"500 club" 500mg of trans-resveratrol per day

I didn't measure my blood pressure while traveling, but ever since returning it's been under 120/80 more often than not, and doesn't seem to vary as much.  It's like 117/66 plus or minus 5 most of the time when I measure it after sitting down for awhile -- at least 10 lower than its previous range -- and I've seen it as low as about 96/50 while lying in bed right after waking up, which is also 10 or 20 less than I've ever seen.  My pulse is now around 60 while sitting down, and I think I've seen it as low as 49 before getting up.  When I take a VO2 Max treadmill test, my average pulse is consistently at least 10 lower than before (under 110 vs. about 120), although the maximum and the VO2 Max score seems to be similar or just a little better than it used to be -- range is about 56 to mid-60's.  And I've lost 4.5kg, probably due to exercising a little more and eating less, taking advantage of the increased stamina and decreased appetite.  (That's good; my BMI was 24.5, just barely still a healthy weight, and now it's 23.4.  I once had my body fat measured, and that indicates that my ideal weight would be 73kg, so it's great that I've gone from 80kg down to 76kg.)

Excellent news. Its hard to isolate the effects of resveratrol because exercising more and losing weight will drop your blood pressure.

I wonder if the stamina and appetite effects might come from fat mobilization (search scholar.google.com for "fat mobilization resveratrol"). It makes sense intuitively that having more efficient access to stored fat would reduce the urge to eat and also supply energy.

The competing theory for the stamina and blood pressure would be extra and more efficient mitochondria allowing more energy to be produced with less oxygen.

The competing theory for the stamina and blood pressure would be extra and more efficient mitochondria allowing more energy to be produced with less oxygen.

I hope this theory is true as I myself am taking 400-600mg a day. Either directly or indirectly the t-res is affecting your blood pressure.

I wonder if the stamina and appetite effects might come from fat mobilization (search scholar.google.com for "fat mobilization resveratrol").  It makes sense intuitively that having more efficient access to stored fat would reduce the urge to eat and also supply energy.

The competing theory for the stamina and blood pressure would be extra and more efficient mitochondria allowing more energy to be produced with less oxygen.

Don't the mitochondria burn fat? We know resveratrol in high doses increases the size and number of mitochondria per cell. This is complementary, not a competing theory.

I am now a proud member of the 500 club. Ordered my first batch of 98% Resv today costing me 70$ for 50 days worth of powder @ Revgenetics. I am going to get blood work done before I start and am going to weigh myself, and I will try to repeat it again every month. It only costs 20$ to get blood work done @ my college.

I also got some resv for my diabetic grandfather, so hopefully it will help with his blood glucose levels (which I have heard it does). I will post more sporatic updates from him.

Actually, has anyone seen improvement or worsening in their blood glucose levels? Is there any reason why this product might be dangerous for a diabetic? I would think it would be great for one. Cheers.

Edited by lucid, 16 June 2007 - 02:03 AM.

Just had my blood glucose (along with a bunch of other parameters) assayed this week. Non-fasting mid-morning (11 AM) blood glucose was 80 mg/dl. Right about where it always is (50-90, for over 25 years). Currently taking 1 gram t-resv./day- mostly synthetic 99%+ purity at the moment.

I just had my latest bp reading by a nurse this past Friday. I trust their readings more than the machine at my local drugstore. It was 118/68 which is definitely improved over my earlier readings (before T-Resv. supplementation). Those tended to be more like ~130/80 and had seemed to be creeping up over the years as I approach my forties. Pulse was 50bpm, body temp was 97.6 but I've always been a bit on the cool side....

With the price of resveratrol dropping significantly there are many more on this board taking on the order of 500mg/day of t-res.  I know that Duke Nukem has been taking around 420mg a day for a while.  Maxhealth is taking 800mg!  Makoss is taking 500mg a day.  I'm sure there are more people. It would be interesting to get all the feedback and logs into one location (and out of the personal supplementation section which gets very little traffic). 

I just received my Country life plus resveratrol and am starting to ramp my dosage starting today (with the goal being 400mg).  I'll post back regularly with updates.
Male 30yo 150lb 7% BF
BP 100/60
Resting Heart Rate: 60bbm

health nutty,
You're a role model for me. I plan to become nutty like you.

I'm currently Male 31yo, 177 lbs. (5'9.5")
%BF unknown but 6 lbs overweight according to BMI
BP & RHR Unknown but healthy as of my last doctor's checkup a couple weeks ago.

I haven't started taking Resveretrol yet but I plan to soon!

Ok, got my shipment in from Revgenetics today:
I got the powder and intend to measure some out with a spoon every day and wash it down with water instead of trying to cap it. Is there any problem with this? Will the tresv that makes contact with the side of my mouth not be absorbed? Does this method effectively waste tresv?

I also want to make sure that the product that I got is legit. It is a white with a slight beige/yellow tint. It is also very crumbly and sticks to my finger surprisingly well when touched.

Hi Lucid,

it's legit, I believe maxwatt has also verified this same powder as well.

Anthony

Hmm also have a very pronounced euphoria now (about an hour after I took the product). I also take an antidepressant, but i never get a feeling like this.

That is curious,

what anti-depressant do you take?

A

cymbalta and welbutrin (just a little bit of each)
cymbalta is a Serotonin-norepinephrine reuptake inhibitor.
welbutrin is norepinephrine reuptake inhibitor and dopamine reuptake inhibitor.

Other people talk about a positive mood boost though, what I felt was stronger than the effect that I normally get from my meds though not quite as long lasting.

I have been taking between 300 and 500mg of t-res every day for several months now (i have recently been taking it along with 200mg of quercetin). I don't keep detailed logs of bio-markers or anything. I was mainly hoping to notice the endurance enhancing benefits. Other supps I take regularly are fish oil, multi-vit, MSM and extra vit D3 (2400IU).

I have to say that I noticed diddly squat. I have been taking the country life brand. Someone once suggested that older people might benefit more - without wishing to sound egotistical I am a very fit athlete in my early 20s so I attributed the lack of noticeable benefit to that.

I have though experienced recent tendon problems (achilles) to which I made no connection to the resveratrol at all. That was until I saw this post in the 'Res into Sweden' thread:

Emodin like resveratrol strongly inhibits angiogenesis for wound healing, inhibits cell growth, inhibits androgen receptors, etc., and while this may seem good for blocking abnormal growth process, ie, prostate cancer cells, this also could have untoward side effects such as diminished wound healing, weakened tendons, ligaments, poor healing of muscle strain, loss of libido, loss of muscle mass from inhibited repair processes, possibly sounds like the syndrome of andropause?? What about increased risk of hemorraghic stroke if blood vessels cannot repair properly. Some inhibition of angiogenesis is valuable to decrease vascular endothelial proliferation and intimal lining thickening that lead to athersclerosis (one benefit of resveratrol), but surely some angiogenesis is needed to maintain vascular integrity and strength. Interestingly, in one animal study resveratrol at a higher dose 20 mg/kg increased both fertility and testosterone levels simulataneously and since it has an anti-aromatase effect could prevent the conversion to estrogen - thus resveratrol may be helpful for andropause, but emodin may not.

Eng ET, Williams D, Mandava U, Kirma N, Tekmal RR, Chen S.
Anti-aromatase chemicals in red wine.
Ann N Y Acad Sci. 2002 Jun;963:239-46.
PMID: 12095950 [PubMed - indexed for MEDLINE]

I normally just browse without posting but I registered so that I could I ask this question; I was wondering whether anyone thought there could be any credence to idea that the resveratrol supplementation could be weakening my tendons?

The fact that I have not experienced any noticeable benefits is enough for me to question its necessity in my regime, but I bought a fair amount to offset international shipping costs and now I'm wondering if I should continue taking the stuff I have already?

Edited by Michael, 27 July 2009 - 01:43 PM.
Trim quote

I doubt your t-resv. supplementation had anything to do with your tendinitis. Maybe if you were taking 3-5 grams/day.....

I have to say that I noticed diddly squat. I have been taking the country life brand. Someone once suggested that older people might benefit more - without wishing to sound egotistical I am a very fit athlete in my early 20s so I attributed the lack of noticeable benefit to that.

Right. To put it another way, if you suddenly felt 30% younger, would you expect to notice the difference? (Not that the workings of resveratrol are likely to be that simple, of course.)

But you might think about more than short-term effects on endurance. If it really extends one's remaining lifespan in humans by a certain percentage, and medical science doesn't find anything better in the next 50 years, you'll get a lot more benefit out of it in the long run than a middle-aged person would. On the other hand, there should be a lot more information about it in a couple of years.

Any effect on heart rate, blood pressure, cholesterol, etc. that you know of?

Actually, has anyone seen improvement or worsening in their blood glucose levels?

At the lower dose I was on when I got my last blood work done, my glucose did not change. To find everyone's past reports of blood results, you might want to start with the list of links I posted here a while back.

I
I have though experienced recent tendon problems (achilles) to which I made no connection to the resveratrol at all. That was until I saw this post in the 'Res into Sweden' thread:

FWIW, I'm also having some tendon problems in my ankle that I twisted a year ago. I seem to have reinjured it without any acute injury. It happened while using active ankle braces as well.

I have been taking between 300 and 500mg of t-res every day for several months now (i have recently been taking it along with 200mg of quercetin). [...] I have to say that I noticed diddly squat. I have been taking the country life brand. [...] I have though experienced recent tendon problems (achilles) to which I made no connection to the resveratrol at all. That was until I saw this post in the 'Res into Sweden' thread:

Emodin like resveratrol strongly inhibits angiogenesis for wound healing, inhibits cell growth, inhibits androgen receptors, etc., and while this may seem good for blocking abnormal growth process, ie, prostate cancer cells, this also could have untoward side effects such as diminished wound healing, weakened tendons, ligaments, poor healing of muscle strain, loss of libido, loss of muscle mass from inhibited repair processes, possibly sounds like the syndrome of andropause?? What about increased risk of hemorraghic stroke if blood vessels cannot repair properly. Some inhibition of angiogenesis is valuable to decrease vascular endothelial proliferation and intimal lining thickening that lead to athersclerosis (one benefit of resveratrol), but surely some angiogenesis is needed to maintain vascular integrity and strength. Interestingly, in one animal study resveratrol at a higher dose 20 mg/kg increased both fertility and testosterone levels simulataneously and since it has an anti-aromatase effect could prevent the conversion to estrogen - thus resveratrol may be helpful for andropause, but emodin may not.

I was wondering whether anyone thought there could be any credence to idea that the resveratrol supplementation could be weakening my tendons?

The fact that I have not experienced any noticeable benefits is enough for me to question its necessity in my regime, but I bought a fair amount to offset international shipping costs and now I'm wondering if I should continue taking the stuff I have already?

As for supressing angiogenesis, I see you are taking 200 mg of quercetin. Quercetin is a very potent inhibitor of angiogenesis, more so than resveratrol.
(see Clin Cancer Res. 2004 Mar 15;10(6):2190-202.
Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats.
Tseng SH, Lin SM, Chen JC, Su YH, Huang HY, Chen CK, Lin PY, Chen Y.
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
PMID: 15041740 )
The amounts that inhibited angiogenesis in tumor cells in live rats were 40 mg/kg (slightly) and 100 mg/kg (much stronger effect.) Healthy cels appear to have been much less affected than tumor cells vis-a-is angiogenesis. I doubt the amount of resveratrol you are taking is anywhere near enough to have an effect on healthy cells.

On the off chance your tendinitis has been due to angiogenesis inhibition somehow weakening your tendons, I would think the quercetin would be a more likely culprit. Another explanation might be that resveratrol strengthened your mitochondria, and your greater muscular strength is straining your tendons, which are slower to respond. I don't actually believe this is the case, though.

Quercetin increases serum levels of resveratrol for a given dose, by competive inhibition of glucoridation in the intestines. However, it also inhibits SIRT1, and may cancel resveratrol's effects at the cellular level to some degree. I prefer using larger doses of resveratrol instead, or simply taking resveratrol with meals (matching the conditions in Sinclair's and Auwerx' rodent studies) -- most meals should competitively inhibit glucoridation. And we know resveratrol was effective in rats.

But what worked in rats was not a 50% extract, with or without grape seed extract or quercetin. It was a 99% pharmaceutically pure synthetic resveratrol. Emodin is present in all 50% extracts, and as you pointned out is an inhibitor of angiogenesis, as well as being a potent laxative. I believe if you want the benefits shown in rats, you have a better chance with a very low emodin extract, say on of 70% purity which will have under 1% of emodin. or a 98% or 99% resveratrol extract. The samples of these I've had tested were below the limits of detectability for emodin, under 0.0004 parts per million.

Edited by Michael, 27 July 2009 - 01:39 PM.
Trim quotes

"most meals should competitively inhibit glucoridation"

Really? I wasn't aware of that. Any more info?

"Can resveratrol kill brain cells?"
This is the heading of a post by Thomas Carter on sci.life-extension.
He dug up some clues as how this could happen. It depends on 2 big
ifs.
1) If resveratrol besides activating SIRT1 can also activate SIRT2.
2) If SIRT2 can somehow harm neurons.

Then, resveratrol -> SIRT2 -> some neurons dead.

1A) According to PMID: 15749705 [PubMed - indexed for MEDLINE]
resveratrol only activates SIRT1. So we don't have to worry.
!B) But, according to other researchers resveratrol can enhance some
effects of SIRT2:

Biochem Biophys Res Commun. 2007 Aug 3;359(3):665-71. Epub 2007 Jun 4.
Resveratrol abolishes resistance to axonal degeneration in slow Wallerian degeneration (Wld(S)) mice: Activation of SIRT2, an NAD-dependent tubulin deacetylase.Suzuki K, Koike T.
Molecular Neurobiology Laboratory, Division of Integrated Life Science, Hokkaido University Graduate School of Life Science, Sapporo 060-0810, Japan.

Resveratrol is a natural polyphenol having a wide range of biological and pharmacological activities. Here we have investigated the effect of resveratrol on neurodegeneration in cultured cerebellar granule cells from slow Wallerian degeneration (Wld(S)) mice, characteristic of substantial delay of degeneration in the distal stump of transected axons. Resveratrol diminished resistance of Wld(S) neurons to axonal degeneration induced by colchicine, a microtubule depolymerizing drug. Resveratrol also decreased the level of tubulin acetylation in Wld(S) neurons and their homogenates. This promoting effect on tubulin deacetylation was mimicked by NAD, suggesting the involvement of SIRT2, an NAD-dependent tubulin deacetylase. Indeed, resveratrol promoted tubulin deacetylation in the presence of GFP-SIRT2 but not GFP-SIRT2 N168A, a catalytically inactive mutant. Moreover, SIRT2 silencing restored the resistance to axonal degeneration in resveratrol-treated Wld(S) neurons. These results suggest that resveratrol abolishes the resistance of Wld(S) mice to axonal degeneration by enhancing SIRT2-mediated tubulin deacetylation.

PMID: 17560549 [PubMed - in process]

2)
Source: Massachusetts General Hospital
Date: June 23, 2007

Novel Parkinson's Disease Drug Target Identified
Science Daily — Researchers at the Massachusetts General Institute for Neurodegenerative Disease (MGH-MIND) have identified a potential new drug target for the treatment of Parkinson's disease and possibly for other degenerative neurological disorders. In an upcoming issue of the journal Science, the investigators describe finding, in cellular and animal models, that blocking the action of an enzyme called SIRT2 can protect the neurons damaged in Parkinson's disease from the toxic effects of alpha-synuclein, a protein that accumulates in the brains of Parkinson's patients
The study, which also suggests that inhibiting this pathway could help in the treatment of other conditions in which abnormal proteins accumulate in the brain, is receiving early online release on the Science Express.

"We have discovered a compelling new therapeutic approach for Parkinson's disease, which we expect will allow our scientists -- as well as those at pharmaceutical and biotech companies -- to pursue innovative new drugs that will treat and perhaps even cure this disorder," says Aleksey Kazantsev, PhD, director of MGH-MIND Drug Discovery Laboratory, who led the Science study. "Since the same sort of aggregation of misfolded proteins has been reported in Huntington's and Alzheimer's diseases - as well as Lewy body dementia, which also involves alpha-synuclein deposits - we plan to test this approach in those conditions as well."

Parkinson's disease -- characterized by tremors, rigidity, difficulty walking and other symptoms -- is caused by the destruction of brain cells that produce the neurotransmitter dopamine. In recent years researchers at several centers have been studying the role of alpha-synuclein accumulations in dopamine-producing neurons, observed in patients with both inherited and sporadic Parkinson's disease. MGH-MIND investigators have discovered that, in Parkinson's, the alpha-synuclein molecule folds abnormally and form aggregates called inclusion bodies. Such inclusions of other abnormal proteins are seen in several disorders, but whether inclusions are toxic or protective to neurons has been controversial.

In a paper published last year in the Proceedings of the National Academy of Sciences, a research team led by Kazantsev analyzed ways to reduce the size of inclusions containing misfolded versions of alpha-synuclein or of the Huntington's disease-associated protein huntingtin. They found that a compound called B2, which promotes the formation of larger inclusions, paradoxically appeared to reduce toxicity in cellular disease models, possibly by reducing the overall number of inclusions.

In the current study, the investigators began by seeking the mechanism underlying the observed effects of B2. Assays of the compound's activity against a panel of key enzymes identified only one significant association -- a weak but selective inhibition of SIRT2, which is known to regulate the cell cycle and may have a role in aging. An experiment using RNA interference to suppress SIRT2 and a related enzyme in human cell lines expressing alpha-synuclein confirmed that only the inhibition of SIRT2 reduced alpha-synuclein toxicity.

Kazantsev's team then developed and identified more powerful inhibitors of SIRT2, based on the structure of B2. One of these novel inhibitors called AGK2 had 10 times the potency of B2 and was shown to protect dopamine-producing neurons from alpha-synuclein toxicity in cultured rat neurons and in an insect model of PD. Several additional compounds that act on the SIRT2 pathway have been identified, some which may be even better than AGK2 as candidates for drug development.

SIRT2 is known to act on a major protein component of microtubules, cellular structures that help move objects within cells, among other functions. The researchers theorize that inhibiting SIRT2 might promote microtubule-dependent transportation of alpha-synuclein into large aggregates; or it could strengthen microtubules that have been destabilized by misfolded alpha-synuclein.

Kazantsev explains, "For Parkinson's disease, we can now pursue a straightforward drug development process by identifying potent and selective candidates from this class of compounds that can be tested in animal studies and eventual human trials. One of the most satisfying aspects is how this discovery validates our approach to drug discovery, which incorporates both the most advanced tools for screening candidate compounds and outstanding collaboration with our clinical and scientific experts in human disease." Kazantsev is an assistant professor of Neurology at Harvard Medical School.

Co-authors of the Science report are first author Tiago Outeiro, PhD, and co-authors Steve Altman, Allison Amore, Michele Maxwell, PhD, Pamela McLean, PhD, Anne Young, MD, PhD, and Bradley Hyman, MD, PhD, of MGH-MIND; Eirene Kontopoulos and Mel Feany, MD, PhD, Brigham and Women's Hospital; Irina Kufareva, PhD, and Ruben Abagyan, PhD, Scripps Research Institute; and Katherine Strathearn, Catherine Volk, and Jean-Christophe Rochet, PhD, Purdue University. The study was supported by private donations to MGH-MIND and grants from the National Institutes of Health and the Massachusetts Biomedical Research Corporation.


If 1A) and 2) are right there is something to worry about.
Sinclair and Kazantsev, please start talking to each other. After all
you both work for Harvad. Invite Suzuki and Koike and have a serious
chat. PLEASE!!!

Researchers at Ohio State University Medical Center and Creighton University School of Pharmacy have shown that Protykin®, a 200:1 standardized extract of Polygonum cuspidatum(root), may help promote wound healing. Exposure to Protykin® caused epidermal (skin) cells to increase production of a growth factor (VEGF) that stimulates the formation of blood vessels in wounds, which is an important step in wound healing.

Source: Khanna S, Roy S, Bagchi D, Bagchi M, Sen CK, Upregulation of Oxidant-Induced VEGF Expression in Cultured Keratinocytes by a Grape Seed Proanthocyanidin Extract, Free Radical Biology & Medicine, 31:38-42, 2001.

This directly contradicts the assumption that because resveratrol killed cancer cells by inhibiting angiogenesis in one study, that resveratrol therefore inhibits angiogenesis in healthy cells.

The brain-cell studies were done in vitro, and one cannot conclude what the effects will be in a live mouse, particularly a live, healthy non-genetically defective strain of mouse. Resveratrol inhibits apoptosis in most experiments that have been done., rather than stimulating it. I would like to see more data.

in the same thread in sci.life-extension rs1000 replied:

The following study also used neurotoxic colchicine in another strain
of rats, and found resveratrol to counteract the effects rather than
exacerbate:

Pharmacology. 2007;79(1):17-26. Epub 2006 Nov 28.

Neuroprotective effects of resveratrol against intracerebroventricular
colchicine-induced cognitive impairment and oxidative stress in rats.

Kumar A, Naidu PS, Seghal N, Padi SS.

Pharmacology Division, University Institute of Pharmaceutical
Sciences, Panjab University, Chandigarh, India. kumaruips@@@@yahoo.com

Alzheimer's disease is a complex and multifactorial neurodegenerative
disease. Central administration of colchicine, a microtubule-
disrupting agent, causes loss of cholinergic neurons and cognitive
dysfunction that is associated with excessive free radical generation.
The present study was aimed at evaluating the effects of trans-
resveratrol in the prevention of colchicine-induced cognitive
impairment and oxidative stress in rats. Intracerebroventricular
administration of colchicine (15 microg/5 microl) induced impaired
cognitive functions in both the Morris water maze task and the
elevated plus-maze task. Chronic treatment with resveratrol (10 and 20
mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to
colchicine injection, significantly improved the colchicine-induced
cognitive impairment. Intracerebroventricular colchicine injection
resulted in free radical generation characterized by alterations in
oxidative stress markers with a significant increase in
malondialdehyde (MDA) and nitrite levels and depletion of reduced
glutathione (GSH) activity in the rat brains. It also showed a
significant decrease in acetylcholinesterase activity. Besides
improving cognitive dysfunction, chronic administration of resveratrol
significantly reduced the elevated MDA and nitrite levels and restored
the depleted GSH and acetylcholinesterase activity. Results of the
present study indicated that trans-resveratrol has a neuroprotective
role against colchicine-induced cognitive impairment and associated
oxidative stress. Copyright © 2007 S. Karger AG, Basel.

PMID: 17135773 [PubMed - indexed for MEDLINE]

As for supressing angiogenesis, I see you are taking 200 mg of quercetin. Quercetin is a very potent inhibitor of angiogenesis, more so than resveratrol.
(see Clin Cancer Res. 2004 Mar 15;10(6):2190-202.
Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats.
Tseng SH, Lin SM, Chen JC, Su YH, Huang HY, Chen CK, Lin PY, Chen Y.
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
PMID: 15041740 )
The amounts that inhibited angiogenesis in tumor cells in live rats were 40 mg/kg (slightly) and 100 mg/kg (much stronger effect.) Healthy cels appear to have been much less affected than tumor cells vis-a-is angiogenesis. I doubt the amount of resveratrol you are taking is anywhere near enough to have an effect on healthy cells.

On the off chance your tendinitis has been due to angiogenesis inhibition somehow weakening your tendons, I would think the quercetin would be a more likely culprit. Another explanation might be that resveratrol strengthened your mitochondria, and your greater muscular strength is straining your tendons, which are slower to respond. I don't actually believe this is the case, though.

Quercetin increases serum levels of resveratrol for a given dose, by competive inhibition of glucoridation in the intestines. However, it also inhibits SIRT1, and may cancel resveratrol's effects at the cellular level to some degree. I prefer using larger doses of resveratrol instead, or simply taking resveratrol with meals (matching the conditions in Sinclair's and Auwerx' rodent studies) -- most meals should competitively inhibit glucoridation. And we know resveratrol was effective in rats.

But what worked in rats was not a 50% extract, with or without grape seed extract or quercetin. It was a 99% pharmaceutically pure synthetic resveratrol. Emodin is present in all 50% extracts, and as you pointned out is an inhibitor of angiogenesis, as well as being a potent laxative. I believe if you want the benefits shown in rats, you have a better chance with a very low emodin extract, say on of 70% purity which will have under 1% of emodin. or a 98% or 99% resveratrol extract. The samples of these I've had tested were below the limits of detectability for emodin, under 0.0004 parts per million.

Thanks Maxwatt, I found that a very informative post. On more considered reflection I agree that resveratrol is unlikely to be linked to the tendintiis, numerours other training factors are much more likely to be the culprit. I may switch to a higher purity extract though when my country life runs out. If anybody can recommend the best way for a UK/Ireland consumer to purchase higher extract resveratrol I'd be very appreciative, if not I'll have a look around.

News from Sirtris:

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Sirtris Pharmaceuticals, Inc. (NASDAQ: SIRT - News), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced today that activation of SIRT1, a member of the sirtuin family of enzymes, was shown to protect against neurodegenerative diseases such as Alzheimer's Disease and Amyotrophic Lateral Sclerosis in animal models. These findings appear in an article published in Volume 26, Number 13 of The European Molecular Biology Organization Journal (EMBO), Kim et al., 2007 entitled "SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis" which is also available now in the advance online publication


It is well established that a progressive loss of neurons with age underlies a variety of debilitating neurological disorders including Alzheimer's Disease and Amyotrophic Lateral Sclerosis (ALS), neurodegenerative diseases which have been associated with reduced mitochondrial function. Sirtuins are a recently discovered class of enzymes that appear to affect the aging process in mammals and increase the number and function of mitochondria.

According to the findings in this paper, resveratrol, a SIRT1 activator, reduced the loss of neuronal function in the brain (hippocampus) and prevented learning impairment in a well established animal model of Alzheimer's Disease. This response was associated with SIRT1 dependent deacetylation of PGC1a. Resveratrol also promoted neuronal survival in cell based models of Alzheimer's Disease and ALS.

http://biz.yahoo.com...05312.html?.v=1

Can anyone get the full paper?

From the Mayo Clinic today. It's another Dr. Sinclair study.

Gene deficiency is a protective barrier to obesity

CD38 plays a role in regulating body weight and obesity
ROCHESTER, Minn. -- A search for the molecular clues of longevity has taken Mayo Clinic researchers down another path that could explain why some people who consume excessive calories don’t gain weight. The study, which was done in laboratory mouse models, points to the absence of a gene called CD38. When absent, the gene prevented mice on high-fat diets from gaining weight, but when present, the mice became obese.

The findings were published this month in the online issue of The FASEB Journal, the journal of the Federation of American Societies for Experimental Biology. The study will appear in the November 2007 print issue of the journal.

“Obesity is a complex problem compounded by multiple factors, one of which is our genes. Genes play a role in about 50 percent of cases, and in this study, we demonstrate that CD38 regulates body weight,” states Eduardo Chini, M.D., Ph.D., an anesthesiologist at Mayo Clinic and corresponding author of the study.

Identifying the signaling mechanisms that lead to obesity caused by a high-fat, high-calorie diet is a critical part of understanding and developing new treatments for obesity, Dr. Chini says.

THE ROLE OF CD38

Research in animal models has shown that caloric restriction can lower cholesterol and blood pressure -- often considered the biomarkers of aging. In addition, published research in animal models shows that caloric restriction, defined as consuming 30 percent to 40 percent less than your average daily intake, can turn on the SIRT1 gene, one of a family of seven genes linked to longevity.

In addition, recent studies have shown that the chemical receptor PGC1 (peroxisome proliferator-activated receptor coactivator) plays a key role in the development of obesity and control of metabolism. The SIRT genes activate PGC1 and in doing so, can offset the negative effects of obesity -- at least in mice. But how the SIRT-PGC1 reaction works, hasn’t quite been explained until now.

In previous laboratory studies by the Mayo Clinic research team, CD38 was shown to be involved in regulating a wide variety of signaling pathways, such as those that regulate energy metabolism. In addition, recent studies in humans also show a possible connection between CD38 and metabolism, specifically metabolic syndrome. Metabolic syndrome includes metabolic-related health issues that usually afflict people who are obese. These health issues include high blood pressure, elevated insulin levels and high cholesterol levels.

In this study, researchers investigated and confirmed that CD38 inhibits SIRT and the expression of PGC1 in mouse models and, as a result, regulates body weight. In the absence of CD38, the SIRT-PGC1 pathway was activated and protected mice models from developing obesity.

THE STUDY

Researchers studied two groups of mice: one with the gene CD38 and the other without. Each group was fed a high-calorie diet with 60 percent of calories from fat. In a second test, each group was fed a standard diet in which 4 percent of calories came from fat.

As a result, the body fat of mice that carried CD38 and were on a high-fat diet nearly quadrupled and their body weight almost doubled. After eight weeks on a high-fat diet, mice with CD38 began to show signs of glucose intolerance, one of the first indicators of diabetes onset. In addition, this group of mice lived for only four-to-six months compared to the second group of mice that lived for 12 months.

For the group of mice that did not carry CD38, their body fat and weight did not change even though they were on a high fat diet. These mice burned more energy, were leaner and otherwise healthy.

“These changes contributed to the ability of these mice to fend off weight gain despite a high-fat diet and lack of exercise. Together these results suggest that a CD38 deficiency has a protective effect against high-fat, diet-induced obesity,” Dr. Chini says.

RESVERATROL

Dr. Chini and colleagues also examined the effects of resveratrol in mice. Resveratrol is a naturally occurring substance found in some plants such as mulberries, peanuts and red grapes used to make wine. It has been marketed as a drug that mimics the effects of moderate exercise without the physical act of exercising and also as a longevity drug, despite the lack of evidence that resveratrol is safe and effective in humans.

Mice with CD38 were treated with 30 milligrams (mg) of resveratrol per day. And, to determine the effects of the SIRT genes on obesity, mice without CD38 received the same dose of sirtinol, a drug that shuts down the SIRT genes.

Researchers found that mice with CD38 that were treated with resveratrol for two weeks were protected from high-fat, diet-induced obesity. By contrast, the protective effect against high-fat, diet-induced obesity in the absence of CD38 in mice was invalidated by sirtinol. Mice without CD38 that were treated with sirtinol gained a statistically significant amount of weight when compared with mice without the gene who were not treated with sirtinol.

This data supports the novel notion that CD38 modulates high-fat, diet-induced obesity by a SIRT- dependent mechanism.
“Together these results identify a novel pathway regulating body weight and clearly show that CD38 is a nearly obligatory component of the cellular cascade that led to diet-induced obesity,” the authors write.

The authors say the study’s results are promising and should be explored in follow-up studies that will focus on the quality of life and longevity in mice.


###
Additional authors of the study include: Maria Thereza Barbosa, M.D.; Sandra Soares, M.D.; Colleen Novak, Ph.D.; James Levine, M.D., Ph.D.; and Pinar Aksoy, Ph.D.; all of Mayo Clinic; and David Sinclair, Ph.D., of Harvard Medical School. Dr. Sinclair is a co-founder of Sirtris Pharmaceuticals.

This study was funded by the American Heart Association and Mayo Clinic.

http://www.eurekaler...c-gdi062607.php

More detail here: http://www.scienceda...70626115338.htm

Edited by velopismo, 27 June 2007 - 05:01 AM.

The abstract is in PMID: 17581637.
From this abstract: "Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration."
According to the paper to be published in EMBO J., the mice work for MIT and Harvard.
On the other hand, according to a press release: "Sirtris Pharmaceuticals, Inc. (NASDAQ: SIRT - News), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced today that activation of SIRT1, a member of the sirtuin family of enzymes, was shown to protect against neurodegenerative diseases". So the mice work for Sirtris Pharmaceuticals? Don't the mice realize there might be a conflict of interest here?

One more thing. Could this mean that the trials for lowering glucose are going nowhere and they are switching to protecting neurons?

The abstract is in PMID: 17581637.
From this abstract: "Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration."
According to the paper to be published in EMBO J., the mice work for MIT and Harvard.
On the other hand, according to a press release: "Sirtris Pharmaceuticals, Inc. (NASDAQ: SIRT - News), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced today that activation of SIRT1, a member of the sirtuin family of enzymes, was shown to protect against neurodegenerative diseases". So the mice work for Sirtris Pharmaceuticals? Don't the mice realize there might be a conflict of interest here?

One more thing. Could this mean that the trials for lowering glucose are going nowhere and they are switching to protecting neurons?

More likely the stock is going nowhere, someone wants to unload a big block at a profit.

The abstract is in PMID: 17581637.
From this abstract: "Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration."
According to the paper to be published in EMBO J., the mice work for MIT and Harvard.
On the other hand, according to a press release: "Sirtris Pharmaceuticals, Inc. (NASDAQ: SIRT - News), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced today that activation of SIRT1, a member of the sirtuin family of enzymes, was shown to protect against neurodegenerative diseases". So the mice work for Sirtris Pharmaceuticals? Don't the mice realize there might be a conflict of interest here?

One more thing. Could this mean that the trials for lowering glucose are going nowhere and they are switching to protecting neurons?

More likely the stock is going nowhere, someone wants to unload a big block at a profit.

Those sneaky mice!

Someone reported some time ago that he experienced numbness in the extremities that might be due to neuropathy.

How are you / is he doing?