Dr Paul Clayton 2010
Resveratrol, a fascinating compound found inter alia in grapes, red wine and peanuts, is a front-runner in the age extension stakes and as good an example of the health benefits of nutrition as you are likely to find anywhere.
A phytoalexin (plant defence compound) used by grapes and peanuts to ward off fungal attack, resveratrol first came to public attention when David Sinclair and his team from Harvard reported that resveratrol was able to increase the lifespan of yeast cells (Howitz et al ’03).
Sinclair’s group found that resveratrol could activate a gene called sirtuin1 (Sirt1 – the yeast equivalent was Sir2), which is also activated during calorie restriction in a number of species including monkeys. Since then, studies in nematode worms, fruit flies, fish and mice have linked resveratrol to longer lives.
Other studies with resveratrol have reported anti-cancer effects, anti-inflammatory effects, cardiovascular benefits, anti-diabetes potential, weight loss, energy endurance enhancement, HRT effects, eye health and protection against Alzheimer’s.
Here are a few examples of recent resveratrol pre-clinical findings with their theoretical (and as yet unproven) health benefits:
Resveratrol prevents the accumulation and multiplication of fat cells (Fischer-Posovszky et al ’10).
Theoretical benefit: May aid weight control, prevent obesity and Type 2 diabetes.
Resveratrol stimulates the regeneration of cells that line healthy blood vessels (Hamed et al ’10).
Theoretical benefit: May prevent atherosclerosis and hypertension.
Resveratrol improves blood flow to the brain (Kennedy et al ’10).
Theoretical benefit: May protect against dementia.
Resveratrol is an alternative to HRT which protects against breast cancer (Sakamoto et al ’10).
Theoretical benefit: Safer HRT therapies.
Resveratrol prevents formation of abnormal blood vessels in the retina (Khan et al ’10).
Theoretical benefit: May prevent loss of vision in diabetes and senior citizens.
So should we all be swallowing resveratrol pills? In my view this would be an unnecessary, expensive and unproven strategy. Despite all the promising pre-clinical work with resveratrol there have been very few clinical trials, so we don’t really know much about the clinical effectiveness of this compound. In fact, a study of resveratrol carried out by Pfizer recently reported a negative result (Pacholec et al ’10).
Nor do we know enough about safety; the supplements currently on the market offer doses of 30 to 150 mg, which are far in excess of dietary levels.
Resveratrol is not unique. Similar molecules occur widely in the diet, such as the curcuminoids (derived from the spice turmeric), the catechins (in green and black tea) [See Superfoods Green Tea], quercitin (in apples and onions) [See Superfoods Apples], and fisetin (in mangoes); and all of these phyto-nutrients appear to have the ability to activate the Sirt1 gene (Kang et al ’08, Chung et al ’10).
Cocoa flavonols [See Superfoods Chocolate] probably have similar effects, and many more related compounds occur in a wide range of fruits, vegetables and other plant foods.
Sadly, this does nothing to support the government’s inane 5-a-day propaganda, an approach so timid that while it confers slight cardiovascular benefits, it has hardly any impact on our terrible cancer statistics at all (Boffetta et al ’10).
To achieve real protection from the degenerative diseases, the historical evidence shows that we would need considerably higher intakes of phytonutrients (Clayton & Rowbotham ’09). These levels are so high that few would be able to obtain the recommended levels of phytonutrients from diet alone.
There is therefore a strong case for supplementation with broad spectrum phytonutrients, containing the appropriate levels of flavonoids and a range of other polyphenols.
Boffetta P, Couto E, Wichmann J and 48 others. Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst. 2010 Apr 21;102(8):529-37.
Clayton P, Rowbotham J. How the mid-Victorians worked, ate and died. Int J Environ Res Public Health. 2009 Mar;6(3):1235-53.
Chung S, Yao H, Caito S, Hwang JW, Arunachalam G, Rahman I. Regulation of SIRT1 in cellular functions: Role of polyphenols. Arch Biochem Biophys. 2010 May 5.
de Boer VC, de Goffau MC, Arts IC, Hollman PC, Keijer J. SIRT1 stimulation by polyphenols is affected by their stability and metabolism. Mech Ageing Dev. 2006 Jul;127(7):618-27.
Fischer-Posovszky P, Kukulus V, Tews D, Unterkircher T, Debatin K-M, Fulda S, Wabitsch M. Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. Am J Clin Nut 2010, 92, 5-15.
Hamed S, Alshiek J, Aharon A, Brenner B, Roguin A. Red wine consumption improves in vitro migration of endothelial progenitor cells in young, healthy individuals. Am J Clin Nut 2010, Volume 92, Pages 161-169.
Howitz KT, Bitterman KJ, Cohen HY et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003 Sep 11;425(6954):191-6.
Kang SK, Cha SH, Jeon HG. Curcumin-induced histone hypoacetylation enhances caspase-3-dependent glioma cell death and neurogenesis of neural progenitor cells. Stem Cells Dev. 2006 Apr;15(2):165-74.
Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nut, Published online ahead of print, doi:10.3945/ajcn.2009.28641.
Khan AA, Dace DS, Ryazanov AG, Kelly J, Apte RS. Resveratrol regulates pathologic angiogenesis by a eukaryotic elongation factor-2 kinase-regulated pathway. Am J Path July 2010, Volume 177, Pages 481-492.
Pacholec M, Bleasdale JE et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem. 2010 Mar 12;285(11):8340-51.
Sakamoto T, Horiguchi H, Oguma E, Kayama F. Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. J Nut Biochem Published online ahead of print: doi: 10.1016/j.jnutbio.2009.06.010.