1084 replies to this topic

[pycnogenol]

Does anyone know if taking d-Limonene (Orange Peel Extract) helps maximize the effectiveness of resveratrol?

Just curious.

(maxwatt — thank you for the PM on bulk luteolin sources)

[Marko]

-

Edited by Marko, 01 September 2009 - 10:41 AM.

[Marko]

Here are the pictures that I have taken:
98% Resveratrol + Water

Hello!
Resveratrol should be red, shouldn't it?

[maxwatt]

Here are the pictures that I have taken:
98% Resveratrol + Water

Hello!
Resveratrol should be red, shouldn't it?

Pure resveratrol is a white powder.

[health_nutty]

Quick update. At some point I was frustrated with the increasing amount of resveratrol that was seemingly needed to obtain "rat like" plasma levels. This was maybe a year ago. Then I recently read about the buccal method and I decided to give it a try again.

Method (one in the morning and once in the evening):
1) Prep with Listerine for 30sec. Spit out then...
2) 100-150mg scoop of 98% resvertrol under the tongue.
3) One cap of vodka (less than a tablespoon).
4) Swish in mouth for 10 minutes
5) Swallow.

There probably isn't nearly enough alcohol to fully dissolve the resveratrol, but i'm hoping it keeps the pores in my mouth open during the the swishing (keeping the mouthwash prep effective for longer).

Using this method I have experienced *significant* anti-inflammatory effects. Like maxwatt's toe, I have a indicator as well: my midback stiffness. The vertebre in my back are significantly more "free" 30 minutes after ingestion. The anti-inflammatory effect is stronger than 600mg of ibuprophen (advil). The anti-inflammatory is also much much greater than the even 800mg of resveratrol (1.6g of 50%) resveratrol I was taking in the past.

I'm a pretty active person (lift, run, play ultimate frisbee). I will keep you guys updated on any performance effects (I should at least get a nice placebo boost).

[tintinet]

I'm a lightweight, so I wonder if the alcohol (albeit a very small amount) is not contributory.

[maxwatt]

Quick update. At some point I was frustrated with the increasing amount of resveratrol that was seemingly needed to obtain "rat like" plasma levels. This was maybe a year ago. Then I recently read about the buccal method and I decided to give it a try again.

Method (one in the morning and once in the evening):
1) Prep with Listerine for 30sec. Spit out then...
2) 100-150mg scoop of 98% resvertrol under the tongue.
3) One cap of vodka (less than a tablespoon).
4) Swish in mouth for 10 minutes
5) Swallow.

There probably isn't nearly enough alcohol to fully dissolve the resveratrol, but i'm hoping it keeps the pores in my mouth open during the the swishing (keeping the mouthwash prep effective for longer).

Using this method I have experienced *significant* anti-inflammatory effects. Like maxwatt's toe, I have a indicator as well: my midback stiffness. The vertebre in my back are significantly more "free" 30 minutes after ingestion. The anti-inflammatory effect is stronger than 600mg of ibuprophen (advil). The anti-inflammatory is also much much greater than the even 800mg of resveratrol (1.6g of 50%) resveratrol I was taking in the past.

I'm a pretty active person (lift, run, play ultimate frisbee). I will keep you guys updated on any performance effects (I should at least get a nice placebo boost).

Are you weighing the amount in your scoop? If you haven't "standardized" your scoop by weighing several different scoops it takes, and using an average, you cannot be sure how much you are taking. You will have to recalibrate your scoop every time you start a new batch of powder.

I doubt if the mouthwash prep is necessary. Just holding the lump of powder in your cheek, and slowly sipping water or tea, I think would have as salubrious an effect. It works for me, anyway.

[health_nutty]

Are you weighing the amount in your scoop? If you haven't "standardized" your scoop by weighing several different scoops it takes, and using an average, you cannot be sure how much you are taking. You will have to recalibrate your scoop every time you start a new batch of powder.

I doubt if the mouthwash prep is necessary. Just holding the lump of powder in your cheek, and slowly sipping water or tea, I think would have as salubrious an effect. It works for me, anyway.

Not weighing it. I'm taking a conservative dose and am not overly concerned if i'm taking 1/2 or double (except for cost). Most of the effect seems to be from method, and in all honesty I could probbly get away with taking even less because of the buccal method. I imagine there is a maximum I can absorb through the mouth and anything over that is swallowed and thus very limited in bioavailability.

[Terri]

If you are getting hives from resveratrol, stop taking it. I took resveratrol for 15 days and now have hives. My reaction was so huge that my ears and lips started to swell, and I became dizzy. I also had severe abdominal cramps. The big reaction came on slowly after what I now see as smaller warnings. I ignored the first warning with the first pill--which made me feel like I had just drunk 10 cups of coffee. I'm convinced that if I continue to take it, I will eventually have a reaction so huge it will kill me. You've been warned.

[pycnogenol]

If you are getting hives from resveratrol, stop taking it. I took resveratrol for 15 days and now have hives. My reaction was so huge that my ears and lips started to swell, and I became dizzy. I also had severe abdominal cramps. The big reaction came on slowly after what I now see as smaller warnings. I ignored the first warning with the first pill--which made me feel like I had just drunk 10 cups of coffee. I thought that "rush" was a good thing. I'm convinced that if I continue to take it, I will eventually have a reaction so huge it will kill me. You've been warned.

Hi Terri,

How much resveratrol were you taking and what brand did you use?

[maxwatt]

I know a woman who broke out with hives when taking resveratrol; it turned out to be a trigger for undiagnosed celiac disease which is now being treated/

[Danniel]

2) 100-150mg scoop of 98% resvertrol under the tongue.
3) One cap of vodka (less than a tablespoon).

Vodka in the morning... My grand-grandfather was swearing that a shot in the morning does miracles.

Will try.

[health_nutty]

2) 100-150mg scoop of 98% resvertrol under the tongue.
3) One cap of vodka (less than a tablespoon).

Vodka in the morning... My grand-grandfather was swearing that a shot in the morning does miracles.

Will try.

FYI, I stopped using alcohol because I'm worried about cancer from 10 minutes of alcohol contact in my mouth.

[X_Danny_X]

i was wondering, i know Res is for expanding your life, but can it also make you look younger or stay younger? meaning prevent your skin from wrinkling, delay gray hair, etc. so basically you will be around 40 or 50 years of age but look around in your 30s.

[niner]

i was wondering, i know Res is for expanding your life, but can it also make you look younger or stay younger? meaning prevent your skin from wrinkling, delay gray hair, etc. so basically you will be around 40 or 50 years of age but look around in your 30s.

No, not really. You probably should look into Sun avoidance, a good UVA/UVB sunscreen, Tretinoin, C/E/ferulic acid, Lutein, Copper peptides, alpha hydroxy acids, BioSil, Biotin... I don't know any way to delay gray hair, except maybe a reversible vasectomy.

[maxwatt]

Applied topically in a cream base, resveratrol in my experience does seem to alleviate fine wrinkles and sun damage. It may be as effective as benzoyl peroxide against acne, and I expect some such product to come out.

I know of no effect on gray hair.

Edited by maxwatt, 05 November 2009 - 01:09 PM.
spellling

[X_Danny_X]

okay thanks, i will look into all of that.

[wizodd]

Resveratrol uptake notes:

From my biochemist:

1) Resveratrol (trans) is destroyed by acidic environments. Over 50% of oral dosages will not be bioavailable. Buffering the compound with an acid neutralizer may increase effectiveness, but has not been tested by us at this time.

2) Since early in 2006, we have had good success using alcohol tincture made by soaking cranberries in 40% alcohol (rum, brandy, vodka.) The resulting tincture is taken sub-lingually, and held in the mouth until dissolved, in practice, the dosage is on the order of 20-50 mg. Over the three year test, our subject (Alzheimer's patient, late 80's) recovered memory to approximately her previous level, although she notes that her historic inability to remember names is unchanged. Mental acuity also is reported to have increased to previous levels. Speculation is that sub-lingual application may have a greater effect upon the brain function due to it's immediate availability to the brain in relatively large amounts opposed to the amounts present after oral ingestion.

There is no reason to suspect that there would be any maximum dosage which can be absorbed sublingually, as the absorbed compounds go directly into the bloodstream. the maximum limit would be the saturation level for resveratrol in the blood--which might never be reached as the compound breaks down or is excreted. Dosage seems limited by individual tolerance for contact with the alcohol--which can be alievieated to some extent by diluting the tincture.

3) Resveratrol exists in a more stable form within fruits and sprouts along with an amino acid which, in a basic pH solution, (e.g. small intestine) transforms it into the trans form. Thus sprouts and berries eaten plain, should provide more resveratrol than is actually present in the trans form within the plant, as the stable form is an order of magnitude more common. This indicates that it may be vastly superior for oral dosage to consume sprouts and berries rather than pure trans resveratrol.

Speculation is that dried berries and sprouts would retain thesimilar proportions of compounds, permitting long term storage of the compound as a binary (stable form & amino acid.) No current experiments planned.

4) Our tests of topically applied resveratrol in glycerin or DMSO carriers have been inconclusive to date. Testing continues.

[niner]

From my biochemist:

1) Resveratrol (trans) is destroyed by acidic environments. Over 50% of oral dosages will not be bioavailable. Buffering the compound with an acid neutralizer may increase effectiveness, but has not been tested by us at this time.

I think your biochemist missed the boat on this one. The trans form is pretty stable in vivo.

[2tender]

Resveratrol uptake notes:

From my biochemist:

1) Resveratrol (trans) is destroyed by acidic environments. Over 50% of oral dosages will not be bioavailable. Buffering the compound with an acid neutralizer may increase effectiveness, but has not been tested by us at this time.

2) Since early in 2006, we have had good success using alcohol tincture made by soaking cranberries in 40% alcohol (rum, brandy, vodka.) The resulting tincture is taken sub-lingually, and held in the mouth until dissolved, in practice, the dosage is on the order of 20-50 mg. Over the three year test, our subject (Alzheimer's patient, late 80's) recovered memory to approximately her previous level, although she notes that her historic inability to remember names is unchanged. Mental acuity also is reported to have increased to previous levels. Speculation is that sub-lingual application may have a greater effect upon the brain function due to it's immediate availability to the brain in relatively large amounts opposed to the amounts present after oral ingestion.

There is no reason to suspect that there would be any maximum dosage which can be absorbed sublingually, as the absorbed compounds go directly into the bloodstream. the maximum limit would be the saturation level for resveratrol in the blood--which might never be reached as the compound breaks down or is excreted. Dosage seems limited by individual tolerance for contact with the alcohol--which can be alievieated to some extent by diluting the tincture.

3) Resveratrol exists in a more stable form within fruits and sprouts along with an amino acid which, in a basic pH solution, (e.g. small intestine) transforms it into the trans form. Thus sprouts and berries eaten plain, should provide more resveratrol than is actually present in the trans form within the plant, as the stable form is an order of magnitude more common. This indicates that it may be vastly superior for oral dosage to consume sprouts and berries rather than pure trans resveratrol.

Speculation is that dried berries and sprouts would retain thesimilar proportions of compounds, permitting long term storage of the compound as a binary (stable form & amino acid.) No current experiments planned.

4) Our tests of topically applied resveratrol in glycerin or DMSO carriers have been inconclusive to date. Testing continues.

Quasimodo and the bells.

[maxwatt]

From my biochemist:

1) Resveratrol (trans) is destroyed by acidic environments. Over 50% of oral dosages will not be bioavailable. Buffering the compound with an acid neutralizer may increase effectiveness, but has not been tested by us at this time.

I think your biochemist missed the boat on this one. The trans form is pretty stable in vivo.

High pH, 11 or so, converts the trans form into the cis form. Otherwise resveratrol is stable in acid environments.

J. Agric. Food Chem. 1996, 44, 1253-1257
Resveratrol: Isomeric Molar Absorptivities and Stability
Brent C. Trela and Andrew L. Waterhouse*

The rate at which resveratrol can be absorbed sublingually is in micrograms and limited by the surface area of the mucosal tissue in the mouth. How many hours would one have to suck on a lozenge without swallwing to get a significant dose??????

[tunt01]

The rate at which resveratrol can be absorbed sublingually is in micrograms and limited by the surface area of the mucosal tissue in the mouth. How many hours would one have to suck on a lozenge without swallwing to get a significant dose??????

dunno, but ive thought for a while that the benefits of the 'french paradox' is conferred upon those who slowly drink their wine and swish it around in their mouth, maximizing the sublingual uptake. cuz 1-2 mg in a glass aint exactly doing much.

[maxwatt]

The rate at which resveratrol can be absorbed sublingually is in micrograms and limited by the surface area of the mucosal tissue in the mouth. How many hours would one have to suck on a lozenge without swallwing to get a significant dose??????

dunno, but ive thought for a while that the benefits of the 'french paradox' is conferred upon those who slowly drink their wine and swish it around in their mouth, maximizing the sublingual uptake. cuz 1-2 mg in a glass aint exactly doing much.

It is questionable if there even is a French Paradox. Apparent French Paradox is more like it. But swishing red wine around under my tongue, this I can get used to.

[2tender]

I think that the french paradox actually was in reference to those older french residents that had been drinking wine as part of their diet for decades, hence ingesting Resveratrol in minute doses as part of their diet. I think that potentiating Resveratrol, for those of us that just started it, consists of; determining if and how much our physiology will tolerate and then dosing consistently in the mornings, using the purest, low emodin content, preferably micronized product available, dosing with a premium, pre-emulsified Quercetin product of at least 250 mgs, exercising at least 3 times weekly. I also think there is an advantage to using more than one type of Resveratrol on a daily basis, such as; 250 mgs of pre-emulsified Resveratrol and 300mgs of micronized powder (mixed with water or juice) combined with some applications of a Transdermal lotion. JMO

Edited by 2tender, 01 December 2009 - 11:19 PM.

[niner]

I think that the french paradox actually was in reference to those older french residents that had been drinking wine as part of their diet for decades, hence ingesting Resveratrol in minute doses as part of their diet.

The so-called "French paradox" concerned the fact that the French ate a significant amount of animal fat, along with a lot of other good things, and yet were not keeling over left and right from cardiovascular disease. It was only a paradox because at the time, our scientific and political establishment was in the thrall of the "all fat is bad, but saturated fat is really really bad" meme. The French paradox is not so paradoxical after all because the meme was wrong. The "paradox" had nothing to do with resveratrol, then or now. That is just marketing fluff.

[meat250]

study here



Chem Biol Drug Des. 2009 Dec;74(6):619-24. Epub 2009 Oct 20.

Resveratrol is not a direct activator of SIRT1 enzyme activity.

Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M.

Department of Neuroscience, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.

Resveratrol is a plant polyphenol capable of exerting beneficial metabolic effects which are thought to be mediated in large by the activation of the NAD(+)-dependent protein deacetylase SIRT1. Although resveratrol has been claimed to be a bona fide SIRT1 activator using a peptide substrate (Fluor de Lys-SIRT1 peptide substrate), recent reports indicate that this finding might be an experimental artifact and need to be clarified. Here, we show that: (i) the Fluor de Lys-SIRT1 peptide is an artificial SIRT1 substrate because in the absence of the covalently linked fluorophore the peptide itself is not a substrate of the enzyme, (ii) resveratrol does not activate SIRT1 in vitro in the presence of either a p53-derived peptide substrate or acetylated PGC-1alpha isolated from cells, and (iii) although SIRT1 deacetylates PGC-1alpha in both in vitro and cell-based assays, resveratrol did not activate SIRT1 under these conditions. Based on these observations, we conclude that the pharmacological effects of resveratrol in various models are unlikely to be mediated by a direct enhancement of the catalytic activity of the SIRT1 enzyme. In consequence, our data challenge the overall utility of resveratrol as a pharmacological tool to directly activate SIRT1.

[maxwatt]

study here



Chem Biol Drug Des. 2009 Dec;74(6):619-24. Epub 2009 Oct 20.

Resveratrol is not a direct activator of SIRT1 enzyme activity.

Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M.

Department of Neuroscience, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.

Resveratrol is a plant polyphenol capable of exerting beneficial metabolic effects which are thought to be mediated in large by the activation of the NAD(+)-dependent protein deacetylase SIRT1. Although resveratrol has been claimed to be a bona fide SIRT1 activator using a peptide substrate (Fluor de Lys-SIRT1 peptide substrate), recent reports indicate that this finding might be an experimental artifact and need to be clarified. Here, we show that: (i) the Fluor de Lys-SIRT1 peptide is an artificial SIRT1 substrate because in the absence of the covalently linked fluorophore the peptide itself is not a substrate of the enzyme, (ii) resveratrol does not activate SIRT1 in vitro in the presence of either a p53-derived peptide substrate or acetylated PGC-1alpha isolated from cells, and (iii) although SIRT1 deacetylates PGC-1alpha in both in vitro and cell-based assays, resveratrol did not activate SIRT1 under these conditions. Based on these observations, we conclude that the pharmacological effects of resveratrol in various models are unlikely to be mediated by a direct enhancement of the catalytic activity of the SIRT1 enzyme. In consequence, our data challenge the overall utility of resveratrol as a pharmacological tool to directly activate SIRT1.

This was covered in its own thread, with references: Thread on (not) activating Sirt1
The gist of the discussion as I recall was that resveratrol does not itself activate Sirt1, but does bind to the Sirt1 enzyme, promoting activation by other substances by a conformational change. Sinclair et al have constructed a model of the Sirt1 molecule, determined the binding sites for resveratrol, and designed drugs to bind even better, by virtue of a more favorable angle between the docking OH atoms that bind to the two critical sites. Resveratrol also actvates AMPK, which may actually mediate its effects as much or more than Sirt1.

Diabetes. 2009 Nov 23. [Epub ahead of print]
AMPK-deficient mice are resistant to the metabolic effects of resveratrol.
Um JH, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, Kim MK, Viollet B, Chung JH.

Laboratory of Biochemical Genetics, National Heart Lung and Blood Institute, National Institutes of Health, 10 Center Dr. Bethesda, MD 20892, USA.
Objective: Resveratrol, a natural polyphenolic compound that is found in grapes and red wine, increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance and reduces fat accumulation in mice. Although it is thought that resveratrol targets Sirt1, this is controversial because resveratrol also activates 5'-AMP activated kinase (AMPK), which also regulates insulin sensitivity and mitochondrial biogenesis. Here, we use mice deficient in AMPKalpha1 or alpha2 to determine if the metabolic effects of resveratrol are mediated by AMPK. Research design and methods: Mice deficient in the catalytic subunit of AMPK (alpha1 or alpha2) and wild type mice were fed high-fat diet or high-fat supplemented with resveratrol for 13 weeks. Body weight was recorded by weekly and metabolic parameters were measured. We also used mouse embryonic fibroblasts (mefs) deficient in AMPK to study the role of AMPK in resveratrol-mediated effects in vitro. Results: Resveratrol increased the metabolic rate and reduced fat mass in wild-type mice but not in AMPKalpha1-/- mice. In the absence of either AMPKalpha1 or alpha2, resveratrol failed to increase insulin sensitivity, glucose tolerance, mitochondrial biogenesis and physical endurance. Consistent with this, the expression of genes important for mitochondrial biogenesis was not induced by resveratrol in AMPK-deficient mice. In addition, resveratrol increased the NAD/NADH ratio in an AMPK-dependent manner, which may explain how resveratrol may activate Sirt1 indirectly. Conclusion: We conclude that AMPK, which was thought to be an off-target hit of resveratrol, is the central target for the metabolic effects of resveratrol.

PMID: 19934007


Biochim Biophys Acta. 2009 Nov 6. [Epub ahead of print]
Biochemical effects of SIRT1 activators.
Baur JA.

Institute for Diabetes, Obesity, and Metabolism, and Department of Physiology, University of Pennsylvania School of Medicine, 415 Curie Blvd, CRB 728, Philadelphia, PA 19104, USA.
SIRT1 is the closest mammalian homologue of enzymes that extend life in lower organisms. Its role in mammals is incompletely understood, but includes modulation of at least 34 distinct targets through its nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase activity. Recent experiments using small molecule activators and genetically engineered mice have provided new insight into the role of this enzyme in mammalian biology and helped to highlight some of the potentially relevant targets. The most widely employed activator is resveratrol, a small polyphenol that improves insulin sensitivity and vascular function, boosts endurance, inhibits tumor formation, and ameliorates the early mortality associated with obesity in mice. Many of these effects are consistent with modulation of SIRT1 targets, such as PGC1alpha and NFkappaB, however, resveratrol can also activate AMPK, inhibit cyclooxygenases, and influence a variety of other enzymes. A novel activator, SRT1720, as well as various methods to manipulate NAD(+) metabolism, are emerging as alternative methods to increase SIRT1 activity, and in many cases recapitulate effects of resveratrol. At present, further studies are needed to more directly test the role of SIRT1 in mediating beneficial effects of resveratrol, to evaluate other strategies for SIRT1 activation, and to confirm the specific targets of SIRT1 that are relevant in vivo. These efforts are especially important in light of the fact that SIRT1 activators are entering clinical trials in humans, and "nutraceutical" formulations containing resveratrol are already widely available.

PMID: 19897059

[JLL]

I think that the french paradox actually was in reference to those older french residents that had been drinking wine as part of their diet for decades, hence ingesting Resveratrol in minute doses as part of their diet.

The so-called "French paradox" concerned the fact that the French ate a significant amount of animal fat, along with a lot of other good things, and yet were not keeling over left and right from cardiovascular disease. It was only a paradox because at the time, our scientific and political establishment was in the thrall of the "all fat is bad, but saturated fat is really really bad" meme. The French paradox is not so paradoxical after all because the meme was wrong. The "paradox" had nothing to do with resveratrol, then or now. That is just marketing fluff.

Yes, this is exactly what I think as well. Resveratrol might still have benefits, of course.

[2tender]

I think that the french paradox actually was in reference to those older french residents that had been drinking wine as part of their diet for decades, hence ingesting Resveratrol in minute doses as part of their diet.

The so-called "French paradox" concerned the fact that the French ate a significant amount of animal fat, along with a lot of other good things, and yet were not keeling over left and right from cardiovascular disease. It was only a paradox because at the time, our scientific and political establishment was in the thrall of the "all fat is bad, but saturated fat is really really bad" meme. The French paradox is not so paradoxical after all because the meme was wrong. The "paradox" had nothing to do with resveratrol, then or now. That is just marketing fluff.

Yes, this is exactly what I think as well. Resveratrol might still have benefits, of course.

Okay, forget the paradox, also forget the "might still" "maybe beneficial" and other theoretical stuff. Resveratrol does work in a beneficial way for some people, with a physiology that will accept and tolerate its actions, most likely middle-aged and older that are not taking a lot of prescribed medications. If you can tolerate it, and this may take some practice by not reacting and attributing every little ache and pain to Resveratrol ingestion. There may be some changes, but they go away with time and a day or 2 of abstinence. Use different types of pure, low emodin, micronized Resveratrol. Use a pre-emulsified licap of 250 mgs pure micronized Resveratrol, at the same time take one 250 mgs MCT Quercetin licap. Swallow with a pre-prepared mixture of; 300 mgs, pure, micronized powdered Resveratrol, 15 grams of Whey, 2 grams of creapure creatine, 3 grams of Glutamine and 30-50 mgs of dry Tocotrienol powder, mixed in 40 ounces of water or juice. Someone try this and then tell me it "Might" have benefits.

[tunt01]

Conclusion: We conclude that AMPK, which was thought to be an off-target hit of resveratrol, is the central target for the metabolic effects of resveratrol.

if this is true, i would think in some ways this is even better than previously anticipated. resveratrol is a cheap version of AICAR.. ?