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== Supplementation ==
==Supplementation==
⚫
Resveratrol is available as a [[nutritional supplement]]. Supplements, first sourced from ground dried [[muscadine]] and red grape skins and seeds (sometimes from residual byproducts of winemaking),<ref name=Ref11>{{cite journal

⚫
|author=Marier JF, Vachon P, Gritsas A, Zhang J, Moreau JP, Ducharme MP
⚫
Resveratrol is available as a [[nutritional supplement]]. Supplements, first sourced from ground dried [[muscadine]] and red grape skins and seeds (sometimes from residual byproducts of winemaking),<ref name="Ref11">{{cite journal
⚫
|title=Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model
⚫
| author=Marier JF, Vachon P, Gritsas A, Zhang J, Moreau JP, Ducharme MP
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|journal=J. Pharmacol. Exp. Ther.
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| title=Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model
⚫
|volume=302
⚫
| journal=J. Pharmacol. Exp. Ther.
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|issue=1
⚫
| volume=302
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|pages=369-73
⚫
| issue=1
⚫
|year=2002
⚫
| pages=369-73
⚫
|pmid=12065739
⚫
| year=2002
|doi=
⚫
| pmid=12065739
| doi=
|issn=
⚫
}}</ref> are now primarily derived from the cheaper, more concentrated [[Japanese knotweed]] which contains up to 187 mg/kg in the dried root.<ref>http://www.ncbi.nlm.nih.gov/pubmed/18050745</ref> Capsules are sold containing from 1mg to 1000mg of resveratrol. Consumer testing organisations have reported that some products do not contain the amount of resveratrol claimed on their labels and web sites. A number of companies have been created during the past 18 months with no previous experience in supplement manufacture to take advantage of resveratrol's popularity.
| issn=
⚫
}}</ref> are now primarily derived from the cheaper, more concentrated [[Japanese knotweed]] which contains up to 187 mg/kg in the dried root.<ref>http://www.ncbi.nlm.nih.gov/pubmed/18050745</ref> Capsules are sold containing from 1mg to 1000mg of resveratrol.


Resveratrol is often called a [[nutraceutical]], like other bioactive plant compounds studied for potential clinical applications: [[curcumin]], [[EGCG]], [[silymarin]], etc.
Resveratrol is often called a [[nutraceutical]], like other bioactive plant compounds studied for potential clinical applications: [[curcumin]], [[EGCG]], [[silymarin]], etc.


As a result of extensive news coverage, sales of supplements greatly increased in 2006, despite cautions that benefits to humans are unproven.
As a result of extensive news coverage,<ref>{{cite news | first=Andrew | last=Rimas | coauthors= | title=MOLECULAR BIOLOGIST DAVID SINCLAIR, MEETING THE MINDS | date=[[2006-12-11]] | publisher=boston.com | url =http://www.boston.com/news/globe/health_science/articles/2006/12/11/his_research_targets_the_aging_process/ | work =Boston Globe | pages = | accessdate = 2007-06-22 | language = }}</ref> sales of supplements greatly increased in 2006,<ref>{{cite news | first= | last= | coauthors= | title= MM2 Group Announces Record Sales of Its Resveratrol Grape Powder | date=[[2006-11-29]] | publisher=Earthtimes.org | url =http://www.earthtimes.org/articles/show/news_press_release,27694.shtml | work =MM2 Group | pages = | accessdate = 2007-06-22 | language = }}</ref> despite cautions that benefits to humans are unproven.<ref>{{cite news | first= | last= | coauthors= | title=Caution urged with resveratrol | date=[[2006-11-30]] | publisher=Upi.com | url =http://www.upi.com/NewsTrack/Science/2006/11/30/caution_urged_with_resveratrol/9504/ | work =United Press International | pages = | accessdate = 2007-06-21 | language = }}</ref><ref>{{cite news | first=John | last=Johnston | coauthors= | title=Boca cardiologist says drink up – sort of | date=[[2006-12-10]] | publisher=boca raton news | url =http://www.bocaratonnews.com/index.php?src=news&prid=18134&category=Main%20Headline | work =bocaratonnews.com | pages = | accessdate = 2007-06-21 | language = }}</ref> Media reports have claimed that a number of prominent scientists take resveratrol supplements, including Sinclair and Nobelist [[Frank Wilczek]].<ref>{{cite web|url=http://www.world-science.net/exclusives/070206_resveratrol.htm</ref>

The US government is concerned about unregulated usage of high dose supplements.


⚫
The US government is concerned about unregulated usage of high dose supplements but a "preliminary study of existing research found no evidence that resveratrol is toxic, even at very high dosages." A relatively small scale study done in January at Leicester University in the UK reported that at doses as high as 5,000mg daily no significant adverse effects were observed.
<ref>{{cite news | first=Zachary | last=M. Seward | coauthors= | title=Quest for youth drives craze for 'red wine' pills | date=[[2006-12-06]] | publisher=naples news | url =http://www.naplesnews.com/news/2006/dec/06/quest_youth_drives_craze_red_wine_pills/?neapolitan | work =naplesnews.com | pages = | accessdate = 2007-06-21 | language = }}</ref>


Resveratrol, is possible to obtain via supplements at dosages that equal the Dr. Sinclair Harvard study. In November of last year Consumer Lab[http://www.consumerlab.com], the leading independent test organisation for supplements and over-the-counter drugs tested the leading resveratrol brands. They reported that not all products contained the amount of resveratrol claimed on their labels and web sites. Life Extension brand, for example contained less than 27% of the claimed resveratrol.Conversely, Biotivia Bioforte[http://www.biotivia.com] was rated as the best value per 100mg and second highest potency product and Biotivia Transmax[http://www.biotivia.com/english/biotivia_product_transmax.php] was the highest potency supplement of those passing the evaluations. Companies whose products were approved by Consumer Lab include Biotivia Bioforte[http://www.biotivia.com/english/biotivia_product_bioforte.php] 250mg and Transmax 500mg, Country Life[http://www.country-life.com] 100mg, French Paradox[http://www.pureprescriptions.com] 2mg, Purevinol[http://www.douglaslabs.com] 25mg, Reserva Gold 5mg, Jarrow[http://www.jarrow.com] 100mg, and Swanson[http://www.swansonvitamins.com] 100mg, and Longevinex[http://www.longevinex.com] 100mg, Many resveratrol supplement makers chose not to participate in the ConsumerLab evaluations in spite of the organisations's voluntary testing program.
The following is an excerpt from a FDA New Dietary Ingredient Notification:{{quotation|First, trans-Resveratrol is excluded from the definition of a “dietary supplement” under 21 U.S.C. 321 (ff) (3) (B), because it is an article authorized for investigation as a new drug for which substantial clinical investigations have been instituted and made public in the U. S.}}{{quotation|FDA authorized trans-Resveratrol, which is also known as “resveratrol” or 3,5,4’-trihydroxystilbene, to be an [[Investigational New Drug]] on January 30, 2001. The Dietary Supplement Health and Education Act (DSHEA) of 1994 defined a “new dietary ingredient” as one that was marketed in the U.S. on or after October 15, 1994. This office does not have any information that indicates that trans-Resveratrol was legally marketed as a dietary ingredient in the U.S. before October 15, 1994.}}


As with any new supplement, buyer beware advised. One supplier, Revgenetics, was even reported in resveratrol news to be filling his capsules by hand in a room of a rented house in Florida.
⚫
"Preliminary study of existing research found no evidence that resveratrol is toxic, even at very high dosages." A relatively small scale study done in January at Leicester University in the UK reported that at doses as high as 5,000mg daily no significant adverse effects were observed.


== Physiological effects ==
== Physiological effects ==

Revision as of 17:13, 1 February 2008

Template:Chembox new

The cis-isomer of resveratrol

Resveratrol is a phytoalexin produced naturally by several plants when under attack by bacteria or fungi. Phytoalexins are antibacterial and anti-fungal chemicals produced by plants as a defense against infection by pathogens. Resveratrol has also been produced by chemical synthesis,[1] and is sold as a nutritional supplement derived primarily from Japanese knotweed. A number of beneficial health effects, such as anti-cancer, antiviral, neuroprotective, anti-aging, and anti-inflammatory effects have been reported, but all of these studies are "in-vitro" (test tube) or in yeast, worms, fruit flies, fish, mice, and rats. Resveratrol is found in the skin of red grapes and is a constituent of red wine but, based on extrapolation from animal trials, apparently not in sufficient amounts to explain the "French paradox" that the incidence of coronary heart disease is relatively low in southern France despite high dietary intake of saturated fats.[2]

The four stilbenes cis- and trans-resveratrol, and their glucosides cis- and trans-piceid are sometimes analyzed together as a group.[3]

Chemical and physical properties

Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenolic phytoalexin. It is a stilbenoid, a derivate of stilbene, and is produced in plants with the help of the enzyme stilbene synthase.

It exists as two geometric isomers: cis- (Z) and trans- (E), with the trans-isomer shown in the top image. The trans- form can undergo isomerisation to the cis- form when exposed to ultraviolet irradiation.[4] Studies find that trans-resveratrol undergoes negligible oxidation in normal atmosphere at room temperature. A study regarding the stability of trans-resveratrol under accelerated conditions and found it to be stable for 48 months. [5]

Plants and foods

Resveratrol is produced by several plants, apparently due to its antifungal properties. It is found in widely varying amounts in grapes (primarily the skins), raspberries, mulberries, in plums, peanuts, berries of Vaccinium species, including blueberries, bilberries, and cranberries, some pines, such as Scots pine and eastern white pine, and the roots and stalks of giant knotweed and Japanese knotweed, called hu zhang in China. Resveratrol was first isolated from an extract of the Peruvian legume Senna quinquangulata (formerly Cassia) in 1974; however, the strength of its anti inflammatory activity was not recognized until 1997[6]

The amount of resveratrol in food varies greatly. Ordinary non-muscadine Red wine contains between 0.2 and 5.8 mg/L,[7] depending on the grape variety, while white wine has much less — the reason being that red wine is fermented with the skins, allowing the wine to absorb the resveratrol, whereas white wine is fermented after the skin has been removed. Wines produced from muscadine grapes, however, both red and white, may contain more than 40 mg/L.[8][3]

In grapes, resveratrol is found primarily in the skin and seeds, with fresh grape skin typically containing about 50 to 100 μg of resveratrol per gram.[9] This is particularly true for muscadine grapes, whose skin and seeds have about 100 times the concentration as the pulp.[10] The amount found in grape skins also varies with the grape cultivar, its geographic origin, and exposure to fungal infection. The amount of fermentation time a wine spends in contact with grape skins is an important determinant of its resveratrol content.[11]

Content in wines and grape juice

Beverage Total resveratrol (mg/L)[11][3] Total resveratrol in a 5 ounce glass (mg)[11][3]
Muscadine Wines 14.1 - 40 2.12 - 6
Red Wines (Global) 1.98 - 7.13 0.30 - 1.07
Red Wines (Spanish) 1.92 - 12.59 0.29 - 1.89
Red grape juice (Spanish) 1.14 - 8.69 0.17 - 1.30
Rose Wines (Spanish) 0.43 - 3.52 0.06 - 0.53
Pinot Noir 0.40 - 2.0 0.06 - 0.30
White Wines (Spanish) 0.05 - 1.80 0.01 - 0.27

The trans-resveratrol concentration in 40 Tuscan wines ranged from 0.3 to 2.1 mg/L in the 32 red wines and had a maximum of 0.1 mg/L in the 8 white wines tested. Both the cis- and trans-isomers of resveratrol were detected in all tested samples. cis-Resveratrol levels were comparable to those of the trans-isomer. They ranged from 0.5 mg/L to 1.9 mg/L in red wines and had a maximum of 0.2 mg/L in white wines.[12]

Reports suggest that some aspect of the wine making process converts piceid to resveratrol in wine, as wine seems to have twice the average resveratrol concentration of the equivalent commercial juices.[3]

"All of the muscadine table wines sampled had greater trans and cis resveratrol concentrations than any other wines sampled. The muscadine table wines varied between 9.2 and 31.9 mg/L cis-resveratrol and between 4.9 and 13.4 mg/L trans-resveratrol."[3]

Content in selected foods

Food Serving Total resveratrol (mg)[13]
Peanuts (raw) 1 c (146 g) 0.01 - 0.26
Peanuts (boiled) 1 c (180 g) 0.32 - 1.28
Peanut butter 1 c (258 g) 0.04 - 0.13
Red grapes 1 c (160 g) 0.24 - 1.25

Ounce for ounce, peanuts have more than half the amount of resveratrol in red wine. The average amount of resveratrol in one ounce of peanuts in the marketplace (about 15 whole) is 79.4 µg/ounce. In comparison, some red wines contains approximately 160 µg/fluid ounce.[14] The concentrations of resveratrol were similar in cranberry and grape juice.[15]

Blueberries have about twice as much resveratrol as bilberries, but there is great regional variation. These fruits have less than ten percent of the resveratrol of grapes. Cooking or heat processing of these berries will contribute to the degradation of resveratrol, reducing it by up to half. [16]

Supplementation

Resveratrol is available as a nutritional supplement. Supplements, first sourced from ground dried muscadine and red grape skins and seeds (sometimes from residual byproducts of winemaking),[17] are now primarily derived from the cheaper, more concentrated Japanese knotweed which contains up to 187 mg/kg in the dried root.[18] Capsules are sold containing from 1mg to 1000mg of resveratrol. Consumer testing organisations have reported that some products do not contain the amount of resveratrol claimed on their labels and web sites. A number of companies have been created during the past 18 months with no previous experience in supplement manufacture to take advantage of resveratrol's popularity.

Resveratrol is often called a nutraceutical, like other bioactive plant compounds studied for potential clinical applications: curcumin, EGCG, silymarin, etc.

As a result of extensive news coverage, sales of supplements greatly increased in 2006, despite cautions that benefits to humans are unproven.

The US government is concerned about unregulated usage of high dose supplements but a "preliminary study of existing research found no evidence that resveratrol is toxic, even at very high dosages." A relatively small scale study done in January at Leicester University in the UK reported that at doses as high as 5,000mg daily no significant adverse effects were observed.

Resveratrol, is possible to obtain via supplements at dosages that equal the Dr. Sinclair Harvard study. In November of last year Consumer Lab[7], the leading independent test organisation for supplements and over-the-counter drugs tested the leading resveratrol brands. They reported that not all products contained the amount of resveratrol claimed on their labels and web sites. Life Extension brand, for example contained less than 27% of the claimed resveratrol.Conversely, Biotivia Bioforte[8] was rated as the best value per 100mg and second highest potency product and Biotivia Transmax[9] was the highest potency supplement of those passing the evaluations. Companies whose products were approved by Consumer Lab include Biotivia Bioforte[10] 250mg and Transmax 500mg, Country Life[11] 100mg, French Paradox[12] 2mg, Purevinol[13] 25mg, Reserva Gold 5mg, Jarrow[14] 100mg, and Swanson[15] 100mg, and Longevinex[16] 100mg, Many resveratrol supplement makers chose not to participate in the ConsumerLab evaluations in spite of the organisations's voluntary testing program.

As with any new supplement, buyer beware advised. One supplier, Revgenetics, was even reported in resveratrol news to be filling his capsules by hand in a room of a rented house in Florida.

Physiological effects

Absorption and Metabolism

Resveratrol bioavailability depends on its conjugate forms: glucuronate and sulfonate, but most in vitro studies use the aglycone form of resveratrol ('aglycone' means without a sugar molecule attached, as in the figure in this article). In humans[19] [20] and rats,[21] [22] [23] resveratrol rapidly undergoes conjugation resulting in less than 5% of the oral dose being observed as free resveratrol in blood plasma. The effect of conjugation on efficacy is debated.[24][25] The studies[20] [21] show rats have 72% more free resveratrol and 6 times more of a glucuronide form as humans for a dose of about 60 mg/kg. The most abundant conjugates in humans, rats, and mice are trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate.[26] Walle suggests sulfate conjugates are the primary source of activity[19], Wang et al suggests the glucuronides,[27] and Boocock et al also emphasized the need for further study of the effects of the metabolites including the possibility of deconjugation to free reservatrol inside cells.

In humans, Walle et al reported at least 70% absorbed and 99% is quickly metabolized to conjugates using 25mg doses. Half life of resveratrol and its metabolites was 9 hours. 73% was excreted in urine and feces after 12 hours. [19] Boocock et al reported 3% of the total metabolites in the blood plasma of humans was free resveratrol, measured as area under the concentration curve. Half life was 4 to 11 hours for the various metabolites. [20]

A study on rats given an oral dose of 50 mg/kg showed resveratrol and its metabolites have an initial apparent half life of 8 minutes but a "terminal" half life of 1.5 hours in blood plasma. The free resveratrol was 46 times less than the glucuronide form (measured as area under the concentration curve).[21]

Cellular Activity

An article in press as of January 2008 discusses resveratrol action in cells. It reports a 14-fold increase in the action of MnSOD.[28] MnSOD reduces superoxide to H2O2, but H2O2 is not increased due to other cellular activity. Superoxide O2- is a byproduct of respiration in complex 1 and 3 of the electron transport chain. It is "not highly toxic, [but] can extract an electron from biological membrane and other cell components, causing free radical chain reactions. Therefore is it essential for the cell to keep superoxide anions in check."[29] MnSOD reduces superoxide and thereby confers resistance to mitochondrial dysfunction, permeability transition, and apoptotic death in various diseases.[30] It has been implicated in lifespan extension, inhibits cancer (e.g. pancreatic cancer [31]), and provides resistance to reperfusion injury and irradiation damage [32] [33] [34]. These effects have also been observed with reservatrol. Ellen et al propose MnSOD is increased by the pathway RESV --> SIRT1 / NAD+ --> FOXO3a --> MnSOD. Resveratrol has been shown to cause SIRT1 to cause migration of FOXO transcription factors to the nucleus [35] which stimulates FOXO3a transcriptional activity [36] and it has been shown to enhance the sirtuin-catalyzed deacetylation (activity) of FOXO3a. MnSOD is known to be a target of FOXO3a, and MnSOD expression is strongly induced in cells overexpressing FOXO3a [37].

Resveratrol interferes with all three stages of carcinogenesis - initiation, promotion and progression. Experiments in cell cultures of varied types and isolated subcellular systems in vitro imply many mechanisms in the pharmacological activity of resveratrol. These mechanisms include modulation of the transcription factor NF-kB,[38] inhibition of the cytochrome P450 isoenzyme CYP1A1[39] (although this may not be relevant to the CYP1A1-mediated bioactivation of the procarcinogen benzo(a)pyrene[40]), alterations in androgenic[41] actions and expression and activity of cyclooxygenase (COX) enzymes.

Resveratrol was reported effective against neuronal cell dysfunction and cell death, and in theory could help against diseases such as Huntington's disease and Alzheimer's disease.[42][43] Again, this has not yet been tested in humans for any disease.

Research at the Northeastern Ohio Universities College of Medicine and Ohio State University indicates that resveratrol has direct inhibitory action on cardiac fibroblasts and may inhibit the progression of cardiac fibrosis.[44]

According to Patrick Arnold it also significantly increases natural testosterone production from being both a selective estrogen receptor modulator[45][46] and an aromatase inhibitor.[47][48]

Life extension

Konrad T. Howitz and Robert Zipkin of BIOMOL International discovered that resveratrol increases the activity of an enzyme called SIRT1. They then contacted David Sinclair of the Harvard Medical School, and cofounder of Sirtris Pharmaceuticals,[17][49] in order to initiate a collaboration. Sinclair found that resveratrol significantly increases the lifespan of yeast and mice.[9]

Experiments published in 2003 in the journal Nature demonstrated that resveratrol significantly extends the lifespan of the yeast Saccharomyces cerevisiae.[50] Later studies showed that resveratrol prolongs the lifespan of the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster by 14% and 18% respectively when in 23 ppm of resveratrol.[51] Resveratrol treatment of C. elegans was reported again in 2007 to have an increase in mean lifespan of 64% and maximal lifespan by 30%.[52] But an independent study of resveratrol found "no significant effects on lifespan in seven independent trials" in Drosophila and found "slight increases in lifespan in some trials but not others" in C. elegans.[53] In 2006, resveratrol was used to extended the maximum lifespan of a short-lived fish, Nothobranchius furzeri, by 59%, and extended its median lifespan by 56%. Also noted were an increase in swimming performance, an increase in cognitive performance (learning tasks), and a lack of neurofibrillary degeneration. The authors observed that "[resveratrol's] supplementation with food extends vertebrate lifespan and delays motor and cognitive age-related decline could be of high relevance for the prevention of aging-related diseases in the human population."[54] In 2006, a report in the journal Nature (the 3rd report in Nature concerning resveratrol that involved Dr. David Sinclair's laboratory at Harvard) showed a 30% increase in lifespan on 22 mg/kg/day resveratrol in a high-calorie (90 Calorie/week), high fat (60% of total calories) diet for ~45 gram mice.[55] This is equivalent to 155 mg resveratrol per day in a 2000 Calorie/day diet. The same group found no effect of resveratrol in mice fed standard laboratory chow (containing 4% of calories from fat). Dr. David Sinclair declares in the Nature publication that he is a co-founder of Sirtris Pharmaceuticals, a company whose goal is to develop drugs to treat age-related diseases.

The fish study increased lifespan 30% on 120 ug/g resveratrol in food and 56% increase on 600 ug/g. No increase was observed with 24 ug/g. The treatment began at 4 weeks of age which is 30% of the maximum recorded lifespan for the species. 50% of the 600 ug/g group lived longer than had ever been observed before in this species (without calorie restriction). 90% of the high-dose group were still sexually active after 90% of the control group were dead. The fish consumed 50 mg of food per gram of body weight each day and at 600 ug resveratrol per gram of food. This dose per calorie consumed is about 200 mg/day for a 2000 Calorie/day diet.

When trying to calculate an equivalent dose for humans, it is not accurate to use the mg dose per body weight method as was commonly reported in the media when the life-extension resveratrol studies came out.[56] This method leads to much larger quantities than is accurate because larger animals have a slower metabolic rate for their weight. The comparative dosage should be based on mg per Calories consumed per day. If the Calories consumed per day are not known, it is estimated from the body weight.[57] This results in the formula: (human dose/kg) = (animal dose mg/kg) x (animal kg/human kg)^(1-P) where P=2/3 is used by convention to give a larger margin of safety for FDA pharmaceutical and EPA toxicology uses, but P=3/4 is more accurate.[58] [59] The absorption, metabolism, and excretion is very different in different species so that even adjusting for metabolic rate is not very accurate. For example, as mentioned in the absorption section, rats have much more free resveratrol and glucuronide forms in their blood than humans for a given dose, eventhough the metabolic rate adjustment implies they should have much less.

The mechanisms of resveratrol's apparent effects on life extension are not fully understood, but they appear to mimic several of the biochemical effects of calorie restriction. This seems to function by means of lipase inhibition, reducing the absorption of fat through intestinal walls. A new report indicates that resveratrol activates SIRT1 and PGC-1α and improve functioning of the mitochondria.[60] Other research calls into question the theory connecting resveratrol, SIRT1, and calorie restriction.[61][62]

Cancer Prevention

In some lineages of cancer cell culture, resveratrol has been shown to induce apoptosis, which means it kills cells and may kill cancer cells.[41][63][64][65][66][67] Resveratrol has been shown to induce Fas/Fas ligand mediated apoptosis, p53 and cyclins A, B1 and cyclin-dependent kinases cdk 1 and 2. Resveratrol also possesses antioxidant and anti-angiogenic properties.[68][69]

Resveratrol is under extensive investigation as a cancer chemopreventive agent.[70][71] Indeed, there are studies showing that small doses of dietary resveratrol can reduce colon carcinogenesis in rats and mice.[72] One German study has already been shown to that under special conditions, resveratrol induces apoptosis in human fat cells. In addition, it inhibits production of cytokines which are involved in the development of obesity-related disorders.[73]

Athletic performance

Johan Auwerx (at the Institute of Genetics and Molecular and Cell Biology in Illkirch, France) and coauthors published an online article in the journal CELL in November 2006. Mice fed resveratrol for 15 weeks had better treadmill endurance than controls. The study supported Sinclair's hypothesis that the effects of resveratrol are indeed due to the activation of SIRT1.

Nicholas Wade's interview-article with Dr. Auwerx[74] states that the dose was 400 mg/kg of body weight (much higher than the 22 mg/kg of the Sinclair study). For an 80 kg (176 lb) person, the 400 mg/kg of body weight amount used in Dr. Auwerx's mouse study would come to 32,000 mg/day. Compensating for the fact that humans have slower metabolic rates than mice would change the equivalent human dose to roughly 4571 mg/day. Again, there is no published evidence anywhere in the scientific literature of any clinical trial for efficacy in humans. There is limited human safety data (see above). It is premature to take resveratrol and expect any particular results. Long-term safety has not been evaluated in humans.

In a study of 123 Finnish adults, those born with certain increased variations of the SIRT1 gene had faster metabolisms, helping them to burn energy more efficiently—indicating that the same pathway shown in the lab mice works in humans too.[75]

Antiviral effects

Resveratrol seems to increase the potency of some antiretroviral drugs against HIV in vitro.[76]

Infection by herpes simplex virus ordinarily activates the cell protein Nuclear Factor κB (NF-κB). A Northeastern Ohio Universities College of Medicine study undertaken in Vero cells found that resveratrol suppresses the activation of this transcription- and apoptosis-related protein. The study further found that multiple viral protein products were reduced or completely blocked, as well as a reduction in viral DNA production.[77]

A cell culture study found that resveratrol blocks the influenza virus from transporting viral proteins to the viral assembly site, hence restricting its ability to replicate. The effect was 90% when resveratrol was added six hours after infection and continued for 24 hours thereafter.[78]

Adverse effects and unknowns

While the health benefits of resveratrol seem promising, one study has theorized that it may stimulate the growth of human breast cancer cells, possibly because of resveratrol's chemical structure, which is similar to a phytoestrogen.[79][80] However, other studies have found that resveratrol actually fights breast cancer.[81][82] Citing the evidence that resveratrol is estrogenic, some retailers of resveratrol advise that the compound may interfere with oral contraceptives and that women who are pregnant or intending to become pregnant should not use the product, while others advise that resveratrol should not be taken by children or young adults under 18, as no studies have shown how it affects their natural development.[83]

There is some evidence that resveratrol might exacerbate West Nile virus, since West Nile is p53 mediated and worsened by increased rates of apoptosis of infected cells. [18]

Scientists are also studying three other synthetic compounds based on resveratrol which more effectively activate the same biological mechanism.[84]

The compound called SRT 1720 seems to be 1000 times more effective than resveratrol, although it only increases SIRT1 activation by 6 times. No data has been publicly produced by Sirtris regarding this difference in SIRT1 efficiency for the new compound.[85]

A study by Professor Roger Corder has identified a particular group of polyphenols, known as oligomeric procyanidins, which they believe offer the greatest degree of protection to human blood-vessel cells. These are found in greatest concentration in European red wines from certain areas, which correlates with longevity in those regions. This new data may impact the supplement market.[86] Because they are present in red wine in more significant quantities, they could offer an alternate explanation of the French paradox.

References

  1. ^ Farina A, Ferranti C, Marra C (2006). "An improved synthesis of resveratrol". Nat. Prod. Res. 20 (3): 247–52. doi:10.1080/14786410500059532. PMID 16401555.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Renaud S, Ruf JC (1994). "The French paradox: vegetables or wine". Circulation. 90 (6): 3118–9. PMID 7994864.
  3. ^ a b c d e f LeBlanc, Mark R. "ULTIVAR, JUICE EXTRACTION..." (PDF). Retrieved 2007-06-18. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  4. ^ Lamuela-Raventos, RM (1995). "Direct HPLC Analysis of cis- and trans-Resveratrol and Piceid Isomers in Spanish Red Vitis vinifera Wines" (PDF). J. Agric. Food Chem. (43). pubs.acs.org: 281–283. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)
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Further reading

See also


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