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    Smoker's Aid^™

 

Promote Healthy Cells & Tissues

   Helps Cleanse the Body of
   Toxic Substances

For Present & Former Smokers &
Those Exposed to Secondary Smoke

A Powerful, Proprietary Flavonoid Complex
Very Useful to Non-Smokers As Well

 

          

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Quality Assurance: This product is manufactured in the United States by one of America's leading laboratories in business since 1955. It is produced from natural sources and contains no yeast, sugar, starch, artificial flavor, dyes, coloring agent or preservatives.

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Smoker’s Aid contains a powerful array of highly concentrated flavonoid anti-oxidants--potent nutrients which target dangerous toxins and help promote healthy cells.

 

(INGREDIENTS LIST)

Oxidation is the process by which the body uses its store of oxygen, and it is vital to life.  However, oxidation also produces free radicals, molecular byproducts which can destroy important enzymes, proteins, and other compounds necessary for healthy functioning.

Researchers have been linking free radical damage with an increased risk of serious diseases, such as cancer and heart disease.  To counteract free radical damage, the body makes use of antioxidants like vitamin C, vitamin E, and glutathione, which scavenge free radicals and help prevent their creation. 

Smoking increases oxidative stress, creating more free radicals which can damage the vascular system.  Smokers, therefore, are at higher risk for diseases caused or aggravated by oxidants.  Supplementing the diet with antioxidants from flavonoids in this formulation may help counteract the harmful effects of smoking on the lungs, cardiovascular system, and other vital organs. 

Some flavonoid antioxidants appear to be more powerful than vitamin C and vitamin E.  The ingredients in Smoker’s Aid provide a well-rounded dose of antioxidants from the richest dietary sources to promote a healthy heart, blood vessels, connective tissues, and lungs. 

 

Grape seed extract and pine bark extract are a rich source of proanthocyanidins, antioxidants known for their role in promoting the health of connective tissues and capillary blood vessels.  Studies conducted at the University of Alabama in Birmingham have suggested that grape seed extract may even help lower blood pressure.  Proanthocyanidins from grape seed and pine bark are specifically able to improve the health of blood vessels by adding extra protection to the endothelium, the surface that separates the artery wall from the bloodstream.  

In addition, grape seed and pine bark extract may provide some benefit to the teeth and gums through their anti-inflammatory effects.  Proanthocyanidins from grape seed extract are one of the few antioxidants which can pass through the blood-brain barrier to protect brain tissues from free radicals.  They also aide the body in producing and using vitamins C and E, allowing for the usage of even more antioxidants.

Anthocyanins from red grape skin extract have been shown to be many times more powerful as antioxidants than vitamin E.  Anthocyanins help protect blood lipoproteins, compounds which carry fat through the body.  Red wine has a reputation for being healthy for the heart.  This reputation is due to red wine’s high concentration of anthocyanins.  Because free radicals are unstable molecules, they steal electrons from important biological compounds, destroying essential proteins, enzymes, and minerals.  Anthocyanins may protect lipoproteins from free radicals.

Antioxidants from bilberry extract are called anthocyanosides.  Anthocyanosides have been found to be important for the health of the eyes, for stable blood flow in the capillaries, and for normal wound healing.  Anthocyanosides accomplish this by stabilizing collagen, the main component of connective tissues and of the fluid of the eye.  Healthy connective tissue is especially important to smokers because smoking raises blood pressure and oxidative stress on these areas.  By maintaining elasticity in the capillaries, anthocyanosides from bilberry extract can add extra protection to these vulnerable regions.

Although Japanese men on average smoke more than American men, there is a lower occurrence of lung cancer in Japan than in America.  Some researchers believe that this discrepancy is due to the fact that green tea is consumed regularly in the japanese diet.  Polyphenols have been identified as the source of green tea’s antioxidant strength.  EGCG is an especially potent polyphenol.  Polyphenols promote a healthy immune system as well as allow for more efficient cholesterol metabolism.  By fighting free radicals caused by smoking, polyphenols from green tea may help reduce the risk of cardiovascular disease, lung cancer, emphysema, and other serious illnesses. 

The benefits of green tea extract extend beyond its antioxidant abilities.  Green tea extract may also exhibit anti-tumor effects, according to Stephen B Strum, M.D., at the Prostate Cancer Research Institute.  Polyphenols from green tea have been cited as part of possible treatments for atherosclerosis, coronary heart disease, high cholesterol, high blood pressure, and cancer.  For more information on research in this field, see below.

By acting as an antioxidant, ginkgo biloba extract protects nerves and the eyes from the damage by free radicals.  Ginkgo supplements can improve concentration, short-term memory, and overall brain function.  Ginkgo may even help reduce the symptoms of Alzheimer’s disease and other forms of dementia.

The two important chemicals in ginkgo are glycosides and terpenoids.  These flavonoids protect the heart muscles, nerves, and retina from free radical damage.  Antioxidants in the brain may allow for optimal performance.

Terpenoids are the compounds which dilate the blood vessels and keep platelets in the blood from clotting together.  Studies performed by the National Institutes of Health have confirmed the health benefits of ginkgo, and in Europe it remains one of the most popular herbal supplements on the market. 

Other uses for ginkgo include treatments for pre-menstrual syndrome, altitude sickness, claudication (pain in the legs caused by blood clots), and depression.  Ginkgo is at least as effective, and possibly even more so, than some prescription drugs in treating claudication and dementia.  For example, for people with early stage dementia, one study showed that ginkgo was more effective at treating symptoms than the prescription drug donepezil (Aricept®), according to the Mayo Clinic.  T

he Mayo Clinic also cites ginkgo biloba extract as a possible treatment for cerebral insufficiency, acute hemorrhoidal attacks, age-associated memory impairment, chemotherapy side effects, deafness, seasonal affective disorder, gastric cancer, glaucoma, macular degeneration, multiple sclerosis, pulmonary interstitial fibrosis, retinopathy, tinnitus, sexual dysfunction, stroke, vertigo, and vitiligo. 

The flavonoids in milk thistle are called silymarins.  Silymarins are antioxidants which protect the liver from free radical damage.  The liver is the detoxification organ for the body, so a healthy liver is essential to good overall health.  Early studies have reported that milk thistle may even protect the liver against cancer. 

Citrus bioflavonoids work with vitamin C to provide powerful antioxidant support.  These antioxidants may help combat aging.  Citrus bioflavonoids are believed to promote healthy eyes.  Like other flavonoids, citrus bioflavonoids have exhibited some anti-cancer effects.

 

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MORE INFORMATION ON FLAVONOIDS:
From the Japan Institute for the Control of Aging:


DNA-damage Biomarker 8-OHdG
"8-OHdG Check"
How to check the oxidative stress and how it influences human health?

1. Oxidative stress causes diseases including cancer and aging.
Currently there is a strong scientific opinion that more than 90 percent of diseases are caused by oxidative stress due to active oxygen, other free radicals and lipid peroxides. Active oxygen, though vital to our body, causes considerable damage to the essential components of human body and disturbs the physiologically important functions of proteins, lipids, enzymes and DNA bearing the genetic code. This leads to disorder in our body, which in turn leads to development of diseases and accelerating aging. It has been demonstrated that oxidative stress causes cancers and many 'life-style related diseases such as arterial sclerosis, high blood pressure, myocardial infarction, cerebral apoplexy, dementia, diabetes, cataract etc.


2. What is 8-OHdG?
It has been calculated that about 2 percent of oxygen inhaled by the respiratory system turn to active oxygen in human body. This can reach to 10 percent in worse case scenario. Active oxygen is produced when our body generates energy and also when microphage cells confronts foreign, invading substances which may cause harm to the body and dispose them appropriately in our body system. Thus, active oxygen is essential and useful to our body. However, danger occurs when excess active oxygen is dispersed and which becomes detrimental to organs, body tissues and blood corpuscles.

Deoxyguanosine (dG) is one of the constituents of DNA and when it is oxidized, it is altered into 8-hydroxy-2'-deoxyguanosine (8-OHdG).


3. Balance of Active Oxygen and Anti-Oxidant System.
Human body is endowed with a counteracting defense system, to suppress excessive active oxygen so that body tissues and metabolic processes are prevented from disruption. This defense system is composed of components such as antioxidant enzymes, trace elements which aid the enzyme activity, vitamins and antioxidants referred to as super vitamins. As long as there exists a balance between the oxidative stress and antioxidant system, human body is maintained in an optimal health state. However, once the level of active oxygen released exceeds the protective capacity provided by the antioxidant system, human body suffers from the ill effects of oxidative stress. This leads to illness, death of cells and unstoppable excessive cell division resulting in cancer, and as a consequence acceleration of the aging process. Therefore, the maintenance of the delicate balance between oxidative stress and antioxidant system in proper order becomes very important.


4. How to check the balance between active oxygen and antioxidant system?
As one of the choice steps, we can measure the concentration and volume of human body components damaged by oxidation. The biomarker substance that aids in this detection should sensitively and proportionally respond to the degree of oxidative stress caused in the body, and should remain stable in the body until it is released and analyzed.

This resulting product is stable in the human body after it is excised from DNA by the repair enzyme system, and ultimately released into blood and excreted via urine. We can measure the concentration of 8-OHdG to determine the total oxidative stress (change) in our body which enables us primarily to evaluate our life style.

Japan Institute for the Control of Aging (Dr. H.Ochi, Director of JaICA) researches with Prof.T.Osawa (Nagoya University) together and has established anti-8-OHdG monoclonal antibody. Even they have developed an original "8-OHdG Check" ELISA Kit using this antibody for the first time in the world.


5. The Science of Control of Aging.
The "8-OHdG Check" kit has another facet in its use in the control of aging process. For steps taken in scientific control of aging, it is necessary to determine the accelerative aging process and provide a feedback action. This means that when the progress of aging is assessed, one can take measures to retard the progress of aging by improving his or her life style or living environment. And detection of such measures facilitates in making further revision, if necessary. Since this check kit can determine the acceleration of degree of oxidative stress during aging, it serves to complete the aging control cycle and defines the science of aging control.

6. Completion of Individual Maximum Life Span in Good Health - to promote active life at least until 85 years.
The fundamental features of completing the individual maximum life span in good health is to establishing the life style, avoiding at most tasks which generate active oxygen, practicing optimum nutrition and optimum exercise. Optimum nutrition related to consuming well-balanced foods high with antioxidants. These guidelines ensures one to complete the allotted maximum life span and enjoy active life until 85 years. To find out whether one's current situation is appropriate or somewhat strayed from the optimal path, it pays to check one's 8-OHdG level at frequent intervals.

8-OHdG is useful as a general oxidative stress marker in the body. However, single marker is not sufficient for the analysis of oxidative stress in detail. For this purpose, we propose a screening system, named Oxidative Stress Profile (OSP). The OSP was developed by the joint efforts of JaICA and our sister institute Genox Corporation in the USA. It evaluates the OSP in an individual's body by analyzing 80 endogenous components in blood, saliva and urine. The recommended strategy is for one to measure 8-OHdG first, and in case of extensive screening needed, employ the OSP analysis to find out the overall oxidative stress state of the body. Now we are developing new profiles for the human health in the world.

Health Sciences Institute……July 13, 2005

Cancer: Help ward off cancer with flavonoids
Once again, scientists are doing their best to sell us some sweets with a study that "reveals" the cardiovascular protection offered by eating dark chocolate.

The results of this new study from the Athens Medical School in Greece shows that aortic flexibility and blood flow improved when 17 "young, healthy volunteers" ate about four ounces of dark chocolate over a three hour period.

Last year in the e-alert "Latest dietary study results are laughable" (28/06/04) I told you about a similar study that sang the praises of dark chocolate. A peek at the details, however, quickly revealed that the cardio benefits of chocolate are almost certainly the work of flavanoids, the antioxidant and anti-inflammatory chemicals that give fruits and vegetables their colour.

In other words, if you're looking for genuine nutrition, skip the chocolate bar and go with an apple instead.

Or grapes. Because another recent study offers evidence that the flavanoid content of certain grapes may inhibit an enzyme that helps cancer cells multiply.


Hold it back
The enzyme goes by the catchy name "topoisomerase II." We'll call it topo2 for short. Previous studies have shown that some cancer cells have topo2 levels hundreds of times higher than levels in normal cells. Based on this evidence, scientists believe that topo2 may be partly responsible for the prolific cell division in some cancers. Likewise, an agent that would inhibit the enzyme might help check cancer cell division.

In an issue of the Journal of Agriculture and Food Chemistry, US researchers at the University of Illinois at Urbana-Champaign (UIUC) report on a laboratory study in which flavonoid-rich extracts from seven different types of red grapes were tested on topo2.

Results showed that several specific components of the seven extracts significantly restrained topo2 activity. Most impressive was the discovery that these components appeared to be more effective than either quercetin or resveratrol, two antioxidant flavonoids that are well-known chemopreventive topo2 inhibitors.

Further studies will be needed to determine the amount of grapes (or grape juice or wine) that would need to be consumed in order to inhibit topo2 activity and stall cancer cell division.


The Helsinki cohort
As HSI members are already aware, dietary flavonoids provide plenty of health benefits.
A large study from the National Public Health Institute in Helsinki, in Finland, examined the effects of different flavonoids on chronic diseases.

The Helsinki researchers used questionnaires and interviews to determine dietary history for more than 10,000 men and women. Flavonoid intakes were estimated based on the known flavonoid concentrations in specific foods. The health of each subject was tracked through national prescription and disease registries for an average of 28 years.

When researchers examined the data they found that subjects who consumed more flavonoid-rich foods were less likely to suffer from a number of chronic diseases, including heart disease, lung cancer, stroke, asthma, and type 2 diabetes.


Prevention for dinner
In addition to the broad conclusions of their study, the Helsinki researchers reported some useful specifics about which flavonoids may work best to help prevent certain diseases.

The stars of the group were quercetin and another flavonoid called kaempferol. Quercetin is most abundant in apples, but is also found in onions, citrus fruits, parsley, green tea and red wine. Kaempferol is also found in onions, as well as in broccoli. Subjects who had high levels of both of these flavonoids in their diets were found to have a 21% lower risk of heart disease than those who ingested small amounts of the two. In addition, subjects with kaempferol-rich diets lowered their risk of stroke by 30 percent.

Diets that include good amounts of quercetin may also provide protection against lung cancer, asthma and type 2 diabetes. And another flavonoid called myricetin, found in cranberries, has been shown to have a preventive effect on prostate cancer.

Results of the study also indicate that antioxidant activity is more effective when many different flavonoids are consumed.
13.07.2005

 

 “Review: Dietary Flavonoids and Cancer Risk: Evidence From Human Population Studies”

Marian L. Neuhouser,  Nutrition and Cancer.  2004, Vol. 50, No. 1, Pages 1-7.  (oi:10.1207/s15327914nc5001_1)

High dietary intake of fruits and vegetables is consistently associated with a reduced risk of common human cancers, including cancers of the lung, breast, prostate, and colon. It is unknown which bioactive compound or compounds in plant foods provide the chemoprotective effects. One class of compounds currently under investigation is flavonoids, a large group of compounds with similar structure, consisting of two phenolic benzene rings linked to a heterocyclic pyran or pyrone. Although there are numerous in vitro and animal model data suggesting that flavonoids influence important cellular and molecular mechanisms related to carcinogenesis, such as cell cycle control and apoptosis, there are limited data from human population studies. This article reviews data from four cohort studies and six case-control studies, which have examined associations of flavonoid intake with cancer risk. There is consistent evidence from these studies that flavonoids, especially quercetin, may reduce the risk of lung cancer. Further research using new dietary databases for food flavonoid content is needed to confirm these findings before specific public health recommendations about flavonoids can be formulated.

Cited by
Marta Rossi, Werner Garavello, Renato Talamini, Carlo La Vecchia, Silvia Franceschi, Pagona Lagiou, Paola Zambon, Luigino Dal Maso, Cristina Bosetti, Eva Negri . (2007) Flavonoids and risk of squamous cell esophageal cancer. International Journal of Cancer 120:7, 1560
CrossRef

Aimée R. Kreimer, Giorgia Randi, Rolando Herrero, Xavier Castellsagué, Carlo La Vecchia, Silvia Franceschi . (2006) Diet and body mass, and oral and oropharyngeal squamous cell carcinomas: Analysis from the IARC multinational case–control study. International Journal of Cancer 118:9, 2293
CrossRef

Barry Halliwell . (2006) Polyphenols: antioxidant treats for healthy living or covert toxins?. Journal of the Science of Food and Agriculture 86:13, 1992
CrossRef

A Q Haddad, V Venkateswaran, L Viswanathan, S J Teahan, N E Fleshner, L H Klotz . (2006) Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Prostate Cancer and Prostatic Diseases 9:1, 68
CrossRef

Renato Talamini, Jerry Polesel, Maurizio Montella, Luigino Dal Maso, Anna Crispo, Luigi G. Tommasi, Francesco Izzo, Marina Crovatto, Carlo La Vecchia, Silvia Franceschi . (2006) Food groups and risk of hepatocellular carcinoma: A multicenter case-control study in Italy. International Journal of Cancer 119:12, 2916
CrossRef

G Deep, R P Singh, C Agarwal, D J Kroll, R Agarwal . (2006) Silymarin and silibinin cause G1 and G2–M cell cycle arrest via distinct circuitries in human prostate cancer PC3 cells: a comparison of flavanone silibinin with flavanolignan mixture silymarin. Oncogene 25:7, 1053
CrossRef

Chung-Pu Wu, Anna Maria Calcagno, Stephen B. Hladky, Suresh V. Ambudkar, Margery A. Barrand . (2005) Modulatory effects of plant phenols on human multidrug-resistance proteins 1, 4 and 5 (ABCC1, 4 and 5). FEBS Journal 272:18, 4725
CrossRef

 

 

“Cocoa, Flavanols and Cardiovascular Risk”
Posted 11/29/2004 
Norman K. Hollenberg; Harold Schmitz; Ian Macdonald; Neil Poulter

There has been a long-standing interest in the relation between what we eat and cardiovascular risk. Over the years, attention has been given to calories, total fat, saturated fat, cholesterol, omega-3 polyunsaturated fatty acids, trans fatty acids, folic acid, antioxidants and, most recently, flavanols. Flavanol concentrations can be moderately high in a number of foods that have been associated with a reduction in cardiovascular risk including red wine, and black and green tea. Some cocoa and chocolate products are extraordinarily rich in flavanols but, as with other flavanol-containing foods, certain post-harvesting and processing procedures can have a striking influence on the flavanol content of chocolate and cocoa.

Endothelial dysfunction with a consequent reduction in nitric oxide production has achieved a central conceptual role in the pathogenesis of atherosclerosis and coronary artery disease, diabetes mellitus and hypertension. Recent evidence that flavanol-rich cocoa activates vascular nitric oxide synthesis in the intact human raises an interesting possibility of a therapeutic potential.

Introduction
Interest in the relationship between what we eat and cardiovascular risk continues to grow. Long-standing interest in calories, total fat, saturated fat and cholesterol has been followed more recently by an interest in omega-3 polyunsaturated fatty acids, trans fatty acids, folic acid, fibre, soluble fibre and antioxidants. Among the most recent candidates that have drawn important attention are the flavonoids - polyphenolic compounds found in a variety of foods of vegetable origin, including tea, cocoa, chocolate, red wine, purple grapes, apples, onions and cranberries. In particular, a specific subclass of flavonoids - known as flavanols - has attracted increasing interest as a result of recent epidemiological,[1,2] mechanistic[3-8] and human intervention studies.[6,8-13] Among the wide variety of dietary flavanol sources, some cocoas and chocolates can be extraordinarily rich in certain flavanols.[14-17]

A possible confounder in epidemiological studies is a contribution from sources of flavonoids that were not part of the analysis. One striking example in this area is cocoa and chocolate, which can contain flavonoid, specifically flavanol, profiles and concentrations very different from those of other sources.[14,18] Equally important is the fact that foods recognised as being flavonoid-rich vary in their flavonoid content substantially, largely due to common techniques used during post-harvest handling of raw materials and processing during food production.[19]

The biological effects of plant flavonoids are wide-ranging and sometimes substantial. A recent review of the biological effects of flavonoids was 77 pages in length and included over 1,000 references, most of them written in the preceding decade.[20] Subjects covered ranged from general effects on mammalian cells to implications for inflammation, cancer and heart disease. In vitro, flavanols found in cocoas and chocolates have shown specific activities related to vascular health and, in particular, mechanisms associated with endothelial function, endothelium-derived nitric oxide synthesis, platelet function, and cellular processes modified by reactive oxygen and nitrogen species.[3-8,13,21]

Epidemiological evidence linking flavonoid consumption to heart disease or mortality in humans is impressive but has often been conflicting.[22-33] For example, there has been enormous interest in the 'French paradox' reflecting the interesting finding that the French do not have a myocardial infarction (MI) rate to match their fat intake. Attempts have been made to implicate red wine as a contributor via its flavonoid content. Regarding flavanols consumed as cocoa and chocolate and their potential influence on cardiovascular risk in epidemiological studies, there is a paucity of data. Such studies examining the potential health effects of foods rich in flavonoids have, at times, shown a very large influence on cardiovascular risk. For example, Mukamal et al. reported the findings in a prospective study on the determinants of mortality after acute MI. Patients who consumed an average of 14 or more cups per week of black tea showed a 39% reduction in mortality during a median follow-up of 3.8 years.[33] Perhaps more striking was the fact that the moderate tea drinkers who averaged only two cups of tea per week showed a 31% reduction. Adjustment for the usual risk factors did not alter this association. Why should the results of studies be in conflict given such a robust influence? There are several reasons: indeed, they provide the rationale for this review focusing on the potential cardiovascular health benefits of flavanols in cocoas and chocolates. Sometimes identifying the responsible mechanism(s) can have a substantial influence on the attempt to resolve such issues.

This review will focus on the fact that key mechanisms responsible for the potential vascular health benefits of flavanols present in cocoas and chocolates may have been identified.[4,8,9] The clinical processes of interest are characterised by endothelial dysfunction. Studies in vitro, in animal models, and in intact humans have provided growing evidence for an action of this class of natural products on endothelial dysfunction. The final common pathway appears to be activation of nitric oxide synthesis. Figure 1 depicts data from one study in which flavanolrich cocoa activated powerfully vessels of the extremity in healthy intact humans entirely via nitric oxide.[9]

This story has at least one of its beginnings a long way from the issue of phytochemicals in foods. The Kuna Indians in Panama, living in their indigenous island home in the Caribbean, do not show the typical rise in blood pressure with age, and hypertension is very rare.[34] In a study that began with the search for protective genes, the observation that migration to Panama City led to a loss of the protection against hypertension made it clear that an environmental factor was involved.

Examination of their diet uncovered the fact that they drank large volumes of a flavanol-rich cocoa.[2] Subsequent in vitro studies suggesting that cocoa extracts can induce endothelium-dependent relaxation[4] led to studies in healthy volunteers,[9] and in patients with vascular risk or disease.[1] In the studies of Heiss et al. ingestion of flavanol-rich cocoa led to an increase in flow-mediated vasodilation of the brachial artery following five minutes of ischaemia, a response that correlated with biochemical evidence of increased nitric oxide bioavailability.[8] In the normal volunteers studied by Fisher et al. flavanol-rich cocoa induced striking dilatation of the vessels of the finger, which was reversed completely by an arginine analogue that blocks nitric oxide synthesis.[9]

Flavanoids, flavanols, flavonol glycosides, flavandiols
Groups of related, naturally occurring chemicals in plants. A number of substances in these classes have anti-oxidant properties and many protect against deleterious changes brought about by free-radicals in the body.


American Journal of Clinical Nutrition

Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam.

Johanna M Geleijnse, Lenore J Launer, Deirdre AM van der Kuip, Albert Hofman and Jacqueline CM Witteman

1 From the Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, Netherlands (JMG, LJL, DAMVDK, AH, and JCMW); the Division of Human Nutrition and Epidemiology, Wageningen University, Netherlands (JMG); and the National Institute of Aging, Bethesda, MD (LJL).

2 Supported by the Unilever Health Institute, Vlaardingen, Netherlands.

3 Reprints not available. Address correspondence to JCM Witteman, Department of Epidemiology & Biostatistics, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, Netherlands. E-mail: witteman@epib.fgg.eur.nl .

Background: Dietary flavonoids may protect against cardiovascular disease, but evidence is still conflicting. Tea is the major source of flavonoids in Western populations.

Objective: The association of tea and flavonoid intake with incident myocardial infarction was examined in the general Dutch population.

Design: A longitudinal analysis was performed with the use of data from the Rotterdam Study—a population-based study of men and women aged  55 y. Diet was assessed at baseline (1990–1993) with a validated semiquantitative food-frequency questionnaire. The analysis included 4807 subjects with no history of myocardial infarction, who were followed until 31 December 1997. Data were analyzed in a Cox regression model, with adjustment for age, sex, body mass index, smoking status, pack-years of cigarette smoking, education level, and daily intakes of alcohol, coffee, polyunsaturated fat, saturated fat, fiber, vitamin E, and total energy.

Results: During 5.6 y of follow-up, a total of 146 first myocardial infarctions occurred, 30 of which were fatal. The relative risk (RR) of incident myocardial infarction was lower in tea drinkers with a daily intake >375 mL (RR: 0.57; 95% CI: 0.33, 0.98) than in nontea drinkers. The inverse association with tea drinking was stronger for fatal events (0.30; 0.09, 0.94) than for nonfatal events (0.68; 0.37, 1.26). The intake of dietary flavonoids (quercetin + kaempferol + myricetin) was significantly inversely associated only with fatal myocardial infarction (0.35; 0.13, 0.98) in upper compared with lower tertiles of intake.

Conclusions: An increased intake of tea and flavonoids may contribute to the primary prevention of ischemic heart disease.

Key Words: Tea • flavonoids • myocardial infarction • ischemic heart disease • population-based study • the Rotterdam Study • Netherlands

Epidemiologic studies have reported a reduced risk of ischemic heart disease in subjects with a high flavonoid intake through tea and other dietary sources (1–3), but findings are still conflicting (4, 5). The potential protective effect of flavonoids has been attributed to antioxidant (6–11), antithrombogenic (12–14), and antiinflammatory (15, 16) properties. Recent animal experiments suggest that flavonoids may also improve vascular function (17–19). In a previous cross-sectional analysis of data from the Rotterdam Study, we observed an inverse association of tea intake with aortic atherosclerosis (20). The present longitudinal study addresses the relation between tea intake and risk of first incident myocardial infarction in this population-based cohort of men and women aged  55 y.


The Rotterdam Study
The Rotterdam Study is a prospective study to assess the occurrence of chronic diseases in an aging population and to clarify the determinants of the diseases (21). The cohort comprises 7983 men and women aged  55 y (78% of the eligible population) who live in a defined district of Rotterdam. From August 1990 until June 1993, baseline data on current and past health, medication use, and risk indicators for chronic diseases were collected during a home interview by a trained research assistant. The participants were subsequently invited to the study center for a clinical examination and an assessment of diet.

Clinical examination
Height and weight were measured while the subjects were wearing indoor clothing and no shoes. Body mass index was computed as weight (in kg) divided by height squared (in m). Sitting systolic and diastolic blood pressures were measured twice with a random-zero sphygmomanometer by a trained research assistant after the subjects had rested for 5 min. The mean of the 2 blood pressure measurements was used in the analysis. A standard electrocardiogram was obtained, which was interpreted by using MEANS (Modular ECG Analysis System; 22). The subjects were considered to have diabetes mellitus if they reported using antidiabetes medication or if their nonfasting random or postload blood glucose concentrations were  11.1 mmol/L. Serum total cholesterol concentrations (mmol/L) were measured with the use of an automated enzymatic procedure (23). HDL cholesterol was measured similarly, after precipitation of the non-HDL fraction.

Dietary assessment
The participants indicated on a checklist all of the foods and beverages that they consumed more than once a month during the preceding year. The completed checklist formed the basis of an interview at the study center by a trained dietitian, who used a validated, semiquantitative food-frequency questionnaire (24). In two-thirds of the dietary interviews, a computerized version of the questionnaire was used, which included data checks. Participants quantified their habitual tea intake as the number of cups ingested per day, week, or month. One cup of tea was considered to equal 125 mL. Only the intake of black tea was assessed because this type of tea is predominantly consumed in the Netherlands. Intakes of total energy, macronutrients, and a large number of micronutrients were calculated from the food data with the use of Dutch food-composition tables (25). The total intake (mg/d) of the flavonols quercetin, kaempferol, and myricetin was computed with the use of published tables by Hertog et al (26, 27). Tea is a major source of flavonoids, <10% of which are flavonols (28, 29).

Follow-up procedures
The present analysis is based on follow-up data collected from baseline (1990–1993) until 31 December 1997. Information on the vital status of the participants was obtained at regular intervals from the municipal population registry. Informed consent for collection of follow-up data from the participants' general practitioners was obtained for 7751 participants of the Rotterdam Study (97%). Fatal and nonfatal events were reported by the general practitioners in the research area (covering 85% of the cohort) by means of a computerized system. All reported events were verified by research physicians who collected information from the patients' medical records at the general practitioners' offices. The information also included copies of discharge letters for hospital admissions of interest. The fatal and nonfatal events were coded independently by 2 research physicians according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) (30). If there was disagreement between reviewers, consensus was reached in a separate session. A medical expert in the field subsequently reviewed the coded events and his or her decision was considered definite if there were discrepancies. Myocardial infarctions included fatal and nonfatal incident events with an ICD-10 code I21. In the case of recurrent myocardial infarctions during follow-up, the first event was used in the analysis. A myocardial infarction was considered fatal if death occurred within 28 d after the onset of symptoms.

Study population
A total of 6521 independently living subjects attended the study center at baseline (82% of the Rotterdam Study cohort) and were eligible for a dietary interview. Diet could not be assessed in 271 participants of the pilot phase of the Rotterdam Study. Additionally, 122 subjects suspected of dementia were not interviewed because of expected difficulties in dietary recall, nor were a random group of 481 subjects because of logistic reasons. The dietitian considered 212 dietary reports unreliable, which were ultimately excluded. Dietary data were thus available for 5435 subjects, who had given informed consent for collection of follow-up data. We excluded 628 subjects with a self-reported history of myocardial infarction, which was verified with an electrocardiogram, who might intentionally have changed their diet. Thus, a total of 4807 subjects comprised the present analysis.

Data analysis
Data were analyzed by using SPSS version 10.0.5 for WINDOWS (SPSS Inc, Chicago). Age- and sex-adjusted partial correlations of tea and flavonoid intakes with lifestyle factors and nutrient intakes were computed to identify potential confounders.

The risk of myocardial infarction with tea intake was estimated by Cox regression analysis with adjustment for age and sex. Associations were obtained separately for total, nonfatal, and fatal myocardial infarction. Survival time was calculated as the number of days from entry into the study until the time of the first myocardial infarction, the time until death, or until 31 December 1997, whichever came first. Tea intake was first entered continuously into the survival model, forcing a linear relation. Subsequently, tea intake was classified on the basis of the frequency distribution of the variable, yielding categories of 0 mL (reference), 1–375 mL (median: 250 mL), and >375 mL (median: 500 mL). The relative risks (RRs) and 95% CIs were obtained by category of tea intake. The same procedure was followed to calculate RRs in tertiles of flavonoid intake (total of quercetin, kaempferol, and myricetin intakes); the RR of a first myocardial infarction was calculated according to 3 categories of flavonoid intake: <22.8, 22.8–32.9, and >32.9 mg/d.

The analyses of tea and flavonoid intakes were repeated in a multivariate model adjusted for age, sex, body mass index, smoking status (current, former, never), pack-years of cigarette smoking (ie, the average number of packs of cigarettes smoked per day x the number of years smoked) for current and former smokers, education level [low (primary education), intermediate (secondary general or vocational education), or high (higher vocational education, university)], and daily intakes of alcohol (0, >0–5, >5–10, >10–20, and >20 g/d), coffee (mL), polyunsaturated fat (g), saturated fat (g), fiber (g), vitamin E (mg), and total energy (kJ). Stratified analyses were performed according to sex. Data were also analyzed separately for current, former, and never smokers to examine in more detail the role of confounding by smoking. In addition, the interaction of tea or flavonoid intake with smoking in determining the risk of myocardial infarction was examined by adding interaction terms to the model.
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The possibility that preexisting illness, which could be related to dietary changes, influenced the risk estimates was examined in an analysis in which data from the first year of follow-up were discarded for all subjects. A total of 52 subjects with an early myocardial infarction were not included in this analysis. Finally, we investigated whether serum HDL or total cholesterol could be intermediary factors in the relation of tea intake with cardiac events by adding these variables to the survival model and examining the changes in risk estimates. Similarly, potential intermediary roles of blood pressure and diabetes mellitus were examined.

The study population comprised 1836 men and 2971 women with a mean (±SD) age of 67.4 ± 7.8 y; 84% of the men and 90% of the women were tea drinkers. The mean daily intake of tea in the total population was 371 ± 257 mL, or  3 cups. The mean intake of flavonoids was 28.6 ± 12.3 mg/d. The general characteristics of the study population by categories of tea intake are presented in Table 1 . After adjustment for age and sex, tea intake was significantly inversely associated with body mass index, smoking status, and serum total cholesterol and significantly positively associated with education level.

A significant association of tea with all dietary intakes was observed after adjustment for age, sex, and total energy. Intakes of flavonoids and tea were strongly correlated (r = 0.81, P < 0.001). The proportions of tea drinkers in consecutive tertiles of flavonoid intake (<22.8, 22.8–32.9, and >32.9 mg/d) were 69%, 95%, and 99%, respectively.

The study had a mean follow-up of 5.6 ± 1.3 y and consisted of 26733 person-years. The incidence of myocardial infarction was 8.3/1000 person-years in men (n = 1836 persons and 84 events) and 3.7/1000 person-years in women (n = 2971 persons and 62 events) free of myocardial infarction at baseline. Thirty subjects experienced a fatal myocardial infarction and 475 subjects died from other causes during follow-up. In the study of the age- and sex-adjusted linear association of tea drinking with incidence of myocardial infarction, a 8.2% risk reduction was observed per 100-mL increase in tea intake (P = 0.02; data not shown). After adjustment for body mass index, smoking status, alcohol intake, education level, and dietary factors, the association was attenuated to a 6.2% risk reduction per 100-mL increase in tea intake (P = 0.09).
The RRs of a first myocardial infarction by categories of tea intake are shown in Table 3 . The incidence of myocardial infarction was inversely associated with tea intake after adjustment for age and sex; the RR was 0.51 (95% CI: 0.30, 0.84) for intakes >375 mL/d ( 3 cups/d) compared with an intake of 0 mL/d.

After additional adjustment for body mass index, smoking status, pack-years of cigarette smoking, education level, and daily intakes of alcohol, coffee, polyunsaturated fat, saturated fat, fiber, vitamin E, and total energy, the association of tea intake with all incident myocardial infarctions was attenuated in the upper category of tea intake (RR: 0.57; 95% CI: 0.33, 0.98). Further adjustment for dietary intakes of riboflavin (mg/d), vitamin B-6 (mg/d), vitamin C (mg/d), ß-carotene (mg/d), bread (g/d), vegetables (g/d), and fruit (g/d) did not change the results. Tea drinking was related both to nonfatal and to fatal myocardial infarctions, but only the association with fatal events in the upper category of tea intake was significant (RR: 0.30; 95% CI: 0.09, 0.94).
The RRs of a myocardial infarction (fatal or nonfatal) by tea intake were no longer significant when the analysis was stratified by sex. In women, the RR was 0.71 (95% CI: 0.32, 1.60) for intakes  375 mL/d and was 0.46 (95% CI: 0.19, 1.10) for intakes >375 mL/d. In men, the RR was 0.76 (95% CI: 0.41, 1.40) for intakes  375 mL/d and was 0.61 (95% CI: 0.30, 1.26) for intakes >375 mL/d, but the interaction term of tea and sex was not significant. The inverse association of tea drinking with myocardial infarction was more pronounced in current smokers [n = 1114 and 38 events; RR of 0.58 (95% CI: 0.27, 1.24) and 0.47 (0.17, 1.47)] than in former smokers [n = 2000 and 72 events; RR of 0.74 (0.35, 1.56) and 0.50 (0.22, 1.14)] or never smokers [n = 1693 and 36 events; RR of 1.22 (0.28, 5.33) and 0.87 (0.19, 3.95)] in the mid and upper categories of tea intake, respectively.

The interaction term for tea intake and smoking status was not significant in the multivariate model. The reduction in risk of myocardial infarction with increasing tea intake remained essentially unchanged after the exclusion of data for 52 subjects who had a myocardial infarction or who died within 1 y of follow-up [multivariate RR: 0.77 (0.45, 1.30) and 0.59 (0.33, 1.06) in the mid and upper categories of tea intake, respectively].

Dietary flavonoids were nearly significantly related to the risk of myocardial infarction, with a 12.7% reduction in risk per 10-mg increase in daily flavonoid intake after adjustment for age and sex (P = 0.07; data not shown). Further adjustment for confounders attenuated the risk reduction to 9.0% per 10-mg increase in flavonoid intake, which was no longer significant. The RRs of myocardial infarction by tertiles of flavonoid intake are shown in Table 4 . For all incident cases of myocardial infarction, a nonsignificant inverse association was observed in the middle (RR: 0.74; 95% CI: 0.49, 1.11) and upper (RR: 0.76; 95% CI: 0.49, 1.18) tertiles of flavonoid intake. In a separate analysis of the risk of nonfatal and fatal myocardial infarctions in relation to flavonoid intake, a nearly significant association, was observed only for fatal events in a comparison of the middle (RR: 0.42; 95% CI: 0.17, 1.06) and upper (RR: 0.35; 95% CI: 0.13, 0.98) tertiles with the lower tertile.

An inverse relation of dietary flavonoid intake with incident myocardial infarction was observed in women in the middle (RR: 0.53; 95% CI: 0.28, 1.00) and upper (RR: 0.59; 95% CI: 0.31, 1.14) tertiles of intake, which was nearly significant. In men, however, dietary flavonoid intake was not associated with incident myocardial infarction in the middle (RR: 0.92; 95% CI: 0.54, 1.56) and upper (0.95; 95% CI: 0.52, 1.76) tertiles. The interaction term for flavonoid intake and sex was not significant in the multivariate model. A subgroup analysis according to smoking status yielded nonsignificantly different RRs of myocardial infarction by flavonoid intake (data not shown).
A repeat of the analyses of tea and flavonoid intakes after adjustment for serum HDL and total cholesterol, systolic and diastolic blood pressures, or diabetes mellitus did not change the results significantly, indicating no strong intermediary roles for these indexes.

We observed significant inverse associations of tea and flavonoid intakes with incident myocardial infarction in the general Dutch population. The reductions in risk were strongest for fatal events.

Tea drinking in Western populations is generally associated with a healthy lifestyle and diet. In the present study, tea intake was higher in lean, educated people who smoked less and consumed a relatively healthy diet. The risk reductions for myocardial infarction were attenuated after adjustment for lifestyle and dietary confounders, which indicates that diet and lifestyle explain part of the protective effect of tea. Although the observed associations were strong, residual confounding could not be excluded. Smoking was associated with tea and flavonoid intakes and is a strong risk factor for myocardial infarction. The association of tea intake, but not of flavonoid intake, with myocardial infarction was weaker in nonsmokers than in smokers.

This finding suggests that smoking, despite adjustment for smoking status and pack-years of cigarette smoking, caused some residual confounding of the risk estimates. An alternative explanation for the differences in RRs between smokers and nonsmokers is that smokers have a greater need for flavonoids (and other antioxidants) because of the vascular damage caused by smoking. The study lacked the power to examine separately the risk of fatal myocardial infarction with tea intake in categories of smoking.


Unfortunately, data on physical activity were not collected during the baseline survey of the Rotterdam Study; therefore, we could not adjust for it. However, we adjusted for total energy intake, which is closely related to energy expenditure, and lifestyle factors such as smoking and alcohol intake. Adjustment for these correlates of physical activity removed some of the confounding, but it is possible that residual confounding remained. Serum HDL-cholesterol, which is favorably affected by physical activity (31), did not differ significantly by categories of tea intake after adjustment for age and sex. Therefore, we believe that physical activity was not a strong confounder in our cohort. Prevalent illness should be taken into account when studying the effect of diet on incident disease or mortality because dietary changes resulting from clinical or subclinical disease could lead to biased risk estimates. For this reason, we excluded subjects with a history of myocardial infarction at baseline. Additional exclusion of subjects with a nonfatal myocardial infarction or fatal event within 1 y of follow-up yielded nonsignificantly different risk estimates.


Flavonoids have been shown to protect against the oxidation of LDL in vitro, to inhibit platelet aggregation, to reduce inflammatory processes, and to improve vascular function (6–17). Black tea contains substantial concentrations of the flavonols quercetin (10–25 mg/L), kaempferol (7–17 mg/L), and myricetin (2–5 mg/L) (26). Regrettably, we could not examine the potential cardioprotective effect of catechins and polyphenols, which are also abundant in tea (28, 29). In men in the Zutphen Elderly Study, tea drinkers had a risk of 5-y mortality from ischemic heart disease that was >50% lower than that of nontea drinkers (1), which is comparable with our findings. No association between tea intake and ischemic heart disease was observed in the Health Professionals Follow-up Study of men, who were on average 10 y younger than our study participants (4). Tea accounted for 25% of the flavonoid intake in the Health Professionals Study, whereas tea intake accounted for >50% of the flavonoid intake in our study. In the Caerphilly Study of Welsh men aged 45–79 y, no protective effect of tea against ischemic heart disease was observed (5). It was later suggested that residual confounding by socioeconomic status blurred the association of tea with ischemic heart disease in the Caerphilly Study (32).

Tea and flavonoid intakes were predominantly related to fatal myocardial infarctions; the relation with nonfatal events was weak or absent in our study. Also, in the Zutphen Elderly Study the RR of mortality from ischemic heart disease was stronger than that of incident myocardial infarction, which included nonfatal events (1). The Finnish study by Knekt et al (2) showed strongly reduced risks of mortality from ischemic heart disease in subjects with a high flavonoid intake. However, no such relation was observed in the Health Professionals Study, in which nonfatal myocardial infarction was the outcome of interest (4). Possibly, subjects with a fatal event had more severe atherosclerosis than did those with no fatal event. In the cohort of the Rotterdam Study, we showed a strong inverse association of tea intake with severe aortic calcification, whereas no association with mild atherosclerosis was observed (20).

Our findings suggest that the severity of underlying cardiovascular disease may modify the relation of flavonoids with coronary events. It is also possible that flavonoids (together with other antioxidants) reduce oxidative stress and prevent excess damage after ischemia, thereby increasing the chance of recovery from a myocardial infarction. Furthermore, flavonoids could be involved in thrombotic processes that may influence the severity of a coronary event (13, 14). Unfortunately, we cannot conclude from our observational data which of the above mechanisms, if any, accounted for the discrepant findings on fatal and nonfatal myocardial infarctions.

In our previous study of the relation between tea intake and aortic atherosclerosis in the Rotterdam Study, we observed a strong inverse relation in women (20). In the present study we observed a strong inverse relation between tea intake and incident myocardial infarction, and the relation was stronger in women than in men. For flavonoid intake, a strong relation with incident myocardial infarction was observed only in women, which raises the hypothesis that flavonoids act not only as antioxidants or antithrombogenic factors but possibly also as phytoestrogens. An estrogenic effect of kaempferol, present in tea, was shown previously in vitro (33). In the female participants of the Rotterdam Study, we found a positive association of tea drinking with prolactin secretion, which was used as a bioassay of estrogenic activity (34).

Another study in women showed a positive association of tea intake with bone mineral density, which is known to be strongly influenced by estrogenic activity (35). The structure of flavonoids shows similarities to that of isoflavones in soy (33, 36), for which beneficial cardiovascular actions have been reported (37). However, the flavonoids in tea are less potent estrogenic compounds than are isoflavones in vitro. More research is needed to assess whether the estrogenic activity of tea is biologically important to the human body.

In conclusion, our findings suggest a protective effect of tea and flavonoid intakes against myocardial infarction. The underlying biological mechanisms for this effect and the potential role of tea flavonoids in cardiovascular disease prevention deserve further study.

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7.         De Whalley CV, Rankin SM, Hoult JR, Jessup W, Leake DS. Flavonoids inhibit the oxidative modification of low density lipoproteins by macrophages. Biochem Pharmacol 1990;39:1743–50.[Medline]

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10.       Viana M, Barbas C, Bonet B, et al. In vitro effects of a flavonoid-rich extract on LDL oxidation. Atherosclerosis 1996;123:83–91.[Medline]

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12.       Hertog MG. Epidemiological evidence on potential health properties of flavonoids. Proc Nutr Soc 1996;55:385–97.[Medline]

13.       Pignatelli P, Pulcinelli FM, Celestini A, et al. The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide. Am J Clin Nutr 2000;72:1150–5.[Abstract/Free Full Text]

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15.       Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure-activity relationships. Biochem Pharmacol 1999;58:759–65.[Medline]

16.       Middleton E. Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol 1998;439:175–82.[Medline]

17.       Duffy SJ, Keaney JF Jr, Holbrook M, et al. Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation 2001;104:151–6.[Abstract/Free Full Text]

18.       Zhao X, Gu Z, Attele AS, Yuan CS. Effects of quercetin on the release of endothelin, prostacyclin and tissue plasminogen activator from human endothelial cells in culture. J Ethnopharmacol 1999;67:279–85.[Medline]

19.       Tomasian D, Keaney JF, Vita JA. Antioxidants and the bioactivity of endothelium-derived nitric oxide. Cardiovasc Res 2000;47:426–35.[Medline]

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21.       Hofman A, Grobbee DE, de Jong PT, van den Ouweland FA. Determinants of disease and disability in the elderly: the Rotterdam Elderly Study. Eur J Epidemiol 1991;7:403–22.[Medline]

22.       De Bruyne M, Kors J, Visentin S, Hoes A, Grobbee DE, van Bemmel J. Diagnostic interpretation of electrocardiograms in population-based research: computer program, research physician, or cardiologist? The Rotterdam Study. J Clin Epidemiol 1997;50:947–52.[Medline]

23.       Van Gent CM, van der Voort HA, de Bruyn AM, Klein F. Cholesterol determinations. A comparative study of methods with special reference to enzymatic procedures. Clin Chim Acta 1977;75:243–51.[Medline]

24.       Klipstein-Grobusch K, den Breeijen JH, Goldbohm RA, et al. Dietary assessment in the elderly: validation of a semiquantitative food frequency questionnaire. Eur J Clin Nutr 1998;52:588–96.[Medline]

25.       Anonymous. NEVO table Nederlands. (Nevo table. Dutch nutrient database.) The Hague: Voorlichtingsbureau voor de Voeding, 1993 (in Dutch).

26.       Hertog MGL, Hollman PCH, van de Putte B. Content of potentially anticarcinogenic flavonoids of tea infusions, wines, and fruit juices. J Agric Food Chem 1993;41:1242–6.

27.       Hertog MGL, Hollman PCH, van de Putte B. Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. J Agric Food Chem 1993;40:2379–83.

28.       Arts IC, Hollman PC, Feskens EJM, Bueno de Mesquita HB, Kromhout D. Catechin intake might explain the inverse relation between tea consumption and ischemic heart disease: the Zutphen Elderly Study. Am J Clin Nutr 2001;74:227–32.[Abstract/Free Full Text]

29.       Lakenbrink C, Lapczynski S, Maiwald B, Engelhardt UH. Flavonoids and other polyphenols in consumer brews of tea and other caffeinated beverages. J Agric Food Chem 2000;48:2848–52.[Medline]

30.       WHO. International statistical classification of diseases and related health problems. 10th rev. Vol 1. Geneva: WHO, 1992.

31.       Margolis S, Dobs AS. Nutritional management of plasma lipid disorders. J Am Coll Nutr 1987;8(suppl):S33–S45.

32.       Katan MB. Flavonoids and heart disease. Am J Clin Nutr 1997;65:1542–3.[Free Full Text]
33.       Miksicek RJ. Estrogenic flavonoids: structural requirements for biological activity. Proc Soc Exp Biol Med 1995;208:44–50.[Abstract]

34.       Geleijnse JM, Witteman JCM, Launer LJ, Lamberts SWJ, Pols HAP. Tea and coronary heart disease: protection through estrogen-like activity? Arch Intern Med 2000;160:3328–9 (letter).

35.       Hegarty VM, May HM, Khaw K-T. Tea drinking and bone mineral density in older women. Am J Clin Nutr 2000;71:1003–7.[Abstract/Free Full Text]

36.       Zand RS, Jenkins DJ, Diamandis EP. Steroid hormone activity of flavonoids and related compounds. Breast Cancer Res 2000;62:35–49.

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Received for publication November 28, 2000. Accepted for publication May 25, 2001.

 

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GRAPE SEED EXTRACT AND PINE BARK EXTRACT (PROANTHOCYANIDINS):

Grape Seed Extract
WebMD:  Heady Over Grapes?
Can the seeds heal? By  Laura Lane WebMD Feature  
         
Sept. 11, 2000 -- At 42, Linda Walsh of Buena Park, Calif., could hardly believe that age spots were spreading up her shins and down her feet. To make matters worse, her hair was beginning to fall out, her joints were becoming stiffer by the day, and fatigue weighed every step she took.
Then she discovered grape-seed extract.

Now, four years later, Walsh's skin is free of blemishes, her hair is lustrous and full, and there's a new bounce in her stride. "I feel good and I look five years younger than before," she says. For this transformation, Walsh gives credit to an extract taken from the seeds of ordinary grapes. She's so enthusiastic that she now sells the extract and other supplements full time.
Indeed, glowing testimonials from people like Walsh have made grape-seed extract one of the most popular supplements in the United States. In 1999, Americans spent $141 million on grape-seed products, a jump of 26% over the previous year, according to The Hartman Group, a market research firm.

So do grape seeds really work? The question is far from settled, but scientists aren't ready to rule out the possibility that they might. The key ingredient in grape seeds has shown promise against disease-causing chemicals in test tubes. And a few preliminary experiments in humans have produced intriguing results.

Super-Antioxidant
One reason it's not easy to weigh the claims for grape-seed extract is that much of the research is done by people with a stake in selling it. Many of the studies most often cited come from the laboratory of Debasis Bagchi, PhD, a Creighton University professor of pharmaceutical and administrative sciences who also works for grape-seed product maker InterHealth Nutraceuticals.

Bagchi has labored to show that a substance within grape-seed extract, oligoproanthocyanidin, or OPC, is a powerful antioxidant. Antioxidants disarm free radicals -- molecules that can damage DNA, cells, and tissues, eventually contributing to heart disease, cancer, and other illnesses. Because of its structure, one OPC molecule can neutralize several free radicals at once, while each molecule of better-known antioxidants like vitamins C and E can handle only one at a time, Bagchi says.

Putting It to the Test
In one experiment, Bagchi and his team placed OPC, vitamin C, and vitamin E in three separate test tubes filled with free radicals similar to those found in the body. After 15 minutes, the researchers found that OPC had knocked out up to 81% of the free radicals in its test tube. By comparison, vitamin C and E neutralized up to 19% and 44%, respectively. (See the February 1997 issue of the journal Research Communications in Molecular Pathology and Pharmacology.)

While such findings are promising, they don't prove that grape-seed extract can actually prevent or cure heart disease, cancer, or any other illness, says Harry Preuss, MD, of Georgetown University, who led the cholesterol study (which was partly funded by InterHealth Nutraceuticals). "The benefits are potentially there," he says. But in order to know how a human being's health is really affected over a long period of time, "You have to do these huge, huge studies." So far, no one has been willing to pay the cost of such a study.

Patching the Pipes
Nor has anyone funded a conclusive study on the other intriguing claim made for grape-seed extract: that it reinforces collagen and elastin, the bricks and mortar of blood vessels and other supportive tissues.

If it can achieve these effects, it could benefit people suffering from a wide range of diseases. For example, it might improve capillary resistance, the ability of capillaries to hold blood. People with diabetes and high blood pressure sometimes have such low capillary resistance that their blood leaks into the surrounding tissue, causing red spots (purpura) on their skin. In one study, published in the June 8-15, 1981, issue of the French journal Semaine des Hopitaux (Hospital Week), researchers found that 13 patients who took OPC experienced much higher capillary resistance than a group of 12 people who took a placebo.

But this research, too, is preliminary -- the study didn't show whether the patients' purpura or other symptoms improved. And a good diet might be just as effective, says Rita Redberg, MD, associate clinical professor of cardiology at the University of California, San Francisco. To avoid diseases of the heart and blood vessels, Redberg says, the surest approach is eating a low-fat, high-fiber diet and getting at least 30 minutes of exercise five times a week. "If you want to do these things and also take grape-seed extract, that's fine," Redberg says.

Or maybe not so fine, says Kedar Prasad, PhD, director of the Center for Vitamins and Cancer Research at the University of Colorado Health Science Center. Taking too much OPC, vitamin C, or other antioxidant, could -- theoretically at least -- add to your risk of cancer. That's because free radicals don't just damage healthy cells; they also act as a check on cancer growth. And some researchers worry that antioxidants may blunt the effects of radiation and chemotherapy used to treat cancer.

Such warnings remain hypothetical, though, and they aren't likely to sway the likes of Linda Walsh. She says that the supplement cured her son's allergies and may prevent her from suffering a heart attack like the ones that killed her mother at age 60 and her father at age 50. "People think I'm exaggerating," she says. "I'm just thankful that I found a product that helped."
Laura Lane, an associate editor at WebMD, has a master's degree in biological sciences from Stanford University. Her work has appeared in The Dallas Morning News, the Tufts University Health and Nutrition Letter, CNN Interactive, Healthy Living magazine, and Shape magazine.
2000 Healtheon/WebMD. All rights reserved.

MONDAY, April 14 (HealthScoutNews) --Moderately high amounts of grape seed extract may blunt salt-sensitive hypertension as well as plant estrogens do, says a University of Alabama at Birmingham study.

The finding may be important for women entering middle age because hypertension rates jump after they reach menopause.

The researchers wanted to determine if the polyphenols in grape seed extract could provide the same benefits as plant estrogens. Previous research found that plant estrogens from soy can reduce salt-sensitive hypertension in young, estrogen-depleted spontaneously hypertensive rats (SHR).

This study concluded that grape seed extract does reduce the hypertensive effects of a high salt diet in the rats to about the same degree as plant estrogens. That means that grape seed extract may be a useful supplement to control hypertension in postmenopausal women.
The findings were presented at the Experimental Biology meeting in San Diego, which runs from April 11 to 15.

SOURCE: American Physiological Society, news release, April 9, 2003
Copyright © 2003 ScoutNews, LLC. All rights reserved.



Grape seed extract lowers blood pressure
In another promising study presented during the annual American Physiological Society meeting, researchers from the University of Alabama in Birmingham reported that an extract of grape seed given to spontaneously hypertensive female rats whose ovaries had been removed caused a reduction in blood pressure comparable to that of plant estrogens or estradiol, one of the hormones provided with hormone replacement therapy. Blood pressure often rises after menopause in women presumably due to the decline in estrogens, the principle hormones made by the ovaries. Postmenopausal women have frequently used hormone replacement therapy to control hypertension and other unwanted menopausal effects, but the use of this therapy has recently been found to be associated with an increased risk of cardiovascular events and reproductive system cancers.

Previous research by the investigators uncovered a similar antihypertensive benefit from phytoestrogens derived from soy. In the current study, the researchers used three week old spontaneously hypertensive rats and surgically removed their ovaries to mimic menopause. The rats were provided with phytoestrogen-free diets containing 1 percent or 8 percent sodium chloride. Half of the rats received the addition of grape seed extract to their food. Predictably, the high (8 percent) salt diets greatly elevated blood pressure, however, the rats on this group who received grape seed extract experienced a much lower elevation. Rats on the 1 percent salt diet did not appear to be affected by grape seed extract. Like the estrogenic compounds, the extract did not produce any change in heart rate, showing a specific effect on blood pressure.

The findings suggest that a different mechanism than estrogen receptor activation may be the cause of the benefits of estrogen therapy in postmenopausal hypertension. The researchers believe that the polyphenols from grape seed extract may be useful as an antihypertensive for women who are postmenopausal.

Grape Seed Extract which is high in Oligomeric Proanthocyanidins (OPC’s or PCO’s) is powerful antioxidant which can reduce the damage done by free radicals, strengthen and repair connective tissue, and promote enzyme activity. OPC’s can also help moderate allergic and inflammatory responses by reducing histamine production.


ANTIOXIDANTS
Antioxidants are important protectors of health because they provide electrons that neutralize "free radicals"--molecules with unpaired electrons which have the power to cause degenerative and life-threatening diseases.

Free radicals are produced from normal oxygen metabolism within the body, and from exposure to certain chemicals, environmental pollutants, sunlight, radiation, burns, cigarette smoke, drugs, alcohol, viruses, bacteria, parasites, dietary fats, and more. The antioxidants known today are vitamins C and E, beta carotene, selenium, bioflavonoids and bioflavanols.

THE PCO BIOFLAVANOID COMPLEX
Bioflavanoids are natural plant components that strengthen and protect living tissue. "Proanthocyanidin" is one of the names used to describe a powerful bioflavonoid complex known as Procyanidolic Oligomers (PCO). "Pycnogenol" was the name originally given to this complex by Dr. Jacques Masquelier, the first to scientifically discover it and the first to patent an extraction process for it from the bark of maritime pine trees. "Pycnogenol" is now a trademarked name for PCO products extracted from pine bark.

PCO extracts have been scientifically studied and medically used in Europe since the 1950s. Scientifically documented, observed benefits include:

•          Enhanced capillary strength and vascular function, which helps the heart and decreases: PMS problems, bruising, edema from injury or trauma, varicose veins, leg swelling and retinopathy.
•          Enhanced immune resistance.
•          Increased peripheral circulation, improving vision.
•          Reduced adverse allergic and inflammatory responses.
•          Reduction in skin aging and loss of elasticity.
The PCO bioflavanoid complex was recently discovered to be 20 times more potent than vitamin C and 50 times more potent than vitamin E as an antioxidant. The advantages of PCO include:
•          It is bioavailable and immediately absorbed from the stomach into the bloodstream.
•          It is distributed to virtually every organ and tissue, and remains in the body for up to 72 hours.
•          Not only does it neutralize free radicals themselves, but it also conserves and regenerates vitamins C and E. Vitamin E is a powerful free radical scavenger, but it is quickly used up. PCO and vitamin C work synergistically to regenerate vitamin E.
•          PCO is one of the few antioxidants that crosses the blood/brain barrier to protect neural tissue.
•          PCO extracts have been proven to be completely safe.

SOURCES OF PCO
The PCO complex is found in many types of foods, but usually only in extremely small amounts. Some of the best sources of PCO are seasonal fruits such as grapes, blueberries, cherries and plums. The PCO is found mainly in the peels, skins, or seeds. Food processing and storage is detrimental to PCO availability.

The PCO bioflavanoid complex can also be found in the barks of the lemon tree and the Landis pine tree, as well as the leaves of the hazelnut tree. The highest known concentration (95%) of the PCO complex is found in grape seeds, and the second-highest (80-85%) in pine bark.

Anti-Inflammatory
One of the first benefits of PCO observed by doctors as early as 1950 was its anti-inflammatory action. This is produced in part by the antioxidant effect, and by inhibiting the release and synthesis of certain compounds that promote inflammation, such as histamine, serine protease, prostaglandins, and leukotrienes. PCO selectively binds to the connective tissue of joints, preventing swelling, helping heal damaged tissue, and lessening pain.

Anti-Histamine
The anti-histamine action of PCO is mediated by an inhibiting effect on the enzyme histidine decarboxylase which is responsible for the production of histamine. This is enhanced by PCO's ability to block hyaluronidase, the enzyme that facilitates the release of histamine into body tissues.

Anti-Allergic
This action is related to the antihistamine effect, as well as PCO's ability to strengthen cell membranes of basophils and mast cells, which contain the allergic chemicals, thus preventing over-reaction or hypersensitivity to pollens and food allergens. Many allergy sufferers have reported significant relief using grape seed extract.

Anti-Ulcer
Ulcers induced or aggravated by stress are known to be related to excessive secretion of histamine in the stomach lining. PCOs help heal ulcers by reducing histamine secretion and by binding to and protecting connective tissue in mucous membranes.

Cardiovascular Disease
Experimental studies have recently discovered that oxidation of LDL cholesterol is a key factor leading to hardening of the arteries and heart disease. The antioxidant effect of Vitamin E has been shown to be a potent inhibitor of this oxidation—and PCO has been shown to be 50 times more potent than vitamin E. PCO has also been shown to prevent the stickiness of blood platelets that can lead to blood clots and strokes. Patients taking grape seed extract PCO have reported reduced blood pressure and cholesterol levels.

Recent studies have shown that drinking wine has a protective effect against heart disease (considered the solution to the mystery of how the French population can indulge in a high-fat diet and have one of the world's lowest incidences of heart disease). And in February of 1995, a study published in "Circulation," the journal of the American Heart Association, showed that six glasses of grape juice were as effective as two glasses of wine in preventing heart disease. This study offers convincing evidence that PCO from grapes, rather than the alcohol, provide wine's protective benefits to the circulatory system.

Cancer Prevention
Although not a cure for cancer, experimental evidence has been available for a long time showing that antioxidants greatly reduce the incidence of all types of cancer. One study showed that the risk of developing cancer is 11.4 times greater for those with low levels of the antioxidants vitamin E and selenium. PCO is a more potent antioxident, and also protects cellular DNA from oxidative damage and cell mutations which can lead to cancer.

Teeth and Gums
Dentists and their patients have reported that PCO provides healing and preventive benefits to the teeth and gums, evidently through its anti-inflammatory effects, free radical deactivation, and connective tissue protection.

Eyes
Clinical studies have shown that antioxidants can halt cataract progression. PCO has a strong affinity for the portion of the retina that is responsible for visual acuity. It prevents free radical damage and reinforces the collagen structures of the retina. In clinical trials of patients with various types of retinal disease, including macular degeneration, all patients given PCO showed significant improvement following therapy. Health professionals monitoring the effects of PCO have reported that it also has helped in the prevention and treatment of glaucoma.

Skin Care
PCO products help protect the skin from ultraviolet radiation damage that leads to wrinkles and skin cancer. Because it stabilizes collagen and elastin, PCO can help improve the elasticity and youthfulness of the skin. PCO strengthens the connective tissue of the skin and fat chambers. People taking grape seed extract PCO have noticed that it helps tonify their skin and reduce cellulite, stretch marks, and old scars. There is speculation that cellulite may be a sign of bioflavanoid deficiency.

Nervous System
Some physicians have reported that patients with multiple sclerosis (MS) have improved while taking PCO. MS is a syndrome of progressive destruction and hardening of the myelin sheath that surrounds the nerves. Current research indicates that MS may be caused by an allergic or autoimmune reaction. Many studies have demonstrated that patients with MS have reduced activity levels of the antioxidant enzyme glutathione peroxidase.

The ability of PCO to reduce the progressive symptoms of MS may be due to its potent antioxidant and anti-allergic qualities. Plus, PCO has the ability to cross the blood-brain barrier, where it may protect the brain's nervous tissue from oxidation. This effect may explain why patients taking PCO often report improved mental clarity.

Lungs
Asthma and emphysema have also been found to benefit from the use of PCOs. Asthma is largely caused by an allergic reaction within the bronchial tubes that leads to bronchial constriction and excessive mucous excretion. Due to its ability to inhibit histamine and other inflammatory chemicals, PCO has been found effective in the treatment of asthma.

Grape seed extract PCO has also been found to reduce the coughing, wheezing, weakness, mucous and recurring respiratory infections usually associated with emphysema. Apparently, PCO reduces the inflammation and damage to the air sacs of emphysema patients.

Grape-seed extract has healing effect
By Holly Wagner, Research Communications

Grape-seed extract may help skin wounds heal faster and with less scarring, a new study suggests.

The extract seemed to aid wound healing in two ways: it helped the body make more of a compound used to regenerate damaged blood vessels, and it also increased the amount of free radicals in the wound site. Free radicals help clear potentially pathogenic bacteria from a wound.

In two related experiments, researchers tested the effects of grape-seed extract on mice and on human skin cells. It's the first evidence suggesting that a natural extract could have such a profound effect on wound healing, said Chandan Sen, the study's lead author and the director of the Laboratory of Molecular Medicine at Ohio State's Heart and Lung Research Institute.

"We saw the healing effects grape-seed extract had on wounds from day one," said Sen, who is also an assistant professor of surgery. "It seemed to enhance the formation of epidermal tissue as well as the deposition of connective tissue."

The researchers treated skin wounds on mice with a topical formulation of grape seed proanthocyanidin extract (GSPE). Proanthocyanidin, one of the main ingredients in grape-seed extract, is thought to be a potent antioxidant. But in a wound site, which is rich in free radicals, the extract assumes some pro-oxidant properties.

The study appears in a recent issue of the journal Free Radical Biology and Medicine.

Each of nine mice in the study was given two small puncture wounds on its back. The researchers applied GSPE to one of the wounds, and covered the other with saline solution as a control. Otherwise, the wounds were left to heal naturally.

The animals were euthanized five days after they were wounded. A small area of skin -- 1 to 1.5 millimeters -- was excised from the edges of the treated and untreated wounds. The researchers looked for signs of enhanced healing in the GSPE-treated samples, and compared these samples to the healing patterns of the saline-treated tissue.

"The skin treated with grape-seed extract was further along in the healing process compared to the saline-treated tissue," Sen said. "The extract-treated skin showed signs of healing faster and the newly formed tissue was denser, meaning that its structure was stronger."

The researchers saw increased levels of VEGF, the compound that helps the body rebuild blood vessels. In previous research, Sen and his colleagues found that GSPE helped turn on the gene responsible for initiating the making of VEGF.

In a related experiment, the researchers also treated human skin cells with GSPE, finding that the extract helped the laboratory-grown cells produce more VEGF.

"More VEGF means blood vessels will form faster and that more nutrients will be carried by the blood to regenerate damaged tissue," Sen said.

In addition to helping blood vessels regenerate, GSPE also seemed to increase free radical levels at the wound site. It may seem odd that an antioxidant could help oxidation -- the formation of free radicals -- flourish.

"Excessive amounts of free radicals are damaging," Sen said. "But in controlled amounts, they help the body function. And skin wounds are rich in free radicals," he said. "There was a longer-lasting free radical effect in the wounds that had been treated with grape-seed extract. We think that's partly why these wounds healed faster and better."

While grape-seed extract is good news for wounded tissue, topical grape-seed extract isn't sold commercially. And consumers shouldn't expect to get the same wound-healing benefits from taking grape-seed extract in vitamin form, Sen said.

"Taken orally, the extract functions like an antioxidant," he said. "But in a wound, where free radicals are abundant, that proanthocyanidin assumes pro-oxidant behavior."

 

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PROANTHOCYANIDINS
Proanthocyanidins: As antioxidants, Proanthocyanidins have been shown to be 20 times more potent than Vitamin C and 50 times more potent than Vitamin E on a cellular level. An important supplement, the proanthocyanidins found in pine bark and grape seed extract work directly to help strengthen all the blood vessels and improve the delivery of oxygen to the cells. Doctor recommended as anti-oxidants, they have become increasingly more important as our environment deteriorates through the introduction of toxins from pollution.

While often considered a recent discovery, proanthocyanidins, a highly specialized group of bioflavonoids, have been extensively studied since the late 1960's for their powerful vascular wall strengthening properties and free radical scavenging activity. Proanthocyanidins are one of the most potent free radical scavengers known, possessing an antioxidant effect up to 50 times more potent then vitamin E and up to 20 times more powerful then vitamin C. Proanthocyanidins also have an affinity for cell membranes, providing nutritional support to reduce capillary permeability and fragility. Although bioflavonoids are widespread in nature, the powerful proanthocyanidin compound is most abundant and available from the bark of the maritime pine and in grape seeds, or pips.

Bilberry extract contains anthocyanidins with visual and vascular enhancing properties. Bilberry reduces visual fatigue and improves light to dark adjustment through its affinity for the rhodopsin-opsin system, the pigment system which mediates both light and dark vision and visual adaptation to dimly lit spaces. In addition, the extract also has potent antioxidant activity, promoting the retina's own enzymatic antioxidant defenses.

In the vascular system the antho-cyanidin extract supports the integrity of vascular walls by increasing vitamin C levels within cells, decreasing the permeabilizing effect of certain proteolytic/lysosomal enzymes, stabilizing cell membranes, and stimulating the synthesis of collagen and connective ground substance tissue. Billberry offers a safe and natural way to enhance the strength and function of the visual and vascular system.

Grape pips (seeds) are a potent source of proanthocyanidins, or pycnogenols. This grape pip extract contains 92-95% pycnogenols by weight. Jacques Masquelier, Ph.D., who pioneered proanthocyanidin research and coined the term "pycnogenol," used the grape seed extract in his second phas of proanthocyanidin ivestigation.

The term "pycnogenol" originally denoted the generic proanthocyanidin extracts. However, it is now a registered trademark name referring specifically to the maritime pine extract. Pycnogenol contains a minimum of 85% pycnogenols by weight. The maritime pine was the original source of proanthocyanidins studied and researched by Jacques Masquelier, Ph.D.

This is a statement of nutritional support. This statement has not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure or prevent disease.

What do they do? Proanthocyanidins—also called “OPCs” for oligomeric procyanidins or “PCOs” for procyanidolic oligomers—are a class of nutrients belonging to the flavonoid family. Proanthocyanidins have antioxidant activity and they play a role in the stabilization of collagen and maintenance of elastin—two critical proteins in connective tissue that support organs, joints, blood vessels, and muscle.1 2 Possibly because of their effects on blood vessels, proantho-cyanidins have been reported in double-blind research to reduce the duration of edema after face-lift surgery from 15.8 to 11.4 days.3 In very preliminary research, proanthocyanidins were reported to have anti-mutagenic activity (i.e., to prevent chromosomal mutations).4

Proantho-cyanidins have been shown to strengthen capillaries in double-blind research using as little as 100 mg per day.5 In another double-blind trial, French researchers reported that women with chronic venous insufficiency had reduced symptoms using 150 mg per day.6 In another French double-blind trial, supplementation with 100 mg taken three times per day, resulted in benefits within four weeks.7

Proanthocyanidins (200 mg per day for five weeks) have improved aspects of vision (visual performance in the dark and after exposure to glare) in healthy people.8 9 A product that is high in proanthocyanidins has been shown to prevent and reverse abnormal blood clotting in smokers.10

Where are they found? Proanthocyanidins can be found in many plants, most notably pine bark, grape seed, and grape skin. However, bilberry, cranberry, black currant, green tea, black tea, and other plants also contain these flavonoids. Nutritional supplements containing

proanthocyanidins extracts from various plant sources are available, alone or in combination with other nutrients, in herbal extracts, capsules, and tablets.

Who is likely to be deficient? Flavonoids and proanthocyanidins are not classified as essential nutrients because their absence does not induce a deficiency state. However, proanthocyanidins may have many health benefits, and anyone not eating the various plants that contain them would not derive these benefits.

How much is usually taken? Flavonoids (proanthocyanidins and others) are a significant source of antioxidants in the average diet. Proanthocyanidins at 50–100 mg per day is considered a reasonable supplemental level by some doctors, but optimal levels remain unknown.

Are there any side effects or interactions? Flavonoids, in general, and proanthocyanidins, specifically, have not been associated with any consistent side effects. As they are water-soluble nutrients, excess intake is simply excreted in the urine.

At the time of writing, there were no well-known drug interactions with Proanthocyanidins.

References:
1. Mitcheva M, Astroug H, Drenska D, et al. Biochemical and morphological studies on the effects of anthocyans and vitamin E on carbon tetrachloride induced liver injury. Cell Mol Bio 1993;39:443–8.

2. Maffei F, Carini M, Aldini G, et al. Free radical scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action. Arzneimittelforschung 1994;44:592–601.

3. Baroch J. Effect of Endotelon in postoperative edema. Results of a double-blind study versus placebo in 32 female patients. Ann Chir Polast Esthet 1984;29:393–5 [in French].

4. Liviero L, Puglisis E. Antimutagenic activity of procyanidins from vitis vinfera. Fitother 1994;65:203–9.

5. Dartenuc JY, Marache P, Choussat H. Resistance Capillaire en Geriatrie Etude d’un Microangioprotecteur. Bordeaux Médical 1980;13:903–7 [in French].

6. Delacroix P. Etude en Double Avengle de l’Endotelon dans l’Insuffisance Veineuse Chronique. Therapeutique, la Revue de Medicine 1981;27–28 Sept:1793–802 [in French].

7. Thebaut JF, Thebaut P, Vin F. Study of Endotelon in functional manifestations of peripheral venous insufficiency. Gazette Medicale 1985;92:96–100 [in French].

8. Corbe C, Boissin JP, Siou A. Light vision and chorioretinal circulation. Study of the effect of procyanidalic oligomers. J Fr Ophtalmol 1988;11:453–60.

9. Boissin JP, Corbe C, Siou A. Chorioretinal circulation and dazzling; use of procyanidolic oligomers. Bull Soc Ophtalmol Fr 1988;88:173–4, 177–9 [in French].

10. Puetter M, Grotemeyer KHM, Wuerthwein G, et al. Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol. Thromb Res 1999;95:155–61.

 

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RED GRAPE SKIN EXTRACT:

“Red wine polyphenols, in the absence of alcohol, reduce lipid peroxidative stress in smoking subjects.”

Abu-Amsha Caccetta R, Burke V, Mori TA, Beilin LJ, Puddey IB, Croft KD.
Department of Medicine (Royal Perth Hospital), The University of Western Australia and The West Australian Heart Research Institute, Perth, Western Australia, Australia.

Phenolic compounds in red wine can exert antioxidant effects on in vitro lipoprotein oxidation. This has led to speculation that red wine consumption mediates unique anti-atherosclerotic effects compared to other alcoholic beverages. However, studies assessing the effects of red wine consumption on lipoprotein oxidation ex vivo have not been conclusive. The recent identification of the F2-isoprostanes as oxidative products of arachidonic acid has provided a reliable measure of in vivo lipid peroxidation. This randomized trial investigated changes in plasma and urinary F2-isoprostane concentrations following red wine, white wine, or dealcoholized red wine consumption in humans.

Eighteen male smokers consumed, in random order, red wine, white wine, or dealcoholized red wine, for two weeks with one week washout between beverages. Plasma and urinary F2-isoprostane concentrations were measured before and after each beverage. Serum gamma-glutamyl transpeptidase (gamma-GT) and urinary 4-O -methylgallic acid were measured as markers of alcohol consumption and phenolic acid absorption, respectively. Plasma F2-isoprostanes (p < .05) decreased significantly with dealcoholized red wine but not with the alcohol-containing beverages. Urinary excretion of F2-isoprostanes showed a similar trend. gamma-GT decreased significantly with dealcoholized red wine and increased with both alcohol-containing beverages (p < .01). Urinary excretion of 4-O-methylgallic acid increased significantly (p < .001) in the 24 h urine samples following red wine or dealcoholized red wine ingestion, but not with white wine. Serum urate increased and beta-carotene decreased with both alcoholic beverages relative to dealcoholized red wine.

There was no change in the antioxidants alpha- and gamma-tocopherol or vitamin C with any of the beverages. The results suggest tha