Resveratrol: What the Research Shows

References

Part of the polyphenol powerhouse in red grapes, resveratrol has antioxidant, anti-inflammatory and anti-aging benefits.

A natural substance found in many plants, including grapes, peanuts¹ and Japanese knotweed (Polygonum cuspidatum),² resveratrol’s introduction into the dietary supplement market was based on the consideration that intake of resveratrol and other polyphenol compounds from red wine may contribute to the “French paradox,” the unexpectedly low rate of death from cardiovascular disease (CVD) in the French population.³ Since then, interest in resveratrol has increased due to research suggesting additional antioxidant, anti-inflammatory, anti-cancer, antiviral and anti-aging effects, as well as possibly playing a role in weight loss and athletic performance.

Resveratrol has been found to exert a number of protective effects on the cardiovascular system. Both in vitro and in vivo research has demonstrated resveratrol inhibited platelet aggregation (i.e., the clumping together of blood platelets) and discouraged formation of blood clots and subsequent blockages in blood vessels that can result in insufficient blood flow, heart attack or stroke.⁴ Resveratrol also promotes vasodilation—the relaxing and expanding of arteries that accommodates increased blood flow—by enhancing the production of a naturally occurring substance in the body called nitric oxide.⁵ Some animal studies suggest high oral doses of resveratrol could decrease the risk of thrombosis (clot formation) and atherosclerosis.^6,7

Resveratrol has also demonstrated antioxidant properties;⁸ however, it is not clear whether these effects are direct or the result of increasing the production of endogenous antioxidant enzymes. In vitro work has shown resveratrol prevents the oxidation of low-density lipoprotein (LDL) cholesterol by chelating copper and directly scavenging free radicals.⁹

The ‘Pros’ of Anti-Effects

Beyond its antioxidant impact, resveratrol has other positive effects. Consider its impact on inflammation. Inflammation is a normal, healthy response by the body to heal itself; however, when inflammation gets out of control, as seen in arthritis, ongoing pain and discomfort result. Resveratrol has the ability to inhibit the activity of the body’s cyclooxygenase (COX) enzymes, as well as other inflammatory substances including hydroperoxidases, and 5-lipoxygenase (5-LOX),^10,11,12,13 and inflammatory cytokines.¹⁴ Some evidence suggests resveratrol is a more potent anti-inflammatory agent than non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen or indomethacin.^15,16 Animal research has shown injections of resveratrol decrease inflammation and reduce cartilage destruction.¹⁷

Another benefit is anti-cancer activity. In vitro research reported resveratrol could inhibit the proliferation of various human cancer cell lines, including those from breast, prostate, stomach, colon, pancreatic and thyroid cancers.¹⁸ In animal research, resveratrol inhibited the development of chemically-induced cancers of the breast,¹⁹ esophagus²⁰ and intestine.²¹ One mechanism by which resveratrol exerts chemoprotection is by inhibiting angiogenesis—the growth of new blood vessels—depriving the tumor of needed blood and nutrients.²² Research also shows long-term inhibition of the COX enzymes significantly reduces the risk of developing many cancers.²³

In vitro studies also found resveratrol has antiviral benefits. It was found in one study to block the influenza virus from transporting certain proteins, thereby restricting the ability of the virus to replicate.24 Likewise, resveratrol suppressed the activation of herpes simplex virus proteins, and reduced the production of viral DNA.²⁵ In addition, resveratrol has also increased the potency of some antiretroviral drugs against HIV.²⁶

Anti-aging is another area of focus in resveratrol research. The compound significantly extends the lifespan of lower organisms such as the yeast Saccharomyces cerevisiae,²⁷ the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster.²⁸ Other research demonstrated resveratrol had similar life extension effects on the short-lived fish, Nothobranchius furzeri, also increasing swimming performance and cognitive performance.²⁹ And in another study, resveratrol improved health and survival of mice on a high-calorie diet.³⁰ The mechanism of action is unknown, but may be related to the production of proteins by the SIR2 gene.

Losing Fat, Getting Fit

Obesity is biologically characterized at the cellular level by an increase in the number and size of adipocytes (fat cells) that develop from pre-adipocytes in adipose tissue. Resveratrol has been shown to inhibit pre-adipocytes,³¹ which may translate into reducing the production of new fat cells. In addition, the SIR2 gene in the body of animals and humans produces the protein sirtuin 1 (Sirt 1). This protein promotes fat mobilization in adipose tissue.³² Resveratrol is also a known activator of Sirt 1, and was shown to protect mice against diet-induced-obesity and insulin resistance.³³ By means of stimulating Sirt 1 in mice, resveratrol was shown to improve glucose balance.³⁴ And, mice fed resveratrol for 15 weeks had better treadmill endurance than control animals.³⁵ The intriguing question of whether resveratrol will have similar effects on humans, however, requires further research.

Supplementing the Diet

Since most research conducted on resveratrol has been in vitro or in vivo animal studies, it is difficult to determine an appropriate dose for humans. In an interview with Johan Auwerx, M.D., a leading resveratrol researcher, he indicated he personally takes 40 mg/d of resveratrol.³⁶ The ingredient has been shown to be free of adverse effects in humans in doses up to 5,000 mg.³⁷ Animal research has shown a similar safety profile.³⁸

A certain amount of resveratrol can be consumed in the diet. The richest sources of it are:

• A 5-oz. glass of red wine (provides about 0.30-1.07 mg of resveratrol).
• A cup of peanuts (raw) (provides about 0.01-0.26 mg of resveratrol).
• A cup of red grapes (provides about 0.24-1.25 mg of resveratrol).

By comparison, a dietary supplement can provide 100 mg of resveratrol per capsule—the equivalent of up to 100 glasses of red wine.

While more research, particularly human research, needs to be conducted on resveratrol, it has myriad potential health benefits with a strong safety profile.

Gene Bruno is the dean of academics and on the faculty of Huntington College of Health Sciences (HCHS). HCHS is an accredited distance learning institution offering undergraduate and graduate degrees, as well as a diploma program in nutrition. HCHS.edu, (800) 290-4226. 

References

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3. Labinskyy N et al. “Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen.” Curr Med Chem. 2006; 13(9):989-96.

4. Baur JA, Sinclair DA. “Therapeutic potential of resveratrol: the in vivo evidence.” Nature Rev Drug Dis. 2006; 5(6):493-506.

5. Wallerath T et al. “Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase.” Circulation. 2002; 106(13):1652-1658.

6. Fukao H et al. “Effect of trans-resveratrol on the thrombogenicity and atherogenicity in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice.” Blood Coagul Fibrinolysis. 2004; 15(6):441-446.

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9. Baur JA, Sinclair DA. “Therapeutic potential of resveratrol: the in vivo evidence.” Nature Rev Drug Dis. 2006; 5(6):493-506.

10. Soleas GJ, Diamandis EP, Goldberg DM. Op Cit.

11. Jang M et al. “Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.” Science. 1997; 275:218-20

12. Takada Y et al. “Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation.” Oncogene. 2004; 23:9247-58.

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15. Hwang D et al. “Inhibition of the expression of inducible cyclooxygenase and proinflammatory cytokines by sesquiterpene lactones in macrophages correlates with the inhibition of MAP kinases.” Biochem Biophys Res Commun. 1996; 226:810-8.

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17. Elmali N et al. “Effects of resveratrol in inflammatory arthritis.” Inflammation. 2007; 30(1-2):1-6.

18. Higdon J. Resveratrol. Micronutrient Information Center: Linus Pauling Institute; 2005.

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20. Li ZG et al. “Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol.” Carcinogenesis. 2002; 23(9):1531-1536.

21. Tessitore L et al. “Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21(CIP) expression.” Carcinogenesis. 2000; 21(8):1619-1622.

22. Baur JA, Sinclair DA. “Therapeutic potential of resveratrol: the in vivo evidence.” Nature Rev Drug Dis. 2006; 5(6):493-506.

23. Ibid.

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25. Faith SA et al. “Resveratrol suppresses nuclear factor-kappaB in herpes simplex virus infected cells.” Antiviral Res. 2006; 72(3):242-51.

26. Heredia A, Davis C, Redfield R. “Synergistic inhibition of HIV-1 in activated and resting peripheral blood mononuclear cells, monocyte-derived macrophages, and selected drug-resistant isolates with nucleoside analogues combined with a natural product, resveratrol.” J Acquir Immune Defic Syndr. 2000; 25(3):246-55.

27. Howitz KT et al. “Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.” Nature. 2003; 425(6954):191-6

28. Wood JG et al. “Sirtuin activators mimic caloric restriction and delay ageing in metazoans.” Nature. 2004; 430(7000):686-689.

29. Valenzano DR et al. “Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate.” Curr Biol. 2006; 16 (3):296-300.

30. Baur JA et al. “Resveratrol improves health and survival of mice on a high-calorie diet.” Nature. 2006; 444(7117):337-42.

31. Hsu C-L, Yen G-Ch. “Induction of cell apoptosis in 3T3-L1 pre-adipocytes by flavonoids is associated with their antioxidant activity.” Mol Nutr Food Res. 2006; 50(11):1072-9.

32. Picard F et al. “Sirt promotes fat mobilization in white adipocytes by repressing PPAR-?.” Nature. 2004; 429:771-76.

33. Lagouge M et al. “Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha.” Cell. 2006; 127(6):1109-22.

34. Koo S-H, Montminy M. “In vino veritas: a tale of two sirt1s?” Cell. 2006; 127(6):1091-3.

35. Lagouge M et al. Op cit.

36. Wade, Nicholas. “Red Wine Ingredient Increases Endurance, Study Shows.” New York Times; Nov. 16, 2006.

37. Boocook DJ et al. Proc Am Assoc Cancer Res. 2006;47:Abstract #5741

38. Juan ME, Vinardell MP, Planas JM. “The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful.” J Nutr. 2002; 132(2):257-260.

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