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Everything You Ever Wanted to Know about Resveratrol + Anti-Aging

Posted Sep 28 2011 5:20pm

Greek Gods loved to drink sweet nectar.  If the modern rumors about resveratrol are true, then surely resveratrol must have been the secret ingredient in their sweet juice, granting everything from cellular life extension to the eradication of cancer cells.

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a phytoalexin, a compound plants like grapes, berries, and peanuts produce naturally when under attack.  Though two distinct forms exist, cis-resveratrol and trans-resveratrol, the trans-formation has been found to be more stable chemically.  For my readers who are concerned about skin care and/or weight loss, there are five proven properties of resveratrol of particular interest:

1.  Resveratrol increases UVB protection when applied topically:  TRUE.

In a 2008 study published in Photochemistry and Photobiology , human skin cells treated with resveratrol prevented UVB-induced damage.  The mechanism?  Resveratrol inhibited the inflammatory NFkB pathway and decreased the skin cells’ production of hydrogen peroxide.  With reduced levels of inflammation, less damage accrued in the cells.

For you cell biologists out there, resveratrol has been found to specifically affect the NFkB pathway by inhibition of the MAPK pathway and targets in the regulatory protein cki-cyclin-cdk network ( Cell and Molecular Biology  review, 2008).   Therefore applying a cream containing resveratrol under a broad-spectrum UVA/UVB sunscreen appears to be a great extra means of protection at this time.  Unfortunately, no one has yet compared the sunscreen-boosting effects of resveratrol to other proven UVB-protection boosters like vitamin C or coffee berry.

2.  Resveratrol prevents and inhibits skin cancer formation in humans:  YET TO BE DEFINITIVELY PROVEN.  

The scientific community was ablaze during the past decade, when resveratrol was found in numerous studies to prevent and inhibit the growth of skin cancer tumors in mice.  Resveratrol prevents tumor formation and growth in several ways, including arresting DNA enzymes essential for tumor growth known as topoisomerase II enzymes ( Cancer Letters , 2010).  

Unfortunately, it is virtually impossible for humans to get the ultra-high concentrations of resveratrol proven to slow or prevent tumor growth.  Even people who ingested 5 grams of resveratrol urinated about 77% of it out within 4 hours, and were only able to obtain a peak plasma concentration of 539 ng/mL resveratrol – not near the peak plasma concentrations found to slow tumor growth in mice ( Cancer Epidemiology, Biomarkers , and Prevention , 2008).

Focus has now shifted to compounds made when resveratrol is metabolized within the cells.  These compounds, classified as gluconurides and sulfates, are currently under investigation for potential chemopreventative properties.

3.  Resveratrol preserves and extends cell life:  YET TO BE DEFINITIVELY PROVEN.

Another current debate in the scientific community is whether or not resveratrol preserves and extends cellular life.  Those in the “yes” camp say resveratrol activates compounds called sirtuins.  Molecules that truly “do it all,” sirtuins act in two ways:

  • 1.  Sirtuins downregulate p53, increasing lifespan, cell survival, and the protection of neurons ( Expert Opinion on Therapeutic Patients , 2009).
  • 2.  Sirtuins activate superoxide dismutase (MnSOD).  Superoxide dismutase production naturally increases in cells as a protective mechanism in times of acute stress, such as UV light, radiation, and certain tumors.  Overexpression of MnSOD has been shown to protect against pro-apoptotic stimuli (or pro-cellular death signals).  What’s more, MnSOD production naturally declines in prolonged conditions, such as cancer, aging, progeria, asthma, and transplant rejection ( Free Radical Research , 2001).

So what’s the problem?  No one is really sure if resveratrol activates sirtuins in the first place.  Numerous studies suggest resveratrol does not influence sirtuin production, including a 2005 study in the Journal of Biological Chemistry , a 2009 study in Chemical Biology and Drug Design , and a 2010 study in the Journal of Biological Chemistry .  If resveratrol does not influence sirtuins or prevent tumor formation, then none of its other proven properties substantiate the claim resveratrol extends cell life.  Research thus far suggests resveratrol may protect against UVB-induced inflammation and damage, but that is all.

4.  Resveratrol helps you lose weight:  YET TO BE DEFINITIVELY PROVEN.

When you starve yourself or significantly reduce the number of calories you eat, your body naturally increases its number of sirtuins for a time.  Sirtuins will have the effects listed above, including increased lifespan and decreased energy utilization.

So, of course, researchers wanted to see if they could trigger sirtuins without the starvation.  (No pain and no weight gain!)  In one positive human trial, extremely high doses (3–5 g) of resveratrol significantly lowered blood sugar, which was of interest because stabilized blood sugar prevents feelings of hunger.  This 28-day study was conducted privately in India by pharmaceutical company Sirtris, but it has never been published in a peer-reviewed scientific publication, only alluded to in the press, including in a 2008 review in Current Opinion in Investigational Drugs .

If you’re ever curious if lowered blood sugar would decrease your appetite, talk to your physician about trying apple cider vinegar caplets .  When taken before a meal, they are proven to stabilize blood sugar for several hours ( BMC Gastroenterology , 2007).  I tried this for a while, and I noticed a decrease in my appetite, though I was never sure if it was the decrease in blood sugar or the 8-oz glass of water required with the pills to ensure the vinegar didn’t tear through my stomach.  At any rate, it’s more proven than resveratrol to stabilize blood sugar at this point, which is why I’m mentioning it here.

5.  Resveratrol influences testosterone production, may be helpful in patients with breast cancer, and should not be used by pregnant women:  TRUE.

Resveratrol has been shown to increase testosterone production in rats.  The mechanism by which this occurs is two-fold: as a selective estrogen receptor modulator and an aromatase (estrogen-producing enzyme) inhibitor ( Archives of Pharmaceutical Research , 2001).  What this means in plain English:  The body can bind to estrogen.  The body can also transform testosterone to estrogen through the action of the enzyme aromatase.   Resveratrol favors increased testosterone in both cases, preventing the body from binding to estrogen, and reducing the level of conversion of testosterone to estrogen.  The result?  More testosterone!

However, before women start throwing out their resveratrol pills, consider this:  Because breast cancer cells proliferate with increased levels of estrogen, resveratrol has been suggested as a potential novel inhibitor of breast cancer tumor growth ( Cancer Research , 2001).

Still, if you are pregnant, whether you have a family history of breast cancer or not, you should not use resveratrol at this time.  A 2010 study in Cancer Letters  suggested resveratrol inhibits DNA break strand activity known as topoisomerase II activity; a second study in the same journal confirmed this.  However, physicians have often suggested that topoisomerase inhibitor drugs not be used during pregnancy because toxic by-products can be harmful to the fetus ( Mutation Research , 2003).   While resveratrol is certainly weaker than the topoisomerase inhibitor drugs mentioned in the study, I am always super-cautious when discussing supplements for pregnant women.
Bottom Line
Despite what you hear about resveratrol, all we know for sure is resveratrol acts as a superior antioxidant, preventing UV-induced oxidative damage, and a mild testosterone enhancer.  We don’t know for sure if resveratrol can act as an anti-aging godsend as a sirtuin activator, or prevent skin cancer tumors as a topoisomerase II inhibitor.  In case it can act as a topoisomerase II inhibitor, pregnant women are best advised not to take it.
It seems difficult to achieve resveratrol levels at therapeutic concentrations from a supplement at this time.  Topical resveratrol creams boost UV protection and prevent inflammation, and it’s likely that the testosterone increase would be minimal and perhaps even unnoticeable, but with mega antioxidants like coffee berry, vitamin C, idebenone, and glutathione on the market, do we really need to be applying something with potential (male) hormonal effects? I’m honestly on the fence about this one.  More research needs to be done before I can justify recommending this to others.  As for myself, I will be staying out of the sun (except for about 15 sunscreen-free minutes per week), eating a healthy diet, taking vitamin D supplements, and applying other antioxidants to my skin until we know more about resveratrol…

Photo source: red wine , originally uploaded by wu.peng .

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