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David Katz, M.D.

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Mice, Men, and the Measure of Resveratrol

Posted: 11/02/11 09:23 AM ET

Based on a small, brief, but nonetheless profound and compelling study in the current issue of the highly regarded scientific journal, Cell Metabolism, I intend to start taking resveratrol.

Rarely is anything that comes in a capsule or pill worth comparing to the power over medical destiny exerted by living well -- good use of feet and forks in particular. Lifestyle can do what no pill can do. That will doubtless prove true of resveratrol as well, but thus far its promise looks all but unprecedented to me. The study in Cell Metabolism did, in fact, compare this particular pill to the power of lifestyle -- and the pill measured up.

And rarely is it prudent to make a leap of faith from mice to men. Rodent studies often suggest benefits that fail to materialize when therapies are tested in humans. But having shown early promise in mice, resveratrol has nimbly made the leap to men (with, presumably, the same implications for women) in the new study.

The study in question assigned 11 obese but otherwise healthy men to 30 days of placebo and 30 days of 150 mg of resveratrol daily in random order. The study was double-blinded, meaning neither the participants nor the researchers knew who was taking what when. The fundamental study hypothesis, based on prior work in animals, was that resveratrol supplementation would mimic the effects of calorie restriction.

Calorie restriction has long shown promise for extending lifespan. Studies in a number of species have shown clear gains in longevity with administration of a nutritionally adequate, but calorically restricted diet (roughly 30 percent fewer calories than would be considered a "normal" level for maintenance of healthy weight). There have been no such studies in humans, for some fairly obvious reasons -- salient among them the fact that if such an intervention worked, it would take longer than the researcher's lifespan to find out!

That said, the metabolic effects of calorie restriction in humans suggest opportunities for both health promotion, and life extension. But there are also some jokes attached to the notion of extending survival by practicing a state of carefully controlled, semi-starvation. Among the better ones: you may live forever, or maybe it will just feel that way. Or: it may well extend your life, but you'll keep wishing you would die!

Of course, adherents to so-called 'CR' deny the downside, and report feeling vital while anticipating a long life. They intend to have the last laugh. Whether or note they get it, I wish them well.

But I also recognize that no matter what the benefits of calorie restriction, most people will not practice it. After all, we know there are profound benefits of controlling weight just by eating the recommended level of calories -- and we can't get most people to do that! So 30 percent less? Fuggedaboutit.

Enter resveratrol.

Resveratrol is a compound concentrated in grape skin -- and thus red wine. Early studies suggested it functioned as a potent antioxidant. While that might be of health benefit on its own, the history of isolated antioxidant supplements is one of perennial disappointment. Our high hopes for clear health benefits with supplements of vitamin C, beta-carotene, vitamin E, lycopene, and combinations have been consistently dashed. Meta-analyses of antioxidant trials suggest no benefit, and potential harm -- serving up a starkly precautionary message.

But resveratrol is not just an antioxidant. It influences mitochondrial function and energy metabolism. And most importantly, resveratrol is a gene modifier. It influences the activity of a gene complex called SIRT1, which influences a wide array of metabolic activity, is considered a regulator of the "health span," and is the very gene complex influenced by calorie restriction.

The new study was published in Cell Metabolism for a reason -- it reports changes in biochemical measures and cell biology and is thus a bit dense in its details. But the take-away message was clear enough. Daily dosing of resveratrol for a month mimicked most effects of calorie restriction, improving energy metabolism in muscle, improving insulin sensitivity, lowering blood pressure, and apparently enhancing fitness. There were no adverse effects of resveratrol.

Of course, there is much we don't know. The beneficial effects of resveratrol might wear off in time, or be too modest to matter. Or perhaps adverse effects might show up late. Calorie restriction, for instance, is associated with reduced fertility, and reduced libido. I count myself among those who would consider the latter of those effects too high a price to pay for any metabolic benefits. We don't know if resveratrol can facilitate weight loss- although that looks promising. We don't know, and won't for a very long time, if it can extend the human life span.

But we do have the first clear evidence that a natural compound can exert the same profound effects on metabolism, weight and genes -- in humans -- as calorie restriction. There is at least reason to hope a meaningful anti-aging effect could be appreciated as well.

Resveratrol has made the leap from mice to men. It will take some time to ascertain the true medical measure of this compound. While it is certainly premature to declare it a "wonder drug," I find myself wondering about that possibility. It's the best contender for a profound medical advance in a pill I have seen in a long time.

And so, I intend to try it for the next six months or so to see what effects I discern (less, of course, if I discern any I don't like!). I can't yet recommend resveratrol to you with any great conviction, but I can share my excitement about its apparent promise -- and I promise to share the results of my personal experience with it. Stay tuned!

-fin

Dr. David L. Katz; www.davidkatzmd.com
www.turnthetidefoundation.org

 

Follow David Katz, M.D. on Twitter: www.twitter.com/DrDavidKatz

Based on a small, brief, but nonetheless profound and compelling study in the current issue of the highly regarded scientific journal, Cell Metabolism, I intend to start taking resveratrol. Rarely is...
Based on a small, brief, but nonetheless profound and compelling study in the current issue of the highly regarded scientific journal, Cell Metabolism, I intend to start taking resveratrol. Rarely is...
 
 
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02:15 AM on 11/09/2011
Only time will tell if I'll live longer but Resveratro­l works for me and my family. I feel healthier. I have more energy and my hair and skin look noticably better. I've used several brands but noticed the best results with Shaklee Vivix. http://healthy-family.myshaklee.com/us/en/whynow_exclusive.html
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rev ta anderson
a pastor with a progressive passion for justice
08:36 AM on 11/05/2011
Yeah! My fav fruit!
07:40 PM on 11/04/2011
I have worked for GNC (don't hold that against me) and have been taking reservatrol for over 2 years steadily and have researched/ heard many users talk about it's effects. I take a pill form that is 250mg and I take that twice daily. What I have noticed is an increased "pump" similar to that of a Nitric Oxide from reservatrol and it lasts longer than an NO pump.

I have noticed, very slightly, a regrowth of hair and more energy. Overall I feel better when taking reservatrol and hope that it may extend my life. I have always been a skinny person so I can't add anything about it battling weight gain.

Many people are skeptical about it's results and benefits and for good reason; nothing has been concluded.

I can say without doubt I feel better on this pill and it is one of two pills I take daily (I also take a Tribulus based testerone booster) Try reservatrol for a month as a pessimist - you may be surprised at the results.

Reservatrol may greatly extend life afterall....If i'm around another 100 years i'll post on this thread again to prove I was right!!!
IMOPINIONH8D
because I want it empty...
08:35 AM on 11/05/2011
Looking forward to reading it.
07:50 AM on 11/04/2011
GlaxoSmithKline (GSK) has discontinued the development programme of SRT501 (resveratrol), following disappointing clinical trial results.
08:02 AM on 11/04/2011
Read why.
02:33 PM on 11/03/2011
Great info & definitely encouraging. Resveratrol is not new nor quackery as it has been referenced in over 2,000 research publications, including studies conducted by Harvard University, the National Cancer Institute, and the National Institute on Aging, part of the National Institutes of Health.
Emerging research reveals we may be able to influence the biological aging processes in positive ways. This has to do with how efficiently cells repair and replicate themselves, which affects your health, well-being & the aging process in various ways. However, we don’t live in a perfect world & our bodies face the daily threats of cellular aging.

Shaklee Corp., the number one natural nutrition company in the U.S. is on the forefront of this scientific research, and their scientists have designed a way to create a unique, natural polyphenol blend with ingredients shown in laboratory studies to fight cellular aging. As a result, Shaklee has developed the world’s best anti-aging supplement called, Vivix.

In laboratory studies, Vivix ingredients have been shown to impact 4 key mechanisms of cellular aging. In fact, Vivix Cellular Anti-Aging Tonic is a revolutionary breakthrough dietary supplement in the fight against cellular aging. A 30-day supply of Vivix delivers the equivalent amount of resveratrol found in 3,000 glasses of red wine, and Vivix ingredients were shown in a laboratory study to be 10X more powerful in slowing a key mechanism of cellular aging than resveratrol alone. I take a teaspoon daily and absolutely love the energy I feel.
07:41 PM on 11/02/2011
Love the Resveratrol!! I've been taking it in liquid form. A few drinks out there provide quite a lot of it. After 3 months of taking it I am full of energy, have lessened my calorie intake. I feel so much better. Finally something without side effects.
07:36 PM on 11/02/2011
Just to share what I have learned for those who are interested. Resveratrol is believed by some to deliver the same long life benefits that can be achieved through ultra-low-calorie eating. Research years back showed that people, and then laboratory mice in research, could dramatically increase lifespan by living on a very small number of calories. The activation of a gene called SIRT1 is thought to be the key here. SIRT1 has been called the "long life gene". What I find fascinating is that underlying all of this, the effect appears to be one of reducing inflammation in the body, which is the fundamental problem behind MANY if not most of our modern diseases. Researchers subsequently found that mice who were given an ultra-low calorie diet only every second day reaped the same benefits as those on full time ultra-low calories or Resveratrol. This method is called alternate day dieting or alternate day fasting. I did this for a year, and for some time blogged about it....a blog I will bring to completion when I get the chance. Using this method I defeated morbid obesity and was off asthma medication after only a month. Just Google "Mardy Roux" and "Winning the Obesity Battle" and you can read all the entries there of my experience.
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Barbara Holtzman
Analyst, Activist, Researcher, Loyal Friend
09:02 PM on 11/02/2011
Yeah here's the thing. The resveratrol product I take enhancers my life. Ultra-low calorie eating, not so much. Same thing with red wine = life enhancement; ultra-low calorie diet, even every other day - no. I'm happy that you did well on this kind of regimen, but for most people, it just doesn't work. And yes, I help people lose weight through private counseling - and keeping them from extremes. I find moderation and eating normally - which most people just don't know how to do anymore, so I have to teach them that as well - works best. My clients get all the results you did, and more. Yes, it's all about inflammation, but there are many ways to fight it. And if I get them on my resveratrol product, which not everyone wants to do, they are even happier.

Again, I'm glad it worked for you, long life and good health.
08:57 AM on 11/03/2011
I gather from your post there Barbara that you know pretty much nothing about alternate day dieting or fasting and certainly nothing about my personal methodology in my own case. And from the brusque tone of your reply, I'm not sure why you're being so defensive. I did not say anything negative about resveratrol. I believe it is an excellent supplement for those who are able to take it. Some of us, however, are not. And yes, there are surely numerous ways to reduce inflammation in our bodies. I would suggest though that the old myth of "moderation" and "eating normally" (whatever THAT is) are more the causes of health problems over the past quarter of a century than they are solutions. I wish you the best, and I hope you sell lots of resveratrol!
07:22 PM on 11/02/2011
Yes, I love it, More research. Keep it coming. Has anyone found any product like Vivix, that is patented, has WHAT it says in it, and you know where the grapes/ingredients came from? I have found some, but none with the quality assurance of Vivix. http://calltofreedom.myshaklee.com/us/en/category.php?main_cat=Nutrition&sub_cat=AntiAging
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Husaria
Question all authority
05:16 PM on 11/02/2011
" Daily dosing of resveratrol for a month mimicked most effects of calorie restriction, improving energy metabolism in muscle, improving insulin sensitivity, lowering blood pressure, and apparently enhancing fitness. There were no adverse effects of resveratrol. "

Yet.

As in we don't know what will happen.........yet

It's a floor wax. No it's a dessert.

It's both a floor wax and a dessert!

Buy some today!
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Barbara Holtzman
Analyst, Activist, Researcher, Loyal Friend
09:05 PM on 11/02/2011
Ah, yeah we do. Resveratrol might not be well known to everyone, but it's well known in the scientific community. It's grape juice, for crying out loud. It's not even know to be an allergen in any context. But we don't need to save or convince everyone.
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Husaria
Question all authority
06:00 AM on 11/03/2011
Data?
12:54 PM on 11/04/2011
As someone who has been involved in scientific research for most of my professional and academic life, I am naturally suspicious of products that claim to be "researched" by "Natural" products manufacturers. I want to see the peer reviewed NHI, FDA sponsored clinical trials, preferable phase III trials, involving a significant participant population where enrolement in the study is carefully and scientifically controllled for confounding variables. Those kinds of studies I would read and pay attention to. I get the joke from Dr. Katz that the participants may outlive the researchers if the longevity effect turns out to be real, but in reality, as an example, longitudinal studies are not uncommon and certainly a well designed study can be implimented by a number of different researchers following participants sequentially.
04:39 PM on 11/02/2011
I had a heart attack shortly after the Resveratrol studies first emerged and quickly added a mega dose to my daily arsenal. Over time I began to experience tendinitis in several parts of my body but severely in my heels. I was diagnosed with plantar fasciitis in BOTH feet at the same time. I had a mild case of it previously years before when I ran 6 miles per day but was able to beat it with stretching and exercise. This time it was supposedly brought on by mild walking every day. I wasn't buying that explanation and an exhaustive information search pointed the finger at the mega dosing of resveratrol. I stopped taking it for 2 weeks and in that time the tendinitis throughout my body and more importantly in my feet went away. I have since resumed taking it in MUCH smaller doses.

My point? DON'T take the mega doses prescribed by the manufacturers. Take smaller, purer amounts and you can garner the benefits and avoid the painful pitfalls.
07:25 PM on 11/02/2011
I have also tried Resveratrol and found that the recommended dosage caused my heels to become very sore. And that was after the very first dose! So I think you may be onto something when you say that you reduced the dosages. What results are you seeing? The key insight around smaller dosages would be, to me at least, an indicator that indeed the amounts of resveratrol in red wine may be sufficient to have a positive impact! I like your name!
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Barbara Holtzman
Analyst, Activist, Researcher, Loyal Friend
09:13 PM on 11/02/2011
And you were taking nothing other than the resveratrol?

What is a "mega-dose?" I take 100mg of trans-resveratrol, with 1290mg of rejuvetrol, a proprietary muscadine grape, European elderberry, and purple carrot extract.

Days I forget to take it, my entire body aches. Days I take it, I feel great, arthritis doesn't hurt, my joints aren't stiff, even my eyesight seems better. Is your anecdotal evidence any better than mine?
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mynamesyow
Scientist, Gonzo, Champion of the Poor
04:01 PM on 11/02/2011
I am a biologist at a Major University and have been studying everything I can about this substance since it first came into the Literature roughly 4 years ago or so and can say that I have never read anything but positive things about this chemical.
Im in my early 30s and I take it on a daily basis and have for roughly a year (missing a few days here and there)and excercise a few times a week and have been in tip top shape and health the entire time.
Im NOT attributing this solely to this chemical, since as a biologist the interplay of Nature and Nurture and Genetics is always on my mind).
BUT of all the 'herbal supplements' out there this one is def heads above anything else in the literature and has generated intense interest (and funding $$$) across the biological and biomedical sciences.
Obviously this Study is too small a sample size to be taken as a the next "cure-all" but adding it to all the research ALREADY accumulated about this substance (easily Googled or Searched on Science Daily) and you'll find that it may just unlock many potential benefits.

Just my 2 cents
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Ranveig Elvebakk
Innovator, author and lecturer on weight and nutri
02:09 PM on 11/02/2011
We trumped Mother Nature with resveratrol? My continued experience with literature and clinical practice is that the metabolic pathways in question are partial and have alternates, thereby eluding every miracle so far, and that our fawning over the latest version falls as flat as melatonin, anorectics neuropeptides, fat blockers and the lot-.
It's supposed ability to improve insulin sensitivity is no miracle, avoiding sugar does the same thing-
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Husaria
Question all authority
05:19 PM on 11/02/2011
Our ancestors, pre ' sugar - ification ' of our diets did the same thing.

They never worried about insulin sensitivity, fat blockers, statins and the like.
01:20 PM on 11/02/2011
Oh good grief. This physician is going to use a substance based on research with ELEVEN (11) subjects who received ONE (1) month of active treatment? Over the last two decades of my career as a clinical research nurse, it has been heartening to watch the medical profession move toward the gold standard of evidence-based medicine. Evidence requires a whole lot more than results from a "small, brief" study, no matter how "profound and compelling" the results. I cannot tell you the number of substances that had to be taken off drug store shelves because proper studies found that there were too many negative side effects with prolonged use. Equally so the number of things that worked okay for one gender but that were found to not help or actually harm the other. Please, Huffington Post, do your readers a favor and stop publishing missives from the Land of Quackery.
01:20 PM on 11/02/2011
To me, this is old hat. i have been taking large does of resveratrol since 2006. I immediately lost 14 lbs over two weeks (it held steady there), had a modest hair growth on my bald head, my cholesterol went down, bp went down, and fatty liver issues went away. a diabetic friend took it and he started loosing 4.5 lbs a month (he was obese) also had modest hair regrowth. His doctors wanted to know what he was doing that caused the improvements.

recently I have added something (sorry but I am trying to figure out how to make some $ off this so no disclosure) a different substance to my regime. My hair growth has become dense and is creeping towards the top of my head! All that in one month. I intend to see my Dr. and get a blood workup again since although I hope this is having positive effects upon me I feel the need to confirm that I am not doing any obvious harm. Of course this is anecdotal and anything anyone else might do should be well thought out and possibly discussed with a DR. if there are any concerns.

I take well over 10 times what Dr. Katz is taking. Still I agree with his opinion.
12:22 PM on 11/02/2011
This is a very thoughtful summary but there are a few points of clarification that I would like to offer: First, while we know that red wine drinkers live longer, are healthier, and have a higher quality of life as compared to nondrinkers (as I discuss in my book Age Gets better with Wine), there isn't enough resveratrol in wine to explain the effect. Additionally, independent studies have shown that resveratrol is not a direct sirtuin activator, so the whole caloric restriction effect is probably unrelated. That is why in mice as in this latest study, there was no lifespan extension but improvement in metabolic parameters in obese subjects only. What is encouraging is that there is any effect at all, since actual clinical trials in humans are so few in number and there are questions about bioavailability with oral resveratrol supplements.
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mynamesyow
Scientist, Gonzo, Champion of the Poor
04:04 PM on 11/02/2011
"and there are questions about bioavailab­ility with oral resveratro­l supplement­s. "

Im a researcher myself and have not read anything specifically about this and this substance. Could you provide a link just out of curiousity? thanks
07:19 PM on 11/02/2011
The reading I have done on this subject indicates that SIRT1 activation will take place in the PRESENCE of resveratrol. Of course it may not be the direct cause of activation, but it appears to play a key role that is probably not well understood at this point.