180 replies to this topic

[rabagley]

While reading this thread I googled for "resveratrol gum" and found an announced (but not available) product. So far just a rash of press releases (so it may be complete vapor), but "Resveratrol Plus Chewing Gum" was announced on July 14, 2009 and seems to be in production as of July 29, 2009.

Since Anthony decided against releasing a gum product, this may be the only commercial game in town for resv-gum.

Edited by rabagley, 21 October 2009 - 08:13 PM.

[magnelectro]

I have tried buccal and sublingual resveratrol delivery in the past but now I mix my resveratrol with water and drink it throughout the day. I tend to believe the results of the study cited in Wikipedia, however incredible. The ease with which this could be confirmed/refuted coupled with the complete absence of evidence to the contrary leads me to believe that financial interests are to blame for the lack of replication of the effectiveness of buccal delivery. No matter what method of administration is used, the plasma half-life of resveratrol is short. Mixing it with your drinking water overcomes this problem while giving all the benefits of both oral and buccal delivery.

Obviously micronized would be better, but I am currently taking 400mg 98% powder daily along with all my other palatable powdered supplements. Mixed with 2-3L pure water results in a resveratrol suspension which I hope will be more effective than oral administration. What do you think?

Has anyone tested resveratrol plasma levels following buccal/sublingual administration? This seems like a HUGE knowledge gap that could easily be filled.

[Hedgehog]

I have tried buccal and sublingual resveratrol delivery in the past but now I mix my resveratrol with water and drink it throughout the day. I tend to believe the results of the study cited in Wikipedia, however incredible. The ease with which this could be confirmed/refuted coupled with the complete absence of evidence to the contrary leads me to believe that financial interests are to blame for the lack of replication of the effectiveness of buccal delivery. No matter what method of administration is used, the plasma half-life of resveratrol is short. Mixing it with your drinking water overcomes this problem while giving all the benefits of both oral and buccal delivery.

Obviously micronized would be better, but I am currently taking 400mg 98% powder daily along with all my other palatable powdered supplements. Mixed with 2-3L pure water results in a resveratrol suspension which I hope will be more effective than oral administration. What do you think?

Has anyone tested resveratrol plasma levels following buccal/sublingual administration? This seems like a HUGE knowledge gap that could easily be filled.

I couldn't find the article on wikipedia.

I read the article of

14C-resveratrol after oral and i.v.
doses in six human volunteers. The absorption of a dietary relevant
25-mg oral dose
However, only trace amounts of
unchanged resveratrol (<5 ng/ml) could be detected in plasma.

The link that wiki has is
INHIBITION OF CANCER GROWTH BY RESVERATROL IS RELATED TO
ITS LOW BIOAVAILABILITY

This article has nothing about resveratrol and humans.

Is there a REAL reference for the correct paper?

[magnelectro]

I couldn't find the article on wikipedia.

I read the article of

14C-resveratrol after oral and i.v.
doses in six human volunteers. The absorption of a dietary relevant
25-mg oral dose
However, only trace amounts of
unchanged resveratrol (<5 ng/ml) could be detected in plasma.

The link that wiki has is
INHIBITION OF CANCER GROWTH BY RESVERATROL IS RELATED TO
ITS LOW BIOAVAILABILITY

This article has nothing about resveratrol and humans.

Is there a REAL reference for the correct paper?

The reference is correct. Here is a PubMed link to "Inhibition of Cancer Growth by Resveratrol is Related to its Low Bioavailability" The quote is pulled from the fourth paragraph of the discussion section. "when t-RES (50 ml of a solution containing 23 μg t-RES/ml) was orally administered to humans (four different people in our laboratory, 26–44 years old), and retained in the mouth for 1.0 min before swallowing, 37 ± 5 μg of RES/l were measured in plasma just 2.0 min after administration." If anyone has trouble obtaining a copy of the full text, please PM me and I will be happy to provide it.

Now the question remains: Has anyone replicated or refuted buccal bio-availability? Is anyone on this board in a position to do so?
It is quite possible that commercial interests are preventing this information from being disseminated. If the buccal absorption is not as good as this paper claims, wouldn't Anthony Loera or other resveratrol retailers want to refute it? If the citation that everyone has been using for more than seven years is a typo or bad science, then why hasn't anyone refuted it?

[Anthony_Loera]

While reading this thread I googled for "resveratrol gum" and found an announced (but not available) product. So far just a rash of press releases (so it may be complete vapor), but "Resveratrol Plus Chewing Gum" was announced on July 14, 2009 and seems to be in production as of July 29, 2009.

Since Anthony decided against releasing a gum product, this may be the only commercial game in town for resv-gum.

I don't think it's the only game in town... just the one that has received more press.

I will see about this later this year.

Cheers
A

[tonyrx7]

Hey, whatever it takes to get that good stuff in! Until somebody have gums for us, meanwhile up me!

Edited by tonyrx7, 20 January 2010 - 05:32 PM.

[browser]

We are looking at Xylitol with possibly a little Stivia... as sweeteners.

Initial consideration was around 50mg-100mg a piece... I am not sure we can add more than this.
Time frame?... 2-3 months (The packaging appears to be the holdup on this...)

I am just not sure about the flavors... and of course, you heard it here first.

Hi Anthony, I was just wondering what happened to this idea? I can't see a gum product on your website, and wondered if you're still working on it, or if the idea was dropped for some reason?

I just couldn't see folks buying a $8 - $10 pack of gum...

It's still being considered, but other things have come up after our initial research into this.

Cheers
A

I could see where suppliers would NOT want RESV gum on the market. Except for suckers who are buying RESV in pill form because they don't know any better and Acai juice to lose weight, word would get out that you can get a hefty dose of RESV in your bloodstream continuously by chewing RESV gum with just a few mg. of RESV in it. The RESV economy would collapse. Suppliers would no longer be able to sell 25 grams of RESV for $75, no longer be able to sell special preparations of RESV in emulsifiers and Quercetin to protect the RESV from the liver. Plants going online to make many kilotons of RESV a month would become a waste of money. I'd imagine RESV manufacturers and suppliers would do anything to prevent RESV gum from going onto the marketplace. Perhaps that's why the outfit that has all of the announcements about RESV gum doesn't have any on the market and why a good idea suddenly becomes a back burner idea. Or an idea a supplier just can't see the public buying.

[Anthony_Loera]

Actually the only reason we haven't was because of the price/education factors.

1- A $10 pack of gum seems quit expensive
2- It appears that you would have the res inside the gum, you then would need to chew, then place inside of cheek. Add to that that the gum does not dissolve and leave the pure resveratrol in your mouth to be absorbed, Most of it would be in the gum.
3- Chewing naturally causes siliva, which wil likely make you swallow the unprotected res, rather than be it absorbed.

Try it out, I want to know if you can chew a piece of gum while having some powdered res in your mouth. What does the saliva do? Do you think you can stop from swallowing it?
If you can't stop from swallowing it, then it might simply become expensive gum.

Test it out, let me know.
A

Edited by Anthony_Loera, 08 March 2010 - 01:37 PM.

[browser]

Actually the only reason we haven't was because of the price/education factors.

1- A $10 pack of gum seems quit expensive
2- It appears that you would have the res inside the gum, you then would need to chew, then place inside of cheek. Add to that that the gum does not dissolve and leave the pure resveratrol in your mouth to be absorbed, Most of it would be in the gum.
3- Chewing naturally causes siliva, which wil likely make you swallow the unprotected res, rather than be it absorbed.

Try it out, I want to know if you can chew a piece of gum while having some powdered res in your mouth. What does the saliva do? Do you think you can stop from swallowing it?
If you can't stop from swallowing it, then it might simply become expensive gum.

Test it out, let me know.
A

Anthony, I see too many references about chewing gum with medication in it as a good way to get the medication. There's a whole industry built around nicotene gum. There's also aspirin gum. In both cases the active ingredient has been shown to be absorbed through the gums. Lozenges also work to deliver active ingredients through the oral mucosa.
RESV dissolves very slowly in saliva. You need 1 liter of saliva to dissolve 30 mg. of RESV. There's mucosa where saliva pools, between the bottom teeth and the gum. Some of the RESV will be absorbed from the saliva there. What's absorbed will go right into the blood stream, bypassing first pass denature by the liver. For you it's $10 a pack of gum. For me, using 125 micron RESV (I see no reason to use micronized), I can make 50 pieces of gum with 100 mg. 98% RESV for $20. That's $0.40 a piece of gum. That's for the first batch. If I buy a gum refill kit, the price drops down to $8 for 50 pieces of gum containing 100 mg. RESV. That's 16 cents per piece of gum.

[peteo]

So after reading this thread what do people think is currently the best way to take Resveratrol?

Pill, Micronized in a pill, Buccal delivery, through the Skin?


if it is Buccal delivery are these any good?
http://www.puritan.c...31206?NewPage=1

Edited by peteo, 08 March 2010 - 06:05 PM.

[maxwatt]

Actually the only reason we haven't was because of the price/education factors.

1- A $10 pack of gum seems quit expensive
2- It appears that you would have the res inside the gum, you then would need to chew, then place inside of cheek. Add to that that the gum does not dissolve and leave the pure resveratrol in your mouth to be absorbed, Most of it would be in the gum.
3- Chewing naturally causes siliva, which wil likely make you swallow the unprotected res, rather than be it absorbed.

Try it out, I want to know if you can chew a piece of gum while having some powdered res in your mouth. What does the saliva do? Do you think you can stop from swallowing it?
If you can't stop from swallowing it, then it might simply become expensive gum.

Test it out, let me know.
A

Anthony, I see too many references about chewing gum with medication in it as a good way to get the medication. There's a whole industry built around nicotene gum. There's also aspirin gum. In both cases the active ingredient has been shown to be absorbed through the gums. Lozenges also work to deliver active ingredients through the oral mucosa.
RESV dissolves very slowly in saliva. You need 1 liter of saliva to dissolve 30 mg. of RESV. There's mucosa where saliva pools, between the bottom teeth and the gum. Some of the RESV will be absorbed from the saliva there. What's absorbed will go right into the blood stream, bypassing first pass denature by the liver. For you it's $10 a pack of gum. For me, using 125 micron RESV (I see no reason to use micronized), I can make 50 pieces of gum with 100 mg. 98% RESV for $20. That's $0.40 a piece of gum. That's for the first batch. If I buy a gum refill kit, the price drops down to $8 for 50 pieces of gum containing 100 mg. RESV. That's 16 cents per piece of gum.

The problem is that gum-delivery systems work best for water-soluble substances. Polar substances,not so much. Some resveratrol does get absorbed by bucal administration, and what is absorbed more efficiently spikes blood serum levels, but not enough. The rate at which the mucosa pass resveratrol into the blood, times the surface area, is not sufficient to deliver a large dose at all. It can only deliver a very small dose efficiently.

[browser]

Actually the only reason we haven't was because of the price/education factors.

1- A $10 pack of gum seems quit expensive
2- It appears that you would have the res inside the gum, you then would need to chew, then place inside of cheek. Add to that that the gum does not dissolve and leave the pure resveratrol in your mouth to be absorbed, Most of it would be in the gum.
3- Chewing naturally causes siliva, which wil likely make you swallow the unprotected res, rather than be it absorbed.

Try it out, I want to know if you can chew a piece of gum while having some powdered res in your mouth. What does the saliva do? Do you think you can stop from swallowing it?
If you can't stop from swallowing it, then it might simply become expensive gum.

Test it out, let me know.
A

Anthony, I see too many references about chewing gum with medication in it as a good way to get the medication. There's a whole industry built around nicotene gum. There's also aspirin gum. In both cases the active ingredient has been shown to be absorbed through the gums. Lozenges also work to deliver active ingredients through the oral mucosa.
RESV dissolves very slowly in saliva. You need 1 liter of saliva to dissolve 30 mg. of RESV. There's mucosa where saliva pools, between the bottom teeth and the gum. Some of the RESV will be absorbed from the saliva there. What's absorbed will go right into the blood stream, bypassing first pass denature by the liver. For you it's $10 a pack of gum. For me, using 125 micron RESV (I see no reason to use micronized), I can make 50 pieces of gum with 100 mg. 98% RESV for $20. That's $0.40 a piece of gum. That's for the first batch. If I buy a gum refill kit, the price drops down to $8 for 50 pieces of gum containing 100 mg. RESV. That's 16 cents per piece of gum.

The problem is that gum-delivery systems work best for water-soluble substances. Polar substances,not so much. Some resveratrol does get absorbed by bucal administration, and what is absorbed more efficiently spikes blood serum levels, but not enough. The rate at which the mucosa pass resveratrol into the blood, times the surface area, is not sufficient to deliver a large dose at all. It can only deliver a very small dose efficiently.

Then why are people having such success with buccal delivery? I put 110 RESV into some Bacardi 151, swished it in my mouth for 30 minutes. By the end of 30 minutes I was very anxious, very nervous. This has been reported by at least one other member/poster before. Also, the


"The most efficient way of administering resveratrol in humans appears to be buccal delivery, that is without swallowing, by direct absorption through the inside of the mouth. For example, with resveratrol lozenges. When one mg of resveratrol in 50 mL solution was retained in the mouth for one min before swallowing, 37 ng/ml of free resveratrol were measured in plasma two minutes later. This level of unchanged resveratrol in blood can only be achieved with 250 mg of resveratrol taken in a pill form.[23]"

text is still in the Wikipedia. We've not been able to verify that this sort of study has been repeated but AFAIK we've not been able to refute the study/statement either, except with the theory that there's not enough surface area, you can't get enough in.

I am on HRT. I swish 100 mg. of pure Testosterone base in oil and fillers around in my mouth twice a day for a few minutes. Quite enough gets into my bloodstream to markedly raise my blood Testosterone. Resveratrol is polar.

[Saintor]

Has the industry moved? Or didn't they find any truth to this?

I guess that if it this would be true, we would have resveratrol lozenges by now.

Just for the sake of it, I tried to chew a pill of Bioforte Transveratrol .... alone it is disgusting (thye are not intended to be used that way obvioulsy). With a gum, the pill just mixes with it and it is quite feasible. I don't even know if there is a reason to do so, 2 years later.

[windymiller]

I bought some 98% resveratrol some months ago intending to take it by the buccal or sublingual route.

I messed about with vodka and red wine etc. and wasn't at all impressed with the solubility - taking far to much alcohol in the process

Then I remembered that folk with angina used to use glyceryl trinitrate sublingually and in the 1950s/60s this meant using cocoa butter as a base.

Now I use dark chocolate!

I buy bars of dark chocolate (itself containing anti-oxidants) and take a square every day. I put it in a little plastic tub (e.g. ex hummous dip) and float it in a little warm water till it melts. Then I stir in about 100mg of the resveratrol powder which is very soluble in the theobroma oil which solidifies on cooling (if I don't overheat it).

This gives me a thin "wafer" of chocolate containing the resveratrol.

It's easy to break off a little and let it dissolve under my tongue or in my cheek at the front. I don't seem to swallow the chocolate which "melts in my mouth". I finish the entite wafer in ten minutes or so.

I don't know if the resveratrol is actually doing anything but I'm remarkably well on the few supplements that I do take and a thought-about diet.

Edited by windymiller, 01 April 2010 - 03:04 PM.

[indio007]

What wrong with snorting it? Someone said it burns. It didn't burn me. Then again it wasn't pure extract either.
This method would make it pass the blood brain barrier slowing delivery to the liver. Analgesic effect of Resveratrol via inter cranial administration in rats has been reported.
I've seen south americans natives snort some pretty harsh shit that will make you drool like a fool for hours. How bad could it be?

[niner]

What wrong with snorting it? Someone said it burns. It didn't burn me. Then again it wasn't pure extract either.
This method would make it pass the blood brain barrier slowing delivery to the liver. Analgesic effect of Resveratrol via inter cranial administration in rats has been reported.
I've seen south americans natives snort some pretty harsh shit that will make you drool like a fool for hours. How bad could it be?

When you say "How bad could it be?", are you looking for a worst-case scenario? That would probably be some form of lung disease. I don't know how likely that would be; not very I suppose. The problem is that you are snorting something that is mostly insoluble in water. What will those particles do when they are lodged in the alveoli? With luck they will slowly absorb, but I wouldn't want to count on that. At any rate, snorting is not exactly an intra-cranial route. That would involve needles. I've seen the video of those South American natives- the one where one of them uses a blowpipe to shoot the drugs up the other guy's nose? Yeah, that was pretty gross with all the stuff coming out of various orifices. I don't think those guys are into life extension. If they had LSD, I bet they'd dump the harsh stuff and never look back...

[indio007]

What wrong with snorting it? Someone said it burns. It didn't burn me. Then again it wasn't pure extract either.
This method would make it pass the blood brain barrier slowing delivery to the liver. Analgesic effect of Resveratrol via inter cranial administration in rats has been reported.
I've seen south americans natives snort some pretty harsh shit that will make you drool like a fool for hours. How bad could it be?

When you say "How bad could it be?", are you looking for a worst-case scenario? That would probably be some form of lung disease. I don't know how likely that would be; not very I suppose. The problem is that you are snorting something that is mostly insoluble in water. What will those particles do when they are lodged in the alveoli? With luck they will slowly absorb, but I wouldn't want to count on that. At any rate, snorting is not exactly an intra-cranial route. That would involve needles. I've seen the video of those South American natives- the one where one of them uses a blowpipe to shoot the drugs up the other guy's nose? Yeah, that was pretty gross with all the stuff coming out of various orifices. I don't think those guys are into life extension. If they had LSD, I bet they'd dump the harsh stuff and never look back...

Thanks for the reply. I didn't know it was water insoluble. That would definitely be pointless to snort.

[2tender]

What wrong with snorting it? Someone said it burns. It didn't burn me. Then again it wasn't pure extract either.
This method would make it pass the blood brain barrier slowing delivery to the liver. Analgesic effect of Resveratrol via inter cranial administration in rats has been reported.
I've seen south americans natives snort some pretty harsh shit that will make you drool like a fool for hours. How bad could it be?

When you say "How bad could it be?", are you looking for a worst-case scenario? That would probably be some form of lung disease. I don't know how likely that would be; not very I suppose. The problem is that you are snorting something that is mostly insoluble in water. What will those particles do when they are lodged in the alveoli? With luck they will slowly absorb, but I wouldn't want to count on that. At any rate, snorting is not exactly an intra-cranial route. That would involve needles. I've seen the video of those South American natives- the one where one of them uses a blowpipe to shoot the drugs up the other guy's nose? Yeah, that was pretty gross with all the stuff coming out of various orifices. I don't think those guys are into life extension. If they had LSD, I bet they'd dump the harsh stuff and never look back...

Interesting comment. I agree that intra-nasal is not the way to go. Regarding the natives blowpipe use; its a tryptamine snuff (DMT, your brain secretes it every night, while you dream and at the moment of death) much more potent than LSD.

Edited by 2tender, 13 April 2010 - 09:21 PM.

[hfreitag]

Hi, I've been lurking around here for a while and am interested in trying buccal as well as oral resveratrol.

I'm just wondering, is it possible to use 50% powder for buccal delivery? I'm most worried about whether emodin also gets absorbed transdermally.

[Anthony_Loera]

Yikes! 50%?? Have you smelled that in it's raw form?

We used to sell 50% micronized powder for about 2-3 months... never saw such a slow moving product... but then again the taste alone was something that made you wince once... then, you had a hard time considering doing THAT again... (yes from personal experience).

Definitely need to have one of those old clothespins when you try it out...

Or one of these new fangled types if you want a pretty nose:

Edited by Anthony_Loera, 26 April 2010 - 11:48 PM.

[hfreitag]

Yikes! 50%?? Have you smelled that in it's raw form?

We used to sell 50% micronized powder for about 2-3 months... never saw such a slow moving product... but then again the taste alone was something that made you wince once... then, you had a hard time considering doing THAT again... (yes from personal experience).

Definitely need to have one of those old clothespins when you try it out...

Or one of these new fangled types if you want a pretty nose:

Lol. Yeah, I agree, the smell and taste is quite horrid, but I can manage to keep it in my mouth for 5 minutes provided I get that resveratrol blood spike. My only worry is if it's safe or not. Does emodin have any toxic effects when absorbed directly into the blood stream?

[health_nutty]

Hi, I've been lurking around here for a while and am interested in trying buccal as well as oral resveratrol.

I'm just wondering, is it possible to use 50% powder for buccal delivery? I'm most worried about whether emodin also gets absorbed transdermally.

I wouldn't recommend it. Among other concerns It is going to seriously stain your teeth. You don't have to use very much of the pure powder so the cost isn't too high. I find that 100mg is plenty.

[maxwatt]

Yikes! 50%?? Have you smelled that in it's raw form?

We used to sell 50% micronized powder for about 2-3 months... never saw such a slow moving product... but then again the taste alone was something that made you wince once... then, you had a hard time considering doing THAT again... (yes from personal experience).

Definitely need to have one of those old clothespins when you try it out...

Or one of these new fangled types if you want a pretty nose:

Lol. Yeah, I agree, the smell and taste is quite horrid, but I can manage to keep it in my mouth for 5 minutes provided I get that resveratrol blood spike. My only worry is if it's safe or not. Does emodin have any toxic effects when absorbed directly into the blood stream?

I don't know about the blood but orally, it can cause ulceration of the small intestines with chronic use. I suspect it's not so good for your gums either.

[John Barleycorn]

Anthony, I see too many references about chewing gum with medication in it as a good way to get the medication. There's a whole industry built around nicotene gum. There's also aspirin gum. In both cases the active ingredient has been shown to be absorbed through the gums. Lozenges also work to deliver active ingredients through the oral mucosa.
RESV dissolves very slowly in saliva. You need 1 liter of saliva to dissolve 30 mg. of RESV. There's mucosa where saliva pools, between the bottom teeth and the gum. Some of the RESV will be absorbed from the saliva there. What's absorbed will go right into the blood stream, bypassing first pass denature by the liver. For you it's $10 a pack of gum. For me, using 125 micron RESV (I see no reason to use micronized), I can make 50 pieces of gum with 100 mg. 98% RESV for $20. That's $0.40 a piece of gum. That's for the first batch. If I buy a gum refill kit, the price drops down to $8 for 50 pieces of gum containing 100 mg. RESV. That's 16 cents per piece of gum.

The problem is that gum-delivery systems work best for water-soluble substances. Polar substances,not so much. Some resveratrol does get absorbed by bucal administration, and what is absorbed more efficiently spikes blood serum levels, but not enough. The rate at which the mucosa pass resveratrol into the blood, times the surface area, is not sufficient to deliver a large dose at all. It can only deliver a very small dose efficiently.

The problem is that this contradicts a large amount of ethnobotanical and indeed conventional medical practice, in which non-polar, poorly water-soluble alkaloids are absorbed sub-lingually or buccally in a quite efficient manner. Plant substances are often chewed with some alkali like CaCO3 in order to ensure that the base has been liberated and to promote absorption. For smallish amounts, the saliva is often alkaline enough to do the job by itself. For example, 5 mg of selegiline.HCl tastes progressively more amine-like with contact time. 500 mg of phenylethylamine.HCl is pushing it (or so I have been told).

Nasal delivery is where water-solubility seems to work. Anything more than about 300 mg is probably overload in practice. Anything that is more than mildly acidic burns and does damage.

So what has all this got to do with polyphenols like resveratrol? They're the opposite of alkaloids, so tend to be poorly water-soluble at acidic pH and soluble under alkaline conditions, where they form a polar, phenolate salt. I assume the pure substance is not supplied in salt form, so one issue with with buccal routes is whether the saliva is alkaline enough to defeat the absorption process. Probably not, and that would seem to correspond with some experience reported around here. It also calls into question the need to dissolve resveratrol in water, water + emulsifier, or alcohol before going the buccal route. Dunno, haven't tried it, I'm playing with chrysin at the moment.

Edited by John Barleycorn, 27 May 2010 - 05:30 AM.

[maxwatt]

Anthony, I see too many references about chewing gum with medication in it as a good way to get the medication. There's a whole industry built around nicotene gum. There's also aspirin gum. In both cases the active ingredient has been shown to be absorbed through the gums. Lozenges also work to deliver active ingredients through the oral mucosa.
RESV dissolves very slowly in saliva. You need 1 liter of saliva to dissolve 30 mg. of RESV. There's mucosa where saliva pools, between the bottom teeth and the gum. Some of the RESV will be absorbed from the saliva there. What's absorbed will go right into the blood stream, bypassing first pass denature by the liver. For you it's $10 a pack of gum. For me, using 125 micron RESV (I see no reason to use micronized), I can make 50 pieces of gum with 100 mg. 98% RESV for $20. That's $0.40 a piece of gum. That's for the first batch. If I buy a gum refill kit, the price drops down to $8 for 50 pieces of gum containing 100 mg. RESV. That's 16 cents per piece of gum.

The problem is that gum-delivery systems work best for water-soluble substances. Polar substances,not so much. Some resveratrol does get absorbed by bucal administration, and what is absorbed more efficiently spikes blood serum levels, but not enough. The rate at which the mucosa pass resveratrol into the blood, times the surface area, is not sufficient to deliver a large dose at all. It can only deliver a very small dose efficiently.

The problem is that this contradicts a large amount of ethnobotanical and indeed conventional medical practice, in which non-polar, poorly water-soluble alkaloids are absorbed sub-lingually or buccally in a quite efficient manner. Plant substances are often chewed with some alkali like CaCO3 in order to ensure that the base has been liberated and to promote absorption. For smallish amounts, the saliva is often alkaline enough to do the job by itself. For example, 5 mg of selegiline.HCl tastes progressively more amine-like with contact time. 500 mg of phenylethylamine.HCl is pushing it (or so I have been told).

Nasal delivery is where water-solubility seems to work. Anything more than about 300 mg is probably overload in practice. Anything that is more than mildly acidic burns and does damage.

So what has all this got to do with polyphenols like resveratrol? They're the opposite of alkaloids, so tend to be poorly water-soluble at acidic pH and soluble under alkaline conditions, where they form a polar, phenolate salt. I assume the pure substance is not supplied in salt form, so one issue with with buccal routes is whether the saliva is alkaline enough to defeat the absorption process. Probably not, and that would seem to correspond with some experience reported around here. It also calls into question the need to dissolve resveratrol in water, water + emulsifier, or alcohol before going the buccal route. Dunno, haven't tried it, I'm playing with chrysin at the moment.

This does not contradict the point that the amount of resveratrol that can be absorbed bucally is limited by the mucosal surface area; though smallish amounts are absorbed quite efficiently, there is a limit beyond which it is futile t take more. The amount has been estimated in earlier posts to be quite low. 500 mg would indeed be pushing it, but a 25 mg dose would probable be efficiently absorbed, perhaps equivalent to a 100 mg dose? I too am guessing. I would like to see some pharmokinetic studies. We have Boococks paper measuring blood serum levels with oral administration. If someone wants to buy ah HPLC column and a standard sample. Hedgehog might be persuaded to take some blood samples and measure the efficiency.

I do have an unpublished paper on oral administration of various drugs and substances I've based my estimates on. If you want, I'll see if I can get you a copy..

[platypus]

I've seen the video of those South American natives- the one where one of them uses a blowpipe to shoot the drugs up the other guy's nose? Yeah, that was pretty gross with all the stuff coming out of various orifices. I don't think those guys are into life extension. If they had LSD, I bet they'd dump the harsh stuff and never look back...

I doubt it, DMT administered that way is far more potent than LSD and I'm sure the the effects differ qualitatively too.

[John Barleycorn]

This does not contradict the point that the amount of resveratrol that can be absorbed bucally is limited by the mucosal surface area; though smallish amounts are absorbed quite efficiently, there is a limit beyond which it is futile t take more. The amount has been estimated in earlier posts to be quite low. 500 mg would indeed be pushing it, but a 25 mg dose would probable be efficiently absorbed, perhaps equivalent to a 100 mg dose?

I seem to recall a factor of 3-5X for selegiline, which agrees with that general ballpark figure. Polyphenols are possibly a bit different because the body actively takes steps to block them.

I'm not sure the quantity is the only determining factor. For example, 750g of aniracetam seems to eventually dissolve away to nothing better than 500 mg of chrysin. It can take up to half an hour. (BTW, don't anyone try it with aniracetam unless they like screaming teeth and gums)! So there are probably differing absorption rates for different substances, even when the polarity and pH is favourable. In fact, some could in theory open the blood vessel membranes up, increase blood flow, all that sort of thing, same as with adding pepper. Can't remember whether alcohol has any impact in this area ...

I do have an unpublished paper on oral administration of various drugs and substances I've based my estimates on. If you want, I'll see if I can get you a copy..

I am sure there is general interest. A casual search turned up this: http://www.ncbi.nlm....pubmed/10341530, but it doesn't provide buccal vs oral multipliers.

[HOTCells]

So what about opening resv caps and sticking the stuff on your gums? Better or worse than just taking the caps orally?

Wouldn't just drinking resveratrol with ice cream and milk be the ultimate buccal delivery? I mix 1,000 mg of tran resveratrol in milk and ice cream with polysorbate 80 right before bed. My thinking is that resveratrol would stay in the mouth and mix with the mucus membranes along the lining of the esophagus for at least a few hours if not longer after drinking. I do this every night before bed (I do brush my teeth) and I still feel the slight burn that resveratrol gives when I wake up in the morning. This tells me that reveratrol is at least present along my esophagus.

[niner]

So what has all this got to do with polyphenols like resveratrol? They're the opposite of alkaloids, so tend to be poorly water-soluble at acidic pH and soluble under alkaline conditions, where they form a polar, phenolate salt. I assume the pure substance is not supplied in salt form, so one issue with with buccal routes is whether the saliva is alkaline enough to defeat the absorption process. Probably not, and that would seem to correspond with some experience reported around here. It also calls into question the need to dissolve resveratrol in water, water + emulsifier, or alcohol before going the buccal route. Dunno, haven't tried it, I'm playing with chrysin at the moment.

Resveratrol and other polyphenols can form a phenolate at high enough pH, but it would be too high (ten-ish, I think) to use biologically. Rapid conjugation of polyphenols remains the bugaboo.

[RenegadeSci]

Anthony, I see too many references about chewing gum with medication in it as a good way to get the medication. There's a whole industry built around nicotene gum. There's also aspirin gum. In both cases the active ingredient has been shown to be absorbed through the gums. Lozenges also work to deliver active ingredients through the oral mucosa.
RESV dissolves very slowly in saliva. You need 1 liter of saliva to dissolve 30 mg. of RESV. There's mucosa where saliva pools, between the bottom teeth and the gum. Some of the RESV will be absorbed from the saliva there. What's absorbed will go right into the blood stream, bypassing first pass denature by the liver. For you it's $10 a pack of gum. For me, using 125 micron RESV (I see no reason to use micronized), I can make 50 pieces of gum with 100 mg. 98% RESV for $20. That's $0.40 a piece of gum. That's for the first batch. If I buy a gum refill kit, the price drops down to $8 for 50 pieces of gum containing 100 mg. RESV. That's 16 cents per piece of gum.

The problem is that gum-delivery systems work best for water-soluble substances. Polar substances,not so much. Some resveratrol does get absorbed by bucal administration, and what is absorbed more efficiently spikes blood serum levels, but not enough. The rate at which the mucosa pass resveratrol into the blood, times the surface area, is not sufficient to deliver a large dose at all. It can only deliver a very small dose efficiently.

The problem is that this contradicts a large amount of ethnobotanical and indeed conventional medical practice, in which non-polar, poorly water-soluble alkaloids are absorbed sub-lingually or buccally in a quite efficient manner. Plant substances are often chewed with some alkali like CaCO3 in order to ensure that the base has been liberated and to promote absorption. For smallish amounts, the saliva is often alkaline enough to do the job by itself. For example, 5 mg of selegiline.HCl tastes progressively more amine-like with contact time. 500 mg of phenylethylamine.HCl is pushing it (or so I have been told).

Nasal delivery is where water-solubility seems to work. Anything more than about 300 mg is probably overload in practice. Anything that is more than mildly acidic burns and does damage.

So what has all this got to do with polyphenols like resveratrol? They're the opposite of alkaloids, so tend to be poorly water-soluble at acidic pH and soluble under alkaline conditions, where they form a polar, phenolate salt. I assume the pure substance is not supplied in salt form, so one issue with with buccal routes is whether the saliva is alkaline enough to defeat the absorption process. Probably not, and that would seem to correspond with some experience reported around here. It also calls into question the need to dissolve resveratrol in water, water + emulsifier, or alcohol before going the buccal route. Dunno, haven't tried it, I'm playing with chrysin at the moment.

This does not contradict the point that the amount of resveratrol that can be absorbed bucally is limited by the mucosal surface area; though smallish amounts are absorbed quite efficiently, there is a limit beyond which it is futile t take more. The amount has been estimated in earlier posts to be quite low. 500 mg would indeed be pushing it, but a 25 mg dose would probable be efficiently absorbed, perhaps equivalent to a 100 mg dose? I too am guessing. I would like to see some pharmokinetic studies. We have Boococks paper measuring blood serum levels with oral administration. If someone wants to buy ah HPLC column and a standard sample. Hedgehog might be persuaded to take some blood samples and measure the efficiency.

I do have an unpublished paper on oral administration of various drugs and substances I've based my estimates on. If you want, I'll see if I can get you a copy..

If you find the old paper on Oral-mucosal Etomidate you can see that they topped out around 100mg, and it's considered water soluble. It just tasted so bad that people wanted to take the shot. They had 20% bioavalibility at that level. I would say 200mg/2g solvent would be pushing it to the maximum level. If you want more, then just take two in sequence.

It also shows the importance of taste and solubility. Resveratrol does have a taste when soluble, and it's strong. That is, if you know how to do it.

http://www.popsci.co...nges-shape-salt

And I know how to do it... Yeah, I'm bragging. Yeah, I'm a young published scientist.

No, I don't know how well it works yet, but I know what solvent to use. We'll test it and publish it soon, and we have the patent.

-Renegade Scientist

RenegadeSci@gmail.com