Commentary

Dear Mr. Morgenthaler,

Thank you for the “Health & Wellness Update.” I look forward to each issue, and the solid information it provides.

Praise for
Smart Publications
Health & Wellness Update

"For sometime now I have enjoyed reading Smart Publications. They are beautifully structured, well written and educational"

"Wealth of information for anyone that chooses alternative healing methods. It's an education in itself just to read one of these newsletters! Every time I get one I read it from cover to cover! Easy to understand and easy to decipher when looking for products. Well done! It's a joy to read."

Red Wine: Nature's Source for Resveratrol and Polyphenols

RESVERATROL IN THE NEWS

Resveratrol has been in the news quite a bit lately. In short, resveratrol is one of the many beneficial compounds found in red wine. Some researchers believe that resveratrol works by mimicking the effects that one would get from practicing a caloric restriction diet. Calorie restriction is well-established as a method of extending lifespan and reducing diseases associated with aging (at least in laboratory animals). And resveratrol may work by triggering the same genes that are triggered by a very low calorie diet … without the hunger. Finally, resveratrol may be part of the explanation for the oft-noted beneficial effects of red wine.3

What is resveratrol?

Resveratrol is a compound found in a variety of plants including cranberries, raspberries, peanuts, pine trees, and grapes. The primary dietary sources in an average person’s diet are peanuts, peanut butter, grapes, and wine. The compound is particularly concentrated in red wines such as pinot noir. Resveratrol is produced in the grape skin in response to a bacterial infection that affects the plant, thus acting as a natural antibiotic.

Resveratrol is classified as a polyphenol because of its chemical structure. Polyphenols make up a huge group of plant compounds that are further broken down into other classifications such as flavonoids and proanthocyanidins, which are potent antioxidants. Resveratrol is also a phytoestrogen, a substance that mimics some of the effects of estrogen while blocking others.

In the early ‘90s, scientists finally discovered that it is the secret ingredient found in the traditional Asian heart remedies that contain Polygonum—a plant that is abundant in resveratrol. These medicines are prescribed for liver and heart conditions. Since then, hundreds of studies have shown that resveratrol is beneficial to a long list of health concerns. And just recently, a Harvard research team found that resveratrol improved the health and survival of obese mice. 3

How does resveratrol work?

Thousands of animal experiments have demonstrated that resveratrol has anti-aging benefits, as well as antioxidant, anti-inflammatory, anticancer, antiplatelet, cholesterol-lowering, and mild estrogenic activities.

There are numerous theories, however, as to how it produces a wide range of health benefits. Harvard researchers have noted there is evidence suggesting that calorie restriction can extend lifespan across a range of species. And after screening thousands of molecules, they found that resveratrol mimics calorie restriction in yeast: activating enzymes that slow aging, increasing the stability of DNA, and extending lifespan by as much as 70%.1,2 Researchers suspect plants make these age-slowing molecules as a defense response.

Another Harvard research team recently found that 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).3

This study is significant because of the obesity epidemic in the United States. Resveratrol may well point the way to a new approach for treating obesity-related disorders and preventing age-related diseases in humans, like cancer, heart disease, and type II diabetes.

Reservatrol had previously been shown to prevent damage to liver tissue, says Matt Kaeberlein, a pathologist at the University of Washington; the compound could be staving off age-related diseases by keeping the liver healthy. He notes that more work needs to be done to determine if resveratrol affects other parts of the body as well. 4

“Even if resveratrol does turn out to be a miracle drug, a wine glass would probably not be the preferred delivery method. According to Kaeberlein, it would take over 300 glasses of wine per day to equal the amount of resveratrol fed to the obese mice in this study.” 4

An earlier study showed that resveratrol might also extend the lifespan of vertebrate animals. Researchers found that adding resveratrol to the daily diet of a small fish that naturally age rapidly and typically live only three months, prolonged its lifespan, delayed the onset of age-related problems, and improved cognitive function.

Researchers found that fish fed the lower dose of resveratrol lived an average of 33% longer than fish fed their normal diets, while those fed the higher dose of resveratrol lived more than 50% longer. The researchers reported that the findings suggest that resveratrol is the first compound to consistently prolong the life of several very different animal groups and could become the stepping-stone for creating drugs to prevent age-related diseases in humans.5

Why should I take a resveratrol supplement if I can get it from wine or peanut butter?

Quite frankly, if you drink enough wine or eat enough peanut butter—every day—you probably could get plenty of resveratrol. But, and that’s a big but (excuse the pun), you’d be consuming so many extra calories that you’d have to spend the entire day exercising in order to not gain weight! And even though wine may be good for you in small doses, alcohol takes a toll on your liver and saps your body of vitamins and minerals. And the worst-case scenario is that it can become addictive.
It’s better in the long run to take a nutritional supplement with a standardized amount of resveratrol, so you don’t have to worry about loading up on calories or alcohol.

What to look for in a resveratrol supplement

• Red wine extract contains varying amounts of resveratrol along with other plant chemicals, so it’s important that the product supplies a standardized extract of resveratrol.
  
  
• Supplements usually contain doses of anywhere from 1 milligram to 100 milligrams of resveratrol per day. On the other hand, an entire bottle of red wine contains only about 10 milligrams of resveratrol. It’s also important to realize that some products label their resveratrol in micrograms (mcg) rather than milligrams (mg). This can make the amount look like a hefty dose, but remember that it takes 1,000 micrograms to equal 1 milligram. For a product that promises 20 mcg per pill, you would need to take 1,000 pills to get a 20 mg dose. 6
  
  
• Look for a standardized extract of proven levels of trans-resveratrol in an easy to take capsule form.
  
  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.6
  
  
  

Scientific studies

Resveratrol has been the subject of intense interest because of its antioxidant, cardioprotective, anti-aging, and anticancer properties. Following are some of the most significant studies:

Reduces cancer risk

Although resveratrol is not 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. 7

Studies have found that resveratrol

• May be particularly beneficial as an adjunct cancer therapy in advanced prostate cancer 8
  
  
• Reduces skin tumors in mice when applied topically 9
  
  
• May be beneficial in the treatment of breast, colon, lung, esophagus, skin, lymph node, brain and testicular cancer, 10, 11 as well as thyroid, melanoma, pancreas, and head and neck squamous cell carcinoma, ovarian and cervical carcinoma 11
  
  
• Decreased induced mammary tumor incidence, number of tumors, and extended cancer latency in female Sprague-Dawley rats 12
  
  
• Can inhibit the growth of colorectal tumor cells 13

Resveratrol helps keep your heart and arteries healthy by

• Preventing cholesterol plaque from forming within artery walls regardless of whether circulating levels of cholesterol are high or low 14
  
  
• Up-regulating nitric oxide and exerting antioxidant protection against cardiac ischemia 15
  
  
• Stopping the proliferation of cells in blood vessels that narrow the arteries, 16 and keeping blood cells from sticking together 17
  
  
• Relaxing the endothelium that lines the arteries, allowing for efficient blood flow 18

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-1.19

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.20  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.

A recent study showed that resveratrol reduces the damaging effects of arthritis on cartilage tissue in animal models. 21

Another recent study showed that resveratrol reduces homocysteine—an amino acid in the blood resulting from inflammation and leading to a higher risk of cardiovascular disease. 22

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 laboratory mice, resveratrol was found to protect neurons against amyloid toxicity, 23,24,25 a prime culprit in the disease, and also increases cognitive ability. 26

Is a mild anti-depressant

Now we know why drinking wine makes you feel good and—at least temporarily—helps you leave your troubles behind. Researchers at the University of Santiago de Compostela in Spain found that resveratrol is a mild but "potentially useful molecule in the treatment of depression." Although they performed an in vitro study rather than a clinical study on humans, resveratrol was compared to molecules used to make commonly used anti-depressants and anti-anxiety drugs, and exhibited the same characteristics.

As a natural enzyme inhibitor resveratrol inhibits both monoamine
oxidase and 5-hydroxytryptamine, as many prescribed drugs do today, and the researchers concluded that if resveratrol shows similar behavior in humans, “it may have interesting therapeutic potential for improving the pharmacological treatment of depression." 27

Recent studies indicate that in addition to resveratrol, the polyphenols in red wine have many beneficial effects on the cardiovascular system.

The French smoke, drink, and eat lots of cheese. Yet, despite a diet that's relatively high in fat, they boast a 42% lower incidence of cardiovascular disease than Americans do. Why? Because in addition to eating a diet that includes whole, high-fiber grains, they drink red wine. Red wine is chock full of antioxidant compounds and resveratrol, which in turn lowers the risk of many diseases.28

Three recent studies have shown that red wine has even more benefits than previously realized.

1) Red wine promotes nitric oxide production

2) Red wine consumption lowers homocysteine levels

3) Red wine polyphenols prevent the oxidation of dietary fats in the digestive tract

While most people are aware that oxidized fats are an important risk factor for cardiovascular disease, most aren't aware that much of the oxidative stress occurs from the normal oxidation of dietary fats within the digestive tract. The subsequent absorption of these oxidation products greatly increases oxidative damage in the body and modifies LDL cholesterol to damaging forms.

Recent research has shown that wine polyphenols are very effective at preventing the rise of oxidized fat products after meals. Because much of our body's oxidative stress is a result of the absorption of these damaging fats after meals, red wine's unique ability to prevent fat oxidation during digestion is a novel means to lower the damaging effects of these oxidized fats on our cardiovascular system. As the author's concluded, "Apparently, wine procyanidins are active in preventing lipid oxidation of foods while in the digestive tract, thus preventing the postprandial plasma rise in oxidants. The likely limited bioavailability of these compounds, therefore, does not affect their relevance as key elements for optimizing nutrition and reducing risk of atherogenesis." 32

Dietary supplementation is a popular and inexpensive way to lower one's risk of heart disease

Don't worry, we're not asking you to drink two glasses of red wine every day over a leisurely four-hour lunch, as the French do (although it doesn't sound like punishment!). Even if you don't drink red wine, you can gain the same benefits by drinking red grape juice or taking a nutritional supplement that contains red wine polyphenols. Because red grape juice is also very high in sugar and calories, red wine extract is the low-calorie choice to obtain the amazing and broad-spectrum benefits of the magical red grape.

The health benefits of wine without the calories and alcohol

While substantial evidence suggests that red wine offers numerous health benefits, the preferred method of obtaining the healthful phytochemicals in wine is a standardized red wine extract.  This helps to avoid the calories and alcohol found in wine.  Many epidemiological and laboratory studies have shown that the polyphenols found in red wine, including resveratrol, have the potential to substantially enhance our health and longevity.  By consuming a standardized extract of red wine that includes both polyphenols and resveratrol, we are able to harness the health promoting properties of red wine in a safe, healthful, and easy to use supplement.

References:

1. 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.
   Abstract
   
   
2. Wolf G. Calorie restriction increases life span: a molecular mechanism. Nutr Rev. 2006 Feb;64(2 Pt 1):89-92.
   Abstract
   
   
3. 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.
   Abstract
   
   
4. Swaminathan, Nikhil “The Fountain of Youth at the Bottom of a Wine Bottle?” Scientific American.com, Nov. 2, 2006.
   Abstract
   
   
5. Dario R. Valenzano, Eva Terzibasi, Tyrone Genade, Antonino Cattaneo, Luciano Domenici, and Alessandro Cellerino. Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate. Current Biology 2006 16: 296-300.
   Abstract
   
   
6. Review Article: Resveratrol, 11/30/06. http://consumerlab.com/results/resveratrol.asp
   
   
   
7. 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.
   Abstract
   
   
8. 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.
   http://www.springerlink.com/content/uh55371825mr591j/
   
   
9. 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 activity of resveratrol, a natural product derived from grapes. Sci 275(5297):218–20.
   Abstract
   
   
10. 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.
    Abstract
    
    
11. 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.
    Abstract
    
    
12. Banerjee S, Bueso-Ramos C, Aggarwal BB. 2002. Suppression of 7,12-dimethylbenz(a) anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-κB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res 62(17):4945–54.
    Abstract
    
    
13. 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. 2006 Nov 20.
    Abstract
    
    
14. 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.
    Abstract
    
    
15. Shen M, Jia GL, Wang YM, Ma H. Cardioprotective effect of resveratrol pretreatment on myocardial ischemia-reperfusion induced injury in rats. Vascul Pharmacol. 2006 Aug;45(2):122-6. Epub 2006 Jun 12.
    Abstract
    
    
16. Haider, U.G. et al. Resveratrol increases serine 15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. Mol. Pharmacol. 200;363:925-32.
    http://intl-molpharm.aspetjournals.org/cgi/content/abstract/63/4/925
    
    
17. 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.
    Abstract
    
    
18. Novakovic A, Bukarica LG, Kanjuh V, Heinle H. Potassium channels-mediated vasorelaxation of rat aorta induced by resveratrol. Basic Clin Pharmacol Toxicol. 2006 Nov;99(5):360-4.
    Abstract
    
    
19. Jang M, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997;275(5297):218-20.
    Abstract
    
    
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.
    Abstract
    
    
21. Elmali N, Baysal O, Harma A, Esenkaya I, Mizrak B. Effects of Resveratrol in Inflammatory Arthritis. Inflammation. 2006 Nov 4.
    Abstract
    
    
22. 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.
    Abstract
    
    
23. Anekonda TS. Resveratrol--a boon for treating Alzheimer's disease? Brain Res Brain Res Rev. 2006 Sep;52(2):316-26.
    Abstract
    
    
24. Wang J, Ho L, Zhao Z, Seror I, Humala N, Dickstein DL, Thiyagarajan M, Percival SS, Talcott ST, Pasinetti GM. Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease. FASEB J. 2006 Nov;20(13):2313-20.
    Abstract
    
    
25. Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. J Biol Chem. 2005 Nov 11;280(45):37377-82. Epub 2005 Sep 14. PMID: 16162502.
    Abstract
    
    
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.
    Abstract
    
    
27. Yanez M, Fraiz N, Cano E, Orallo F.( -)-Trans-epsilon-viniferin, a polyphenol present in wines, is an inhibitor of noradrenaline and 5-hydroxytryptamine uptake and of monoamine oxidase activity. Eur J Pharmacol. 2006 Aug 7;542(1-3):54-60.
    Abstract
    
    
28. Energy Times, "The French Paradox," pg. 80. September 1999.
    
    
29. Folts, JD. Potential health benefits from the flavonoids in grape products on vascular disease. Adv Exp Med Biol 2002;505:95-111.
    
    
30. Olszewski, A. J.; et al. Reduction of plasma lipid and homocysteine levels by pyridoxine, folate, cobalamin, choline, riboflavin, and troxerutin in atherosclerosis. Atherosclerosis 75 no. 1 (Jan, 1989): 1-6.
    
    
31. Dixon JB, Dixon ME, O'Brien PE. Reduced plasma homocysteine in obese red wine consumers: a potential contributor to reduced cardiovascular risk status. Eur J Clin Nutr 2002 Jul;56(7):608-614.
    
    
32. Ursini F, Sevanian A. Wine polyphenols and optimal nutrition. Ann N Y Acad Sci 2002 May;957:200-209.