Resveratrol dosing strategy

Started by health_nutty , Nov 07 2006 05:37 PM

Please log in to reply

21 replies to this topic

#1 health_nutty

Guest
2,410 posts
94 ₮

Location:California

Posted 07 November 2006 - 05:37 PM

What do you guys think of tiny doses of trans-resveratrol taken throughout the day?

"More recently, Italian researchers studied resveratrol from red wine and found, 30 minutes after ingestion, only a small amount of free (unsulfated, unglucuronidated) resveratrol was present in the blood circulation. There were large variances in absorption from individual to individual, and researchers concluded that this “raises some doubts about the health effects of dietary resveratrol consumption.” [Molecular Nutrition Food Research 2005 Apr 14] But don’t throw away your red wine pills just yet.

Even though very small amounts of free resveratrol are measured in the blood circulation and living tissues of humans following oral consumption of resveratrol, it should be noted that miniscule concentrations of resveratrol, only ~500 nanomolar (billionth of a gram), are required to protect nerve cells. [Nature Genetics 37: 349-50, 2005]

Moreover, three studies indicate the inclusion of quercetin with resveratrol inhibits sulfation in the liver and improves bioavailability. [Xenobiotica 30: 609-17, 2000; 30: 857-66, 2000; 30:1047-54, 2000] Additionally, lecithin has been found to enhance the oral absorption of polyphenols like quercetin and resveratrol. [J Agriculture Food Chemistry 13; 50:1706-12, 2002]

But an important biochemical aspect of why resveratrol exerts seemingly magical properties has been overlooked. The metabolic process of glucuronidation in the liver actually appears to protect resveratrol from degradation, extending its half life and maintaining its biological properties for up to nine hours. [Biochemistry Journal 374 (Pt 1):157-63, 2003]"

http://www.resveratr....com/page40.htm

#2 Athanasios

Guest
2,616 posts
163 ₮

Location:Texas

Posted 07 November 2006 - 06:06 PM

Here is a paper that goes into resveratrol absorption and metabolism.

http://dmd.aspetjour...full/32/12/1377

#3 health_nutty

Topic Starter
Guest
2,410 posts
94 ₮

Location:California

Posted 07 November 2006 - 06:46 PM

Cnorwood,
Thanks for the link. Do you have any opinions on the subject?

#4 health_nutty

Topic Starter
Guest
2,410 posts
94 ₮

Location:California

Posted 07 November 2006 - 06:53 PM

Btw, here is an "article" for the opposite strategy: overwhelm your liver's ability to "inactivate" resveratrol.

http://www.t-nation....c.do?id=1158493

#5 Athanasios

Guest
2,616 posts
163 ₮

Location:Texas

Posted 07 November 2006 - 07:46 PM

Cnorwood, Thanks for the link. Do you have any opinions on the subject?

I am still waiting on further research before I supplement with it. I am waiting for a way that more non-conjugated resveratrol can be achieved and sustained in the plasma, or evidence that the metabolites can be made biologically active in our tissues.

I feel this way about carnosine and curcumin as well.

#6 xanadu

Guest
1,917 posts
8 ₮

Posted 07 November 2006 - 11:13 PM

Why does it have to be present in the plasma? Does it do it's work there or in the tissues? I think it does it's work in the tissues so why would you want it to remain in the bloodstream? Taking it several times a day couldn't hurt and may help.

#7 Athanasios

Guest
2,616 posts
163 ₮

Location:Texas

Posted 08 November 2006 - 12:15 AM

Why does it have to be present in the plasma?

To try and clarify,
I want it to be shown that the metabolites can become bioactive, or I want them to have found a way to keep resveratrol from being conjugated to a non-bioactive form. Basically I want to see that it works in humans, or I could say I am waiting for them to solve the issue of bioavailability.

#8 spacetime

Guest
191 posts
5 ₮

Posted 08 November 2006 - 08:09 PM

Why does it have to be present in the plasma? Does it do it's work there or in the tissues? I think it does it's work in the tissues so why would you want it to remain in the bloodstream? Taking it several times a day couldn't hurt and may help.

How do you think it gets to the tissues? That's right, through the bloodstream and this is why plasma levels are so important. If it doesn't make it to the bloodstream it won't make it to your tissues.

#9 xanadu

Guest
1,917 posts
8 ₮

Posted 08 November 2006 - 08:50 PM

emitecaps wrote

"How do you think it gets to the tissues? That's right, through the bloodstream and this is why plasma levels are so important. If it doesn't make it to the bloodstream it won't make it to your tissues."

There is no problem getting into the plasma. People are talking about maintaining plasma levels which is a different thing. It may be that the res is absorbed, goes through the bloodstream and ends up in the tissues. You can't measure tissue levels so you assume it's gone and not doing any work.

#10 opales

Guest
892 posts
15 ₮

Location:Espoo, Finland

Posted 09 November 2006 - 12:26 PM

To clarify things:

http://lpi.oregonsta...rol/#metabolism

Information about the bioavailability of resveratrol in humans is important because much of the basic research on resveratrol has been conducted in cultured cells exposed to unmetabolized resveratrol at concentrations that are often 10-100 times greater than peak concentrations observed in human plasma after oral consumption (10). Although cells that line the digestive tract are exposed to unmetabolized resveratrol, research in humans suggests that other tissues are exposed primarily to resveratrol metabolites. Little is known about the biological activity of resveratrol metabolites, and it is not known whether some tissues are capable of converting resveratrol metabolites back to resveratrol (7).

#11 DukeNukem

Guest
2,008 posts
141 ₮

Location:Dallas, Texas

Posted 09 November 2006 - 08:55 PM

Opales,

How are Dr. Sinclair's mice getting their resveratrol? Through their diet, right?

Also, we've gotten it through wine and seen measurable consequences (French Paradox).

So, I think the evidence is strong that somehow, someway resveratrol does it thing even if digested.

I'm in. In fact, I've upped my dosage to 200mg daily. (Still under Dr. Sinclair's.)

#12 doug123

Guest
2,424 posts
-1 ₮

Location:Nowhere

Posted 09 November 2006 - 09:06 PM

Here is the clip I think Olli extracted his bit from:

[quote name='http://lpi.oregonstate.edu/infocenter/phytochemicals/resveratrol/#metabolism']Metabolism and Bioavailability

Although trans-resveratrol appears to be well-absorbed by humans when taken orally, its bioavailability is relatively low due to its rapid metabolism and elimination (7). When healthy men and women took an oral dose of 25 mg of trans-resveratrol, only traces of the unchanged resveratrol were detected in plasma (blood), while plasma concentrations of resveratrol metabolites peaked 30-60 minutes later at concentrations around 2 micromoles/liter (7, 8). The bioavailability of resveratrol from grape juice, which contains mostly glucosides of resveratrol (piceid) may be even lower than that of trans-resveratrol (9). Information about the bioavailability of resveratrol in humans is important because much of the basic research on resveratrol has been conducted in cultured cells exposed to unmetabolized resveratrol at concentrations that are often 10-100 times greater than peak concentrations observed in human plasma after oral consumption (10). Although cells that line the digestive tract are exposed to unmetabolized resveratrol, research in humans suggests that other tissues are exposed primarily to resveratrol metabolites. Little is known about the biological activity of resveratrol metabolites, and it is not known whether some tissues are capable of converting resveratrol metabolites back to resveratrol (7).[/quote]

There seems to be no question that the stuff is absorbed. It's bioavailabilty is low, however...so it seems to simply be a question of optimizing dosage.

I can't afford Sardi's encapsulated stuff with these dosages...I'm going to try to look for a raw material supplier that carries trans-resveratrol sourced from a reputable company in EU or Japan. Anyone know of one?

A natural products insider search reveals that 135 suppliers are selling resveratrol...I wonder how much of it is trans resvertarol and how much of it is crap.

http://www.naturalpr...rch.asp?sc=2397

#13 xanadu

Guest
1,917 posts
8 ₮

Posted 09 November 2006 - 09:35 PM

Duke hit the nail on the head as usual. All theory aside, the fact remains that resveratrol does a lot of good even when taken in the diet in the form of wine or perhaps grapes. The people that showed health benefits that started all this research did not take megadoses, they got very small amounts in the diet and presumably, their plasma levels were low. I don't think megadosing is doing any harm but you are probably excreting the vast majority of it.

cnorwood, the stuff is totally harmless, that seems to be agreed upon. The only thing you are risking in trying it at this stage is the small amount of money it costs. It and fish oil are must haves in the diet.

#14 Athanasios

Guest
2,616 posts
163 ₮

Location:Texas

Posted 09 November 2006 - 10:22 PM

Yes, I see it as likely to be harmless too. It is the money that I am most worried about.

We do not know if the french paradox is due to the resveratrol, anymore than the antioxidants and other polyphenols in the wine. I also think there is a point of diminishing returns on antioxidants in the blood stream.

What I want to know is if and how much trans-resveratrol must a human take to activate Sirt1. The amount of non-conjugated resveratrol in human plasma after oral dosage is much less relative to the mouse taking the equivalent dose, and most of the benefits appear to be when the mouse gets dosages that overwhelm the enzymes that metabolize resveratrol.

#15 DukeNukem

Guest
2,008 posts
141 ₮

Location:Dallas, Texas

Posted 09 November 2006 - 11:36 PM

If you go to Sardi's site, he gives some explanation based on research on how resveratrol works despite its apparent low bio-availability. Look on the left side under "Contents" and you'll see an entire area on resveratrol.

His blog is worth checking once a week (current top topic is resveratrol):
http://www.knowledge...og/kohblog.html

#16 Athanasios

Guest
2,616 posts
163 ₮

Location:Texas

Posted 09 November 2006 - 11:57 PM

Thanks for the pointer and the link.

What I found on Sardi's site is the hope that beta-glucuronidase makes resveratrol active again in tissues. Confirmation of this is one of the things that I am watching for. If true, we would have no need to overwhelm our enzymes. What makes me skeptical is that the best benefits in mice were when large dosages capable of overwhelming their enzymes were given.

#17 opales

Guest
892 posts
15 ₮

Location:Espoo, Finland

Posted 10 November 2006 - 12:18 PM

One thing to remember is that cells in gastrointestinal tract *do* expose to unmetabolized resveratrol. Drinking red wine with meal reduces postprandial lipid hydroperoxides [1], and certain CR society member has reported DRASTIC reductions in blood glucose levels by taking Longevinex 45 minutes prior to meals (see Google Video link below),

http://video.google....308329673719932

hypothesising the effect being due to "competing with glucose transporters in the gut ( no studies prove this, but
there is [2]."

(quoted from)
http://lists.calorie...ber/002108.html

[1]Ursini F, Zamburlini A, Cazzolato G, Maiorino M, Bon GB, Sevanian A.
Postprandial plasma lipid hydroperoxides: a possible link between diet
and atherosclerosis.
Free Radic Biol Med. 1998 Jul 15;25(2):250-2. Review.
PMID: 9667503 [PubMed - indexed for MEDLINE]

[2] Park JB. Inhibition of glucose and dehydroascorbic acid uptakes by resveratrol in human transformed myelocytic cells.
J Nat Prod. 2001 Mar;64(3):381-4.
PMID: 11277764 [PubMed - indexed for MEDLINE]

#18 kenj

Guest
747 posts
67 ₮

Location:Copenhagen.

Posted 10 November 2006 - 08:07 PM

Using the current available power of Nature, I'm definitely upgrading my resveratrol dose (on semi-empty stomach). Yessss.

#19 health_nutty

Topic Starter
Guest
2,410 posts
94 ₮

Location:California

Posted 11 November 2006 - 01:34 AM

Anyone else adopting the strategy of just adding some powder to your beverages you sip on throughout the day?

#20 mitkat

Guest
1,948 posts
13 ₮

Location:Toronto, Canada

Posted 11 November 2006 - 01:38 AM

Okay, I've dragged my heels on this supp long enough. I've been taking grape seed extract s u p e r consistently for 6 or 7 months, but I know it's not even in the same ballpark. Where is everyone buying from? Sorry if this has been talked about in another thread, I gave a quick search, couldn't find it.

Favourite suppliers?

#21 Agarikon

Guest
45 posts
-1 ₮

Posted 11 November 2006 - 05:05 AM

In the video the Opale posted, Paul McGlothin, the one lecturing mentions it may not be a good idea to take resveratrol and curcumin, because curcumin upregulated P53 and increases apoptosis and resveratrol appears to do the opposite. I take both of these supplements..does anyone know anything about this?

#22 VP.

Guest
498 posts
200 ₮

Posted 11 November 2006 - 07:54 PM

In the video the Opale posted, Paul McGlothin, the one lecturing mentions it may not be a good idea to take resveratrol and curcumin, because curcumin upregulated P53 and increases apoptosis and resveratrol appears to do the opposite. I take both of these supplements..does anyone know anything about this?

I am only layman when it comes to Biochemistry but this study seems to contradict Mr. McGlothin's statement. http://www.biomedcen.../1471-2407/5/97

It has been shown that emodin, curcumin and resveratrol induce apoptosis through p53-dependent pathways [28,29].

Here is another study http://mct.aacrjourn...nt/full/4/4/554

Resveratrol and curcumin, a yellow pigment of turmeric, can regulate inflammatory and immune responses through the suppression of NF-B activation (6, 36) and enhances tumor necrosis factor–related apoptosis-inducing ligand–induced apoptosis in LNCaP prostate cancer cells

Anyone out there who can translate these studies?