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Maximizing Resveratrol Effectiveness Redux


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#1 browser

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Posted 17 March 2010 - 03:38 PM


This is a somewhat surprising and very worrying development (given that my son is on resveratrol and docetaxel - a chemo drug related to pacitaxel):

Eur J Cancer. 2010 Mar 9.
Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells invitro and in vivo.

Fukui M, Yamabe N, Zhu BT.

Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.

It was reported recently that resveratrol could sensitise a number of cancer cell lines to the anticancer actions of several other cancer drugs, including paclitaxel. In the present study, we further investigated whether resveratrol could sensitise human breast cancer cells to paclitaxel-induced cell death. Unexpectedly, we found that resveratrol strongly diminished the susceptibility of MDA-MB-435s, MDA-MB-231 and SKBR-3 cells to paclitaxel-induced cell death in culture, although this effect was not observed in MCF-7 cells. Using MDA-MB-435s cells as a representative model, a similar observation was made in athymic nude mice. Mechanistically, the modulating effect of resveratrol was partially attributable to its inhibition of paclitaxel-induced G(2)/M cell cycle arrest, together with an accumulation of cells in the S-phase. In addition, resveratrol could suppress paclitaxel-induced accumulation of reactive oxygen species (ROS) and subsequently the inactivation of anti-apoptotic Bcl-2 family proteins. These observations suggest that the strategy of concomitant use of resveratrol with paclitaxel is detrimental in certain types of human cancers. Given the widespread use of resveratrol among cancer patients, this study calls for more preclinical and clinical testing of the potential benefits and harms of using resveratrol as a dietary adjuvant in cancer patients.


Comments, anyone?


I have prostate cancer. I'm getting Vitamin C IVs to stimulate my immune system and also create ROS to kill cancer cells. I'm also taking at least 3 grams of Resveratrol a day in the form of Nitro 250 plus buccal Resveratrol powder. Bill Sardi of Longev* started me off on Resveratrol. Bill told me the mechanism by which Resveratrol at higher doses would kill cancer is oxidation, i.e. ROS. The literature shows Bill's statement was wrong. Bill told me to take 10 grams of fish oil daily to aid in the oxidation and that the IVC would help in the oxidation. Well, it looks as though Resveratrol is actually preventing the IVC from killing cancer cells with ROS. Dr. Snuffy Myers, the prostate cancer survivor and expert prostate cancer prostate cancer oncologist tells his patients to take 500-1000 mg. each of Resveratrol and Quercetin in the form of Nitro 250 and MCT Quercetin but that prostate cancer patients should only take Resveratrol while under the care of a physician who knows all the medical implications of Resveratrol. This is better said than done since use of Resveratrol is very new and scarcely researched.

Thanks for the very helpful post. More things to ponder.


The thing about Quercetin is that it's a very strong inducer of Nrf2 - which drives the anti-oxidant response that protects the cell from oxidative damage...


I'm aware of that. I'm taking the high dose of Resvaratrol for its other chemo effects. I'm taking the Quercetin to make sure the potent dose of Resveratrol isn't deactivated during first pass by the liver. I'm looking for info on just how much Resveratrol taken at one time will swamp the liver's action against. Any ideas?


Nothing concrete. However, it seemed to me that synergism with curcumin is a line of inquiry worth following. Not only does curcumin attack multiple cancer pathways, it also inhibits liver metabolism to some extent. Have you looked at this?

This is a real minefield - the anti-cancer effects of resveratrol vary by cell line even within cancer subtype... I guess that's to be expected given the complex genomic instability of cancer but it makes it hard to make a decision in the absence of well validated clinical trials.


I read about the experiments with bioavailability of curcumin. It looks like just dissolving the stuff in hot coconut milk is the way to go. I'll place an order for some curcumin today and start downing it. I tried this before and everything got stained yellow as the curcumin oozed out from where the sun doesn't shine even in sleep. But, it can't be half as bad as the gastric distress in squirts I get from the MCT Quercetin.

#2 maxwatt

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Posted 18 March 2010 - 02:47 AM

This is a somewhat surprising and very worrying development (given that my son is on resveratrol and docetaxel - a chemo drug related to pacitaxel):

Eur J Cancer. 2010 Mar 9.
Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells invitro and in vivo.

Fukui M, Yamabe N, Zhu BT.

Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.

It was reported recently that resveratrol could sensitise a number of cancer cell lines to the anticancer actions of several other cancer drugs, including paclitaxel. In the present study, we further investigated whether resveratrol could sensitise human breast cancer cells to paclitaxel-induced cell death. Unexpectedly, we found that resveratrol strongly diminished the susceptibility of MDA-MB-435s, MDA-MB-231 and SKBR-3 cells to paclitaxel-induced cell death in culture, although this effect was not observed in MCF-7 cells. Using MDA-MB-435s cells as a representative model, a similar observation was made in athymic nude mice. Mechanistically, the modulating effect of resveratrol was partially attributable to its inhibition of paclitaxel-induced G(2)/M cell cycle arrest, together with an accumulation of cells in the S-phase. In addition, resveratrol could suppress paclitaxel-induced accumulation of reactive oxygen species (ROS) and subsequently the inactivation of anti-apoptotic Bcl-2 family proteins. These observations suggest that the strategy of concomitant use of resveratrol with paclitaxel is detrimental in certain types of human cancers. Given the widespread use of resveratrol among cancer patients, this study calls for more preclinical and clinical testing of the potential benefits and harms of using resveratrol as a dietary adjuvant in cancer patients.


Comments, anyone?





Comment, If you have Cancer throw out your Resveratrol, the study suggests Resveratrol deactivates Taxol chemotherapy efficacy in certain Cell lines.

We might be able to say, AVOID Taking any ANTIOXIDANTS or VITAMINS if we have Cancer.


Not so fast. It depends on the strain of cancer. There are many. Most respond. Some do not. It depends on which mutated pathways a particular cell line is vulnerable to, or depends on, and which ones resveratrol activates or blocks. Small cell lung cancer does not respond to resveratrol, though it does not seem to exacerbate it. Many if not all breast cancer cell lines respond, and perhaps prostate cancer does as well -- there seems to be some in vitro evidence. Vitamin C antagonizes the action of some cancer treatments, yet IV vitamin C kills other types of cancer, Perhaps taking a biopsy of the cancer cells, and testing them in the lab, will be the way to go.


I know that prostate cancer is killed by IV Vitamin C. Brightspot.org does this day and night.

The thought occurred to me that this study just might be flawed. It happens. Later reports might prove this one wrong. Then again cancer isn't a single disease nor are the various strains which attack an organ so it's entirely possible Resveratrol use will have to be evaluated for each cell line.

Now one question is would the people in the study be better off taking the Taxol chemo or high doses of Resveratrol?


I just got my labs back. It appears that the 800 mg. a day of RESV in Longev* as suggested by Bill Sard1 was a bad idea. My PSA, which had been declining with the Vitamin C IVs and the IP6+Inositol rose by 27% with the 800 mg. Longev* RESV. I've only been on 3 grams of the Nitro 250 RESV and MCT Quercetin for 11 days but I agree with Maxwatt about the Quercetin being a bad idea.

Maxwatt, can I get enough curcumin into my blood stream to prevent sulphonation of RESV? I'm looking at taking 12 grams of curcumin ??dissolved?? in hot coconut milk then cooled down. I'd switch to just micronized Resveratrol, which I might mix into the coconut milk. Since whole milk and whey protein have been used as dispersal agents for RESV, it seems to me I can kill two birds with one stone and mix, say 5 grams of micronized RESV into the hot coconut milk. Any thoughts? Also, I'm searching for which CYP enzyme sulphonates RESV but I'm coming up dry. Would you know which CYP enzyme it is, Maxwatt?

Any clues on how much RESV taken at a time would swamp the liver's ability to sulphonate it?



Here's a patent application for curcumin and resveratrol I came upon. It specifically mentions prostate cancer and PSA.

Patent application title: PHARMACEUTICAL COMPOSITION COMPRISING CURCUMIN AND RESVERATROL AND USES THEREOF IN MEDICAL FIELD
Inventors: Damiano Turini Stefan Coccoloni
Agents: YOUNG & THOMPSON
Assignees:
Origin: ALEXANDRIA, VA US
IPC8 Class: AA61K3112FI
USPC Class: 424765


Probably a gram or more of resveratrol would overcome sulfonation to some degree, but blood levels do not increase linearly with doses beyond one gram, perhaps to saturation of a transport mechanism.

This was posted here a few years ago, and shows which sulfotransferases sulfonate resveratrol:

(exerpt) Xenobiotica. 2005 Dec;35(12):1101-19.
Sulfation of resveratrol in human liver: evidence of a major role for the sulfotransferases SULT1A1 and SULT1E1……
Sulfation of resveratrol, a polyphenolic compound present in grapes and wine with anticancer and cardioprotective activities, was studied in human liver cytosol. In the presence of 3'-phosphoadenosine-5'-phosphosulfate, three metabolites (M1-3) whose structures were identified by mass spectrometry and NMR as trans-resveratrol-3-O-sulfate, trans-resveratrol-4'-O-sulfate, and trans-resveratrol-3-O-4'-O-disulfate, respectively. ……. Incubation in the presence of human recombinant sulfotransferases (SULTs) demonstrated that M1 is almost exclusively catalysed by SULT1A1 and only to a minor extent by SULT 1A2, 1A3 and 1E1, whereas M2 is selectively formed by SULT1A2. M3 is mainly catalysed by SULT1A2 and 1A3. …………PMID: 16418064



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#3 ppp

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Posted 18 March 2010 - 07:58 AM

I just got my labs back. It appears that the 800 mg. a day of RESV in Longev* as suggested by Bill Sard1 was a bad idea. My PSA, which had been declining with the Vitamin C IVs and the IP6+Inositol rose by 27% with the 800 mg. Longev* RESV. I've only been on 3 grams of the Nitro 250 RESV and MCT Quercetin for 11 days but I agree with Maxwatt about the Quercetin being a bad idea.

Maxwatt, can I get enough curcumin into my blood stream to prevent sulphonation of RESV? I'm looking at taking 12 grams of curcumin ??dissolved?? in hot coconut milk then cooled down. I'd switch to just micronized Resveratrol, which I might mix into the coconut milk. Since whole milk and whey protein have been used as dispersal agents for RESV, it seems to me I can kill two birds with one stone and mix, say 5 grams of micronized RESV into the hot coconut milk. Any thoughts? Also, I'm searching for which CYP enzyme sulphonates RESV but I'm coming up dry. Would you know which CYP enzyme it is, Maxwatt?

Any clues on how much RESV taken at a time would swamp the liver's ability to sulphonate it?


Have you considered the LongVida form of curcumin? Technically it's called a Solid Lipid Curcumin Particle Formulation. Developed at UCLA it has been shown to offer very high bioavailability compared to other forms of curcumin. It's available from a number of suppliers now. Check out longvida.com for more details. Alternatively there is good evidence that curcumin becomes more bioavailable in the presence of omega-3 fish oils.

#4 Anthony_Loera

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Posted 18 March 2010 - 09:17 AM

How does it compare to BCM-95 BioCurcumin with 7 times the absorption of regular curcumin? (yes it's the stuff we use in our products as well)

Published Studies:
1. Human Clinical Study to evaluate the bioavailability of BCM-95 (Published: September 2006
Spice India pg 11-16)
2. A Pilot Cross-Over Study to evaluate human oral bioavailability of BCM-95, A Novel
Bioenhanced Preperation of Curcumin (Published: Indian Journal of Pharmaceutical Sciences
July-Aug 2008 pg 445-450)
3. Six-Month Randomized Placebo-Controlled, Double-Blind, Pilot Clinical Trial of Curcumin in
Patients with Alzheimers Disease (Published: Journal of Clinical Psychopharmacology, Vol 28,
Number 1, Feb 2008 pg 110-114)
4. Curcumin effects on Blood Lipid profile in a 6-month human Study (Published: Elsevier
Pharmacological Research 56(2007) pg 509-514)


Can you provide the UCLA study please so that we can compare the two?
I believe BCM-95 is the best, however If we are not using the best form of Curcumin in our products, I simply need to know.

So a comparison is in order I believe, thanks.

Edited by Anthony_Loera, 18 March 2010 - 09:23 AM.


#5 ppp

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Posted 18 March 2010 - 02:47 PM

How does it compare to BCM-95 BioCurcumin with 7 times the absorption of regular curcumin? (yes it's the stuff we use in our products as well)

Published Studies:
1. Human Clinical Study to evaluate the bioavailability of BCM-95 (Published: September 2006
Spice India pg 11-16)
2. A Pilot Cross-Over Study to evaluate human oral bioavailability of BCM-95, A Novel
Bioenhanced Preperation of Curcumin (Published: Indian Journal of Pharmaceutical Sciences
July-Aug 2008 pg 445-450)
3. Six-Month Randomized Placebo-Controlled, Double-Blind, Pilot Clinical Trial of Curcumin in
Patients with Alzheimers Disease (Published: Journal of Clinical Psychopharmacology, Vol 28,
Number 1, Feb 2008 pg 110-114)
4. Curcumin effects on Blood Lipid profile in a 6-month human Study (Published: Elsevier
Pharmacological Research 56(2007) pg 509-514)


Can you provide the UCLA study please so that we can compare the two?
I believe BCM-95 is the best, however If we are not using the best form of Curcumin in our products, I simply need to know.

So a comparison is in order I believe, thanks.


Take a look at this recent paper:

J Agric Food Chem. 2010 Feb 24;58(4):2095-9.
Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.

Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG.

ACTREC, Tata Memorial Centre, Sector-22, Kharghar, Navi Mumbai 410210, India. vgota@actrec.gov.in

Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients. Doses of 2, 3, and 4 g of SLCP were evaluated in 11 patients with osteosarcoma. Plasma curcumin levels were measured using a validated high-performance liquid chromatography method. The limit of detection of the assay was 1 ng/mL of curcumin. In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected. In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics. Overall, good tolerability was noted in both healthy and osteosarcoma groups.


There is also a UCLA paper on Alzheimers that mentions the higher availability of LongVida, but I don't have it to hand.

#6 browser

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Posted 18 March 2010 - 10:27 PM

Probably a gram or more of resveratrol would overcome sulfonation to some degree, but blood levels do not increase linearly with doses beyond one gram, perhaps to saturation of a transport mechanism.

This was posted here a few years ago, and shows which sulfotransferases sulfonate resveratrol:


Looks to me like I want to inhibit sulphonation with aspirin.

( From the link ): Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum……………. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum) . 5. PMID: 10923862

Aspirin is highly bio-available and it's main metabolite is salicylic acid. OK, 4 1/2 times more salicylic acid is required than Quercetin. But Quercetin isn't very bio-available. By my calculations, two adult aspirins 15 minutes ahead of time would be overkill.

Edited by browser, 18 March 2010 - 10:30 PM.


#7 browser

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Posted 18 March 2010 - 11:31 PM

How does it compare to BCM-95 BioCurcumin with 7 times the absorption of regular curcumin? (yes it's the stuff we use in our products as well)

Published Studies:
1. Human Clinical Study to evaluate the bioavailability of BCM-95 (Published: September 2006
Spice India pg 11-16)
2. A Pilot Cross-Over Study to evaluate human oral bioavailability of BCM-95, A Novel
Bioenhanced Preperation of Curcumin (Published: Indian Journal of Pharmaceutical Sciences
July-Aug 2008 pg 445-450)
3. Six-Month Randomized Placebo-Controlled, Double-Blind, Pilot Clinical Trial of Curcumin in
Patients with Alzheimers Disease (Published: Journal of Clinical Psychopharmacology, Vol 28,
Number 1, Feb 2008 pg 110-114)
4. Curcumin effects on Blood Lipid profile in a 6-month human Study (Published: Elsevier
Pharmacological Research 56(2007) pg 509-514)


Can you provide the UCLA study please so that we can compare the two?
I believe BCM-95 is the best, however If we are not using the best form of Curcumin in our products, I simply need to know.

So a comparison is in order I believe, thanks.


The LongVida website is amazingly cagey and snide. It takes pot shots at BCM-95's tumeric oils, takes pot shots at bioperine, but refuses to mention how powerful it is, saying, well, that's difficult to measure and say. One of the sellers claims it's 65 times as powerful as 95% curcumin.

I'm struggling trying to find the meat in LongVida's patent.

#8 maxwatt

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Posted 19 March 2010 - 12:47 AM

How does it compare to BCM-95 BioCurcumin with 7 times the absorption of regular curcumin? (yes it's the stuff we use in our products as well)

Published Studies:
1. Human Clinical Study to evaluate the bioavailability of BCM-95 (Published: September 2006
Spice India pg 11-16)
2. A Pilot Cross-Over Study to evaluate human oral bioavailability of BCM-95, A Novel
Bioenhanced Preperation of Curcumin (Published: Indian Journal of Pharmaceutical Sciences
July-Aug 2008 pg 445-450)
3. Six-Month Randomized Placebo-Controlled, Double-Blind, Pilot Clinical Trial of Curcumin in
Patients with Alzheimers Disease (Published: Journal of Clinical Psychopharmacology, Vol 28,
Number 1, Feb 2008 pg 110-114)
4. Curcumin effects on Blood Lipid profile in a 6-month human Study (Published: Elsevier
Pharmacological Research 56(2007) pg 509-514)


Can you provide the UCLA study please so that we can compare the two?
I believe BCM-95 is the best, however If we are not using the best form of Curcumin in our products, I simply need to know.

So a comparison is in order I believe, thanks.


The LongVida website is amazingly cagey and snide. It takes pot shots at BCM-95's tumeric oils, takes pot shots at bioperine, but refuses to mention how powerful it is, saying, well, that's difficult to measure and say. One of the sellers claims it's 65 times as powerful as 95% curcumin.

I'm struggling trying to find the meat in LongVida's patent.

Looks like you dissolve curcumin in an oil, add to water, and beat it in a blender until there are microscopic droplets of curcumin bearing oil.

#9 browser

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Posted 19 March 2010 - 02:35 AM

How does it compare to BCM-95 BioCurcumin with 7 times the absorption of regular curcumin? (yes it's the stuff we use in our products as well)

Published Studies:
1. Human Clinical Study to evaluate the bioavailability of BCM-95 (Published: September 2006
Spice India pg 11-16)
2. A Pilot Cross-Over Study to evaluate human oral bioavailability of BCM-95, A Novel
Bioenhanced Preperation of Curcumin (Published: Indian Journal of Pharmaceutical Sciences
July-Aug 2008 pg 445-450)
3. Six-Month Randomized Placebo-Controlled, Double-Blind, Pilot Clinical Trial of Curcumin in
Patients with Alzheimers Disease (Published: Journal of Clinical Psychopharmacology, Vol 28,
Number 1, Feb 2008 pg 110-114)
4. Curcumin effects on Blood Lipid profile in a 6-month human Study (Published: Elsevier
Pharmacological Research 56(2007) pg 509-514)


Can you provide the UCLA study please so that we can compare the two?
I believe BCM-95 is the best, however If we are not using the best form of Curcumin in our products, I simply need to know.

So a comparison is in order I believe, thanks.


The LongVida website is amazingly cagey and snide. It takes pot shots at BCM-95's tumeric oils, takes pot shots at bioperine, but refuses to mention how powerful it is, saying, well, that's difficult to measure and say. One of the sellers claims it's 65 times as powerful as 95% curcumin.

I'm struggling trying to find the meat in LongVida's patent.

Looks like you dissolve curcumin in an oil, add to water, and beat it in a blender until there are microscopic droplets of curcumin bearing oil.

And add an anti-oxidant like ascorbate. I can do that. Now what to do with the lab stuff I was going to use to make curcumin in Jello? I guess I could try making Resveratrol in Jello instead.

#10 niner

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Posted 19 March 2010 - 03:03 AM

Take a look at this recent paper:

J Agric Food Chem. 2010 Feb 24;58(4):2095-9.
Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.

Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG.

ACTREC, Tata Memorial Centre, Sector-22, Kharghar, Navi Mumbai 410210, India. vgota@actrec.gov.in

Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients. Doses of 2, 3, and 4 g of SLCP were evaluated in 11 patients with osteosarcoma. Plasma curcumin levels were measured using a validated high-performance liquid chromatography method. The limit of detection of the assay was 1 ng/mL of curcumin. In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected. In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics. Overall, good tolerability was noted in both healthy and osteosarcoma groups.

Browser, the above paper found a peak plasma curcumin level of 22.4ng/ml using 650mg of a formulated curcumin. That gives you some idea of bioavailability, but the peak level is only achieved momentarily. If you want to inhibit SULT1A1 long enough to have an effect on resveratrol metabolism, you will need to have a concentration of curcumin that is above the IC50 of curcumin for SULT1A1. The gut sulfotransferases may actually be the most important here; the IC50 of curcumin for these is 25 nM. For resveratrol, 1ng/ml = 4.4 nM. The formulated curcumin is in the ballpark of being a plausible inhibitor of resveratrol metabolism, but without much room to spare. The showed a peak of 98 nM with 650 mg of SLCP. Because the peak concentration is so peaky, it probably would not be high enough for long enough to do much good, though for a little while it would be well over the 25nM IC50. If you used several grams of curcumin, and it was a good formulation, it just might work.

Xenobiotica. 2003 Apr;33(4):357-63.

Curcumin is a potent inhibitor of phenol sulfotransferase (SULT1A1) in human liver and extrahepatic tissues.

Vietri M, Pietrabissa A, Mosca F, Spisni R, Pacifici GM.

Department of Neurosciences, Section of Pharmacology, Medical School, Via Roma 55, I-56126 Pisa, Italy.

1. Curcumin has anti-carcinogen effects and is under clinical evaluation as a potential colon cancer chemopreventive agent. The first aim was to see whether curcumin inhibited phenol sulfotransferase (SULT1A1) and, if so, to study the variability of the IC(50) of curcumin for SULT1A1 in 50 human liver samples. For comparative purposes, the inhibition of catechol sulfotransferase (SULT1A3) in five human liver specimens was studied. The second aim was to measure the IC(50) of curcumin against SULT1A1 in five samples of human duodenum, colon, kidney and lung. 2. Curcumin was a potent inhibitor of SULT1A1 in human liver; the mean +/- SD and median of IC(50) were 14.1 +/- 7.3 nM and 12.8 nM, respectively. The IC(50) ranged from 6.2 to 30.6 nM between the 5th and 95th percentiles and the fold of variation was 4.9. The distribution of IC(50) was positively skewed (skewness 1.2) and deviated from normality (p = 0.0004). 3. Curcumin inhibited human SULT1A3, and the inhibition was studied in five liver specimens with an IC(50) of 4324 +/- 1026 nM. This inhibition was greater than the IC(50) of curcumin for SULT1A1 (p < 0.0001). 4. In the extrahepatic tissues, the IC(50) of curcumin for SULT1A1 was 25.9 +/- 4.8 nM (duodenum), 25.4 +/- 6.8 nM (colon), 23.4 +/- 2.2 nM (kidney) and 25.6 +/- 5.6 nM (lung). Inhibition in these tissues is greater than that of curcumin for SULT1A1 in human liver (p < 0.0001). 5. In conclusion, curcumin is a potent inhibitor of SULT1A1 in human liver, duodenum, colon, kidney and lung. The IC(50) of curcumin for SULT1A1 varied 4.9-fold in human liver. The comparison of the present data with those of the literature revealed that the IC(50) of curcumin in the liver and extrahepatic tissues is one order of magnitude lower that the peak serum concentration of curcumin after therapeutic doses of 4 g to humans.

PMID: 12745871



#11 niner

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Posted 19 March 2010 - 03:24 AM

Probably a gram or more of resveratrol would overcome sulfonation to some degree, but blood levels do not increase linearly with doses beyond one gram, perhaps to saturation of a transport mechanism.

This was posted here a few years ago, and shows which sulfotransferases sulfonate resveratrol:


Looks to me like I want to inhibit sulphonation with aspirin.

( From the link ): Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum……………. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum) . 5. PMID: 10923862

Aspirin is highly bio-available and it's main metabolite is salicylic acid. OK, 4 1/2 times more salicylic acid is required than Quercetin. But Quercetin isn't very bio-available. By my calculations, two adult aspirins 15 minutes ahead of time would be overkill.

Not 4 1/2 times more; 4.5 Million times more. pM = picomolar; pico = 1e-12, micro = 1e-6. Two adult aspirin might be about right though. We talked about this at some length a couple years ago. The conversation starts around here in the mother of all resveratrol threads. Note the enhanced possibility of GI bleeds from mixing aspirin and resveratrol, along with the possibility of suppressing that problem discussed there.

#12 browser

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Posted 19 March 2010 - 03:39 AM

Take a look at this recent paper:

J Agric Food Chem. 2010 Feb 24;58(4):2095-9.
Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.

Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG.

ACTREC, Tata Memorial Centre, Sector-22, Kharghar, Navi Mumbai 410210, India. vgota@actrec.gov.in

Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients. Doses of 2, 3, and 4 g of SLCP were evaluated in 11 patients with osteosarcoma. Plasma curcumin levels were measured using a validated high-performance liquid chromatography method. The limit of detection of the assay was 1 ng/mL of curcumin. In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected. In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics. Overall, good tolerability was noted in both healthy and osteosarcoma groups.

Browser, the above paper found a peak plasma curcumin level of 22.4ng/ml using 650mg of a formulated curcumin. That gives you some idea of bioavailability, but the peak level is only achieved momentarily. If you want to inhibit SULT1A1 long enough to have an effect on resveratrol metabolism, you will need to have a concentration of curcumin that is above the IC50 of curcumin for SULT1A1. The gut sulfotransferases may actually be the most important here; the IC50 of curcumin for these is 25 nM. For resveratrol, 1ng/ml = 4.4 nM. The formulated curcumin is in the ballpark of being a plausible inhibitor of resveratrol metabolism, but without much room to spare. The showed a peak of 98 nM with 650 mg of SLCP. Because the peak concentration is so peaky, it probably would not be high enough for long enough to do much good, though for a little while it would be well over the 25nM IC50. If you used several grams of curcumin, and it was a good formulation, it just might work.

Xenobiotica. 2003 Apr;33(4):357-63.

Curcumin is a potent inhibitor of phenol sulfotransferase (SULT1A1) in human liver and extrahepatic tissues.

Vietri M, Pietrabissa A, Mosca F, Spisni R, Pacifici GM.

Department of Neurosciences, Section of Pharmacology, Medical School, Via Roma 55, I-56126 Pisa, Italy.

1. Curcumin has anti-carcinogen effects and is under clinical evaluation as a potential colon cancer chemopreventive agent. The first aim was to see whether curcumin inhibited phenol sulfotransferase (SULT1A1) and, if so, to study the variability of the IC(50) of curcumin for SULT1A1 in 50 human liver samples. For comparative purposes, the inhibition of catechol sulfotransferase (SULT1A3) in five human liver specimens was studied. The second aim was to measure the IC(50) of curcumin against SULT1A1 in five samples of human duodenum, colon, kidney and lung. 2. Curcumin was a potent inhibitor of SULT1A1 in human liver; the mean +/- SD and median of IC(50) were 14.1 +/- 7.3 nM and 12.8 nM, respectively. The IC(50) ranged from 6.2 to 30.6 nM between the 5th and 95th percentiles and the fold of variation was 4.9. The distribution of IC(50) was positively skewed (skewness 1.2) and deviated from normality (p = 0.0004). 3. Curcumin inhibited human SULT1A3, and the inhibition was studied in five liver specimens with an IC(50) of 4324 +/- 1026 nM. This inhibition was greater than the IC(50) of curcumin for SULT1A1 (p < 0.0001). 4. In the extrahepatic tissues, the IC(50) of curcumin for SULT1A1 was 25.9 +/- 4.8 nM (duodenum), 25.4 +/- 6.8 nM (colon), 23.4 +/- 2.2 nM (kidney) and 25.6 +/- 5.6 nM (lung). Inhibition in these tissues is greater than that of curcumin for SULT1A1 in human liver (p < 0.0001). 5. In conclusion, curcumin is a potent inhibitor of SULT1A1 in human liver, duodenum, colon, kidney and lung. The IC(50) of curcumin for SULT1A1 varied 4.9-fold in human liver. The comparison of the present data with those of the literature revealed that the IC(50) of curcumin in the liver and extrahepatic tissues is one order of magnitude lower that the peak serum concentration of curcumin after therapeutic doses of 4 g to humans.

PMID: 12745871


Thanks. I've been wanting this information. I chilled on the idea of using Curcumin to protect Resveratrol because of bioavailability. I'm still not convinced. Even with taking a few grams of this LongVida or making my own based on what I glean from the patent. The UCLA study on the LongVida also said that

In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics.

This sounds to me like a CYA for their not getting the formulation all that good after all. But whatever, there's no way of knowing if I'm going to be the lucky one to get a high sustained level of curcumin, high enough to prevent sulphonation of the Resveratrol. No one has challenged my observation that I could also use aspirin to inhibit sulphonation of the Resveratrol. Best I use Resveratrol, the most bio-available curcumin I can buy but prefer to make and two adult aspirins.

#13 Anthony_Loera

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Posted 19 March 2010 - 01:22 PM

Hmmm...

From the BCM-95 clinical study:

The product at 2 g/ day levels was well tolerated by all the volunteers who had participated in the study without even mild adverse reactions. The method of estimation of curcumin from blood plasma was validated by doing the recovery (80%) analysis. The peaks obtained for the curcumin reference standard as well as curcumin from the blood plasma were matched and typical plasma sample profile is shown in fig. 1. The concentration time profile of control curcumin versus BCM-95ÆCG (BiocurcumaxTM) is shown in fig. 2 and that of curcumin-lecithin-piperine versus BCM-95ÆCG (BiocurcumaxTM) is shown in fig. 3. The values were analysed statistically by Anova and the difference shown by test and control groups were significant (P<0.05). As evident from fig. 2 the absorption of curcumin was faster from BCM- 95ÆCG (BiocurcumaxTM) peaking in the first hour (mean 315.8 ng/g). This value dropped a bit during the succeeding hour at 274.6 ng/g and then reached the maximum at 4.5 h (456.88 ng/g). Thereafter the values gradually decreased. However, even at 8 h some residual curcumin remained in the blood. In contrast, the absorption of control curcumin was relatively slower, peaking at 2 h (149.8 ng/g) and then virtually disappeared from the blood by 4.5 h.


So peak dose from
SLCP was 22.43 ng/ml from 650mg
BCM-95 was 456.88.ng/g from 2000mg

Now since the density (am please correct me if I am wrong) should be the same as both are measuring curcumin in the blood so the conversion from ng/ml to ng/g is probably 1:1, doesn't BCM-95 still beat SLCP by around 5x or 6x?

I am trying to figure this out, since we may change our curcumin in the next batch if absorption is higher. Besides I am horrible at conversions so I maybe completely off on my estimates.

Cheers
A

Edited by Anthony_Loera, 19 March 2010 - 01:24 PM.


#14 niner

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Posted 19 March 2010 - 02:17 PM

From the BCM-95 clinical study:

The product at 2 g/ day levels was well tolerated by all the volunteers who had participated in the study without even mild adverse reactions. The method of estimation of curcumin from blood plasma was validated by doing the recovery (80%) analysis. The peaks obtained for the curcumin reference standard as well as curcumin from the blood plasma were matched and typical plasma sample profile is shown in fig. 1. The concentration time profile of control curcumin versus BCM-95ÆCG (BiocurcumaxTM) is shown in fig. 2 and that of curcumin-lecithin-piperine versus BCM-95ÆCG (BiocurcumaxTM) is shown in fig. 3. The values were analysed statistically by Anova and the difference shown by test and control groups were significant (P<0.05). As evident from fig. 2 the absorption of curcumin was faster from BCM- 95ÆCG (BiocurcumaxTM) peaking in the first hour (mean 315.8 ng/g). This value dropped a bit during the succeeding hour at 274.6 ng/g and then reached the maximum at 4.5 h (456.88 ng/g). Thereafter the values gradually decreased. However, even at 8 h some residual curcumin remained in the blood. In contrast, the absorption of control curcumin was relatively slower, peaking at 2 h (149.8 ng/g) and then virtually disappeared from the blood by 4.5 h.

So peak dose from
SLCP was 22.43 ng/ml from 650mg
BCM-95 was 456.88.ng/g from 2000mg

Now since the density (am please correct me if I am wrong) should be the same as both are measuring curcumin in the blood so the conversion from ng/ml to ng/g is probably 1:1, doesn't BCM-95 still beat SLCP by around 5x or 6x?

Anthony, this report doesn't make sense to me. The talk about "absorption" peaking in the first hour, but then reaching a maximum at 4.5 hours. This doesn't sound like they are reporting a plasma level. They report the absorption of control curcumin peaking at 149.8 ng/g. By this measure, the BCM-95 is only a few times better than control. It just isn't clear to me what they're measuring here, but I'm pretty sure it's not comparable to the SLCP number.

#15 Anthony_Loera

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Posted 19 March 2010 - 02:41 PM

niner,

thanks for the post, and...now I am confused. :p

I got the info from here:
http://www.bcm95.com...-Over-Study.pdf

I think it's length of time then in the blood...not absorption? hmmm... yup I guess I read that tooooo fast for my own good.

Cheers
A

Edited by Anthony_Loera, 19 March 2010 - 02:46 PM.


#16 browser

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Posted 20 March 2010 - 03:27 PM

How does it compare to BCM-95 BioCurcumin with 7 times the absorption of regular curcumin? (yes it's the stuff we use in our products as well)

Published Studies:
1. Human Clinical Study to evaluate the bioavailability of BCM-95 (Published: September 2006
Spice India pg 11-16)
2. A Pilot Cross-Over Study to evaluate human oral bioavailability of BCM-95, A Novel
Bioenhanced Preperation of Curcumin (Published: Indian Journal of Pharmaceutical Sciences
July-Aug 2008 pg 445-450)
3. Six-Month Randomized Placebo-Controlled, Double-Blind, Pilot Clinical Trial of Curcumin in
Patients with Alzheimers Disease (Published: Journal of Clinical Psychopharmacology, Vol 28,
Number 1, Feb 2008 pg 110-114)
4. Curcumin effects on Blood Lipid profile in a 6-month human Study (Published: Elsevier
Pharmacological Research 56(2007) pg 509-514)


Can you provide the UCLA study please so that we can compare the two?
I believe BCM-95 is the best, however If we are not using the best form of Curcumin in our products, I simply need to know.

So a comparison is in order I believe, thanks.


The LongVida website is amazingly cagey and snide. It takes pot shots at BCM-95's tumeric oils, takes pot shots at bioperine, but refuses to mention how powerful it is, saying, well, that's difficult to measure and say. One of the sellers claims it's 65 times as powerful as 95% curcumin.

I'm struggling trying to find the meat in LongVida's patent.

Looks like you dissolve curcumin in an oil, add to water, and beat it in a blender until there are microscopic droplets of curcumin bearing oil.


Here are the things I find important and useful in the patent.

[0010] Three factors limit curcumin absorption and need to be addressed: 1) rapid glucuronidation/sulfation of curcumin's phenolic hydroxy! groups and high "first pass" clearance; T) curcumin is unstable in aqueous solution at pH 7 and above; and 3) curcumin is very hydrophobic and typically is not water soluble at acidic pH and when delivered as a dry powder in existing supplements. (Most of the curcumin is never absorbed and simply passes through the GI tract and is excreted.)


Perhaps my intended chemistry experiment to dissolve Curcumin in water/NaOH with pH of 9 (curcumin is soluble at a pH of 8.5), add gelatin then lower the pH isn't an optimal idea.

[0043] Efficacy. In vivo data acquired by administering to mice curcumin freshly dissolved in base (0.5M NaOH) and rapidly diluted into neutralizing PBS [phosphate buffered saline -- my addition] (where it is unstable) and delivered immediately via gavage or by i.p. or i.m. showed that plasma levels in the 0.25-0.5 micromolar range gave brain levels sufficient to give IC50's for -50% inhibition of pro-inflammatory EL-IB, iNOS and a cell death-related MAP kinase (active c- jun kinase (p)JNK).

Curcumin is very hydrophobic and typically is not dissolved when delivered as a powder extract in common nutraceuticals. Most curcumin activities require 100-2,000 nanomolar (0.1-2 micromolar) levels in vitro, but current supplements result in negligible, low nanomolar blood levels (see Sharma et al., 2004

[0044] For comparison, on a drug wt/ kG body weight basis, which generally exaggerates human doses, this is 1 mg/ 3Og= 33.3 mg/ kG and translates to ~ 2.5 gms per 75kG person, which is well within the range given to patients in clinical trials. [0045] Thus, one example of a practical formulation combining all 3 principles (solubilization with lipid, protection with antioxidant, and competitive inhibition and synergy with tetrahydrocurcumin), for humans would be 165 mg curcumin, 165 mg tetrahydrocurcumin, 17.7 mg of stabilizing antioxidant ( ascorbate, lipoate, NAC, GSH etc)

Formula 3. Olive oil/DHA curcumin

Curcumin, docosahexaenoic acid, an antioxidant or antioxidant mix (vitamin C or lipodated vitamin C, alpha lipoic acid, vitamin E). Our data shows that when curcumin is dissolved in oil, plasma curcumin remains low, but red blood cell curcumin is quite high, which explains bioavailability despite negligible plasma levels. No other group has reported this fundamental observation that appears to be the simplest method of enhancing bioavailability.

Other healthful oils can be used (fish oil, canola oil, other high omega-3 oil). In this formulation, curcumin in oil can be microencapsulated.





The tetrahydrocurcumin is used to prevent sulphonation. I've already established

Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum……………. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. PMID: 10923862


that two adult aspirin, which I took 20 minutes before taking my 12 Nitro 250 capsules sans 12 MCT Quercetin this morning, can inhibit sulfphonation of Resveratrol. An anti-oxidant (like Vitamin C) is used to prevent glyconation.

I conclude that I can make the following:

1) A solution of Resveratrol (non-micronized) and Curcumin in water made alkaline to a pH of 9 with NaoH. Add gelatin for dispersal. Add Vitamin C, two aspirin and enough acetic acid to make the slurry neutral.

OR

2) A solution made with (perhaps non-micronized) Resveratrol, Curcumin, Vitamin C and aspirin in olive oil whirled in a home blender for 10+ minutes.

I'm suggesting non-micronized Resveratrol to lower cost. If the Resveratrol dissolves in the solutions (then precipitates out in the first solution) it doesn't matter if I use micronized at $2.5 a gram from Revg* or non-micronized $1 a gram Resveratrol from Vitaspace. Since there's a transport issue at around 5 grams, if I want to take more, it's best if I down one of these two solutions twice a day and supplement with buccal Resveratrol.

Why not just by Revg* or LongVida's bio-available Curcumin? Curcumin is currently available from Vitaspace at $0.14 a gram if bought in 1 kg. quantities. Revg*'s Curcumin costs $1.20 a gram. LongVida's Curcumin costs $1.50 a gram. I'm looking at taking 12 grams a day (woe to my GI tract). I'm aiming at using non-micronized Resveratrol if I can get a nice oil solution or very finely divided precipitate in a gelatin slurry. If I can make the solution cheaply, I can prepare and down it multiple times a day without having to rob a banker of his 'performance' bonus.

In either case I'm going to have a massive case of diarrhea and I'll have to get used to yellow everything once again.

BTW, I researched Stephen Martin, Ph.D.'s suggestion to dissolve Curcumin in coconut milk because the Curcumin will go directly into the lymphatic system then into the bloodstream. There are two arguments against this. One, coconut oil, which comprises 70% of coconut milk, doesn't have an affinity for Curcumin. Second, coconut oil contains MCTs. These aren't absorbed by the lymphatic system. They go the normal route into the liver like other things taken down the gullet.

Maxwatt, the talk of using Curcumin in place of Quercetin to prevent sulphonation, finding not enough Curcumin is absorbed to do this, my decision to use aspirin instead and the discussion on how to increase Curcumin and perhaps Resveratrol's bioavailablity might be off topic enough to be a separate thread. Perhaps these posts could be part of the Maximizing Resveratrol Effectiveness, How/when to take? thread?


Edited by browser, 20 March 2010 - 03:42 PM.


#17 niner

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Posted 22 March 2010 - 03:42 AM

The tetrahydrocurcumin is used to prevent sulphonation. I've already established

Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum……………. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. PMID: 10923862

that two adult aspirin, which I took 20 minutes before taking my 12 Nitro 250 capsules sans 12 MCT Quercetin this morning, can inhibit sulfphonation of Resveratrol. An anti-oxidant (like Vitamin C) is used to prevent glyconation.

I've not heard of vitamin C (or antioxidants in general) inhibiting what I presume is glucuronidation; I suspect this is wrong. We should probably be more careful with terminology here, since glycation is very different from glucuronidation, and sulfonation is very different from sulfation. The phase II metabolic enzymes that are eating up the compounds we care about are engaged in glucuronidation and sulfation.

I conclude that I can make the following:

1) A solution of Resveratrol (non-micronized) and Curcumin in water made alkaline to a pH of 9 with NaoH. Add gelatin for dispersal. Add Vitamin C, two aspirin and enough acetic acid to make the slurry neutral.

OR

2) A solution made with (perhaps non-micronized) Resveratrol, Curcumin, Vitamin C and aspirin in olive oil whirled in a home blender for 10+ minutes.

I prefer option 2. With option 1, you run a risk of chemical degradation, and I suspect the gelatin would fall apart. I would pre-treat with the aspirin in advance of the resveratrol, so your blood levels are already up. You might want to look up the pharmacokinetics of aspirin, and see what the tmax is, then take it that amount of time (or a bit less) before the resveratrol. You'll also want to ascertain that you are actually getting concentrations of salicylic acid (which will require deacetylation of the aspirin=acetylsalicylic acid) that are significantly above the IC50 for sulfation inhibition. I continue to think that if the picomolar IC50 for quercetin is really right, that it should be simple to hit that level, even if the bioavailability of quercetin is lousy. 1pM is one millionth of 1 microM.

BTW, I researched Stephen Martin, Ph.D.'s suggestion to dissolve Curcumin in coconut milk because the Curcumin will go directly into the lymphatic system then into the bloodstream. There are two arguments against this. One, coconut oil, which comprises 70% of coconut milk, doesn't have an affinity for Curcumin. Second, coconut oil contains MCTs. These aren't absorbed by the lymphatic system. They go the normal route into the liver like other things taken down the gullet.

I'm a little surprised that curcumin wouldn't go into coconut oil. It's pretty darn hydrophobic, but longer chain oils are more hydrophobic. I didn't know that MCTs bypass lymphatic transport. Olive oil is probably a better choice.

Maxwatt, the talk of using Curcumin in place of Quercetin to prevent sulphonation, finding not enough Curcumin is absorbed to do this, my decision to use aspirin instead and the discussion on how to increase Curcumin and perhaps Resveratrol's bioavailablity might be off topic enough to be a separate thread. Perhaps these posts could be part of the Maximizing Resveratrol Effectiveness, How/when to take? thread?

This could certainly be a separate thread, though it would just get lost in one of the resveratrol black hole threads. Better to be on its own.

#18 maxwatt

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Posted 22 March 2010 - 10:23 AM

This topic has been split from "Resveratrol attenuates paclitaxel activity?"

Much of the discussion here includes information in this thread: http://www.imminst.o...&...st&p=390697

#19 maxwatt

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Posted 22 March 2010 - 11:43 PM

LEF markets a curcumin claimed to attain higher blood levels by virture of including some turmeric, containing other compounds from the plant that are not in the pure extract. They cited in their ad copy a study showing better absorption. It is possible that sacrificial inhibition by some of these compounds results in higher blood levels.

#20 browser

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Posted 23 March 2010 - 12:30 AM

Probably a gram or more of resveratrol would overcome sulfonation to some degree, but blood levels do not increase linearly with doses beyond one gram, perhaps to saturation of a transport mechanism.

This was posted here a few years ago, and shows which sulfotransferases sulfonate resveratrol:


Looks to me like I want to inhibit sulphonation with aspirin.

( From the link ): Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum……………. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum) . 5. PMID: 10923862

Aspirin is highly bio-available and it's main metabolite is salicylic acid. OK, 4 1/2 times more salicylic acid is required than Quercetin. But Quercetin isn't very bio-available. By my calculations, two adult aspirins 15 minutes ahead of time would be overkill.


Mea culpa. I didn't pay attention to the different scales. Yes, pico 1 million times less needed to prevent sulphanation of Resveratrol in the liver and gut than salicylic acid. I'm still going to go with aspirin because Quercetin inhibits the oxidation I want from Resveratrol and my intraveneous Vitamin C.

#21 browser

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Posted 23 March 2010 - 12:52 AM

The tetrahydrocurcumin is used to prevent sulphonation. I've already established

Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum……………. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. PMID: 10923862

that two adult aspirin, which I took 20 minutes before taking my 12 Nitro 250 capsules sans 12 MCT Quercetin this morning, can inhibit sulfphonation of Resveratrol. An anti-oxidant (like Vitamin C) is used to prevent glyconation.

I've not heard of vitamin C (or antioxidants in general) inhibiting what I presume is glucuronidation; I suspect this is wrong. We should probably be more careful with terminology here, since glycation is very different from glucuronidation, and sulfonation is very different from sulfation. The phase II metabolic enzymes that are eating up the compounds we care about are engaged in glucuronidation and sulfation.


I must be more careful with terms and scales. Quercetin is in the order of magnitude a million times more inhibitary of sulphation of Resveratrol than salicylic acid. But Quercetin is something to avoid when aiming to kill cancer with ROS from Resveratrol and IV Vitamin C. So I'll stick with the aspirin. The Vitaminc C and ascorbate is mentioned in the LongVida patent application PCT/US2007/005829 as ways prevent hydrolysis and oxidation of Curcumin, not to prevent its glucuronidation. Vitamin C or an equivalent anti-oxidant is part of the LongVida product if it follows the patent. I'll keep the Vitamin C in the mix. I do agree that the oil solution is superior than the high pH to dissolve, add gelatin then lower pH solution.

I'm hoping that the Resveratrol will dissolve in the oil. I can use $1 a gram Resveratrol then instead of micronized Resveratrol at $2.50 a gram. I'm looking to take 10 grams of Resveratrol and 12 grams of Curcumin split into two doses because there's a transport limit of around 5 grams of Resveratrol. With such quantities, I'd like to cut down on the cost of materials.

#22 Anthony_Loera

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Posted 23 March 2010 - 12:48 PM

LEF markets a curcumin claimed to attain higher blood levels by virture of including some turmeric, containing other compounds from the plant that are not in the pure extract. They cited in their ad copy a study showing better absorption. It is possible that sacrificial inhibition by some of these compounds results in higher blood levels.



LEF Markets BioCurcumin or BCM-95 (check the label on their super curcumin product)

http://www.lef.org/m...curcumin_01.htm

Yes, it is the same stuff we use in our products.

A

Edited by Anthony_Loera, 23 March 2010 - 12:50 PM.


#23 browser

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Posted 24 March 2010 - 12:41 AM

The tetrahydrocurcumin is used to prevent sulphonation. I've already established

Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum……………. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. PMID: 10923862

that two adult aspirin, which I took 20 minutes before taking my 12 Nitro 250 capsules sans 12 MCT Quercetin this morning, can inhibit sulfphonation of Resveratrol. An anti-oxidant (like Vitamin C) is used to prevent glyconation.

I've not heard of vitamin C (or antioxidants in general) inhibiting what I presume is glucuronidation; I suspect this is wrong. We should probably be more careful with terminology here, since glycation is very different from glucuronidation, and sulfonation is very different from sulfation. The phase II metabolic enzymes that are eating up the compounds we care about are engaged in glucuronidation and sulfation.


I must be more careful with terms and scales. Quercetin is in the order of magnitude a million times more inhibitary of sulphation of Resveratrol than salicylic acid. But Quercetin is something to avoid when aiming to kill cancer with ROS from Resveratrol and IV Vitamin C. So I'll stick with the aspirin. The Vitaminc C and ascorbate is mentioned in the LongVida patent application PCT/US2007/005829 as ways prevent hydrolysis and oxidation of Curcumin, not to prevent its glucuronidation. Vitamin C or an equivalent anti-oxidant is part of the LongVida product if it follows the patent. I'll keep the Vitamin C in the mix. I do agree that the oil solution is superior than the high pH to dissolve, add gelatin then lower pH solution.

I'm hoping that the Resveratrol will dissolve in the oil. I can use $1 a gram Resveratrol then instead of micronized Resveratrol at $2.50 a gram. I'm looking to take 10 grams of Resveratrol and 12 grams of Curcumin split into two doses because there's a transport limit of around 5 grams of Resveratrol. With such quantities, I'd like to cut down on the cost of materials.


Resveratrol won't dissolve in the oil. Looks like it's going to be down a couple of aspirins, blend Vitamin C and Curcumin into olive oil, down those then down a whey protein isolate/micronized Resveratrol shake.

#24 niner

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Posted 24 March 2010 - 03:02 AM

Resveratrol won't dissolve in the oil. Looks like it's going to be down a couple of aspirins, blend Vitamin C and Curcumin into olive oil, down those then down a whey protein isolate/micronized Resveratrol shake.

I tried to dissolve resveratrol in olive oil a long time ago, and it didn't work for me either, though I didn't try very hard. It goes into 95% ethanol pretty easily. (Readily available in states that don't outlaw Everclear.) Resveratrol is not profoundly hydrophobic; it has 3 hydroxyls after all. You might have better luck with something a little less hydrophobic than olive oil. Maybe coconut oil? You could also try heating the oil, and could try sonication if you have a sonicator. Maybe a mix of ethanol and an oil, or dissolve in ethanol first, then drip into oil.

#25 maxwatt

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Posted 24 March 2010 - 03:23 AM

Resveratrol won't dissolve in the oil. Looks like it's going to be down a couple of aspirins, blend Vitamin C and Curcumin into olive oil, down those then down a whey protein isolate/micronized Resveratrol shake.

I tried to dissolve resveratrol in olive oil a long time ago, and it didn't work for me either, though I didn't try very hard. It goes into 95% ethanol pretty easily. (Readily available in states that don't outlaw Everclear.) Resveratrol is not profoundly hydrophobic; it has 3 hydroxyls after all. You might have better luck with something a little less hydrophobic than olive oil. Maybe coconut oil? You could also try heating the oil, and could try sonication if you have a sonicator. Maybe a mix of ethanol and an oil, or dissolve in ethanol first, then drip into oil.


Solubility is limited, but it does dissolve. Slightly heating it and stirrig for a long, long time are needed. A magnetic lab stirrer is recommended.

#26 browser

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Posted 27 March 2010 - 04:17 PM

Resveratrol won't dissolve in the oil. Looks like it's going to be down a couple of aspirins, blend Vitamin C and Curcumin into olive oil, down those then down a whey protein isolate/micronized Resveratrol shake.

I tried to dissolve resveratrol in olive oil a long time ago, and it didn't work for me either, though I didn't try very hard. It goes into 95% ethanol pretty easily. (Readily available in states that don't outlaw Everclear.) Resveratrol is not profoundly hydrophobic; it has 3 hydroxyls after all. You might have better luck with something a little less hydrophobic than olive oil. Maybe coconut oil? You could also try heating the oil, and could try sonication if you have a sonicator. Maybe a mix of ethanol and an oil, or dissolve in ethanol first, then drip into oil.


Solubility is limited, but it does dissolve. Slightly heating it and stirring for a long, long time are needed. A magnetic lab stirrer is recommended.


My Curcumin came and I hadn't bought a blender yet to blend the Curcumin into olive oil, add some Vitamin C, then finally blend in Resveratrol. This morning I took 20 mg. Bioperine and two adult aspirins. Waited 20 minutes. During the 20 minutes I dissolved 12 grams of Curcumin into hot coconut milk. It seemed to dissolve, but it's hard to tell with coconut milk. I chilled the solution then added 5 grams of Resveratrol non-micronized powder and a few dabs of liposomal Vitamin C. The Resveratrol seemed to dissolve. Downed 3 grams of Nitro 250 with the coconut milk mixture. I've been doing buccal Resveratrol and have been getting light headed and high as a kite. No other meds or supplements. Am not hungry for breakfast and will probably have to take a late lunch for lack of appetite. This is /not/ a placebo effect.

#27 2tender

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Posted 27 March 2010 - 04:28 PM

Thanks, I really appreciate your detailed posting here. It is helpful. When I was taking higher doses of Resveratrol with my regimen I got that "kite" feeling too. Interesting at times, but to me it was indicative of excessive dosing and prompts me to cut dose. In your case, however, high dosing is exactly what may be needed, and hopefully, for a short period. When do you plan on cutting doses? How are your recent test results doing? Is there remission yet? PSA levels?

#28 browser

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Posted 27 March 2010 - 06:28 PM

Thanks, I really appreciate your detailed posting here. It is helpful. When I was taking higher doses of Resveratrol with my regimen I got that "kite" feeling too. Interesting at times, but to me it was indicative of excessive dosing and prompts me to cut dose. In your case, however, high dosing is exactly what may be needed, and hopefully, for a short period. When do you plan on cutting doses? How are your recent test results doing? Is there remission yet? PSA levels?


My recent PSA was up by 27%. That's where it was 6 months ago. I attribute this to my following Bill Sard1's suggestion to take <<<OMG, the megadosing!!!>>> 8 capsules of L0ngev1nex a day, which he supplied. It's too early for another PSA with high dosing (3+ grams of RESV in the form of Nitro). I just recently cut out the Quercetin (in the form of 3 grams of MCT Quercetin plus 9 grams of Jarrow Quercetin) with the 3 grams of Nitro.

For safety sake and based on the research report on Resveratrol acting as a pro-oxidant in the morning and an anti-oxidant in the evening, I'm taking my other supplements like Pom capsules, Life Extension Mix, Blueberry Extract and the like in the evening. I take Resveratrol bucally only before noon because of the impact Resveratrol has on the circadian genes. The 100 mg. sublingual pure Testosterone I take twice a day (I take loads of DIM and other things to prevent E2 and DHT creation) appears to be working especially well the more I increase the amount of Resveratrol.

When will I go to a lower dose of Resveratrol? I'm going to take a run of 2-3 months like this, expect my PSA to plummet, then take a breather and cut back to say 1 gram of Nitro or micronized in whey protein isolate.

#29 2tender

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Posted 27 March 2010 - 07:08 PM

Sounds good. Is the "T" medication called "Striant" ? Its administrated by attaching it to the upper gumline? What do you think of that medication? I agree that Resveratrol and androgens mix well, so do a lot of other guys.

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#30 ppp

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Posted 27 March 2010 - 09:21 PM

Resveratrol won't dissolve in the oil. Looks like it's going to be down a couple of aspirins, blend Vitamin C and Curcumin into olive oil, down those then down a whey protein isolate/micronized Resveratrol shake.

I tried to dissolve resveratrol in olive oil a long time ago, and it didn't work for me either, though I didn't try very hard. It goes into 95% ethanol pretty easily. (Readily available in states that don't outlaw Everclear.) Resveratrol is not profoundly hydrophobic; it has 3 hydroxyls after all. You might have better luck with something a little less hydrophobic than olive oil. Maybe coconut oil? You could also try heating the oil, and could try sonication if you have a sonicator. Maybe a mix of ethanol and an oil, or dissolve in ethanol first, then drip into oil.


Solubility is limited, but it does dissolve. Slightly heating it and stirring for a long, long time are needed. A magnetic lab stirrer is recommended.


My Curcumin came and I hadn't bought a blender yet to blend the Curcumin into olive oil, add some Vitamin C, then finally blend in Resveratrol. This morning I took 20 mg. Bioperine and two adult aspirins. Waited 20 minutes. During the 20 minutes I dissolved 12 grams of Curcumin into hot coconut milk. It seemed to dissolve, but it's hard to tell with coconut milk. I chilled the solution then added 5 grams of Resveratrol non-micronized powder and a few dabs of liposomal Vitamin C. The Resveratrol seemed to dissolve. Downed 3 grams of Nitro 250 with the coconut milk mixture. I've been doing buccal Resveratrol and have been getting light headed and high as a kite. No other meds or supplements. Am not hungry for breakfast and will probably have to take a late lunch for lack of appetite. This is /not/ a placebo effect.


I have to say that the mixture sounds vile - what was the taste like? Please keep us all posted on how this goes - I for one am very interested in this.




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