Trans-Resveratrol

INGREDIENTSDoctor’s Best trans-Resveratrol with ResVinol-25™, a proprietary extract providing concentrated levels of polyphenols and trans-resveratrol from red wine matrix and the root of the Japanese knotweed (Polygonum cus-pidatum) plant. Designed to ensure potency and purity of the extract from batch to batch, ResVinol-25™ is a high-quality extract subjected to rigorous ProfileProven™ analytical and quality assurance procedures. The product is extensively tested for heavy metals, bacterial and fungal contaminants, and pesticides to verify purity and compliance with acceptable standards

Resveratrol (3, 4’, 5-trihydroxystilbene) is a naturally occurring compound that belongs to a group of non-flavonoid polyphenols called stilbenes. Interest in potential health benefits for humans was spurred upon obser-vation of resveratrol being produced by grapevines (and other plants) in response to stress, UV radiation, and microbial attacks.1

BENEFITSSupports Immune System Function*Promotes a Normal, Balanced Inflammatory Response*A summary report on resveratrol noted that its ability to modulate im-mune function and promote a balanced inflammatory response works not through one simple mechanism, but through several complex pathways.2

As shown in mice, resveratrol inhibited the TNF-alpha cytokine pathways that are critical in regulation of immune cells. Resveratrol can inhibit in-flammatory enzymes and the synthesis of pro-inflammatory mediators and eicosanoids.3-5 In mouse mast cells, resveratrol inhibited TNF-alpha and histamine release, in turn blocking production of unfavorable eicosa-noids. In lung cells, resveratrol appears to inhibit macrophage release of IL-8 chemokines in vitro, limiting overreaction of white blood cells.6 An in vitro study conducted with human polymorphonuclear leukocytes (or PMN-L, a type of white blood cell) showed that even tiny amounts of res-veratrol specifically inhibited the formation of pro-inflammatory metabo-lites of arachidonic acid.7 * These statements have not been evaluated by the Food and Drug Administration.

This product is not intended to diagnose, treat, cure or prevent any disease.

Trans-Resveratrol 100

Trans-Resveratrol 200

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Supports Cardiovascular Health*Enhances Cerebral Circulation*The “French Paradox” has led to extensive research into the physiological effects of the bioactive components of red wine—the active ingredients in Best trans-Resveratrol. To build on evidence of the potent cardiovascular effects of resveratrol seen in animal studies, the focus has now shifted to working with human samples. In 20 healthy adults examined before and after 15 days of controlled wine consumption, an increase in blood nitric oxide (NO) production was reported.8 Nitric oxide is a gas responsible for signaling the smooth muscle in blood vessels to relax, thus promoting healthy circulatory function. In a particularly convincing study using blood vessel tissue derived from humans, resveratrol promoted nitric oxide-in-duced vascular relaxation and overall enhanced endothelial (blood vessel) function.9

Results from a cutting-edge crossover study published in 2010 provide ex-citing new evidence of other possible benefits of resveratrol supplemen-tation. In this randomized, double-blind, placebo-controlled investigation, 22 healthy adults each received placebo, 250mg trans-resveratrol, and 500mg trans-resveratrol on separate days. In a dose-dependent fashion, supplementation with trans-resveratrol resulted in higher cerebral blood flow in the prefrontal cortex during cognitive tasks (compared to placebo). The researchers also measured the bioavailability of their supplements, confirming that resveratrol and its metabolites were present in the blood following supplementation at both doses. They concluded that resveratrol, when taken orally, can influence brain function.10

Facilitates Potent Antioxidant Activity*Supports the Integrity and Activity of Neuronal Cells*Although the mechanisms behind all its actions are not yet fully under-stood, resveratrol is revered for its antioxidant functions. Scientists do know that resveratrol counters lipid peroxidation both by the chelation of copper and the quenching of free radicals. In one of many in vitro trials investi-gating its antioxidant functions, trans-resveratrol worked at 95% efficiency to deter lipid peroxidation. Under the same oxidative stress load, vitamins E and C worked at efficiencies of only 65% and 37%, respectively.11 In a 2010 study, researchers observed resveratrol’s action on erythrocytes (red blood cells) derived from 23 healthy volunteers. When the erythrocytes were subjected to oxidative stress, resveratrol protected the cell glutathi-one levels—evidence of protection from oxidative stress.12

Numerous studies have examined the role of resveratrol in protecting the nervous system from oxidative damage. In one such study the researchers examined resveratrol’s action on in vitro brain cell samples and noted less depletion of the antioxidant glutathione, less accumulation of oxidative agents, and less neuronal damage. These scientists also noted a protective role from sirtuin activity, revealing that the benefits of resveratrol in this scenario can be multifactorial.13 In a recent study, resveratrol prevented an increase in acetylcholinesterase activity in rats, which helped preserve their cognitive function—memory in particular. These observations led to con-clusions that resveratrol may help ameliorate oxidative stress that occurs in several areas of the brain, thereby influencing neurotransmission.14 Several previous studies, such as one showing preserved cognitive function in rats (presumably from resveratrol’s antioxidant activity), build a strong case for the usefulness of resveratrol in supporting brain function in mammals.15

Promotes Healthy Aging*May Enhance Healthy Glucose Metabolism*Perhaps the most intriguing aspect of resveratrol activity is its apparent ability to increase the longevity of numerous species—ranging from simple organisms, like yeast, to those with complex genomes, like mice. In sev-eral organisms, both caloric restriction and resveratrol consumption have demonstrated the ability to activate sirtuins, a group of proteins that have been linked to aging, metabolism, and cellular stress tolerance.16, 17 Acti-vation of sirtuins is a proposed mechanism behind resveratrol’s apparent ability to extend the lifespan of yeast, worms, fruit flies, and vertebrate fish. Since dietary restriction in humans can in many respects lead to a higher quality of life during the aging process, the prospect of a compound that

mimics this dietary restriction garners great attention in the scientific com-munity.

A groundbreaking study published in 2006 demonstrated the ability of resveratrol to shift the physiology of mice consuming excess calories (including some of the health concerns instigated by excessive diets) to one of mice consuming a standard diet—all without significant changes in body weight. In simpler terms, the resveratrol enabled the overeating mice to have a level of health enjoyed by mice that ate a proper diet.18

In a subsequent study using mice, researchers concluded that resveratrol seemed to mimic the effect of a restricted-calorie diet at the transcrip-tional (genetic) level, and was able to benefit tissues of the heart, liver, and muscle in a manner similar to dietary restriction.19 These results are reinforced by yet another study where researchers found that, in mice, a low dose of resveratrol mimicked the effects of a restricted-calorie diet on gene expression in vital organs that affect aging; however, the research-ers concluded that in this case it was due to factors other than influence on sirtuins.20 More research is needed to fully comprehend how resvera-trol works, but the volumes of papers published attest to the multifaceted wonders of resveratrol and its companion red wine phenolic compounds.

Lastly, it should be mentioned that a good deal of interest has been generated by the apparently favorable actions of resveratrol on glu-cose metabolism, as seen in animal studies.21,22 A recent in vitro study demonstrated trans-resveratrol’s influence on how skeletal muscle re-sponds to glucose, presumably through the action of sirtuins.23 Fur-thermore, a 2010 in vitro resveratrol study even shows positive met-abolic interactions with human fat cells.24 While the implications of results like these are provoking, clinical trials need to be conducted

High Potency Trans-Resveratrol 600

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

to determine the degree of practicality for such uses of resveratrol.

In sum, more research is needed to fully comprehend how resveratrol works inside the human body, but the volumes of in vitro and in vivo data attest to the multifaceted potential of the compounds found in a bottle of Best trans-Resveratrol.

SAFETYMost studies have shown that resveratrol is rapidly absorbed and metab-olized in humans. In a 2010 review of safety data from human studies that administered resveratrol at high doses, no serious side effects were reported.25 Although long-term data is not available for humans, long-term resveratrol supplementation at moderate to high (but not extremely high) doses in rodents did not produce side effects.19,26 Because human research is limited, pregnant women should check with a physician prior to using the product.

SCIENTIFIC REFERENCES

1. Bagchi, D., Resveratrol and human health. Keats good healthguide. 2000, Los Angeles, CA: Keats Publishing. 72.

2. de la Lastra, C.A. and I. Villegas, Resveratrol as an anti-inflamma-tory and anti-aging agent: mechanisms and clinical implications.Mol Nutr Food Res, 2005. 49(5): p. 405-30.

3. Martinez, J. and J.J. Moreno, Effect of resveratrol, a natural poly-phenolic compound, on reactive oxygen species and prostaglan-din production. Biochemical Pharmacology, 2000. 59(7): p. 865-870.

4. Subbaramaiah, K., et al., Resveratrol inhibits cyclooxygen-ase-2 transcription and activity in phorbol ester-treated humanmammary epithelial cells. Journal of Biological Chemistry, 1998.273(34): p. 21875-21882.

5. de la Lastra, C.A. and I. Villegas, Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Bio-chem Soc Trans, 2007. 35(Pt 5): p. 1156-60.

6. Donnelly, L.E., et al., Anti-inflammatory effects of resveratrol inlung epithelial cells: molecular mechanisms. Am J Physiol LungCell Mol Physiol, 2004. 287(4): p. L774-83.

7. Kimura, Y., H. Okuda, and M. Kubo, Effects of stilbenes isolatedfrom medicinal plants on arachidonate metabolism and degran-ulation in human polymorphonuclear leukocytes. Journal of Eth-nopharmacology, 1995. 45(2): p. 131-139.

8. Gresele, P., et al., Resveratrol, at concentrations attainable withmoderate wine consumption, stimulates human platelet nitricoxide production. J Nutr, 2008. 138(9): p. 1602-8.

9. Rakici, O., et al., Effects of resveratrol on vascular tone and endo-thelial function of human saphenous vein and internal mammary artery. Int J Cardiol, 2005. 105(2): p. 209-15.

10. Kennedy, D.O., et al., Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind,placebo-controlled, crossover investigation. Am J Clin Nutr, 2010. 91(6): p. 1590-7.

11. Stojanovic, S., H. Sprinz, and O. Brede, Efficiency and mechanism of the antioxidant action of trans-resveratrol and its analoguesin the radical liposome oxidation. Arch Biochem Biophys, 2001.391(1): p. 79-89.

12. Pandey, K. and S. Rizvi, Protective effect of resveratrol on mark-ers of oxidative stress in human erythrocytes subjected to in vitro oxidative insult. Phytother Res, 2010. 24: p. 11-14.

13. Okawara, M., et al., Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults. Biochem Pharmacol,2007. 73(4): p. 550-60.

14. Schmatz, R., et al., Resveratrol prevents memory deficits and the

neuroprotective mechanisms. Behav Pharmacol, 2006. 17(5-6):p. 485-92.

16. Calabrese, V., et al., Cellular stress response: a novel target forchemoprevention and nutritional neuroprotection in aging, neu-rodegenerative disorders and longevity. Neurochem Res, 2008.33(12): p. 2444-71.

17. Baur, J.A. and D.A. Sinclair, Therapeutic potential of resveratrol:the in vivo evidence. Nat Rev Drug Discov, 2006. 5(6): p. 493-506.

18. Baur, J.A., et al., Resveratrol improves health and survival of miceon a high-calorie diet. Nature, 2006. 444(7117): p. 337-342.

19. Pearson, K.J., et al., Resveratrol delays age-related deteriorationand mimics transcriptional aspects of dietary restriction withoutextending life span. Cell Metab, 2008. 8(2): p. 157-68.

20. Barger, J.L., et al., A low dose of dietary resveratrol partially mim-ics caloric restriction and retards aging parameters in mice. PLoSONE, 2008. 3(6): p. e2264

21. Palsamy, P. and S. Subramanian, Resveratrol, a natural phytoalex-in, normalizes hyperglycemia in streptozotocin-nicotinamide in-duced experimental diabetic rats. Biomed Pharmacother, 2008.62(9): p. 598-605.

22. Szkudelski, T., Resveratrol-induced inhibition of insulin secretionfrom rat pancreatic islets: evidence for pivotal role of metabol-ic disturbances. Am J Physiol Endocrinol Metab, 2007. 293(4): p.E901-7.

23. Breen, D.M., et al., Stimulation of muscle cell glucose uptake byresveratrol through sirtuins and AMPK. Biochem Biophys ResCommun, 2008. 374(1): p. 117-22.

24. Fischer-Posovszky, P., et al., Resveratrol regulates human adipo-cyte number and function in a Sirt1-dependent manner. Am JClin Nutr, 2010. 92(1): p. 5-15.

25. Cottart, C.H., et al., Resveratrol bioavailability and toxicity in hu-mans. Mol Nutr Food Res. 54(1): p. 7-16.

26. Juan, M.E., M.P. Vinardell, and J.M. Planas, The daily oral adminis-tration of high doses of trans-resveratrol to rats for 28 days is not harmful. J Nutr, 2002. 132(2): p. 257-60.

increase in acetylcholinester-ase activity in streptozoto-cin-induced diabetic rats. Eur J Pharmacol, 2009. 610(1-3): p. 42-8.

15. Kumar, P., et al., Effect of res-veratrol on 3-nitropropionicacid-induced biochemical and behavioural changes: possible

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