30 replies to this topic

[ppp]

The phytoalexin resveratrol has been described to have chemopreventive and chemotherapeutic effects in several tumor models while its effects on osteosarcoma have not been extensively studied. Additionally, resveratrol is a potent activator of the Sirt1/Sir2 (silent information regulator 2) family of NAD-dependent deacetylases which plays a role in calorie restriction-mediated tumor suppression. In the present study, we evaluated the effect of resveratrol on growth and apoptosis in four osteosarcoma cell lines (HOS, Saos-2, U-2 OS and MG-63) and a normal human osteoblast cell line (NHOst). We found that Sirt1 protein was relatively higher expressed in the tumor cells than normal osteoblasts. Consistently, resveratrol induced apoptosis in a dose-dependent fashion in the osteosarcoma cells but had minor effect on normal osteoblasts. Also, a similar effect could be elicited by another Sirt1 activator, isonicotinamide. In addition, the pro-apoptotic effect of resveratrol could be enhanced by nutrition restriction elicited by l-asparaginase. We postulate that these effects by resveratrol are mediated via Sirt1 but further studies are needed to confirm or refute this theory.

PMID: 19285066

My son has osteosarcoma which has been treated with both first and second-line chemo, but the response has been less than we would have hoped. The above paper shows that the four main osteosarcoma cell lines respond well to resveratrol in doses from 5uM upwards. Not said in the paper but confirmed by the research team is that the response was independent of the p53 status of the cell lines. So, the obvious thing now is to add resveratrol to his self-medication. I'm hoping that the collected wisdom here can help with some questions:

Firstly, what's the most bioavailable supplement on the market? Should I go for a lipsomal formulation (http://www.e-spa.net...ratrol_8oz.html or http://www.nanolipos...ESVERATROL.html), or something else (http://store.revgene...tro250-caps.htm). Or something else that I've missed altogether...

Secondly, what's the preferred dosing schedule? One big dose or several divided? With or without food?

Thirdly, my son is also taking nano-curcumin and EGCG. The evidence I've found shows that these are not antagonistic with resveratrol, anyone disagree?

I know that's a lot to ask, but I'm hoping that the combined experience in this forum can help me cut through the fog of competing claims and counter-claims.

Thanks

Edited by ppp, 05 May 2009 - 09:37 AM.

[alexd]

The phytoalexin resveratrol has been described to have chemopreventive and chemotherapeutic effects in several tumor models while its effects on osteosarcoma have not been extensively studied. Additionally, resveratrol is a potent activator of the Sirt1/Sir2 (silent information regulator 2) family of NAD-dependent deacetylases which plays a role in calorie restriction-mediated tumor suppression. In the present study, we evaluated the effect of resveratrol on growth and apoptosis in four osteosarcoma cell lines (HOS, Saos-2, U-2 OS and MG-63) and a normal human osteoblast cell line (NHOst). We found that Sirt1 protein was relatively higher expressed in the tumor cells than normal osteoblasts. Consistently, resveratrol induced apoptosis in a dose-dependent fashion in the osteosarcoma cells but had minor effect on normal osteoblasts. Also, a similar effect could be elicited by another Sirt1 activator, isonicotinamide. In addition, the pro-apoptotic effect of resveratrol could be enhanced by nutrition restriction elicited by l-asparaginase. We postulate that these effects by resveratrol are mediated via Sirt1 but further studies are needed to confirm or refute this theory.

PMID: 19285066

My son has osteosarcoma which has been treated with both first and second-line chemo, but the response has been less than we would have hoped. The above paper shows that the four main osteosarcoma cell lines respond well to resveratrol in doses from 5uM upwards. Not said in the paper but confirmed by the research team is that the response was independent of the p53 status of the cell lines. So, the obvious thing now is to add resveratrol to his self-medication. I'm hoping that the collected wisdom here can help with some questions:

Firstly, what's the most bioavailable supplement on the market? Should I go for a lipsomal formulation (http://www.e-spa.net...ratrol_8oz.html or http://www.nanolipos...ESVERATROL.html), or something else (http://store.revgene...tro250-caps.htm). Or something else that I've missed altogether...

Secondly, what's the preferred dosing schedule? One big dose or several divided? With or without food?

Thirdly, my son is also taking nano-curcumin and EGCG. The evidence I've found shows that these are not antagonistic with resveratrol, anyone disagree?

I know that's a lot to ask, but I'm hoping that the combined experience in this forum can help me cut through the fog of competing claims and counter-claims.

Thanks

I take mega doses of resveratrol that I obtain via an extract of japenese knot weed root. I chose that route due to costs and with your son's illness I would not suggest you go the way I have since the amount of resveratrol in any one dose is likely to be 50% but I have not verified it. Still if you want to obtain it just ask me and I will reply. I am sure people here can give you the information to find the most effective versions.

What I am suggesting is that you pay attention to how long the substance stays in the blood. I space my capsules throughout my waking day because the blood serum level lasts for about an hour and one half. (Someone please share the real number here!) Now the blood serum level may not be a good indicator of the effects of the substance but as far as I know it is something we can measure.

I have noticed a definite threshold in how it affects me. At these large dosages I first lost 14 lbs off my gut in two weeks, my grey facial hair is slowly and noticeably turning dark and when exercising I do not get easily winded. Some of this mirrors the effects on rats ( I think my mother's side of the family has ancestral rodents!) that were done at the Louis Pasteur Institute on 2006.

Here is th url for the article.Please note the dosage levels in kilograms for this experiment and how it compares to an earlier experiment (there is a link to it in the article) that was done on obese mice. In the first experiment the results were significant but did not have the same physical manifestations as in the French experiment. I am taking approx half the amount per kilo gram that were given to the French mice. I am 56 years old and people now look at a two year old picture on my drivers license and without prompting say I look younger. I have experienced a desirable lowering of my blood pressure and chlorestrol levels. So something is happening.

Incidently I had a friend who unfortunately has passed away due to late stage colon cancer. I gave him the extract and told him to take a capsule every hour and one half. For what ever reason he did not take it. (fear of the unknown what ever). When things had gone too far he reviewed the info I gave him and said he should have tried it. This is from someone smarter than most of us. I think you are ahead of the game on this. Also as I stated elsewhere an obese diabetic friend of mine who also has someone else's liver take about half of what I take which means he takes at least 1/3 less per kilo than I do, has improvements in his blood sugar levels, has lost some weight and had suffered a loss of feeling in his feet and now that feeling has returned.

I suggest starting at very high doses in the first week or two and then moderating to high doses after that.

If anyone out there has better information that contradicts or adds to what I have said please correct me. I would rather this person have a better chance of fighting this illness than trying to prove that I am right.

Best of luck.

Also if you want I will at my own expense send you what extract I have next day mail. I am expecting another shipment (I buy it in small bulk quantities and put it in capsules myself) and if I go without it for a few days it will not change my life. Just private message me. I think the purified versions are a better choice but this is something I can do perhaps just as a stopgap until you obtain other versions of resveratrol.

Best of luck.

[tunt01]

My son has osteosarcoma which has been treated with both first and second-line chemo, but the response has been less than we would have hoped. The above paper shows that the four main osteosarcoma cell lines respond well to resveratrol in doses from 5uM upwards. Not said in the paper but confirmed by the research team is that the response was independent of the p53 status of the cell lines. So, the obvious thing now is to add resveratrol to his self-medication. I'm hoping that the collected wisdom here can help with some questions:

Firstly, what's the most bioavailable supplement on the market? Should I go for a lipsomal formulation (http://www.e-spa.net...ratrol_8oz.html or http://www.nanolipos...ESVERATROL.html), or something else (http://store.revgene...tro250-caps.htm). Or something else that I've missed altogether...

Secondly, what's the preferred dosing schedule? One big dose or several divided? With or without food?

Thirdly, my son is also taking nano-curcumin and EGCG. The evidence I've found shows that these are not antagonistic with resveratrol, anyone disagree?

I know that's a lot to ask, but I'm hoping that the combined experience in this forum can help me cut through the fog of competing claims and counter-claims.

Thanks

Most studies on substances tend to be diet+substance or diet-substance, so there isn't a plethora of data on combined regimens, though it would be nice. I think the body of evidence suggests there are actually synergistic effects with resveratrol + other molecules like quercetin and piperidine (possibly also curcumin/EGCG, as Sinclair seems to have eluded to this). There is pretty direct evidence that piperidine, quercetin/lutoelin stop the sulfonation effect of the liver on resveratrol which improves bioavailbility. I would point out that Dr. Sinclair used to take Longevinex, which is a mixture containing quercetin/resveratrol (you can read the ingredients).

Most people take resveratrol in the AM upon waking. A lot of people seem to take it on an empty stomach, though I take it with an oatmeal mix in the AM. I think it is a food molecule and should be treated as such. I take a relatively lighter dose though (125 mg). I recognize osteosarcoma is a very serious cancer, but please bear in mind that constant, very very high doses of resveratrol may lead to cardio (heart) damage. Persistent megadosing has risks in the other direction, though they may be of little concern to you given the circumstances. This other thread on the forum where 2 dogs were cured of their cancer w/ a megadose of resveratrol might be worth a quick read. Constant low-dose resveratrol may allow the cancer to adapt/mutate, I've no idea really. I'm not aware of the 'appropriate' course of action with resv + cancer.

regards

pro

Edited by prophets, 05 May 2009 - 04:23 PM.

[maxwatt]

The phytoalexin resveratrol has been described to have chemopreventive and chemotherapeutic effects in several tumor models while its effects on osteosarcoma have not been extensively studied. Additionally, resveratrol is a potent activator of the Sirt1/Sir2 (silent information regulator 2) family of NAD-dependent deacetylases which plays a role in calorie restriction-mediated tumor suppression. In the present study, we evaluated the effect of resveratrol on growth and apoptosis in four osteosarcoma cell lines (HOS, Saos-2, U-2 OS and MG-63) and a normal human osteoblast cell line (NHOst). We found that Sirt1 protein was relatively higher expressed in the tumor cells than normal osteoblasts. Consistently, resveratrol induced apoptosis in a dose-dependent fashion in the osteosarcoma cells but had minor effect on normal osteoblasts. Also, a similar effect could be elicited by another Sirt1 activator, isonicotinamide. In addition, the pro-apoptotic effect of resveratrol could be enhanced by nutrition restriction elicited by l-asparaginase. We postulate that these effects by resveratrol are mediated via Sirt1 but further studies are needed to confirm or refute this theory.

PMID: 19285066

My son has osteosarcoma which has been treated with both first and second-line chemo, but the response has been less than we would have hoped. The above paper shows that the four main osteosarcoma cell lines respond well to resveratrol in doses from 5uM upwards. Not said in the paper but confirmed by the research team is that the response was independent of the p53 status of the cell lines. So, the obvious thing now is to add resveratrol to his self-medication. I'm hoping that the collected wisdom here can help with some questions:

Firstly, what's the most bioavailable supplement on the market? Should I go for a lipsomal formulation (http://www.e-spa.net...ratrol_8oz.html or http://www.nanolipos...ESVERATROL.html), or something else (http://store.revgene...tro250-caps.htm). Or something else that I've missed altogether...

Secondly, what's the preferred dosing schedule? One big dose or several divided? With or without food?

Thirdly, my son is also taking nano-curcumin and EGCG. The evidence I've found shows that these are not antagonistic with resveratrol, anyone disagree?

I know that's a lot to ask, but I'm hoping that the combined experience in this forum can help me cut through the fog of competing claims and counter-claims.

Thanks

Bioavaiability: There are two resveratrol formulations that achieve higher blood-serum levels than shown with straight resveratrol powder, as shown in tests whose results I have seen. One is micronized resveratrol in Tween80; this is available from the company that sponsors this forum, whose banner is at the top of this page.
The second is a combination of resveratrol, polydatin, luteolin and HPMC; the tests are unpublished, and it is not available commercially at this time, though the ingredients are readily available.
I have not seen tests of serum levels for the liquid liposomal products you linked to. I know resveratrol is less stable in liquid. It may be a good product, or it might not be.

Dosing schedule: For healthy people, I have concluded that once a day, in the morning, is likely to work best. With cancer, we do not know whether or not a sustained high levels from 2x or 3x a day dosing is better than a single daily dose. Sorry we do not know more. In your son's situation I would start with three-a-day dosing, and depending on results, eventually transition to a once-a-day regimen.

Curcumin and EGCG should not interfere with resveratrol, and are likely to be complementary.

[maxwatt]

The phytoalexin resveratrol has been described to have chemopreventive and chemotherapeutic effects in several tumor models while its effects on osteosarcoma have not been extensively studied. Additionally, resveratrol is a potent activator of the Sirt1/Sir2 (silent information regulator 2) family of NAD-dependent deacetylases which plays a role in calorie restriction-mediated tumor suppression. In the present study, we evaluated the effect of resveratrol on growth and apoptosis in four osteosarcoma cell lines (HOS, Saos-2, U-2 OS and MG-63) and a normal human osteoblast cell line (NHOst). We found that Sirt1 protein was relatively higher expressed in the tumor cells than normal osteoblasts. Consistently, resveratrol induced apoptosis in a dose-dependent fashion in the osteosarcoma cells but had minor effect on normal osteoblasts. Also, a similar effect could be elicited by another Sirt1 activator, isonicotinamide. In addition, the pro-apoptotic effect of resveratrol could be enhanced by nutrition restriction elicited by l-asparaginase. We postulate that these effects by resveratrol are mediated via Sirt1 but further studies are needed to confirm or refute this theory.

PMID: 19285066

My son has osteosarcoma which has been treated with both first and second-line chemo, but the response has been less than we would have hoped. The above paper shows that the four main osteosarcoma cell lines respond well to resveratrol in doses from 5uM upwards. Not said in the paper but confirmed by the research team is that the response was independent of the p53 status of the cell lines. So, the obvious thing now is to add resveratrol to his self-medication. I'm hoping that the collected wisdom here can help with some questions:

Firstly, what's the most bioavailable supplement on the market? Should I go for a lipsomal formulation (http://www.e-spa.net...ratrol_8oz.html or http://www.nanolipos...ESVERATROL.html), or something else (http://store.revgene...tro250-caps.htm). Or something else that I've missed altogether...

Secondly, what's the preferred dosing schedule? One big dose or several divided? With or without food?

Thirdly, my son is also taking nano-curcumin and EGCG. The evidence I've found shows that these are not antagonistic with resveratrol, anyone disagree?

I know that's a lot to ask, but I'm hoping that the combined experience in this forum can help me cut through the fog of competing claims and counter-claims.

Thanks

I take mega doses of resveratrol that I obtain via an extract of japenese knot weed root. I chose that route due to costs and with your son's illness I would not suggest you go the way I have since the amount of resveratrol in any one dose is likely to be 50% but I have not verified it. Still if you want to obtain it just ask me and I will reply. I am sure people here can give you the information to find the most effective versions.

What I am suggesting is that you pay attention to how long the substance stays in the blood. I space my capsules throughout my waking day because the blood serum level lasts for about an hour and one half. (Someone please share the real number here!) Now the blood serum level may not be a good indicator of the effects of the substance but as far as I know it is something we can measure.

I have noticed a definite threshold in how it affects me. At these large dosages I first lost 14 lbs off my gut in two weeks, my grey facial hair is slowly and noticeably turning dark and when exercising I do not get easily winded. Some of this mirrors the effects on rats ( I think my mother's side of the family has ancestral rodents!) that were done at the Louis Pasteur Institute on 2006.

Here is th url for the article.Please note the dosage levels in kilograms for this experiment and how it compares to an earlier experiment (there is a link to it in the article) that was done on obese mice. In the first experiment the results were significant but did not have the same physical manifestations as in the French experiment. I am taking approx half the amount per kilo gram that were given to the French mice. I am 56 years old and people now look at a two year old picture on my drivers license and without prompting say I look younger. I have experienced a desirable lowering of my blood pressure and chlorestrol levels. So something is happening.

Incidently I had a friend who unfortunately has passed away due to late stage colon cancer. I gave him the extract and told him to take a capsule every hour and one half. For what ever reason he did not take it. (fear of the unknown what ever). When things had gone too far he reviewed the info I gave him and said he should have tried it. This is from someone smarter than most of us. I think you are ahead of the game on this. Also as I stated elsewhere an obese diabetic friend of mine who also has someone else's liver take about half of what I take which means he takes at least 1/3 less per kilo than I do, has improvements in his blood sugar levels, has lost some weight and had suffered a loss of feeling in his feet and now that feeling has returned.

I suggest starting at very high doses in the first week or two and then moderating to high doses after that.

If anyone out there has better information that contradicts or adds to what I have said please correct me. I would rather this person have a better chance of fighting this illness than trying to prove that I am right.

Best of luck.

Also if you want I will at my own expense send you what extract I have next day mail. I am expecting another shipment (I buy it in small bulk quantities and put it in capsules myself) and if I go without it for a few days it will not change my life. Just private message me. I think the purified versions are a better choice but this is something I can do perhaps just as a stopgap until you obtain other versions of resveratrol.

Best of luck.

If the above extract is 50% resveratrl, I would not recommend taking high doses due to the other substances from knotweed that will be present int he extract: physcion and emodin, to name two. These are intestinal irritants and may cause ulcers if taken chronically in large amounts.

FWIW peak serum levels are obtained in bout 30 minutes.

Edited by maxwatt, 06 May 2009 - 12:42 AM.

[alexd]

The phytoalexin resveratrol has been described to have chemopreventive and chemotherapeutic effects in several tumor models while its effects on osteosarcoma have not been extensively studied. Additionally, resveratrol is a potent activator of the Sirt1/Sir2 (silent information regulator 2) family of NAD-dependent deacetylases which plays a role in calorie restriction-mediated tumor suppression. In the present study, we evaluated the effect of resveratrol on growth and apoptosis in four osteosarcoma cell lines (HOS, Saos-2, U-2 OS and MG-63) and a normal human osteoblast cell line (NHOst). We found that Sirt1 protein was relatively higher expressed in the tumor cells than normal osteoblasts. Consistently, resveratrol induced apoptosis in a dose-dependent fashion in the osteosarcoma cells but had minor effect on normal osteoblasts. Also, a similar effect could be elicited by another Sirt1 activator, isonicotinamide. In addition, the pro-apoptotic effect of resveratrol could be enhanced by nutrition restriction elicited by l-asparaginase. We postulate that these effects by resveratrol are mediated via Sirt1 but further studies are needed to confirm or refute this theory.

PMID: 19285066

My son has osteosarcoma which has been treated with both first and second-line chemo, but the response has been less than we would have hoped. The above paper shows that the four main osteosarcoma cell lines respond well to resveratrol in doses from 5uM upwards. Not said in the paper but confirmed by the research team is that the response was independent of the p53 status of the cell lines. So, the obvious thing now is to add resveratrol to his self-medication. I'm hoping that the collected wisdom here can help with some questions:

Firstly, what's the most bioavailable supplement on the market? Should I go for a lipsomal formulation (http://www.e-spa.net...ratrol_8oz.html or http://www.nanolipos...ESVERATROL.html), or something else (http://store.revgene...tro250-caps.htm). Or something else that I've missed altogether...

Secondly, what's the preferred dosing schedule? One big dose or several divided? With or without food?

Thirdly, my son is also taking nano-curcumin and EGCG. The evidence I've found shows that these are not antagonistic with resveratrol, anyone disagree?

I know that's a lot to ask, but I'm hoping that the combined experience in this forum can help me cut through the fog of competing claims and counter-claims.

Thanks

I take mega doses of resveratrol that I obtain via an extract of japenese knot weed root. I chose that route due to costs and with your son's illness I would not suggest you go the way I have since the amount of resveratrol in any one dose is likely to be 50% but I have not verified it. Still if you want to obtain it just ask me and I will reply. I am sure people here can give you the information to find the most effective versions.

What I am suggesting is that you pay attention to how long the substance stays in the blood. I space my capsules throughout my waking day because the blood serum level lasts for about an hour and one half. (Someone please share the real number here!) Now the blood serum level may not be a good indicator of the effects of the substance but as far as I know it is something we can measure.

I have noticed a definite threshold in how it affects me. At these large dosages I first lost 14 lbs off my gut in two weeks, my grey facial hair is slowly and noticeably turning dark and when exercising I do not get easily winded. Some of this mirrors the effects on rats ( I think my mother's side of the family has ancestral rodents!) that were done at the Louis Pasteur Institute on 2006.

Here is th url for the article.Please note the dosage levels in kilograms for this experiment and how it compares to an earlier experiment (there is a link to it in the article) that was done on obese mice. In the first experiment the results were significant but did not have the same physical manifestations as in the French experiment. I am taking approx half the amount per kilo gram that were given to the French mice. I am 56 years old and people now look at a two year old picture on my drivers license and without prompting say I look younger. I have experienced a desirable lowering of my blood pressure and chlorestrol levels. So something is happening.

Incidently I had a friend who unfortunately has passed away due to late stage colon cancer. I gave him the extract and told him to take a capsule every hour and one half. For what ever reason he did not take it. (fear of the unknown what ever). When things had gone too far he reviewed the info I gave him and said he should have tried it. This is from someone smarter than most of us. I think you are ahead of the game on this. Also as I stated elsewhere an obese diabetic friend of mine who also has someone else's liver take about half of what I take which means he takes at least 1/3 less per kilo than I do, has improvements in his blood sugar levels, has lost some weight and had suffered a loss of feeling in his feet and now that feeling has returned.

I suggest starting at very high doses in the first week or two and then moderating to high doses after that.

If anyone out there has better information that contradicts or adds to what I have said please correct me. I would rather this person have a better chance of fighting this illness than trying to prove that I am right.

Best of luck.

Also if you want I will at my own expense send you what extract I have next day mail. I am expecting another shipment (I buy it in small bulk quantities and put it in capsules myself) and if I go without it for a few days it will not change my life. Just private message me. I think the purified versions are a better choice but this is something I can do perhaps just as a stopgap until you obtain other versions of resveratrol.

Best of luck.

If the above extract is 50% resveratrl, I would not recommend taking high doses due to the other substances from knotweed that will be present int he extract: physcion and emodin, to name two. These are intestinal irritants and may cause ulcers if taken chronically in large amounts.

FWIW peak serum levels are obtained in bout 30 minutes.

Thanks, you might be correct on physcion and emodin except that I have not experienced any undue laxative effects. Do you know how to ascertain the amounts of these substances in a given sample? Just had a colonoscopy and no problems or observation of any unusual aspects were reported.

[niner]

Of the products you are considering, I would stay away from the nano-liposomal ones. These appear to be the same formulation, right down to the stevia and peach flavoring. The problem with them is that they fail to provide some key information: There is no mention of the source, type, or purity of the resveratrol contained (or ostensibly contained) in the liposomes. Is it synthetic? A 50% extract? Emodin content? Another missing bit is any sort of certificate of analysis, ensuring that the heavy metal, microbial, and other contaminant levels are acceptable. Finally, I didn't see any evidence of clinical data with this formulation or even a formulation like it. While the concept is good, the delivery on this product raises some red flags. Call me old fashioned, but pharmaceuticals from Tijuana scare me.

Since the in vitro experiments showed activity at concentrations of 5uM and up, this raises the question of the dose required in a human. In order to achieve a plasma level of 5uM with ordinary resveratrol, a fairly substantial dose is required, perhaps 10gm in an adult. The micronization and tween formulation will reduce the amount needed, but I can't say exactly what the factor would be. My guess would be somewhat less than 10, meaning that a dose of near 1000mg might be appropriate. This is well within the range that people in this forum have reported using, at least with other formulations of resveratrol. Resveratrol may be effective at lower doses, but you are on the cutting edge here and knowledge is limited. It might be worth looking up the protocols for the various resveratrol cancer trials, if they are available. The most commonly reported side effects from resveratrol in general are GI disturbances and joint/tendon pain. I have heard that the tween formulation has a lower incidence of GI problems than other formulations, but don't have first hand knowledge to this effect.

I wish you the best of luck. Keep us posted.

[ppp]

Also if you want I will at my own expense send you what extract I have next day mail. I am expecting another shipment (I buy it in small bulk quantities and put it in capsules myself) and if I go without it for a few days it will not change my life. Just private message me. I think the purified versions are a better choice but this is something I can do perhaps just as a stopgap until you obtain other versions of resveratrol.

Best of luck.

Alex, thanks for the kind offer. It's very much appreciated. I'm in the UK, so ordering direct from a supplier and getting it couriered over is going to be fastest.

Pan

[ppp]

Of the products you are considering, I would stay away from the nano-liposomal ones. These appear to be the same formulation, right down to the stevia and peach flavoring. The problem with them is that they fail to provide some key information: There is no mention of the source, type, or purity of the resveratrol contained (or ostensibly contained) in the liposomes. Is it synthetic? A 50% extract? Emodin content? Another missing bit is any sort of certificate of analysis, ensuring that the heavy metal, microbial, and other contaminant levels are acceptable. Finally, I didn't see any evidence of clinical data with this formulation or even a formulation like it. While the concept is good, the delivery on this product raises some red flags. Call me old fashioned, but pharmaceuticals from Tijuana scare me.

Since the in vitro experiments showed activity at concentrations of 5uM and up, this raises the question of the dose required in a human. In order to achieve a plasma level of 5uM with ordinary resveratrol, a fairly substantial dose is required, perhaps 10gm in an adult. The micronization and tween formulation will reduce the amount needed, but I can't say exactly what the factor would be. My guess would be somewhat less than 10, meaning that a dose of near 1000mg might be appropriate. This is well within the range that people in this forum have reported using, at least with other formulations of resveratrol. Resveratrol may be effective at lower doses, but you are on the cutting edge here and knowledge is limited. It might be worth looking up the protocols for the various resveratrol cancer trials, if they are available. The most commonly reported side effects from resveratrol in general are GI disturbances and joint/tendon pain. I have heard that the tween formulation has a lower incidence of GI problems than other formulations, but don't have first hand knowledge to this effect.

I wish you the best of luck. Keep us posted.

Thanks for the advice. From what you and other people have said it looks like the Tween80 product is what I'm going to opt for. Four tablets a day delivers the 1000mg you've suggested. I don't suppose anyone has experience of taking this amount of the product daily?

Pan

[ppp]

The phytoalexin resveratrol has been described to have chemopreventive and chemotherapeutic effects in several tumor models while its effects on osteosarcoma have not been extensively studied. Additionally, resveratrol is a potent activator of the Sirt1/Sir2 (silent information regulator 2) family of NAD-dependent deacetylases which plays a role in calorie restriction-mediated tumor suppression. In the present study, we evaluated the effect of resveratrol on growth and apoptosis in four osteosarcoma cell lines (HOS, Saos-2, U-2 OS and MG-63) and a normal human osteoblast cell line (NHOst). We found that Sirt1 protein was relatively higher expressed in the tumor cells than normal osteoblasts. Consistently, resveratrol induced apoptosis in a dose-dependent fashion in the osteosarcoma cells but had minor effect on normal osteoblasts. Also, a similar effect could be elicited by another Sirt1 activator, isonicotinamide. In addition, the pro-apoptotic effect of resveratrol could be enhanced by nutrition restriction elicited by l-asparaginase. We postulate that these effects by resveratrol are mediated via Sirt1 but further studies are needed to confirm or refute this theory.

PMID: 19285066

My son has osteosarcoma which has been treated with both first and second-line chemo, but the response has been less than we would have hoped. The above paper shows that the four main osteosarcoma cell lines respond well to resveratrol in doses from 5uM upwards. Not said in the paper but confirmed by the research team is that the response was independent of the p53 status of the cell lines. So, the obvious thing now is to add resveratrol to his self-medication. I'm hoping that the collected wisdom here can help with some questions:

Firstly, what's the most bioavailable supplement on the market? Should I go for a lipsomal formulation (http://www.e-spa.net...ratrol_8oz.html or http://www.nanolipos...ESVERATROL.html), or something else (http://store.revgene...tro250-caps.htm). Or something else that I've missed altogether...

Secondly, what's the preferred dosing schedule? One big dose or several divided? With or without food?

Thirdly, my son is also taking nano-curcumin and EGCG. The evidence I've found shows that these are not antagonistic with resveratrol, anyone disagree?

I know that's a lot to ask, but I'm hoping that the combined experience in this forum can help me cut through the fog of competing claims and counter-claims.

Thanks

Bioavaiability: There are two resveratrol formulations that achieve higher blood-serum levels than shown with straight resveratrol powder, as shown in tests whose results I have seen. One is micronized resveratrol in Tween80; this is available from the company that sponsors this forum, whose banner is at the top of this page.
The second is a combination of resveratrol, polydatin, luteolin and HPMC; the tests are unpublished, and it is not available commercially at this time, though the ingredients are readily available.
I have not seen tests of serum levels for the liquid liposomal products you linked to. I know resveratrol is less stable in liquid. It may be a good product, or it might not be.

Dosing schedule: For healthy people, I have concluded that once a day, in the morning, is likely to work best. With cancer, we do not know whether or not a sustained high levels from 2x or 3x a day dosing is better than a single daily dose. Sorry we do not know more. In your son's situation I would start with three-a-day dosing, and depending on results, eventually transition to a once-a-day regimen.

Curcumin and EGCG should not interfere with resveratrol, and are likely to be complementary.

Three a day dosing sounds reasonable, it's the size of the dose that is the next question. Another poster has suggested a dose of 1000mg (of the Tween80 product), but doing that three times a day seems excessive. Twice a day might be more doable. Has anyone tried taking 2000mg of the Nitro250 daily?

Pan

[ppp]

Most studies on substances tend to be diet+substance or diet-substance, so there isn't a plethora of data on combined regimens, though it would be nice. I think the body of evidence suggests there are actually synergistic effects with resveratrol + other molecules like quercetin and piperidine (possibly also curcumin/EGCG, as Sinclair seems to have eluded to this). There is pretty direct evidence that piperidine, quercetin/lutoelin stop the sulfonation effect of the liver on resveratrol which improves bioavailbility. I would point out that Dr. Sinclair used to take Longevinex, which is a mixture containing quercetin/resveratrol (you can read the ingredients).

Does that mean some people are using piperidine/bioprene to enhance the bioavailability of resveratrol (in the same way that people do with curcumin)?

Pan

[tunt01]

Does that mean some people are using piperidine/bioprene to enhance the bioavailability of resveratrol (in the same way that people do with curcumin)?

Pan

i'm not sure if it is in the same way which curcumin enhances it, but it prevents the liver from completing digesting it. there are posts about this on the issue of sulfonation.

[maxwatt]

Of the products you are considering, I would stay away from the nano-liposomal ones. These appear to be the same formulation, right down to the stevia and peach flavoring. The problem with them is that they fail to provide some key information: There is no mention of the source, type, or purity of the resveratrol contained (or ostensibly contained) in the liposomes. Is it synthetic? A 50% extract? Emodin content? Another missing bit is any sort of certificate of analysis, ensuring that the heavy metal, microbial, and other contaminant levels are acceptable. Finally, I didn't see any evidence of clinical data with this formulation or even a formulation like it. While the concept is good, the delivery on this product raises some red flags. Call me old fashioned, but pharmaceuticals from Tijuana scare me.

Since the in vitro experiments showed activity at concentrations of 5uM and up, this raises the question of the dose required in a human. In order to achieve a plasma level of 5uM with ordinary resveratrol, a fairly substantial dose is required, perhaps 10gm in an adult. The micronization and tween formulation will reduce the amount needed, but I can't say exactly what the factor would be. My guess would be somewhat less than 10, meaning that a dose of near 1000mg might be appropriate. This is well within the range that people in this forum have reported using, at least with other formulations of resveratrol. Resveratrol may be effective at lower doses, but you are on the cutting edge here and knowledge is limited. It might be worth looking up the protocols for the various resveratrol cancer trials, if they are available. The most commonly reported side effects from resveratrol in general are GI disturbances and joint/tendon pain. I have heard that the tween formulation has a lower incidence of GI problems than other formulations, but don't have first hand knowledge to this effect.

I wish you the best of luck. Keep us posted.

Thanks for the advice. From what you and other people have said it looks like the Tween80 product is what I'm going to opt for. Four tablets a day delivers the 1000mg you've suggested. I don't suppose anyone has experience of taking this amount of the product daily?

Pan

The amount of resveratrol is not more than man of us here take or have been taking.
The other ingredient is Tween80. The WHO (World Health Organization) sets the acceptable daily intake of both Tween 80 at 25 mg per kilogram of body weight, which means an adult weighing 70 kilos could consume 1,750 mg of Tween 80 daily on a long term chronic basis without any toxic potential. They have a built-in safety margin with this figure, so I am sure this is a conservative figure. However, I do not know the amount of Tween 80 per capsule; I am guessing it is the same as the resveratrol, at 250 mg. If so, four capsules daily would be safe.

I hope Anthony can tell us how much Tween 80 is in a capsule.

[bluemoon]

Hi ppp,

I had osteosarcoma as well. We are all cheering for your son, and I'm glad you found this site with so many who can help.

Edited by Holmes, 07 May 2009 - 12:06 PM.

[Anthony_Loera]

Maxwatt,

I believe we have spoken about this before my friend.

The same reason Shaklee doesn't state the amount of there inactive ingredients in Vivix, is the same reason we don't state the amount of inactive ingredients in our own product as well.

Needless to say, we abide by both FDA GRAS safety as well as by the World Health Organization's recommendations for food and supplements.

Cheers
Anthony

[ppp]

Hi ppp,

I had osteosarcoma as well. We are all cheering for your son, and I'm glad you found this site with so many who can help.

Good to hear from you. Hope things have cleared up for you and that you are doing well.

Do you mind if I ask if there were any off-label things that you did while you were being treated? Any pointers you have would be appreciated...by mail if necessary.

[maxwatt]

Maxwatt,

I believe we have spoken about this before my friend.

The same reason Shaklee doesn't state the amount of there inactive ingredients in Vivix, is the same reason we don't state the amount of inactive ingredients in our own product as well.

Needless to say, we abide by both FDA GRAS safety as well as by the World Health Organization's recommendations for food and supplements.

Cheers
Anthony

The reason I ask, is that the WHO sets maximum safe daily intake of Tween80 at 25 mg/kg body weight. That's 1750 mg for a 70 kg man. One capsule, or two, won't exceed that, but there are people who may be taking four or eight a day. If you don't want to divulge a trade secret, you could recommend an upper limit on the number of capsules that should be consumed per day.

[Anthony_Loera]

Hi Maxwatt,

I understand what you are saying. However, our recommendation is not based on how much tween is in the capsules, but on micronized resveratrol content in the capsules. Remember, for regular non-micronized resveratrol, the company has always suggested no more than 500mg for every 50lbs of body weight. We where the first to state this recommendation in January 2007.

Knowing that absorption for micronized dry powder (not the Nitro250) may be increased by 2x when compared to regular non-micronized resveratrol, we recommend for folks to take no more than 500mg for every 100lbs of body weight. If we continue, we can see that an emulsion with the micronized powder can be absorbed better than dry micronized powder.

From a business prospective the company simply recommends 1 capsule a day for most healthy folks.
From a personal standpoint, and not a company one, I personally take a couple capsules a day because of my previous (2 grams/day intake) of regular resveratrol.

Most folks that take more (although I have not heard of 8 a day), usually do so by the request of a doctor.

Cheers
A

Edited by Anthony_Loera, 07 May 2009 - 05:18 PM.

[ppp]

Hi Maxwatt,

I understand what you are saying. However, our recommendation is not based on how much tween is in the capsules, but on micronized resveratrol content in the capsules. Remember, for regular non-micronized resveratrol, the company has always suggested no more than 500mg for every 50lbs of body weight. We where the first to state this recommendation in January 2007.

Knowing that absorption for micronized dry powder (not the Nitro250) may be increased by 2x when compared to regular non-micronized resveratrol, we recommend for folks to take no more than 500mg for every 100lbs of body weight. If we continue, we can see that an emulsion with the micronized powder can be absorbed better than dry micronized powder.

From a business prospective the company simply recommends 1 capsule a day for most healthy folks.
From a personal standpoint, and not a company one, I personally take a couple capsules a day because of my previous (2 grams/day intake) of regular resveratrol.

Most folks that take more (although I have not heard of 8 a day), usually do so by the request of a doctor.

Cheers
A

What would you recommend for the Nitro250? I'm considering 2000mg daily for my son in an attempt to reach the cytotoxic levels shown to kill osteosarcoma cells.

[Anthony_Loera]

What would you recommend for the Nitro250? I'm considering 2000mg daily for my son in an attempt to reach the cytotoxic levels shown to kill osteosarcoma cells.

Hi ppp,

I cannot provide medical advice to you.
However, I do know of others that take 2-4 capsules of this for dietary purposes, who are under the care of oncologists.

A

[ppp]

What would you recommend for the Nitro250? I'm considering 2000mg daily for my son in an attempt to reach the cytotoxic levels shown to kill osteosarcoma cells.

Hi ppp,

I cannot provide medical advice to you.
However, I do know of others that take 2-4 capsules of this for dietary purposes, who are under the care of oncologists.

A

Thanks, that's reassuring.

[maxwatt]

you could take 2 to 4 nitro capsules, and add additional 98 or 99% resveratrol up to several grams, or use Hedgehogs formulation, which combines resveratrol, polydatin and luteolin to obtain higher serum levels.

[bluemoon]

Do you mind if I ask if there were any off-label things that you did while you were being treated? Any pointers you have would be appreciated...by mail if necessary.

I wish I could help, but that was a long time ago, so nothing like that then.
I remember a doctor wrote a book (around 2000-2004?) about treating his own brain tumor in addition to chemo, and based on the reviews, his attitude was to try most things that are non toxic. Does anyone know the title? I'm fairly sure this is a quality book, not hype.

[niner]

Most studies on substances tend to be diet+substance or diet-substance, so there isn't a plethora of data on combined regimens, though it would be nice. I think the body of evidence suggests there are actually synergistic effects with resveratrol + other molecules like quercetin and piperidine (possibly also curcumin/EGCG, as Sinclair seems to have eluded to this). There is pretty direct evidence that piperidine, quercetin/lutoelin stop the sulfonation effect of the liver on resveratrol which improves bioavailbility. I would point out that Dr. Sinclair used to take Longevinex, which is a mixture containing quercetin/resveratrol (you can read the ingredients).

Does that mean some people are using piperidine/bioprene to enhance the bioavailability of resveratrol (in the same way that people do with curcumin)?

Just for the record, we should be calling this piperine, lest someone actually get their hands on and consume some piperidine, a cyclic amine used in the manufacture of PCP. There is an extract of black pepper, called bioperine, which contains 95% piperine. (Bioprene is a trade name for a plastic.) Piperine is a glucuronidation inhibitor, so compounds such as resveratrol that are conjugated and cleared via glucuronidation will have a longer half life if that pathway is inhibited. Piperine does nothing to assist in the absorption of drugs as is sometimes stated. It may enhance the bioavailability of a drug, but only if the drug is cleared by glucuronidation. Quercetin is reported to strongly inhibit the sulfation of resveratrol, which is the primary pathway by which it is cleared. Quercetin itself is cleared pretty rapidly, and also induces the expression of even more of the enzyme that you're trying to inhibit, so it gets complicated.

[tunt01]

thx for correcting my error. i knew i was making a mistake somewhere and i sat starring at it for a moment, but couldn't put my finger on it. was too tired :(.

fwiw - i use black pepper directly instead of a pill, when i take it with resveratrol.

[ppp]

you could take 2 to 4 nitro capsules, and add additional 98 or 99% resveratrol up to several grams, or use Hedgehogs formulation, which combines resveratrol, polydatin and luteolin to obtain higher serum levels.

Hedgehogs formulation? Do you have a pointer to this?

[maxwatt]

you could take 2 to 4 nitro capsules, and add additional 98 or 99% resveratrol up to several grams, or use Hedgehogs formulation, which combines resveratrol, polydatin and luteolin to obtain higher serum levels.

Hedgehogs formulation? Do you have a pointer to this?

Hedgehog's formulation

email me by going to my profile and scrolling down to the email button. I have information about this and other things that might be helpful.

hedgehog has done blood serum measurements, this combination increases the levels, though I don't think the piperine or cyclodextrin are that helpful.

[ppp]

you could take 2 to 4 nitro capsules, and add additional 98 or 99% resveratrol up to several grams, or use Hedgehogs formulation, which combines resveratrol, polydatin and luteolin to obtain higher serum levels.

Hedgehogs formulation? Do you have a pointer to this?

Hedgehog's formulation

email me by going to my profile and scrolling down to the email button. I have information about this and other things that might be helpful.

hedgehog has done blood serum measurements, this combination increases the levels, though I don't think the piperine or cyclodextrin are that helpful.

Email doesn't work for me I'm afraid...

[maxwatt]

you could take 2 to 4 nitro capsules, and add additional 98 or 99% resveratrol up to several grams, or use Hedgehogs formulation, which combines resveratrol, polydatin and luteolin to obtain higher serum levels.

Hedgehogs formulation? Do you have a pointer to this?

Hedgehog's formulation

email me by going to my profile and scrolling down to the email button. I have information about this and other things that might be helpful.

hedgehog has done blood serum measurements, this combination increases the levels, though I don't think the piperine or cyclodextrin are that helpful.

Email doesn't work for me I'm afraid...

If you upgrade to membership status you will be able to use the PM and email features. I apologize that they were disabled for registered users due to spammers registering then PMing us with spam and viral links.

Google "zerumbone osteosarcoma" and you will find that zerumbone, extracted from ginger, is effective against osteosarcoma cell lines in a test tube. Then go to kingherbs dot com and look for information about the substance.

Edited by maxwatt, 11 May 2009 - 12:28 PM.

[Anthony_Loera]

Thanks Max,

I didn't know that the PM and email was available for members.

A