Resveratrol: Can we bring the science into practice?

Kelly C. Heim, Ph.D., Nutritional Pharmacologist at Pure Encapsulations

Why do we grow old? Dr. Leonard Guarente, a professor of biology at the Massachusetts Institute of Technology, asked himself this question in 1991 and began to seek answers. Over the next four years, he observed different types of cells, some of which lived much longer than others. He explored their genetic and biochemical distinctions. By 1997, Guarente had discovered the reason for the cells’ longevity – they expressed very high levels of an anti-aging gene.1

In animals, this gene (known as SIRT1) is activated when calories are restricted. When laboratory animals are fed 40% less, they live up to 60% longer.2 Concurrently, they exhibit “youthful” metabolic features, handling glucose in a healthy manner and regenerating mitochondria, the cellular energy powerhouses that are important for heart health, fat metabolism and brain function as we age. In 1999, Guarente’s main collaborator, Australian biologist Dr. David Sinclair, continued this research in Harvard Medical School’s Department of Genetics. In 2003, Sinclair’s group published a study showing that resveratrol, a natural compound found in grapes, red wine and certain fruits, activates the SIRT1 gene.3

Sinclair’s group soon discovered that resveratrol mimics the metabolic benefits of a low-calorie diet. Middle-aged mice that were fed a high-calorie diet plus resveratrol lived just as long as mice consuming a lower-calorie diet. Of the 153 metabolic pathways affected by overeating, resveratrol maintained homeostasis in 144. Despite their excess food intake, the animals receiving resveratrol maintained healthy clinical metabolic features, such as blood glucose homeostasis and an abundance of mitochondria.4*

Since 2003, resveratrol has graced the titles of over 3,500 studies and scholarly reviews.   Although resveratrol does not counteract weight gain, it helps the body handle the carbohydrates and fats from the diet—a process that often changes as part of the aging process.5* Since the award-winning work of Guarente and Sinclair involved cells and animals, not human subjects, a critical question remains: How much resveratrol should people consume?

The dosage question can only be answered by randomized, placebo-controlled human clinical trials showing clinically measurable results using available formulations at affordable and safe doses. Although more than 50 clinical investigations have been published in the last decade, there is little consistency with dosage. Some have administered 500 milligrams per day of the isolated compound—much higher than the amount attainable through the diet (red wine, one of the richest dietary sources, delivers about 1 milligram per glass).6

The resveratrol content of fruits such as grapes and berries is low, and naturally varies depending on the growth conditions and poorly tractable agrarian variables. Red grapes cultivated during a dry season or in a sunny climate will contain very little resveratrol compared to grapes grown in damp conditions.8 The consensus is that food is not a meaningful source. The scientific spotlight has shifted to dietary supplements providing moderate, safe, consistent and affordable doses.

Countless resveratrol formulations have entered the marketplace, providing a variety of doses, forms and bioavailability enhancements. For patients and doctors alike, navigating the selection can be overwhelming. Selecting clinically researched preparations is the only way to make a truly rational decision. Ideally, the dosage and form should correspond to the dose in a published human trial, and the results of that trial should be pertinent to patient objectives. These evidence-based formulations deliver the compound in a form and at a dose that has been validated by at least one human clinical trial. Unfortunately, “evidence-based” is not a term you will find on a label, and these products are hard to find. Some manufacturers, such as Pure Encapsulations in Sudbury, Massachusetts, focus on science-driven formulations. The company has a solid history as a trusted source of the supplements used by academic researchers for clinical studies.

In 2010, researchers at the State University of New York at Buffalo sought to evaluate a low-dose product containing natural resveratrol against cytokines, insulin and markers of “youthful” energy metabolism. The authors selected Pure Encapsulations Resveratrol, which provides 40 mg per capsule from a reliable botanical source (Polygonum cuspidatum extract, which has a long history of use) for the 6-week randomized, placebo-controlled clinical study. Measurements of metabolic gene expression and biomarkers of insulin function indicated that 1 capsule per day produced statistically significant support for metabolic health measurements after only 3 weeks.7 The study also showed that the supplement increased antioxidant capacity and maintained healthy levels of cytokines—chemical signals in the body that increase during stress and aging. A 2013 study independently confirmed that the same supplement maintained healthy cytokine levels in healthy individuals.8*

Although this product has not been evaluated in longevity studies, the published data indicate statistically significant and clinically relevant support for healthy metabolism and antioxidant defenses at a low daily dose that is safe, well tolerated and reliable. For patients, the take-away message is simple—meaningful health-promoting effects can be achievable in a single daily capsule.* For the many health care providers recommending resveratrol to their patients, an evidence-based formulation is empowering. With the data in their hands, they can bring the science into practice with confidence.

*These statements have not been evaluated by the Food & Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.

The information contained herein is for informational purposes only and does not establish a doctor-patient relationship. Please be sure to consult your physician before taking this or any other product. Consult your physician for any health problems.

References

  1. Sinclair, D.A. and Guarente, L. 1997. Extrachromosomal rDNA circles—a cause of aging in yeast. Cell 91:1033-1042.
  1. Fontana, L. 2009. The scientific basis of caloric restriction leading to longer life. Curr Opin Gastroenterol 25:144-150.
  1. Howitz, K.T., Bitterman, K.J., Cohen, H.Y., et al. 2003. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191-196.
  1. Baur, J.A., Pearson, K.J., Price, N.L., et al. 2006. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337-342.
  1. Bhatt, J.K., Thomas, S., and Nanjan, M.J. 2012. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res 32:537-41.
  1. Sato, M., Suzuki, Y., Okuda, T., and Yokotsuka, K. 1997. Contents of resveratrol, piceid, and their isomers in commercially available wines made from grapes cultivated in Japan. Biosci Biotechnol Biochem 61:1800-5.
  1. Ghanim, H., Sia, C.L., Abuaysheh, S., et al. 2010. An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J Clin Endocrinol Metab 95:E1-E8.
  1. Zahedi, H.S., Jazayeri, S., Ghiasvand, R., Djalali, M., Eshraghian, M.R. 2013. Effects of Polygonum cuspidatum containing resveratrol on inflammation in male professional basketball players. Int J Prev Med 4(Suppl 1):S1-S4.
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