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 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 precipiated 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.
Calorie restruction changes 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.
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. 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 conclusion of this new 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.”
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)  and P. marsupium .
“It was also identified in the leaves of Vitis vinifera , in infected grape berries of var. Chardonnay and Gamay , and in healthy and immature berries of var. Pinot Noir and Gamay . Pterostilbene has also been found in berries of some Vacciunium species . Pterostilbene, one of the most extensively studied secondary metabolites found in grapes and wine, is a dimethylether analog of resveratrol that is well known for its hypolipidemic activity. A considerable amount of research effort has been expended to address the biochemical and physiological effects of pterostilbene in animal and microbial systems.
“For example, the antioxidative activity of pterostilbene was first demonstrated in vitro by its inhibition of methyl linoleate oxidation . Pterostilbene was reported to scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radicals and to inhibit the oxidation of citronellal, and lipid peroxidation in rat liver microsomes and in cultured human fibroblasts .
“Pterostilbene isolated from Anogeissus acuminata (Family Combretaceae) is cytotoxic against a number of cancer cell lines, including human breast cancer and murine lymphoid neoplasma cells [8,9]. More recently, it has been demonstrated that pterostilbene can reduce cholesterol levels in vivo in hamsters through the activation of the peroxisome proliferator-activated receptor α (PPARα) . Pterostilbene has been reported to reduce glucose and increase plasma insulin levels significantly in normal and diabetic rats . Furthermore, pterostilbene has been shown to be cancer-chemopreventive [8,12] and anti-inflammatory .”
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.”
Resources and References for the 2008 Study, “Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol.”
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. 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.)
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.
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).
Cells from resveratrol-treated and non-treated rats were tested ex vivo for responsiveness to ACTH and cells from normal rats were tested in vitro for responsiveness to ACTH in the presence and absence of resveratrol. Corticosterone and progesterone production were measured by RIA and expression of steroidogenic enzymes analyzed by PAGE/Western blotting.
That’s how they did the experiment. What happened is that the resveratrol inhibited corticosterone production by what laymen call the stress gland, that is, the adrenal gland.
Corticosterone production was inhibited 47% by 50 microM resveratrol in vitro and 20% ex vivo, whereas progesterone production was elevated to 400% of the control value in in vitro experiments. Resveratrol treatment decreased adrenal cytochrome P450 c21-hydroxylase expression in vivo and cell culture conditions.
So how much resveratrol would it take to decrease your adrenal cytochrome and hydroxylas expression in a human? That’s the big question you have to consider when you take resveratrol. In other words, how much can you take for benefits and still be safe without turning off your adrenal gland or using up your body’s detox nutrients?
At least the experiment revealed that no changes to cell ‘viability’ happened with the rats. That is the resveratrol didn’t mutate or destroy the rat’s cells.
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 last year? 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.”