1084 replies to this topic

[PWAIN]

I have also tried the buccal delivery and would love to see some blood work. Where is Hedgehog when you need him? ;-) Mine is usually absorbed/disappears in ~45-60 minutes and I do notice the effects from taking it this way. I cant say if its better or stronger
than oral delivery as that's pretty subjective but buccal does seem to work.

I have been using buccal delivery for my Resveratrol for a few weeks now. I stopped for about a week and have since resumed and I have noticed the change. It is like I feel bullet proof when I take Resveratrol this way. I think I must be getting a pretty good dose and would love to see someone test blood levels like this. I take about half a teaspoon full of res and leave it between teeth and gums overnight. By morning, it has usually gone or there is just a little bit left.

Has anyone else been doing this or is anyone else game to try it?

I definately feel different and it is not the buzz that you get when you first start taking Res.

What I like it that there is no waste - what isn't absorbed buccally goes the oral route anyway. To get it to hang around, I try not to let it get too wet ie. no drinking liquids etc - of course it is wet against the cheek where it counts. I also have to try keep my tongue out of the area:).

I suspect that buccal is delivering a good dose but would like to get verification of whether I am wasteing my time. HeeeedgeHoggg....

[kaben]

You'll need more than a baby aspirin, but not more than a normal therapeutic dose, if I remember correctly. Taking that much aspirin every day for the rest of your life is a good way to ensure that the rest of your life isn't so long, though.

That is why we try one baby 81 Mg aspirin a day, minutes prior to the RSV dose.
I do not think a single aspirin dose will cause any GI harm.
But will prevent the RSV from liver processing.

YES - NO?

NO. A baby aspirin will give you about a 30 uM peak plasma level, one hour after you take it. The IC50 for sulfation inhibition is about 60 uM. You need to be there to cut the sulfation in half, but what you really want is more than half because half won't help much. You also want to keep the salicylic acid at or above that level for a couple hours after you take the res. By definition, you're only at the peak level very briefly. I think to get what you want, you'll need at least one regular size (325 mg) aspirin, preferably two. You should take it about 30-60 minutes before the res. Then, yeah, you should get some inhibition of sulfation. That's more aspirin than I would want to take long term.

Hi All,

Two observations. First, Aspirin in combination with a COX-2 inhibitor, of which resveratrol is a kind, may cause much more GI damage than either alone. Second, melatonin taken in standard 5 mg doses 30 minutes prior to taking Aspirin may prevent GI damage.

Niner, Hedgehog, Maxwatt, etcetera: could you perhaps apply your expertise to the following two papers? The former implies that Aspirin followed by resveratrol may be a very bad idea, while the latter implies that the following regime might safely inhibit resveratrol sulfation:
- a 5 mg tablet of melatonin,
- followed after 30 minutes by two 325 mg tablets of safety-coated Aspirin,
- followed after 30-60 minutes by resveratrol.


First paper:
J.L. Wallace and S. Fiorucci. A magic bullet for mucosal protection...and Aspirin is the trigger! Trends in Pharmacological Sciences. 2003; Vol. 24 No. 7: 323-6

Abstract:

Aspirin can induce gastric ulcers, largely because it inhibits the synthesis of gastroprotective prostaglandins. Co-administration of aspirin and a selective cyclooxygenase 2 inhibitor results in more gastric damage than that induced following administration of either drug alone. This is because aspirin triggers the cyclooxygenase-2-dependent synthesis of 15®-epi-lipoxin A4, a substance that acts to diminish injury to the stomach. Lipoxins can also be produced independently of the actions of aspirin on cyclooxygenase 2, and might enhance epithelial integrity in various mucosal tissues.

Second paper:
P.C. Konturek et al. Melatonin and its precursor L-tryptophan prevent acute gastric mucosal damage induced by Aspirin in humans. Journal of Physiology and Pharmacology. 2008; 59, suppl 2: 67-75

Abstract:

Melatonin (MT) and its precursor L-tryptophan (Trp) are implicated in the protection of gastric mucosa against noxious agents. However, the role of MT and Trp on the gastric mucosal injury induced by aspirin (ASA) in human has not been investigated. Studies in animals showed that both MT and Trp given intragastrically prevents the formation of gastric mucosal lesions induced by ASA. The aim of the present study was to determine the influence of MT and Trp given orally to healthy humans on gastric mucosal lesions induced by ASA. The present study included 21 healthy, Hp-negative male volunteers with intact gastro-duodenal mucosa aging 20-50 yr. They were divided in 3 groups; group1: 7 volunteers receiving daily 2 x 1g ASA (Polfa, Rzeszow) during 11 days; group 2: 7 healthy volunteers receiving 2x1g ASA and MT (Lekam, Zakroczyn) (5 mg 30 min prior to ASA) during 11 days and group 3: 7 healthy volunteers receiving 2x1g ASA and Trp (Ardeytropin, Germany) (0.5 g 30 min prior to ASA) during 11 days. Mucosal damage was evaluated at 3rd, 7th and 11th days of ASA administration by endoscopy using Lanza score. Plasma melatonin was measured using RIA and gastric mucosal generation of PGE2 was assessed also by RIA. ASA caused marked mucosal injury at all days of its administration except day 11th when only moderate lesions were evident. Pre-treatment with MT or Trp alone was accompanied by a significant decrease in gastric mucosal lesion score. Gastric mucosal generation of PGE2 was suppressed by about 90% in subjects treated with ASA without or with MT or Trp. We concluded that: MT and its precursor Trp significantly attenuate gastric mucosal lesions induced by aspirin. The action of Trp may be be mediated by MT produced in gastrointestinal tract from Trp. The gastroprotective action of MT and Trp is independent on gastric mucosal PGE2 generation.

[niner]

You'll need more than a baby aspirin, but not more than a normal therapeutic dose, if I remember correctly. Taking that much aspirin every day for the rest of your life is a good way to ensure that the rest of your life isn't so long, though.

That is why we try one baby 81 Mg aspirin a day, minutes prior to the RSV dose.
I do not think a single aspirin dose will cause any GI harm.
But will prevent the RSV from liver processing.

YES - NO?

NO. A baby aspirin will give you about a 30 uM peak plasma level, one hour after you take it. The IC50 for sulfation inhibition is about 60 uM. You need to be there to cut the sulfation in half, but what you really want is more than half because half won't help much. You also want to keep the salicylic acid at or above that level for a couple hours after you take the res. By definition, you're only at the peak level very briefly. I think to get what you want, you'll need at least one regular size (325 mg) aspirin, preferably two. You should take it about 30-60 minutes before the res. Then, yeah, you should get some inhibition of sulfation. That's more aspirin than I would want to take long term.

Two observations. First, Aspirin in combination with a COX-2 inhibitor, of which resveratrol is a kind, may cause much more GI damage than either alone. Second, melatonin taken in standard 5 mg doses 30 minutes prior to taking Aspirin may prevent GI damage.

Niner, Hedgehog, Maxwatt, etcetera: could you perhaps apply your expertise to the following two papers? The former implies that Aspirin followed by resveratrol may be a very bad idea, while the latter implies that the following regime might safely inhibit resveratrol sulfation:
- a 5 mg tablet of melatonin,
- followed after 30 minutes by two 325 mg tablets of safety-coated Aspirin,
- followed after 30-60 minutes by resveratrol.

First paper:
J.L. Wallace and S. Fiorucci. A magic bullet for mucosal protection...and Aspirin is the trigger! Trends in Pharmacological Sciences. 2003; Vol. 24 No. 7: 323-6

Aspirin can induce gastric ulcers, largely because it inhibits the synthesis of gastroprotective prostaglandins. Co-administration of aspirin and a selective cyclooxygenase 2 inhibitor results in more gastric damage than that induced following administration of either drug alone. This is because aspirin triggers the cyclooxygenase-2-dependent synthesis of 15®-epi-lipoxin A4, a substance that acts to diminish injury to the stomach. Lipoxins can also be produced independently of the actions of aspirin on cyclooxygenase 2, and might enhance epithelial integrity in various mucosal tissues.

Second paper:
P.C. Konturek et al. Melatonin and its precursor L-tryptophan prevent acute gastric mucosal damage induced by Aspirin in humans. Journal of Physiology and Pharmacology. 2008; 59, suppl 2: 67-75

Melatonin (MT) and its precursor L-tryptophan (Trp) are implicated in the protection of gastric mucosa against noxious agents. However, the role of MT and Trp on the gastric mucosal injury induced by aspirin (ASA) in human has not been investigated. Studies in animals showed that both MT and Trp given intragastrically prevents the formation of gastric mucosal lesions induced by ASA. The aim of the present study was to determine the influence of MT and Trp given orally to healthy humans on gastric mucosal lesions induced by ASA. The present study included 21 healthy, Hp-negative male volunteers with intact gastro-duodenal mucosa aging 20-50 yr. They were divided in 3 groups; group1: 7 volunteers receiving daily 2 x 1g ASA (Polfa, Rzeszow) during 11 days; group 2: 7 healthy volunteers receiving 2x1g ASA and MT (Lekam, Zakroczyn) (5 mg 30 min prior to ASA) during 11 days and group 3: 7 healthy volunteers receiving 2x1g ASA and Trp (Ardeytropin, Germany) (0.5 g 30 min prior to ASA) during 11 days. Mucosal damage was evaluated at 3rd, 7th and 11th days of ASA administration by endoscopy using Lanza score. Plasma melatonin was measured using RIA and gastric mucosal generation of PGE2 was assessed also by RIA. ASA caused marked mucosal injury at all days of its administration except day 11th when only moderate lesions were evident. Pre-treatment with MT or Trp alone was accompanied by a significant decrease in gastric mucosal lesion score. Gastric mucosal generation of PGE2 was suppressed by about 90% in subjects treated with ASA without or with MT or Trp. We concluded that: MT and its precursor Trp significantly attenuate gastric mucosal lesions induced by aspirin. The action of Trp may be be mediated by MT produced in gastrointestinal tract from Trp. The gastroprotective action of MT and Trp is independent on gastric mucosal PGE2 generation.

Hi kaben, thanks for the abstracts. These are both nice finds. The first paper does at the very least raise a concern about combining aspirin with resveratrol. The second paper is an interesting approach at dealing with the problem, but I would have two concerns. The first is that the protection from gastric lesions afforded by melatonin is probably not 100%. If you were taking it for a long time, you might run into a problem anyway. Safety coated aspirin probably would not work, because their absorption is delayed until they hit the gut. You would want the blood level of the aspirin to be raised ahead of the resveratrol. My other concern is that the amount of melatonin needed is pretty large. You probably wouldn't want to take it during the day. YMMV; I get pretty whacked on just one mg of melatonin.

[malbecman]

Hi kaben, thanks for the abstracts. These are both nice finds. The first paper does at the very least raise a concern about combining aspirin with resveratrol. The second paper is an interesting approach at dealing with the problem, but I would have two concerns. The first is that the protection from gastric lesions afforded by melatonin is probably not 100%. If you were taking it for a long time, you might run into a problem anyway. Safety coated aspirin probably would not work, because their absorption is delayed until they hit the gut. You would want the blood level of the aspirin to be raised ahead of the resveratrol. My other concern is that the amount of melatonin needed is pretty large. You probably wouldn't want to take it during the day. YMMV; I get pretty whacked on just one mg of melatonin.

I agree, 5mgs of melatonin wouldnt work for me. I'd be out before I could get to the rest of the pills...........

[kaben]

Hi kaben, thanks for the abstracts. These are both nice finds. The first paper does at the very least raise a concern about combining aspirin with resveratrol. The second paper is an interesting approach at dealing with the problem, but I would have two concerns. The first is that the protection from gastric lesions afforded by melatonin is probably not 100%. If you were taking it for a long time, you might run into a problem anyway. Safety coated aspirin probably would not work, because their absorption is delayed until they hit the gut. You would want the blood level of the aspirin to be raised ahead of the resveratrol. My other concern is that the amount of melatonin needed is pretty large. You probably wouldn't want to take it during the day. YMMV; I get pretty whacked on just one mg of melatonin.

I agree, 5mgs of melatonin wouldnt work for me. I'd be out before I could get to the rest of the pills...........

Thank you, niner, it hadn't occurred to me that regular Aspirin would work better than coated Aspirin.

Regarding niner's and malbecman's concerns over melatonin, yes, it zonks me out too. I use melatonin to help me sleep, under the advice of my doctor, who advises that I take a 5 mg tablet 45 minutes before I go to bed (contradicting the label, which suggests 20 minutes). She has also told me that unlike many medicines, I can use melatonin for this purpose for the rest of my life without fear of harmful side effects. Once-daily melatonin-Aspirin-resveratrol might work well before bed.

Regarding niner's first concern over long-term GI damage, the second-to-last paragraph of the Konturek et al paper contains the following observation that the body may adapt to limit Aspirin's damage:

It is of interest that at day 11, we observed a significant decrease in mucosal lesion score in patients taking daily large dose of ASA (2 g/day). This may be due to the phenomenon of gastric mucosal adaptation. Further studies should clarify whether MT may be involved in the mechanism of already described in humans gastric mucosal adaptation to ASA (19) and whether regular pretreatement with MT or Trp could be useful in protecting the gastric mucosa from the damage in patients treated regularly for long period of time with ASA, e.g. in prevention of cardiac or cerebral vascular diseases.

See the associated chart in figure 4:

Fig. 4. Endoscopic grading of gastric mucosal injury according to the LANZA score in subjects treated with aspirin alone or aspirin with melatonin or aspirin and L-tryptophan. The score was evaluated before start of therapy (day 0) or at days 3, 7 and 11 after start of treatment. Asterisk indicates a significant change as compared to day 0. Cross indicates a significant change as compared to the values obtained in the group of subjects treated with aspirin alone. In this and subsequent figures each point represent mean of seven determinations in seven volunteers. Asterisk and cross (#) indicate a significant change as compared to the values at dey 3 recorded in subjects ingesting ASA with placebo.

I did not know what the LANZA score was, and I found the following definition:

The Lanza score is a scoring system created by Lanza FL to attribute a severity score for NSAIDs’ induced erosive mucosal injuries in the stomach or duodenum. This type of score is registered during gastroscopic examinations and attributes the following grades to the following lesions:

• 0: Normal stomach or proximal duodenum
• 1: Mucosal haemorrhages only
• 2: One or two erosions
• 3: 3-10 erosions
• 4: >10 erosions or an ulcer

Erosions are defined as white-based mucosal breaks of any size and flat. Ulcers are defined as mucosal breaks of at least 3 mm or more demonstrating unequivocal depth.

This is perhaps why doctors consider long-term Aspirin use an acceptable risk as a treatment for heart disease. The risk of GI damage might not go away, but it also might not increase over time (so the rate of GI incidents might level-off or decrease). The consensus seems to be that people are better-off who exchange each heart attack for two or three GI bleeds.

As the paper above states, further studies will be required to learn the long-term gastroprotective effects of melatonin.

I'm very curious to know whether melatonin might protect against the high damage of combined Aspirin and a COX-2 inhibitor. I haven't found any studies yet. I've considered informal self-experimentation, as hedgehog has done. There would be expenses and risks, and it would require the cooperation and supervision of a doctor, but happily not an analytical lab.

(Edited for typos.)

Edited by kaben, 30 September 2008 - 02:00 AM.

[Anthony_Loera]

This morning I received "water soluble" trans-resveratrol.
In our company we have been talking about some methods to produce this, and now we have some to play with.

I think hedge has a pretty good idea of how this is done.

Having placed a teaspoon of it in water, it appears to initially clump to itself (much like coffee powdered creamer), but after continued mixing with a spoon... it did dissolve into the water.
Unlike the high pressure emulsion, which results in a form of milky white water (Kind of like fat free milk), the water soluble res liquid was crystal clear.

The taste was not bad, but I can definitely taste the resveratrol in my mouth. I can say that after a couple of sips, I knew this stuff was absorbed quickly because of my past experience with other resveratrol items we are considering. The question now is how much ended up in my blood? From my experience using DMSO-res (with micronized res) topically, or basic micro-res sublingualy. I came out of this with the impression that this soluble-res retained in the mouth, may be better absorbed than micro-res.

Again, I am not sure we can make this stuff available to everyone in the near future because of the expense, but it's a step we are considering.

Cheers
A

Edited by Anthony_Loera, 14 October 2008 - 03:43 PM.

[D413]

I agree with the previous poster I would go with the tween(20) for the suspension agent, further more to modify a process I use commercially at work i would recommend trying a 1:2 mol solution of t-rev:tween20 adding about 10 volumes of water and then microwaving it till the solution goes clear. This will make a very fine dispersion encapsulated with tween20 it can be added slowly to one "XX" volume of water and remain clear in solution (you have to near boil the solution in the microwave). volumes may need slight modification for this application
or zanthum and guar gum can be used as suspension agents if a solvent is used. try googling "nitro glycerin" for hints on suspension tech using natural gums.

hope that helps some body or is some food for thought.........

[Mortal Combat]

Could glucuronidation be actually making resveratrol more bioavailable? Certain hormones(hardly water-soluble ones I suppose) are glucuronidated to allow for easier transport around the body. (I hope to see studies testing the effects of sulfonate/glucuronate metabolites of T-res in vivo.)

[Reverse]

"HPBCD" " THPB-P -- hydroxypropyl BCD "

http://www.cyclodex....p?page_id=4&n=4

___--- so this would be MUCH better to use insted of ethanol or glycerol, all this stuff is on hit so lets figure this RSV, ALCAR, Quercitin, Ellegiac acid, in a THPB-P base - powerhouse delivery..

There has been some use of Beta Cyclodextrin as a host for Resveratrol in the literature. In (J Pharmacol Exp Ther. 2002 Jul;302(1):369-73. Free Full Text. PMID: 12065739) they prepared an aqueous solution of 20% hydroxypropyl beta cyclodextrin that contained 6 mg/ml. That is a HUGE boost in solubility. Resveratrol in water alone is 0.03 mg/ml, so that's a 200-fold increase. They saw a peak plasma concentration of resveratrol aglycone (not yet glucuronidated) of 6.5 uM at an oral dose of 50 mg/kg. They did not look at resveratrol without CD complexation, but in a human study (Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1246-52. PMID: 17548692) Humans given a comparable dose of uncomplexed resveratrol had a peak plasma level of 2.4 uM from an oral dose of 5 grams. That would be 50 mg/kg if you weighed 100 kg. The rat peak occurred in the first few minutes, while the human peak occurred at 1.5 hours. Whether the time difference is due to complexation or species I don't know. Without looking at both complexed and uncomplexed RSV in the same species, I don't know how much we can take from this, but I'm struck by the apparent poor improvement in plasma levels from CD complexation, considering the effect that it has on solubility.

I am in the pharmaceutical field and typically cyclodextrins are just used for taste masking. CD's are used in a variety of applications other than pharmacy as well, including odor eliminating products like Fabreeze. HPB-Cyclodextrin has the advantage of higher aqueous solubility than CD because the propyl groups decrease intermolecular interaction between CD molecules and increases intermolecular interaction between HPB-CD and water. I am not saying that complexation can't increase bioavailbility but it is highly unlikely since the cyclodextrin molecule itself is typically degraded in the harsh environment of the stomach. CD's are great for masking taste though, especially of compounds that are extremely bitter, such as amines. It increases the size of individual molecules and doesn't allow them to reach the taste receptors. One problem with CD's is the large amount of it you would have ot use to achieve the result you wish as well. You would want >1:1 molar ratio to put Le Chatlier's principle in your favor to increase the likelihood of complexation and it would be quite expensive to do this.

Mortal Combat: Actually glucoronidation doesn't typically occur to increase transport "around" the body, it increases transport to the kidney's where the compound is ultimate excreted. The problem with the method of trying to overcome glucoronidation and sulfonation is that your body is one step ahead. Sulfonation enzymes/substrates are high affinity low capacity systems and glucoronidation enzymes/substrates are low affinity high capacity, so whether you are taking lower doses or higher doses your body is going to find a way to excrete it.

As I have mentioned before I have come up with an idea to increase bioavailability by acetylation of the hydroxyl groups. This allows it to pass through the intestinal mucosa, make it through the first pass and through ester hydrolysis return to its original trihydroxy form. Will some be lost? Yup. However, this eliminates the problem of losing SIRT1 activity by adding things like quercetin and piperine.

Edited by Reverse, 14 November 2008 - 05:04 PM.

[Anthony_Loera]

Hi Reverse,

I was thinking of using "water soluble" powder/mix for a "sublingual" increase in absorption.

A

[Reverse]

Hi Reverse,

I was thinking of using "water soluble" powder/mix for a "sublingual" increase in absorption.

A

You wouldn't really want a cyclodextrin if you want to use sublingual. You not only make it more hydrophilic you essentially prevent it from crossing the lipophilic membrane. You would also increase the molecular size of the complexation and therefore also decrease likelihood of it crossing the membrane. You would want to look more into liposomes if you are looking for a sublingual delivery.

[Reverse]

Hi kaben, thanks for the abstracts. These are both nice finds. The first paper does at the very least raise a concern about combining aspirin with resveratrol. The second paper is an interesting approach at dealing with the problem, but I would have two concerns. The first is that the protection from gastric lesions afforded by melatonin is probably not 100%. If you were taking it for a long time, you might run into a problem anyway. Safety coated aspirin probably would not work, because their absorption is delayed until they hit the gut. You would want the blood level of the aspirin to be raised ahead of the resveratrol. My other concern is that the amount of melatonin needed is pretty large. You probably wouldn't want to take it during the day. YMMV; I get pretty whacked on just one mg of melatonin.

I agree, 5mgs of melatonin wouldnt work for me. I'd be out before I could get to the rest of the pills...........

Thank you, niner, it hadn't occurred to me that regular Aspirin would work better than coated Aspirin.

Regarding niner's and malbecman's concerns over melatonin, yes, it zonks me out too. I use melatonin to help me sleep, under the advice of my doctor, who advises that I take a 5 mg tablet 45 minutes before I go to bed (contradicting the label, which suggests 20 minutes). She has also told me that unlike many medicines, I can use melatonin for this purpose for the rest of my life without fear of harmful side effects. Once-daily melatonin-Aspirin-resveratrol might work well before bed.

Regarding niner's first concern over long-term GI damage, the second-to-last paragraph of the Konturek et al paper contains the following observation that the body may adapt to limit Aspirin's damage:

It is of interest that at day 11, we observed a significant decrease in mucosal lesion score in patients taking daily large dose of ASA (2 g/day). This may be due to the phenomenon of gastric mucosal adaptation. Further studies should clarify whether MT may be involved in the mechanism of already described in humans gastric mucosal adaptation to ASA (19) and whether regular pretreatement with MT or Trp could be useful in protecting the gastric mucosa from the damage in patients treated regularly for long period of time with ASA, e.g. in prevention of cardiac or cerebral vascular diseases.

See the associated chart in figure 4:

Fig. 4. Endoscopic grading of gastric mucosal injury according to the LANZA score in subjects treated with aspirin alone or aspirin with melatonin or aspirin and L-tryptophan. The score was evaluated before start of therapy (day 0) or at days 3, 7 and 11 after start of treatment. Asterisk indicates a significant change as compared to day 0. Cross indicates a significant change as compared to the values obtained in the group of subjects treated with aspirin alone. In this and subsequent figures each point represent mean of seven determinations in seven volunteers. Asterisk and cross (#) indicate a significant change as compared to the values at dey 3 recorded in subjects ingesting ASA with placebo.

I did not know what the LANZA score was, and I found the following definition:

The Lanza score is a scoring system created by Lanza FL to attribute a severity score for NSAIDs’ induced erosive mucosal injuries in the stomach or duodenum. This type of score is registered during gastroscopic examinations and attributes the following grades to the following lesions:

• 0: Normal stomach or proximal duodenum
• 1: Mucosal haemorrhages only
• 2: One or two erosions
• 3: 3-10 erosions
• 4: >10 erosions or an ulcer

Erosions are defined as white-based mucosal breaks of any size and flat. Ulcers are defined as mucosal breaks of at least 3 mm or more demonstrating unequivocal depth.

This is perhaps why doctors consider long-term Aspirin use an acceptable risk as a treatment for heart disease. The risk of GI damage might not go away, but it also might not increase over time (so the rate of GI incidents might level-off or decrease). The consensus seems to be that people are better-off who exchange each heart attack for two or three GI bleeds.

As the paper above states, further studies will be required to learn the long-term gastroprotective effects of melatonin.

I'm very curious to know whether melatonin might protect against the high damage of combined Aspirin and a COX-2 inhibitor. I haven't found any studies yet. I've considered informal self-experimentation, as hedgehog has done. There would be expenses and risks, and it would require the cooperation and supervision of a doctor, but happily not an analytical lab.

(Edited for typos.)

Wow your doctor recommended 5mg? Was the reasoning for the protective effects or the sleep enhancing benefit? If for sleep enhancement, I have studies showing 300mcg being as effect as 3mg for inducing sleep but without the nasty hangover. Melatonin has an 8+ half life so it can make you really groggy in the morning. It is a very potent antioxidant though and lately they have been finding that it protects the body in a multitude of ways. I love the stuff!

If you guys are interested our company just released a more potent analog .

[gattaca]

Melatonin has an 8+ half life so it can make you really groggy in the morning.

No it doesn't. It has a very short half-life.

[Reverse]

Melatonin has an 8+ half life so it can make you really groggy in the morning.

No it doesn't. It has a very short half-life.

Its effects do. You don't need very much to elicit response. By taking 5mg you are greatly increasing the amount present at any given time throughout the night, hence the fact you will get more groggy in the morning after taking 10mg than if you would taking 300 micrograms, yet you would feel the same sleep inducing effects. I misspoke using the term "half life".

[gattaca]

Melatonin has an 8+ half life so it can make you really groggy in the morning.

No it doesn't. It has a very short half-life.

Its effects do. You don't need very much to elicit response. I misspoke using the term "half life".

Just trying to make sure the information here is correct. Melatonin is so amazing that I have a difficult time recommending it to someone without sounding like a crank.

[Reverse]

Melatonin has an 8+ half life so it can make you really groggy in the morning.

No it doesn't. It has a very short half-life.

Its effects do. You don't need very much to elicit response. I misspoke using the term "half life".

Just trying to make sure the information here is correct. Melatonin is so amazing that I have a difficult time recommending it to someone without sounding like a crank.

Haha I am the same way. I mentioned before our company has released a stronger analog of it. If you'd like to try it let me know, it releases next week. I will send you like 5 days worth to try out. It is actually really cheap.

[niner]

"HPBCD" " THPB-P -- hydroxypropyl BCD "

http://www.cyclodex....p?page_id=4&n=4

___--- so this would be MUCH better to use insted of ethanol or glycerol, all this stuff is on hit so lets figure this RSV, ALCAR, Quercitin, Ellegiac acid, in a THPB-P base - powerhouse delivery..

There has been some use of Beta Cyclodextrin as a host for Resveratrol in the literature. In (J Pharmacol Exp Ther. 2002 Jul;302(1):369-73. Free Full Text. PMID: 12065739) they prepared an aqueous solution of 20% hydroxypropyl beta cyclodextrin that contained 6 mg/ml. That is a HUGE boost in solubility. Resveratrol in water alone is 0.03 mg/ml, so that's a 200-fold increase. They saw a peak plasma concentration of resveratrol aglycone (not yet glucuronidated) of 6.5 uM at an oral dose of 50 mg/kg. They did not look at resveratrol without CD complexation, but in a human study (Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1246-52. PMID: 17548692) Humans given a comparable dose of uncomplexed resveratrol had a peak plasma level of 2.4 uM from an oral dose of 5 grams. That would be 50 mg/kg if you weighed 100 kg. The rat peak occurred in the first few minutes, while the human peak occurred at 1.5 hours. Whether the time difference is due to complexation or species I don't know. Without looking at both complexed and uncomplexed RSV in the same species, I don't know how much we can take from this, but I'm struck by the apparent poor improvement in plasma levels from CD complexation, considering the effect that it has on solubility.

I am in the pharmaceutical field and typically cyclodextrins are just used for taste masking. CD's are used in a variety of applications other than pharmacy as well, including odor eliminating products like Fabreeze. HPB-Cyclodextrin has the advantage of higher aqueous solubility than CD because the propyl groups decrease intermolecular interaction between CD molecules and increases intermolecular interaction between HPB-CD and water. I am not saying that complexation can't increase bioavailbility but it is highly unlikely since the cyclodextrin molecule itself is typically degraded in the harsh environment of the stomach. CD's are great for masking taste though, especially of compounds that are extremely bitter, such as amines. It increases the size of individual molecules and doesn't allow them to reach the taste receptors. One problem with CD's is the large amount of it you would have ot use to achieve the result you wish as well. You would want >1:1 molar ratio to put Le Chatlier's principle in your favor to increase the likelihood of complexation and it would be quite expensive to do this.

Yeah, you're right. As I noted, they didn't get that much of a boost in plasma level, despite the huge increase in solubility. Resveratrol's problem isn't absorption, it's conjugation. These days everyone has pretty much abandoned CDs in favor of HPMC or a variety of other carriers. Dairy products are one, for example. I never knew that CDs would work so well for taste masking, but it makes sense. That might come in handy some day.

[kenj]

Any problems in mixing resv powder in soy milk and drops of alcohol? Works convenient for me, stirring for a few minutes.

[gattaca]

Melatonin has an 8+ half life so it can make you really groggy in the morning.

No it doesn't. It has a very short half-life.

Its effects do. You don't need very much to elicit response. I misspoke using the term "half life".

Just trying to make sure the information here is correct. Melatonin is so amazing that I have a difficult time recommending it to someone without sounding like a crank.

Our company has released a stronger analog of melatonin. I will send you like 5 days worth to try out. It is actually really cheap.

No need to send me any, especially if it's cheap. PM me the name and I'll look into it.

[bentl]

Our company has released a stronger analog of melatonin. I will send you like 5 days worth to try out. It is actually really cheap.

No need to send me any, especially if it's cheap. PM me the name and I'll look into it.

I would appreciate it if you would PM me as well.

Thanks!

[tintinet]

Stonger version of melatonin? To what end? Health/life extension, or better sleep, or both?

I'd also like to try some and find out more about it, thanks.



1: Exp Gerontol. 2008 Aug;43(8):749-56. Epub 2008 Apr 6.Click here to read Links
Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice.
Rodríguez MI, Escames G, López LC, López A, García JA, Ortiz F, Sánchez V, Romeu M, Acuña-Castroviejo D.

Instituto de Biotecnología, Departamento de Fisiología, Universidad de Granada, Facultad de Medicina, Granada, Spain.

We investigated whether chronic melatonin administration influences mitochondrial oxidative stress and life span in mice. Diaphragmatic mitochondria from female senescent prone (SAMP8) and senescent resistant (SAMR1) mice at 5 and 10 months of age were studied. Mitochondrial oxidative stress was determined by measuring the levels of lipid peroxidation, glutathione and glutathione disulfide, and glutathione peroxidase and reductase activities. Mitochondrial function was assessed by measuring the activity of the respiratory chain complexes and the ATP content. The results suggest that the age-dependent mitochondrial oxidative damage in the diaphragm of SAMP8 mice was accompanied by a reduction in the electron transport chain complex activities and in ATP levels. Furthermore, melatonin administration between 1 and 10 months of age normalized the redox and the bioenergetic status of the mitochondria and increased the ATP levels. Melatonin also increased both half-life and longevity, mainly in SAMP8 group. These results suggest an age-related increase in mitochondria vulnerability to oxidation in SAM mice at 10 months of age that was counteracted by melatonin therapy. The effects of melatonin on mitochondrial physiology probably underline the ability of the indoleamine to increase maximal life span in these animals.

PMID: 18485648 [PubMed - in process]

[lotusman]

Have you tried lecithin granules at all? I have found consistency that seems to work quite well. I am mixing it up a few days worth at a time. If it gets too thick I can just add a little water and shake it up, it i add too much water I can just add a few more granules.

Is there any functional difference between lecithin granules and lecithin powder? Does one work better than the other? Does anyone know why lecithin is produced in granules? Is there a reason it is made both as a powder and as granules?

Thanks.

[bentl]

Is there any functional difference between lecithin granules and lecithin powder? Does one work better than the other? Does anyone know why lecithin is produced in granules? Is there a reason it is made both as a powder and as granules?

I find that granules are easier to work with. I usually put about 10 grams in half a cup of water, stir it for a few seconds, let it sit for about 20 minutes for the granules to dissolve, and then another quick stir to check for any remaining granules. Then add resv.

Edited by bentl, 15 December 2008 - 12:06 AM.

[gloria yin]

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.

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.

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.

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.

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.

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.

when we did the experiment we found that resveratrol is easily dissolved in Ethanol、methanol,maybe 75%Ethanol + water is also good ,but it is hard dissolved in water.

[drtzali]

I've been mixing one scoop (which I assume is 500mg) with a bit of lecithin and bee pollen powder, then letting that combination sit under my tongue for a few minutes, and then swallowing it. Anyone have experience with this type of administration or comments on how I might improve this routine?

thanx

[sUper GeNius]

Just wanted to inform of what seems like a pretty good method of administering resveratrol under the tongue. I put a small amount in half a capsule, and then place the half cap under the tongue. The resveratrol is well controlled that way, one can even carry on a conversation.

[Crepulance]

Seems to lightweights like me anyway, that taking a shot of everclear every morning would give me an unwanted buzz?


Crep

Just wanted to inform of what seems like a pretty good method of administering resveratrol under the tongue. I put a small amount in half a capsule, and then place the half cap under the tongue. The resveratrol is well controlled that way, one can even carry on a conversation.

Did you by chance take any pics of it simply dissolved in milk?


Crep

[hmm]

I have also tried the buccal delivery and would love to see some blood work. Where is Hedgehog when you need him? ;-) Mine is usually absorbed/disappears in ~45-60 minutes and I do notice the effects from taking it this way. I cant say if its better or stronger
than oral delivery as that's pretty subjective but buccal does seem to work.

I have been using buccal delivery for my Resveratrol for a few weeks now. I stopped for about a week and have since resumed and I have noticed the change. It is like I feel bullet proof when I take Resveratrol this way. I think I must be getting a pretty good dose and would love to see someone test blood levels like this. I take about half a teaspoon full of res and leave it between teeth and gums overnight. By morning, it has usually gone or there is just a little bit left.

Has anyone else been doing this or is anyone else game to try it?

I definately feel different and it is not the buzz that you get when you first start taking Res.

What I like it that there is no waste - what isn't absorbed buccally goes the oral route anyway. To get it to hang around, I try not to let it get too wet ie. no drinking liquids etc - of course it is wet against the cheek where it counts. I also have to try keep my tongue out of the area:).

I suspect that buccal is delivering a good dose but would like to get verification of whether I am wasteing my time. HeeeedgeHoggg....

What's going on with you buccal guys lately? Do you still find it a viable option? I have started getting a very deep pain in the right side of my abdomen after taking resveratrol, and if I run directly after taking rsv, the pain expands downward into my pelvic area, making me feel like I just got kicked in the nuts. And after completing an hour of running, it takes about 3 or 4 hours for the throbs of pain to go away. I don't know exactly what is wrong down there, but I have stopped rsv for a few days and then re-started rsv 4 times now with the problem disappearing the day after stopping and re-appearing right after resuming. It is starting to look like buccal may be my last best option for taking rsv...

[stephen_b]

I have started getting a very deep pain in the right side of my abdomen after taking resveratrol, and if I run directly after taking rsv, the pain expands downward into my pelvic area, making me feel like I just got kicked in the nuts. And after completing an hour of running, it takes about 3 or 4 hours for the throbs of pain to go away. I don't know exactly what is wrong down there, but I have stopped rsv for a few days and then re-started rsv 4 times now with the problem disappearing the day after stopping and re-appearing right after resuming. It is starting to look like buccal may be my last best option for taking rsv...

Hopefully it's not a inguinal hernia. Do you have any bulges in the abdominal wall near the pain site? I had surgery for that in December.

[hmm]

I have started getting a very deep pain in the right side of my abdomen after taking resveratrol, and if I run directly after taking rsv, the pain expands downward into my pelvic area, making me feel like I just got kicked in the nuts. And after completing an hour of running, it takes about 3 or 4 hours for the throbs of pain to go away. I don't know exactly what is wrong down there, but I have stopped rsv for a few days and then re-started rsv 4 times now with the problem disappearing the day after stopping and re-appearing right after resuming. It is starting to look like buccal may be my last best option for taking rsv...

Hopefully it's not a inguinal hernia. Do you have any bulges in the abdominal wall near the pain site? I had surgery for that in December.

Actually I AM wondering if it is some kind of hernia that is too subtle for the doctors to see it or feel. After I stopped taking rsv the most recent time, I was almost relieved when the pain started happening again after a couple of weeks of no rsv. Still, however, I wasn't able to go back to using the 99% rsv powder, I guess simply because my bowels had just gotten tired of it (or gotten tired of it always being administered in micronized-with-booze fashion). I tried bucaal, but it became a major ordeal of large amounts of time swishing white rsv/alcohol paste around my mouth that intermittently dribbled out between my lips, without any discernible beneficial effects. As a last resort I tried the Tween80 product and that has been working out really well for around a month so far (500 mg per day).

I'm still trying to figure out the mystery pain. I can actually prevent it from happening if I drink 20 ounces of water halfway through my run, or after running I can make most of the pain go away fairly quickly if I drink a quart of water rapidly. First I need to deal with a 1/2 inch kidney stone in that area to try to rule that out as a cause. The doctors don't think a kidney stone could cause that kind of pain, though the pain does seem to begin in that area of my body, but I think even the doctors see addressing the kidney stone as the first step in getting to the bottom of the issue. Otherwise, maybe the pain IS caused by some kind of subtle hernia. I thought the uniqueness of the symptoms and the way it is sensitive to hydration might make this an easy problem to diagnose, but apparently the symptoms are so unique they don't ring a bell with anybody...