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Maximizing Resveratrol Effectiveness


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#1 oaklandj

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Posted 12 July 2007 - 12:53 AM


I've been on a relatively heavy dose of resveratrol (Revgenetic's R500) for a couple of weeks, and I'm wondering how I can make sure that I'm getting the most out of it: to get the health/longevity benefits, and to make sure I'm not throwing all this money down the toilet.

Does anyone have any evidence for taking it one way or the other:
• One large dose vs. Several smaller doses spaced throughout the day
• On an empty stomach vs with a meal
• At the beginning of the day vs at the end
• Dissolved into alcohol (?) and drunk vs. taken with water
• Taken with quercetin or any other substance that enhances uptake & prevents metabolism or elimination by the body

I guess there's a question of whether metabolism is a good thing or not. I've read that glucuronidation/sulfation in the liver actually helps carry the molecule to its intended cell nucleus targets.

I've found it's a bit hard to separate some people's contentions & practices from what we've read with respect to other vitamins. For instance, vitamin C should be spaced out during the day, hence time-release formulas, but for gene-flipping that might not be ideal for resveratrol. (I don't know) The same for on an empty stomach vs with a meal – sometimes it seems like a philosophical discussion more than anything else.

Would be interested to hear what others have read and found out. (I realize that there are still a lot of unknowns, but maybe some have found more info than I have)

#2 niner

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Posted 12 July 2007 - 01:20 AM

The problem with resveratrol is that it is not very bioavailable. This is mainly because it is glucuronidated and sulfated very quickly, both in the gut and in the liver. As a result, it is difficult to get a high enough concentration of native resveratrol in the blood to do much good. For this reason, I would recommend taking the dose all at once rather than spreading it out. You will get a higher blood level that way, and might benefit from any possible swamping of metabolic mechanisms that might occur from the higher dose.

I would also lean toward taking it on an empty stomach rather than with a meal, mainly with an eye toward maximizing the concentration in the gut. I'm open to suggestions on this point.

If you dissolve it in alcohol and drink it, it will precipitate in the stomach when the alcohol is diluted, so I don't think you gain much there. The particle size and morphology of the precipitate are a question; it's conceivable that you might get a smaller particle size than you started with, which would be good, or you might get a clumpy aggregate. I don't know. I take it in a capsule, myself.

Quercetin might help. There's been a lot of discussion of it on imminst. I'm quite interested in using the Sirtris SRT-501 approach; use a very fine (microns) particle size and create a suspension in a water polyethylene glycol (PEG) solution. The PEG coats the particles and enhances absorption. I don't know how large the particles can be to still get a benefit from this method. For most of us, the only route to a smaller particle size other than buying it that way would be simple grinding, as with a mortar and pestle. I doubt that this would be considered "micronizing", but it might improve things.

Finally, with respect to metabolism being a good thing, I think the answer is no. I have not seen any reports in the literature that resveratrol metabolites are active. There has been speculation that this might be the case, and there has also been speculation that perhaps such conjugates are cleaved in the target cell, liberating free resveratrol. However, these are only speculations. If conjugative metabolism were somehow eliminated, the bioavailability of resveratrol would be much better.

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#3 lucid

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Posted 12 July 2007 - 04:09 AM

As niner said, taking it with peg (aka Miralax at your drug store) is thought to be a good idea.

I think I might go buy a little everclear and do some experiments with seeing how the resveratrol precipitates when the resv/alcohol solution is mixed with water. I will note how quickly it takes for all of the precipitate to form and if I go out and buy a little scale I will measure the %of original that precipitates in the first hour.
Anyone have a very cheap scale that they would recommend? One that is good to measure to ~5mg accuracy.
*edit*Just bought this guy online, It looks pretty legit and will measure to 10 mg. for only 25$
http://www.wholesale...products_id=379*/edit*


Next, i will see how resveratrol precipitation compares when Miralax is mixed in... I doubt any of the precipitate will make it to the bottom of the container. I imagine the process will work like this: Resv is disolved in the alcohol -> miralax is added -> water is added to mixture, bringing alcohol concentration down to about 20% -> resveratrol precipitates and soon there after is picked up by peg3350 and goes into suspension. It would seems this would decrease particle size, but I won't have anyway to measure particle size that I can think of...

Hopefully I will see that the alcohol precipitate in the first experiment creates smaller particles when precipitating, but again I won't be able to measure that more than by just looking at it / feeling it. Then I will see no precipitate form in the second experiment. I might do some reading about how chemists might decrease particle size in their experiments. I will report back later.
*edit* I can't find much on precipitation particle size, apparently if the drug is highly soluable in the solvent: which I believe resveratrol is in ethanol, then you can expect fairly large particle size, perhaps performing the mixing @ very low temperatures could decrease particle size of the precipitate when mixing.*/edit*
Here is a weird idea that I just had that I am not sure will work: put lots of salt and our solute (resv) into an ethanol solution, evaporate the ethanol making the resv and salt precipitate together. I imagine that the resv would precipitate onto a developing salt crystaline structure. Then once the ethanol has dried, immerse in water to pull the salt into solution leaving hopefully a very fine resveratrol dust, not sure how well this would work, but I am going to try the first and second experiments mentioned in this post once my scale comes in.

Edited by lucid, 12 July 2007 - 06:38 AM.


#4 malbecman

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Posted 12 July 2007 - 11:52 PM

As niner said, taking it with peg (aka Miralax at your drug store) is thought to be a good idea.




I have also played a little w/ lecithin as my emulsifier and it seems to do a good job at keeping the resveratrol in solution. It looks much more
like a milky suspension that does not settle w/ time (as opposed to resveratrol in straight water). Lecithin doesnt really taste that bad and should
be available at your local health food store.

#5 oaklandj

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Posted 13 July 2007 - 12:13 AM

These are interesting suggestions. But I have some questions:

* How can you selectively dissolve resveratrol from ground knotweed? Or does it not matter? (Is it the inert fiber that's the problem in absorption?)
* Are you microencapsulating (using PEG) the ground knotweek particles, or are you suggesting using alcohol to bring out the resveratrol (and I assume any other alcohol-soluble components in it like emodin)?
* Wouldn't the PEG slow down the absorption of the resveratrol? (Assuming you want a sudden absorption to slow down metabolism)

Thanks!

#6 lucid

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Posted 13 July 2007 - 12:31 AM

* How can you selectively dissolve resveratrol from ground knotweed? Or does it not matter? (Is it the inert fiber that's the problem in absorption?)

I am using 98% resveratrol extract, so there isn't much knotweed left in what I am using. I believe others reported that when mixing 50% resv with an emulsifier, the resv didn't make quite such a milky liquid, not sure though.

* Are you microencapsulating (using PEG) the ground knotweek particles, or are you suggesting using alcohol to bring out the resveratrol (and I assume any other alcohol-soluble components in it like emodin)?

I have been mixing PEG3350 with powdered resveratrol and water every day. I am going to try to use the alcohol to dissolve the resveratrol and hopefully in doing so decrease the particle size. Then I will mix the dissolved resveratrol with water and peg3350 which should hopefully encapsulate the now much smaller resveratrol precipitates.

* Wouldn't the PEG slow down the absorption of the resveratrol? (Assuming you want a sudden absorption to slow down metabolism)

As I understand it, it should increase absorption speed via increasing surface area of the particles. Apparently sirtris documented this when testing their srt501 which we believe to be micronized resveratrol and an emulsifier.

#7 lucid

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Posted 13 July 2007 - 03:33 PM

Mmk. I have done a preliminary little experiment and it looks to have good results for decreasing particle size.
Step one: fill shot glass 1/4 with everclear.
Step two: put about 300 mg of 98% extract trans-resv into shot glass.
Step three: mix for about 3 minutes.
The solution will now be perfectly clear where as the resv is dissolved.
Step four: mix into water (Possibly with peg3350 mixed into it)
When you pour the clear shot into the clear water, it will instantly precipitate making a white cloud in the water, pretty cool looking.
Even without peg3350 mixed in, it is easy to tell that the resv is mixed in much better than it was with just water. While I have no way to measure particle size reduction, I imagine it is very large.

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Step six: Drink.

#8 Anthony_Loera

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Posted 13 July 2007 - 03:41 PM

[lol]
I think you just came up with a great new drink!

... specially if you can light it on fire before you swig it... [tung]
I would call it the "The Phoenix..." or something. Maybe instead of lighting it we put some redbull into it... hmmm

"Please, make my Phoenix shaken... not stirred..."
(runs off to try it out...)

#9 tintinet

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Posted 13 July 2007 - 07:07 PM

What's next- aerosolized for inhalation?

#10 lucid

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Posted 13 July 2007 - 08:11 PM

I will try and take some pictures of it tomorrow when I dose, but I am pretty sure that when done this way the particles are pretty close to miconized. They appear finer than silt so I would guess <5 micro meters, but it is hard to say without measuring... Anyone know an easy way to measure particle size (only thing I have heard of is x-ray diffraction...)

What's next- aerosolized for inhalation?

Next thing i'm going to try is an IV injection, it will improve blood serum levels by about 6x. But then again I would probably die from infecting myself...

#11 tintinet

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Posted 13 July 2007 - 08:55 PM

Anyone try the transdermal patches yet?

WRT IV- make sure you're using a totally pure and clean preparation- you'd not want a bunch of gunk stuck in your pulmonary capillaries.

#12 lucid

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Posted 13 July 2007 - 09:09 PM

WRT IV- make sure you're using a totally pure and clean preparation- you'd not want a bunch of gunk stuck in your pulmonary capillaries.

Yeh I was kidding bout IV injection. [glasses]

#13 niner

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Posted 14 July 2007 - 03:35 AM

I will try and take some pictures of it tomorrow when I dose, but I am pretty sure that when done this way the particles are pretty close to miconized. They appear finer than silt so I would guess <5 micro meters, but it is hard to say without measuring... Anyone know an easy way to measure particle size (only thing I have heard of is x-ray diffraction...)

Wow lucid, way to go with the experimentation! For particle sizes in the micron range, it's usually measured via diffraction at visible wavelengths, or thereabouts. The equipment would be prohibitively expensive (except maybe for duke...) but maybe microscopy would work. It shouldn't be difficult to find a size standard that was around .001 inches, like a fine wire or a hair or something, and you could measure that with a cheap micrometer. Then by comparing the particles to the width of the standard on a microscope slide, you could get a reasonable sense of the particle size. Ten microns is .4 thousandths, if I did the math right. (Sorry about the archaic units)

I wonder if the suspension could be filtered without inducing agglomeration? Maybe it could be resuspended in a decent tasting aqueous medium. (Schlitz Malt Liquor, Tang, Peach Snapple, Horlicks, or any combination of these...)

Anthony, if you're reading, do you have any idea what the particle size of your 98% powder is?

#14 lucid

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Posted 14 July 2007 - 06:13 AM

Anthony, if you're reading, do you have any idea what the particle size of your 98% powder is?

This is from the 'tres bio-availibility' thread.

I really doubt that your powder is anything like nanoparticles. Here is a link to an FDA document regarding a resveratrol product. Note that the powder is 100 mesh, which is typical.

Here we can find a chart detailing what 100 mesh means: average particle size of 0.149mm. That's 149,000nm or roughly 500 times larger than what is called for in the patent. Even if your powder is 10 times finer (which I doubt), that's still 50 times larger than you want it to be.

So noway seems to be saying we could expect resv to be around 149 um.

The equipment would be prohibitively expensive (except maybe for duke...) but maybe microscopy would work.

What about maybe using like a 10 micron air filter? Would that work with water? Those are pretty cheap.

#15 tintinet

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Posted 14 July 2007 - 10:27 AM

Yeh I was kidding bout IV injection. [glasses]


Ya. Getting into injections strikes me as a bit extreme (lunatic fringe?). Although I am tempted by melanotan....

#16 lucid

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Posted 15 July 2007 - 01:36 AM

Here are the pictures that I have taken:
98% Resveratrol + Water
So this is resveratrol mixed in water: I have stirred it for 10 minutes, notice very low absorption in the water.
Posted Image
98% Resveratrol + PEG3350+Water
So this is resveratrol mixed in water with PEG3350 added: I have stirred it for a couple minutes, particle size isn't too small, but it is clear that it is now mixing in with the water.
Posted Image
98% Resveratrol mixed in Ethanol (Everclear) in a shot glass (No water)
Here the resveratrol is mixed in with Ethanol and it is completely clear where as the ethanol is disolved.
Posted Image
98% Resveratrol mixed in Ethanol (Everclear) + Water
Here the resveratrol is mixed in with Ethanol and is then mixed with a larger amount of water. Notice that the mixture is much clearer than the Resveratrol + PEG3350 + Water. You can also (though not in the picture) see very small particles in the water, It is certainly smaller than a silt.
Posted Image
98% Resveratrol mixed in Ethanol (Everclear) and PEG3350 then mixed in water.
Here the resveratrol is mixed in with Ethanol and PEG3350 and is then then mixed with a larger amount of water. The closest thing I can compare this to is milk. I can not see any particles in the suspension. It is a creamy color.
Posted Image
I recommend washing this down with some fruit juice mixed in... Its pretty difficult to take plain. I wash it down with some pomegranate juice.

#17 niner

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Posted 15 July 2007 - 03:56 AM

Lucid, my hat's off to you; I think you made 501. Rather than a 10 micron filter, I suspect what you may want is more like a 25-50 micron screen; I think 10 would clog too fast. Such a thing is probably purchasable, though for how much I can only speculate. (too much...) My gut sense is that the particle size is probably "good enough" from your description and the pictures. I wonder what is the minimum amount of ethanol you can get away with? Though I'm sure a quarter shot a day wouldn't kill me, regular drinking doesn't seem to be good for my mood or waistline, although my cholesterol levels like it. At the moment I'm avoiding EtOH except socially. If you've really created a 501 mimic like I think, we should be able to get by with a lot less rsv. What was Sirtris' claim on blood levels, a factor of 4? 10? I forget.

This is beautiful work. Nice job!

#18 maxwatt

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Posted 15 July 2007 - 04:03 AM

If you evaporate the water and ethanol (vodka, anyone?) the particulate matter left should be a water-soluble mixture of PEG3350 and resveratrol. It could be capped. I'm sure one could sell a powder like this for "cosmetic" purposes. A capsule might need FDA approval or it will invite their scrutiny.

#19 lucid

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Posted 15 July 2007 - 04:26 AM

(vodka, anyone?)

Yeh, vodka didn't work nearly as well. It certainly worked better than plain water, but the resveratrol wouldn't go clearly into solution, i have to recommend everclear.

particulate matter left should be a water-soluble mixture of PEG3350 and resveratrol. It could be capped. I'm sure one could sell a powder like this for "cosmetic" purposes. A capsule might need FDA approval or it will invite their scrutiny.

Good idea, I might try evaporating some, it's pretty hot in atlanta, so I doubt it will take long ;)

#20 sUper GeNius

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Posted 15 July 2007 - 06:03 AM

lucid,

What's the minimum amount of alcohol you think one could use?

#21 lucid

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Posted 15 July 2007 - 12:34 PM

Just made my morning brew. It took about .7ounces of 95% ethanol to dissolve 500mg of t-resv. I will have more specific numbers next week as to specific resv weights, alcohol amounts, and water amounts (mine are just 'eye balled' right now).

Edited by lucid, 15 July 2007 - 12:57 PM.


#22 lucid

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Posted 15 July 2007 - 03:02 PM

Would alcohol be a more effective delivery method than miralax?

The problem is that when you consume the alcohol, the resveratrol will precipitate out when the mixture gets to your stomach. The SRT501 study showed that delivery with a micronized particle mixed with tween was far superior to delivery of the micronized particle alone. And I am not sure (at all) how this would work, but I imagine that during the precipitation process, the resveratrol particles might aggregate together. If this is the case, then possibly the PEG3350 could micro-encapsulate the small particles before they aggregate. The PEG3350+Ethanol+Resv+water looked noticably better than the non-PEG version.

I believe there had been some discussion about taking the resveratrol sublingually with alcohol. I don't know how well this would work: Considering the alcohol resveratrol mixture is clear, it is going to be difficult to know how much of the resveratrol has been absorbed.

#23 maxwatt

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Posted 15 July 2007 - 05:02 PM

lucid,

What's the minimum amount of alcohol you think one could use?


There is evidence to support that a constant low level of ethanol is life-extending. Like less than half an ounce, every four hours....

#24 Brainbox

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Posted 15 July 2007 - 05:11 PM

Biotech layman question: would the PEG3350 microencapsulating have the side effect of reduced availability as well?

#25 niner

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Posted 16 July 2007 - 02:41 AM

Biotech layman question: would the PEG3350 microencapsulating have the side effect of reduced availability as well?


Not according to Sirtris' data. They find that PEG enhances bioavailability which is the whole point of the exercise. Micronizing and mixing with PEG is a standard formulating trick for hydrophobes. I'm a little surprised they could patent it, but the USPTO never fails to amaze me.

#26 oaklandj

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Posted 16 July 2007 - 06:50 PM

Lucid, wow! Thank you for sharing those pics & descriptions on your dissolution/encapsulation methods. I showed it to my father, who's also a recent "convert" to resveratrol dosing.

I also like malbecman's use with lecithin. I have the 50% capsules from RevGenetics now, and until I exhaust those and purchase their 99% powder, I'll probably take it with lecithin. Then I'll use the alcohol (hope I can get Everclear here in California) and Miralax/PEG 3350 protocol. Should be easy enough to take and tolerate provided I take a strong-tasting juice chaser. ;)

#27 sUper GeNius

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Posted 16 July 2007 - 08:25 PM

Biotech layman question: would the PEG3350 microencapsulating have the side effect of reduced availability as well?

Not according to Sirtris' data. They find that PEG enhances bioavailability which is the whole point of the exercise. Micronizing and mixing with PEG is a standard formulating trick for hydrophobes. I'm a little surprised they could patent it, but the USPTO never fails to amaze me.


I don't recall seeing any specific PEG data. I do know they mentioned it in the patent. I thought the data involved Tween80.

#28 niner

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Posted 16 July 2007 - 09:57 PM

I don't recall seeing any specific PEG data. I do know they mentioned it in the patent. I thought the data involved Tween80.

You're right. Tween80, AKA polysorbate 80, has some polyether structure in common with PEG, but they aren't the same compound. They are both emulsifiers and have been used in similar applications, but Tween is more surfactant-like. Sorry for the zone-out.

#29 asnufu

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Posted 17 July 2007 - 10:30 AM

Great work, Lucid. I can't help but marvel at the fact that comparatively simple table-top ingredients - a laxative, a heavy-duty wine cooler and some plant concentrate - might significantly impact maximum lifespan and overall health. What we really need now, though, is some bloodwork to demonstrate plasma concentration and lipid profile before and after as well as other relevant biomarkers. I'll be having mine done in a few months, but I'm on a metformin/plain 'ol resv regimen, so if lucid or someone else experimenting with PEG/ethanol spiking could volunteer some information, that'd be great...

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#30 inawe

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Posted 17 July 2007 - 02:44 PM

I'm just a little surprised that the same people who complained about the effects of emodin are now using 99% resveratrol and mixing it with a laxative. But if it makes them run faster ...




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