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Resveratrol, a substance found in the skin of red grapes and in other fruits, has attracted quite a bit of attention in recent years for its potential disease-prevention and anti-aging capabilities

Another Piece of the Healthy Living Puzzle?

Resveratrol, a substance found in the skin of red grapes and in other fruits, has attracted quite a bit of attention in recent years for its potential disease-prevention and anti-aging capabilities. Resveratrol is a type of natural phenol produced naturally by several plants when under attack by pathogens such as bacteria or fungi. Resveratrol acts as a strong antioxidant protecting important cellular structures from oxidative stress and damage and also seems to activate several beneficial genetic pathways that may play a role in increasing longevity.

The history and evolution of resveratrol as a promising player in the wellness/preventative medicine arena has been ever-changing. The groups of Howitz and Sinclair (a well-known Harvard University scientist) reported in 2003 in the journal “Nature” that resveratrol significantly extends the lifespan of the yeast Saccharomyces cerevisiae.[1] Subsequent studies by Sinclair showed that resveratrol also prolongs the lifespan of the worm C. elegans and the fruit fly Drosophila melanogaster[2]. These results sparked a great deal of interest in the potential benefits of resveratrol for more complex organisms.

In 2006, the first positive result of resveratrol supplementation in a vertebrate was documented. Using a short-lived fish, Nothobranchius furzeri, with a median life span of nine weeks, investigators found a maximal dose of resveratrol increased the median lifespan of these fish by 56%. Obviously these results are intriguing and should resveratrol prove to have even one-tenth of that effect on humans… it would be epic! Now let’s keep in mind that clinical research on resveratrol (particularly in humans) is in its infancy and, as with all research, there have been some conflicting or inconsistent results.

It has been proposed that resveratrol’s potential benefits for humans could range from anti-neoplastic properties (anti-cancer), to better glucose control in diabetics and better cholesterol levels in heart disease patients, to as far as anti-aging and increasing longevity for everyone. As of yet, there is not strong clinical evidence to support these claims (research is ongoing), but many preliminary results and early studies look very promising. For example, clinical trials to investigate the effects of resveratrol on colon cancer and melanoma (skin cancer) in humans are currently underway. The strongest evidence to date of the anticancer properties of resveratrol (although not confirmed in humans yet) exists for tumors that it can contact directly, such as skin and gastrointestinal tract tumors. In one particular study, resveratrol (1 mg/kg orally) reduced the number and size of esophageal tumors in rats treated with a carcinogen [4]; and in another study, small doses (0.02–8 mg/kg) of resveratrol, given prophylactically, reduced or prevented the development of intestinal and colon tumors in rats given different carcinogens [3]. Similarly, topical application of resveratrol in mice, both before and after ultraviolet light exposure, inhibited skin damage and decreased skin cancer incidence.

Now we all know someone who has either had a “heart attack” or “stroke” or is at risk of these devastating events (heart disease is the leading cause of death in the US according to CDC records). Many of you may already know that drinking a moderate amount of red wine (1-2 servings daily, with a serving equal to a 3 finger pour as Dr. Kerr would tell you) may help to reduce the risk of heart disease [5]. This is a central element of “the French paradox.” The French paradox is the observation that the French suffer a relatively low incidence of coronary heart disease, despite having a diet relatively rich in saturated fats and cholesterol. It has been suggested that the high red wine consumption of the French is a primary factor in the trend. Studies suggest the resveratrol in red wine may play an important role in this phenomenon (along with the beneficial effects of moderate alcohol intake). There are several ways that resveratrol may help delay or prevent coronary heart disease including: inhibiting platelet aggregation, inhibiting LDL oxidation (LDL is “bad cholesterol,” but when it is oxidized it is “really bad cholesterol”), and several effects on the smooth muscle of the arteries and veins.

As alluded to above, several studies have shown resveratrol possesses hypoglycemic (lowering blood sugar) and hypolipidemic (lowering lipids/cholesterol) effects in diabetic rats. Thus far in human clinical trials, resveratrol has shown promise for potentially lowering human blood glucose levels [5,6]. As if the potential benefits of resveratrol already discussed weren’t enough, in November 2008 researchers at the Weill Medical College of Cornell University reported that dietary supplementation with resveratrol significantly reduced plaque formation in animal brains, a component of Alzheimer's disease and other neurodegenerative diseases [8]. Furthermore, in a study using rabbits to investigate resveratrol’s effects in an inflammatory arthritis model, resveratrol showed promise as a potential therapy for arthritis. When administered to rabbits with induced inflammatory arthritis, resveratrol protected cartilage against the progression of the disease [9].

The mechanisms of resveratrol's apparent effects on life extension (albeit in simpler life-forms thus far) are not fully understood, but they appear to mimic several of the biochemical effects of calorie restriction. Some studies indicate resveratrol activates sirtuin 1, one of the proposed “survival” genes activated for self-preservation during times of bodily “stress” (such as with severe calorie restriction). Let’s not forget about grandma or grandpa who might be suffering from the early stages of Alzheimer’s disease. Resveratrol may offer some benefit on that front as well… in at least 2 studies resveratrol was reported to be effective against neuronal cell dysfunction and cell death, and, in theory, could be effective against neurological diseases such as Huntington's disease and Alzheimer's disease [10,11].

Now, before you go out and start buying all of the resveratrol off of the shelves of your local vitamin or supplement store, keep in mind that much more research is needed to clearly establish not only the potential benefits of resveratrol, but also the potential risks, if any, and appropriate dosing recommendations. I just thought that I would give everyone an introduction, “Resveratrol 101” if you will, to this promising supplement and hopefully spark your interest. These are exciting times in medicine with almost daily advancements in genetics, HRT, anti-aging, etc. and we here at Defy Medical are committed to being at the forefront of your health and wellness care!

Justin M. Saya, M.D.
Medical Director, Defy Medical

References:

  1. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (September 2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan". Nature 425 (6954): 191–6.
  2. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (August 2004). "Sirtuin activators mimic caloric restriction and delay ageing in metazoans". Nature 430 (7000): 686–9.
  3. Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR, Kim AL (November 2007). "Resveratrol: a review of preclinical studies for human cancer prevention". Toxicol. Appl. Pharmacol. 224 (3): 274–83.
  4. Li ZG, Hong T, Shimada Y, Komoto I, Kawabe A, Ding Y, Kaganoi J, Hashimoto Y, Imamura M (September 2002). "Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol". Carcinogenesis 23 (9): 1531–6.
  5. "Sirtris Announces SRT501 Lowers Glucose in Twice-Daily Dosing Clinical Trial; Study Suggests Dose Response for Proprietary Formulation of Resveratrol in Type 2 Diabetics" (Press release). Sirtris Pharmaceuticals. April 17, 2008.
  6. "Sirtris Continues to Lead The Way In Resveratrol Based Research". My Resveratrol Experience. 2009-04-10. Retrieved 2011-01-22.
  7. Szmitko PE, Verma S (January 2005). "Cardiology patient pages. Red wine and your heart". Circulation 111 (2): e10–1.
  8. Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE (February 2009). "Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease". Neurochem. Int. 54 (2): 111–8.
  9. Elmali N, Baysal O, Harma A, Esenkaya I, Mizrak B (April 2007). "Effects of resveratrol in inflammatory arthritis". Inflammation 30 (1–2): 1–6.
  10. Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, Néri C (April 2005). "Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons". Nat. Genet. 37 (4): 349–50.
  11. Marambaud P, Zhao H, Davies P (November 2005). "Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides". J. Biol. Chem. 280 (45): 37377–82.
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