13 replies to this topic

[recon]

Hi,

 

I have several questions about resveratrol and other stilbenoids such as pterostilbene. I have done some small looking-up but I may be very wrong in my conclusions so I need your expertise on this. I hope this will stimulate some well-needed discussions in this dying subforum.

 

1) What is the optimal dosage for resveratrol? (high-dose vs low-dose)

 

Studies seem to converge towards lower dosage compared to higher dosage. I have not yet look into what constitutes a higher dosage compared to a lower dosage since I lack the knowledge of metabolic conversion from rat dosing to human dosing. Still, the bioavailability of resveratrol is so low that maybe a high-dose may be require to even have a low-dose bioavailability.

 

 

Cho, Su-Jung, Un Ju Jung and Myung-Sook Choi. "Differential effects of low-dose resveratrol on adiposity and hepatic steatosis." British Journal of Nutrition 108.12 (2012): 2166–2175. 20 October 2017.

<https://doi.org/10.1...7114512000347>.

"A low dose of RV (0·005 %) appeared to be more effective than a higher dose of RV (0·02 %) for suppressing adiposity and hepatic steatosis development with a significant decrease in body weight gain, plasma TAG and total cholesterol levels."

 

Effects of resveratrol on body weight and food intake in diet-induced obese mice -

"In HFD-fed mice, supplementation of RV at a low dose (0·005 %) significantly suppressed body weight gain after 3 weeks, but the higher dose of RV (0·02 %) was surprisingly not effective [...]"

 

Effects of resveratrol on fat accumulation in diet-induced obese mice -

"Only the low dose of RV (0·005 %) effectively reduced the weight of the epididymal and retroperitoneal adipose depots in HFD-fed mice (Fig. 1). Hence, overall total visceral adipose weight was significantly lowered by RV supplementation, although the low dose appeared to be more effective than the higher dose [...]"

 

Effect of resveratrol on plasma and hepatic lipid levels in diet-induced obese mice -

"Remarkably, RV was more effective at a low dose (0·005 %), but not at a higher dose (0·02 %), for reducing plasma TAG and total cholesterol levels in HFD-fed mice. [...]

RV caused a marked decrease in the number and size of liver fat droplets, and the low dose of RV (0·005%) appeared to be more effective than the higher dose of RV (0·02 %)."

 

 

Pearson, Kevin J., et al. "Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan." Cell Metabolism 8.2 (2008): 157–168. 20 October 2017.

<https://dx.doi.org/1...t.2008.06.011>.

 

 

Survival -

"In the lower-dose (HCLR) group, maximum life span was also increased, while this effect did not reach significance for the higher dose (HCR) [...]"

 

"While the HCR group had a very slight decrease in body weight that was not statistically significant, the HCLR group displayed a significant increase in body weight, despite consuming a similar amount of food [...]"

 

 

2) Should resveratrol be taken with meal?

 

I find that this is irrelevant. I take it along with meal as to take it with niacin and others. I hope for resveratrol to activate NAMPT. Given that I take resveratrol with meal, a standard meal seems to be better than a high-fat one.

 

Vaz-da-Silva, M, et al. "Effect of food on the pharmacokinetic profile of trans-resveratrol." Int J Clin Pharmacol Ther. 46.11 (2008): 564-70. 20 October 2017. <https://www.ncbi.nlm...bmed/19000554>.

"The rate of absorption of trans-resveratrol following an oral 400 mg single-dose was significantly delayed by the presence of food, as reflected by Cmax and tmax. However, the extent of absorption, as reflected by AUC- yen, was not affected in a relevant way."

 

la Porte, C, et al. "Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects." Clin Pharmacokinet. 49.7 (2010): 449-54. 20

October 2017. <https://doi.org/10.2...0000000-00000>.

 

"In order to maximize trans-resveratrol exposure, it should be taken with a standard breakfast and not with a high-fat meal."

 

 

3) What should be taken along with resveratrol?

 

Leucine - synergistic effect to Sirt1

https://www.ncbi.nlm...pubmed/22913271

 

NAD+ precursors - the precursors convert to NAM in the intestine and NAMPT converts them back, and resveratrol seems to activate NAMPT.

 

 

4) What is the optimal dosage for pterostilbene?

 

Pterostilbene seems to be the same as resveratrol.

"a bell-curve that may favor lower dosages such as is found in food consumption rather than higher dosages from supplementation."

https://examine.com/.../pterostilbene/

 

This is my primary question that I want to know. 50 mg is sold everywhere but MegaResveratrol sold at around 250 mg. That is 5x the dosage per supplementation. Should I be taking that much?

 

Edited by recon, 21 October 2017 - 02:16 AM.

[maxwatt]

recon wrote "should I be taking that much?"

 

As he pointed out from the studies he cited, there is a U-shaped dose/response curve for many of the effects.  But it depends on what your goal is on taking these, or any supplement.

 

https://www.ncbi.nlm...les/PMC5610395/ showed greater glucose control in human type 2 diabetics with resveratrol at doses greater than 100 mg vs under 100 mg.

 

Self experimenters in this forum found exercise benefits in highly trained athletes at doses of 400 mg; studies looking for this effect at lower doses found none.

 

There are many other such if you look for them.  So determine what you wish to achieve and tune the dosage to achieve that effect.  Hopefully with an objective measure, such as blood work before,during and after.  Or a bicycle power meter to measure your output, or time to complete a fixed distance running course. And with a competent coach to help you  sort out  the effect from the training effect one might expect with an exercise program.  Et cetera.

 

 

[recon]

recon wrote "should I be taking that much?"

As he pointed out from the studies he cited, there is a U-shaped dose/response curve for many of the effects. But it depends on what your goal is on taking these, or any supplement.

https://www.ncbi.nlm...les/PMC5610395/ showed greater glucose control in human type 2 diabetics with resveratrol at doses greater than 100 mg vs under 100 mg.

Self experimenters in this forum found exercise benefits in highly trained athletes at doses of 400 mg; studies looking for this effect at lower doses found none.

There are many other such if you look for them. So determine what you wish to achieve and tune the dosage to achieve that effect. Hopefully with an objective measure, such as blood work before,during and after. Or a bicycle power meter to measure your output, or time to complete a fixed distance running course. And with a competent coach to help you sort out the effect from the training effect one might expect with an exercise program. Et cetera.

Thanks maxwatt! I’m trying to determine the best dosage for just mere Sirtuin activation. Just worried that pterostilbene and resveratrol may work in some sort of a feedback system that will eventually downregulate things.

And, what about you?
Do you take pterostilbene or resveratrol? How much and how do you take them? What’s your rationale?

[maxwatt]

PM me if you want to discuss this

[sensei]

The newest studies out show resveratrol analogues revert senescent cells to normal -- that started to divide within 12-24 hours.

 

"In the new study, the researchers found that splicing factors can be switched back on with chemicals, making senescent cells not only look physically younger, but start to behave more like young cells and start dividing.

The researchers applied compounds called resveratrol analogues—chemicals based on a substance naturally found in red wine, dark chocolate, red grapes and blueberries—to cells in culture that caused splicing factors to be switched back on.

Within only a few hours, the cells appeared younger and started to rejuvenate to behave like young cells and divide.

“When I saw some of the cells in the culture dish rejuvenating I couldn't believe it,” Eva Latorre, Ph.D., a research associate at the University of Exeter, said in a statement. “I repeated the experiments several times and in each case the cells rejuvenated.”"

 

 

https://www.rdmag.co...ing-aging-cells

 

 

of note, resveratrol itself does not have the same action/activity

 

[recon]

The newest studies out show resveratrol analogues revert senescent cells to normal -- that started to divide within 12-24 hours.

"In the new study, the researchers found that splicing factors can be switched back on with chemicals, making senescent cells not only look physically younger, but start to behave more like young cells and start dividing.
The researchers applied compounds called resveratrol analogues—chemicals based on a substance naturally found in red wine, dark chocolate, red grapes and blueberries—to cells in culture that caused splicing factors to be switched back on.
Within only a few hours, the cells appeared younger and started to rejuvenate to behave like young cells and divide.
“When I saw some of the cells in the culture dish rejuvenating I couldn't believe it,” Eva Latorre, Ph.D., a research associate at the University of Exeter, said in a statement. “I repeated the experiments several times and in each case the cells rejuvenated.”"


https://www.rdmag.co...ing-aging-cells


of note, resveratrol itself does not have the same action/activity

That’s a great find. I haven’t take a proper look at it but it seemed to be in-vitro.

Nevertheless, it supports my use of pterostilbene alongside resveratrol.

[Oakman]

of note, resveratrol itself does not have the same action/activity

 

I understood just the opposite. In the charts and graphs, typically #1 was resveratrol, the rest being analogs or related compounds. In each case Resveratrol had effects on senescence factors. What varied among the resveralogues was which factors were more effected.

 

Overall, my understanding of the study's purpose was to determine how and why different resveralogues factors were effective, NOT that resveratrol by itself was not.  To wit...

 

"Unfortunately, resveratrol has multiple biological effects, including a reduction of pro-inflammatory cytokine expression [23] as well as its canonical activity against SIRT1 [24] thus a ‘clean’ assessment of the effects of moderation of splicing factor levels on cell physiology cannot be achieved using this compound alone.

 

We have overcome this limitation through development of a novel library of resveratrol-related compounds (resveralogues) which are all capable of either directly or indirectly influencing the expression of multiple splicing factors of both SRSF and HNRNP subtypes, whilst exhibiting differential activity against SIRT1 and SASP. Treatment of senescent human fibroblasts from different developmental lineages with any of these novel molecules shifts expression patterns of multiple splicing factors to those characteristic of much earlier passage cells."

 

I would say a good analogy is that they were trying to find the best 'bullet(s)' to hit the senescence target, rather than using the reveratrol 'buckshot' approach. This is also helpful if the goal may be to develop a patentable compound for commercial use.

[sensei]

Resveratrol itself does not reverse senescent cells.

Structural analogues of Resveratrol do.

This is fact.

Resveratrol can help to extend the lifespan of cells before senescence occurs, but does not cause reversal/rejuvenation of senescent cells, resulting in cellular division.

Edited by sensei, 03 December 2017 - 06:42 PM.

[sensei]

Not to mention there are multiple anecdotal reports and potentially some studies that show Resveratrol can cause tendon rupture.

That's why the synthetically produced Resveratrol analogs which in the cited study in the previous posts were not naturally occurring as far as I recollect make more sense to use 4 the reversal of senescent cells

[hav]

The newest studies out show resveratrol analogues revert senescent cells to normal -- that started to divide within 12-24 hours.

 

....

 

of note, resveratrol itself does not have the same action/activity

 

Looking at chart 5 of the study, it looks to me that in many cases resveratrol itself outperformed the analogs with senescent cells. It outperformed all but the #4 analog which beat it slightly on MRC5 lung cells.  The analogs did best on HF043 human neonatal foreskin fibroblasts cells but I'm not sure what specific application that might suggest.  Resveratrol and it's #2 metabolite significantly outperformed all analogs on more typical NHDF human skin cells, significantly outperformed the control in all cases, and significantly exceeded all analogs in telomere lengthening, achieving lengths only slightly shorter than those of young cells.  Personally, I would only be interested in the analogs for oral supplementing if they offered a bio-availability advantage.  Maybe there might be an advantage using analogs in a topical skin treatment application?

 

Howard

[Oakman]

Readers here may be interested in this thread - as no matter how 'good' some of this sounds, it is in vitro and Resveratrol orally has notoriously poor bioavailability (not absorption) due to being broken down into metabolites so quickly by the liver, etc.. So an idea being discussed is to try to delay the breakdown, keeping blood levels up for as long as is feasibly possible.  

[recon]

Do we have commercially available versions of the top performing analogues in the studies?

[Asta]

I prefer pterostilbene to resveratol. Took resveratol years ago, an noticed no change. However, it was when resveratol got its first media blurb. Everyone saying to drink red wine etc. 

I suspect I got an early, quickie money scheme batch. 

I take pterostilbene daily right now. Helps with energy levels.

 

Can anyone recommend a good resveratol to buy? 

[Oakman]

Emperical Labs, Lipisomal Resveratrol / Curcumin - this, or any other liposomal formulation has the best chance of actually getting into your tissues.