Researchers have determined that consumption of resveratrol a component of red wine lowers inflammatory markers such as C-Reactive Protein and the clotting factor fibrinogen. The study authors evaluated the effect of resveratrol on cardiovascular risk factors and inflammatory biomarkers.

They studied 48 subjects (male and female) who never or rarely drank red wine and randomly subdivided them into two groups. The first group of 24 subjects consumed 250 ml per day of red wine during meals for the first 4 weeks, followed by 4 weeks when they returned to their usual wine intake. The second group of 24 subjects drank their usual wine intake for the first 4 weeks, followed by 4 weeks when the diet was supplemented with 250 ml per day of red wine.

The researchers measured a number of cardiovascular risk factors in the subjects. At the end of the red wine intake period, LDL/HDL, fibrinogen, plasma C-Reactive Protein and oxidized LDL were significantly decreased, while levels of HDL (the “good” cholesterol) and total plasma antioxidant capacity were significantly increased. C-Reactive Protein is a marker of inflammation and elevated levels may indicate an increased risk of heart disease. Fibrinogen plays a key final role in the cascade that results in the clotting of blood.

Elevated blood levels of fibrinogen have been identified in a number of studies to be a major risk factor for coronary heart disease and strokes. LDL, the “bad” cholesterol, causes damage to the body after it is attacked by free radicals and oxidized, and reducing LDL oxidation can help mitigate its harmful effects on blood vessels. According to the researchers, “Our results show a positive effect of resveratrol on many risk factors and on some inflammatory biomarkers, suggesting that a moderate consumption of red wine in the adult population is a positive component of the Mediterranean diet.”

Reference: Avellone G, Di Garbo V, Campisi D, De Simone R, Raneli G, Scaglione R, Licata G. Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis. Eur J Clin Nutr. 2006; 60:41-7. Anyone who does not want to consume wine can try CP’s Red Wine Polyphenols or the red-wine-derived component Resveratrol.

Resveratrol Update:

Effects Extend Beyond Cardiovascular Support

In last month’s newsletter, I reported on the cardiovascular effects of resveratrol, a naturally occurring plant compound, as well as its powerful antioxidant abilities and its ability to activate the human longevity gene. Beyond these other effects, resveratrol may be important in prostate, uterus, breast and skin health.

Prostate Health

In one study, resveratrol-fed mice undergoing prostate mutagenesis showed an 87 percent reduction in risk of developing prostate tumors.1 The mice fed resveratrol for seven months experienced the highest risk reduction. Other mice with a less serious form of prostate mutagenesis were 49 percent more likely to have tumor growth halted or slowed compared to mice not consuming the compound. These same researchers are conducting a human study examining the resveratrol concentrations that may produce a similar effect to that found in animals.

Other researchers have proposed that resveratrol’s effects are due to its anti-inflammatory actions. Stanford University researchers found that in normal prostate cells, resveratrol exposure increased expression of a substance known as MKP5, which reduces inflammatory mechanisms.2

Health Opportunities for Women

A recent study looked at resveratrol’s effect on breast mutagenesis in mice.3 The researchers found a significantly lower tumor growth, decreased angiogenesis, and increased rate of apoptosis (cell death) in mutagenic cells in mice given resveratrol compared with controls. In vitro, they found a significant increase in apoptosis in resveratrol-exposed cells.

In another in vitro study, high resveratrol doses triggered apoptosis (cell death) in five out of six uterine cancer cell lines and inhibited uterine cancer cell proliferation.4

Skin Health

Scientists also have looked at resveratrol’s effects on UVB-radiation-mediated skin tumor development in mice.5 In this study, the control mice were subject to chronic UVB exposure (twice weekly, for 28 weeks). The mice received either a pre-treatment (30 minutes before each UVB exposure) or post-treatment (5 minutes after UVB exposure) topical resveratrol application. The topical application with resveratrol (both pre and post treatment) significantly inhibited tumor incidence and delayed onset of tumor development. Resveratrol also enhanced apoptosis in UVB-exposure-mediated skin tumors.

Potential Mechanism of Action

A review by Shankar, et al. examined resveratrol’s molecular mechanisms.6 Shankar reports “the chemoprevention properties of resveratrol are due to its ability to modulate the cell signaling pathways that lead to a diversity of bioactivities related to human health. Resveratrol has been shown to inhibit tumor initiation, promotion, and progression.”

Another report mirrors Shankar’s findings in stating that resveratrol acts on mutagenesis by affecting the three phases (tumor initiation, promotion and progression) and suppresses the final steps of neoplasia and metastasis.7 According to the report, resveratrol activates apoptosis and arrests the cell cycle in cells that have undergone transformation. Additionally, resveratrol does not present any cytotoxicity (cell toxicity) in animal models or safety concerns in humans.

Resveratrol also exerts some interesting effects on angiogenesis, the development of new blood vessels needed by cancer cells to spread throughout the body. At the same time that resveratrol can increase angiogenesis when the heart is in need of extra oxygen, resveratrol has stopped angiogenesis in experimentally induced tumors.8

Other Research

In animal and in vitro studies, colon cancer9, melanoma10, leukemia11-12 and pancreatic cancer cells13 were inhibited after exposure to resveratrol. In humans, some studies have associated high-resveratrol diets with an improvement in breast health.14 Furthermore, consumption of red wine, which contains high quantities of resveratrol, has been linked to a reduced lung cancer risk.15

Conclusion

Although clinical trials in humans are clearly needed, resveratrol is emerging as one of the most well researched natural substances with promising reports in the medical literature studying its inhibitory effects on the mutagenic process.

References

1. McNally, Alex. Red wine linked to anti-cancer potential. NUTRAingredients.com 2007 March 3.

2. Nonn L, Duong D, Peehl, DM. Chemopreventative anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells. Carcinogenesis. 2007 June; 28(6): 1188-96.

3. Garvin S, Ollinger, K, Dabrosin, C. Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Letters. 2006 Jan; 231(1): 113-22.

4. Sexton E, Van Themsche C, LeBlanc K, Parent S, Lemoine P, Asselin E. Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells. Mol Cancer. 2006 Oct 17;5:45.

5. Aziz MH, Reagan-Shaw S, Wu J, Longley, BJ, Ahmad, N. Chemoprevention of skin cancer by grape constituent resveratrol: relevance to human disease? The FASEB Journal. 2005 July; 19(9): 1193-95.

6. Shankar S, Singh G, Srivastava, RK. Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Frontiers in Bioscience Publications. 2007 Sept; 1(12): 4839-54.

7. Delmas D, Lancon, A, Colin, D, Jannin, B, Latruffe N. Resveratrol as a chemopreventative agent: a promising molecule for fighting cancer. Current Drug Targets. 2006 April; 7(4): 423-42.

8. Chen Y, Tseng SH.  Pro- and anti-angiogenesis effects of resveratrol. In Vivo. 2007 Mar-Apr;21(2):365-70.

9. Trincheri NF, Nicotra G, Follo C, Castino R, Isidoro C. Resveratrol induces cell death in colorectal cancer cells by a novel pathway involving lysosomal cathepsin D. Carcinogenesis. 2007 May;28(5):922-31.

10. Lao CD, Demierre MF, Sondak VK. Targeting events in melanoma carcinogenesis for the prevention of melanoma. Expert Rev Anticancer Ther. 2006 Nov;6(11):1559-68.

11. Horvath Z, Saiko P, Illmer C, Madlener S, Hoechtl T, Bauer W, Erker T, Jaeger W, Fritzer-Szekeres M, Szekeres T. Resveratrol, an ingredient of wine, acts synergistically with Ara-C and tiazofurin in HL-60 human promyelocytic leukemia cells. Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1019-24.

12. . Li T, Fan GX, Wang W, Li T, Yuan YK. Resveratrol induces apoptosis, influences IL-6 and exerts immunomodulatory effect on mouse lymphocytic leukemia both in vitro and in vivo. Int Immunopharmacol. 2007 Sep;7(9):1221-31. 

13. Golkar L, Ding XZ, Ujiki MB, Salabat MR, Kelly DL, Scholtens D, Fought AJ, Bentrem DJ, Talamonti MS, Bell RH, Adrian TE. Resveratrol inhibits pancreatic cancer cell proliferation through transcriptional induction of macrophage inhibitory cytokine-1. J Surg Res. 2007 Apr;138(2):163-9. 

14. La Vecchia C, Bosetti C. Diet and cancer risk in Mediterranean countries: open issues. Public Health Nutr. 2006 Dec;9(8A):1077-82. 

15. Ruano-Ravina A, Figueiras A, Barros-Dios JM. Type of wine and risk of lung cancer: a case-control study in Spain. Thorax. 2004 Nov;59(11):981-5.

Information in this article is for educational purposes only, and is not intended as medical advice.

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