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Antixoidant in red wine, berries, and dark chocolate shows no benefit says study

A new study, "Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults," published online May 12, 2014 in JAMA Internal Medicine shows that the antioxidant, resveratrol found at low doses in berries, red wine, and dark chocolate isn't so healthy after all and doesn't lengthen your lifespan, according to the latest news reports. But the study didn't look at resveratrol supplements at specific, tailored doses on humans or even on mice.

Antixoidant in red wine, berries, and dark chocolate shows no longevity benefit says study.
Photo by Matej Divizna/Getty Images

You may wish to checkout the May 13, 2014 CNN news article, "Antioxidant in red wine has no benefit at low doses." What scientists are referring to is resveratrol, not as a supplement, because the jury is still out on supplements and longevity when it comes to resveratrol, but simply to drinking red wine and eating dark chocolate. You also can read the May 13, 2013 Forbes article, "Are Red Wine And Chocolate Not So Healthy After All?" The big picture here is the scientists looked at resveratrol in food such as berries, red wine, and dark chocolate. They didn't study the effects of resveratrol supplements at different doses on people. You also may wish to check out the WebMD article, "Resveratrol in Red Wine Not Such a Health-Booster?"

It's low-doses of resveratrol as found in food or wine that has been found not to improve longevity. But the study focuses on levels of resveratrol naturally occurring in food and wine, not in resveratrol supplements.

Scientists only looked at the relationship between resveratrol levels and health outcomes occurring naturally in foods and wine that are thought to be related to resveratrol, such as cancer, and heart disease, and lifespan

Even though the study found no relationship between the resveratrol in the foods and health, the question remains what other foods did the people eat, for example lots of white flour, what type of fats, or the amount of sugar in their diet? A few decades ago, various scientists wrote about the “French paradox," whereby people in France consumed moderate levels of red wine and happen to have lower levels of heart disease even after eating a lot of saturated fat. But was the lower levels of heart disease related to the genetic components of the people rather than to their diet? Take cholesterol, for example. If you don't have enough (inherited) cholesterol receptors on your liver that you inherited, how is the cholesterol going to be removed from your blood before it gets deposited and calcified in your arteries?

Some studies have shown that light to moderate alcohol consumption does in fact correlate with healthier hearts. The new study does not contradict these conclusions. If health is about a specific dose, not too high, and not too low of resveratrol, in other studies, researchers at Harvard Medical School and the National Institutes of Health identified a specific chemical in red wine – resveratrol – that seems to significantly delay the effects of aging in mice, when given in very high doses.

If you read the CNN article, it mentions that currently, Americans spend some $30 million per year on resveratrol supplements, even though there have been no long-term studies in humans to measure resveratrol’s effect on longevity. In the latest study from Johns Hopkins University, the amount of resveratrol studied came from the chocolate and red wine in the diets of the study's participants. These people ate berries, another source of resveratrol, dark chocolate, and a moderate amount of red wine. The amount of resveratrol in people's foods is very much less than what was fed to the mice in the experiments where the mice were fed resveratrol supplements.

Is resveratrol's effects dose specific?

Take too much and there's a change in one of your liver enzymes. You need to know what's the dose that is best for you, tailored to your body's responses to resveratrol, the supplement. One resveratrol capsule, for example could be the same as drinking hundreds of glasses of red wine, which nobody does in a day. So that's where the study is questioned by numerous consumers.

On the other hand, the study had a huge cohort. It was long term, and it looked at dietary resveratrol levels, not resveratrol supplements. That study didn't show people lived any longer eating foods that naturally contain resveratrol such as berries, dark chocolate, or red wine. But the study didn't include the benefits of eating grapes on certain ailments such as osteoarthritis.

A study that shows resveratrol influences lifespan would need a group of participants with low, unpredictable levels of resveratrol from their food compared to another group with a standardized dose of resveratrol supplements. Then there's the factor of whether the people would be absorbing the resveratrol or whether the dose was too high and changed the enzymes in the liver. For more information, check out the news article, "Red wine and dark chocolate won't save your life."

Other studies tout the affects of resveratrol supplements on lab animals

Scientists know that if you take more than 300 mg of resveratrol, it inhibits an enzyme in the liver. The May, 2010 issue of Dr. Sherry Rogers' Total Wellness newsletter has a "resveratrol warning" on page 8, basically, there are still unanswered research questions.

Only scientists don't know as yet what purpose that liver enzyme has that the resveratrol is turning off. Some people take high doses of resveratrol without knowing what it's doing and how effective it is at various doses. Even at lower doses, resveratrol can turn off the adrenal or 'stress' gland and use up nutrients that your body uses to detoxify itself.

The word 'detox' has become a buzz word that some doctors tell patients to be aware of so when they hear the word, their knee-jerk reaction is to think 'quack.' But what detox actually means is when your body gets rid of toxic substances such as mercury and lead by itself.

That it is cleanses itself, using the vitamin C and other nutrients already in your body from food. Think in terms of how your body cleansed itself before the days of vitamin and mineral supplements. That's what the word 'detox' actually means--a cleansing process your body uses.

Regarding resveratrol, check out the study, "Phytoestrogen resveratrol suppresses steroidogenesis by rat adrenocortical cells by inhibiting cytochrome P450 c21-hydroxylase." The authors are Supornsilchai V, Svechnikov K, Seidlova-Wuttke D, Wuttke W, Söder O, published in Hormone Research in Pediatrics, 64:280-86, 2005. (Pediatric Endocrinology Unit, Q 2:08, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden.)

A Swedish study looked at the effects of resveratrol on rats. But rats are used in scientific studies to see how a substance reacts also with humans, since the genes are not as far apart as you'd believe

The main point of the resveratrol study that you should be aware of is that resveratrol is a phytoestrogen. As a phytoestrogen, it's going to act like a phytoestrogen in your body. The phytoestrogen resveratrol is found in grapes, mulberries and peanuts, all of which are consumed regularly by humans.

Resveratrol is also used in chemotherapy against cancer and aging and as a cardioprotectant. The aim of the present study had focused on characterizing the effects of resveratrol on rat adrenal steroidogenesis and to study the underlying mechanism.

If you're curious about how the scientists tested the resveratrol, they began by isolating the adrenocortical cells from the adrenal glands of normal male rats (in vitro) and from male rats administered resveratrol in their diet for 12 weeks (ex vivo).

No changes in cell viability or morphology were caused by exposure to resveratrol in both ex vivo and in vitro experiments. So basically, the study concluded that resveratrol suppresses corticosterone production by primary rat adrenocortical cell cultures in vitro and ex vivo by inhibiting cytochrome P450 c21-hydroxylase.

The big picture for us humans is that we have to consider, do we want our corticosterone production suppressed? And do we want our cytochrome inhibited?

If these natural functions are inhibited, what happens to the rest of our body--our cells, organs, and blood? Is it good or bad to have something in our body's normal function suppressed or inhibited? Now the question remains, does the rat experiment transfer over to humans?

Will the same situation happen in people? What happens when and if the adrenal or stress gland might be turned off? How can we know it will happen in humans because it happened in rats? Are the genes pretty much the same at that basic level? And what type of detox nutrients will the resveratrol use up?

Those are the types of questions you have to ask when you're told to take resveratrol to increase your life span. You want the big picture--more facts. And how much should you take? If only 20 mg is effective, why are people being sold bottles of 250 mg of resveratrol when scientists know at 300 mg one of your liver enzymes is inhibited? Think about it.

As yourself, with all the various brands of resveratrol, how do you find out which sources are best? Is resveratrol surrounded by too much marketing? Where is the health information on side effects made available to the average consumer?

Is resveratrol on a marketing bandwagon ever since one company had been features on the television news program, 60 Minutes several years ago? Where can you find the information in plain language about what resveratrol can do in what doses?

On the other hand, check out the 2006 study reported in the Harvard Medical School newsletter article of how resveratrol extended the life span of obese mice, "Small Molecule Increases Lifespan and 'Healthspan' of Obese Mice."The resveratrol mimicked caloric restriction. The article reported, "After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet in mice."

You also could check out the site of the National Institute on Aging's Laboratory of Experimental Gerontology, Aging, Metabolism, and Nutrition Unit. Basically, when it comes to resveratrol, continue research is required so that the public as well as scientists can better understand resveratrol's roles and the best applications for it.

UC Davis studies the health benefits associated with a variety of berries, fruits, vegetables, and specific plant foods. Latest scientific studies on how nutrition influences longevity genes currently focuses on a plant extract related to resveratrol called pterostilbene, pronounced terro-STILL-bean. Basically, pterostilbene is extracted from blueberries, grapes, and also the bark of a tree that grows in India called the Kino.

UC Davis also studied how resveratrol mimicks caloric restriction

You also could check out the site of the National Institute on Aging's Laboratory of Experimental Gerontology, Aging, Metabolism, and Nutrition Unit. Basically, when it comes to resveratrol, continue research is required so that the public as well as scientists can better understand resveratrol's roles and the best applications for it. Also see, UC Davis M.I.N.D. Institute.

How limited are researchers' knowledge of what's helpful and what's subtoxic when it comes to taking polyphenols? In the latest study of the health effects of polyphenols, there were concerns with the work on cell uptake of quercetin and resveratrol.

Several years ago, in the Sacramento-Davis area, one of the results of a UC Davis study on resveratrol, a polyphenol, was a reduced incidence of diabetes in the mice studied. In humans, high calorie diets usually mean increased glucose and increased insulin levels that may lead to diabetes or frequent high-glucose (sugar) spikes.

Primary adipocytes were incubated with the polyphenols, but it is not clear whether or not the concentrations used were subtoxic. So as research continues, would you keep taking your resveratrol and quercetin supplements? Or would you try to get as polyphenols from fruits?

According to a December 23, 2010 news article from the Boston University Medica Center, "Study on effects of resveratrol and quercetin on inflammation and insulin resistance," a new study on the effects of resveratrol and quercetin on inflammation and insulin resistance opened up the question of how phytochemicals work in the human body to stop inflammation.

The researchers looked at resveratrol and quercetin from a clinical point of view, to study the role of phytochemicals acting as antioxidants and anti-inflammatory agents

Can resveratrol and quercetin from foods be extremely important in inflammation-associated chronic conditions such as cardiovascular disease, diabetes, and cancer? Quercetin and resveratrol may indeed play an important role in this regard, according to the latest study. These phytochemicals from plants need to be investigated further to establish the clinical importance of natural dietary compounds in the prevention of chronic degenerative conditions.

A study was carried out to examine the extent to which quercetin and trans-resveratrol (RSV) prevented inflammation or insulin resistance in primary cultures of human adipocytes treated with tumor necrosis factor-a (TNF-a)—an inflammatory cytokine elevated in the plasma and adipose tissue of obese, diabetic individuals.

Cultures of human adipocytes were pretreated with quercetin and trans-RSV followed by treatment with TNF-a. Subsequently, gene and protein markers of inflammation and insulin resistance were measured.

The authors report that quercetin, and to a lesser extent trans-RSV, attenuated the TNF-a–induced expression of inflammatory genes such as interleukin (IL)-6, IL-1b, IL-8, and monocyte chemoattractant protein-1 (MCP-1) and the secretion of IL-6, IL-8, and MCP-1.

Forum members were concerned about certain aspects of the study, especially the extrapolation of in vitro results to in vivo situations. The in vitro conditions the authors describe are minimally representative of an in vivo condition.

In vivo, after consumption of quercetin or resveratrol, these compounds undergo extensive metabolism, leading to glucuronidated, sulphated or methylated compounds. In a previous study, quercetin 3-glucoside was transformed to 3,4-dihydroxyphenylacetic acid, acetate and butyrate in cells from human gut; only 3'-methylquercetin has been detected in human plasma, present at a concentration of 0.1 to 0.2 µM after 3 h. The authors of the current paper are using concentrations up to 60 µM, concentrations which have not been found in vivo.

In a study on resveratrol and quercetin, most researcher's current knowledge is limited about local concentration of the molecules scientists are studying in subcellular compartments, their interaction with alternative targets, and eventually their transformation into products that could be more or less active on a given specific pathway.

The real difficult and important issue is the identification of a reasonable convergence -- if not agreement -- between data originating from extremely distant approaches. In this case, the notion that metabolic diseases are related to a homeostatic imbalance in adipose tissue, linked to a different redox status, linked to activation of specific pathways, and that different redox sensitive polyphenols do have a protective effect, encompasses the evidence produced by extremely distant approaches.

If you look at the December 23, 2010 news article, "Study on effects of resveratrol and quercetin on inflammation and insulin resistance," you can note that contributions to that critique by the International Scientific Forum on Alcohol Research were provided by the following members: David Vauzour, PhD, Dept. of Food and Nutritional Sciences The University of Reading, UK. But what's happening in the Sacramento area regarding the study of resveratrol?

In the Sacramento-Davis regional area, UC Davis studies resveratrol

Several years ago, Biotivia provided high quality resveratrol to researchers in the Sacramento/Davis area at the University of California, Davis, Albert Einstein Medical School, the Canadian Health Ministry and many other researchers, either at no charge or at a large discount for their human trials, according to the diet.blog.com forum posting under the article, "Fountain of Youth or Waste of Money."

Where is the data on human patients? See the January 8, 2008 Reuters ( Biotivia news) resveratrol news article, "Resveratrol-Like Drug Works in Humans--Sirtris." Also see the UC Davis article, "Resveratrol improves health and survival of mice on a high-calorie diet."

One of the results of the UC Davis study was a reduce incidence of diabetes in the mice studied

In humans, high calorie diets usually mean increased glucose and increased insulin levels that may lead to diabetes. That article and blog forum also gives some reasons why human trials aren't progressing fast enough on the effects of resveratrol on aging. There will be a human study conducted by the National Institute on Aging - but the results won't be available for a couple of years, according to that article. Will the complex human body produce the same results as test tube studies? Also see, Nutrition Action Healthletter, March, 2009.

If you're familiar with your adrenal gland, you'll realize that it's also sometimes called the stress gland. The biochemical experiments are still being done with resveratrol to answer some of the questions about how safe is it and what's a dose that's safe and still works.

How scientists in various universities discovered this plant extract, resveratrol is by examining Ayurvedic medicine, the folkloric medical treatments used in India based on plant extracts. The purpose of looking at these plant extracts is that when tested on animals such as mice, the blueberry and grape extracts used in laboratories appears to make the mice live longer by switching on their longevity gene tags in such a way that it imitates caloric restriction. Most veterinarians know that by restricting calories, but not essential nutrients/nutrition, animals live longer when they eat better while eating less.

If you look at pterostilbene and resveratrol, you'll notice that both compounds have similar structures

They have similar, but not exactly the same functions. But when you combine pterostilbene with resveratrol, the both together work exceptionally well to simulate certain beneficial conditions produced by caloric restriction. Remember that caloric restriction is not fasting or starving. The person or animal gets the essential nutrition with fewer calories.

What scientists found was that pterostilbene and resveratrol taken together or combined in one supplement translate into more benefits that by taking resveratrol by itself. You can check out all the scientific studies listed at the end of the latest article in the Special Winter Edition of Life Extension Magazine (2009), "The 'Other' Resveratrol: A Novel Method to Simulate the Genetic Effects of Caloric Restriction," by Tiesha D. Johnson, RN, BSN.

According to that article, "resveratrol activates genes close the the beginning of the molecular cascade precipitated by caloric restriction." This starts as an 'upstream' action. What happens next is that the activated genes using the pterostilbene then continue to activate numerous disease-preventing genes in a 'downstream' process from the sites connected with resveratrol's upstream action. So as resveratrol works in an upstream action, pterostilbene works the genes in a downstream action.

Pterostilbene amplifies and complements resveratrol's ablity to help turn off those 'epigenetic' gene tags that switch off the cancer and diabetes causing gene tags and switch on the longevity gene tags that support healthy blood fats (lipids)

It's all happening during the normal cycle of gene expression. Basically, the pterostilbene, made from blueberry and/or grape extracts, mimics the beneficial effects of calorie restriction at the molecular level. The idea, scientists report, is that caloric restriction is supposed to suppress cancer development, according to studies.

Does calorie reduction/restriction change your gene expression all over the metabolic process? What the plant extracts do is increase activity of fat-sensing complexes that lower blood fats and sugar levels. Basically, scientists are using plant extracts from fruits for chemoprevention. Is it the antioxidants in resveratrol or the anti-inflammatory actions in pterostilbene?

If you look at both resveratrol and pterostilbene, both are called stillbenes. They've been used for hundreds of years in India as folkoric cures for illness in Ayurvedic medicine that is now being studied by Western scientists to see how these plant extracts change gene expression.

The extracts are being tested to see which are good for helping to prevent cancer, lower cholesterol, enhance insulin sensitivity, or increase life span of humans and/or animals

These plant extracts mimic caloric restriction at your molecular level, say recent studies. See, "Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol." The way these plant extracts work is by mimicking caloric restriction. Resveratrol and pterostilbene both act at different locations in the body to control gene expression. They complement each other. Can they increase the quantity of life or the quality of life?

Basically, if you eat a cup of blueberries, you get 20mcg of pterostilbene. Yes, even at that level, the blueberries provide some benefits. But how much more pterostilbene do you need? What is a safe level? A dose of 3 mg daily of pterostilbene in a supplement provides the equivalent of 140 cups of blueberries daily. No one eats like that. So should you take a supplement with pterostilbene or resveratrol combined with pterostilbene? How much is science and how much is marketing?

You only need a small dose of pterostilbene, say recent studies. So in various supplements, it is being added to resveratrol and other supplements. You will probably want to read more about the studies. For further information, you can see the March, 2008 article at BMC Medical Genemics, 20;1:7. See, "Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol."

The 2008 UC Davis study showed that pterostilbene has a significant effect on methionine metabolism

The conclusion of the 2008 UC Davis study, reported that, "Using transcript profiling, we have identified the cellular pathways targeted by pterostilbene, an analog of resveratrol. The observed response in lipid metabolism genes is consistent with its known hypolipidemic properties, and the induction of mitochondrial genes is consistent with its demonstrated role in apoptosis in human cancer cell lines. Furthermore, our data show that pterostilbene has a significant effect on methionine metabolism, a previously unreported effect for this compound." Apoptosis applied to that study means getting rid of human cancer cell lines. Apoptosis refers to the disintegration of cells into membrane-bound particles that are then eliminated by phagocytosis or by shedding.

That 2008 study, "Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol." also reported the following: "Pterostilbene is a naturally-occurring phytoalexin identified in several plant species. It belongs to a group of phenolic compounds known as stilbenes, and is found in the heartwood of sandalwood (Pterocarpus santalinus) [1] and P. marsupium [2].

For further information on the healthful benefits of blueberries, see my other Examiner articles, "Does an alkaline diet with added blueberries increase your bone density?" and regarding resveratrol, see, "How to find reliable information on resveratrol."

Regarding resveratrol, check out the study, "Phytoestrogen resveratrol suppresses steroidogenesis by rat adrenocortical cells by inhibiting cytochrome P450 c21-hydroxylase." The authors are Supornsilchai V, Svechnikov K, Seidlova-Wuttke D, Wuttke W, Söder O, published in Hormone Research in Pediatrics, 64:280-86, 2005. (Pediatric Endocrinology Unit, Q 2:08, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden.)

The Swedish study looked at the effects of resveratrol on rats. But rats are used in scientific studies to see how a substance reacts also with humans, since the genes are not as far apart as you'd believe. Mice share 90% of their DNA with humans.

The main point of the resveratrol study that you should be aware of is that resveratrol is a phytoestrogen

As a phytoestrogen, it's going to act like a phytoestrogen in your body. The phytoestrogen resveratrol is found in grapes, mulberries and peanuts, all of which are consumed regularly by humans. Resveratrol is also used in chemotherapy against cancer and aging and as a cardioprotectant. The aims of the recent studies on resveratrol as a phytoestrogen had focused on characterizing the effects of resveratrol on rat adrenal steroidogenesis and to study the underlying mechanism.

The big picture for us humans is that we have to consider, do we want our corticosterone production suppressed? And do we want our cytochrome inhibited? If these natural functions are inhibited, what happens to the rest of our body--our cells, organs, and blood? Is it good or bad to have something in our body's normal function suppressed or inhibited? Now the question remains, does the rat experiment transfer over to humans?

Will the same situation happen in people? What happens when and if the adrenal or stress gland might be turned off? How can we know it will happen in humans because it happened in rats? Are the genes pretty much the same at that basic level? And what type of detox nutrients will the resveratrol use up?

Those are the types of questions you have to ask when you're told to take resveratrol to increase your life span. You want the big picture--more facts. And how much should you take? If only 20 mg is effective, why are people being sold bottles of 250 mg of resveratrol when scientists know at 300 mg one of your liver enzymes is inhibited? Think about it.

As yourself, with all the various brands of resveratrol, how do you find out which sources are best? Is resveratrol surrounded by too much marketing? Where is the health information on side effects made available to the average consumer? On the other hand, check out on of the 'older' studies from 2006. That study reported in the Harvard Medical School newsletter article of how resveratrol extended the life span of obese mice, "Small Molecule Increases Lifespan and 'Healthspan' of Obese Mice."