Mega-dose Resveratrol, Sirtuin1 gene Target Discredited; Lower Dose, Array
of Small Molecules (Longevinex(R)) Exert Greater Effect
SAN DIMAS, Calif., Sept. 10 /PRNewswire/ -- While the red wine molecule resveratrol (rez-vair-ah-trawl) has recently attracted scientific and public attention as a longevity molecule that allegedly mimics the effects of a calorie-restricted diet, the science surrounding this molecule has taken a dramatic turn in recent months, according to Bill Sardi, spokesperson for Longevinex(R) (long-jev-in-ex), a major brand resveratrol supplement.
Published research studies now show:
-- Mice fed high-dose resveratrol did not live as long as mice fed a plain standard calorie diet. Animals on the lower dose (360 milligram human equivalent) lived longer than those on the higher dose (1565 mg) of resveratrol. [Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. Cell Metabolism 2008 Aug;8(2):157-68]
-- The Sirtuin1 gene, once called the "holy grail" of longevity and believed to be the gene target of calorie restriction, has not been found to be universally activated by a limited calorie diet. A calorie-restricted diet results in more Sirtuin1 gene-derived proteins by exerting stabilization effects, not by activation of the gene. This new finding throws a scientific cloud over the use of Sirtuin1 gene activation tests as a measure of resveratrol activity. [Tissue-specific regulation of SIRT1 by calorie restriction. Genes Dev. 2008 Jul 1; 22(13):1753-7; Regulation of SIRT1 protein levels by nutrient availability. FEBS Letters. 2008 Jul 9; 582(16):2417-23]
-- While researchers once advised consumers to wait for stronger synthetic molecules that can stimulate the Sirtuin1 gene by 1000-fold or more, actual studies with warm-blood mammals showed over-activation of the Sirtuin1 gene increases the occurrence of heart failure by more than 7.5 fold. [Sirt1 regulates aging and resistance to oxidative stress in the heart. Circulation Research 2007; 100: 1512-21]
-- While it was initially believed only mega-dose resveratrol would be effective, and that strong Sirtuin1 gene activators would be required, a much lower dose of resveratrol (100 milligrams human equivalent of trans resveratrol, 4 to 320 times lower than previous studies, when provided in a patent-applied for matrix of other small molecules), exerted a 9-fold greater genomic effect than plain resveratrol or a calorie-restricted diet. In this study, calorie restriction significantly differentiated (up or down-regulated) 198 genes, and resveratrol, its molecular mimic, significantly influenced 225 genes, while resveratrol-based matrix (Longevinex(R)) significantly differentiated 1711 genes. [Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart. Experimental Gerontology 2008 Sep;43(9):859-66]
Sardi says websites selling resveratrol supplements still parrot earlier but now outdated news reports about Sirtuin1 genes and mega-doses appear oblivious to the striking changes in resveratrol science that have been recently published. "Paying heed to the current data now available, mega-dose resveratrol is ill-advised and may be related to uncommon but reported side effects, namely Achilles heel tendon inflammation, skin rash, joint stiffening, flu-like symptoms and numbness in fingertips, all which are reversible," says Sardi.
Some marketers of resveratrol supplements still misguidedly refer to the 2006 study published in Nature Magazine where mice lived longer on a resveratrol-fed diet, but these mice were fed a 60% fat-calorie diet which could not possibly be achieved by humans. (Humans consume about 35% fat calories). The fat-engorged mice did live longer on resveratrol, but this experiment is not comparable to humans eating a normal diet. [Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006 Nov 16; 444(7117):337-42]
The Sirtuin1 gene does not appear to be the "holy grail" of longevity by itself, as once claimed. The Sirtuin family of genes works in tandem with other genes, such as FOXO1 and PGc1alpha. [Interaction of aging-associated signaling cascades: inhibition of NF-kappaB signaling by longevity factors Foxos and SIRT1. Cell Mol Life Science. 2008 Apr; 65(7-8):1049-58; Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. Proceedings National Academy of Science: 2005 Aug 9; 102(32):11278-83]
Nor does a singular molecule such as resveratrol appear to work as well as resveratrol combined with quercetin or other small molecules. [Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model. Translational Oncology 2008 March; 1(1):19-27; Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Science 2008 May 7; 82(19-20):1032-9]
Sardi says other key genes, particularly the FOXO1 gene, which plays a key role in a variety of biological processes, including metabolism, cell proliferation, and oxidative stress response, may play a stronger role than the Sirtuin1 gene in producing longevity.
At the National Library of Medicine online there are now 706 published journal reports on FOXO1, and 471 on Sirtuin1. In the gene array study published in the September 2008 issue of Experimental Gerontology, only Longevinex(R), and not calorie restriction of plain resveratrol, activated the FOXO1 gene.
Longevinex(R) has since abandoned the Sirtuin1 gene activation test as a measure of dietary supplement activity. In the Longevinex(R) mouse study, the Sirtuin1 gene was down-regulated, however, Longevinex(R) still could have resulted in more Sirtuin1 gene-derived protein via stabilization pathways. Only messenger RNA, not Sirtuin1 gene protein, was measured in this genomic test.
Longevinex(R) was formulated as an emulsified, stabilized, and bioavailability-enhanced resveratrol supplement over four years ago and a patent applied for in 2004. The 3rd generation Longevinex(R) now features micronized and microencapsulated trans resveratrol in a matrix of quercetin, rice bran phytate, vitamin D3 and ferulic acid. To learn more, visit http://www.longevinex.com
|SOURCE Resveratrol Partners, LLC|
Copyright©2008 PR Newswire.
All rights reserved