Poly-MVA - Energy To Get The Job Done - Part Two
Why is this supplement often credited or associated with providing energy? While Poly-MVA does indeed have the ability to be a highly effective free radical scavenger, its ability to donate electrons to the mitochondria of the cell is critical to explaining its dramatic benefits. Anecdotal clinical evidence of the reports of additional energy led to my early hypotheses regarding its possible benefits in stroke and ischemia. Following an interruption of blood flow to any tissue, in my particular case it is the brain, there is deprivation of oxygen and glucose. Providing an alternative energy source can maintain the integrity of the electron transport chain within the mitochondria.
The LAPd complex was demonstrated, by Dr. Garnett, to shuttle electrons to oxidized DNA, however, this energy flow does not appear to proceed directly to DNA. By conducting a competition assay with lipoic acid, which works at complex I of the mitochondria as a cofactor as pyruvate is converted to acetyl CoA, one can attenuate the beneficial effects. This is critical since mitochondrial health is a major concern during myocardial and cerebral ischemia. By providing this alternative energy source, the electron transport chain components do not readily dissociate (coenzyme Q-10 = ubiquinone; cytochrome C). In a normal cell this would obviously provide a boost, but serve as a supplement to an ischemic cell.
Can Poly-MVA be taken with other vitamins and free radical scavengers? Since lipoic acid palladium complex is a highly efficient redox molecule, normal daily recommended values of vitamins have not been of consequence in our laboratory studies. However, excessive doses of anti-oxidants may attenuate Poly-MVA's benefits. As mentioned above, administration of alpha lipoic acid in our competition assay hindered the redox benefits of Poly-MVA. However, alpha lipoic acid alone only offers a fraction of the ischemic protection offered by the polymer.
MECHANISMS OF ACTION
Poly-MVA's proposed mechanisms of action directly related to its structural formulation. Dr. Garnett's complex is a liquid crystal polymer and provide a unified redox. Redox polymers more efficiently accept charge, and therefore serve as potent anti-oxidants. Furthermore, they can also donate charge and serve as alternative energy sources. This electron transfer appears to be the key to its physiological effectiveness. When glucose enters a cell it is broken down under anaerobic conditions (absence of oxygen) into pyruvate. Pyruvate subsequently enters the mitochondria, via complex I, and is quickly oxidized, in the presence of alpha-lipoic acid, to acetyl-CoA. In aerobic respiration, acetyl-CoA is then channeled into the Krebs/Citric Acid Cycle to create the reduced form of nicotinamide adenine dinucleotide (NADH). NADH donates its electron to the electron transport chain to drive the phosphorylation of adenosine triphosphate (ATP). The energy needs of the body are supplied by splitting ATP into adenosine diphosphate (ADP) and a free phosphate molecule.
Studies have demonstrated that LAPd provides electrons to DNA (to replace the electrons lost in normal cells as a result of the oxidative damage associated with radiation and chemotherapy) via the mitochondria. This electron transfer will provide an additional energy source to normal cells. However, cancer cells are metabolically challenged, as well as, function in a hypoxic environment. Since excess electrons have less oxygen to accept them in the cancer cell, a local generation of free radicals occurs at the mitochondrial membrane. This activates apoptosis by facilitating the release of cytochrome C from the inner mitochondrial membrane, allowing the formation of an apoptotic complex in the cytoplasm. This complex, results in the subsequent activation of the caspase cascade of enzymes that destroy the malignant cells. Given that healthy cells are richly oxygenated, LAPd is nontoxic to them and they actually benefit from the energy boost.
Recent findings have focused on the role of Poly-MVA and a malignant cell's ability to physiologically adapt to a hypoxic environment. These physiological changes are mediated by a molecule called HIF-1 (hypoxia inducible factor-1), which increases in hypoxic conditions to promote an increases in: Vascular Endothelial Growth Factor (VEGF) - a promoter of angiogenesis; Glucose Transport 1 (GLUT1) and glycolytic enzymes - critical components in anaerobic respiration; and Erythropoietin (EPO) - responsible for the differentiation of red blood cells). Poly-MVA appears to decrease the production of HIF-1 thus restricting the ability of the cells to adapt to its environment and subsequently making it more vulnerable to the apoptotic cell death discussed above.
About the author:
FRANCIS J. ANTONAWICH, Ph.D. received his B.S. Degree in Neuroscience from the University of Rochester in 1988. His graduate studies were completed in Dr. Fleur Strand's Laboratory of Physiology and Neuroendocrinology at New York University. Visit www.polymva.com for more information.