Resveratrol (3,5, 4’-trihydroxystilbene) and pterostilbene (3,5-dimethoxy-4’-hydroxystilbene) are both chemically classified as stilbene compounds.

Biologically, they are both phytoalexins.The phytoalexins are generally lipophilic substances that are products of a plant’s secondary metabolism, and they often accumulate at infection sites to concentrations, which are inhibitory to the development of fungi, bacteria and other pathogens.1

Pterostilbene is closely related structurally to resveratrol and shares many of the same characteristics, yet possesses some of its own unique therapeutic potential. Despite what appears to be subtle differences in chemical structure, they translate into significant variances in absorption, bioavailability and biological activity. The result of a simple substitution of a hydroxyl group-OH (resveratrol) with a methyl group-CH3 (pterostilbene), these differences offer advantages with regard to absorption, bioavailability and chemical stability.2

Regardless of differences in absorption and biological activity, stilbenes, including resveratrol and pterostilbene, work synergistically to influence the expression of genes involved in longevity and likely complement one another in increasing both the quantity and quality of life. Both resveratrol and pterostilbene have demonstrated significant cardiovascular and antioxidant benefits.In addition, they both share anticarcinogenic and anti-inflammatory properties as well as support healthy insulin function and blood sugar metabolism.

Resveratrol

Found in red grapes, red wine, peanuts and many other foods, resveratrol has demonstrated significant antioxidant properties and has been proposed to be a key factor in the “French Paradox.”3 Resveratrol has been proposed to reduce the risk for cardiovascular disease via its ability to reduce the oxidation of LDL (bad) cholesterol as well as the uptake of oxidized LDL cholesterol into the walls of blood vessels.4,5 In addition, resveratrol helps promote the synthesis of nitric oxide, a compound which contributes to the relaxation of blood vessels. Through these and other mechanisms, resveratrol helps promote cardiovascular health.

Resveratrol has also been shown to play a role in all major stages of carcinogenesis, including initiation, promotion and progression. The mechanisms whereby resveratrol exerts its effects include the ability to impact cell growth, cell death, angiogenesis (growth of new blood vessels) and metastasis.6,7

Resveratrol has been shown to mimic the biological effects of a low calorie diet. Studies done in several different organisms clearly demonstrate the influence of resveratrol on some of the changes associated with longer lifespan including improved insulin function, more and better functioning mitochondria as well as better motor function.8,9

The ability of resveratrol to influence genes (sirtuins) that are believed to play a significant part in the aging process has researchers carefully evaluating resveratrol as a potential “anti-aging” compound.Likely not the fountain of youth, however, resveratrol holds much promise as a component of a healthy lifestyle.

Pterostilbene

Naturally found in small berries such as blueberries, huckleberries and grapes, pterostilbene is the lesser-known chemical cousin of resveratrol. The differences In chemical structure allow pterostilbene to be more lipophilic (fat-soluble) than resveratrol, thereby allowing for greater cellular uptake (via the lipid-filled cell membrane) and increased metabolic stability.

For stilbene compounds such as pterostilbene and resveratrol, the key to biological activity in bioavailability— when administered orally, pterostilbene shows 95 percent bioavailability while resveratrol only has 20 percent bioavailability.10 In addition, pterostilbene’s half-life is seven times longer than resveratrol, 105 minutes and 14 minutes respectively.11 Pterostilbene has several pharmacological actions including hypocholesterolemic, anti-inflammatory, anticarcinogenic and antioxidant.

PPAR-alpha is a protein involved in numerous biological functions, one being cholesterol metabolism. Pterostilbene and resveratrol both have hypolipidemic properties; however, only pterostilbene has been shown to be a PPAR-alpha agonist, suggesting a difference in their mechanism of action. Pterostilbene has been shown to reduce total and LDL cholesterol as well as increase HDL; similar mechanism shared by a class of lipid-lowering prescription drugs known as fibrates (i.e., ciprofibrate).12

Inflammation is a major component of many chronic diseases. Pterostilbene has been shown to lower the production of inflammatory cytokines (cell signaling proteins) TNF-alpha and, IL-1 beta as well as reduce COX-2 gene expression, all of which contribute to a significant anti-inflammatory effect.13,14 Chronic inflammation in the colon increases the risk for colon cancer and studies show a reduced risk for colon cancer when antiinflammatories are used (i.e,. aspirin and other NSAIDS). With pterostilbene, one has a natural anti-inflammatory, which may provide similar benefits, but more human studies are needed to determine the extent of those benefits.

Similar to resveratrol, pterostilbene has been shown to have anticarcinogenic effects via multiple mechanisms, including inhibiting enzymes that stimulate cancer growth (COX-2), stimulating apoptotic (programmed cell death) mechanisms in cancer cells and reducing the metastases of several forms of cancer.15 Cancer cells communicate with each other across special connectors called gap junctions. Pterostilbene disrupts those gap junctions, interfering with cancer cell-to-cell communication, which is required to maintain their viability. Disruption of gap junctions is a mechanism that appears to be truly unique to pterostilbene.

With regard to blood sugar and diabetes, pterostilbene was shown to lower blood glucose levels, and increase insulin levels in diabetic rats better than the pharmaceutical drug Metformin, and at a much lower dose.16

Pterostilbene has been shown in animal study models to support glucose metabolism, insulin function and significantly reduce glycosylated hemoglobin, a marker of long-term maintenance of healthy blood glucose levels. Glycation is a process whereby glucose attaches itself to proteins causing significant cellular and tissue damage over time and is believed to be a contributing factor to cellular aging.16 Pterostilbene, like resveratrol is a powerful antioxidant, and, in addition, has the ability to influence the expression of genes involved in the aging process. Most of the research on pterostilbene has been done in cell culture and laboratory animals.The University of Mississippi is currently conducting a study on the effects of pterostilbene on cholesterol levels in humans. More human clinical studies are sure to follow as this compound offers a wide variety of health benefits, along with an excellent safety profile.

Conclusion

Pterostilbene, despite sharing many similarities with the better-known stilbene resveratrol, offers some very important advantages. The chemical structure of pterostilbene allows for a much greater absorption and bioavailability profile than resveratrol. These two features are what will clearly determine clinical efficacy. Studies show that resveratrol and pterostilbene work synergistically, therefore it would be advantageous for those individuals wanting to achieve maximum benefits from these two compounds, to take them together.Since they are found together in many foods, when taking a supplement, one would ideally want to come as close as possible to consuming them as they are found in food. This way, one can achieve the maximum synergistic benefits of these two gifts from nature.

References:

1 Kuç J, Rush J. Phytoalexins. Archives of Biochemistry and Biophysics.
1985;236:455-472.

2 Kapetanovic I, et al. Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog pterostilbene in rats. Cancer, Chemother Pharmacol 2010;68:593-601.

3 Renaud S, De Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992;339:1523-1526.

4 Frankel E, et al. Inhibition of human LDL oxidation by resveratrol. Lancet 1993;341:1103-1104.

5 Fremont L, et al. Antioxidant activity of resveratrol and alcohol-free wine polyphenols Related to LDL oxidation and polyunsaturated fatty acids. Life Sci 1999;64:2511-2521.

6 Kraft T, et al. Fighting cancer with red wine? Molecular mechanisms of resveratrol.Crit Rev Food Sci 2009;49:782-799.

7 Athar M, et al. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol Appl Pharmacol 2007;224:274-283.

8 Valenzano D, et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in short-lived vertebrate.Curr Biol 2006;16:296-300.

9 Sinclair D, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006;444:337-342.

10 Lin H , et al. Determination of pterostilbene in rat plasma by a simple HPLC-UV method and its application in pre-clinical pharmacokinetic study.Biomed Chromatogr 2009;23:1308.

11 Remsberg C, et al.Pharmacometrics of pterostilbene: Preclinical pharmacokinetics and metabolism, anticancer, anti-inflammatory, antioxidant and analgesic activity. Phytother Res 2008;22:169.

12 Rimando A, et al. Pterostilbene, a new agonist for the peroxisome proliferatoractivated receptor ·-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem 2005;53:3403-3407.

13 Burn J, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomized controlled trial. Lancet 2011;378:2051-2052.

14 Mikstacka R, et al. Inhibition of human recombinant cytochromes P450 CYP1A1 and CYP1B1 by trans-resveratrol methyl ethers. Mol Nutr Food Res 2007;51:517-524.

15 Tolomeo M, et al. Pterostilbene and 3’-hydroxypterostilbene are effective apoptosis- inducing agents in MDR and BCRABL- expressing leukemia cells. Int J Biochem Cell Biol 2005;37:1709-1726.

16 Pari L, Satheesh M. Effect of pterostilbene on hepatic key enzymes of glucose metabolism in streptozotocin- and nicotinamide- induced diabetic rats. Life Sci 2006;79: 641–5.

Brian Tanzer, MS, CNS is a former instructor, Department of Health and Nutrition Sciences, Brooklyn College and Department of Natural and Applied Sciences, LaGuardia Community College, both in New York. He also has several years of experience in the nutraceutical industry in research, product development, technical support and product education. An active member of the American College of Nutrition and American Society for Nutrition, Tanzer is currently head of research and technical support for Reliance Private Label Supplements (Somerset, NJ). E-mail him at brian.tanzer@reliancevitamin.com.