1084 replies to this topic

[maxwatt]

Has anybody tried to dissolve RES in a saline solution and used an eye dropper?

Saline is mostly water, and RES is not particularly soluble in water.

How about a Saline solution with some EtOH. For example dissolve Res in EtOH and then dump it into the saline solution. However, I'm not sure if it is a good idea to put EtoH on your eye let alone Res. However that might be the best way to keep your eye nerves from damage.

Go buy some mice in a pet store, and try it on them first. You should be able to tell if they go blind at least, or scream in pain.

[Hedgehog]

Has anybody tried to dissolve RES in a saline solution and used an eye dropper?

Saline is mostly water, and RES is not particularly soluble in water.

How about a Saline solution with some EtOH. For example dissolve Res in EtOH and then dump it into the saline solution. However, I'm not sure if it is a good idea to put EtoH on your eye let alone Res. However that might be the best way to keep your eye nerves from damage.

Go buy some mice in a pet store, and try it on them first. You should be able to tell if they go blind at least, or scream in pain.

LOL, naw I was curious to see if anybody else has tried. I should be getting my first shipment of SIRT1 drugs soon (res, Quercetin, Myricetin Vit C amd Vit E every other day)

I do a lot of long distance training and it will be interesting to see if it has any effects. I have a group that I train with and it should become clear if it has any effects.

[maxwatt]

I'm thinking the main reason they used acetone and then hexane was so they could pull it off easily (evaporate it) and form a dry powder for their capsules. I see no reason why the PC should not also complex with resveratrol in a solvent water and act like it normally does as an emulsifier. I think the main message to take is that you need to mix the 2 ingredients in equimolar amounts or up to a 2:1 equimolar ratio. Since the various phosphatidyl choline derivatives have MWs (760-800 Da) that are approx. 3X the MW of resveratrol (228 Da), that means on a weight basis you would want 3X-6X times as much lecithin as resveratrol. Maybe we all need to double check how much lecithin we are using a little more carefully instead of just saying, "I used ~1/4 tsp........"

The problem I have with the lecithin granules I have is they do not dissolve completely; whether I lack the patience to stir forever or the foresight to leave it overnight, I strain out the undissolved lumps, and don't know how much lecithin has ended up in the mixture with any precision. Are there lecithin products that dissolve easil in water or oil?

[Anthony_Loera]

Has anybody tried to dissolve RES in a saline solution and used an eye dropper?

Not yet....

[health_nutty]

I'm thinking the main reason they used acetone and then hexane was so they could pull it off easily (evaporate it) and form a dry powder for their capsules. I see no reason why the PC should not also complex with resveratrol in a solvent water and act like it normally does as an emulsifier. I think the main message to take is that you need to mix the 2 ingredients in equimolar amounts or up to a 2:1 equimolar ratio. Since the various phosphatidyl choline derivatives have MWs (760-800 Da) that are approx. 3X the MW of resveratrol (228 Da), that means on a weight basis you would want 3X-6X times as much lecithin as resveratrol. Maybe we all need to double check how much lecithin we are using a little more carefully instead of just saying, "I used ~1/4 tsp........"

The problem I have with the lecithin granules I have is they do not dissolve completely; whether I lack the patience to stir forever or the foresight to leave it overnight, I strain out the undissolved lumps, and don't know how much lecithin has ended up in the mixture with any precision. Are there lecithin products that dissolve easil in water or oil?

Vitamine Shoppe brand granules dissolves completely overnight (although it probably only needs 10-20 minutes). Stirring or shaking doesn't seem to affect the time, but I can blend it in my vita-mix and it will mix within seconds.

[Anthony_Loera]

A customer of mine who frequents this forum has sent me a link to the following article, and has all the credit of finding this.
Thanks to Mr. Delaney who sent me the article.

He mentions ß-Lactoglobulin is found in buttermilk...

The Article:
http://www.cyberpres...5/CPNOUVELLISTE

It is in french, but here is the rough translation using bablefish:

Your new friend anti-cancer, the resvératrol

Brigitte Trahan
The Short story writer
Three-rivers

The virtues anti-cancer of the resvératrol, a polyphenolic natural substance contained in particular in the red wine, are recognized more and more by science. But here that a team of researchers of Université of Quebec with Three-Rivers, in collaboration with Institute Cancer of the New Jersey and the Laval University, succeeded in including/understanding how and why the resvératrol can act of the kind.

Heidar-Ali Tajmir-Riahi, researcher with the department of Chemistry-biology and his colleague, Christophe N soukpoé-Kossi, part-time lecturer at the same department, showed that the resvératrol binds to albumin, the most abundant protein in the blood plasma. It can thus be distributed everywhere in the human body and go to place thereafter in the heart even propeller of the ADN. From there, it can fight the free radicals when the latter, which play usually a vital part in the biological processes, take part in reactions being able to damage the cells and to cause cancer.

Work of Heidar-Ali Tajmir-Riahi made it possible to also include/understand that the resvératrol intervenes in the three stages of the formation of a cancer, that is to say initiation, the promotion and the progression of this last. "the study of the interaction between the resvératrol and the ADN is thus of major importance at the biological level", estimates it.

The resvératrol is a phytoalexin, i.e. a substance naturally produced by certain plants in reaction to various aggressions like the ultraviolet radiation, the bacteria or the mushrooms. "One finds resvératrol in 70 kinds of plants, particularly the groundnuts, the blackberries and under the skin of the red grapes", explains the scientist.

The red wine is particularly rich in resvératrol, but its concentration in the wine will be influenced by the process of fermentation, explains the researcher. The more first the fermentation will be long (that during which the skin of the grape is present), the more there will be resvératrol in the wine.

"In one gram of grape skin, one finds indeed between 50 and 100 micrograms of resvératrol", illustrates it. The analyses show that one liter of red wine can contain enters 14 milligrams and 40 milligrams of resvératrol, according to process's of fermentation, notes the scientist. "In our laboratory, we noted that the resvératrol reacts with the ADN, but also with the ARN", explains Heidar-Ali Tajmir-Riahi (the ADN contains genetic information and the ARN transports this information to the cells).

"If it acted on cancer, it was clear that there was an interaction with the ADN and showed we it", explains the researcher who counts with his credit 160 publications in international reviews with revision by the pars.

Thanks to albumin

But still was necessary it to find by which means the resvératrol is able to go to the ADN to intercalate itself there. "It had already been shown by other research that the drugs use serum albumin to go to destination and to make effect. Us are thus left this fact to check if the resvératrol used the same weak connection to be transported, which was well the case ", explains the chemist.

However, in laboratory, the researcher and his colleague noted that the resvératrol is almost not water soluble which is the most abundant matter of the human body. They however discovered that while reacting with proteins of the whey (ß-Lactoglobulin), it becomes more water soluble and can thus be better conveyed in the system.

Perhaps this new discovery, resulting from work united with Muriel Subirade of the Laval University, will be published in the periodical "Biomacromolecules" this month and will make it possible to improve the fight against cancer and the effectiveness of the drugs, hopes for Heidar-Ali Tajmir-Riahi.

Edited by Anthony_Loera, 20 December 2007 - 05:31 PM.

[maxwatt]

A customer of mine who frequents this forum has sent me a link to the following article, and has all the credit of finding this.
Thanks to Mr. Delaney who sent me the article.

He mentions ß-Lactoglobulin is found in buttermilk...

The Article:
http://www.cyberpres...5/CPNOUVELLISTE

It is in french, but here is the rough translation using bablefish:

Your new friend anti-cancer, the resvératrol

...[deleted]

I assume ß-Lactoglobulin is also found in whole milk, as well as in whole milk yogurt.

[Anthony_Loera]

A customer of mine who frequents this forum has sent me a link to the following article, and has all the credit of finding this.
Thanks to Mr. Delaney who sent me the article.

He mentions ß-Lactoglobulin is found in buttermilk...

The Article:
http://www.cyberpres...5/CPNOUVELLISTE

It is in french, but here is the rough translation using bablefish:

Your new friend anti-cancer, the resvératrol

...[deleted]

I assume ß-Lactoglobulin is also found in whole milk, as well as in whole milk yogurt.

You are right, I think buttermilk may contain more of this in comparison though. Does anyone know off the bat?

A

[malbecman]

I also find that using warm water helps the lecithin dissolve much more rapidly/completely. Still, it can take like ~10 minutes.....

I'm thinking the main reason they used acetone and then hexane was so they could pull it off easily (evaporate it) and form a dry powder for their capsules. I see no reason why the PC should not also complex with resveratrol in a solvent water and act like it normally does as an emulsifier. I think the main message to take is that you need to mix the 2 ingredients in equimolar amounts or up to a 2:1 equimolar ratio. Since the various phosphatidyl choline derivatives have MWs (760-800 Da) that are approx. 3X the MW of resveratrol (228 Da), that means on a weight basis you would want 3X-6X times as much lecithin as resveratrol. Maybe we all need to double check how much lecithin we are using a little more carefully instead of just saying, "I used ~1/4 tsp........"

The problem I have with the lecithin granules I have is they do not dissolve completely; whether I lack the patience to stir forever or the foresight to leave it overnight, I strain out the undissolved lumps, and don't know how much lecithin has ended up in the mixture with any precision. Are there lecithin products that dissolve easil in water or oil?

[health_nutty]

I assume ß-Lactoglobulin is also found in whole milk, as well as in whole milk yogurt.

It is found in any product containing whey.

[stephen_b]

From this article,

The main protein found in whey, beta lactoglobulin, shows a high capacity to bind flavors.

Another site says that beta-lactoglobulin is 57% of cow whey.

Stephen

[stephen_b]

Here's another (PMID 18067252):

β-Lactoglobulin (β-LG), the major whey protein in the milk of ruminants, has a high affinity for a wide range of compounds. Resveratrol (3,5,4′-trihydroxystilbene), a natural polyphenolic compound found in grapes and red wine, exhibits many physiological effects associated with health benefits. In this study, the interaction of resveratrol with β-LG was investigated using circular dichroism, fluorescence and UV–vis absorbance. Self-association of resveratrol possibly occurs at high concentrations. Resveratrol interacts with β-LG to form 1:1 complexes. Resveratrol is bound to the surface of the protein because β-LG-bound polyphenol is in a weaker hydrophobic environment relative to 75% ethanol. The binding constant for the resveratrol−β-LG interaction is between 104 and 106 M−1, as determined by protein or polyphenol fluorescence. The β-LG−resveratrol interaction may compete with self-association of both the polyphenol and the protein. It has no apparent influence on β-LG secondary structure but partially disrupts tertiary structure. Complexing with β-LG provides a slight increase in the photostability of resveratrol and a significant increase in its hydrosolubility.

Stephen

[missminni]

does this mean half and half, my first method of taking Res, is the best?

[stephen_b]

does this mean half and half, my first method of taking Res, is the best?

I'm not sure how much beta-lactoglobulin is in half'n'half, or whether the protein is affected by pasteurization (whey denatures with heat, and since it's a milk protein, and half-n-half has more fat ...). I would think that a whey powder would be a better choice. I've just ordered some jarrow at iHerb.

Stephen

[Anthony_Loera]

Is that...

Whey Protein Isolate, or Whey Protein Concentrate?
I am thinking Isolate with a 50% or better β-LG may be something to consider for mixing rsv.


I am considering this one, but still looking:
http://www.bulkfoods...arch=fromSearch

a

Edited by Anthony_Loera, 20 December 2007 - 09:47 PM.

[stephen_b]

I am thinking Isolate with a 50% or better β-LG may be something to consider for mixing rsv.

The Jarrow product claims "100% Ultrafiltered Whey Protein from milk (comprising major isolate fractions: 51% Beta Lactoglobulin, 20% Alpha-Lactalbumin, 10% Immunoglobulin, 10% Albumin and 7% minor fractions, betamicroglobulin, lactoferrin and relaxin), and lecithin (from soy)".

Looks like it could contain up to 2% soy lecithin too, if I can add good.

Stephen

[Hedgehog]

Formulation of poorly soluble compounds.

See attachement

I had to delete a couple of slides due to making this presentation public.

[Anthony_Loera]

Thanks hedgehog_info

very, very interesting.

A

[edward]

So does this mean no more vodka, miralax, lecithin experiments... All we need is some whey protein and buttermilk? If so I will be so overjoyed. Just throw my resveratrol in with my morning protein shake (breakfast) and im good to go, no laborious prep work needed? Note also that plasma albumin, which the French article mentions resveratrol binds to is very close in structure to egg whites so maybe we could whip up a res-omelette?

I was under the impression before that proteins were a no no to take with plant based supplements, green tea, polyphenols, flavoniods, resveratrol etc. and any binding that would occur between said proteins and plant compounds would have a negative effect on absorption????

edit: clarity

Edited by edward, 21 December 2007 - 01:21 AM.

[maxwatt]

I assume ß-Lactoglobulin is also found in whole milk, as well as in whole milk yogurt.

It is found in any product containing whey.

You read it HERE first.

How about heavy cream and resveratrol, then whip it and serve over fresh organic blueberries?

[edward]

I assume ß-Lactoglobulin is also found in whole milk, as well as in whole milk yogurt.

It is found in any product containing whey.

You read it HERE first.

How about heavy cream and resveratrol, then whip it and serve over fresh organic blueberries?

Yes but you were referring to the Res dissolving in the milk fat which would act as a carrier. According to the French article it is the ß-Lactoglobulin which will act as the carrier and thus we can use whey protein and not have to bother with drinking milk fat each time we dose Res.... no?

edit: So just throw it in your protein shake? Again I was always under the opinion that proteins reduced the bioavailability of plant compounds? I still think its too go to be true?

Edited by edward, 21 December 2007 - 01:26 AM.

[stephen_b]

Another concern: I read that whey denatures easily. Is it (and β-LG) destroyed by pasteurization?

Stephen

[Hedgehog]

I just read
SIRT1 stimulation by polyphenols is affected by their stability and metabolism
By de Boer et al
I found this quote and was wondering if somebody could help explain it a little more.

Both ECg and EGCg stimulated the activity of recombinant
SIRT1, while EC and EGC were not able to stimulate SIRT1.
Thus the attached gallic acid group seems to be necessary for a
stimulating activity of catechins. An advantage of this
gallolyation of the polyphenolic backbone is that these
polyphenols are hardly conjugated to glucuronides and sulfates
in the human body. Therefore, EGCg is present in human
plasma for 77–90% in its free form (Manach et al., 2005),
whereas other polyphenols, like resveratrol, myricetin and
quercetin, are conjugated to glucuronides and sulfates. Tissues,
other than gastro-intestinal tract tissues, are also mainly
exposed to conjugates of resveratrol (Wenzel et al., 2005) and
quercetin (de Boer et al., 2005), while EGCg was found in
tissues in its unconjugated form (Meng et al., 2002). This may
have a significant impact on the bioactivity of EGCg in the
human body.

From what I understand resveratrol, myricetin and quercetin form a peroxide during the conversion to its breakdown products. What I'm confused about is it the H202 or the breakdown products that could be potentially inhibiting the SIRT1 gene???

What I found interesting is that EGCg is REALLY bio-available seen at 77-90% in the plasma. However, they noticed that if you don't add Vit-C it could inhibit SIRT1. However, if you find over half of the (77-90%) in the plasma is that a wining percentage?

After doing some research I found this that seems to contradict the bio-availabilty of EGCG.
Piperine Enhances bioavailability

(–)-Epigallocatechin-3-gallate (EGCG), from green tea (Camellia sinensis), has demonstrated chemopreventive activity in animal models of carcinogenesis. Previously, we reported the bioavailability of EGCG in rats (1.6%) and mice (26.5%)

Maybe humans just absorb it more???
Interesting fact about piperine

Piperine appeared to increase EGCG bioavailability by inhibiting glucuronidation and gastrointestinal transit.

Small intestinal EGCG levels in CF-1 mice following treatment with EGCG alone had a C_max = 37.50 ± 22.50 nmol/g at 60 min that then decreased to 5.14 ± 1.65 nmol/g at 90 min; however, cotreatment with piperine resulted in a C_max = 31.60 ± 15.08 nmol/g at 90 min, and levels were maintained above 20 nmol/g until 180 min. This resulted in a significant increase in the small intestine EGCG AUC (4621.80 ± 1958.72 vs. 1686.50 ± 757.07 (nmol/g·min)).

From another paper (Human bioavailability)

In regard to the EGCG bioavailability, pharmacokinetic studies in humans indicate the peak plasma concentration of EGCG is ~0.2 to 1 µg/mL (38, 39),

Bio-bioavailability of EGCG

Edited by hedgehog_info, 21 December 2007 - 03:54 AM.

[maxwatt]

I assume ß-Lactoglobulin is also found in whole milk, as well as in whole milk yogurt.

It is found in any product containing whey.

You read it HERE first.

How about heavy cream and resveratrol, then whip it and serve over fresh organic blueberries?

Yes but you were referring to the Res dissolving in the milk fat which would act as a carrier. According to the French article it is the ß-Lactoglobulin which will act as the carrier and thus we can use whey protein and not have to bother with drinking milk fat each time we dose Res.... no?

edit: So just throw it in your protein shake? Again I was always under the opinion that proteins reduced the bioavailability of plant compounds? I still think its too go to be true?

Not at all.... Not only whole milk, but non-fat milk dissolve resveratrol. It's the milk proteins binding to resveratrol, (as they do to tea polyphenols.) The milk fat might help to improve absorption, but this is not yet known. Whipped cream just adds to the pleasure. Who said the road to immortality nust be paved with asceticism? My post on the solubility of resveratrol in milk predates the information on milk proteins as a vehicle. PS, even tea polyphenols have been shown to be released, the binding isn't permanent to milk proteins, they are not rendered inactive as was once thought. Resveratrol apparently dissociates even more easily.

Seriously, we have a number of competing delivery mechanisms here. Lecithin or other surfactant, such as Miralax, or Tween80; Whey protein, milk or other milk products. Sublingual, aided by an ethanolic beverage. transdermally, via DMSO. A combination of a surfactant and an oil to make a liposome. How do we test them or otherwise which is most effective?

I think the use of whey protein in one form or another may be the easiest for home use. I'm going to let some chocolate ice cream melt, mix in the resveratrol, and refreeze it.

Edited by maxwatt, 21 December 2007 - 03:16 AM.

[niner]

"Resveratrol interacts with β-LG to form 1:1 complexes." BLG is 18.4 KDa, while resveratrol is 228 Daltons, so for 1 gram of resveratrol you'll need 18,400/228 = 80 grams of the protein. For a 5 gram dose, you're looking at a bit less than a pound of the protein. That's a lot of milk... Might it be the case that resveratrol also binds to other milk proteins? At perhaps greater than 1:1? It should also be solubilized by milk fat, which is already in suspension.

Also, this makes me wonder if human serum albumin is not acting as a carrier protein for resveratrol in the blood. Might that be a mechanism for it to dodge secondary metabolism?

[VP.]

So does this mean no more vodka, miralax, lecithin experiments... All we need is some whey protein and buttermilk? If so I will be so overjoyed. Just throw my resveratrol in with my morning protein shake (breakfast) and im good to go, no laborious prep work needed? Note also that plasma albumin, which the French article mentions resveratrol binds to is very close in structure to egg whites so maybe we could whip up a res-omelette?

I was under the impression before that proteins were a no no to take with plant based supplements, green tea, polyphenols, flavoniods, resveratrol etc. and any binding that would occur between said proteins and plant compounds would have a negative effect on absorption????

edit: clarity

You definitely nailed it Maxwatt. I'm jazzed that this may work. I always liked taking my resveratrol with milk and now it looks like this might be the way to go (after DMSO/Res belly rubs that is).

[Hedgehog]

From reading what Piperine has done for other drugs it might very well increase the bio-availabilty by of Res upwards of 50%. It has been shown to do this for other drugs in humans that are metabolized by the same pathway. I have been trying to figure out how long it inhibits glucuronidation? My guess is that this is a very good thing to administer with Res to keep it in its active form in the blood stream.



Animal data...

Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine.
40-50% inhibition of glucuronidation

Ref

More info in a patent

[Hedgehog]

I thought it was funny that the mice were put on a unhealthy diet composed of HIGH fat. However, since Res is soluble in fat in probably increased the absorbption of res thus negating the effects a high fat diet.

Just my 2 cents...

[sUper GeNius]

From reading what Piperine has done for other drugs it might very well increase the bio-availabilty by of Res upwards of 50%. It has been shown to do this for other drugs in humans that are metabolized by the same pathway. I have been trying to figure out how long it inhibits glucuronidation? My guess is that this is a very good thing to administer with Res to keep it in its active form in the blood stream.



Animal data...

Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine.
40-50% inhibition of glucuronidation

<a href="http://"http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&uid=8347144&cmd=showdetailview&indexed=google"" target="_blank">Ref</a>

More info in a patent

I do take my t-res with some Bioperine. AOR formiulation does contain Biperine, luteolin and quercitin.

[Hedgehog]

[/quote]

I do take my t-res with some Bioperine. AOR formiulation does contain Biperine, luteolin and quercitin.

[/quote]

Do you take Bioperine every day? If so how many mg do you take? I'm a little worried about chronically altering my degradation enzymes.