ALLNatural Resveratrol

Resveratrol, an Anti-Aging Wonder

trans-Resveratrol is an anti-aging factor found in red wine that extends life expectancy and improves health and well-being by mimicking the effects of reduced caloric intake.  Trans-Resveratrol turns on genes that enables our cells to become much more hardy and less prone to oxidative damage and aging.  It has the effect of recharging our metabolic machinery.

ALLNatural Resveratrol is 98% pure, of high strength and does not contain Emodin which can cause side effects such as diarrhea.

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The Health Benefits of Resveratrol

Dr. David Sinclair, a scientist from Harvard Medicine School demonstrated that trans-resveratrol can prolong life expectancy in a wide range of animals.  In 2008, he told Barbara Walter’s Nationwide TV audience that the science of aging “has split the atom” and with the advent of imminent scientific discoveries, living to 120 to 150 years of age will not be unrealistic.

trans-Resveratrol may be one of the most important anti-aging supplements ever discovered as it has been shown to increase life-span of between 33% to 60%.  In addition to life-extension, trans-Resveratrol also has the following benefits:

Cardiovascular Health

Cardiovascular Health

trans-Resveratrol modifies almost all steps in the initiation of cardiovascular disease. Platelets become less sticky, blood vessels relax, and the damage to tissues in the event of a heart attack or stroke is profoundly reduced.

Anti-Inflammatory and Insulin Resistance

trans-Resveratrol supplements have been shown to reduce inflammation and insulin resistance which can help with obesity and diabetes.

Cancer Prevention

Preclinical studies show great promise for human cancer prevention including skin, breast, prostate, intestine and lung cancers.

Anti-Oxidative Effect and Inhibited Accumulation of Fats

Helps to prevent oxidation of certain fats, such as low-density lipoprotein (LDL) cholesterol and triglyceride.

Enhanced Muscle Endurance

trans-Resveratrol supplements have been shown to increase energy production in the energy factory of the muscles (mitochondria), especially in athletes.

Neurodegenerative Disorders

Resveratrol has been shown to enhance memory and reaction time which can be beneficial for people with neurodegenerative conditions such as Alzheimer’s.

Natural Sources of trans-Resveratrol

Reveratrol (trans form) is not only found in red grapes and red wine but it is also present in many plant species, most of which are consumed by humans.  One of the richest sources of this compound is Ploygonum cuspidatum (Giant Knotweed).  It has been used in Traditional Chinese and Japanese herbal medicines for centuries. ANNP’s resveratrol is produced from Polygonum cuspidatum.

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Authorized for Sale by Health Canada

ALLNatural Nutritional Products Inc. has been issued a Natural Product Number (NPN 80024931), a requirement by Health Canada for the sale of nutraceuticals. This number insures you that the product has been reviewed and approved by Health Canada and it is safe, effective and of high quality. Many supplements sold online and in stores have a low concentration of resveratrol.

ALLNatural Resveratrol vs Red Wine

Although red wine is a good source of trans-resveratrol its concentration is low, generally less than 30 mg per liter.  As a result a very large amount of wine (up to 10 liters/day) would be required to have the same intake as obtained with the supplement.  Daily intake of ALLNatural Resveratrol provides an excellent alternative to the consumption of red wine.

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Frequently Asked Questions

Resveratrol (3, 5, 4’-trihydroxystilbene) is a nutraceutical product that is most commonly obtained from the roots of Polygonum cuspidatum, a plant used in traditional Chinese and Japanese medicine. Initially characterized as a phytoalexin, resveratrol attracted little interest until 1992, when it was postulated to explain some of the cardioprotective effects of red wine (The “French Paradox”; high intake of saturated fats in France but a low incidence at cardiovascular disease). Since then, more than 6,000 scientific publications has been shown that resveratrol can prevent or slow the progression of a wide variety of illnesses including heart disease, cancer, diabetes, obesity, liver disease, pancreatitis, neurodegenerative disorders, oxidative damage of muscle cells as well as enhancing stress resistance and extension of the life-span of various organisms from yeast to vertebrates. ALLNatural Nutritional Products (ANNP) Inc. is one of the first nutraceutical company to be issued a licence from Health Canada (Natural Product Number, NPN) to market resveratrol. There are two isomeric forms of resveratrol (trans- and cis-resveratrol). All Natural Nutritional Products Inc. markets the trans-form which occurs naturally in plants and has a higher biological activity than cis-resveratrol.

Clinical studies have demonstrated that an intake of 450 mg of resveratrol or higher per day per person is safe. Clinical trials with humans have found that resveratrol was safe and reasonably well tolerated over the short test period at doses of up to 5 g/day which is 10 times higher than the recommended intake by Health Canada and ANNP Inc. Studies with model animals, rats, have shown that an intake of 750 mg/kg (equivalent to an daily intake of 52 g of resveratrol for a 70 kg person) causes no harmful effects. Health Canada has approved the use of 500 mg of 98% resveratrol per day (two-250 mg capsules). Resveratrol should not be taken by pregnant women or young children. Please consult your physician or Health Care Practitioner for further details.

Prokop et al. (Journal of Medicinal Food. 9:11-14, 2006) reported that the trans- form of resveratrol when stored in capsules in bottles at room temperature is stable in excess of four years, well beyond the shelf-life of most nutritional supplements.

Resveratrol may occur in the trans- and cis-isomeric forms; that is, they have the chemical formula but can exist in different configurations. Several reports suggest that trans-resveratrol is the most bioactive form of this molecule. Usually plant tissues contain primarily trans-resveratrol, whereas processed plant extracts may contain up to 50% of the cis-isomer. The cis-form is somewhat unstable as it is readily converted (isomerised) into the trans-form. All Natural Nutritional Products Inc. only markets the trans-form of resveratrol.

Emodin is a natural contaminant of resveratrol as it is present in the herbal plant (Polygonum cuspidatum) from which resveratrol is isolated. It is increasingly removed as the purity of resveratrol is increased. However, products containing 50% resveratrol may contain sufficient emodin (from 3 to 10%) to cause a strong laxative effect if the daily intake of 50% resveratrol is 500 mg (2 capsules × 250 mg/capsule). In contrast, 98% resveratrol contains essentially no emodin, therefore, it should not have a laxative effect. For resveratrol supplements, the purer the better.

Many foods contain resveratrol but the amount (concentration) in most foods is very low. For example, peanuts, pistachios and grapes can contain up to 8 micrograms of resveratrol per gram of product (that is, 8 parts of resveratrol per million parts of the food). Blueberries and bilberries contain about 16 to 32 ng resveratrol per gram (that is 16 to 32 parts resveratrol per billion parts of the berry). Red wines, which is one of the better sources of resveratrol, can contain up to 14 µg resveratrol per ml (14 parts/million) of wine. White wines have a much lower concentration (up to 2 µg/ml). The plant with the highest amount of resveratrol is the root of Polygonum cuspidatum (Giant Knotweed) which contains about 0.5 mg resveratrol per gram of the root (0.5 parts/thousand parts of the root). In contrast, the Super-strength 98% resveratrol product from All Natural Nutritional Products Inc. contains very high concentration of resveratrol (0.98g/g) which is about 125,000 times more than that of red wine. Therefore, In order to obtain a recommended dosage of 500 mg per day of resveratrol, you only need is to take 2 capsules of ALLNatural Super-strength Resveratrol 98%, instead of drinking 36 liters of red wine, which is quite impossible.

The beneficial results of taking resveratrol, like that of many other nutraceuticals including vitamins, “do not begin to exert health effects for many days or even weeks”. Long term studies, nevertheless, have proven that resveratrol provides many benefits to health and well being.

Health Canada has approved a daily intake of 500 mg/day of 98% resveratrol (two-250 mg/capsules, one in the morning and one in the evening). Presumably the intake of 50% resveratrol should be 1000 mg (1 g) per day. Although resveratrol has been shown to be safe at high dosages it is recommended that the daily intake should not exceed one gram of 98% resveratrol.

While resveratrol has been around in plants and fruits since the beginning of time, resveratrol supplements have only been on the market for a few years. There are basically no long term human clinical studies on resveratrol supplements to test if there are any long term side effects. So, if you are looking for a study that can guarantee resveratrol supplements will be free of side effects over the long term – you are out of luck. The good news is that we have a long history of drinking wine, eating grapes and peanuts and giant knotweed roots, all of which contain resveratrol, without any serious side effects (of course, drinking too much wine can have side effects – but that is a whole different topic). In addition, scientists have done animal toxicity tests on resveratrol and found it to be safe, even at very high dosages. Here is a quote from WebMD on the potential side effects of resveratrol – “So far, studies have not discovered any severe side effects, even when resveratrol is taken in large doses. However, resveratrol supplements might interact with blood thinners such as warfarin (Coumadin), and nonsteroidal anti-inflammatory medications such as aspirin and ibuprofen, increasing the risk for bleeding.”

Since we don’t have long term studies to look at, the best we can do in terms of advising on potential side effects is to look at anecdotal evidence. Here are some possible resveratrol side effects: upset stomach, jittery feeling or excess energy, joint pain, diarrhea, decreased appetite and light headedness. We want to stress the above list is by no means exhaustive or scientific. These are just side effects that users of various resveratrol supplements have reported. The side effects may have been caused by resveratrol or some other ingredient in the supplement. In addition, the vast majority of people do not report any side effects.

Yes. Many of the stomach and diarrhea related side effects are a result of the emodin found in some resveratrol supplements. When a resveratrol extract is made from Japanese Knotweed it can contain a high percentage of emodin. It is best to avoid emodin as it can cause diarrhea. The problem with avoiding emodin is that it is not listed on the label. The only way to make sure you are taking a resveratrol supplement that does not contain emodin is to use a supplement that contains only 98% trans-resveratrol. This is another reason why ALLNatural Nutritional Products Inc. highly recommends the use of ALLNatural Super-strength, 98% trans-resveratrol as it essentially has NO EMODIN. So, by using this resveratrol product you eliminate the side effects that the emodin would cause.

Many scientific studies have shown that resveratrol can prevent numerous health related problems including liver disease, pancreatitis and neurodegenerative disorders, and protect muscle cells against oxidative stress. It also enhances stress resistance and has been shown to extend the life-span of various organisms from yeast to vertebrates. Detailed reviews by scientific experts on each of the above benefits are given in the Educational Section of the website.

No. Please contact your Physician or Health Care Practitioner for further details. Additional research must be carried out in order to confirm the safety of resveratrol for pregnant women.

Yes. Multivitamins can be taken at the same time as resveratrol. They are both natural supplements and there is no harm taking both at the same time.

Some resveratrol products sold in Canada may not have a Natural Product Number and often have concentration that intake (products providing more than 500 mg per day). Also many products with 50% or less trans-resveratrol also contain significant amounts of emodin may have some beneficial effects, but is a laxative and may cause cramping. The 98% trans-resveratrol should be consumed to avoid these problems.

A recent study has demonstrated that of 29 resveratrol supplements sold in stores in Canada or on the internet, 16 contained less 100 mg of resveratrol per capsule with 8 having less than 25 mg per capsule (Omar et al., J Agric Food Chem 62:5812-5817, 2014. (http://pubs.acs.org/doi/abs/10.1021/jf5001277)

The intake of two capsules per day of these products would result in a daily intake of resveratrol below recommended levels, some for below the recommended levels of intake.  Also the cost per mg resveratrol varies greatly, among different products, especially for products containing a low amount of resveratrol per capsule. The customer should compare prices of resveratrol products not on the basis of cost per capsule but on cost per amount of active ingredient.

Science and Research

What is Resveratrol

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) was first isolated from the root of white hellebore (Veractrum grundiforum O. Loes) in 1940, and later in 1963, from the roots of Polygonum cuspidatum, a plant used in traditional Chinese and Japanese medicine. Initially characterized as a phytoalexin, resveratrol attracted little interest until 1992, when it was postulated to explain some of the cardiprotective effects of red wine.

Resveratrol Diagrams

Figure 1. Trans-resveratrol and related structures. Piceid (trans-resveratrol-3-O-β-D glucoside) is found in grapes and other natural sources of resveratrol. Resveratrol-3-sulphate, resveratrol-3-O-glucuronide and dihydroresveratrol are metabolites of resveratrol. The positions of hydroxyl groups are indicated on the parent molecule (Baur, J. A. & Sinclair, D. A. Nature Reviews Drug Discovery 2006).

Resveratrol and the French Paradox

Since the beginning of the 1992s, various reports began to emerge that resveratrol, a compound present in red wine, might contribute in part to the “French Paradox”, a phenomenon that refers to the relatively low rate of cardiovascular disease (CVD) in France despite high intake of dietary saturated fat (Renaud and de Lorgeril, 1992).

Resveratrol (3,5,4′-trihydroxytransstilbene, RSV) is a small polyphenolic compound found in various berries, nuts, grapes, and other plant sources, including traditional Asian medicines. Although this polyphenol exists as cis- and trans-isomers, trans-RSV is the preeminent and biological active form found in dietary sources and supplements.

The growing interest in the use RSV is due to its protection against inflammation, oxidative stress, heart disease, diabetes, liver disease, neurodegenerative disorders, cancer and as a caloric restriction the mimetic (Baur and Sinclair, 2006; Cottart et al., 2014). RSV has gained considerable interest in the medical community as a possible preventative agent for several human chronic diseases (Baur and Sinclair, 2006).

Safety of Resveratrol

Biological Effects of Resveratrol in Humans

Resveratrol Benefits
Figure 2. Summary of the effects of resveratrol in human clinical trials when conducted in patients with type 2 diabetes, obesity, cardiovascular disease, cancer or skin disorders.
The symbol denotes lack effect, and ↑↓ opposite action in some trials (Novelle et al., Aging Research Reviews, 2015).

Resveratrol’s many benefits are being widely studied

The number of scientific publication on reseveratrol as shown in Figure 3 has exploded since the benefits of red wine were first postulated by Renaud and de Lorgeril, 1992. This is an indication of the importance of resveratrol to health and wellbeing.

Resveratrol Citations

Figure 3. Resveratrol citations appearing on PubMed as function of year.  The PubMed databases was searched using the key word “resveratrol”. The plot shows the cumulative number of scientific publication identified for each year after the creation of Medline in 1963.  Data from Baur and Sinclair, 2006. The total number of scientific publications on resveratrol can also be obtained on Google Scholar under the subheading “in the title of the article”. The total number of publications up to 2015 was 12,400 with the publication in 2015 alone being 1190.  Clearly, the enormity of the scientific research is a reflection of the many benefits of reseveratrol to Health and Wellbeing.

Summary of recent publications on the multiple benefits of resveratrol

The results of a recent symposium on resveratrol have been published in Biochimica et Biophysica ACTA- Molecular Basis of Disease, 2015. The titles of these publication and others given below. The abstract and full publication can be obtained by clicking on the title.

Amount of duration of resveratrol intake

Trans-resveratrol 98% should be taken over long period of time from Health Canada recommended a rate of 500 mg/day (2 × 250 mg/cap) in order to receive its full benefits.

ALLNatural Nutritional Products (ANNP) Inc. has been issued a licence from Health Canada to market its resveratrol under the brand name of ALLNatural Resveratrol 98%, Super strength. A Natural Product Number (NPN 80024931) is a requirement for sale of all nutritional products.

Scientific reviews on the benefits of resveratrol

Resveratrol is a constituent of red wine and a member of natural, plant derived chemicals known as polyphenols.  The scientific publications in this section reviews the many different health benefits of resveratrol including its antioxidant, anti-inflammatory, anti-proliferative, and anti-angiogentic effects and some of the signaling pathway that are among molecular targets.

As a result resveratrol prevents the progression of a wide variety of diseases including heart disease, cancers, diabetes, obesity, liver disease, and neurodegenerative disorders, and extends of life span. The following publications are peer reviewed papers on the biological activity of resveratrol and can be accessed by clicking on them.

Baur, J. A. and D. A. Sinclair. Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews 5:493-506, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16732220

Baur, J. A. Resveratrol, sirtuins, and the promise of DR mimetic. Mech Ageing Dev 131:261-269, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20219519

Bhat, K. P.L.et al. Biological effects of resveratrol. Antioxid Redox Signal 3(6):104-164, 2001.  http://www.ncbi.nlm.nih.gov/pubmed/11813979

Catalgol, B. et al. Resveratrol: French paradox revisited. Frontiers in Pharmacol 3:1-18, 2012. http://www.frontiersin.org/Cardiovascular_and_Smooth_Muscle_Pharmacology/10.3389/fphar.2012.00141/abstract

Frémont, L. Biological effects of resveratrol. Life Science 66:663-673, 2000. http://www.sciencedirect.com/science/article/pii/S0024320599004105

Novelle et al. Resveratrol supplements: Where we are now and where we should go? Aging Research Reviews 21:1-15, 2015. http://www.sciencedirect.com/science/article/pii/S1568163715000045

Park, S-J. et al. Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting  cAMP Phosphodiesterases. Cell. 148:421-433, 2012. http://www.cell.com/abstract/S0092-8674%2812%2900030-X

Timmers, S. et al. The journey of resveratrol from yeast to human. Aging 4(3):146-158, 2012.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348475/

The scientific reviews in this section show that one of the principal targets of resveratrol is an enzyme that results in an increase in cyclic adenosine monophosphate (cAMP), an important second messenger.

This messenger, in turn, increases the activity of sirtuin which enhances the amount of NAD+ bringing about some of the many metabolic benefits of resveratrol including enhanced weight loss and the prevention of metabolic diseases associated with aging.

Agarwal, B.  and J. A. Baur. Resveratrol and life extension. Ann. N. Y. Acad. Sci.1215, 138-143, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05850.x/abstract

Baur, J. A. Resveratrol, sirtuins, and the promise of a DR mimetic. Nutrition and Ageing 131 (4):261-269, 2010.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862768/   

Bhullar et al. Lifespan and healthspan extension by resveratrol. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. 1852 (6), 1209–1218, 2015. http://www.sciencedirect.com/science/article/pii/S0925443915000216

Canto, C and J. Auwerx. Caloric restriction, SIRT1 and longevity.  Trends Endocrinol Metab 20(7):325-331, 2009. http://www.sciencedirect.com/science/article/pii/S1043276009000915

Hubbard, B. J. et al., Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 339(6124):1216-1219, 2013.  <http://www.sciencemag.org/content/339/6124/1216>

Kelly, G. S. A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 2.  Altern Med Rev 2010 Dec;15(4):313-28. http://www.ncbi.nlm.nih.gov/pubmed/21194247

Park, S-J. et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148 (Feb 3):421-433, 2012. http://ac.els-cdn.com/S009286741200030X/1-s2.0-S009286741200030X-main.pdf?_tid=751b6b4e-073e-11e2-bd0c-00000aacb361&acdnat=1348597740_408062864e60e0b3946f915d58a44c4d

Timmers, S. et al. Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans. Cell Metab 14(5):612-622, 2012. http://www.cell.com/cell-metabolism/abstract/S1550-4131%2811%2900386-X

Caloric restriction appears to be the most robust means to extend life span and delay physiological deterioration associated with aging. The publications given below demonstrates that resveratrol mimics the effects of caloric restriction and therefore brings about many of its beneficial effects including loss of weight and its associate benefits such as protection against age-related disease resulting in increased quality of life and longevity.

Baile, C. A. Effect of resveratrol on fat mobilization. Ann N Y Acad Sci 1215, 40-47, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05845.x/abstract

Dal-Pan A. et al. Caloric restriction or resveratrol supplementation and ageing in a non-human primate: first-year outcome of the RESTRIKAL study in Microcebus murinus. Age (Dordr) 33(1):15-31, 2011.  http://www.ncbi.nlm.nih.gov/pubmed/20532988

de Ligt et al. Resveratrol and obesity: Can resveratrol relieve metabolic disturbances? Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease1852 (6):1137–1144, 2015. http://www.sciencedirect.com/science/article/pii/S0925443914003421

Park, S-J. et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148(3):421-33, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22304913

Timmers, S. et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metabolism 14:612-622, 2011. http://www.cell.com/cell-metabolism/retrieve/pii/S155041311100386X

The scientific information in this section demonstrate that the preventative and therapeutic action of resveratrol in relation to diabetes is complex and involves different effects. Resveratrol decreases blood glucose in animals with hyperglycemia, contributes to the protection of the insulin secreting beta cells in diabetes, decreases blood insulin levels, decreases oxidation damage of the pancreatic tissues and may improve insulin action. It seems quite possible that resveratrol alone or in combination with current anti-diabetic therapies, will be used in preventing diabetes.

Bhukla, Y. and R. Singh. Glycoxidative stress-induced mitophagy modulates mitochondrial fates. Ann. N. Y. Acad. Sci. 1215, 1-7, 2011.  http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05630.x/abstract

Szkudelski and Szkudelska. Resveratrol and diabetes: from animal to human studies. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. 1852 (6): 1145–1154, 2015. http://www.sciencedirect.com/science/article/pii/S0925443914003196

Szkudelski, T and K. Szkudelska. Anti-diabetic effects of resveratrol. Ann N Y Acad Sci 1215, 34-39, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05844.x/abstract

Turan, B. et al. Resveratrol and diabetic cardiac function: focus on recent in vitro and in vivo studies. J. Bioenergetics Biomembranes 44(2):281-296, 2012.  http://link.springer.com/article/10.1007/s10863-012-9429-0?null

Li et al. (2012) has recently reviewed the cardiovascular effects and molecular targets of resveratrol. They have summarized the multiple cardiovascular benefits of resveratrol and highlight the direct and indirect target molecules mediating these effects. Resveratrol stimulates endothelio production of nitric oxide, reduces oxidative stress, inhibits vascular inflammation and prevents platelet aggregation.

In animal models, resveratrol protects the heart from ischemia-reperfusion injury, reduces blood pressure and cardio-hyperphytrophy, and slows the progression of atherosclerosis. Some of the indirect molecular actions of resveratrol include it effects on the estrogen receptor α, the adenosine receptors, cyclooxygenase 1, histone/ protein diacectylase sirtuin 1, AMP-protein kinase, Akt kinase, nuclear factor – E2 – related factor – 2 and NF-kß.

Petrovski et al (2011) have reviewed the abundant preclinical evidence on the beneficial effects of resveratrol on human cardiovascular disease (DVD). These studies show that resveratrol decreases the occurrence of ischemia heart disease, heart failure and hypertension.

Tomé-Carneiro (2012) reported that the consumption of resveratrol (16 mg/day/person) in a one year clinical trial improved the inflammatory and fibrinolytic status in patients who were taking a statin for the prevention of CVD and were at high CVD risk (i.e., with diabetes or hypercholesterolemia plus ≥ 1 other risk factor).  This study demonstrated for the first time that dietary supplement with resveratrol enhances the effects of a statin (pravastatin) and that dietary intervention with resveratrol could complement the gold standard therapy (the use of statins) for the prevention of CVD.

Magyar et al. (2012) demonstated that resveratrol had a clinically measurable cardioprotective effect in patients after mycocardial infraction. They reported that resveratrol improved left ventricle diastolic function, endothelial function, lowered LDL-cholesterol level and protected against unfavorable hemorheological changes in patients with CVD. In conclusion, numerous studies have shown that resveratrol provides multiple levels of protection against CVD in humans and that it is particularly beneficial in patients suffering from CVD and in patients taking statins.

Csiszar, A. Anti-inflammatory effects of resveratrol: possible role in prevention of age-related cardiovascular disease. Ann N Y Acad Sci 1215, 117-122, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05848.x/abstract

Li, H. et al. Cardiovascular effects and molecular targets of resveratrol. Nitric Oxide 26:102-110, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22245452

Magyar, K. et al. Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clinical Hemorheology and Microcirculation.50:179-183, 2012.  http://www.ncbi.nlm.nih.gov/pubmed/22240353

Petrovski, G. et al. Resveratrol in cardiovascular health and disease. Ann N Y Acad Sci 1215, 22-33, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05843.x/abstract

Tomé-Carneiro, J. et al. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Am J Cardiol 110(3):356-363, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22520621

Wu, J. M. and T-C. Hsieh.  Resveratrol: a cardioprotective substance. Ann.NY Acad Sci 1215:16-21, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05854.x/pdf

The scientific publications in this section review current information on the mechanism by which resveratrol inhibits cancer. Resveratrol affects all three discrete stages of carcinogenesis (initiation, promotion, and progression) by modulating signal transduction pathways that control cell division and growth, apoptosis, inflammation, angiogenesis and metastasis, and hence is considered by some to be quite effective at cancer prevention.

Carter et al. Resveratrol and cancer: focus on in vivo evidence. Endocr Relat Cancer 21:R209-R225, 2014. http://erc.endocrinology-journals.org/content/21/3/R209.short

Gupta, S. C. Chemosensitization of tumors by resveratrol. Ann N Y Acad Sci 1215, 150-161, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05852.x/abstract

Lin, H-Y. et al. Resveratrol and apoptosis. Ann N Y Acad Sci 1215, 79-88, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05846.x/abstract

Namasivayam, N. Chemoprevention in experimental animals. Ann N Y Acad Sci 1215, 60-71, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05873.x/abstract

Pezzuto, J. M. The phenomenon of resveratrol: redefining the virtues of promiscuity. Ann N Y Acad Sci 1215, 123-130, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05849.x/abstract

Shukla, Y. and R. Singh. Resveratrol and cellular mechanisms of cancer prevention. Ann N Y Acad Sci 1215, 1-8, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05870.x/abstract

Singh et al. Resveratrol and cancer: Challenges for clinical translation.  Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease 1852(6):1178-1185, 2015. http://www.sciencedirect.com/science/article/pii/S0925443914003342

Varoni et al. Anticancer molecular mechanisms of resveratrol. Front Nutr 2016. http://journal.frontiersin.org/article/10.3389/fnut.2016.00008/abstract

Bishayee et al. (2010) in their review given below concluded that there exists great potential for the use of resveratrol as preventive agents in a wide spectrum of liver diseases. Resveratrol has been found to offer protection against liver damage by hepatotoxins such as ethanol, ibuprofen, carbon tetrachloride, acetaminophen induced toxicity, cadmium-induced lipid peroxidation; a atherogenic high fat diet; ischemia – reperfusion injury; and transplant and surgical models as well as irradiation.

Bishayee, A. et al. Resveratrol and liver disease: from bench to bedside and community. Liver international 28:1103-1114, 2010. http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02295.x/full

Ma et al. (2011) in the review given below reports that resveratrol inhibits the production of severe acute pancreatitis by reducing production of reducing cytokines, thus improving microcircutition, modulating cell apoptosis and blocking calcium overload.

Ma, Q. et al. The beneficial effect of resveratrol on severe acute pancreatitis. Ann N Y Acad Sci 1215, 96-112, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05847.x/abstract

Dirks-Naylor (2009) reports that resveratrol in skeletal muscle alters metabolism, inhibits protein catabolism, improves its function and protects against cellular stress. First, resveratrol alters metabolism to favor fatty acid oxidation and has anti-hyperglycemic effects by enhancing glucose transportation in skeletal muscle; secondly, it inhibits protein degradation in skeletal muscle; third, it improves strength and endurance of skeletal muscle and lastly, it protects skeletal muscle from oxidative injury and death.

Dirks-Naylor, A. J. Cellular effects of resveratrol in skeletal muscle. Life Sciences 84:637-640, 2009.http://www.sciencedirect.com/science/article/pii/S0024320509000861

Janet C. Tou. Resveratrol supplementation affects bone acquisition and osteoporosis: Pre-clinical evidence toward translational diet therapy. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. 1852(6):1186–1194, 2015. http://www.sciencedirect.com/science/article/pii/S0925443914003093

Anekonda (2006) in his review claimed that resveratrol is an ideal compound for the prevention of neurogenative diseases. Researchers have shown that resveratrol can help prevent disorders such as Huntington’s disease, Parkinson’s disease and Alzheimer’s disease. Resveratrol diminishes neurological related plaque formation in a region specific manner. The largest reductions were reported to be 48% in the media cortex, 89% in the striatum and 90% in the hypothalamus.  Karuppagounde et al. (2009) reported on the possible mechanism by which these beneficial effects are achieved.

Bastianetto  et al. Neuroprotective action of resveratrol. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease 1852(6):1195-1201, 2015. http://www.sciencedirect.com/science/article/pii/S0925443914002920

Karuppagounder et al. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem Int, 54: 111-118, 2009. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892907/

Quincozes-Santos, A. and C. Gottfried. Resveratrol modulates astroglial functions: neuroprotective hypothesis. Ann N Y Acad Sci 1215, 72-78, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05857.x/abstract

Richard, T. et al. Neuroprotective properties of resveratrol and derivatives. Ann N Y Acad Sci 1215, 103-107, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05865.x/abstract

Walle, T. Neuroprotective properties of resveratrol and derivatives. Ann N Y Acad Sci 1215, 103-107, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05865.x/abstract

Aldawsari et al. Anti-inflammatory and antioxidant properties of a novel resveratrol–salicylate hybrid analog. Bioorganic & Medicinal Chemistry Letters. 26(5):1411–1415, 2016. http://www.ncbi.nlm.nih.gov/pubmed/26850006

Lançon et al. Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases. Molecules 21(3):304, 2016. http://www.mdpi.com/1420-3049/21/3/304/htm

Ma et al. Anti-inflammatory effect of resveratrol through the suppression of NF-κB and JAK/STAT signaling pathways. Acta Biochim Biophys Sin 47 (3): 207-213, 2015. https://abbs.oxfordjournals.org/content/47/3/207.full

Poulsen et al. Resveratrol and inflammation: Challenges in translating pre-clinical findings to improved patient outcomes. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease 1852(6):1124–1136, 2015. http://www.sciencedirect.com/science/article/pii/S0925443915000071

Patel et al. (2011) reviewed the published literature on the safety of resveratrol when consumed by humans. They report that an intake of 1 g resveratrol per day was well tolerated in healthy individuals whereas the consumptional of 2.5 to 5.0 g/day of resveratrol may cause mild to moderate gastrointestinal symptoms.

Very high doses of resveratrol (5 g/person/day) have been safely used in clinical trials (Timmers et al., 2012). Studies with rats have shown that an intake of 750 mg resveratrol/kg body weight/day (equivalent to a daily intake of 52 g resveratrol/day for a 70 kg person) was safe (Williams et al., 2009).  This amount is about 100 fold greater than the recommended intake. Therefore, an intake of 98% resveratrol (2 × 250 mg/day) as recommended by ANNP and approved by Health Canada should not result in any adverse effects in the majority of individuals.

Discontinue its use if there are adverse effects.

Edwards, S. A. et al. Safety of resveratrol with examples for high purity, trans-resveratrol, resVida. Ann N Y Acad Sci 1215, 131-137, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05855.x/abstract

Patel, K. R., et al. Clinical trials of resveratrol. Ann N Y Acad Sci 1215, 161-169, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05853.x/full

Almeida, L. et al. Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res 53:S7-S15, 2009.

Brown, V. A. et al. Repeat Dose Study of the Cancer Chemopreventive Agent Resveratrol in Healthy Volunteers: Safety, Pharmacokinetics and Effect on the Insulin-like Growth Factor Axis. Cancer Res. 70(22): 9003–9011, 2010.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982884/?too..

David J. Boocock, D. J. et al. Phase I Dose Escalation Pharmacokinetic Study in Healthy Volunteers of Resveratrol, a Potential Cancer Chemopreventive Agent. Cancer Epidemiol Biomarkers Prev 16(6):1246–52, 2007. http://cebp.aacrjournals.org/content/16/6/1246.short

Timmers, S. et al. The journey of resveratrol from yeast to human. Aging 4(3):146-158, 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348475/

Williams, L. D.  Safety studies conducted on high-purity transresveratrol in experimental animals. Food Chem Toxicol  4721702182, 2009.http://journals.ohiolink.edu/ejc/article.cgi?issn=02786915&issue=v47i0009&article=2170_sscohtiea

Studies by Prokop et al. (2006) and Jensen et al. (2010) demonstrated that dry trans-resveratrol is stable when stored at ambient room temperature and low relative humidity conditions for a period of more 42 months. These data demonstrate that ANNP’s products when stored under the above condition will not deteriorate over a period of more than three years.

Jensen, J. S. et al. Preformulation stability of trans-resveratrol and trans-resveratrol glucoside (piceid). J. Agric. Food Chem. 58:1685-1690, 2010. http://pubs.acs.org/doi/abs/10.1021/jf903009f

Prokop, J. et al. Resveratrol and its glycon piceid are stable polyphenols. J. Med Food 9:11-14, 2006.  http://www.ncbi.nlm.nih.gov/pubmed/16579722

Trela, B. C. and A. L. Waterhouse. Resveratrol: isomeric molar absorptivities and stability. J Agri Food Chem 44:1253-1257, 1996. http://pubs.acs.org/doi/abs/10.1021/jf9504576

Emodin is a laxative with a broad therapeutic window. Emodin is a product that occurs in Polygonum cuspidatum and extracts of its rhizome. The concentration in the rhizome of emodin is about 5 mg/g while that of resveratrol (free and glycoside form) is about 14 mg/g (Zhao et al. 2005).

Although emodin has been shown to have many beneficial effects it is a laxative (Srinivas et al., 2007) and can cause gastrointestinal upsets: rumbling, excessive and uncontrolled gas, and discomfort. A commonly sold product from the same herb often contains 50% resveratrol. These products usually contain from 2 to 5% but sometimes as high as 10% emodin. Even at 5%, a 500 mg capsule containing 250 mg of resveratrol will contain 25 mg emodin which if taken twice per day can have a strong laxative effect.

The emodin content of 98% resveratrol is low (usually much less than 1%) and therefore does not have a laxative effect.

In contrast to emodin, resveratrol is not known to cause diarrhea and cramping. It is, therefore, important to select product containing 98%  resveratrol or a 50% resveratrol product that contains less than 2% emodin. For resveratrol supplements, the purer, the better.

Sato, M. et al. Myocardial protection by Protykin, a novel extract of trans-resveratrol and emodin. Free Radical Res Vol. 32( 2):135-144, 2000. http://informahealthcare.com/doi/abs/10.1080/10715760000300141; (Read More): http://informahealthcare.com/doi/abs/10.1080/10715760000300141

Zhao, R. et al. Rapid Quantitative HPTLC Analysis, on One Plate, of Emodin, Resveratrol, and Polydatin in the Chinese Herb Polygonum cuspidatum. Chromatographia 61 (5-6): 311-314, 2005. http://www.springerlink.com/content/c2g0l6tan8cduubk/?MUD=MP

Giuliano, V. Emodin – a moving substance. AGING SCIENCES – Anti-Aging Firewalls . Posted on 22. June 2009http://www.anti-agingfirewalls.com/2009/06/22/emodin-%E2%80%93-a-moving-substance/

Shieh DE, et al. Emodin-induced apoptosis through p53-dependent pathway in human hepatoma cells. Life Science 74(18):2279-2290, 2004.   http://www.ncbi.nlm.nih.gov/pubmed/14987952

Srinivas, G. et al. Molecular mechanism of emodin action: Transition from laxative ingredient to an antitumor agent. Med Res Rev 27(5):591–608, 2007. http://onlinelibrary.wiley.com/doi/10.1002/med.20095/abstract

Timmer, S. et al. The journey of resveratrol from yeast to human. Aging (Albany NY). 4(3):146-58, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22436213

Over 28 peer reviewed clinical trials involving human subjects have been carried out to date. The results of these trials are summarized in the review by Patel et al. (2011) and Timmers et al. (2012), given below. This includes trials dealing with bioavailability (16 trials), oxidative stress and inflammation (2 trials), cardiovascular effects (2 trials), cancer (4 trails), and diabetes, obesity and metabolism (4 trials). The general conclusion from these trials is that resveratrol shows much promise for improvement of general health status and prevention of diseases in human.

Delmas, D. et al.  Transport, stability, and biological activity of resveratrol. Ann N Y Acad Sci 1215, 48-59, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21261641

Patel. K. R. et al. Clinical trials of resveratrol. Ann N Y Acad Sci 1215, 161-169, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05853.x/full

Timmers, S. et al. The journey of resveratrol from yeast to human. Aging 4(3):146-158, 2012.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348475/

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