1708 replies to this topic

[tintinet]

Interesting idea, but, I suppose, to comply with apparent FDA regulations, we'd have to stick to a max purity of 50%, no?

Perhaps it might be worth it, if we could eventually recoup our investment provided a sufficient market.

[niner]

Perhaps the way we feel from taking resveratrol is unrelated to its long term health benefits.

Resveratrol is known to be a seratonin/noradrenaline reuptake inhibitor. No harm in this- most people benefit from antidepressants. It doesn't seem to have any of the downside associated with common pharmaceutical SSRIs or SNRIs, so what the hell. I think this is at least part, and probably a large part of the good feeling. While the activity I'm describing is not part of the sirtuin activation, I could still make the argument that, at least for some people, it's a health benefit. Given the known long term adverse health consequences of depression, I would even say that, at least for some people, it is a long term health benefit. This is in addition to the sirtuin modulated long term benefits.

I speculate that people who say resveratrol is better than amphetamine-like drugs might be part of the 20% or so of people for whom a big enough dose of an SSRI can kick off a hypomanic state. Such a state can be fairly long lasting, like weeks or even months, and feels great. It's not a full blown mania like a bipolar person might experience; it's usually a perfectly fine state to be in, you just feel great. Corticosteroids and ALCAR can also do this.

[niner]

For about $50,000 we could build our own 40 ft HPLC extractor, and make our own from Cissus quadrangularis, which has no emodin. Maybe.

Even if you used knotweed, if you get it pure enough the emodin should not be a problem. If you start with a commercial extract in the 50-96% range, maybe it would not take that expensive of a prep chromatography rig to really clean it up.

I wonder how hard it would be to line up a custom sythesis house to make us some 4'-OAc resveratrol? Ordinary resveratrol can be 4' acetylated enzymatically using a commercially available enzyme. I think there might be a little chemistry involved as well, but the yield was pretty good as I recall.

[gingerperth]

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It's called "Nutricide - Criminalizing Natural Health, Vitamins, and Herbs", made by a medical doctor.

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[tracer]

Have Duke drink red wine instead of beer, citing the health benefits of the resveratrol.  We need a public icon of masculinity to support the drinking of wine so my buddies stop giving me shit about it.  [tung]

There's nothing wrong with red wine. I'm in South Africa where one may elect to consume either beer or red wine without fear of one's masculinity being called into question. However, Chardonnay, Rose and random fruity cocktails are not allowed for men (I think it's actually been legislated). But a good woody Cab Sav is almost universally appreciated.

I think the reputation of red wine may have been irrevocably damaged by UB-40's red-red-whining though.

[maxwatt]

For about $50,000 we could build our own 40 ft HPLC extractor, and make our own from Cissus quadrangularis, which has no emodin. Maybe.

Even if you used knotweed, if you get it pure enough the emodin should not be a problem. If you start with a commercial extract in the 50-96% range, maybe it would not take that expensive of a prep chromatography rig to really clean it up.

Not necessarily. The more you try to get out, the lower the yield. Starting with a commercial extract would be more expensive even if you could do it.

I wonder how hard it would be to line up a custom sythesis house to make us some 4'-OAc resveratrol?  Ordinary resveratrol can be 4' acetylated enzymatically using a commercially available enzyme.  I think there might be a little chemistry involved as well, but the yield was pretty good as I recall.

Interesting thought. If they knew what you wanted it for, no company would be be likely to do it for you. If you did it abroad, your FDA declaration on import might raise a red flag.

The synthesis could likely be carried out on a small scale by any graduate chemistry student.

I'd wait for some published data, at least phase 1b, before I'd have an idea if this is desirable.

[markymark]

there are three trials listed with Resv at: http://clinicaltrials.gov

http://clinicaltrial...l&submit=Search

Edited by markymark, 12 March 2007 - 10:41 AM.

[markymark]

Thanks tintinet.
I agree to that, and also to venegances proposal to also include the Resv-glycon...puh lots of permutations for RCTs...

steelheader stated
"The feeling is completely wholesome and is analogous to something many of you take completely for granted. It feels like being younger. For me not way younger, like back in my early fifties. More like in my early sixties. Which is still a huge change.

I've noticed a little dosage creep myself. If "fading" happens at the current dose (about 750mg/day)I'm going to buy a bag of prunes to compensate for going off emodin and take a break for a week or two."

I feel this is a very important point. Getting used to feel better happens with viartually everything in life, isn't it?

Therefore cycling, or at least to stay away off RSV one day per week might be considered?

[maxwatt]

Therefore cycling, or at least to stay away off RSV one day per week might be considered?

I don't think so, if you would be foregoing the health benefits (it's supposed to be a CR mimetic, after all.)

I'd thought the feel-good effect was just feeling like I did 10 years ago, and that I got used to feeling that way quickly. If so, find other ways to feel good.

I think it was niner who said resv is an SSRI, which makes it an anti-depressant *anyone have references?). I don't think doctors recommend cycling anti-depressants like Prozac and Valium, so why would resveratrol be different?

[tintinet]

Hard to know what's the best approach to resveratrol dosing. Some folks, including a few with "expert" qualifications, do dose all their supplements in an intermittent fashion in an effort to minimize possible toxicity or tachyphylaxis.

Although the psychological side effects of resveratrol are terrific, it's certainly not the primary reason that motivated me to start taking it initially. But the mood boost might be hard to relinquish. Anyone tried, yet? I wonder if one might experience a rebound exacerbation of depressed mood with a cold turkey cessation. Any volunteers?

[crayfish]

I'm starting on resveratrol supplements soon and from the comments on this forum, look forward to it! I don't take any other nutraceuticals, the capsules I've ordered are 180mg but only 100mg of this is resveratrol (80mg polyphenols) and I think it's only 25% purity - so certainly nothing like the doses other posters are taking! I'll see if I experience any positive effects though and maybe move up to a purer supplement if I like it.

[malbecman]

Speaking about the potential fading of the increased energy and beneficial mood effects. I've been on 5mg/kg/d since the beginning of the New Year and I think these new effects I initially noticed have now just become my new "status quo".

I now expect if I go for a 6 mile run on my 40 yr old body now, I won't feel really tired or banged-up the next day like I used to (sic). I expect that I can multi-task more efficiently now at work and, yes, I also went off my SSRI my doc had put me on late last spring when multiple outside events unexpectedly came crashing in and I was feeling overwhelmed.

While there was that initial appetite suppression and my weight went down initially along with my caloric intake. But now my body seems to adjusted to this and my weight isn't changing anymore (not that I'm trying to lose weight). I eat regularly but my sense of appetite/feeling hungry really seems to have dimished.

Remember, if you drink a beer after not drinking for awhile, you really notice the alcohol. Drink 2 beers every night and after awhile, one beer won't even faze you mentally (although it would still be affecting you physiologically). Our bodies and minds are wonderful at adapting to whatever is the status quo for them.

[health_nutty]

Speaking about the potential fading of the increased energy and beneficial mood effects.  I've been on 5mg/kg/d since the beginning of the New Year and I think these new effects I initially noticed have now just become my new "status quo".

I'm feeling the same way.

[maxwatt]

Effects noted after nine weeks of resveratrol use, starting at 400 mg, increasing every other week to 1.8 g/day. Using Orchid synthetic and a 98% extract in powder form, taken with meals.

Blood sugar: unchanged. Still borderline.
Cholesterol: decreased 6%
HDL: increased 30%.

Mood, energy: good, not tired by exercise that should have knocked me out (eg, >2 hour fast bike ride) but when I do get tired, the urge to lie down and sleep is overpowering. Awaken quickly, no sleep hangover, even if I've slept too little. My "default" walking pace is faster.

Less sensitive to cold.
Ruddier complexion.
Arthritis is less painful, especially fingers. One finger that would "jam" when flexed no longer does. Big toe still hurts, where I first noticed arthritis symptoms.
Am able to crack my knuckles for the first time in over 10 years.

This isn't a cure-all. I still need pain meds for an old back injury.

[steelheader]

It has been suggested that a number of popular supplements (quercetin, green tea, niacinamide) might counter the gene switching action of resveratrol suposedly related to its long term health and longevity benefits.

I've been assuming that my strong and positive effects from resveratrol proved that those supplements did not, in my case at least, counter the gene switching action of resveratrol.

From the current discussion it appears likely that the desirable effects so many of us feel from resveratrol furnish no evidence one way or the other that the desired gene switching action is taking place.

Is that right?

[health_nutty]

Outstanding! Your total cholesterol went down 6% while your HDL went up 30%! That is phenomenal. The not getting tired by exercise is pretty impressive too!

Do you supplement your resveratrol with any goodies such as OPC's or lecithin?

Effects noted after nine weeks of resveratrol use, starting at 400 mg, increasing every other week to 1.8 g/day.  Using Orchid synthetic  and a 98% extract in powder form, taken with meals. 

Blood sugar: unchanged.  Still borderline.
Cholesterol:  decreased 6%
HDL:            increased 30%.

Mood, energy: good, not tired by exercise that should have knocked me out (eg, >2 hour fast bike ride)  but when I do get tired, the urge to lie down and sleep is overpowering.  Awaken quickly, no sleep hangover, even if I've slept too little.  My "default" walking pace is faster.

Less sensitive to cold.
Ruddier complexion.
Arthritis is less painful, especially fingers. One finger that would "jam" when flexed no longer does.  Big toe still hurts, where I first noticed arthritis symptoms.
Am able to crack my knuckles for the first time in over 10 years.

This isn't a cure-all.  I still need pain meds for an old back injury.

[shadowrun]

I used to crash after work...Just getting up the steam to cook or go to the gym took all my willpower

Now I actually do things and have energy to do more - I don't slow down until 11PM

[health_nutty]

From the current discussion it appears likely that the desirable effects so many of us feel from resveratrol furnish no evidence one way or the other that the desired gene switching action is taking place.

Is that right?

I don't believe there is any evidence (for or against) that the benefits reported are related to gene switching.

[niner]

From the current discussion it appears likely that the desirable effects so many of us feel from resveratrol furnish no evidence one way or the other that the desired gene switching action is taking place.

Is that right?

Well, results like Maxwatt reported, with improved cholesterol readings, are hard to pin on an SSRI-like effect. Short of doing a full-blown gene expression analysis, quantitative blood work seems like the hardest data we have.

[tintinet]

For me, beyond the general energy boost with elimination of almost all sensation of fatigue, the mood elevation is really key, although a bit unsettling, as I find myself laughing for no particular reason... "it's all keeps adding up- I think I'm cracking up!",
but in a good way. [lol]

[maxwatt]

Outstanding!  Your total cholesterol went down 6% while your HDL went up 30%!  That is phenomenal.  The not getting tired by exercise is pretty impressive too!

Do you supplement your resveratrol with any goodies such as OPC's or lecithin?

No, I take a number of things but no OPC's or lecithin, except by diet.

[health_nutty]

Outstanding!  Your total cholesterol went down 6% while your HDL went up 30%!  That is phenomenal.  The not getting tired by exercise is pretty impressive too!

Do you supplement your resveratrol with any goodies such as OPC's or lecithin?

No, I take a number of things but no OPC's or lecithin, except by diet.

Okay, now I'm curious. What else do you take?

[niner]

I think it was niner who said resv is an SSRI, which makes it an anti-depressant *anyone have references?). I don't think doctors recommend cycling anti-depressants like Prozac and Valium, so why would resveratrol be different?

Yes, that was me lazily not including a reference... here it is. Note that not only is resveratrol an inhibitor of reuptake of serotonin and noradrenaline, but it is also an MAO inhibitor. All I can tell from the abstract is that resveratrol is not as potent as prozac (fluoxetine), but exactly how potent is hard to say. Given that a normal starting dose for prozac is 20 mg/d, and the relative concentration ranges given for RSV and fluoxetine in the abstract differ by about an order of magnitude, that would suggest that we are right in the antidepressant range with the doses of resveratrol that people here are taking. Note, however, that the effects of conjugation haven't been taken into account in this study. Nevertheless, the kinds of mood effects and appetite suppression that people are seeing are certainly consistent with these mechanisms. The MAO inhibition is a little worrying, if it is significant, especially if one is megadosing. Could be some possibility of bad interactions with other drugs or even amino acids. Given the lack of toxicity seen with resveratrol to date, I would guess that the MAOI activity is at least not acutely bad. (ps: valium's not an antidepressant)

Biochem Biophys Res Commun. 2006 Jun 2;344(2):688-95. Epub 2006 Apr 17.
Inhibitory effects of cis- and trans-resveratrol on noradrenaline and 5-hydroxytryptamine uptake and on monoamine oxidase activity.

Yanez M, Fraiz N, Cano E, Orallo F.

Departamento de Farmacologia, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela (La Coruna), Spain.

    This study investigated for the first time the potential effects of cis- and trans-resveratrol (c-RESV and t-RESV) on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake by synaptosomes from rat brain, on 5-HT uptake by human platelets, and on monoamine oxidase (MAO) isoform activity. Both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the uptake of [3H]NA and [3H]5-HT by synaptosomes from rat brain and the uptake of [3H]5-HT by human platelets. In both experimental models, t-RESV was slightly more efficient than c-RESV. Furthermore, in synaptosomes from rat brain, the RESV isomers were less selective against [3H]5-HT uptake than the reference drug fluoxetine (0.1-30 microM). On the other hand, both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the enzymatic activity of commercial (human recombinant) MAO isoform (MAO-A and MAO-B) activity, c-RESV being slightly less effective than t-RESV. In addition, both RESV isomers were slight but significantly more selective against MAO-A than against MAO-B. Since the principal groups of drugs used in the treatment of depressive disorders are NA/5-HT uptake or MAO inhibitors, under the assumption that the RESV isomers exhibit a similar behaviour in humans in vivo, our results suggest that these natural polyphenols may be of value as structural templates for the design and development of new antidepressant drugs with two important biochemical activities combined in the same chemical structure: NA/5-HT uptake and MAO inhibitory activity.

PMID: 16631124

[maxwatt]

Outstanding!  Your total cholesterol went down 6% while your HDL went up 30%!  That is phenomenal.  The not getting tired by exercise is pretty impressive too!

Do you supplement your resveratrol with any goodies such as OPC's or lecithin?

No, I take a number of things but no OPC's or lecithin, except by diet.

Okay, now I'm curious. What else do you take?

I'll show you mine, but you have to show me yours.

I have a Tupperware-style box about 12x12 where I keep my non-refrigerated supplements. If I want to add something, I eliminate what isn't working, or duplicates the effect of something else I use or eat. I haven't needed a bigger box yet, though the lipid formulations go in the fridge, and the exotic chemicals and prescription drugs have their own box. Currently:

Low dose multi vitamin and mineral tablet from food sources. I find if I take more than a couple of times the RDA of B1 and B2, I get suicidally depressed and anti-social. (The LEF essential multi, with very unequal amounts of these, made me quite paranoid.)
Additional biotin, folic acid, mega B12 and D3. I am cutting back the folic acid to around 800mcg. D3 is 2000 to 4000 units, I'm outside a lot.
200 IU gamma-tocopherol in a mixed tocopherol base. I believe more is counter-productive.
bilberry, lutein and zeaxanthine. (My night vision is so good I can detect half a photon;)
EPA from salmon, herring, sardines; I eat enough of them I felt I could do without the supplement.
GLA from black current oil.
R-ALA and ALC (just dumped CoQ10)
NALC (N-Acetyl-Cysteine)
Was using Milk Thistle extract (Silymarin) until I found a source of high purity resveratrol.
n-tert butyl hydroxylamine
Cycling ALT-711 and a SOD mimetic.

Am using ashwaganda and maca, probationally. May cut the maca for a while, it's one variable too many to evaluate.

By prescription, Vicophen (codeine and ibuprufen) for a chronic back injury.
Rhodiola as an occasional stimulant.

Alcohol several times a week. I drink a pomegranate liquor when I don't drink red wine at dinner. Tonight's Yellowtail was awful but my wife liked it. Prefer a Montepulciano. Buffalo instead of beef (EPA source). Salmon. Cook with olive or grape seed oil. Lots of vegetables and fruit, especially berries. Grape seed or hemp seed oil for salads.

I take resveratrol with meals, as did Sinclair's mice. I just swallow the powder and wash it down, either before or after the meal. I don't know if it's optimum, but it works.

I'm thinking of adding metformin, as a CR mimetic, but I want to consult an endocrinologist first.

FWIW, I use a Cardiocheck Meter, it takes chips and test strips for Total Cholesterol, HDL, and LDL. It will measure blood sugar too, but the blood sampling procedure is awkward. I'm getting better at it, but still mess up half the readings. The test strips are expensive. I use the CVS house brand $20 meter for blood sugar.

-------------------------
PS: Niner, thanks for the reference.

[health_nutty]

Looks good Maxwatt, thanks for sharing.

Here's mine:
http://www.imminst.o...=238&t=13063&s=

[Ghostrider]

For me, beyond the general energy boost with elimination of almost all sensation of fatigue, the mood elevation is really key, although a bit unsettling, as I find myself laughing for no particular reason...  "it's all keeps adding up- I think I'm cracking up!",
but in a good way.  [lol]

Tintinet, what dosage / brand are you taking? Gimme some of that!

[tintinet]

I've always favored moderation (although this policy, at time, includes moderation), so
I get resveratrol from a variety of sources.

Recently, I was using Orchid synthetic highly pure (>99% trans-resv) along with Country Life, NSI, Biotest, and BAC sources, depending upon what was handy in the cupboard.

More recently I've been using 98% Purity Polygonum cuspidatum extract, NOW Natural Resveratrol, and Country Life Resveratrol Plus, with some rotation of the aforementioned components.

Almost always taken with meals, in divided doses to reach a daily total of approx. 1 gram/day (Yeah, I know: not very moderate for most folks!).

[Ghostrider]

I've always favored moderation (although this policy, at time, includes moderation), so
I get resveratrol from a variety of sources. 

Recently, I was using Orchid synthetic highly pure (>99% trans-resv) along with Country Life, NSI, Biotest, and BAC sources, depending upon what was handy in the cupboard.

More recently I've been using 98% Purity  Polygonum cuspidatum extract, NOW Natural Resveratrol, and Country Life Resveratrol Plus, with some rotation of the aforementioned components.

Almost always taken with meals, in divided doses to reach a daily total of approx. 1 gram/day (Yeah, I know: not very moderate for most folks!).

Try this, if you don't mind. Take 300 mg / 130 lbs of Country Life Resveratrol Plus just once in the morning for one day and tell me how you feel compared to your usual dosage. On the second week of taking my higher than usual dosage of 200 mg (tried 300 mg for first time today), I do not feel as energetic as I did last week. I am suspecting that my effects might have been mostly placebo, but I know my mood was better and I recall having more energy. Or maybe I am building up tolerance to the stuff.

[steelheader]

I think it was niner who said resv is an SSRI, which makes it an anti-depressant *anyone have references?). I don't think doctors recommend cycling anti-depressants like Prozac and Valium, so why would resveratrol be different?

Yes, that was me lazily not including a reference... here it is. Note that not only is resveratrol an inhibitor of reuptake of serotonin and noradrenaline, but it is also an MAO inhibitor. All I can tell from the abstract is that resveratrol is not as potent as prozac (fluoxetine), but exactly how potent is hard to say. Given that a normal starting dose for prozac is 20 mg/d, and the relative concentration ranges given for RSV and fluoxetine in the abstract differ by about an order of magnitude, that would suggest that we are right in the antidepressant range with the doses of resveratrol that people here are taking. Note, however, that the effects of conjugation haven't been taken into account in this study. Nevertheless, the kinds of mood effects and appetite suppression that people are seeing are certainly consistent with these mechanisms. The MAO inhibition is a little worrying, if it is significant, especially if one is megadosing. Could be some possibility of bad interactions with other drugs or even amino acids. Given the lack of toxicity seen with resveratrol to date, I would guess that the MAOI activity is at least not acutely bad. (ps: valium's not an antidepressant)

Biochem Biophys Res Commun. 2006 Jun 2;344(2):688-95. Epub 2006 Apr 17.
Inhibitory effects of cis- and trans-resveratrol on noradrenaline and 5-hydroxytryptamine uptake and on monoamine oxidase activity.

Yanez M, Fraiz N, Cano E, Orallo F.

Departamento de Farmacologia, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela (La Coruna), Spain.

    This study investigated for the first time the potential effects of cis- and trans-resveratrol (c-RESV and t-RESV) on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake by synaptosomes from rat brain, on 5-HT uptake by human platelets, and on monoamine oxidase (MAO) isoform activity. Both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the uptake of [3H]NA and [3H]5-HT by synaptosomes from rat brain and the uptake of [3H]5-HT by human platelets. In both experimental models, t-RESV was slightly more efficient than c-RESV. Furthermore, in synaptosomes from rat brain, the RESV isomers were less selective against [3H]5-HT uptake than the reference drug fluoxetine (0.1-30 microM). On the other hand, both c-RESV and t-RESV (5-200 microM) concentration-dependently inhibited the enzymatic activity of commercial (human recombinant) MAO isoform (MAO-A and MAO-B) activity, c-RESV being slightly less effective than t-RESV. In addition, both RESV isomers were slight but significantly more selective against MAO-A than against MAO-B. Since the principal groups of drugs used in the treatment of depressive disorders are NA/5-HT uptake or MAO inhibitors, under the assumption that the RESV isomers exhibit a similar behaviour in humans in vivo, our results suggest that these natural polyphenols may be of value as structural templates for the design and development of new antidepressant drugs with two important biochemical activities combined in the same chemical structure: NA/5-HT uptake and MAO inhibitory activity.

PMID: 16631124

[edbear]

I do not feel as energetic as I did last week.  I am suspecting that my effects might have been mostly placebo, but I know my mood was better and I recall having more energy. 

I had the same effect - about three weeks of amazing energy and lost appetite, which then went away and hasn't returned. I suspect it may not have been entirely placebo, but in the absence of any additional evidence that's where I'm classifying it.

That being said I still find I have a higher tolerance for exercise now than I've had in a while.