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Using Gelatin as a Resveratrol Delivery Vehicle


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#1 maxwatt

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Posted 11 March 2010 - 01:38 PM


I came across a patent for water-soluble curcumin which involve raising pH to obtain a water soluble basic form, then adding gelatin, and lowering pH leaving the curcumin bound to the gelatin in solution.

I wondered if it were possible to make an equivalent drink to SRT501 using gelatin instead of HPMC/DOSS or Tween80.

I've done some kitchen chemistry to see what would work with resveratrol. First, i did not try to change the pH, to avoid conversion to cis-resveratrol. Add half a teaspoon (5 ml) of unflavored gelatin to 4 ounces (125 cc) of water. Heating to 100 degrees and stirring vigorously is necessary for it to dissolve quickly. Then add 500 mg of 98% resveratrol power and stir vigorously for 30 seconds. When I did this, the solution turned milky white. Inspection revealed some small particles which remained suspended, only the largest (under 5%) settling. After half an hour the solution was still cloudy, most of the suspended particles too small to see as such even with a hand-lens. Some visible particles remained suspended due to Van der Waals forces. Note, the resveratrol I used was not micronized; I believe using micronized resveratrol would result in no settling of resveratrol particles.

I suppose one could use flavored gelatin. Unflavored gelatin makes for a bland-tasting drink. Heated to 300 degrees and baked in muffins, resulted in the loss through decomposition of about 30% of the resveratrol in one published study. The stability at 100 degress or less should be no problem, or you could let the solution cool to room temperature before adding resveratrol.

I've been using my fasting blood glucose as a proxy measurement to attempt to evaluate the effectiveness of different delivery systems for resveratrol. Very preliminary, I've only one measurement so far, but this method resulted in lower fasting glucose for me than just swallowing resveratrol powder or attempting bucal delivery. It could be a coincidence, or confounding factors, so I will keep measuring.

I hope Browser finds this a suitable delivery system for his problem. I expect Anthony will go to the supermarket to buy some gelatin this morning. Maybe we can come up with a recipe for resveratrol Jello Shots.

Mixing the solution and storing it refrigerated should prove stable for at least a month. Trela investigated the stability of resveratrol in aqueous solution and found it stable for that long, as long as the pH was below 11 and it was not exposed to UV light. I expect a few days storage will not be a problem.

#2 Anthony_Loera

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Posted 11 March 2010 - 03:14 PM

Hi Maxwatt,

I have to try this out, but I am in a Hotel in Anaheim and don't have bulk powder with me.

I would certainly like to test it with regular res, micronized res, and some cyclodextrin res I had made late last year. This cyclodextrin res looks milky white in plain water (but tastes horrible!), so I find your post very interesting. I am probably going to compare all three.

If they all look pretty much the same... maybe it is a much tastier alternative!

Thanks for posting that Maxwatt.
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#3 malbecman

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Posted 11 March 2010 - 05:05 PM

Yes, it sounds pretty interesting/promising. Do keep us posted.......

Thanks,

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#4 ppp

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Posted 12 March 2010 - 07:18 AM

Yes - please do keep us posted on this...

#5 maxwatt

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Posted 12 March 2010 - 01:00 PM

Yes - please do keep us posted on this...


The effect seems to be consistent over several days: more response dispersed in gelatin than taken as a powder held in the mouth and/or swallowed. This is now my preferred method of administration.

I want to test whether morning or evening dosing is better. We have discussed in this forum that resveratrol interacts with CLOCK genes that affect circadian rhythm. I had thought morning application would be better, but I now have a way to measure using fasting blood glucose as a proxy for blood serum levels. It would help if others here could make similar measurements comparing morning to evening dosing, and comparing methods of administration.

A glucose monitor is relatively cheap, and a reasonably accurate one can be purchased at most drug stores for around $20. 50 test strip for $32, and 50 lancets for $10 if one needs continuing supplies.

I hope some of us can take measurements, and see how resveratrol is affecting our fasting blood glucose, and post here.

Be aware that capillary glucose can run as much as 25% higher than venous levels, so a "high" reading (over 100, or over 120) is no cause for alarm, but do look at the numbers the doctor gets on your next physical.

#6 Blue

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Posted 12 March 2010 - 01:16 PM

I've been using my fasting blood glucose as a proxy measurement to attempt to evaluate the effectiveness of different delivery systems for resveratrol.

How do you know that you are not simply measuring resveratrol 's intestinal anti-glucosidase activity? Which may be unrelated or even inversely related to blood resveratrol in humans if intestinal absorption is prevented/delayed?

#7 maxwatt

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Posted 12 March 2010 - 02:15 PM

I've been using my fasting blood glucose as a proxy measurement to attempt to evaluate the effectiveness of different delivery systems for resveratrol.

How do you know that you are not simply measuring resveratrol 's intestinal anti-glucosidase activity? Which may be unrelated or even inversely related to blood resveratrol in humans if intestinal absorption is prevented/delayed?

Good point.l As it is fasting glucose, after a fast pf around 8 hours or more, there should be a wash-out of any anti-glucosidase activity. I think it is a measure of of gluco-neogenesis, insofar as it is reduced.

#8 Blue

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Posted 12 March 2010 - 03:00 PM

Acarbose affects fasting glucose. At least in diabetics after a long intake. Not sure why. Will it do the same after only one day in the healthy? Not sure but can it be excluded? The earlier patent holder may have looked at this but who knows where that data is.
http://archinte.high...act/154/21/2442

#9 Blue

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Posted 12 March 2010 - 03:32 PM

"The main hepatic effect of butyrate is a sparing effect on glycogen storage explained (i) by competition between butyrate and glucose oxidation, glucose being preferentially directed to glycogenosynthesis during the post-prandial state; and (ii) by a likely reduced glycogenolysis from the newly synthesized glycogen. This first demonstration of the improvement of liver glycogen storage by acute butyrate supply may be an important contribution to explaining the beneficial effects on glucose homeostasis of nutritional supply increasing butyrate amount such as fiber diets."

"It must be kept in mind that under our experimental conditions (acute butyrate supply and gastric absorption), the observed effects could not be strictly transposed to fiber diets. Whatever the case, the hepatic sparing effect of butyrate on both glucose oxidation and glycogen store, could be one of the molecular basis for the effects of dietary fibers on the prevention of insulin resistance. In the muscle, the prevention of insulin resistance in rats supplemented in fiber has been explained by the effect of butyrate increasing GLUT-4 via PPARγ [44]. To our knowledge, our work is the first to propose a biochemical mechanism in the liver to better understand how one of the main end-products of dietary fibers may regulate glucose metabolism. Since these data were obtained after acute intake of butyrate, the chronic effects remain to be studied. The use of dietary fibers could be a simple, non-invasive and socially acceptable method to improve the metabolic pathways involved in metabolic syndrome."

"More anecdotaly, butyrate effect should in part contribute to the effect of acarbose used in the pharmacological prevention of diabetes. Indeed, in rats fed with "Westernized" diets, acarbose treatment suppressed starch digestion in the small bowel but there was compensatory salvage by bacterial fermentation in the large bowel. Cecal total SCFA pool size was increased more than 4-fold, with even bigger increases for butyrate. These changes in butyrate were reflected in increased molar proportions of butyrate in blood from both the portal vein and heart [42]. Acarbose could effectively increased colonic butyrate production by several mechanisms such as reduced starch absorption and larger concentrations of starch-fermenting and butyrate-producing bacteria."
http://www.biomedcen.../1472-6793/8/19

Seems not unlikely that an increased butyrate concentration from colon metabolism or its effects on glycogen may well still be in effect the day after intake of a glucosidase inhibitor.

One possibility which should avoid this possible confounding factor would be to avoid eating any complex carbohydrates.

#10 browser

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Posted 12 March 2010 - 05:28 PM

Yes - please do keep us posted on this...


The effect seems to be consistent over several days: more response dispersed in gelatin than taken as a powder held in the mouth and/or swallowed. This is now my preferred method of administration.

I want to test whether morning or evening dosing is better. We have discussed in this forum that resveratrol interacts with CLOCK genes that affect circadian rhythm. I had thought morning application would be better, but I now have a way to measure using fasting blood glucose as a proxy for blood serum levels. It would help if others here could make similar measurements comparing morning to evening dosing, and comparing methods of administration.

A glucose monitor is relatively cheap, and a reasonably accurate one can be purchased at most drug stores for around $20. 50 test strip for $32, and 50 lancets for $10 if one needs continuing supplies.

I hope some of us can take measurements, and see how resveratrol is affecting our fasting blood glucose, and post here.

Be aware that capillary glucose can run as much as 25% higher than venous levels, so a "high" reading (over 100, or over 120) is no cause for alarm, but do look at the numbers the doctor gets on your next physical.


Are you dispersing RESV in gelatin by mixing RESV and gelatin powder together than adding to water or are you following the patent approach to make water soluble RESV?

I'm going to place an order for
Acetic Acid from Amazon in an attempt to duplicate the soluble curcumin patent. Curcumin is very exciting to the cancer patient (of which I am one) if you can only get it into the blood stream.

#11 maxwatt

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Posted 12 March 2010 - 08:44 PM

Yes - please do keep us posted on this...


The effect seems to be consistent over several days: more response dispersed in gelatin than taken as a powder held in the mouth and/or swallowed. This is now my preferred method of administration.

I want to test whether morning or evening dosing is better. We have discussed in this forum that resveratrol interacts with CLOCK genes that affect circadian rhythm. I had thought morning application would be better, but I now have a way to measure using fasting blood glucose as a proxy for blood serum levels. It would help if others here could make similar measurements comparing morning to evening dosing, and comparing methods of administration.

A glucose monitor is relatively cheap, and a reasonably accurate one can be purchased at most drug stores for around $20. 50 test strip for $32, and 50 lancets for $10 if one needs continuing supplies.

I hope some of us can take measurements, and see how resveratrol is affecting our fasting blood glucose, and post here.

Be aware that capillary glucose can run as much as 25% higher than venous levels, so a "high" reading (over 100, or over 120) is no cause for alarm, but do look at the numbers the doctor gets on your next physical.


Are you dispersing RESV in gelatin by mixing RESV and gelatin powder together than adding to water or are you following the patent approach to make water soluble RESV?

I'm going to place an order for
Acetic Acid from Amazon in an attempt to duplicate the soluble curcumin patent. Curcumin is very exciting to the cancer patient (of which I am one) if you can only get it into the blood stream.


No the mixing is done separately, see first post in this topic where I described the process I am using.

Blue: if the lowered fasting glucose is due to anti-glucosidase activity, itwould also show up with other anti-gluciidase agents. I do not have acarbose, but I did experiment at one time with mulberry leaf extract, said to be as effectie as acarbose. I did not notice a change in fasting glucose over several days. Either the extractis not as effective as acarbose, or the lowered glucose I am observing is due to another effect, of resveratrol to some other factor.

When I eat low-carb, my fasting glucose is not lowered consistently. Also, I've been taking resveratrol pretty consistently at high doses, as a powder. No effect on fasting glucose noted from that, comparing off and on regimens for resveratrol. Something about complexing with gelatin is different., o there is some confounding factor I'm not aware of.

#12 maxwatt

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Posted 13 March 2010 - 12:19 PM

I've been using my fasting blood glucose as a proxy measurement to attempt to evaluate the effectiveness of different delivery systems for resveratrol.

How do you know that you are not simply measuring resveratrol 's intestinal anti-glucosidase activity? Which may be unrelated or even inversely related to blood resveratrol in humans if intestinal absorption is prevented/delayed?

Good point.l As it is fasting glucose, after a fast pf around 8 hours or more, there should be a wash-out of any anti-glucosidase activity. I think it is a measure of of gluco-neogenesis, insofar as it is reduced.


Actuall, I've not been able to find any reference to resveratrol being much of an anti-glucosidase.

#13 Blue

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Posted 13 March 2010 - 12:55 PM

http://www.ncbi.nlm....pubmed/16478243

But you are right that surprisingly few seem to care about this effect which unlike the others is not dependent on tissue bioavailability which is very poor for resveratrol in humans. But then few seem interested in that a surprising number of healthy foods are very good glucosidase inhbitors. Even more surprising when considering how good a drug acarbose is. Maybe the best typ II diabetes drug we have:
http://www.ncbi.nlm....les/PMC2040135/

#14 browser

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Posted 13 March 2010 - 03:43 PM

<<<SNIP>>>
I hope Browser finds this a suitable delivery system for his problem. I expect Anthony will go to the supermarket to buy some gelatin this morning. Maybe we can come up with a recipe for resveratrol Jello Shots.

<<<SNIP>>>

I am becoming more tolerant of the 12 Nitro 250 and 12 MCT Quercetin plus my 90 mg. porcine thyroid downed with water upon arising. The cannonball to the gut effect is gone. There's still a lot of burping and some indigestion from all the medium chain triglycerides. That's abating. Today, no squirts from downing all of those capsules. This method of taking RESV appears doable but it's still expensive. I have added buccal RESV and RESV bubble gum. I'm not looking at taking such expensive RESV for years. I figure it'll be a few months. I need to cancel my monthly autoship of Nitro 250 and MCT Quercetin. If I use the gelatin approach I could take 5 grams of RESV and 5 grams of MCT Quercetin for the same money I'm spending on the Nitro. If only Anthony would give the same break on 6 X 25 grams of micronized RESV as he gives on 4 boxes.

Maxwatt, you don't mention Quercetin or wine extract. Don't you take anything to protect the RESV for the first time it hits the liver?

I'm wondering just how much RESV I need to down at one time to overwhelm the liver so I don't need to take MCT Quercetin with the RESV. Any educated guesses? I do notice that my urine as more yellow to red when I take 3 grams of Jarrow Quercetin capsules versus 3 grams of MCT Quercetin. Wonder why?

#15 maxwatt

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Posted 13 March 2010 - 05:34 PM

<<<SNIP>>>
I hope Browser finds this a suitable delivery system for his problem. I expect Anthony will go to the supermarket to buy some gelatin this morning. Maybe we can come up with a recipe for resveratrol Jello Shots.

<<<SNIP>>>

I am becoming more tolerant of the 12 Nitro 250 and 12 MCT Quercetin plus my 90 mg. porcine thyroid downed with water upon arising. The cannonball to the gut effect is gone. There's still a lot of burping and some indigestion from all the medium chain triglycerides. That's abating. Today, no squirts from downing all of those capsules. This method of taking RESV appears doable but it's still expensive. I have added buccal RESV and RESV bubble gum. I'm not looking at taking such expensive RESV for years. I figure it'll be a few months. I need to cancel my monthly autoship of Nitro 250 and MCT Quercetin. If I use the gelatin approach I could take 5 grams of RESV and 5 grams of MCT Quercetin for the same money I'm spending on the Nitro. If only Anthony would give the same break on 6 X 25 grams of micronized RESV as he gives on 4 boxes.

Maxwatt, you don't mention Quercetin or wine extract. Don't you take anything to protect the RESV for the first time it hits the liver?

I'm wondering just how much RESV I need to down at one time to overwhelm the liver so I don't need to take MCT Quercetin with the RESV. Any educated guesses? I do notice that my urine as more yellow to red when I take 3 grams of Jarrow Quercetin capsules versus 3 grams of MCT Quercetin. Wonder why?


I don't take quercetin. I tried it, and found it reversed the anti-arthritic effects I was getting from resveratrol, and I began to experience tendinitis and joint pain. This reversed when I discontinued the quercetin and stuck with resveratrol. I later tried luteolin, which is several times more potent than quercetin at inhibiting the enzymes that sulfonate resveratrol. Same problem, except this time when I discontinued luteolin, the tendinitis remained, and did not abae until I increased my vitamin D so that blood levels were well over 30.

I've not tried either quercetin or luteolin since correcting my D levels. It is possible that the pain was due to the anti-aromatase activity of resveratrol, and that quercetin and luteolin were raising my blood levels of resveratrol enough for this to kick in, causing joint pain due to low serum levels of D. This is only speculation. It's possible there is some other reaction to these polyphenols going on. There are also a few people who have posted here who had a similar reaction to quercetin as I did. Several people report having experienced joint pain on resveratrol alone, and some have reported that increasing their intake of vitamin D3 has eliminated the joint pain.

#16 maxwatt

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Posted 13 March 2010 - 05:38 PM

http://www.ncbi.nlm....pubmed/16478243

But you are right that surprisingly few seem to care about this effect which unlike the others is not dependent on tissue bioavailability which is very poor for resveratrol in humans. But then few seem interested in that a surprising number of healthy foods are very good glucosidase inhbitors. Even more surprising when considering how good a drug acarbose is. Maybe the best typ II diabetes drug we have:
http://www.ncbi.nlm....les/PMC2040135/


Amazing. How many other reports of glucosidase inhibition are there? The search terms I used turned up none!

If resveratrol is actually more effective that acarbose at glucosidase inhibition this would explain the intestinal discomfort and diarrhea some people experience with resveratrol. A similar side effect occurs with acarbose, and is treated by step-wise modulation of the dosage.

An anti-glucosidase effect would also explain some but not all of the metabolic effects of resveratrol in Sinclair's fat-mouse study.

Edited by maxwatt, 13 March 2010 - 07:19 PM.
speling


#17 Blue

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Posted 13 March 2010 - 05:59 PM

Some examples of healthy foods containing glucosidase inhibitors.
Green tea: http://www.ncbi.nlm....pubmed/16806089
Pine bark extract (Pycnogenol): http://www.ncbi.nlm....pubmed/15925302
Tumeric: http://www.ncbi.nlm....pubmed/16387392
Various berries, red grape, red wine, green tea: http://www.ncbi.nlm....pubmed/15796622

#18 Blue

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Posted 13 March 2010 - 06:09 PM

I think the tumeric study is especially interesting since the tumeric component curcumin is often cited as the reason for the near absence of Alzheimer in some parts of India. But curcumin seems not to be absorbed by humans even in Indian dietary doses.

Edited by Blue, 13 March 2010 - 06:10 PM.


#19 browser

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Posted 13 March 2010 - 07:55 PM

I don't take quercetin. I tried it, and found it reversed the anti-arthritic effects I was getting from resveratrol, and I began to experience tendinitis and joint pain. This reversed when I discontinued the quercetin and stuck with resveratrol. I later tried luteolin, which is several times more potent than quercetin at inhibiting the enzymes that sulfonate resveratrol. Same problem, except this time when I discontinued luteolin, the tendinitis remained, and did not abae until I increased my vitamin D so that blood levels were well over 30.

I've not tried either quercetin or luteolin since correcting my D levels. It is possible that the pain was due to the anti-aromatase activity of resveratrol, and that quercetin and luteolin were raising my blood levels of resveratrol enough for this to kick in, causing joint pain due to low serum levels of D. This is only speculation. It's possible there is some other reaction to these polyphenols going on. There are also a few people who have posted here who had a similar reaction to quercetin as I did. Several people report having experienced joint pain on resveratrol alone, and some have reported that increasing their intake of vitamin D3 has eliminated the joint pain.


I can't luteolin as a supplement. Did you get it from a chemical supply house or import it from China? There's evidence luteolin works against prostate cancer, my theme this year.

#20 zawy

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Posted 13 March 2010 - 08:42 PM

Several people report having experienced joint pain on resveratrol alone, and some have reported that increasing their intake of vitamin D3 has eliminated the joint pain.

My mother and I experienced an elimination of joint pains once we started taking vitamin D3 when I had not yet heard of resveratrol. I suspect it's a major benefit of 4,000 IU/day doses that will take forever to be common knowledge.

#21 sagecucumber

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Posted 15 March 2010 - 11:19 PM

Max, I'm curious if you've used your FBG with other delivery methods besides buccal and your gelatin recipe and if so, what was the result? The sales pitch doesn't seem as compelling as mixing in a whey protein drink or with lecithin or tween 80. It would be nice to have a little more info before buying in (although I did try it out this morning - I'm going to have to go with flavored gelatin).

Btw, I thought your big toe was the gold standard test for resv.

#22 maxwatt

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Posted 16 March 2010 - 12:04 AM

Max, I'm curious if you've used your FBG with other delivery methods besides buccal and your gelatin recipe and if so, what was the result? The sales pitch doesn't seem as compelling as mixing in a whey protein drink or with lecithin or tween 80. It would be nice to have a little more info before buying in (although I did try it out this morning - I'm going to have to go with flavored gelatin).

Btw, I thought your big toe was the gold standard test for resv.


I'd settled on just taking powder orally, with water, holding it under my tongue ore in my cheek and letting it diserse as I siped a glass of water. Th toe has been stable for years. Then I thought I could use the blood glucose meter to put some numbers on things, and tried to compare with the gelatin method. Gelatin should be similar to whey protein as a dispersant or carrier, via protein binding. You can usefruit juice (pomeganate?) witht he gelatin instead of water.

I don't mind the bland taste of plain gelatin.

#23 aaCharley

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Posted 21 March 2010 - 08:49 AM

I came across a patent for water-soluble curcumin which involve raising pH to obtain a water soluble basic form, then adding gelatin, and lowering pH leaving the curcumin bound to the gelatin in solution.
<snip>


I'm not much of a researcher, but wonder if this is the particular patent application you reference?
Water-soluble curcumin complex United States Patent 4368208

As I read through it I note that it also has this information:
Ground turmeric may be extracted with organic solvents to remove the curcumin and the fixed and volatile oils from the cellulose plant material of the rhizomes, to form oleoresins. Solvents such as isopropanol, ethanol, acetone, and ethylene dichloride and others are typically used to prepare oleoresins of turmeric, which may typically contain about 30% curcumin, 30% volatile oils, 30% fixed oils, and 10% polysaccharides. Oleoresins are used by the food industry to color pickles, baked goods, poultry products, and in seasoning mixtures for various other food products.

And that causes me to ask two questions.
First, once you have got the curcumin disolved and in the gelatin, how will you use it. Isn't the problem that it is modified and broken down in the digestive system before it can be absorbed and enter the blood stream. I'm understand how using a gelatin version taken orally will address that problem. Will you use some other method to administer the curcumin?
Seoond, I find it interesting that the oil component is nearly twice the curcumin component in the initial pass of processing the root. So many plant oils have been shown to carry the nutritional benefits of the plant that I wonder if they make up some of the benefit that seems to show up in the studies of the India population. Once you have it solubile, can you then use that to create the liposomal form with a method such as can be done with the Vitamin C.

Thanks for the good ideas.

#24 MrSpud

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Posted 30 October 2010 - 07:14 PM

FYI - Gelatin is an effective emulsifier, not as good as lecithin or Polysorbate 80, but it does work. Probably that's why it looks milky. Curcumin is oily and not very water soluble, so increasing it's water solubility by sort of making a salt with acid and them making a stable emulsion with the gelatin would be why the curcumin work. If you are just dumping in resveratrol and not increasing it's solubility, you might be doing nothing more that the other emulsifiers would do.

That said, you could go the other direction an disperse the res in gelatin and then pour it on a cookie sheet and dry it down to a film, peel it off and cut out gelatin wafer squares that could then be used sublingually. You could even go all out and pour the gelatin/res into little molds (like the clear plastic part of a blister pack where you have little depressions where normally a tablet would fit into) and freeze dry it and make an instant melt delivery system (google zydis if you want to read more about this). Or, if you find that a slower time delayed delivery system works better you can crosslink the gelatin/res with a small amount of reducing sugar (glucose or xylose would work fine) and dry it into a sheet and cut out squares.

Just thoughts.....

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#25 MrSpud

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Posted 30 October 2010 - 08:45 PM

For the reference junkies ;)
http://www.ncbi.nlm..../pubmed/9839999
http://www.freepaten...om/4371516.html
http://www.ehow.com/...rying-home.html

Edited by MrSpud, 30 October 2010 - 08:50 PM.





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