is natural for this short-lived strain, further exaggerating the correction when LS is NORMALIZED (not extended) by resveratrol.

We've seen that in mice a zillion times with antioxidants: BHT, melatonin, etc etc. And indeed,

there is no direct evidence suggesting that resveratrol can activate Sirtuins in vivo in either C. elegans or D. melanogaster. There are, however, several examples of other antioxidant compounds reported to increase longevity in invertebrates (e.g. (54-61)), suggesting that [the modest] life span extension by resveratrol could result from its antioxidant properties rather than its putative Sirtuin-activating properties.

In addition to its antioxidant properties, resveratrol has also been reported to specifically inhibit ... mitochondrial respiratory capacity at complex III through competition with coenzyme Q. These activities of resveratrol may be particularly relevant to its longevity promoting effects in C. elegans, as several mutants with decreased mitochondrial function have been reported to increase life span in this organism, and decreased coenzyme Q levels, accomplished either through dietary or genetic  manipulations, have a similar effect.

This latter effect is because, absent CoQ, these animals can't compensate by producing more endogenously; CoQ is the site where most mtROS are generated, as it "fumbles" electrons passed to it from Complex I, so reducing levels or blocking it reduces mtROS and extnds LS in these critters ...

We suggest that further studies of the longevity promoting properties of resveratrol should consider the full spectrum of biological processes likely to be altered by this important compound. This will allow for a mechanistic understanding of the effects of resveratrol on the life span of invertebrates, and perhaps, mammals.

After all of this, that is an awfully big "perhaps."

-Michael


1. Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell S, Napper A, Curtis R, Distefano PS, Fields S, Bedalov A, Kennedy BK. Substrate specific activation fo sirtuins by resveratrol. J Biol Chem. 2005 Jan 31; [Epub ahead of print] PMID: 15684413 [PubMed - as supplied by publisher]

2: Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE,
Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA.
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.
Nature. 2003 Sep 11;425(6954):191-6. Epub 2003 Aug 24.
PMID: 12939617 [PubMed - indexed for MEDLINE]

3: Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D.
Sirtuin activators mimic caloric restriction and delay ageing in metazoans.
Nature. 2004 Aug 5;430(7000):686-9. Epub 2004 Jul 14. Erratum in: Nature. 2004
Sep 2;431(7004):107.
PMID: 15254550 [PubMed - indexed for MEDLINE]

4. Minois N, Frajnt M, Wilson C, Vaupel JW.
Advances in measuring lifespan in the yeast Saccharomyces cerevisiae.
Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):402-6. Epub 2004 Dec 29.
PMID: 15625107 [PubMed - in process]

5: Kaeberlein M, Kirkland KT, Fields S, Kennedy BK.
Sir2-independent life span extension by calorie restriction in yeast.
PLoS Biol. 2004 Sep;2(9):E296. Epub 2004 Aug 24.
http://biology.plosj...al.pbio.0020296
"Deletion of FOB1 and overexpression of SIR2 have been previously found to increase life span by reducing the levels of toxic rDNA circles in aged mother cells [a mechanism not likely relevant to mammals -MR]. We find that combining calorie restriction with either of these genetic interventions dramatically enhances longevity, resulting in the longest-lived yeast strain reported thus far. Further, calorie restriction results in a greater life span extension in cells lacking both Sir2 and Fob1 than in cells where Sir2 is present. These findings indicate that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes."

Transcript of the Jim Lehrer NewsHour on PBS Television show with transcript of extended interview with Dr. David Sinclair:

http://www.pbs.org/n...nclair_ext.html

EXTENDED INTERVIEW:
DR. DAVID SINCLAIR

February 2005

Scientists have isolated a series of genes found in many different plants and animals that seem to control the aging process. Dr. David Sinclair, associate professor of pathology at Harvard Medical School, talks about how these anti-aging genes work and the prospects of marketable anti-aging drugs.  ....

See also transcript and video clip:

http://www.pbs.org/n...ging_2-28.html#

SCIENCE OF AGING

February 28, 2005

  Some scientists have discovered a set of "anti-aging" genes in animals that -- when manipulated -- have similar life-extending effects as calorie-restrictive diets. Correspondent Tom Bearden reports on the research into the relationship between genes and aging.  ....

Edited by milt_johnson, 23 March 2005 - 10:38 PM.

Also on the PBS site is a Q & A with Dr. Stephen Helfand of the University of Connecticut and Dr. David Sinclair of Harvard Medical School


One of the questions:
Linus of Glendale, Calif. asks:

What kinds of food would be beneficial to exploit this finding, or what kinds of food should be avoided?

Dr. David Sinclair responds:

It is not yet known if we can get enough of these molecules for our diets to make a health difference. But there is some epidemiological data suggesting we might. For example, the French Paradox is a controversial theory that the French have better cardiovascular health because of their red wine consumption.

The life extending molecules are made by most plants and therefore are in most foods we eat but usually only in trace amounts. Resveratrol, one of the best life-extending molecules in lower organisms, is concentrated in red wine because of the extraction process and its storage in a dark air-tight container. Only trace amounts are found in grape juice. Quercetin, a similar looking molecule, is in apples and onions. Head for wines and foods that have been stressed before, during or after harvesting. Avoid plants that have been pampered or products that have been exposed to light or air for long periods, since they are often light- and oxygen-sensitive.

Plants make these molecules when they are stressed, e.g., when they lack water or nutrients, are exposed to too much sun, or have an infection. Pinot Noir is a wimpy grape and wines made from them tend to have the most resveratrol. Californian wines on average tend to have less resveratrol because the plants are not as stressed as say upstate New York where the dampness means that the vines can suffer from fungal infections. My laboratory has a theory that plants make these molecules to turn on their own defenses via the SIR2 protein.

A word about resveratrol: This small molecule from red wine is currently in human clinical trials to treat colon cancer and oral herpes, and, in mice, protects against stroke, heart attack, spinal cord injury, heart disease, and is one of the most effective cancer treatments ever discovered.


Seems like MR Sinclair is bullish on resveratrol


but also this question


Randall Bosin of Chevy Chase, Md. asks:

Is it likely that drinking red wine, eating grapes or taking resveratrol in the form of supplements can slow down aging? If so, how much, say, red wine would one have to drink to achieve this? Also, is there a good way a layperson can keep up with research in this field?

Dr. David Sinclair responds:

Resveratrol is not an easy molecule to protect from oxidation. Most commercially available supplements I have tested have no ability to stimulate SIR2 enzymes.

How about red wine? First, I should say that resveratrol influences many proteins that are linked to better health, not only SIR2. But can a glass of red wine provide enough resveratrol? Based on the older studies, the answer is a resounding "no." This is still the prevailing view. After drinking red wine, levels of resveratrol in blood barely reach the concentrations thought to be required for SIR2 activation, and, what's more, resveratrol is processed by the liver into a variety of different forms within about 15 minutes of entering the bloodstream.

That said, I am no longer dismissive of the idea that we get enough of these molecules in our diet. For example, recent work by my lab and others show that we may only need trace amounts of resveratrol to protect our cells from death and damage (250 nM). These levels might be achievable by drinking red wine. What's more, resveratrol's processed forms -- which circulate in our bodies over nine hours -- might also be bioactive.

Where to get info? If you can access the scientific literature (say using PubMed) there is abundant information. For the lay public, there is almost nothing available, I'm afraid. It is all too new. A colleague, Lenny Guarente, has written a book called "Ageless Quest." He and I are writing an article for Scientific American, which should be out in 2005.

You can read the rest here:


http://www.pbs.org/n...h05/aging1.html

Milt, It looks so far that no one has proof that it does any thing in pill form and theres also a debate if resveratrol does any thing at all.

I hope it works, but things like this come and go so you have to take every thing with a grain of salt.

heres another good article about resveratrol and Longevinex

http://www.betterhum...ID=2004-06-28-1


Controversial compound

So why isn't everyone taking resveratrol? After all, it's already available in pill form. Why aren't doctors recommending it?

It's not that such a pill wouldn't be welcome. Bill Sardi, a journalist and the creator of the resveratrol supplement Longevinex, says that a pill that mimics caloric restriction is vital as it would be difficult to get people to eat less. "Most of the Western countries have added about 1,000 calories to their diet in the last 30 years," he says. "We need something to bail us out of the metabolic problems such as obesity and diabetes because we're probably not going to change the dietary habits of the public at large."

Sardi met with Sinclair last fall after he read about his and Howitz's discovery. By then, many companies had already created resveratrol pills, but experiments showed that they had no biological activity in vitro.

In order for resveratrol supplements to be effective, Sardi thought, the pills should replicate the dark, airtight environment of a sealed wine bottle to prevent oxidation that decreases resveratrol's effectiveness. Sardi decided to create a resveratrol supplement that also contained quercetin, which, like resveratrol, is a polyphenol found in red wine. He teamed with Capsugel, a division of Pfizer headquartered in Morris Plains, New Jersey, to put the liquid-suspended ingredients of his supplement Longevinex into an airtight capsule under nitrogen, which preserves it from oxidation.

Sardi and his company claim that Longevinex supplements provide the health benefits of red wine without the calories, alcohol and sulphite preservatives. In addition, based on resveratrol experiments performed by numerous scientists (an analysis of which is in Sardi's book The Antiaging Pill), he also believes that the supplements can help extend human life and prevent aging-related diseases.

Before Sardi, or anyone else, can legally make this claim, however, more tests are needed. But scientists are hopeful that resveratrol is the key to mimicking caloric restriction in humans. "In the laboratory [resveratrol] can promote survival of cultured human cells under various stresses and stimulate cellular antioxidant defensives," says Howitz. "It is still an open question whether the same will be true in laboratory mice, not to mention humans."

Howitz is reluctant to make claims about the effectiveness of resveratrol in humans because it's more difficult to achieve and maintain the same levels of resveratrol in a person as researchers can in a Petri dish of cultured cells, as demonstrated in a recent study by Thomas Walle at the Medical University of South Carolina in Charleston.

Walle and his team of researchers tracked the absorption of resveratrol in six human subjects. Testing 15 minutes after an oral dose and then repeatedly for the next 72 hours, they weren't able to find the free form of resveratrol in the subjects' bloodstream. The body quickly metabolized the resveratrol and most of it was found bound to other chemicals in the subjects' urine within 12 hours of ingestion.

"We found no evidence that any resveratrol will reach into the systemic circulation," Walle told Reuters Health in April, "and the reason for that is very extensive metabolism of resveratrol as it is being absorbed into the body. It is completely broken down into metabolites very rapidly." Walle's team did find signs that resveratrol accumulated in cells in the oral cavity and along the digestive tract and could be active in those areas.

Some researchers also fear that since resveratrol is a phytoestrogen—a plant compound with estrogen-like effects in the body—it could increase a woman's risk for breast cancer. Sardi dismisses this fear, however. He says that in a Petri dish, at high concentrations and prolonged exposures, resveratrol would act like estrogen and promote the growth of breast cancer cells. But he says that this is unlikely to happen in the human body for two reasons. "Since resveratrol works in a few minutes and the liver is glucuronidating, it's gone and out of the body and you don't have a prolonged estrogen-like effect in the body," he says. "Secondly, resveratrol as a molecule is about one-7,000th the strength of your natural estrogen."

Elusive evidence

Since there haven't been any clinical trials done in mice or humans with resveratrol pills, however, it's too early to tell whether or not they actually work and what their long-term effects on humans might be. The fact that longevity studies in humans by definition take many years—which is why researchers use short-lived species such as yeast as models of aging—has been a barrier to resveratrol's wide use. "While I can show with little or no room for doubt that pure resveratrol is an effective activator of Sirt1 enzyme," says Howitz, "getting an answer on whether resveratrol has an antiaging effect in mice will take several years." Humans will take even longer.

Still, Walle's finding and the difficulty of conducting longevity studies hasn't dampened enthusiasm for resveratrol's antiaging potential. Sardi, for example, doesn't believe that a blood level measure is an accurate test of resveratrol's activity. He says that resveratrol works as a nutrigenomic, directly switching genes on and off. He thinks that resveratrol works quickly and could feasibly get into and out of "genetic machinery" in five minutes. Sardi also says that quick metabolization can be addressed. Longevinex's supplement, for example, includes other antioxidants also found in red wine, such as quercetin, which Sardi says inhibit the sulphation and glucuronidation that caused the quick metabolization of resveratrol in Walle's study.

Recent studies support Sardi's assertions. This June, BIOMOL conducted a biochemical assay testing 14 brands of resveratrol dietary supplements and found that only Longevinex exhibited significant Sirt1 activation. "Longevinex did stimulate Sirt1 activity," says Howitz, "an effect in all likelihood due to its content of resveratrol and quercetin, two known Sirt1 activators."

While Howitz says that they don't have enough information to understand why other resveratrol pills don't activate the enzyme, he believes it may be because they contain mixtures of various plant polyphenols. While resveratrol and quercetin stimulate Sirt1, other polyphenols such as cyanidin and epigallocatechin inhibit enzyme activity. Howitz also says that Longevinex's effectiveness in humans can only be determined through "actual human testing," which Sardi and his company plan to do in the next few months.

And so, those interested in whether resveratrol is the real antiaging deal might not need to wait long for evidence one way or the other. Sardi is completing a protocol for a study in humans to measure the effects of Longevinex to see if the supplement can mimic caloric restriction in humans. Sinclair is planning pure resveratrol studies on mice, which should be completed in two years. If the mouse studies are successful, he says, he'll then test monkeys—but these studies would take years to complete. Sardi, Howitz and Sinclair all agree that the best way to determine if a resveratrol pill mimics caloric restriction in humans is to see if the pill causes a decrease in insulin levels, blood pressure and body temperature, and causes an increase in high density lipoprotein—"good cholesterol."

For now, though, the jury's still out, and that hasn't been great for Sardi's sales. He admits that he has only a few thousand customers and that there wasn't the explosion of interest he expected when he began selling the supplements in January. Most people don't want to live longer, he says, because they don't want to get sick and don't understand that resveratrol could help prevent many diseases associated with aging. "They don't even think it's possible," he says. "They can't imagine that they would be healthy."

Too good to be true? At this point, it's buyer beware.

heres a post about LEF's version of Resveratrol that seems to refute some of longevinex claims

http://forum.lef.org...px?f=35&m=17704


- "The supplier of Life Extension's resveratrol provided the following reply:
A competitor claims that all resveratrol products on the market but the one it sells are "unstable" and without "biological activity". This company claims that resveratrol has to be produced in an oxygen-free environment in order to be stable; otherwise it will break down and become worthless. The definition of "biological activity" according to this company is the ability to extend the life of yeast cells as exemplified by a commercial kit known as the "Fluor de Lys". In this assay kit, something is considered "bioactive" if it causes lysine 382 of a p53 gene to fluoresce. The validity of this test was recently brought into question when it was learned that the results don't hold up in vivo (Kaeberlein, et al. JBC Papers in Press, 1/31/05).

The usual definition of "biologically active" is something has an effect on a biological system, such as a cell, an organ or the like. In that regard, Life Extension's I3C/resveratrol product was recently shown to have biological activity in human colorectal cancer cells where it activated a gene that causes cancer cells to die (Lee, et al. Biochem Biophys Res Comm 328:63). LE's resveratrol/I3C combination worked better than either I3C or DIM alone to activate this gene in human colorectal cancer cells. We will be reporting on this study soon.

Life Extension would never steer you wrong. Our resveratrol is the of the highest quality available. It is made from organic French grapes and a plant known as Polygonum cuspidatum. It is maintained in a natural matrix of complimentary polyphenols and related compounds that help it remain stable and absorbable in the body. Quercetin, which naturally occurs alongside resveratrol, is added in a synergistic amount for stability and enhanced bioavailability. As to the question of how long LE resveratrol "stays in the blood", we hope not long since we want to see it in tissues doing something. In general, resveratrol doesn't stay in circulation very long; it's absorbed through mucous membranes and can be detected in the plasma of animals in as little as five minutes. We will be able to report to you soon about which genes LE resveratrol affects. In the meantime, know that LE resveratrol has undergone and passed an accelerated stability study where it maintained potency for up to two years. It has been tested for potency and meets or exceeds the stated potency.

Resveratrol in its natural matrix is reported to be very stable. According to the USDA, peanuts stored for up to 3 years still contained resveratrol (Sanders, et al. J Agric Food Chem 48:1243), and freeze-dried grape powder also contained resveratrol (Meng, et al. J Agric Food Chem 52:935). Last but not least, although light can have a negative effect on resveratrol, you don't have to worry that the resveratrol in your peanut butter will disappear if it's exposed to air: it won't (Ibern-Gomez, et al. J Agric Food Chem 48:6352). Despite the claims of a competitor, LE resveratrol is stable, of the highest quality, and biologically active--something you will soon be hearing more about in the near future." - Posted by the Moderator

I'll stay out of the debate except to comment (as a doc):

"Why aren't doctors recommending it?"

There would have to be 10 double blind studies showing it was better then sliced bread..and then most docs still wouldn't recommend it as they don't believe in supplements....

Ah, maybe here is the key to finding cheapest source though more research needs to be done (and perhaps as well as found out by yours truly), "Polygonum cuspidatum."

That plant is quite common and extracts leaving behind the tannin I suppose, are available at apparently less cost than other sources of resveratrol. But as scott suggested, there may be a real barrier to finding that data and it may not be shouted from every roof top.

I am keeping close tabs on this thread and appreciate the exposition of both sides of the "debate." Will do some more research myself such as a quick google search on Polygonum cuspidatum which brings up a lot of sources. Now I want to see the clinical trial studies on these extracts. That Japanese knotweed is quite common and there are other knotweeds that should be looked at. Maybe the tannin could be removed by a person at home from the common "weed" leading to the best source for personal consumption.

Longevinex ... provides the key RED WINE POLYPHENOLS as extracted from red grape skins and other botanical sources (Giant knotweed, botanical name Polygonum), without the drawbacks of alcohol, calories or preservatives associated with wine itself."

.... Resveratrol, from botanical sources, is available and included in Longevinex capsules. The packaging process uses LICAPS- Capsugel.

Resveratrol by Longevinex: http://www.longevinex.com

Longevinex also availabe at: http://www.puritypro...uct.asp?sku=184

Edited by milt_johnson, 23 March 2005 - 10:41 PM.

Hmmmm, I wonder if this is another candidate for delivery via DMSO.

Apparently, peanut sprouts are a good source: http://www.sproutnet..._kernels_to.htm

The following is the only place I found so far where they claim the knotweed source is many times more concentrated than grape sources: http://www.askshelly...ge_of_menopause

Protyki®n trans-resveratrol is similar in chemical structure to the synthetic hormone DES, yet it has no serious side effects. A natural substance found in grapes and other plant foods, Protykin® trans-resveratrol is extracted from the root of the Chinese medicinal herb Polygonum cuspidatum. It contains more than 1,000 times the amount of natural resveratrol available in wine or grape-derived products and is the most concentrated natural source of trans-resveratrol available on the market today.

The root extracts of Polygonurn cuspidaturn are known as Hu-Chang and Ko-jo-kon (Chinese and Japanese respectively). One should be able to get it from a Chinese herbal supply of which we have many here in the San Francisco bay area.

Huckleberries also appear to have it in appreciable amounts and that grows wild and produces large crops of berries here on the North coast of California http://www.annieappl.../berandres.html . I've been trying to find the results of this study but so far only the announcing that the study has been done. Any one interested in looking for relative concentrations of the two forms of resveratrol in various plants including huckleberry?

Concerning bioavailability, one should suspect that is dependent on what matrix is taken. I think, just off the cuff, the plant sources rather than the extract might be more persistent and release in a timed fashion rather than the pure form.

Oh, maybe it is worth noting that somewhere along my research I found statements that red wine from cooler regions had more than from hot regions. Apparently stress, especially coolness and more moisture, cause the resveratrol to increase in concentration as a result of more need for defense from one main fungi that attacks grapes and ellicits its production and possibly other fungi too. I didn't note the URL.

Edited by Chip, 14 March 2005 - 02:13 AM.

Might be relatively easy and cheap to acquire. Since the botanical sources grow in oxygenated atmosphere and are probably harvested and stored without nitrogen gas use, one wonders as to the claims.

Looking at the indication for which the knotweed has been used for centuries as an herbal medicine, looks like some antioxidants of power and breadth of effect are gotten just from the herb. I don't discount Chinese herbal medicine until I've seen data refuting its claims, which does and has happened but looking at the long resulting use of herbs for treating maladies, one wonders as to whether or not this is evidence that a tea of the stuff could be used as a source of resveratrol. I read that use of ethanol in its extraction is more efficient than water. The extraction process, guess I got more research to do. Apparently there are a number of different processes and I wonder if it could be reduced to a kitchen table process.

Oh Oh Oh

The bark of the lower stems of the knotweed are used as well as the bark of the rhizomes. They are red colored! Red wine is red (doh) I haven't seen one of those wild huckleberries for a couple of years but they were outside my door for a couple of decades. They have red stems and often a red tint to the dark purple berry. There is also a very pungent totally red huckleberry that is not as common. It needs to be looked at carefully! Peanut skins are almost red.

I'm seeing red and I like it.

Edited by Chip, 14 March 2005 - 03:33 AM.

Uh, milt. The same reasoning that leads to the expensive packaging of Longevinex suggests making a liquid extract when you are ready and in the amount that you want could work. I understand they store it in a liquid form which is why it must be encapsulated carefully under anaerobic conditions. Right use of the word anaerobic? Locked up in plant cells may be the most efficient way to keep it in your pantry, extracting doses when you want to take them. Dried and/or frozen huckleberries, knotweed from your corner lot, peanut sprouts. Need to do more research to figure out the most efficient source(s). That data is not readily available partly due to the desire to keep people from finding their own sources, preserving dependence through ignorance maybe for money?

Ah, I tell you, this privitazation of information is a bulwark against finding out what we can do efficiently. Every time I found a paper that would have given me the concentration of trans-resveratrol in Japanese knotweed I ran into being required to pay $30 for the priveledge. From the following news story at http://news.bbc.co.u...and/2180344.stm they quote an expert in plant phenols talking about Polygonum cuspidatum

Professor Alan Crozier has found the root of the plant, which is known as Itadori in the Far East, contains large amounts of rezveratrol.

Rezveratrol is widely held to offer protection against cancer and possibly heart disease.

The protective substance is found in much smaller concentrations in grapes, wine, peanuts and soy.

Prof Crozier said: "Rezveratrol is a very strong anti-cancer agent and it is present in red wine, not in huge amounts, but it is there. This stuff is rolling in rezveratrol."

The Glasgow University-based human nutrition expert said that the knotweed's root can be used to make tea.

He said: "It's used as a herbal tea and it's supposed to reduce the effects of arthritis, rheumatism, cardio-vascular disease. You name it, it stops it and prevents it."

'Very invasive weed'

The professor's research on the plant is at an early stage, but he believes it potential to support people's health warrants further study.

He said: "You don't have something that is used for three or four centuries and has no effect whatsoever.

"But to demonstrate scientifically that there are truly protective effects needs a lot serious experimentation."

Just how much trans-resveratrol is in Polygonum cuspidatum shavings? Could we just use the tea of the lower stem and root shavings to give us the doses we want? Just how much is in huckleberries and blueberries? Has any one gotten around these folks seeking to make a buck off of human suffering? Cursed to be a spirit in a material world!

That is all understood. We have statements that the herb does show in clinical trials many of the benefits of resveratrol from wine and I see some of those at pub-med.

However, tests conducted by Harvard researcher David Sinclair, Ph.D., and Cornell’s Leroy Creasy, Ph.D., a professor of plant science, failed to find any significant biological activity of resveratrol in dietary supplements including tablets, capsules or liquid herbal extracts.

If an aqueous extract is bottled with a little air then we might expect the resveratrol to become ineffective. If you make a hot tea and drink it right away, you are going to get some of that resveratrol faster than it can be rendered useless by exposure to air and this would help explain the results found for the knotweed. Furthermore, the resveratrol appears to be locked up in the bark cells of the knotweed and does not evaporate until it is extracted. Consuming the herb rather than the extract should be able to provide active trans resveratrol through digestion. I believe I recall that HCl is used for some of the most efficient extraction and that is what we have in our stomachs.

Looks to me like the Longevinex brand justification is a careful selection of data to be literally true but largely misleading. Valuable to see that extracts are rendered useless, if we are to trust these claims but they totally do not address consuming the herb itself, perhaps as a tea to be drunk immediately upon infusing the herb with hot water or powdered bark put in capsules. Consuming huckleberries and blueberries should also be studied for active resveratrol delivery. Do the dried fruits provide it? I see mention that raisins have a significant amount.

I think I know where I have seen some knotweed of the proper kind growing in our vicinity. Gonna take my kids for a bike ride with my trusty back-pack. There should also be some huckleberries in the nearby coast foothills that I can reach within a half hour drive. From what I can tell, one cup of the tea of the lower stems (more bark than pith compared to the roots) of the knotweed might give one all the resveratrol needed. I see that concentration in the knotweed is also directly related to sunshine and UV exposure. Summer time harvesting would be best. I also notice the way it is made available by Chinese herbalists is basically the whole root sliced thinly crosswise. Collecting the small stems begins to look more effective than buying the herb from our local herbalist. Still, it would be nice to have some statistics to support my hypothesis and it is not that the research hasn't been done, it's just not made freely available. That is the data that I need. What you have shared here over and over again, milt, does not provide me with that data. I want to see how much of the trans-resveratrol is in what parts of what plants. Is the lower bark of Polygonum cuspidatum and a couple of other knotweeds the best source as long as it taken in its matrix? I suspect so.

I see another thing here milt, that gives me further cause to question this research, your presentation. I see few of your own words, lots of copying and pasting including stuff that is obviously copyrighted as with the choicepoint quotes. I was caught out on another of the problems with your presentation myself in another thread, I passed on an URL without investigating whether or not I was giving useful data in lieu of the thread's subject. I drill down into that list of providers you gave and I see it is basically just a cut and a paste of URLs from a search engine. I start to investigate them and I find that many do not have resveratrol for sale and those that do supply only a purified extract, again not answering my questions, not addressing my hypothesis that non-extracted essentially dietary and herbal supplementation means exist to increase the resveratrol in our systems. Another thing is the use of the blue font. That is your privilege but it makes people who prepare for best reading for the default font color, perhaps, change their viewing settings to make the blue font less of an abstraction or try to stomach potential eye strain.

Adherence to some sound information sharing methods aside, I see that peanuts are considered a good source, especially the skin and roots. Makes me wonder about the peanut shells. Maybe they'd make a nice tea. Think next time I'm at the main health food store in our area I'll pick up some raw peanuts and maybe some peanut butter. Of course I'll seek to get that which includes the skins. I bet it would be possible to filter the skins off, maybe they have even collected at the base of the supply bin at the store. I could get peanut skins for the price of peanuts possibly, pack em undried into capsules and keep them in the fridge. A recent article I came across via a Google news search on resveratrol suggested peanuts at an ounce and a half a day, small handful and a half, accruing many health benefits.

I've seen a couple of articles mentioning plums as a significant source of resveratrol. I've yet to see any concentration statistics for various plant sources except that analysis of peanut sprouts I pointed to earlier. I wonder what would happen if you put the pea sprouts under UV light for a few hours? What about prunes? How much is in what berries to what extent? There is a red thimbleberry that I used to seek out at ripening time on the North coast of Calif. It is bright red and big and, though perhaps a bit seedy for some, one of my favorite berries. It grows in the fog belt so probably has to fend off fungi well. There is also Salal which has a big blueberry like fruit that is one of my favorites, again, within the fog belt. Salal's stems are largely red near the base.

Such a paucity of information out there that is not geared towards supporting the establishment of profit industry, be it the wine or supplement industries.

Not a soap box but some real communication. Thank you for not using the blue font and expressing your own views.

I see evidence that I can not cite right now, perhaps later in my wanderings I'll come across it again, that too much resveratrol leads to the opposite, quickening of the aging process so its a two sided sword. Buy supplements and give yourself the 2 mg a day and then try to keep it out of your diet to avoid the danger of getting too much or scrap the supplement approach and incorporate more foods and perhaps some tea now and then. I just bought some raw organically grown peanuts at my local health food store. Their benefits for cardiovascular health, besides weight loss, may be indicative that just a small handful and a half gives one the required dose of resveratrol each day. I have decided I'm going to move the family out of the city to where we can get wild berries more often, prohibitively expensive here in the city. I also plan on looking for the Japanese knotweed and collect some of the base stems for tea. Amongst all the sources I don't think it adds any more work than it requires to feed oneself.

Sounds like the Longevinex product is sound and their reasoning and testings spurred my approach, getting resveratrol from the plant sources rather than an extract. That will require less money, less labor. I would like to see more of the statistics as to how much active resveratrol can be supplied by various plant foods and teas both for the purpose of supplying enough and not too much. I find it interesting that the listed contents of each Longevinex capsule contains twice as much weight as the capsule. They need to repair their list of ingredients as I suspect that is what is wrong and not physics.

Thanks for the informative discussion.

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

I wonder why boiled peanuts might show as much resveratrol as red grapes, not too dissimilar from that in red wine. The proportions of serving are a bit skewed, less than a half though. Wonder if boiling them causes a stress to the live bean that causes a quick resveratrol synthesis in the peanut.

From http://www.holisticb...ages/notes1.htm I get

Although grape skins (and red wine) are high in resveratrol, grape leaves are one hundred times richer in resveratrol than the fruit.

Edited by Chip, 17 March 2005 - 02:21 AM.