1708 replies to this topic

[ryan1113]

The pro-aging and DNA damaging effects of emodin. Posted by someone to sci.life-extension today:






Zhonghua Xin Xue Guan Bing Za Zhi. 2006 Jan;34(1):44-9.

Involvement of p53-dependent pathway in the antiproliferative activity
of emodin in human smooth muscle cell.


[Article in Chinese]


Wang XF, Ge JB, Sun AJ, Xu DL, Wang KQ.


Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital,
Fudan University, Shanghai 200032, China.


OBJECTIVE: To investigate whether p53 pathway participates in the
effect of emodin on vascular smooth muscle cell proliferation.
METHODS: The effects of emodin on vascular smooth muscle cell
proliferation were evaluated by cell count, senescent-associated beta-
galactosidase staining, and annexin V staining. DNA synthesis was
determined by (3)H-thymidine corporation, cell cycle was analyzed by
FACS, the p53 protein level was measured by Western blot and cDNA
expression array technology was used to demonstrate the effect of
emodin on the simultaneous expression of a large number of genes in
cultured vascular smooth muscle cells. RESULTS: Emodin at 1.6-3.1
microg/ml inhibited VSMC growth, at 6.3-12.5 microg/ml promoted VSMC
aging and induced VSMC apoptosis at 25.0 microg/ml 24 hours after
exposure. Unscheduled DNA synthesis, which was a sensitive indicator
for DNA injury, was observed in VSMC following 24 hours emodin
exposure. The mRNA and protein levels of p53 were up-regulated in a
concentration-dependent manner. Proliferation/carcinogenesis-related
genes were down-regulated and other genes related to cell senescence,
apoptosis, and DNA damage/repair were up-regulated in VSMC after
exposure to emodin for 24 hours. Emodin readily permeated VSMC
membrane and mostly located in the cytoplasm and few of them in the
nucleus. CONCLUSIONS: The p53 pathway in VSMC was activated post
emodin exposure in a concentration-dependent manner and which might be
responsible for the observed antiproliferative effects of emodin in
vascular smooth muscle cells.


PMID: 16626549 [PubMed - in process]

[tintinet]

And yet:

Inhibition of protein kinase CKII activity by resveratrol, a natural compound in red wine and grapes.

* Yoon SH,
* Kim YS,
* Ghim SY,
* Song BH,
* Bae YS.

Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea.

Resveratrol is a phytoalexin found in grapes and other foods that has been shown to have anticancer and anti-inflammatory effects. Because protein kinase CKII is involved in cell proliferation and oncogenesis, we examined whether resveratrol could modulate CKII activity. Resveratrol was shown to inhibit the phosphotransferase activity of CKII with IC(50) of about 10 microM. Steady state studies revealed that resveratrol acted as a competitive inhibitor with respect to the substrate ATP. A value of 1.2 microM was obtained for the apparent K(i). Resveratrol also inhibited the catalytic reaction of CKII with GTP as substrate. Furthermore, resveratrol inhibits endogenous CKII activity on protein substrates in HeLa cell lysates. These results suggest that resveratrol is likely to function by inhibiting oncogenic disease, at least in part, through the inhibition of CKII activity.

PMID: 12204772 [PubMed - indexed for MEDLINE]


Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, selectively inhibits the activity of casein kinase II as a competitive inhibitor.

* Yim H,
* Lee YH,
* Lee CH,
* Lee SK.

College of Pharmacy, Seoul National University, Korea.

Ser/Thr protein kinases play important roles in signal transduction pathways that control the proliferation and differentiation of eukaryotic cells. In this paper, we present evidence that emodin, an anthraquinone derivative, selectively inhibits casein kinase II (CKII), a Ser/Thr kinase, as a competitive inhibitor. The results with ethyl acetate extracts of the rhizomes of Rheum palmatum showed that emodin significantly inhibited the activity of cyclin B/cdc2 protein kinase (cdc2). We measured IC50 values for emodin on the activities of several Ser/Thr protein kinases, including cAMP-dependent protein kinase (PKA), protein kinase C (PKC), cdc2, casein kinases I (CKI) and CKII. Interestingly, emodin inhibited CKII activity with an IC50 value of 2 microM, which was two to three orders of magnitude lower than those against the other kinases. Enzyme kinetic assays showed that emodin inhibited CKII activity as a competitive inhibitor against ATP with a Ki value of 7.2 microM. Collectively, we suggest that emodin is a selective CKII inhibitor, whose action mechanism is mediated through competitively binding to the ATP binding site.

PMID: 10083837 [PubMed - indexed for MEDLINE]

[niner]

Emodin may be a 2 uM CKII inhibitor in vitro, I'm not really sure of the significance of that; but the Wang paper sees effects in cells using concentrations that are relevant to what some people may be consuming from lower quality resveratrol extracts. Concentrations may be higher in the gut- is the laxative effect related to damage to the intestinal lining? Not to be a resveratrol pimp, but it's not too late to get involved in the group puchase of pure resveratrol. (Act Now! Operators are standing by!)

100th post! What do I win?

[marqueemoon]

^Niner, I was under the impression that Orchid wasn't selling the pure stuff for human consumption anymore.

[tom a]

I don't know quite what to make of the study regarding emodin above, but it does seem that at least some of the characteristics they found in emodin are shared with resveratrol itself:

http://clincancerres.../full/10/6/2190

Results: Resveratrol was demonstrated to exert cytotoxic effects and induce glioma cell apoptosis in a concentration- and time-dependent manner (P < 0.05). Resveratrol (40 mg/kg/day) exerted significant antitumor effects on s.c. tumors, including slower tumor growth rate, longer animal survival time, and higher animal survival rate (P < 0.05). In contrast, resveratrol affected intracerebral tumors at only an increased dose (100 mg/kg/day), prolonging animal survival (P < 0.05) without affecting survival rate. The expression of vascular endothelial growth factor in the glioma cells and the proliferation of ECV304 cells were inhibited by resveratrol in a concentration-dependent manner. Immunohistochemical analyses showed that the s.c. gliomas from resveratrol-treated rats had fewer microvessel densities than did control rats (P < 0.01).

Conclusions: Resveratrol caused significant glioma cell cytotoxicity and apoptosis, exerted antitumor effects on the s.c. and intracerebral gliomas, and inhibited angiogenesis in s.c. gliomas. Thus, resveratrol might be considered a possible treatment strategy for gliomas.

As best I can make out, it seems to be believed in general that resveratrol inhibits the growth of new vascular structures -- I assume this is why people sometimes assert that resveratrol may make it take longer to heal from certain injuries.

I certainly have no idea whether or not emodin and resveratrol are creating apparently similar effects -- inhibition of growth of vascular structures -- in ways that are importantly different, or whether those mechanisms really cancel each other out in this or other contexts.

[niner]

Niner, I was under the impression that Orchid wasn't selling the pure stuff for human consumption anymore.

Another supplier has been lined up. Paul's having samples analyzed, and if it looks good we will get it. I think Orchid will still sell it, they just bailed out on the group purchase because of the high profile of it, I think.

[marqueemoon]

Niner, when's the deadline to get in on the purchase?

[niner]

I think there's still a couple more weeks at least. It probably would have been sooner if not for the trouble with Orchid. A post from a couple weeks ago is here: http://www.imminst.o...=0 although it dates to before the switch to a different supplier. If interested, you should send email to paul@morelife.org

[jack868]

Greetings...

[jack868]

Hi everyone, I wanted to introduce myself to this fine group. I am a science journalist based in New York City. I write about a wide variety of topics, but one in particular that I'm interested in is resveratrol. (I take the stuff myself, in addition to having written a few articles about it).

I've followed these forums with interest for a while. I've also read many of the studies on RSV. One thing that's obviously lacking in the studies is much quality information on specific *commercial* products, as opposed to lab-grade RSV. I think everyone here seems to be pretty much aware of that information gap; in fact, I think that's why many or most of us are here!

I wanted to propose an idea, and I am interested in any opinions you may have on this. I see this is the "500 club," so people posting here are taking fairly large amounts of RSV. Some of you have reported some clear noticeable effects, such as loss of appetite. I wonder if those of you who have been sticking with one regimen fairly regularly could submit postings describing in full the regimen (which brands you take, the dosage)... and the effects you have noticed. That way, the group as a whole can piece that info together into a cogent picture with some really useful information as to which products are most effective.

I think such an approach should work in principle, but there are also a host of reasons why it might not work immediately. In such a case I think it could be modified to make it workable.

For instance, this approach might lead to some chaos and confusion, in which case it might be a good alternative for us to collectively devise a clear, standard questionnaire which RSV users could fill out. Another possible hangup: some RSV sellers might decide to chime into the discussion. Their views would have to be filtered out as possibly biased. (The logistics of doing that would have to be worked out, but I think it wouldn't be too hard -- I can think of a few ways to prevent it.)

Another problem is that even RSV users with no ties to any RSV sellers might be prone to exaggerate their experiences or the benefits they have seen, just because they're understandably excited about the stuff. We will need to ask everyone to think hard and be honest about what their experiences are.

How do you all feel about my proposal? Comments/feedback would be most appreciated!

[stephen_b]

If people could post before and after blood chemistry results it could remove some of the subjectivity.

Stephen

[tintinet]

Although disorganized in structure and lacking completeness, many resveratrol supplementers are posting perceived effects here.

Not sure that your proposal would add anything to those reports as it really wouldn't constitute a coherent "study" without more strict dosage, single source, control for other factors, etc.

[jack868]

Stephen and Tintinet, I think you both make good points.

Tintinet wrote that "more strict dosage, single source, control for other factors etc." would need to be described, if my idea were to work. I believe we can actually do some of these things (though not all). As for dosage: My suggestion is in fact that people be asked to describe it clearly. As for ability to control for other factors: this is of course limited, but people could at least list their weight. As for single source: of course, we can't require that people use only a single source for their RSV. But we can at least keep track of who uses single versus who uses multiple, which I think could help.

Of course we'll still be dealing with limited info. But overall, I think more info -- and better organized -- is always better than less, and worse organized.

Tintinet also wrote:

Although disorganized in structure and lacking completeness, many resveratrol supplementers are posting perceived effects here.

That's true. Thus, my idea is to build on that by trying to add that structure and completeness, to the extent we can.

Also, Stephen wrote:

If people could post before and after blood chemistry results it could remove some of the subjectivity.

I think that's a great idea!

[ryan1113]

If people could post before and after blood chemistry results it could remove some of the subjectivity.

No. Blood work doesn't reveal as much as you think it does. The only thing it might be useful for is showing that acute ingestion with high dose resveratrol doesn't have toxic effects by throwing things out of range (CBC, liver enzymes, etc). Beyond that, it would be very difficult to show any potential benefits from blood work aside from possibly showing that a number of people had lower fasting blood glucose or VLDL/LDL cholesterol than they did before starting resveratrol, and that would require that they had blood testing a short time before starting it for comparison. And given the fact that most everyone on here is taking their own extensive cocktail of various items and are always trying new things, the chances of making any good observations tied to resveratrol are about zero.

[tom a]

jack868,

I guess I wonder what you really expect to find out about different resv. products via your suggested methods.

My understanding is that at base most resv. products are much the same, at least at this juncture. Most seem to come from a 50% resveratrol extract, where most of the remaining 50% would appear to have few important differences. One big issue is emodin content, but that too seems to hang on the purity of the extract. I guess there's one difference in some resv. products, in that they deliberately have quercetin added in (Longevenix is an example).

But mostly they seem the same in content, at least at this stage. I'd expect that the dosage level of resveratrol might make a difference.

What are you really anticipating you might find out?

[jack868]

More interesting feedback. Tom A. wrote:

I guess I wonder what you really expect to find out about different resv. products via your suggested methods. My understanding is that at base most resv. products are much the same, at least at this juncture. [Note, I'm not sure why this post of Tom's doesn't seem to actually appear on the forum -- I saw it in the reply page.]

Anyway... Interesting point. You may well be right. But I've seen some test results that unsettlingly, suggest there may be dramatic disparities in quality. I'd rather that not be true (since if it is, everybody's choices become more limited -- and some of us may have been wasting money). Nonetheless, here's the evidence.

According to the 2/27/04 issue of Science:

[Harvard's David] Sinclair purchased a dozen samples peddled as resveratrol and tested them in his lab. Only one passed the test... Sinclair briefly became a paid consultant to the company that makes it, Longevinex.

(Note: the company's lawyer has told me that actually, Sinclair never received any compensation.)

Now, I'm in no way vouching for Longevinex over other products, and there are a few possible reasons to think Sinclair may have gotten this wrong. But be that as it may, I've never seen those results convincingly refuted. Sinclair remains, after all, a Harvard guy, a man of some credibility. And he himself takes Longevinex, which presumably says something.

Secondly, probably many of you have seen the "test results" posted on the Longevinex website purporting to show their product blasting all competitors out of the water. I'd be tempted to write this off as company propaganda, except for two things. First, it appears to match the Sinclair findings. Second, I personally checked with the head of the company that conducted those tests, Biomol (a reputable company involved in quite a bit of published research, and unconnected to Longevinex). He confirmed for me that the tests were conducted, and that Longevinex indeed performed best.

On the other hand, there's contrary evidence suggesting other companies do have valuable products, and that there's no great disparity in quality. Here's some of that evidence: (1) I've seen a published study testing the RSV content of five supplements, and it found that they all had pretty close to the labeled amounts of trans-resveratrol. (2) it's never been conclusively explained why one product would have tested so much better than the others, though interesting reasons have been suggested. (3) The methodology used for those tests on the website, is one whose merits have come under some debate among scientists since then. (4) Also, there are anecdotal reports of people feeling that they got good results with other products, for whatever reason.

This is why I'd like to get to the bottom of the story. I don't think anyone really likes the idea that just one company has quality RSV. Then everyone has to depend on one company (which may be pretty expensive), and healthy competition vanishes. If the claims are true, then fair enough, but I'd like to get to the bottom of this by whatever means are available. That's a strong part of the motivation for the small project I've proposed. I admit it will probably be of limited usefulness, but still I think better than nothing. It might interestingly complement the results that I understand are due to return from Consumer Labs in a few weeks. (If I'm not mistaken, those tests focus on RSV content. But the Sinclair/Longevinex side have argued that proper tests must assess biological activity, not just content.)

Let me get to another intriguing bit of feedback, from ryan1113:

Blood work doesn't reveal as much as you think it does.

If this is correct, then, maybe the blood results should be left out of the picture for now. I still think other noticeable changes could still be useful indicators. For instance, (1) a few people have mentioned lower appetite. (2) Some people have reported reversal of hair graying with RSV. I can say for myself that I had this effect (I'm in my 30's) after I started taking it, although it was temporary -- the gray started creeping back a month or two later. (3) I think some people reported increased energy/libido. Now, Number 3 is highly subjective -- easily confounded by emotional effects. But the first two are actually not terribly subjective, especially Number 2, but even Number 1 (yes, emotion has some effect on appetite. But I think usually fairly temporary and small effects, except in cases of severe disturbances or traumas).

All these factors, while still subjective, I think get to something important: RSV's "biological activity," as opposed to content alone.

[tintinet]

If people could post before and after blood chemistry results it could remove some of the subjectivity.

No. Blood work doesn't reveal as much as you think it does. The only thing it might be useful for is showing that acute ingestion with high dose resveratrol doesn't have toxic effects by throwing things out of range (CBC, liver enzymes, etc). Beyond that, it would be very difficult to show any potential benefits from blood work aside from possibly showing that a number of people had lower fasting blood glucose or VLDL/LDL cholesterol than they did before starting resveratrol, and that would require that they had blood testing a short time before starting it for comparison. And given the fact that most everyone on here is taking their own extensive cocktail of various items and are always trying new things, the chances of making any good observations tied to resveratrol are about zero.

All true:

1. My general statement above regarding controls and more strict usage
was assuming the statement Ryan clarifies: most people who post about
resveratrol here are taking many other supplements the effects of which
might confound observation of resveratrol effects.

2. I also assume most people posting regarding resveratrol supplementation here
have not done rigorous blood work (CBC with diff., liver enzymes, extensive
other serology) and physiologic testing: BP, pulse, core body temp., accurate
body fat analysis, strength, endurance, etc.



Nonetheless, at least some effort to centralize our percieved and measured possible
resveratrol supplementation effects with respect to relative dosing and method (i.e.
encapsulated vs. powder; with food or without; with wine or without; time of supplementation;
type of resveratrol used- synthetic vs. extract and purity and source producer); etc. would
likely be interesting and, to a degree, more informative than mere random posting.

[tom a]

jack868,

I do wonder how much the poor efficacy Sinclair and Biomol may have found in the supplements back in 2003 or 2004 don't mainly reflect the state of the industry at that time. It wasn't widely understood either by vendors or customers just what the significance of trans-resveratrol, in particular, might be; I have the impresssion that a lot of people simply confused resveratrol with other red wine or grape extracts.

I think that after the Nature study in Nov 2006 both vendors and customers focused very clearly on trans-resveratrol, and this brought about a new generation of products and potency.

As I said, I think the industry standard at this point seems to have converged temporarily around a 50% trans-resveratrol product. My guess is that even Longevenix uses such a mix, but then adds quercetin and a couple of other relatively unimportant ingredients to the capsules.

It's certainly possible that quercetin in particular DOES significantly enhance the bioavailability of resveratrol. That is why it was added by Longevenix, and I gather (though don't know for certain) that that may have been suggested by Sinclair himself, who generally has emphasized the importance of pure trans-resveratrol (as opposed to its metabolites) entering the system. Indeed, Sitris, the company he co-founded, apparently has a variation of the resveratrol molecule that is intended to engender that very effect.

On the other hand, quercetin was NOT included directly in the diets of the mice reported on in the studies in Nature or the Auxwerx study in Cell. Moreover, there's some evidence -- hardly conclusive -- to suggest that quercetin might actually counteract to a degree the effect of resveratrol. For that reason, many of us are a bit leery of it; we feel safer going with what was used in the studies.

What I do think will be important is to be pretty clear about just what really is in the various capsules. This isn't magic, and if there's a difference in effect, it has to be based on something real. There are of course ways to determine the actual contents of capsules, and such information should ground any inferences about efficacy. Our reports are useful, but prey to so much subjectivity that I doubt that fine discriminations between products will be reliable.

Edited by tom a, 21 February 2007 - 04:11 PM.

[jack868]

Tom A,

I certainly hope you're right. And you make a good case. Nonetheless, I see some contrary evidence. You led with the following remarks:

I do wonder how much the poor efficacy Sinclair and Biomol may have found in the supplements back in 2003 or 2004 don't mainly reflect the state of the industry at that time. It wasn't widely understood either by vendors or customers just what the significance of trans-resveratrol, in particular, might be; I have the impresssion that a lot of people simply confused resveratrol with other red wine or grape extracts.

I think that after the Nature study in Nov 2006 both vendors and customers focused very clearly on trans-resveratrol, and this brought about a new generation of products and potency.

The contrary evidence, in my view, is that study I mentioned -- in which researchers tested five popular RSV products (not including Longevinex) and found that they all had very close to the labeled amount of (specifically trans) RSV. That study was done no later than 2004. This is clear because the paper (Babu et al., 6/05 issue of Chemical & Pharmaceutical Bulletin) contains this note: "Received January 6, 2005." That is, the publishers received the manuscript on that date. So already in 2004, both scientists and the pill-makers knew of the importance of trans-resveratrol. And the manufacturers made their products accordingly, and basically honestly, if this study is any indication. Yet strangely enough, this is roughly the same time frame when Sinclair would have conducted his study showing that all of the products but one were worthless. It makes me wonder, what's going on here? You're absolutely right -- there's no magic, and the same content should lead to the same effects -- yet that's apparently not what happened here. It seems perhaps that we are missing some information about the content. (I imagine the contents of pills can be very complex, whereas the assays usually only test for one ingredient.)

It occurred to me that perhaps the difference is related to the liquid or solid state of the substance. The RSV capsules usually contain liquid, I believe, whereas in pill form the RSV obviously must be solid. But this is just a guess.

I agree, as you say, that recent times have seen an increase in the potency of the marketed pills; they have more labeled trans-RSV. But that is mainly a quantitative increase rather than a qualitative change, as far as I can see. The older pills simply had less trans-RSV. But presumably Sinclair, being a smart guy, would have taken the differing quantities into account in his tests. So this still doesn't resolve the puzzle in my view.

Among your arguments, the one that I admit is hardest to counter is this:

Our reports are useful, but prey to so much subjectivity that I doubt that fine discriminations between products will be reliable.

This may be true, and if so, it would kill my idea. But I still think that there is evidence for some effects that are clear enough that self-reports can be accepted as valid. For instance, Addison Strack wrote in this forum earlier:

Wow, jesus, you need to really watch yourself, because skipping meals is very easy to do unintentionally on resveratrol. I've had two apples and for some reason I feel fine with making that my dinner.

That sounds to me like the description of a pretty "unmistakable" effect, as far as subjective effects go. In addition, reversal of hair graying is pretty unmistakable, because it's easily seen with the eyes. There may be others, but I would need to hear some suggestions from the group on this. One guy told me not long ago that since taking RSV he had been waking up each morning with, shall we say, something very woody in his pajamas. Is that subjective? Somewhat; for one thing, other products can cause that too. But not that many. Also, simply meeting someone that you have the hots for could cause that. But I think these confounding effects aren't too hard to identify and rule out, if you're honest with yourself.

[tom a]

jack868,

You make an interesting argument that there's something odd going on with the apparently conflicting results between Sinclair's study that showed only one product exhibited real efficacy, and the other result that showed a number of products with significant and fairly accurately labeled amounts of transresveratrol.

But there's at least one point worth noting: the study Sinclair conducted was likely in 2003 (not clear when in 2003), since it was reported as being performed in the past in Science of Feb 2004, and the study submitted in Jan 2005 likely was conducted toward the very end of 2004. That difference in timeframes could be significant.

I'd say that perhaps the quercetin in Longevenix made the difference, but my impression anyway is that quercetin would have an effect only on how things work in vivo (by allowing more resveratrol to get into the system in pure, rather than metabolized form), and I gather that the test Sinclair and Biomol use is employed in vitro.

[tom a]

One other point: Longevinex came out with its pill some time in 2003, I gather. If Sinclair's test was immediately after the introduction of that pill, and other vendors had not yet had time to respond to the entry of this new product, it wouldn't be surprising if their "red wine extract" products did not yet have much or any trans-resveratrol.

[jack868]

Tom A,

You raise the possibility that other manufacturers might have improved their product during the time between when Sinclair did the tests, and the Babu et al. study. This possibility seemed worth investigating to me, so I did some research on the Net to try to clarify the issue. After reviewing my results, it looks to me like the manufacturers would have had to react pretty fast -- all of them in well under a year.

Although Sinclair probably did his tests in '03, I suspect manufacturers wouldn't have generally known about it until it was mentioned somewhere in the media; that first occurred with the Science article of Feb. '04, as best I can tell. (I searched the Ebsco online database of published articles -- a pretty wide-ranging database, but not complete.)

There's one way the manufacturers might have found out the information a bit earlier: as part of the buzz surrounding the Longevinex release. But I think that doesn't change the timeframe by more than a month or so, because Longevinex became available in Jan. '04 (its availability was first announced in a press release late that month, republished here.)

So basically, I think the competing manufacturers would have had to revise their products in several months, which seems unreasonably short. Remember, before the Babu et al. study could be submitted to a journal, the researchers would first have to go through several steps that I imagine would take months: planning, ordering products, conducting and actually writing up the findings. I suspect the researchers would have had to order the products well before the end of '04.

[stephend]

Hello, this is my first post; I have been monitoring this group for a while and find the topics very intriguing.

I am not as educated in science as many of you appear to be. Like many of you I am interested in longevity, but I am also interested in enhanced physical performance. I am in very good health and a “Middle of the Road” age grouper athlete (46 years old) in both triathlons and marathons. I have just received today, my first order of RevGenetics R500 (I know I saw the controversy posted previously about RevGenetics but at the price I have to try, did I mention I am cheap?)

I was going to start usage immediately (1500-2000 mg trans-RSV daily). However I am willing to wait to have some “before testing” performed if it might help with discovery, however not sure what to have tested or cost. I already track my 5-6 day a week training, food/calorie intake, heart rate (resting & training) I receive a regular blood test once a year with my physical. I also had my Lactic threshold measured last March. I do not take a lot of other supplements (presently and for the past several years, 1-One A Day men’s, 1500 mg Glucosamine and 800 IU vitamin E daily). Suggestions or comments?

[Anthony_Loera]

Hi jack868,

this is Anthony Loera from RevGenetics. By the way, what is your real name and what scientific journals do you write for, it's very exciting to see someone who writes for the scientific community reading the posts here.

Regarding manufacturers revising the products, it is a strong possibility that they did not revise the products until after the tests. Currently I believe there are 2 methods (out of many) where Longevinex may be producing the product, and cutting down costs. I say this, as I believe these methods also (in their own way) are part of the process that is currently taking place with the RSV supplier community, regarding production and wholesale distribution.

1- The company can buy the 'patented' machinery and process from a 3rd party (a pharma-wallmart as I put it) which I contacted this morning.
(I called to talk about a new line of RegGenetics RSV caps, as many folks believe I should add this to our product line), personally I believe, like many of my customers, that this is not necessary... but I will see about adding it to help those who are on the fence, come down and use RevGenetics.

2- The second is to call on this 3rd party (the pharma-wallmart) and farm-out the work to them, as they hold the patents to the equipment and method in which the pills are made.

Many powder manufacturers, I believe, will (or have already) re-formulated the products to be inline with this main 'pharmaceutical-wallmart' supplier wants. To give you a better understanding.... It would be like our good friend wallmart asking manufacturers for powder with a specific purity. Of course since this pharmaceutical 'Wallmart' is getting the best price because they buy the largest amounts, I am pretty sure manufacturers/bottlers like RevGenetics, Longevinex, and others will buy their powder from this Pharma-Wallmart, as they guarantee purity and possibly have the lowest price available.

Back again to the main powder manufacturers around the world... if they do not produce a quality product, they will not be considered by our large pharma-wallmart. It is because of this, that most RSV sellers, will begin to have (or already have) a decent product. Most RSV suppliers want the big pharma-wallmart to consider their own product, so because of good ol' supply and demand, the consumer gets a great product at a good price. We all benefit, RSV Supplier, Capsule Manufacturer, bottler, wholesaler, retailer, consumer... It is really a great process that I am seeing happen.

In 1-2 years time, I believe the only difference will be how RSV is marketed. Look at the marketing for vitamins, and other herbs, to see what the future holds for Resveratrol.

Thanks
Anthony Loera
RevGenetics

Edited by revgenetics, 22 February 2007 - 01:19 AM.

[health_nutty]

Hello, this is my first post; I have been monitoring this group for a while and find the topics very intriguing. 

I am not as educated in science as many of you appear to be.  Like many of you I am interested in longevity, but I am also interested in enhanced physical performance.  I am in very good health and a “Middle of the Road” age grouper athlete (46 years old) in both triathlons and marathons. I have just received today, my first order of RevGenetics R500 (I know I saw the controversy posted previously about RevGenetics but at the price I have to try, did I mention I am cheap?)

I was going to start usage immediately (1500-2000 mg trans-RSV daily).  However I am willing to wait to have some “before testing” performed if it might help with discovery, however not sure what to have tested or cost.  I already track my 5-6 day a week training, food/calorie intake, heart rate (resting & training) I receive a regular blood test once a year with my physical.  I also had my Lactic threshold measured last March.  I do not take a lot of other supplements (presently and for the past several years, 1-One A Day men’s, 1500 mg Glucosamine and 800 IU vitamin E daily).  Suggestions or comments?

That is a huge dose of tres! You are going from 0 to 1.5 - 2 grams? How did you choose a dose? What does that come out to in terms of mg/kg (i.e. how much do you weigh)

I would really be interested in seeing before and after blood work at that dosage. I would also be very interesting to hear if it makes any improvement in your training.

Great to have from you, I'm looking forward to your contributions!

[maxwatt]

jack868,
.....
I'd say that perhaps the quercetin in Longevenix made the difference, but my impression anyway is that quercetin would have an effect only on how things work in vivo (by allowing more resveratrol to get into the system in pure, rather than metabolized form), and I gather that the test Sinclair and Biomol use is employed in vitro.

My understanding is that the testing was done with the standard Fleur de Lys kit available from Biomol; it is an in vitro test. Quercetin is a strong activator of SIRT1 in vitro, but is known from another Sinclair paper not to extend the life span of round worms, because the liver glucornates Quercetin, and this metabolic product blocks activation of SIRT1 in vivo.

So the other products had maybe a tad or a smidgeon of resveratrol, like 5 mg, and Longevinex, with 30 mg, and a lot more Quercetin, passed the test like mad. While no specific study has shown Quercetin blocks the action of resveratrol, we know it might, given the action of its metabolites. Further, we know that resveratrol alone was very effective in Sinclair and Auwerx's studies.

Don't add quercetin to your resveratrol. It isn't needed, and might be counterproductive.

As for stephend, I suggest ramping up you resveratrol dose; start at 1/4 or 1/8 of what you intend to eventually use. This is especially the case with resveratrol from P. cuspidatum, due to the resveratrol content. You might be able to get your dose up by adapting to the laxative effect of even the small amount claimed to be in Revgenetics; but starting at 1500 mg will probably be vvery uncomfortable.

[tom a]

jack868,

Not to obsess on the point TOO much, but it's possible that vendors other than Longevinex may have started the process to introduce transresveratrol as soon as Sinclair's 2003 Nature study was released, in which he first announced the power of transresveratrol to extend the life of yeast. This was published online in August of 2003. I gather that Longevinex may already have been available or in the works at that time (again, I've read that Sinclair himself was involved in its design, which would account for Longevinex's early launch).

In any case, it certainly WOULD be useful to know, at minimum, exactly when Sinclair and Biomol conducted the test on the various products. Apriori, I'd expect that this would have been done very soon after or in the midst of the launch of Longevinex, but an actual date would be very useful in framing this issue.

[jack868]

Tom A. wrote:

Not to obsess on the point TOO much, but it's possible that vendors other than Longevinex may have started the process to introduce transresveratrol as soon as Sinclair's 2003 Nature study was released, in which he first announced the power of transresveratrol to extend the life of yeast. This was published online in August of 2003. I gather that Longevinex may already have been available or in the works at that time (again, I've read that Sinclair himself was involved in its design, which would account for Longevinex's early launch).

In any case, it certainly WOULD be useful to know, at minimum, exactly when Sinclair and Biomol conducted the test on the various products. Apriori, I'd expect that this would have been done very soon after or in the midst of the launch of Longevinex, but an actual date would be very useful in framing this issue.

I don't think you're obsessing at all. I think all your posts have been well reasoned, including the last one. Whether it's a small or a big point doesn't matter, as long as it's relevant. No one can obsess on details too much when investigating important facts.

After all these points have been considered, though, I humbly would like to direct attention back to the original proposal I made: the idea of trying to encourage posters here to describe their precise regimens, including brand names, and the results they have seen, so that someone (I offer myself) can try to compile that info into a dataset revealing something useful about the comparative quality of the products. Several posters, including Tom, have made very true comments pointing out the limitations of this method. I have argued that even taking all those valid points into account, my idea could still come up with something useful. At worst, it would just be a waste of time (mostly my own I suppose), nothing else lost. Comments/reactions?

Anthony, in response to your question, my name is http://members.aol.com/jekluc/a.bmp. (Sorry, I put that in image form ... I don't like my name shown all over the Internet.) I mentioned earlier that I'm a science journalist. I'm the founder and chief writer for a science news website called World Science (world-science.net). The site doesn't specifically concentrate on resveratrol, but I've written a few articles about it (it's certainly hard not to be interested in a topic such as this!) Before founding that site, I wrote science stories for other publications including the Washington Post and Discover magazine.

Anthony, you made some interesting observations about how Walmart might become a force in the RSV market. You present an interesting product and many of us are sure hoping you can prove it to be of good quality. However, I don't think your latest post clarifies what I've been trying to find out. I'm trying to find out about the quality of currently existing pills. Although you make some intriguing predictions, you don't seem to have much info relevant to comparing presently existing products. For instance, you mistakenly suggest that our friend Longevinex uses powder:

I am pretty sure bottlers like RevGenetics, Longevinex, and others will start buying their powder from Wallmart, as they guarantee purity and a low price.

But in fact, they don't use powder. I've broken three or four of their pills by accident. They contain a wet goop, which may even be a key difference (see above.)

Finally, Maxwatt wrote:

My understanding is that the testing was done with the standard Fleur de Lys kit available from Biomol; it is an in vitro test.

Yes, this is true of the test that the Longevinex company commissioned. However, it appears not to be true of the tests that Sinclair separately conducted, with apparently similar results (Feb. '04 Science.) The company president has told me that Sinclair did those tests with yeast cells. I have not been able to confirm that with Sinclair personally.

[tintinet]

...As for stephend, I suggest ramping up you resveratrol dose; start at 1/4 or 1/8 of what you intend to eventually use.  This is especially the case with resveratrol from P. cuspidatum, due to the resveratrol content.  You might be able to get your dose up by adapting to the laxative effect of even the small amount claimed to be in Revgenetics; but starting at 1500 mg will probably be vvery uncomfortable.

I think you meant to type "emodin content" in the second sentence quoted above, no?

[marqueemoon]

Don't add quercetin to your resveratrol.  It isn't needed, and might be counterproductive.

Maxwatt, what about the fact that people supposedly consume 25-50mg of Quercetin in their food on a daily basis. Would it be wise to also avoid foods with Quercetin or is it too impractical?