Resveratrol

[BBB]

Doc,

I believe that you were straddling the fence as far as the value of resveratrol is concerned. Lately it appears that you are more convinced of its beneficial value. I’m I correct?

 

[BurghHardcore]

Not to answer for the doc...b/c I'm curious about his reply...but I do recall seeing on a thread in here that it was more of the delivery methods used, dosing patterns/amounts that he was unsure about than the overall use of Resveratrol itself.

In for the Docs reply!

 

[dinoiii]

This may be my most straightforward post of all time...

BurghHardcore is correct - I have cautioned most strongly against delivery methods. Oral is just fine PROVIDED the dose is large enough.

Oh goody, does this mean it's a "complete" AI in anti-E formulas? Feck no! In fact, a monotherapy with it in most instances where an AI is truly needed would prove messy. The two things that must be considered in hormonal modulation attempts with this compound are that NOT all situations/environments see resveratrol acting the same way.

(1) Levels of endogenous estrogen...In times of HIGH estrogen, resveratrol works as an antagonist. In times of LOW estrogen, resveratrol actually works in some instances as an AGONIST. It is because of this agonistic activity that women are often cautioned against use, especially if they know their ER status.

(2) Ratio of ER's...this we have spoken at length about (ER-B vs. ER-A)

Now, it doesn't stop there. It also possesses a quick peak after doses are administered which would mean, multiple daily doses are required in order to achieve adequate blockade and steady serum states of any hormonal offering.

I love it's life extension (cancer prevention/cardiovascular/longevity) data! In fact, the telomeric DNA expression stuff is unreal.

So, I guess what I am saying is - the compound is ok - even in an anti-E formula - provided people know what to do with it. This can probably be said about any compound though. It's a reason I have issue with formulas that don't really do well instructing on how to use them best which is a problem that even goes deeper than being under-dosed.


D_

 

[broons]

What about Buccal delivery? There is a study from 2002 wherein 1mg resveratrol in 50ml of solution was held and swished in the mouth for 1 minute. After two minutes, blood levels of resveratrol reached 37ng/ml. However, its hard to tell what blood levels were two minutes after that and it is limited to the one study. I think buccal may offer better absorption in that it is not subjected to first pass liver metabolism but only up to a point due to limited surface area. Perhaps even doing some Listerine beforehand would be even better as permeability would most likely be imcreased.

 

[RawStrength]

How about subres from taurus nutrition? They have a oral delivery, any good?

 

[dinoiii]

What about Buccal delivery? There is a study from 2002 wherein 1mg resveratrol in 50ml of solution was held and swished in the mouth for 1 minute. After two minutes, blood levels of resveratrol reached 37ng/ml. However, its hard to tell what blood levels were two minutes after that and it is limited to the one study. I think buccal may offer better absorption in that it is not subjected to first pass liver metabolism but only up to a point due to limited surface area. Perhaps even doing some Listerine beforehand would be even better as permeability would most likely be imcreased.

As above; Resveratrol already has a quick peak...I imagine that is why study authors settled on measurement at 2 minutes although I am not in recollection of the study you speak of so am not 100% on that as I haven't read their methods or discussion.

It is estimated that the permeability of the buccal mucosa is 4-4000 times (notice the WIDE range) greater than that of the skin. As indicative by the wide range in this reported value, there are considerable differences in permeability between different regions of the oral cavity because of the diverse structures and functions of the different oral mucosae. In general, the permeabilities of the oral mucosae decrease in the order of sublingual greater than buccal, and buccal greater than palatal. This rank order is based on the relative thickness and degree of keratinization of these tissues, with the sublingual mucosa being relatively thin and non-keratinized, the buccal thicker and non-keratinized, and the palatal intermediate in thickness but keratinized.

To it's credit and discredit; it contradicts what is known about sublingual versus buccal in the advantage department. Due to two important differences between the sublingual mucosa and the buccal mucosa, but focusing on one might do the most justice. First difference being in the permeability characteristics of the region, where the buccal mucosa is less permeable and is thus not able to give a rapid onset of absorption (i.e., more suitable for a sustained release formulation). So, we are talking about something that should SLOW absorption but sees a peak at what might look like 2 minutes (failing compared to regular oral delivery).

Interesting comment on Listerine; although I don't know that that would be anything more than sheer pontification. Grand scheme, it couldn't hurt...BUT would the likely increased cost of such delivery methods be worth it and/or necessary from an end-result standpoint...I am unsure.

How about subres from taurus nutrition? They have a oral delivery, any good?

I think this looks interesting with the permeability increasing agent - cyclodextrin. The problem is that I would be inclined to believe that this would even heighten serum response levels...in other words, make the peak even quicker than buccal above. I honestly don't know nor am I a believer that Taurus Nutrition has sound evidence for other than it looks good on paper, but me saying it is at least "interesting" must say something as I am not easily impressed. The company seems to postulate quite a bit with their products - not that they don't openly admit that though.


I guess in "worst case" scenario, it would mean that you would need to dose it multiple times in the day and then some; but I would love to predict and/or plot out a dose-response curve.


D_

 

[broons]

I know that at one point a certain company toyed with the idea of resveratrol gum but abandoned it (in reference to buccal delivery methods)

I have heard alot about emulsified resveratrol with Tween 80 as being one of the most superior in bioavailability as far as oral supplementation, although I haven't looked too deeply into it.

 

[BPjohn123]

Interesting, thanks for you take on this doc

 

[Primal2]

Whats your opinion of topical Resveratrol? PA's prototype nutrition sells a Resveratrol spray. Is it the best way?

 

[broons]

I am not a huge fan of piperine but the increase of AUC and (C)max was pretty compelling from this mice study.

Mol Nutr Food Res. 2011 Jun 29. doi: 10.1002/mnfr.201100117. [Epub ahead of print] Enhancing the bioavailability of resveratrol by combining it with piperine. Johnson JJ, Nihal M, Siddiqui IA, Scarlett CO, Bailey HH, Mukhtar H, Ahmad N. Source Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA. Abstract Scope: Resveratrol (3,5,4'-trihydroxystilbene) is a phytoalexin shown to possess a multitude of health-promoting properties in pre-clinical studies. However, the poor in vivo bioavailability of resveratrol due to its rapid metabolism is being considered as a major obstacle in translating its effects in humans. In this study, we examined the hypothesis that piperine will enhance the pharmacokinetic parameters of resveratrol via inhibiting its glucuronidation, thereby slowing its elimination. Methods and results: Employing a standardized LC/MS assay, we determined the effect of piperine co-administration with resveratrol on serum levels resveratrol and resveratrol-3-O-?-D-glucuronide in C57BL mice. Mice were administered resveratrol (100mg/kg; oral gavage) or resveratrol (100mg/kg; oral gavage)+piperine (10mg/kg; oral gavage), and the serum levels of resveratrol and resveratrol-3-O-?-D-glucuronide were analyzed at different times. We found that the degree of exposure (i.e. AUC) to resveratrol was enhanced to 229% and the maximum serum concentration (C(max) ) was increased to 1544% with the addition of piperine. Conclusion: Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed to study the mechanism of improved bioavailability of resveratrol via its combination with piperine as well as its effect on resveratrol metabolism.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID: 21714124

 

[dinoiii]

Whats your opinion of topical Resveratrol? PA's prototype nutrition sells a Resveratrol spray. Is it the best way?

I suppose that depends on how we are defining "best."

I am personally not a fan of transdermal as I think compliance rates (even with the best of intentions) are MISERABLE - of which, discussion of transdermal as "best" is completely moot.

As for bioavailability, I am uncertain I care when serum levels are heightened the "most" because it's going to be long-term serum elevations that yield benefit. Again; multiple daily dosing parameters are probably "best" with all kinds of administration. But, I am unsure a discussion about best is in the acute setting, or alternatively stated, "best" method should not equal HASTENED high serum levels, but SUSTAINED high serum levels (completely different things).


D_