Oxaloacetate Oxaloacetate  is a four-carbon molecule found in the mitochondrion that condenses with acetyl CoA to form citrate in the first reaction of the Krebs cycle. Also known as the Citric Acid Cycle, the Krebs Cycle consists of a series of reactions that produce high- energy electron carriers to be used in the electron transport chain in the production of adenosine triphosphate (ATP).  ATP is the main energy source for the majority of all cellular functions. Without adequate ATP, cells do not function. Oxaloacetate is a critical component in the production of ATP and must be constantly regenerated in order for the Krebs cycle and the electron transport chain to continue. Oxaloacetate has been documented to... • Increase Lifespan and Health Span* ¹ • Provide Potent antioxidant protection* ^2,3,4,5,6,7 • Reduce fasting glucose levels and reduce insulin resistance* ^8,9 • Protect brain mitochondrial DNA*¹⁰ • Mimic some of the molecular pathways of Calorie Restriction* ^1,11 • Protect rentinal RPE cells in age-related macular degeneration* ¹² • Protect prancreatic islet cells* ¹³ • Protect brain neurons*¹⁴ • Prevent the growth of human lung cancer cells, while not affecting normal cells (in culture)* ¹⁵ While these tests have been conducted primarily on animals or in culture due to either the destructive nature of the tests, or the time to perform the tests, and do not prove efficacy in humans, they do provide an insight into the working mechanisms of oxaloacetate supplementation and has major implications for use in humans.* RR has evaluated this research and has selected benaGene^TM as our supplier. What is benaGene? benaGene is composed of two compounds already found within your body: the bio-identical human metabolite oxaloacetic acid (oxaloacetate in water) and Vitamin C. Oxaloacetate is central to metabolism and is found in every cell of your body. Why should I take benaGene? There are many reasons: 1) Within the last five years, there have been several studies by major universities documenting that an increase in the NAD+/NADH ratio results in statistically significant increases in lifespan and health-span in laboratory animals. Equally as exciting, this same increase in the NAD+/NADH ratio has also been shown to increase individual human cell lifespan in vitro. benaGene is a bio-identical human metabolite that increases the NAD+/NADH ratio, and has been proven to result a 25% increase in lifespan in laboratory animals (p < 0.001). Health-span of the animals is also remarkably increased. 2) Clinical trials using oxaloacetate have documented significant glucose level reductions in diabetic patients. A separate study in non-diabetic patients documented a reduction in the amplitude of glucose swings, allowing better overall blood sugar management. No negative side effects were reported. Although benaGene lowers high glucose levels, it does not cause hypoglycemia (abnormally low glucose levels) in non-diabetic patients. 3) benaGene is a powerful anti- oxidant, and has been shown to protect neurological tissue, pancreatic tissue and eye tissue. Other benaGene benefits Anecdotal benefits reported in Canada and Europe (where the product has been on the market for several years), other than an increase in lifespan and better glucose management include the following: 1) Reduction in sugar cravings. 2) Improved energy. 3) Improvement in sleep. 4) Reduction in constipation. 5) Reduction in the ability to create and store fat. Individual results may vary. If I am taking resveratrol, should I also take benaGene? Resveratrol is thought to work by stimulating the Sirtuin proteins which use NAD+ as a substrate. benaGene works by making more NAD+ available. The two compounds can work synergistically. Is there proof that benaGene increases Lifespan? Yes, but only in animals. To properly conduct a statistically valid test in humans, we would need 130 years. Note that calorie restriction has also not been proven in humans, but has been proven in yeast, worms, flies, guppies, spiders, mice, rats, dogs, and a 20-year study just confirmed that monkeys also live significantly longer (and healthier) under calorie restriction. Human populations that have undergone reduced calorie consumption (without stavation) also have higher percentages of persons over 100 years old. RR has tested oxaloacetate and has selected benaGene^TM as our supplier. We are very impressed with this product and highly recommend it! benaGene is available from all RR practitioners. Our results consistently show users experience... • Deeper sleep patterns • Increased energy • Increased sense of relaxation and well-being References 1. Williams, D.S., et al., Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway. Aging Cell, 2009. 8(6): p. 765-768. 2. Desagher, S., J. Glowinski, and J. Premont, Pyruvate protects neurons against hydrogen peroxide-induced toxicity. J Neurosci, 1997. 17(23): p. 9060-7. 3. Desagher, S. and J.C. Martinou, Mitochondria as the central control point of apoptosis. Trends Cell Biol, 2000. 10(9): p. 369-77. 4. Bhattacharya, R. and R. Tulsawani, In vitro and in vivo evaluation of various carbonyl compounds against cyanide toxicity with particular reference to alpha-ketoglutaric acid. Drug Chem Toxicol, 2008. 31(1): p. 149-61. 5. O'Donnell-Tormey, J., et al., Secretion of pyruvate. An antioxidant defense of mammalian cells. J Exp Med, 1987. 165(2): p. 500-14. 6. Puntel, R.L., C.W. Nogueira, and J.B. Rocha, Krebs cycle intermediates modulate thiobarbituric acid reactive species (TBARS) production in rat brain in vitro. Neurochem Res, 2005. 30(2): p. 225-35. 7. Puntel, R.L., C.W. Nogueira, and J.B. Rocha, N-methyl-D-aspartate receptors are involved in the quinolinic acid, but not in the malonate pro- oxidative activity in vitro. Neurochem Res, 2005. 30(3): p. 417-24. 8. Yoshikawa, K., Studies on the anti-diabetic effect of sodium oxaloacetate. Tohoku J Exp Med, 1968. 96(2): p. 127-41. 9. Cash, A., Oxaloacetic Acid Supplementation as a Mimic of Calorie Restriction. Open Longevity Science, 2009. 3: p. 22-27. 10. Yamamoto, H.A. and P.V. Mohanan, Effect of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA damage and seizures induced by kainic acid in mice. Toxicol Lett, 2003. 143(2): p. 115-22. 11. Greer, E.L., et al., An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr Biol, 2007. 17(19): p. 1646-56. 12. Wood, J.P. and N.N. Osborne, Zinc and energy requirements in induction of oxidative stress to retinal pigmented epithelial cells. Neurochem Res, 2003. 28(10): p. 1525-33. 13. Chang, I., et al., Pyruvate inhibits zinc-mediated pancreatic islet cell death and diabetes. Diabetologia, 2003. 46(9): p. 1220-7. 14. Zlotnik, A., et al., Brain neuroprotection by scavenging blood glutamate. Exp Neurol, 2007. 203(1): p. 213-20. 15. Farah, I.O., Differential modulation of intracellular energetics in A549 and MRC-5 cells. Biomed Sci Instrum, 2007. 43: p. 110-5. * 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 purchase, please contact one of our authorized practitioners or the Foundation. © Resonance Research Foundation, Inc. 1991-2013