Is There Anything to the Hype?
In the last few months, the buzz surrounding resveratrol, the polyphenol found in grape skins and red wine, has reached a fever pitch.
Dr. Mehmet Oz, the celebrity doctor often seen on the Oprah Winfrey Show, has been making the rounds of the day-time talk shows to promote resveratrol and its anti-aging properties. CBS newsmagazine 60 Minutes devoted an entire segment to resveratrol and its passionate believers who hope to live well into their 100’s through the use of mega-doses of resveratrol.
Not to be outdone, Barbara Walters from ABC News even hosted a prime time special entitled “Live to be 150” which also quite prominently featured resveratrol.
Each of these headline making stories raised awareness (and sales!) of resveratrol. But does the hype match the facts? People are taking doses of resveratrol equal to 100, 300, even 500 glasses of wine! They seem to think that if a little is good, then more must be better. The research seems to indicate a more moderate approach is called for, but let’s look at what we really know about resveratrol and then you can decide if it is right for you.
Caloric restriction prolongs life
It has been well documented that limiting caloric intake while maintaining a normal diet in regards to other nutrients like vitamins and minerals can delay the aging process in laboratory animals.1
How caloric restriction slows aging is unknown. One theory suggests that fewer calories force an optimization of the metabolism. Another theory suggests caloric restriction affects genes that program the aging process.2
Whatever the mechanism, caloric restriction has been repeatedly shown to extend lifespan in laboratory mammals and scientists now know that resveratrol affects many of the same genes that are affected by caloric restriction. Thus, resveratrol has been called a “caloric restriction mimetic.”
For example, after screening thousands of molecules, Harvard researchers found that resveratrol mimics caloric restriction in yeast by activating enzymes that slow aging, increasing the stability of DNA, and extending lifespan by as much as 70%.3
Another Harvard research team found resveratrol improved the health and survival of obese mice. Resveratrol increased insulin levels while decreasing glucose levels, resulting in healthier liver and heart tissue when compared to obese mice that did not receive treatment. “After six months, resveratrol essentially prevented most of the negative effects of the high-calorie diet in mice,” said study co-author Rafael de Cabo of the National Institute of Aging (NIA).4
What’s more, a research study published in 2008 led by researchers from University of Wisconsin, Madison, found that the caloric restriction mimetic effects of resveratrol can be attained with low doses.5 The authors had this to say in their abstract:
“Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics
some aspects of caloric restriction.”
This last finding is particularly important. The focus for many resveratrol advocates has been on mega-doses. Doses equal to hundreds of glasses of wine. The fact that low doses of resveratrol can mimic caloric restriction brings the compound back into the realm of a dietary supplement, and out of the realm of pharmaceutical experimentation. When it comes to efficacious doses of dietary supplements— particularly ones that are being hyped as much as resveratrol— it is probably better to be safe than sorry.
Resveratrol benefits beyond caloric restriction
While the anti-aging aspects of resveratrol get most of the headlines, the other health benefits associated with resveratrol are impressive. Following are some of the most significant recent scientific developments regarding resveratrol:
Resveratrol and cardiovascular health
A number of studies have shown resveratrol’s antioxidant properties promote healthy circulation and may prevent atherosclerosis. Some of the findings include:
- Preventing cholesterol plaque from forming within artery walls regardless of whether circulating levels of cholesterol are high or low6
- Up-regulating nitric oxide and exerting antioxidant protection against cardiac ischemia7
- Stopping the proliferation of cells in blood vessels that narrow the arteries,8 and keeping blood cells from sticking together9
- Relaxing the endothelium that lines the arteries, allowing for efficient blood flow to and from the heart10
Resveratrol reduces cancer risk
Although resveratrol is essentially non-toxic to healthy cells, it is able to selectively target and kill cancer cells and stop them from spreading. Resveratrol acts on the process of carcinogenesis by affecting the three phases: tumor initiation, promotion and progression phases, and suppresses the final steps of carcinogenesis, i.e. angiogenesis and metastasis.11
When it comes to reducing cancer risk, studies have found that resveratrol:
- May be particularly beneficial as an adjunct cancer therapy in advanced prostate cancer12
- Reduces skin tumors in mice when applied topically13
- May be beneficial in the treatment of breast, colon, lung, esophagus, skin, lymph node, brain and testis cancer,14 as well as thyroid, melanoma, pancreas, and head and neck squamous cell carcinoma, ovarian and cervical carcinoma15
- Decreased induced mammary tumor incidence, number of tumors, and extended cancer latency in female Sprague-Dawley rats16
- Can inhibit the growth of colorectal tumor cells17
Resveratrol’s anti-cancer properties show tremendous promise. There are many studies now underway (some funded by big drug companies) to try and move from the animal and test tube study successes to human clinical studies. Their goal of course is to develop a cancer treatment that the drug companies can patent and charge top dollar for.
Resveratrol reduces inflammation
Inflammatory processes are inherent in many chronic diseases including arthritis, heart disease, and cancer.
Resveratrol has been shown to reduce inflammation via inhibition of prostaglandin production and cyclooxygenase- 2 activity—COX-1 (a protein that acts as an enzyme to speed up the production of certain chemical messengers— prostaglandins). The prostaglandins work within certain cells that are responsible for inflammation and other functions.
The anti-inflammatory effects of resveratrol were first described in 1997 after a study on an animal model determined its primary activity to be the inhibition of COX-1.18 Then a study led by some of the same researchers from Cornell Medical College in New York City revealed resveratrol’s COX- 2 inhibitory effects.19 In this study, the researchers exposed human mammary and oral epithelial cells to phorbol esters, which induce COX-2 expression and the production of prostaglandin E2. The addition of pure resveratrol inhibited both these effects, reversing the increases in COX-2 mRNA and protein. In addition to modifying gene expression, they also found resveratrol to directly inhibit COX-2 activity.
Inflammation plays a role in arthritis, and a 2006 study showed resveratrol reduces the damaging effects of arthritis on cartilage tissue in animal models.20 And still another study showed that resveratrol reduces homocysteine—an amino acid in the blood resulting from inflammation and leading to a higher risk of cardiovascular disease.21
Resveratrol shows promise as a treatment for Alzheimer’s disease Several recent studies suggest that resveratrol works on some of the mechanisms of Alzheimer’s disease. In a study published in 2009 by researchers from Cornell University, resveratrol was found to protect against beta-amyloid plaque formation which many researchers believe to be one of the major causes of neurodegenerative diseases like Alzheimer’s.22
Other research into resveratrol’s neuro-protective properties has shown that it can protect neurons against amyloid toxicity23 and it increases the cognitive ability of Alzheimer’s mice.24
Is resveratrol right for you?
While the science does appear to back up the claims for resveratrol, caution should still be taken when selecting a resveratrol supplement. If you do decide that you want the benefits that come with daily resveratrol supplementation, you need to make sure you are getting the correct form of resveratrol and the proper dosage.
Resveratrol exists in two forms: cis-resveratrol and trans-resveratrol. These forms contain the same type and number of atoms, but the orientation of the atoms is slightly different. Cis- and trans-resveratrol have some biological activities in common while other activities are specific to only one form or the other. Trans-resveratrol is commercially available and has been the subject of more research than cis-Resveratrol— although not all research has adequately established or identified the form used.25 To be safe, you’ll want to make sure you get a standardized extract of trans-resveratrol.
The dosage is extremely important
Resveratrol supplements usually contain doses of anywhere from 1 milligram to 100 milligrams of resveratrol per day. But you should be aware that an entire bottle of red wine contains only about 10 milligrams of resveratrol. As you may know, resveratrol first gained fame because of the French Paradox. The French Paradox was the name given to the phenomena whereby the people in France, despite a diet of high fat foods and cigarette smoking, had a lower incidence of cardiovascular disease than Americans. Resveratrol, in the form of red wine—which the French drink quite a bit—is thought to be the reason for this paradox.
So when you see resveratrol supplements that say they are equal to 100 or more glasses of wine, you should be wary. No one, not even someone in France, is drinking that much wine on a daily basis. The temptation here, of course, is that if a little is good, more must be better. When it comes to resveratrol, that simply may not be the case. Instead, look for capsules that contain trans-resveratrol in amounts equal to a bottle, or three or four glasses of wine, and also contain other red wine polyphenols to better simulate what you would get from actually drinking red wine. Remember, low dosage resveratrol supplementation mimics caloric restriction and better reflects the amounts used in many of the scientific studies that support resveratrol’s health benefits.
- Wolf G. Calorie restriction increases life span: a molecular mechanism. Nutr Rev. 2006 Feb;64(2 Pt 1):89-92.
- de Magalhaes, J. P., and Church, G. M. (2005). “Genomes optimize reproduction: aging as a consequence of the developmental program.”Physiology (Bethesda) 20:252-259.
- Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004 Aug 5;430(7000):686-9. Epub 2004 Jul 14.
- Baur JA, et al Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. Epub 2006 Nov 1.
- Barger JL, Kayo T, Vann JM, Arias EB, Wang J, et al. (2008) A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice. PLoS ONE 3(6): e2264. doi:10.1371/journal.pone.0002264.
- Wang Z, Zou J, Cao K, Hsieh TC, Huang Y, Wu JM. Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. Int J Mol Med. 2005 Oct;16(4):533-40.
- Shen M, Jia GL, Wang YM, Ma H. Cardioprotective effect of resvaratrol pretreatment on myocardial ischemia-reperfusion induced injury in rats. Vascul Pharmacol. 2006 Aug;45(2):122-6. Epub 2006 Jun 12.
- Haider, U.G. et al. Resveratrol increases serine 15-phosphory¬lated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells.Mol. Pharmacol. 200;363:925-32.
- Zbikowska, H.M. et al. Antioxidants with carcinostatic activity (resveratrol, vitamin E and selenium) in modulation of blood platelet adhesion. J. Physiol. Pharmacol. 2000;51:513-20.
- Novakovic A, Bukarica LG, Kanjuh V, Heinle H. Potassium channels-mediated vasorelaxation of rat aorta induced by resvera trol.Basic Clin Pharmacol Toxicol. 2006 Nov;99(5):360-4.
- Delmas D, Lancon A, Colin D, Jannin B, Latruffe N. Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer.Curr Drug Targets. 2006 Apr ;7:423-42.
- Jubilee R. Stewart and Catherine A. O’Brian Resveratrol antagonizes EGFR-dependent Erk1/2 activation in human androgen-independent prostate cancer cells with associated isozyme-selective PKC alpha inhibition. Invest New Drug, 2004;22(2):107-117.
- Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Bleecher CWW, Fong HHS, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM. 1997. Cancer chemopreventive activ¬ity of resveratrol, a natural product derived from grapes. Sci275(5297):218–20.
- Murray GI, Taylor MC, McFadyen MC, Mckay JA, Greenlee WF, Burke MD, Melvin MF. 1997. Tumor-specific expression of cytochrome P450 CYP1B1. Cancer Res 57(14):3026–31.
- Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 2004 Sep-Oct;24(5A):2783-840.
- Banerjee S, Bueso-Ramos C, Aggarwal BB. 2002. Suppression of 7,12-dimethylbenz(a) anthracene-induced mammary carcinogen¬esis in rats by resveratrol: role of nuclear factor-?B, cyclooxygen¬ase 2, and matrix metalloprotease 9. Cancer Res 62(17):4945–54.
- Trincheri NF, Nicotra G, Follo C, Castino R, Isidoro C. Resvera¬trol induces cell death in colorectal cancer cells by a novel pathway involving lysosomal cathepsin D. Carcinogenesis. 2006 Nov 20.
- Jang M, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997;275(5297):218-20.
- Subbaramaiah K, et al. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J Biol Chem 1998;273(34):21875-82.
- Elmali N, Baysal O, Harma A, Esenkaya I, Mizrak B. Effects of Resveratrol in Inflammatory Arthritis. Inflammation. 2006 Nov 4.
- Schroecksnadel K, Winkler C, Wirleitner B, Schennach H, Weiss G, Fuchs D. Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro. Clin Chem Lab Med. 2005;43(10):1084-8.
- Karuppagounder SS, et al.Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem Int, 2009 Feb;54(2):111-8. Epub 2008 Nov 8.
- Anekonda TS. Resveratrol–a boon for treating Alzheimer’s disease? Brain Res Brain Res Rev. 2006 Sep;52(2):316-26.
- Luo L, Huang YM. [Effect of resveratrol on the cognitive ability of Alzheimeros mice] Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2006 Aug;31(4):566-9.
- Consumer Lab Review Article: Resveratrol, 11/30/06.