1708 replies to this topic

[Anthony_Loera]

Just a link to Sirtris possible NCE formulations from international patents:

http://www.wipo.int/...&DISPLAY=STATUS
http://www.wipo.int/...p?wo=2007019416
http://www.wipo.org/...p?wo=2007019417
http://www.wipo.int/...p?wo=2007019346
http://www.wipo.int/...p?wo=2007019344


have fun.

[ilanso]

Seems to me that rather than looking for ways to maximize the serum concentration of t-res, our quest should be directed at finding the optimum dose that doesn't trigger too serious an inhibition of aromatase, with its negative joint consequences.
In another thread, there was mention of silymarin's collusion with t-res in what regards SIRT1. It was also purported to be pro-estrogenic, the opposite of t-res. Perhaps combining the two may do the trick (possibly with Miralax as common excipient for enhanced absorption) if the safe t-res dose alone turns out to be too low for the desired clinical effects.
It would be interesting as well to conduct a little poll on the estradiol (E2) readings of the "500 club" members before and after joining it. It might give us an idea of the threshold beyond which E2 is severely reduced. I personally had it tested on 09/06 (was 42) and a month later (was 10). These are both "before" figures and right now I can't recall the reason for the drop (although it was intended, as at the time I was aiming for low numbers, such as the 14 I had scored on 12/04). I also spotted Krillin's 33, but ignore the context. I also wonder how stable these levels are throughout the day and what other external factors might influence their fluctuation. Also what the sweet spot is for an E2 high enough to not lead to osteoarthritis-type symptoms and low enough to protect against prostate cancer (or BPH). In a month or so I hope to get my "after" result.

[markymark]

Seems to me that rather than looking for ways to maximize the serum concentration of t-res, our quest should be directed at finding the optimum dose that doesn't trigger too serious an inhibition of aromatase, with its negative joint consequences.

inhibition of aromatase is a desired feature of t-res! where does "too serious inhibition of aromatase" begin?

isn't the overall problem: obesity and its consequences?
thus, the, (or one) enemy of every obese man (and also woman) is too much estradiol, through increased netto aromatase capacity due to increased adipose tissue
if t-res protects against overt estradiol presence in the obese and in turn leads to some more testosterone this is fine!

the oversimplistic testosterone-causes-prostate-cancer-argument is false, as we know.
moreover t-res seems to protect against prostate cancer, as far as the animal data show

therefore effective aromatase-inhibition by t-res should be in the end regarded as a useful effect..

[rwoodin]

I have experienced a number of joint pains in the knees, hips and feet these past few months. Also had an injured achilles tendon - which had me really hobbling around for a couple, few weeks and is just now resolving after a couple months. My feet, in general, have been 'killing me' lately. They are very sore in the heals and toes on the bottom of the feet. I supplement with anywhere from 0.5 to 3 grams tres 99% per day. I think maybe I'll back off to .5 gram a day for a month and see how the feet feel. Might be just coincidence. I was also taking a high glycemic creatine mix for a couple months. But I've been off that for at least the last two months and the feet are still sore....Glad I read the postings in this thread.

[ilanso]

http://www.docguide....5256F27006E69C3

Declining Estradiol Levels More Predictive of Fracture Risk Than Low Testosterone in Aging Men: Presented at ASBMR

By Bonnie Darves

SEATTLE, WA -- October 8, 2004 -- Sex hormone levels may play a greater role in determining which men will be at higher risk of osteoporosis-related fractures than previously thought, according to a study presented at the American Society for Bone and Mineral Research annual meeting.

While low levels of free testosterone are a predictor of hip bone loss, declines in estradiol levels play a stronger role than testosterone, the study's lead author, Jane Cauley, DrPH, associate professor of epidemiology, University of Pittsburgh School of Medicine, Pennsylvania, said on October 5th.

While men with higher levels of free testosterone and total testosterone have less bone loss than men with lower testosterone levels, that relationship does not translate into higher bone mineral density (BMD), she said.

Dr. Cauley and colleagues in the Osteoporotic Fracture in Men Study conducted a study in 2,619 men aged 65 and older.

"Men who experienced the greatest decline in estradiol experienced greater bone loss, independent of their testosterone levels," Dr. Cauley said. "We found that estradiol, not testosterone, is the major predictor of BMD and bone loss rates in men, regardless of weight, age, and baseline BMD."

She said that men who had the largest declines in estradiol over the 1.8 years of the study lost 0.72% total hip BMD annually, compared with a decline of 0.42% in those in the top baseline estradiol quintile. Lumbar spine BMD also was 7% higher in the estradiol top-quintile group than in the bottom-quintile group, Dr. Cauley noted.

She added that her team members were somewhat surprised to find no correlation between advancing age and estradiol levels in the cohort. There were men with relatively high baseline estradiol levels in all age groups, including the group older than 80 years, but 65% of men experienced some estradiol loss over the study period, she added.


[Presentation title: "Sex Steroid Hormones in Older Men: Cross-Sectional and Longitudinal Associations With Bone Mineral Density (BMD). The Osteoporotic Fracture in Men Study (MrOS). Abstract 1058]

[stephen_b]

It would be interesting as well to conduct a little poll on the estradiol (E2) readings of the "500 club" members before and after joining it.

After supplementing with 2 g transresveratrol for a couple of months, my E2 measurement was 38 pg/mL. I might have that number for a blood test I took 7 years ago available later. Any thoughts on whant one's estradiol should be?

Stephen

[rabagley]

good link ilanso, thanks.

[ilanso]

Can't find a good reference on the lower bound for E2. The labs range only says <52 or so. Literature mentions it in terms of quartile/quintiles. Seems that a Goldilocks approach is warranted - I would shoot for the middle of the range (26) and start worrying when it gets into the lowest quintile (<10). Again, the highest one, although great for BMD, may get too close to the prostate/breast cancer promoting zone.

http://www.annals.or...ract/133/12/951

Association of Hypogonadism and Estradiol Levels with Bone Mineral Density in Elderly Men from the Framingham Study
right arrow Shreyasee Amin, MD, FRCP©, MPH; Yuqing Zhang, DSc; Clark T. Sawin, MD; Stephen R. Evans, MPH; Marian T. Hannan, DSc, MPH; Douglas P. Kiel, MD, MPH; Peter W.F. Wilson, MD; and David T. Felson, MD, MPH

19 December 2000 | Volume 133 Issue 12 | Pages 951-963

Background: Both hypogonadism and low estrogen levels adversely affect bone health in young men. In elderly men, who are at greatest risk for osteoporotic fracture, the influence of hypogonadism on bone mineral density remains unclear, as does the relative effect of estrogen status compared to hypogonadism.

Objective: To examine the relation of hypogonadism and estrogen status to bone mineral density in elderly men.

Design: Community-based, prospective cohort study.

Setting: Framingham, Massachusetts.

Patients: Male participants of the Framingham Study.

Measurements: Total testosterone, total estradiol, and luteinizing hormone were measured in participants at all four biennial examinations from 1981 to 1989. Values from at least three of four examinations were averaged. Hypogonadism was defined as a mean testosterone level less than 10.4 nmol/L (<3.0 ng/mL) or a mean luteinizing hormone level of 20 IU/L or greater. An alternate definition of hypogonadism based only on a mean testosterone level less than 10.4 nmol/L (<3.0 ng/mL) was also used. In 1988–1989, bone mineral density was measured at the proximal femur (femoral neck, Ward triangle, and trochanter) and lumbar spine by using dual-photon absorptiometry and at the radial shaft by using single-photon absorptiometry. The association of hypogonadism with bone mineral density was examined with adjustment for confounders, including estradiol levels. A similar model that adjusted for hypogonadism was used to examine the association of estradiol level (ranked as quartiles) with bone mineral density.

Results: Of 448 men with bone mineral density measurements, 405 had evaluable hormone levels (mean age, 75.7 years [range, 68 to 96 years]); 71 (17.5%) of the 405 men were hypogonadal. Bone mineral density at any site did not significantly differ in hypogonadal men compared with eugonadal men (for example, bone mineral density at the femoral neck was 0.89 g/cm2 vs. 0.87 g/cm2, respectively; P > 0.2), even when alternate definitions of hypogonadism were used. In contrast, compared with the lowest estradiol quartile, men with higher estradiol levels had greater mean bone mineral density at all sites (for example, bone mineral density at the femoral neck was 0.84 g/cm2, 0.88 g/cm2, 0.86 g/cm2, and 0.91 g/cm2 from the lowest to the highest estradiol quartile; P for trend = 0.002). The difference in mean bone mineral density between men in the lowest and those in the highest estradiol quartile levels was similar to the effect of 10 years of aging on bone mineral density.

Conclusions: In elderly men, hypogonadism related to aging has little influence on bone mineral density, but serum estradiol levels have a strong and positive association with bone mineral density.

[bixbyte]

Just a link to Sirtris possible NCE formulations from international patents:

http://www.wipo.int/...&DISPLAY=STATUS
http://www.wipo.int/...p?wo=2007019416
http://www.wipo.org/...p?wo=2007019417
http://www.wipo.int/...p?wo=2007019346
http://www.wipo.int/...p?wo=2007019344


have fun.

The Einstein of the fountain of youth?
But, I agree with the other posters, DOSE.
Give us the correct Dose!

[krillin]

I also spotted Krillin's 33, but ignore the context.

I was on 120 mg at the time and was too chicken to increase it. After what Cymbalta and Lexapro did to me, I didn't want any SNRI effects.

I'm down to 20 mg resveratrol (what comes with Pomeratrol) and 1 g 80% milk thistle + 1/2 teaspoon Miralax. I think the milk thistle is having an anti-inflammatory effect, but haven't noticed anything else.

[craigb527]

I have taken some very large doses over the past couple weeks with no negative noticeable side effects. I got bloodwork done before I started taking res, will get it done again in a couple of weeks. What should I look for?

Edited by craigb527, 24 October 2007 - 03:00 AM.

[stephen_b]

I have taken some very large doses over the past couple weeks  with no negative noticeable side effects.  I got bloodwork done before I started taking res, will get it done again in a couple of weeks.  What should I look for?

C-reactive protein and iron levels would be interesting to me.

Stephen

[ilanso]

Starting from:

resveratrol can act as a powerful systemic aromatase inhibitor when very large amounts are taken

I was wondering how much "large" is.
The only relevant poll response so far was:

stephen_b
After supplementing with 2 g transresveratrol for a couple of months, my E2 measurement was 38 pg/mL

From this n=1 study, one can draw a plethora of conclusions: 2g is not enough (or absorption was low), he didn't get the "real thing", his other supplements compensated for it, etc.
Here is a long term study that implies the inhibition is dose-dependent (albeit not specifically t-res, but grape seed extract):
http://www.cbcrp.org...sp?grant_id=281

Symposium Abstract (2005)
Suppression of aromatase/estrogen biosynthesis is thought to have potential for chemoprevention of breast cancer. Aromatase is the enzyme that converts androgen to estrogen. An abnormally high expression of aromatase in breast tissue is considered to be a risk factor for breast cancer. In our laboratory, we found that of seven fruit juices tested, grape juice was the most effective in inhibiting the activity of human placental aromatase activity.

During the last several years, we have learned that: (1) the methanol extract of grape juice and red wine suppresses aromatase in a dose-dependent manner; (2) the extract suppresses the proliferation of an aromatase over-expressing and estrogen receptor-positive breast cancer cell line – MCF-7aro; (3) oral administration of the extract completely stops aromatase-induced hyperplasia and other changes in the mammary tissue of aromatase transgenic mice; (4) procyanidin B dimers, the major phytochemicals in the seeds and skins of grapes, are the chemicals responsible for the anti-aromatase activity; and (5) oral feeding of procyanidin B dimers reduces androgen-dependent MCF-7aro tumor growth in nude mice.
........
Symposium Abstract (2007)
Aromatase is the enzyme that converts androgen to estrogen. It is expressed at higher levels in breast cancer tissues than normal breast tissues. Grape seed extract (GSE) contains high levels of procyanidin dimers that have been shown in our laboratory to be potent inhibitors of aromatase. In this study, GSE was found to inhibit aromatase activity in a dose-dependent manner and reduce androgen-dependent tumor growth in an aromatase-transfected MCF-7 (MCF-7aro) breast cancer xenograft model, agreeing with our previous findings.

We have also examined the effect of GSE on aromatase expression. RT-PCR experiments showed that treatment with 60 µg/ml of GSE suppressed the levels of exons I.3-, PII-, and I.6-containing aromatase mRNA in MCF-7 and SK-BR-3 cells. The levels of exon I.1- containing mRNA, however, did not change with GSE treatment. Transient transfection experiments with luciferase-aromatase promoter I.3/II or I.4 reporter vectors showed the suppression of the promoter activity in a dose-dependent manner. The GSE treatment also led to the down-regulation of two transcription factors, cAMP-responsive element binding protein-1 (CREB-1) and glucocorticoid receptor (GR). CREB-1 and GR are known to up-regulate aromatase gene expression through promoters I.3/II and I.4, respectively. We believe that these results are exciting in that they demonstrate GSE to be potentially useful in the prevention/treatment of hormone-dependent breast cancer through the inhibition of aromatase activity as well as its expression.

If that's true, the before and after E2 readings could be used as a t-res degree of activity biomarker- i.e. one could stop increasing the dose the moment E2 drops (say 15%, or to an absolute target such as 26). To increase the chances of this working, one would have to always test at the same hour of the day and keep all other variables constant.

[levkamensky]

So nobody experienced anything analogous to Auwerx's mice even the ones taking huge doses? Does this thing work for anyone beyond barely perceptible half-imaginary effects? I see everyone's reports end with a "but it could be placebo effect". Has anyone had any effects where such doubts wouldn't ever enter your mind? I have been taking 1000 mg (500 mg trans) for a month and haven't noticed anything.

Special message for the person with grapes in his dp, keep your petty childish insults to yourself and respond with intelligence next time. Unlike you I don't have time to troll forums and call people you don't know names. Learn some respect for Christ's sake!

Edited by levkamensky, 24 October 2007 - 10:37 PM.

[Anthony_Loera]

Increased endurance, yes... most definitely. Doubled? Not sure, I didn't do a before and after.

A

[levkamensky]

I already have great endurance. Power and speed is where I could use some improvement.

Jogging 40 minutes a day 6 days a week will give you uber endurance.

[levkamensky]

Anthony thanks you have been very helpful. It's good to know that at least endurance is a definite effect.

[craigb527]

So nobody experienced anything analogous to Auwerx's mice even the ones taking huge doses? Does this thing work for anyone beyond barely perceptible half-imaginary effects? I see everyone's reports end with a "but it could be placebo effect". Has anyone had any effects where such doubts wouldn't evem enter your mind? I have been taking 1000 mg (500 mg trans) for a month and haven't noticed anything.

I experienced increased enduarance, less muscle fatigue, etc. I was taking large doses in order to experience this. When I started taking resveratrol I could do about 15 pushups before tiring. A week after taking heavy doses, I could do 50. When I began I was lifting two 35 pound dumbells over my head 30 to 35 times before tiring, after a week I could do it 100 times. Also, my muscles did not get sore at all during workouts or the next day. When I put at the end of my
statement it could be a placebo effect, I was being facetious. If it was a placebo effect, then the placebo effect made me stronger. But, I don't want to say, "Yes, run out and do heavy doses, you'll get stronger!" because I don't want to be responsible for health problems other individuals may incur from heavier doses. Also, I would recover very quickly after a workout, no heavy breathing like usual and the next day my muscles wold not be sore. One thing I noticed though, is that while my endurance was improved, I felt unmotivated to get things done. A kind of laziness while not exerting energy. Also, I am not sure if I became stronger or if it is more endurance, I have not attempted to see if I can actually lift more or just do more reps.

[levkamensky]

Anthony, your site makes the following claim, "No one else offers a 500mg capsule of Resveratrol."

Is your 500mg capsule 100% trans-resveratrol?

Craig, 50 pushups and the dumb bell reps in one set without pausing?

I don't feel the laziness at all. I am on a diet of strictly only botanical fruit. I eat one cage free egg per week, and I eat some soya products such as tofu, and nuts for protein. A diet high in animal products or even plant products will make you feel drowsy and heavy.

[levkamensky]

OK, sorry I see here, 1000 mg pill with 500 trans.

Hmm so if I take 4 pills a day then I will be taking 2,000 mg trans for only 150 bucks a month. That's an excellent deal.

I need to order a refill now... Has anyone here independently tested Anthony's pills to make sure they really contain 500 mg trans?

[craigb527]

Anthony, your site makes the following claim, "No one else offers a 500mg capsule of Resveratrol."

Is your 500mg capsule 100% trans-resveratrol?

Craig, 50 pushups and the dumb bell reps in one set without pausing?

I don't feel the laziness at all. I am on a diet of strictly only botanical fruit. I eat one cage free egg per week, and I eat some soya products such as tofu, and nuts for protein. A diet high in animal products or even plant products will make you feel drowsy and heavy.

Yes, without pausing. Also without heavy breathing and muscles not sore afterword. I have always, in the past, been terrible at pushups, hated doing them because I could do so few.

[levkamensky]

That's good to know. I just did ten. Need to get back into shape... I was like 210lb and this semi-fruitarian diet got me back to 180, so now I am ready to test out the miracle pill's effect.

[craigb527]

I weigh 225 and haven't lost any weight from resveratrol. But, like I said, I experienced increased endurance at higher doses.

[levkamensky]

We seem to have a consensus about increased endurance which is good.

It would be interesting to see if people buying resveratol from certain vendors have stronger effects then others.

It would also be interesting to know if anyone here takes doses equivalent to Auwerx's mice (at least 6 grams), do they have much different effects from the people taking around 2 grams, like weight loss?

[craigb527]

If your asking me, Anthony Loera is the person to buy from. Good price and excellent custumer service. I don't need to test his product, I feel the effects.

http://www.revgenetics.com/order.html

[craigb527]

We seem to have a consensus about increased endurance which is good.

It would be interesting to see if people buying resveratol from certain vendors have stronger effects then others.

It would also be interesting to know if anyone here takes doses equivalent to Auwerx's mice (at least 6 grams), do they have much different effects from the people taking around 2 grams, like weight loss?

Auwerx's mice equivalent is 6 grams? Didn't know that. I have exceeded that. No weight loss.

[levkamensky]

That is nice, but just to be sure. In G-d we trust everyone else must pay cash. My parents are biochemists. They may be able to test it for me. But if someone here already tested it, I'd appreciate the feedback. (An I already know maxwatt's opinion.) If this product is what it claims it is, I could recommend it to some people. I have a website too.

Biotiva makes the following claims,

- Preserved in nitrogen gas to insure 24 month active life.
- No quercetin or chemicals that interfere with resveratrol.
- Enhanced bio availability equals higher potency and effects.

How does Anthony’s product compare in respect to these points?

His capsules have anti-UV coating is it right? What about the encapsulation process?

I am a little concerned about trans-resveratol turning into cis-resveratol.

[levkamensky]

We seem to have a consensus about increased endurance which is good.

It would be interesting to see if people buying resveratol from certain vendors have stronger effects then others.

It would also be interesting to know if anyone here takes doses equivalent to Auwerx's mice (at least 6 grams), do they have much different effects from the people taking around 2 grams, like weight loss?

Auwerx's mice equivalent is 6 grams? Didn't know that. I have exceeded that. No weight loss.

Actually Auwerx's mice equivalent is 7 - 8 grams, but I heard 6 is the mximum you can take safely. That's good to know. Have you tried products from other vendors?

For the last week I have been taking my res. with grapefruit juice as maxwatt suggested, and haven't noticed much difference.

[levkamensky]

I am still curious if this holds any weight --->>

http://www.longevine...tory=Imitations

I would like to see someone take 6,000 mg of Longevinex's resveratol, and see if they experience effects similar to Auwerx's mice. Unfortunately it's beyond my means.

[craigb527]

We seem to have a consensus about increased endurance which is good.

It would be interesting to see if people buying resveratol from certain vendors have stronger effects then others.

It would also be interesting to know if anyone here takes doses equivalent to Auwerx's mice (at least 6 grams), do they have much different effects from the people taking around 2 grams, like weight loss?

Auwerx's mice equivalent is 6 grams? Didn't know that. I have exceeded that. No weight loss.

Actually Auwerx's mice equivalent is 7 - 8 grams, but I heard 6 is the mximum you can take safely. That's good to know. Have you tried products from other vendors?

For the last week I have been taking my res. with grapefruit juice as maxwatt suggested, and haven't noticed much difference.

As far as I know, Resveratrol is not toxic. I am not sure what can be taken safely, it seems 20 different people will state 20 different things. I have taken 150 mg/kg without feeling any noticeable negative side effects. I have read that someone taking 5 grams experienced 2.4 uM blood level and that a level of at least 5 uM was needed for chemopreventive activity in vitro, so I tried some higher doses hoping to achieve levels over 5 uM.

The results of the range-finding study demonstrated that the maximum dose of resveratrol that can be delivered to mice on a daily basis is limited by mortality associated with impaction of unabsorbed test material in the gastrointestinal tract, rather than by any specific toxicity of the agent itself. In this study, 40% mortality was observed in male C57BL/6 mice receiving the highest dose of resveratrol (5000 mg/kg/day). In all early deaths in this group, a large mass of unabsorbed test article was identified at necropsy in the stomach and/or intestines. No pattern of early deaths was seen in male mice receiving lower doses of resveratrol, or in female mice at any resveratrol dose level.

link http://www.pubmedcen...i?artid=1855246