gah i just hit one of those damned ads by accident and lost the post i had been working on grrrr
on chelation of heavy metals..
Chelation in Metal Intoxication
Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.
Vitamins, essential metals or amino acid supplementation during chelation therapy has been found to be beneficial in increasing metal mobilization and providing recoveries in number of altered biochemical variables [204-206]. These antioxidants (vitamin C and E, α-lipoic acid etc.) when given either alone or in combination with a chelating agent proved to be effective in mobilizing metal from soft as well as hard tissue .
203. Flora, S.J.S.; Mittal, M.; Mehta, A. Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Ind. J. Med. Res. 2008, 128, 501-523.
204. Pachauri, P.; Saxena, G.; Mehta, A.; Mishra, D.; Flora, S.J.S. Combinational chelation therapy abrogates lead induced neurodegeneration in rats. Toxicol. Appl. Pharmacol. 2009, 240, 255-265.
205. Flora, S.J.S.; Pande, M.; Mehta, A. Beneficial effect of combined administration of some naturally occurring antioxidants (vitamins) and thiol chelators in the treatment of chronic lead intoxication. Chem. Biol. Inter. 2003, 145, 267-280.
206. Pande, M.; Flora, S.J.S. Lead induced oxidative damage and its response to combined administration of α-lipoic acid and succimers in rats. Toxicology 2002, 177, 187-196.
Int. J. Environ. Res. Public Health 2010, 7 2788
207. Kannan, G.M.; Flora, S.J.S. Combined administration of n-acetyl cysteine and monoisoamyl DMSA on tissue oxidative stress during arsenic chelation therapy. Biol. Trace Elem. Res. 2006, 110, 43-59
so in terms of nutritional antioxidants, such as A, C, E and lipoic acid, that last one is the one i know the least about.
LA is negligible in food according to whfoods; here are their listed risk factors for deficient LAhttp://www.whfoods.com/genpage.php?tnam ... t&dbid=117
Interestingly, because lipoic acid is found in the mitochondria (energy production units) of animal cells, individuals who eat no animal products may be at higher risk for lipoic acid deficiency than individuals who do. Vegetarians who eat no green leafy vegetables may also be at special risk, since the chloroplasts in these leaves house most of the lipoic acid...
funny, i was both those things for many years :S
Since lipoic acid protects proteins during aging, older individuals may be at greater risk of deficiency.
Similarly, because lipoic acid is used to help regulate blood sugar, individuals with diabetes may be at special risk of deficiency.
Individuals with poor protein intake, and particularly those with poor intake of the sulfur-containing amino acids (the building blocks of protein that contain sulfur, namely, methionine, cysteine, and taurine) may also be at higher risk of lipoic acid deficiency. The reason for this connection is simple: lipoic acid gets its sulfur atoms from these sulfur-containing amino acids.
Because lipoic acid is asorbed primarily through the stomach, individuals with stomach disorders (for example, hypochlorhydria, or low stomach acid) may also be at increased risk of deficiency.
more on the protein/sulfur idea to follow. also i have to refresh my memory on the stomach acid thing!
moving on, LA supplements are synthetic according to wikipedia, so i'd tend to look at mammalian biosynthesis and try to figure out how it might be impaired, then how to fix
about lipoic acid synthetase
The protein encoded by this gene belongs to the biotin and lipoic acid synthetases family. It localizes in mitochondrion and plays an important role in alpha-(+)-lipoic acid synthesis. It may also function in the sulfur insertion chemistry in lipoate biosynthesis.
okay looking at lias deficiency...
Lipoic Acid Synthetase Deficiency Causes Neonatal-Onset Epilepsy, Defective Mitochondrial Energy Metabolism, and Glycine Elevationhttp://www.sciencedirect.com/science/ar ... 9711004897
Lipoic acid is an essential prosthetic group of four mitochondrial enzymes involved in the oxidative decarboxylation of pyruvate, α-ketoglutarate, and branched chain amino acids and in the glycine cleavage. Lipoic acid is synthesized stepwise within mitochondria through a process that includes lipoic acid synthetase. We identified the homozygous mutation c.746G>A (p.Arg249His) in LIAS in an individual with neonatal-onset epilepsy, muscular hypotonia, lactic acidosis, and elevated glycine concentration in plasma and urine. Investigation of the mitochondrial energy metabolism showed reduced oxidation of pyruvate and decreased pyruvate dehydrogenase complex activity. A pronounced reduction of the prosthetic group lipoamide was found in lipoylated proteins.
Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human diseasehttp://intl-dmm.biologists.org/content/5/2/155.short
Iron-sulfur (Fe-S) clusters are ubiquitous cofactors composed of iron and inorganic sulfur. They are required for the function of proteins involved in a wide range of activities, including electron transport in respiratory chain complexes, regulatory sensing, photosynthesis and DNA repair. The proteins involved in the biogenesis of Fe-S clusters are evolutionarily conserved from bacteria to humans, and many insights into the process of Fe-S cluster biogenesis have come from studies of model organisms, including bacteria, fungi and plants. It is now clear that several rare and seemingly dissimilar human diseases are attributable to defects in the basic process of Fe-S cluster biogenesis. Although these diseases –which include Friedreich’s ataxia (FRDA), ISCU myopathy, a rare form of sideroblastic anemia, an encephalomyopathy caused by dysfunction of respiratory chain complex I and multiple mitochondrial dysfunctions syndrome – affect different tissues, a feature common to many of them is that mitochondrial iron overload develops as a secondary consequence of a defect in Fe-S cluster biogenesis. This Commentary outlines the basic steps of Fe-S cluster biogenesis as they have been defined in model organisms. In addition, it draws attention to refinements of the process that might be specific to the subcellular compartmentalization of Fe-S cluster biogenesis proteins in some eukaryotes, including mammals. Finally, it outlines several important unresolved questions in the field that, once addressed, should offer important clues into how mitochondrial iron homeostasis is regulated, and how dysfunction in Fe-S cluster biogenesis can contribute to disease.
linking up to sulfur (ah, the cruciferous veggies, we're deep into dr wahls territory now hehe)
Sulfur in Human Nutrition and Applications in Medicinehttp://www.thorne.com/altmedrev/.fulltext/7/1/22.pdf
The sulfur-containing amino acids (SAAs) are methionine, cysteine
, cystine, homocysteine, homocystine, and taurine
neat links right back to risk factors for low LA. so. on to action items. this study is available in full text so i will probably have a read at some point
Effects of micronutrients on metal toxicity.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533267/
full text http://www.ncbi.nlm.nih.gov/pmc/article ... 6-0213.pdf
so the next thing is, what's your diet like by and large? would you undertake dietary/supplemental modifications to help with metal removal?
if so, could you please send me a private message (or just post here if you are comfortable) everything you eat or drink starting with everything yesterday, today, and tomorrow. as detailed as possible with serving size estimates if you can. i'm off to have my breakfast i've been an hour and a half on this one! remind me to look at pyruvate later.
oh yeah and there's a research scientist at Keele you might be able to look up, name of Ferns.