276 replies to this topic

[Oakman]

Liposomal and sublingual appear to me to be the only efficient candidates to quickly and easily get free-R throughout the body. Why fight a battle against P450 enzymes if you don't have to, at least initially? I have both formulations arriving after Xmas and a plan on using them to complement each other towards a minimum 24hr perfusion of R as the in vitro study suggests is needed to turn splicing genes back on.

 

Any inhibition of hepatic P450 enzymes attempted after that would merely be a plus to the treatment protocol, not a requirement. 

[Daniel Cooper]

I don't even think I would fool with sublingual.  Based on what sensei posted it seems like liposomal is the way to go all around.  

 

Which liposomal formulation will you be doing?

 

 

 

[Oakman]

I don't even think I would fool with sublingual.  Based on what sensei posted it seems like liposomal is the way to go all around.  

 

Which liposomal formulation will you be doing?

 

 

https://www.biotivia...oduct/transmax/

Edited by Oakman, 21 December 2017 - 04:54 PM.

[sensei]

I have both formulations arriving after Xmas and a plan on using them to complement each other towards a minimum 24hr perfusion of R as the in vitro study suggests is needed to turn splicing genes back on.

I'm not so sure the 24 hours is applicable to liposomal delivery.

Much more resveratrol will be delivered to the cytoplasm of the cells via liposomal delivery, than just culture medium as in the study.

There is no data regarding the absorption rate via serum, nor a concentration (internal to the cell) necessary to achieve the seen effects.

[Daniel Cooper]

 

I don't even think I would fool with sublingual.  Based on what sensei posted it seems like liposomal is the way to go all around.  

 

Which liposomal formulation will you be doing?

 

 

https://www.biotivia...oduct/transmax/

 

 

 

Yeah, I understand buccal/sublingual delivery.  

 

That gets it into the bloodstream.  But "naked" resveratrol would still be subject to metabolism by the liver while liposomal resveratrol would be shielded from that metabolism, would it not?

[Oakman]

I realized that the Biotivia product I mentioned is not liposomal. duh. rather enhanced bioavalability

Perhaps a little discussion of available delivery types would help?

Which works better, cost, and best results, any combo that make sense and why.

 

1) bucal 

2) sublingual (same as bucal?)

 

then

2) liposomal

3) bioavalability ingredients

4) micronized

5) something else?

 

 

[Nate-2004]

Wouldn't just dumping the capsule contents or R powder under the tongue be sufficient enough? Maybe dissolve it in some ethanol first? Might burn a little but why not?

 

2400mg of trans-R into 10ml Ethanol would result in 240mg/ml. You could keep 1 ml under your tongue every other hour all day long and this would possibly accomplish more than trusting liposomal manufacturers to do it properly.

Edited by Nate-2004, 21 December 2017 - 07:59 PM.

[Oakman]

Wouldn't just dumping the capsule contents or R powder under the tongue be sufficient enough? Maybe dissolve it in some ethanol first? Might burn a little but why not?

 

2400mg of trans-R into 10ml Ethanol would result in 240mg/ml. You could keep 1 ml under your tongue every other hour all day long and this would possibly accomplish more than trusting liposomal manufacturers to do it properly.

 

Why not indeed! I for whatever works best, whatever that is. The trouble is that it's unclear which method does, in fact, work well enough to do what's needed without overdosing. That's one of my concerns, is that in a quest to get maximum bio-availability and maintain >24 hr serum levels, we inadvertently overdose. Being able to equal concentrations used in the in vitro study, might, if possible, be an answer. But what is needed dose-wise for any of the formulations is unclear to me to do that.

 

Here they talk about the effects of micro-dosing...

 

"LOW DOSE STUDIES Up until recently, there have been insufficient studies on humans to help answer the question about optimal dosages. As a result, many researchers believe that a beneficial human dosage would need to be as high as the dosages given to the mice in the groundbreaking “Harvard Study”. This study was published in the journal Nature and demonstrated improved health and survival in mice fed a high-fat diet supplemented with resveratrol. The mice in this study received a resveratrol dosage of 22.4 mg/kg day, which translates to about 1.5–2 grams in humans – a potentially worrisome dose when considering that one animal study reported that higher dosages potentiate a death signal by down-regulating redox proteins and up-regulating proapoptotic proteins. It’s important to note that this was a preliminary study in which a high dose was used in order to achieve an observable effect. Including those done on humans, more sensible dosing studies have been completed that provide evidence that a lower dosage of resveratrol is safer and more effective. These studies may help put to rest the concern that resveratrol’s benefits can only be achieved at high dosages. They may also eliminate safety concerns associated with mid-range dosages: • 5 mg/day (twice a day) for four weeks improved insulin sensitivity and reduced oxidative stress.

 

• 150 mg/day for 30 days induced metabolic changes in obese humans, mimicking the effect of calorie restriction. • 40 mg/day for six weeks suppressed oxidative and inflammatory stress in healthy subjects. • Sponsored research in animal models demonstrated that the “biological effects of resveratrol can be achieved at a dose that is more than 10-fold lower than that used in the Harvard study.”

• A study in mice reported that dietary consumption of a low dose of resveratrol, at doses that can be readily achieved in humans, partially mimics caloric restriction and inhibits some aspects of the aging process."

[sthira]

Have you guys read the "500 Club" resveratrol thread on this site from like eight or ten years ago? It might be interesting to revisit that -- seems like we're slowly drifting back to what's been done before by a larger group of motivated resveratrol people. We all got really excited abour more and more resveratrol, I recall, and I don't think it ever amounted to too much.

Anthony's resveratrol seemed purest at the time, I think he still sells it.

Injecting the stuff into veins seems pretty extreme, given the lack of givens.

[Daniel Cooper]

Looks like Pure Bulk is selling 98% trans-resveratrol on their site.

 

 

 

[Nate-2004]

 

Wouldn't just dumping the capsule contents or R powder under the tongue be sufficient enough? Maybe dissolve it in some ethanol first? Might burn a little but why not?

 

2400mg of trans-R into 10ml Ethanol would result in 240mg/ml. You could keep 1 ml under your tongue every other hour all day long and this would possibly accomplish more than trusting liposomal manufacturers to do it properly.

 

Why not indeed! I for whatever works best, whatever that is. The trouble is that it's unclear which method does, in fact, work well enough to do what's needed without overdosing. That's one of my concerns, is that in a quest to get maximum bio-availability and maintain >24 hr serum levels, we inadvertently overdose. Being able to equal concentrations used in the in vitro study, might, if possible, be an answer. But what is needed dose-wise for any of the formulations is unclear to me to do that.

 

Here they talk about the effects of micro-dosing...

 

"LOW DOSE STUDIES Up until recently, there have been insufficient studies on humans to help answer the question about optimal dosages. As a result, many researchers believe that a beneficial human dosage would need to be as high as the dosages given to the mice in the groundbreaking “Harvard Study”. This study was published in the journal Nature and demonstrated improved health and survival in mice fed a high-fat diet supplemented with resveratrol. The mice in this study received a resveratrol dosage of 22.4 mg/kg day, which translates to about 1.5–2 grams in humans – a potentially worrisome dose when considering that one animal study reported that higher dosages potentiate a death signal by down-regulating redox proteins and up-regulating proapoptotic proteins. It’s important to note that this was a preliminary study in which a high dose was used in order to achieve an observable effect. Including those done on humans, more sensible dosing studies have been completed that provide evidence that a lower dosage of resveratrol is safer and more effective. These studies may help put to rest the concern that resveratrol’s benefits can only be achieved at high dosages. They may also eliminate safety concerns associated with mid-range dosages: • 5 mg/day (twice a day) for four weeks improved insulin sensitivity and reduced oxidative stress.

 

• 150 mg/day for 30 days induced metabolic changes in obese humans, mimicking the effect of calorie restriction. • 40 mg/day for six weeks suppressed oxidative and inflammatory stress in healthy subjects. • Sponsored research in animal models demonstrated that the “biological effects of resveratrol can be achieved at a dose that is more than 10-fold lower than that used in the Harvard study.”

• A study in mice reported that dietary consumption of a low dose of resveratrol, at doses that can be readily achieved in humans, partially mimics caloric restriction and inhibits some aspects of the aging process."

 

 

It doesn't seem conceivable that such a low dose only once a day, when it basically leaves your system in a couple hours, would do much of anything at all. I can see how maybe redosing low doses sublingually every hour or two might do something without overdosing.

[Nate-2004]

Have you guys read the "500 Club" resveratrol thread on this site from like eight or ten years ago? It might be interesting to revisit that -- seems like we're slowly drifting back to what's been done before by a larger group of motivated resveratrol people. We all got really excited abour more and more resveratrol, I recall, and I don't think it ever amounted to too much.

Anthony's resveratrol seemed purest at the time, I think he still sells it.

Injecting the stuff into veins seems pretty extreme, given the lack of givens.

 

I'll have to go back and look to see what they were trying back then. It's always good to revisit things, especially in light of the study posted originally on this thread.

[Rocket]

Looks like liposomal resveratrol is readily available. Seems to be resveratrol + curcumin.  Amazon has several vendors.

 

Yeah I saw those products a few days ago...... So if the R is getting into the tissues and not being broken down, why are there no reviews of people reporting to be feeling rejuvenated? Cellular rejuvenation, one would assume, would be huge.

[Oakman]

 

 

Wouldn't just dumping the capsule contents or R powder under the tongue be sufficient enough? Maybe dissolve it in some ethanol first? Might burn a little but why not?

 

2400mg of trans-R into 10ml Ethanol would result in 240mg/ml. You could keep 1 ml under your tongue every other hour all day long and this would possibly accomplish more than trusting liposomal manufacturers to do it properly.

 

Why not indeed! I for whatever works best, whatever that is. The trouble is that it's unclear which method does, in fact, work well enough to do what's needed without overdosing. That's one of my concerns, is that in a quest to get maximum bio-availability and maintain >24 hr serum levels, we inadvertently overdose. Being able to equal concentrations used in the in vitro study, might, if possible, be an answer. But what is needed dose-wise for any of the formulations is unclear to me to do that.

 

Here they talk about the effects of micro-dosing...

 

"LOW DOSE STUDIES Up until recently, there have been insufficient studies on humans to help answer the question about optimal dosages. As a result, many researchers believe that a beneficial human dosage would need to be as high as the dosages given to the mice in the groundbreaking “Harvard Study”. This study was published in the journal Nature and demonstrated improved health and survival in mice fed a high-fat diet supplemented with resveratrol. The mice in this study received a resveratrol dosage of 22.4 mg/kg day, which translates to about 1.5–2 grams in humans – a potentially worrisome dose when considering that one animal study reported that higher dosages potentiate a death signal by down-regulating redox proteins and up-regulating proapoptotic proteins. It’s important to note that this was a preliminary study in which a high dose was used in order to achieve an observable effect. Including those done on humans, more sensible dosing studies have been completed that provide evidence that a lower dosage of resveratrol is safer and more effective. These studies may help put to rest the concern that resveratrol’s benefits can only be achieved at high dosages. They may also eliminate safety concerns associated with mid-range dosages: • 5 mg/day (twice a day) for four weeks improved insulin sensitivity and reduced oxidative stress.

 

• 150 mg/day for 30 days induced metabolic changes in obese humans, mimicking the effect of calorie restriction. • 40 mg/day for six weeks suppressed oxidative and inflammatory stress in healthy subjects. • Sponsored research in animal models demonstrated that the “biological effects of resveratrol can be achieved at a dose that is more than 10-fold lower than that used in the Harvard study.”

• A study in mice reported that dietary consumption of a low dose of resveratrol, at doses that can be readily achieved in humans, partially mimics caloric restriction and inhibits some aspects of the aging process."

 

 

It doesn't seem conceivable that such a low dose only once a day, when it basically leaves your system in a couple hours, would do much of anything at all. I can see how maybe redosing low doses sublingually every hour or two might do something without overdosing.

 

 

Well, if we're talking about dosing for 24hrs, multiple doses are needed. 2400mg is a lot of R, isn't it? 250mg-500mg is the normal daily dose I've seen.

But the low does studies are about R being effective at lowest daily doses, 40-150mg, not 240mg X10. So say, six daily small doses ~4 hrs apart would need to be real tiny to end up with a small daily dose. I guess the question is - How much is enough, but not too much? Supps often have different effects at high and low doses. Another thing to consider.

[Daniel Cooper]

FYI - These guys have liposomal resveratrol without the curcumin.

 

I know absolutely nothing about this vendor btw.

 

Liposomal Resveratrol

[Rocket]

I bought one of the brands of liposomal R. They all seem to be 75mg/dose. I bought a larger bottle. My plan is to dose 2-3 doses every 3 hours throughout the day (or 4x).

[Daniel Cooper]

I bought one of the brands of liposomal R. They all seem to be 75mg/dose. I bought a larger bottle. My plan is to dose 2-3 doses every 3 hours throughout the day (or 4x).

 

 

Did you get one that is R + Curcumin or R only?

[Rocket]

It has C in it as well.

[Oakman]

I had been wondering why the liposomal formulations seem to combine R + C, but it seems to greatly increase serum concentrations, in mice, compared to either substance alone.

 

http://onlinelibrary.../ijc.24336/full

 

 

Also here,

 

"Greatest enhancement in permeability was received by resveratrol when combined with other agents: quercetin (310%), curcumin (300%), and quercetin and curcumin (323% and 350% with piperine). Increased permeability was recorded in case of curcumin when combined with quercetin alone (147%) and both quercetin and resveratrol (188%); addition of piperine resulted in a 229% increase in permeability [133]."

[Nate-2004]

Well, if we're talking about dosing for 24hrs, multiple doses are needed. 2400mg is a lot of R, isn't it? 250mg-500mg is the normal daily dose I've seen.

But the low does studies are about R being effective at lowest daily doses, 40-150mg, not 240mg X10. So say, six daily small doses ~4 hrs apart would need to be real tiny to end up with a small daily dose. I guess the question is - How much is enough, but not too much? Supps often have different effects at high and low doses. Another thing to consider.

 

 

Yeah I just don't know, based on the charts posted earlier, that taking it in doses that small throughout the day would put even a blip on the radar. One of the charts showed that the non-metabolite trans-Resveratrol was only detectable in relatively small amounts (10 to 15 ng/ml) for less than an hour and a half at a higher dose than you're talking about.  It's so rapidly metabolized that it's not even going to do a damn thing. There has to be a reason why people aren't showing the results they're seeing in vitro (original post) on senescent cells and telomeres.

Edited by Nate-2004, 22 December 2017 - 11:44 PM.

[Rocket]

Well, in about a week I'll be able to report on taking 225mg doses of liposomal R+C 4 to 5x throughout the day. My fear is losing muscle mass like was reported on the bodybuilding forums by injecting R.

[Oakman]

 

Well, if we're talking about dosing for 24hrs, multiple doses are needed. 2400mg is a lot of R, isn't it? 250mg-500mg is the normal daily dose I've seen.

But the low does studies are about R being effective at lowest daily doses, 40-150mg, not 240mg X10. So say, six daily small doses ~4 hrs apart would need to be real tiny to end up with a small daily dose. I guess the question is - How much is enough, but not too much? Supps often have different effects at high and low doses. Another thing to consider.

 

 

Yeah I just don't know, based on the charts posted earlier, that taking it in doses that small throughout the day would put even a blip on the radar. One of the charts showed that the non-metabolite trans-Resveratrol was only detectable in relatively small amounts (10 to 15 ng/ml) for less than an hour and a half at a higher dose than you're talking about.  It's so rapidly metabolized that it's not even going to do a damn thing. There has to be a reason why people aren't showing the results they're seeing in vitro (original post) on senescent cells and telomeres.

 

 

I agree, but it seems that it would be possible to adjust for that. That chart you mentioned was for ordinary R 500mg oral. It wasn't a bad result actually, just a lot of R to get and stay at higher levels. Bottom line, it did work.

 

Seeing as I don't know which way to administer will provide the desired results against senescent cells, I'm going to try both high and low doses, in 3 different timed formulations of R+ extras. Each week I'll do a 24-36 hr "Imersion therapy". Because the time frames are short, all the protocols should be safe.

 

First, I ordered a combo C & R liposomal (200mg/75mg dose), second a pure form of R used in human studies (500-2000mg dose), and last the bucal version (150mg dose) above. I have EMIQ (Quercetin), whey-cucumin complex curcumin, and peperine to add for additional bioavailability.  For these experiments I am also adding AC-11 to each protocol to (in theory) support DNA repair of telomere ends when the RNA splicing genes are rejuvenated and produce splicing factors anew. Exciting!

[Nate-2004]

 

Looks like liposomal resveratrol is readily available. Seems to be resveratrol + curcumin.  Amazon has several vendors.

 

Yeah I saw those products a few days ago...... So if the R is getting into the tissues and not being broken down, why are there no reviews of people reporting to be feeling rejuvenated? Cellular rejuvenation, one would assume, would be huge.

 

 

I agree. My best guess is liposomes aren't the answer or perhaps the manufacturing process for some of these on sale are not legit or badly executed. The main goal should be preventing enzymes from eating it up too quickly, which means discovering which enzymes these are specifically. However I should be seeing a lot of rejuvenation as well even after a couple rounds of this.

Edited by Nate-2004, 23 December 2017 - 05:21 PM.

[Oakman]

 

 

Looks like liposomalresveratrol is readily available. Seems to be resveratrol + curcumin.  Amazon has several vendors.

 

Yeah I saw those products a few days ago...... So if the R is getting into the tissues and not being broken down, why are there no reviews of people reporting to be feeling rejuvenated? Cellular rejuvenation, one would assume, would be huge.

 

 

I agree. My best guess is liposomes aren't the answer or perhaps the manufacturing process for some of these on sale are not legit or badly executed. The main goal should be preventing enzymes from eating it up too quickly, which means discovering which enzymes these are specifically. However I should be seeing a lot of rejuvenation as well even after a couple rounds of this.

 

 

Liposomes are truly fascinating. But their certainly could be junk available too. The liposomal R+C I'm waiting for turns out to be from a local Colorado manufacturer. I didn't realize when I ordered from Amazon that they were close by! Hopefully theirs is a quality product and does what it's supposed to. Their promo sheet highlights their experience and the inferior competition, so here's hoping anyway.

Edited by Oakman, 24 December 2017 - 12:35 AM.

[Rocket]

Looks like liposomalresveratrol is readily available. Seems to be resveratrol + curcumin. Amazon has several vendors.

Yeah I saw those products a few days ago...... So if the R is getting into the tissues and not being broken down, why are there no reviews of people reporting to be feeling rejuvenated? Cellular rejuvenation, one would assume, would be huge.

I agree. My best guess is liposomes aren't the answer or perhaps the manufacturing process for some of these on sale are not legit or badly executed. The main goal should be preventing enzymes from eating it up too quickly, which means discovering which enzymes these are specifically. However I should be seeing a lot of rejuvenation as well even after a couple rounds of this.

Liposomes are truly fascinating. But their certainly could be junk available too. The liposomal R+C I'm waiting for turns out to be from a local Colorado manufacturer. I didn't realize when I ordered from Amazon that they were close by! Hopefully theirs is a quality product and does what it's supposed to. Their promo sheet highlights their experience and the inferior competition, so here's hoping anyway.

Have you come up with your dosing regimen? I will be taking about 1 to 1.2g throughout the day of l-R... Not sure how much l-C but quite a bit.

Edited by Rocket, 24 December 2017 - 02:00 AM.

[Oakman]

Well, I’ve come up with some ideas, yes.  First, is it possible to, try and duplicate uM levels of the in vitro studies? That appears difficult, but with intestinal and hepatic reductions for R so great, it seems best to bypass them as much as possible, and focus mostly on methods that do not include P450 enzyme degradation..

 

That's where I hope alternative R formulations brings some relief. Sublingual/Buccal, liposomal, and micronized offer different routes to bio-availability, but after reading way too many studies and papers recently, what stands out to me each version is only somewhat useful to overcome the bio-availability issue. So an idea might be to combine modalities to obtain some serum R from each.

 

Here's a draft for a 30 hr regimen with five cycles.  Optional - I’m taking: AC-11 350 mg 7am/7pm/7am.

 

Sources --------------------------------

S-B for Sublingual/Buccal  -  trans-resveratrol 75mg tablet in flavored base

L  for Liposomal   - Resveratrol/Curcumin  75 mg/200 mg mix per 6 ml

O-M  for Oral Micronized*  -   +15% assimilated, 2-3x Cmax & AUC  500mg capsule

U for UltraCUR - Curcumin bound to Whey protein isolate 25 mg C per 1000mg whey

 

Schedule ------------------------------

7am             1pm           7pm             1am            7am                       Total Free-R**

S-B 75 mg   S-B 75 mg  S-B 75 mg   S-B 75 mg  S-B 75 mg                375 112 mg

L 37.5 mg     L 37.5 mg   L 37.5 mg   L 37.5 mg   L 37.5 mg                  188  94 mg

         --->   ---->    ---->                                              Curcumin               500 250 mg

O-M 250mg  O-M 250mg O-M 250mg O-M 250mg O-M 250 mg         1250  50 mg

U 500 mg      U 250 mg    U 500 mg    U 250 mg    U 250 mg             (1750) (44) mg

                                                                                estimated total free R** 256mg

                                                                                estimated total free C** 294mg

     

*Can be taken with Lecithins, palm oils, rapeseed oils, soybean oils, sunflower oils, whey protein isolate shake.  ** Estimated bioavailable free R, C

 

Another way to look at the free R issue and the schedule above is on a time continuum with each modality creating a rising/falling curve with variable length and AUC. Then each curve overlaps and sums within the six hour period, to give the total bioavailable concentration once you add the C. Finally, the addition of C increases bioavailability a bit further for maximal dose.

 

Nothing below is real or based on any studies, simply an illustration.....

 

 

Edited by Oakman, 26 December 2017 - 05:18 PM.

[Nate-2004]

Monday:

 

20 ML Ethanol + 2400mg R + 2400mg Q + 50mg Dasatinib -> Shake

 

1 ML under tongue each hour and a half (120mg R) for 12 hrs

 

Rejuvenation? Actually maybe some. There's really no telling without a what to test as far as biomarkers go. I notice I look great in the mirror at least and for the last couple days I've felt pretty damn good. I realized I should only do this once a week because I'm still going back and forth between fission / fusion which means sulforaphane is going to ramp up the P450 enzymes that gobble up the R, so I have to do the R on days when I'm doing the NR.

 

I didn't realize adding C can improve the bioavailability. I may replace the Dasatinib with C on Sunday. I really should only be including D every 6 months.

Edited by Nate-2004, 26 December 2017 - 10:30 PM.

[Daniel Cooper]

I don't quite understand what you're trying to achieve with that combo.

 

The resveratrol to rescue and rejuvenate senescent cells, and the quercetin and dasatinib to induce apoptosis in senescent cells?  

 

Would seem to be at cross purposes.

 

 

 

[Rocket]

I don't quite understand what you're trying to achieve with that combo.

The resveratrol to rescue and rejuvenate senescent cells, and the quercetin and dasatinib to induce apoptosis in senescent cells?

Would seem to be at cross purposes.

Seems like in this case it might not make sense to take that stack. Either kill senescent cells or rejuvenate them... How can you do both at the same time. Granted I am not a cell biologist, but...

It may be best to run them in alternating cycles. Run the R to rejuvenate for 8 weeks, then a short run of D to kill whatever senescent cells remained senescent. So on and so forth.

Edited by Rocket, 27 December 2017 - 02:06 AM.

[Nate-2004]

I don't quite understand what you're trying to achieve with that combo.

 

The resveratrol to rescue and rejuvenate senescent cells, and the quercetin and dasatinib to induce apoptosis in senescent cells?  

 

Would seem to be at cross purposes.

 

The thought crossed my mind but Q goes well with R in that it will inhibit the P450 enzymes that metabolize R. Yes, part of the goal is to help R rescue senescent cells, but I don't think that necessarily means D+Q's induction of apoptosis in senescent cells is necessarily going to prevent the former.

 

Also, it'd been 6 months since my last round of D+Q, I figured I would do it differently this time, with the sublingual ethanol solution.

 

Rocket's idea above might be a better idea, but there's no evidence for or against doing it all at the same time.

Edited by Nate-2004, 27 December 2017 - 03:47 AM.