161 replies to this topic

[trh001]

The survival curves in this recent life span study in fish *very* nice. At 0.06% of diet, the curves look similar to those seen with caloric restriction (CR), yet the authors note that gene expression studies suggest distinct, or largely non-overlapping mechanisms. This brings up the possibility of synergism between much milder forms of CR (say 10-20% ad libitum, or isocaloric wrt to ad lib, fasting via alternate day feeding) and resveratrol.

----------------------------------
Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate.
Curr Biol. 2006 Feb 7;16(3):296-300.
PMID: 16461283 [PubMed - in process]


"Life extension by resveratrol is associated with a change in the slope of the mortality trajectory, i.e., the time-dependent increase in death risk is lowered in resveratrol-fed fishes compared to control-fed ones. A similar effect is observed in Drosophila when the temperature is reduced and was linked to a reduction in the age-dependent accumulation of biochemical irreversible damage [34]. This effect is different from the life extension induced by dietary restriction, which, at least in Drosophila, is tied to time-restricted reduction in the acute risk of death without changes in the slope of the mortality rate [34]. If this interpretation can be extended to N. furzeri, it would further suggest caution when equating the effects of resveratrol with dietary restriction. We observed that resveratrol induced an early increase in death rate after administration, suggesting a possible hormetic role, i.e., its weakly toxic action would stimulate a stress response and eventually increase lifespan and retard ageing. This view is in agreement with the resveratrol-dependent activation of detoxification enzymes observed in in vitro studies [35]."

"In two independent trials, 120 ìg/g food caused an increase of median and maximum lifespan of 33% and 27%, respectively (p < 0.001, log rank test; Figure 1A), and 600 ìg/g food induced 56% and 59% increase in median and maximum lifespan, respectively (p < 0.001, log rank test; Figure 1A). 600 ìg/g food was significantly more effective than 120 ìg/g food in prolonging lifespan (p = 0.01, log rank test)."

[trh001]

No reply from Longevinex yet.

It sounds as if lef.org will be coming forward with assays that attempt to measure certain metrics that may point to biological relevance of resveratrol formulations. Meanwhile, there's probably nothing wrong with Sardi's product, other than, perhaps, it's price. One could hedge one's bets, and take both LEF and Longevinex (I do, at the moment), while waiting for the outcome. It's too promising a molecule (and market), so I doubt things will stay ill-defined much longer. Especially since the ante's been upped wrt the recent publication
Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate.
Curr Biol. 2006 Feb 7;16(3):296-300.
PMID: 16461283 [PubMed - in process]

[opales]

Rumor has it that Sinclair's groups mouse lifespan studies (not finished yet) show positive results. We can only hope that they used genetically normal mice, as long as the actual mechanics are unclear, using modified mice is not very convincing.

[syr_]

If beneficial effects have been seen in people eating diets high in resveratrol containing foods such as grapes, red wine and so forth, why is it neccessary to take such large amounts? Is it because the study was done with large amounts? If mediteranean people have better health from taking what must be small amounts, I'll bet you that you don't need 40 to 50mg per day. You probably only need 1 to 4mg or some amount like that. Maybe even less than 1mg per day.

I also agree on this. AOR product with 5mg of trans-resveratrol + grapes extract sounds solid and not expensive at just 1-2 caps a day.

[london710]

found this:

http://www.vitacost....RedWineExtracts

Supplement Facts
Serving Size: 1 Capsule
Servings per container: 120

Amount Per Serving % Daily Value

Japanese Knotweed Extract (Polygonum cuspidatum)(root)(providing 37.5 mg [50%] Trans-resveratrol) 75 mg *

Red Wine Extract (standardized to 30% polyphenols)(skin and seed) 25 mg *

Grape Seed Extract (ActiVin®)(standardized to 85% phenolic and 75% oligomer polyphenol)(seed) 50 mg *

price 15.99$




-Also new scientist mentions the fish study in their newest issue, in this Dr. Paul Kroon Institute of Food Research of Norwich, UK calculated that a normal person would have to consume 75 bottles of red wine a day to reach a comparable resveratrol intake to that of the longest living fish. Fwiw.

[FunkOdyssey]

That's not too outrageous, if that 4mg of resveratrol per liter figure from the study I posted is represenatitive of most red wine. You're talking about 225mg of resveratrol. You could obtain that easily with the NSI product (six capsules daily).

The economy of NSI's resveratrol, and the fact that it is labelled specifically for trans-resveratrol, kinda blows everything else out of the water. Anyone see any problems with it?

My only concern is that you might be getting too much grape seed extract if you took six a day. A group is studying GSE right now as an alternative to arimidex, letrozole, etc. for breast cancer patients because they say it is a potent aromatase inhibitor. I wonder what affect 300mg daily might have on your hormonal profile (probably a desirable effect for older men).

Edited by funkodyssey, 11 February 2006 - 03:38 PM.

[opales]

I would not start with mega dosing with these results. There is no evidence of dose response on other in vivo studies (however, there is evidence for dose response on in vitro studies). Even more compellingly, as has been noted here, human studies, eg. epidemological results point to small doses, one glass of red wine a day.

If you choose do so however, I suggest work it up there. There was an increased death rate after start of treatment with the fish which can be explained by (in my view most plausible) theory that resveratrol is in fact a stressor and works by inducing natural stress response as was hypothesized in the fish study.

As regards hedging, I would advice on getting a glass of that red wine couple a times a week just in case.

[trh001]

"As regards hedging, I would advice on getting a glass of that red wine couple a times a week just in case."

If your theory on stress response is correct, won't I be so relaxed and mellow from my Merlot, that any benefit from 'hormesis' will be compromised?

[DukeNukem]

Pinot noir is the best source of resvertrol, I've read, due the the grapes.

[syr_]

Isnt it due to the region where the plants are cultivated? pinot is produced everywhere in the world...

[FunkOdyssey]

Its some combination of the type of grapes and the region. Pinot Noir from New York state have the highest levels of resveratrol recorded from wine anywhere.

They are letting wine makers label their wine for resveratrol content now, so you don't have to guess at this anymore.
Message on a Bottle: Wineries Push To Put Antioxidant Content on Labels

Here's an example of a TTB approved label with resveratrol content (luckily the FDA doesn't review these or they would censor the crap out of this):
http://www.willamett...-pn-02-back.jpg

An article that backs up Pinot Noir and New York state as the premier wine and state for resveratrol content:
http://www.news.corn...esveratrol.html

"New York's relatively humid climate explains the higher concentrations of resveratrol in the wines," Creasy said. "Resveratrol is a natural fungicide, and the more humid the climate, the more is produced to combat mildew. During the long contact between the grape skins and the juice in producing red wines, the resveratrol is transferred into the wine."

Pinot Noir is especially high in resveratrol be cause the variety's thin skin and tight clusters make it particularly susceptible to problems resulting from moisture.

[FunkOdyssey]

By the way, Longevinex never replied to that e-mail I sent them. Take that as you will. [ang]

AOR replied to my chromium picolinate concerns in less than 48 hours. [thumb]

[trh001]

"Pinot Noir is especially high in resveratrol be cause the variety's thin skin and tight clusters make it particularly susceptible to problems resulting from moisture."

I suspect there'll be a collective groan in response to this, but the problems resulting from mold are typically what? Mold? Yeast? If the former, what toxins might make their way into the wine? If the latter, of less, if any, concern. Aflatoxin is (I'm sure you all know) the most potent human liver carcinogen know, or it was the last time I checked. Aspergillis flavis (sp.) is the mold that produces it. It's effective in very low concentrations.

Now, if one eats peanut butter, it's probably moot, as the flavatoxin levels are rather high from mould infected peanuts being ground into the mix.

I'd be *more* than happy for someone to cite information that proves the above to be of no concern, as I'm an avid fan of aged grape juice, in moderation.

[FunkOdyssey]

Oh snap. I spoke to soon about not receiving a reply from Longevenix. Bill Sardi sent me a series of e-mails (eight in total, I'm not sure why exactly, it was pretty weird). I'll show you all of them.

Bill Sardi returns fire:

In a message dated 2/14/2006 9:59:59 PM Pacific Standard Time, Longevinex writes:


This statement is false.  Life Extension Foundation, Advanced Orthomolecular Research, Jarrow Formulas, and Source Naturals all label products with resveratrol content, to name just a few.


Yes, and they ignore FDA regulations!

To say it again, resveratrol is a drug.  It was not being sold as a dietary supplement in 1994.  Solgar, a supplement company, attempted to market resveratrol a few years ago and was informed resveratrol is a drug.  Longevinex is labelled as a red wine and botanical extract.

Bill Sardi

In a message dated 2/14/2006 9:59:59 PM Pacific Standard Time, Longevinex writes:


For the record, how much trans-resveratrol is actually contained in a capsule of Longevinex?


40 mg............... we had to put the resveratrol dosage on the website, but it is not on the product label.  Talk to the FDA about this.  We just comply with the rules.

Bill Sardi

In a message dated 2/14/2006 9:59:59 PM Pacific Standard Time, Longevinex writes:

Ask the other company you talk about why they added 20 mg of trans resveratrol to their product, mislead their customers into thinking it is from red wine, when it is from polygonum cuspidatum, a large green leafed plant from China.  Ask the other companies if they know why lab researchers protect resveratrol from light and oxygen exposure prior to use.  Ask other providers if they know the difference between trans and cis resveratrol?  If so, how does trans turn to cis?  If they know how, what do they do to prevent conversion from trans to cis?  Have they tested their products 1-2 years after it is on the shelf, to show the trans resveratrol is maintained?  - Bill Sardi, President, LONGEVINEX

In a message dated 2/14/2006 9:59:59 PM Pacific Standard Time, Longevinex writes:


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). 


Misleading answer............... in the study above, the peanuts were kept cold, in the dark, and were shelled.  Freeze-dried grape powder retains a miniscule amount of resveratrol.  Italian company attempted to introduce red wine pill but couldn't get the freeze drying to retain resveratrol.  -B Sardi

Shawn

Go to this website:  http://www.fda.gov/o...901/rpt0085.pdf

You can read the FDA letter to Solgar regarding the designation of resveratrol.

B Sardi

In a message dated 2/14/2006 9:59:59 PM Pacific Standard Time, Longevinex writes:


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). 


Contact Konrad Howitz at BIOMOL, who makes the Sirtuin 1 analysis kit, and ask them why they continue to offer it to laboratories if it is not a valid test?  www.biomol.com  Sirtuin 1 testing in supplements is not in vivo.

B Sardi

Se Pu. 2004 Nov;22(6):583-8.

[Study on thermostability and photo-isomerization of trans-resveratrol by high performance liquid chromatography and liquid chromatography-electrospray ionization-mass spectrometry]

[Article in Chinese]

Liu Y, Wen D, Chen Z, Liao Y, Liu H.

College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

The thermostability and photo-isomerization reaction mechanism of trans-resveratrol were studied by using high performance liquid chromatography (HPLC) and liquid chromatography-electrospray ionization-mass spectrometry ( LC-ESI-MS). A reversed-phase Hypersil-ODS column was used with the mobile phase consisting of 60/40 methanol-water, with addition of 0.05% trifluoroacetic acid for HPLC, and 0.1% formic acid and 5 mmol/L ammonium formate for LC-ESI-MS, at a flow rate of 0.5 mL/min. Diode array detection was set at 300 nm and the injection volume was 20 or 10 microL. Mass spectrometric conditions were in the negative mode. The results of thermostability test under 4, 20 and 40 degrees C indicated that the concentration of trans-resveratrol, after storage for 600 h, was decreased slightly under 4 degrees C, decreased by 5% under 20 degrees C, and 10% under 40 degrees C. In addition, the photo-isomerization reaction of trans- and cis-resveratrol under 254 nm and 365 nm UV irradiation was investigated by LC-ESI-MS, showing that the isomerization is based on p-status, and that some secondary reactions are radical induced.

Resveratrol Caps
60 capsules
Item Catalog Number: 655
Findings from published scientific literature indicates that resveratrol may be the most effective plant extract for maintaining optimal health.106*

Red wine contains resveratrol, but the quantity varies depending on where the grapes are grown, the time of harvest, and other factors. After years of relentless research, a standardized resveratrol extract is now available as a dietary supplement. This whole grape extract contains a spectrum of polyphenols that are naturally contained in red wine such as proanthocyandins, anthocyanins, flavonoids, etc.

The resveratrol used in these products is extracted from organic grapes and is in a natural matrix that includes many other polyphenols.

Supplement Facts
Serving Size 1 capsule

Servings Per Container 60

Amount Per Serving
Resveratrol [from whole red grape (Vitis vinifera)      20 mg
and Polygonum cuspidatum (root) extract]


Polygonum is not from red grapes, it is a different plant, Giant Knotweed.  How much of the 20 mg of resveratrol in this product is derived from red wine vs. giant knotweed?  Why was it recently added to the formula?

What do you guys think of his response?

[FunkOdyssey]

I did find this in particular to be thought-provoking:

Ask the other company you talk about why they added 20 mg of trans resveratrol to their product, mislead their customers into thinking it is from red wine, when it is from polygonum cuspidatum, a large green leafed plant from China.  Ask the other companies if they know why lab researchers protect resveratrol from light and oxygen exposure prior to use.  Ask other providers if they know the difference between trans and cis resveratrol?  If so, how does trans turn to cis?  If they know how, what do they do to prevent conversion from trans to cis?  Have they tested their products 1-2 years after it is on the shelf, to show the trans resveratrol is maintained?  - Bill Sardi, President, LONGEVINEX

LEF has really not provided any indication that they are aware of the difference between trans-resveratrol and cis-resveratrol, or that they know how much of each is in their product and whether or not conversion takes place. The same holds true of just about every other resveratrol supplement out there. AOR and NSI do label specifically for trans-resveratrol, but do not provide any evidence that it is maintained in that form.

[kevink]

That was great. Thanks for posting it.

[FunkOdyssey]

No problem. I sent him another e-mail to pick his brain about what he felt the optimal dosage for maximum life extension / health benefits would be, I'll let you know what he says.

[DukeNukem]

Bill Sardi is 100% correct about the labeling issue. The FDA restricts this on product labels, but their jurisdiction doesn't reach out to web sites. The fact that they're complying correctly with the FDA rules, while no one else is, is actually a feather in their cap as far as integrity goes.

[wannafulfill]

fantastic work digging that up funkodyssey, I hope the other companies don't miss this important oppotunity to reply and add to the conversation

[FunkOdyssey]

Bill Sardi called me at my desk at work here and talked to me for almost an hour. I am amazed that he took that much time to talk to me (or call me at all for that matter).

Some interesting things Bill had to say in random order:

He has tested most of the competing products on the market and many of them do "serendipitously" contain some amount of trans-resveratrol despite the fact that no special measures were taken to protect it from light, heat, and oxygen exposure. However, you have no way to know for sure how much you are getting as the amount of actual trans-resveratrol present varies considerably. He claims that two year old Longevinex capsules are so close to the original 40mg of trans-resveratrol content that they are not able to determine any rate of degradation at all.

Testing for the effectiveness of resveratrol supplements is difficult because the only reliable indicator seems to be life span / mortality rate. For example, resveratrol prevents heart attacks, but does not necessarily affect cholesterol or blood pressure. You would have to perform a dissection and look at the artery walls (as they are able to do with test animals) to see the evidence of resveratrol's prevention of atherosclerosis.

Bill believes that resveratrol is the ultimate supplement and is the molecule that could put the drug industry out of business, due to its extraordinarily wide-ranging benefits. When asked what diseases/disorders resveratrol can help, his response is "what can't it do?" Diabetes, heart disease, cancer, and alzheimer's were on his list among others. He told me a geneticist he knows that is in his 80's was suffering from leukemia and was told he had only a few weeks left to live. He started taking 32 longevinex capsules daily (not per anyone's recommendation, but of his own accord), which proved to be completely safe, and he has remained alive over a year now.

Bill says resveratrol has an oral bioavailability of approximately 71% and that negative reports of its bioavailability are pharmaceutical industry propaganda. He says resveratrol is combined with something in the liver (glucarate maybe?) and travels the bloodstream in that complex. He also says resveratrol is a very small molecule and is able to penetrate the nucleus of cells, and has a half-life of approximately 14 minutes. For these reasons, testing for blood levels of resveratrol is futile and stating that resveratrol is not bioavailable because it is not present in free form in the blood is very misleading. He also says lecithin has been shown to help resveratrol cross the blood-brain barrier and that is why it is included in Longevinex.

He says resveratrol is miraculous and uncanny in its ability to turn off and on so many genes as a single molecule, in a manner that is highly beneficial. Bill claims resveratrol is nature's answer to gene-targeting drugs and is likely superior to anything we will able to synthesize for a long time.

As far as dosage, Bill wasn't able to give me anything really concrete. More is essentially better, weight is a factor (twice the weight requires twice the dose), he felt more was needed to resolve advanced disease as opposed to what is required for prevention and life extension. I should have asked him to get into more detail here and I will in a follow-up email.

He told me that everyone who is putting resveratrol on their labels is violating FDA regulation and could be subject to enforcement action at any time. He says trans-resveratrol bought cheaply from China in large quantity is being used to formulate most resveratrol products, and supplement makers are using the Chinese manufacturer's pre-shipping test of trans-resveratrol content as evidence for their resveratrol content claims, then turning a blind eye to issues of degradation into the cis-resveratrol form.

He said 500mg is being used in Italy (if I remember correctly) right now in a cancer study, although he's not sure how they made the pills. He said he would like to sell 300mg capsules but doubted many people would purchase them since they would cost about $3 a day and he has trouble moving the 40mg product he has already.

I know I am forgetting alot of interesting details but I hope I remembered the more important ones. I was pretty impressed with his knowledge and his passion for resveratrol, and the amount of time he gave me.

[DukeNukem]

Like Bill, I take two Longevinex a day (morning and night). Plus, I take other products during the day that have small amounts of resveratrol, such as Green Tea Max in ALL of my drinks...
http://www.greenteamax.com/

This is truly a miracle molecule, and should be in everyone's program.

[FunkOdyssey]

He also just sent me this information regarding trans-resveratrol's potential to degrade into cis-resveratrol:

As a botanical extract, resveratrol is highly photosensitive and can be altered to a different form (isomerized).  Resveratrol exists in two molecular configurations (isomers), as trans and cis resveratrol.  Trans is the desired stable form.  Exposure to UV radiation, either from a solar or fluorescent lamp source, can hasten the conversion of trans to cis resveratrol.  Researchers advise that “trans resveratrol should be handled with caution” to preserve its molecular integrity.  [Journal Agriculture Food Chemistry 44: 1253-57, 1996]



Other research papers mention that light can convert trans resveratrol into the less stable cis resveratrol.  [Journal Nutrition 132:257-260, 2002; J Chromatogr B Biomed Sci Appl.  21;702:103-10, 1997; Neurosignals14: 61-70, 2005]  In one experiment, the photo conversion of 100% trans to cis resveratrol was rapid, about 8 percent per minute at room temperature when exposed to ultraviolet radiation, and after 10-15 minutes of exposure time cis resveratrol was greater than trans resveratrol.  [Electrophoresis 22: 2574-79, 2001]  An experiment published in 1996 reveals that trans-resveratrol is stable for months when protected from light, except in high pH buffers.  [Journal Agriculture Food Chemistry 44: 1253-57, 1996] 



Resveratrol is generally stable in heat as it withstands thermal assault by the sun in botanical sources.  However, trans resveratrol has been tested and shown to degrade after 600 hours (25 days) by 5 percent if kept under 36 degrees Fahrenheit (2 degrees Celsius) and by 10% if kept under 104 degrees Fahrenheit (40 degrees Celsius).  [College of Chemistry, Peking Univ., Beijing, China, Se Pu 22:583-8, 2004]  Long-term stability of trans resveratrol may or may not be maintained in dietary supplements that are generally produced for a 2-year shelf life. This obviously depends upon the packaging.  Heat reflective foil packaging may be beneficial.

[FunkOdyssey]

This site has all the resveratrol related information you could ever want to know. Bill Sardi directed me to this site, so I'm not sure how impartial it is, but it does have a massive number of positive resveratrol studies (check recent articles)

http://www.resveratrolnews.com/

edit: Upon closer review, I have the nagging suspicion that the entire website is written and maintained by Bill Sardi. Hmm.

Edited by funkodyssey, 15 February 2006 - 07:38 PM.

[FunkOdyssey]

He keeps sending me more, lol...

Since there is considerable controversy over the stability of resveratrol in wine and dietary supplements, it should be noted that the following study employed research-grade resveratrol (Sigma and CalBiochem Biochemicals) which was kept frozen. 

Researchers noted that “Resveratrol, was quite labile (exhibited abnormal, highly variable effects) and became ineffective over time” and a “fresh stock was used when the activity seemed to decrease.”
 
Beata O, Wachowicz B, Holmsen H, Fukami MH, Resveratrol inhibits polyphosphoinositide metabolism in activated platelets, Biochim Biophys Acta. 2005 July 25

[xanadu]

I just went to the longevinex website and saw that their stuff is on backorder. I guess they sold out?

[FunkOdyssey]

They aren't, its just a glitch. You can actually get it cheaper from purityproducts.com ($29.99 for 1, $25.95 for 3, $21.95 for 12). Bill Sardi seems to have some kind of cross-promotional thing going on with them because on his Knowledge of Health site (http://www.knowledgeofhealth.com/) he lists his personal regimen and includes Purity Products stuff. He also takes 3 longevinex daily.

Some of his marketing and advertising tactics don't rub me the right way (plugging his product under the guise of health journalism and possibly through anonymous articles). What impression do you guys get after checking out longevinex.com, resveratrolnews.com, and knowledgeofhealth.com?

[DukeNukem]

Funk -- I've been a HUGE Sardi fan for about two years, and I've read a few of his books, like The Iron Timebomb (which further modified my diet and added IP-6 to my supplement program).

I buy my Longevinex for Purity, too, in batches of 12 to get those extra savings.

Sardi also radically affected my use of vitamin C (I take 10-12 grams spread throughout the day). Okay, yeah, he's probably making some money by helping design supplements like Longevinex, and as an adviser with Purity. And?

It's not like LEF doesn't do the same. But as long as the research and advice is solid, then I cut them a break. There are 100's of others out there selling supplements that have only one-tenth the integrity, or knowledge of their products.

BTW, does Sardi know where his messages are being reprinted? Might be nice to have him join us here. Maybe he isn't even aware of this group.

[FunkOdyssey]

He is aware of us, I mentioned it in my last phone conversation that I was forwarding his responses here. He said he's been to the website before.

[trh001]

I've spoken to Sardi. He strikes me as passionate, possibly genuine....but a bit desperate. He's a charming sales person, who's possibly in love with his product, or the idea of what might be achieved (as are we all), but he's invested (emotionally? financially?) too heavily to be objective.

[syr_]

Likewise, eating tomatoes is a poor way to get lycopene.  Eating fish can be a dangerous way to get enough EPA/DHA.

Why? I always have a good tomatos in my diet and I thought I dont need extra lycopene. Maybe I have to change my mind. Whats bad in eating a good quantity of tomatoes?
About fish, depends on the source. If they are not full of mercury and other s*hit, its definitely a healthy food.

Edited by syr_, 20 February 2006 - 07:24 PM.