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"500 club" 500mg of trans-resveratrol per day


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#31 tintinet

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Posted 23 January 2007 - 09:12 AM

Some of the RSV I take is accompanied by quercetin at times; at other times not so much...depends upon the preparation and whether I'm eating at that time or no...

I've got many different RSV preparations at this point...

Best? Likely the high purity (>99% trans-RSV) synthetic Orchid RSV Sinclair utilized in the recently published Nature rodent study, IMO.

#32 shadowrun

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Posted 23 January 2007 - 08:04 PM

I'm taking about 400-500 mg a day of Country Life RSV -
Is anyone else getting an effect with this brand?

I don't expect it to work overnight and I do take it with food and fish oil -

At the very least I wanted to supplement with grape skin and grape seed extract cost wise its the same as supplements that just containing grape seed

I figured I couldnt go wrong...

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#33 tintinet

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Posted 23 January 2007 - 09:17 PM

I've not tried the Country Life, but, at about 1 gram/day, including 500 mg Orchid high purity synthetic and 500 mg from various branded plant extracts, I've experienced very little I might attribute to RSV intake, so far. Still, I've only been taking higher doses for a relatively short period.

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#34 health_nutty

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Posted 23 January 2007 - 09:48 PM

I'm taking about 400-500 mg a day of Country Life RSV -
Is anyone else getting an effect with this brand?

I don't expect it to work overnight and I do take it with food and fish oil -

At the very least I wanted to supplement with grape skin and grape seed extract cost wise its the same as supplements that just containing grape seed

I figured I couldnt go wrong...


I am getting an effect with the Country Life Rsv plus. Increased energy, mood, appetite suppression, etc.

#35 shadowrun

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Posted 23 January 2007 - 11:38 PM

Maybe I should up my dosage...Its cheap enough
But at 5mg/kg I figured 400-500 would be sufficient
I figure with the other "stuff" in the Country Life I can't go wrong

I'll give it more time and report back in a week or 2

#36 eternalone

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Posted 23 January 2007 - 11:55 PM

fearfrost,

QUOTE:

You might want to check out
http://tinyurl.com/ycpjzp

If you have $30, I bet this article would answer a lot of questions... and mine too so if you pay, please share smile.gif Actually I will probably end up getting the article within the next week and I will link to it on a server if I do.

Thanks for the abstract. Very interesting. I'll see if I can get the whole article for free at my university and I'll post it here. No promises, but I will try.

Yes, I have also experienced the appetite suppression. I went from eating 4 times a day, to just 2 times. Breakfast and dinner. And I feel great.

#37 tintinet

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Posted 24 January 2007 - 01:08 AM

I can get the article for free, but may take a little while, via Lonesome Doc request.....will submit the request today.

#38

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Posted 24 January 2007 - 01:19 AM

http://www.sciencedi...fa9bea381ae658c


SIRT1 stimulation by polyphenols is affected by their stability and metabolism

Vincent C.J. de Boer, Marcus C. de Goffau, Ilja C.W. Arts, Peter C.H. Hollman and Jaap KeijerCorresponding Author Contact Information, E-mail The Corresponding Author

RIKILT – Institute of Food Safety, Wageningen University and Research Centre, Wageningen, The Netherlands

Received 7 December 2005; revised 6 February 2006; accepted 23 February 2006. Available online 17 April 2006.


Abstract

Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to stimulate the deacetylase activity of recombinant SIRT1 protein and could therefore be potential regulators of aging associated processes. However, inconsistent data between effects of polyphenols on the recombinant SIRT1 and on in vivo SIRT1, led us to investigate the influence of (1) stability of polyphenols under experimental conditions and (2) metabolism of polyphenols in human HT29 cells, on stimulation of SIRT1. With an improved SIRT1 deacetylation assay we found three new polyphenolic stimulators. Epigallocatechin galate (EGCg, 1.76-fold), epicatechin galate (ECg, 1.85-fold) and myricetin (3.19-fold) stimulated SIRT1 under stabilizing conditions, whereas without stabilization, these polyphenols strongly inhibited SIRT1, probably due to H2O2 formation. Using metabolically active HT29 cells we were able to show that quercetin (a stimulator of recombinant SIRT1) could not stimulate intracellular SIRT1. The major quercetin metabolite in humans, quercetin 3-O-glucuronide, slightly inhibited the recombinant SIRT1 activity which explains the lack of stimulatory action of quercetin in HT29 cells. This study shows that the stimulation of SIRT1 is strongly affected by polyphenol stability and metabolism, therefore extrapolation of in vitro SIRT1 stimulation results to physiological effects should be done with caution.

#39 eternalone

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Posted 24 January 2007 - 04:08 AM

Well I have to make a correction in what I said previously. I have been taking RSV for a while now but sparingly. I obtained a pretty high purity RSV via Sigma-Aldrich (99% by GC) several years ago and was only adding a couple of scoopfuls to a glass of wine on occasion. This is before I found out about the Sinclair longevity study, and was still in the dark about how much to take. So I was cautious. This past December I started taking higher doses of RSV but in the form of Solaray, Pure Encapsulations, and most recently Nature's Way. Although my initial intake may have not been on the scale of the Sinclair study, I am still glad I exposed my body to RSV in my mid-twenties.

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#40 fearfrost

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Posted 24 January 2007 - 05:41 AM

eternalone, check this out:
http://www.imminst.o...=0

the article that I mentioned about quercetin/resveratrol. Very interesting read. I am no longer taking quercetin, only resveratrol.

Cheers!

#41 shadowrun

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Posted 24 January 2007 - 06:24 PM

Would RSV with Fish Oil or any oil (lecithin) be better?
Does it really matter if we have it with food?

#42 tintinet

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Posted 24 January 2007 - 07:30 PM

There have been comments stating RSV's solubility is better in lipids than water. Taking it with food attempts to mimic the conditions of Sinclair's rodent study.

#43 shadowrun

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Posted 24 January 2007 - 07:58 PM

Thanks for the response -
Now I'm trying to find 2 regular times throughout the day when I eat and don't take other supplements to schedule in my RSV

#44 malbecman

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Posted 24 January 2007 - 09:27 PM

Usually to achieve the highest circulating blood levels, you want to take a drug on an empty stomach-that gives the most rapid absorption without a lot of food or liquid in the way. (BTW, you take NSAIDs on a full stomach as they usually irritate an empty stomach). Of course, the most rapid absorption and highest circulating blood levels would be to smoke it or do an iv administration like meth users but I don't think any of us want to go that far. The blood levels often spike ihigh n IV use which can often cause adverse effects from a drug which you wouldnt see from oral administration.

They fed RSV to the rodents in Sinclairs study as it is the easiest way to administer it orally-the rodents just do it themselves. Otherwise, you end up having to gavage (basically, force it down a feeding tube) the rodents every day which is a really messy and tiresome task, esp. for a long term study. Some poor grad student would end up doing that for months at a time.

RSV is pretty water insoluble so mixing it in with some oil might help its absorption but would add calories. You can see the physicochemical properties here:

http://www.ansci.cor...esveratrol.html


Hope that helps, let me know if you have any more metabolism or pharmacokinetic type questions.

Cheers,

Malbec

#45 shadowrun

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Posted 24 January 2007 - 10:00 PM

malbecman

Putting what you've said into perspective

Optimally - We should use RSV on an empty stomach

Most of the members on the board take fish oil so perhaps an independent dose of fish oil or another oil base (Lecithin,vitamin E?)

(Fish Oil, E, Lecithin, RSV combo!)

So RSV on an empty stomach with an oil base would be the closest to optimal we can get

(- minus anyone who would experiment with an IV or another method)

BTW - I had a roommate in college who was working on DNA - He spent 3-4 hours a day artificially inseminating mice for his proffessor... He had a god complex - it definately brought him back down to earth

#46 eternalone

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Posted 24 January 2007 - 11:00 PM

Fearfrost and ludongbin,



http://www.sciencedi...fa9bea381ae658c


SIRT1 stimulation by polyphenols is affected by their stability and metabolism

Vincent C.J. de Boer, Marcus C. de Goffau, Ilja C.W. Arts, Peter C.H. Hollman and Jaap KeijerCorresponding Author Contact Information, E-mail The Corresponding Author

RIKILT – Institute of Food Safety, Wageningen University and Research Centre, Wageningen, The Netherlands

Received 7 December 2005;  revised 6 February 2006;  accepted 23 February 2006.  Available online 17 April 2006.


Abstract

Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to stimulate the deacetylase activity of recombinant SIRT1 protein and could therefore be potential regulators of aging associated processes. However, inconsistent data between effects of polyphenols on the recombinant SIRT1 and on in vivo SIRT1, led us to investigate the influence of (1) stability of polyphenols under experimental conditions and (2) metabolism of polyphenols in human HT29 cells, on stimulation of SIRT1. With an improved SIRT1 deacetylation assay we found three new polyphenolic stimulators. Epigallocatechin galate (EGCg, 1.76-fold), epicatechin galate (ECg, 1.85-fold) and myricetin (3.19-fold) stimulated SIRT1 under stabilizing conditions, whereas without stabilization, these polyphenols strongly inhibited SIRT1, probably due to H2O2 formation. Using metabolically active HT29 cells we were able to show that quercetin (a stimulator of recombinant SIRT1) could not stimulate intracellular SIRT1. The major quercetin metabolite in humans, quercetin 3-O-glucuronide, slightly inhibited the recombinant SIRT1 activity which explains the lack of stimulatory action of quercetin in HT29 cells. This study shows that the stimulation of SIRT1 is strongly affected by polyphenol stability and metabolism, therefore extrapolation of in vitro SIRT1 stimulation results to physiological effects should be done with caution.


Well, this was a very interesting and informative article. WOW! Thanks for posting it on the yahoo resveratrol group. So, after reading the article it reinforces why I am not pairing my RSV with quercetin anymore.
Furthermore, from what I read I am going to start pairing RSV with Vitamin C and consume it with an alkaline drink such as green tea or alkanilized water.
So now my combo will consist of RSV, Lecithin, Vitamin C, Fish Oil caps, a couple teaspoons of EVOO.

#47 opales

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Posted 24 January 2007 - 11:14 PM

Male 30yo 150lb 7% BF
BP 100/60
Resting Heart Rate: 60bbm


I'm not sure how accurate my home omron bp monitor  is but here are the numbers after day 2:
BP: 124/75 (previous measurement was at doctors office)
bpm: 58


Wait, a 24 point rise in systolic BP and 15 point increase in diastolic BP, no? Not quite what I expected [huh], any updates?

#48 malbecman

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Posted 24 January 2007 - 11:18 PM

Shadowrun,

Right, I would take RSV on an empty stomach with some kind of oil to help absorption. Food can really slow down absorption and lower the blood levels.

I take my RSV on an empty stomach around mid-late morning. It def. inhibits my appetite so that lunch can easily become an afterthought if one isnt careful. It sometimes makes me burp once and I taste it but doesnt upset my stomach or anything (these are polyg. extract caps).

I feel sorry for your roommate inseminating all those animals, that is def. grad student work. I had one colleague who worked on horse insemination. They would wear football helmets when collecting semen from the stallions. [lol]

-M

On another note, RSV already stands for Respiratory Syncitial Virus, the major cause of bronchitis in children so maybe we need another abbreviation without the negative connotations.

Edited by malbecman, 24 January 2007 - 11:50 PM.


#49 health_nutty

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Posted 25 January 2007 - 12:20 AM

Opales,
I'm chalking up the change to my home monitor being uncalibrated (and old). I'll bring my home monitor in next time I go to the doctor.

#50 shadowrun

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Posted 25 January 2007 - 12:52 AM

Eternalone

What is EVOO?

Do you really think its better to take with Vitamin C and an alkaline drink?
(Can you please provide a link with the info)

Thanks!

Malbecman...That was definately a graphic image! [lol]

#51 Shepard

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Posted 25 January 2007 - 01:09 AM

What is EVOO?


Extra Virgin Olive Oil

#52 shadowrun

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Posted 25 January 2007 - 04:39 AM

Thanks Shepard

...I'd never of guessed it

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#53 tintinet

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Posted 25 January 2007 - 09:17 AM

I'm sticking with the rodents, for now, and consuming the majority of my RSV in divided doses with food (sometimes with small snack containing a small amount of healthy lipids) from early AM to later PM.

I'm also using a variety of sources. Although I have no reservations about the Orchid product, the others, IMO, remain uncertain WRT to absolute purity, trans-RSV content, and possible contaminant content.

#54 shadowrun

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Posted 25 January 2007 - 05:20 PM

I just wanted to update - I haven't noticed much from the RSV before

I started taking 200 mg in the morning on an empty stomach with 2 teaspoons of Fish Oil and 1 Vitamin E (100 mg natural E tablet)

I've noticed increased energy - more mental alertness - very slight headache -
I would definately not recommend anyone take this near bed time -

With my other supplements - Scheduled feedings (like a zoo animal) work - gym and life in general - I haven't been able to get my second dose in me at a conducive enough time - I'll prob stick around 200 mg for a little while longer

#55 maxwatt

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Posted 25 January 2007 - 05:44 PM

I'm sticking with the rodents, for now, and consuming the majority of my RSV in divided doses with food (sometimes with small snack containing a small amount of healthy lipids) from early AM to later PM. 

I'm also using a variety of sources.  Although I have no reservations about the Orchid product, the others, IMO, remain uncertain WRT to absolute purity, trans-RSV content, and possible contaminant content.


I suspect it doesn't matter, divided doses versus all-at-once. The molecule binds to SIRT1 and SIRT5, and probably all seven SIRT genes.
As long as it gets into your cells, you will reach a saturation point for the amount you are taking over time, and this will be the same either way.

There has been speculation a large dose is needed to bypass the liver, but I've seen no evidence of that. Nothing in the metabolic process seems to be rate limiting, either for or against. Blocking by other substances (Quercetin metabolites) might be a problem with food, but normally the amount of such things doesn't reach the pharmacological level of 50 mg doses of resveratrol. I suspect taking with food or without, makes no difference.

The above is speculation based on what is known about resveratrol's metabolism and mode of action (Sinclair's papers, mostly) but no studies have been done that specifically address the issue in humans.

I've noticed no stimulant effect from RESV (how's that for an abbreviation?). I do have a sense of physical well-being I could attribute to it.

#56 malbecman

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Posted 25 January 2007 - 06:20 PM

Health nutty, you said:
"I'm chalking up the change to my home monitor being uncalibrated (and old). I'll bring my home monitor in next time I go to the doctor."

Dont forget, your bp can also vary quite a bit from day to day, depending on whether you've just been for a bike ride or had a cup of coffee.

I would also give the ResV time to act, don't forget you are starting a whole cascade of events in your body that just begins by ResV binding Sirt1 and then affecting transcription, production of new proteins to affect their targets, etc, etc. It will all take some time. Don't forget, Sinclair et al were looking at a major portion of the rodent's life when studying their effects. I would wait at least several month if not a year or more to draw any conclusions....

Just my 2 cents,

Malbec

#57 tintinet

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Posted 25 January 2007 - 09:06 PM

...I've noticed no stimulant effect from RESV (how's that for an abbreviation?).  I do have a sense of physical well-being I could attribute to it.


I've had a similar experience. Although during the first intitial period of increasing my RESV (also the Biotest product's moniker) from a baseline of Longevinex and a bit of additional input via other herbal supplement preparations, to 5 mg/kg I thought I did notice increased stamina, but lately I've not been feeling so. Perhaps I have gone past my optimal dosage point for such effects...(now closer to 10 mg/kg/day). OTOH, I have noted a persistent buoyant mood and general sense of robust physical and mental wellness. Perhaps placebo, from start to current observations?

#58 health_nutty

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Posted 31 January 2007 - 06:44 AM

I'm taking 600mg per day now (1 cap with every feeding). I haven't noticed any significant laxative effect after the first two days (much less the second day). The energy boost is also gone (or I've gotten used to it). No noticable gains in endurance or unusual gains in weightlifting.

#59 shadowrun

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Posted 31 January 2007 - 07:32 AM

I'm at 2 weeks on 400 MG a day
I take the RSV all at once in the morning with a tablespoon of fish oil and water (sometimes a 100 mg Natural Vit E cap)
Does drinking it with an Alkaline Drink really impart a benefit?

The first few days I noticed the energy affect and enhanced alertness. The 3rd day I had a minor heacache for 30 minutes. I no longer feel anything and I have experienced no laxative effect with the Country Life. I'm thinking of moving on to the BAC powder

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#60 maxwatt

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Posted 31 January 2007 - 02:00 PM

I'm taking 600mg per day now (1 cap with every feeding).  I haven't noticed any significant laxative effect after the first two days (much less the second day).  The energy boost is also gone (or I've gotten used to it).  No noticable gains in endurance or unusual gains in weightlifting.


I found the same thing about energy, but when I got tired I got VERY tired. After a few days this effect vanished. After three weeks, I'm beginning to feel it again, but it's more subtle. I just feel stronger, but haven't tried to measure it. Power output on an ergonometer has increased slightly. No headaches. Appetite only slightly diminished, still like wine but seem to drink less at dinner. I had been taking it twice a day, divided doses, recently started taking it all in the morning for convenience. I do not think it makes a difference. Absolute blood levels do not, IMO, matter, as much as the amount taken in by your cells over time.

I would trust Country Life and BAC to test their material. The trans-resveratrol content will be very close to 50%, probably slightly higher. cis-resveratrol is not an issue except when exposed to ultraviolet light (sunlight, fluorescent, halogen) for more than a few hours. Stability is not an issue in dry form, at room temperature or lower.

The issue is emodin content. The other substances in the herb, present in the extract, are not harmful, and almost certainly do not inhibit the effect of resveratrol. Apparently three of the 50% products (Bioforte, Country Life, BAC) are low emodin, in that users have reported only slight, transient laxative effects. I think that these emodin levels would limit ones dosage to not more than 500 mg of resveratrol daily (or one gram of powder). I have reports that at least two people are unable to acclimate by ramping up to higher dosages of emodin; its physiological effects can only be adjusted to to a certain point.

In a word: if you want to take higher doses of resveratrol than 400 or 500 mg, you need to use the Orchid high-purity resveratrol along with Paul's group who are buying it. If you don't want to deal with having to adjust to the amount of emodin, use high-purity resveratrol. Likewise if you are one of those people who cannot tolerate any amount of emodin.

If enough people chipped in I could have a sample tested specifically for trans- and cis-resveratrol, and emodin. Bacteria, fungus, and heavy metals are other possibilities, but I trust Country Life completely in this regard, and believe the others are taking reasonable precautions as well. It would probably be a waste of time.

I think that a cooperative purchase of bulk powder can be made (with independent testing), which would bring the final cost/gm to not more than half that of the BAC powder.




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