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IA Novel Dehydroascorbate-lysine Advanced Glycation Endproduct is Markedly Altered by UVA Irradiation
Invest Ophthalmol Vis Sci 2002;43: E-Abstract 847. © 2002 ARVO
We have isolated and determined the structure of a new glycation product of lysine and dehydroascorbic acid. This compound was extensively degraded by irradiation with UVA light in the presence of a water-soluble human lens extract. Our results suggest that measurements of the amounts of advanced glycation end products in the eye lens could underestimate the extent of glycation, because of subsequent structural alterations due to UVA light. The damage of lens proteins in vivo therefore could be a result from the combined action of glycation and UVA light.
Are Diabetic Neuropathy, Retinopathy and Nephropathy Caused by Hyperglycemic Exclusion of Dehydroascorbate Uptake by Glucose Transporters? @ 2001
Vitamin C exists in two major forms. The charged form, ascorbic acid (AA), is taken up into cells via sodium-dependent facilitated transport. The uncharged form, dehydroascorbate (DHA), enters cells via glucose transporters (GLUT) and is then converted back to AA within these cells. Cell types such as certain endothelial and epithelial cells as well as neurons that are particularly prone to damage during diabetes tend to be those that appear to be dependent on GLUT transport of DHA rather than sodium-dependent AA uptake. We hypothesize that diabeticneuropathies, nephropathies and retinopathies develop in part by exclusion of DHA uptake by GLUT transporters when blood glucose levels rise above normal. AA plays a central role in the antioxidant defense system. Exclusion of DHA from cells by hyperglycemia would deprive the cells of the central antioxidant, worsening the hyperglycemia-induced oxidative stress level. Moreover, AA participates in many cellular oxidation–reduction reactions including hydroxylation of polypeptide lysine and proline residues and dopamine that are required for collagen production and metabolism and storage of catecholamines in neurons. Increase in the oxidative stress level and metabolic perturbations can be expected in any tissue or cell type that relies exclusively or mainly on GLUT for co-transport of glucose and DHA including neurons, epithelial cells, and vascular tissues. On the other hand, since DHA represents a significant proportion of total serum ascorbate, by increasing total plasma ascorbate concentrations during hyperglycemia, it should be possible to correct the increase in the oxidative stress level and metabolic perturbations, thereby sparing diabetic patients many of their complications.
Vitamin C Metabolomic Mapping in the Lens with 6-Deoxy-6-fluoro-ascorbic Acid and High-Resolution 19F-NMR Spectroscopy
. Metabolomics, or metabolic profiling, is an emerging discipline geared to providing information on a large number of metabolites, as a complement to genomics and proteomics. In the current study, a fluorine-labeled derivative of ascorbic acid (F-ASA), a major antioxidant- and UV-trapping molecule in the aqueous humor and the lens, was used to investigate the extent to which the lens accumulates potentially toxic degradation products of vitamin C.
METHODS. Human lens epithelial cells (HLE-B3) and rat lenses were exposed to hyperglycemic or oxidative stress in vitro or in vivo and probed for accumulation of F-ASA, fluoro-dehydroascorbate (F-DHA), fluoro-2,3-diketogulonate (F-DKG), and their degradation products in protein-free extracts, by proton-decoupled 750-MHz 19F-nuclear magnetic resonance (NMR) spectroscopy.
RESULTS. F-ASA and F-DHA were taken up into HLE B-3 cells by an Na+-dependent transporter. Their uptake was unexpectedly only slightly affected by hyperglycemia in vitro, unless glutathione was severely depleted. Glycemic stress catalyzed oxidation of F-ASA into a single novel F-compound at −212.4 ppm, whereas F-DHA and F-DKG were the major degradation products observed after GSH depletion. In contrast, F-ASA uptake was markedly suppressed in diabetic cataractous rat lenses, which accumulated both the F-DHA and the −212.4-ppm compound. In an unexpected finding, the latter formed only from F-ASA and not F-DHA or F-DKG, suggesting a novel pathway of in vivo F-ASA degradation. Both the cells and the intact rat and human lenses were permeable to several advanced F-ASA and F-DHA degradation products, except F-DKG. The unknown compound at −212.4 ppm was the only F-ASA degradation product that spontaneously formed in rabbit aqueous humor upon incubation with F-ASA.
CONCLUSIONS. These studies suggest the existence of a novel ascorbic-acid–degradation pathway in the lens and aqueous humor that is influenced by the nature of the oxidant stress. Under similar culture conditions, intact lenses are more prone to hyperglycemia-mediated oxidant stress than are lens epithelial cells, but both are permeable to various F-ASA degradation products, the structure and biological roles of which remain to be established.
From the book The Maillard reaction in foods and medicine
Dicarbonyl compounds, such as dehydroascorbate (DHA), 3-deoxyglucosone(3DG)'7 and methylglyoxal (MGO),11 are present in tissues at micromolar concentrations,are increased in blood of diabetic patients, and brown proteins efficiently under anaerobic conditions.
Inhibitory effects of pyridoxal phosphate, ascorbate and aminoguanidine on nonenzymatic glycosylation @ 2002
Abstract
Nonenzymatic glycosylation of serum albumin was studied in the presence of naturally occuring metabolites, pyridoxal, pyridoxal phosphate and ascorbate/dehydroascorbate, and a hydrazine compound, aminoguanidine. Pyridoxal, pyridoxal phosphate, ascorbate and dehydroascorbate, at concentrations of 0.1 mM or greater, significantly inhibited the nonenzymatic glycosylation of albumin. Aminoguanidine was the most potent inhibitor of nonenzymatic glycosylation and 54% or 85% inhibition occurred when 5 or 50 mM aminoguanidine, respectively, was present in the incubation mixture containing 20 mM glucose. A major effect of aminoguanidine was to lower the free glucose concentration in the incubation mixture by a direct reaction with glucose as judged by thin layer chromatography. The present studies suggests that vital metabolites such as pyridoxal phosphate and ascorbate may be potentially important in controlling glucose-induced nonenzymatic glycosylation of proteins. Pyridoxal phosphate forms a Schiff base with proteins as does glucose and therefore may be a preferable drug, over aminoguanidine which is a hydrazine, for inhibiting the effects of glucose-induced nonenzymatic glycosylation.
INHIBITION OF PROTEIN GLYCATION AND ADVANCED GLYCATION END PRODUCTS BY ASCORBIC ACID AND OTHER VITAMINS AND NUTRIENTS @ 1996
A number of vitamins and nutrients were found to be potent inhibitors of both the glycation reaction and the subsequent end products. The nutrients were effective at physiological concentrations and exhibited dose-response relationships. The inhibitors included ascorbic acid, tocopherol, pyridoxal, niacinamide, sodium selenite, selenium yeast, and carnosine.
A significant correlation was found between the inhibition of glycation and the inhibition of AGE formation (p < 0.001). One of the nutrients, ascorbic acid, was used in a pilot study. Eighteen normal subjects, 7 college age and 10 middle age, were supplemented with 1000 mg of ascorbic acid in the form of Re-natured vitamin C for a period of 4 weeks. Serum protein glycation was decreased an average of 46.8% (p < 0.01). These results underline the importance of nutrition in diabetes and indicate the possibility of therapeutic use of these nutrients for the prevention of diabetic complications.
VanCanada wrote:at minute77 second30:
vit C is key as an antioxidant. But...Dr. Mark Obrenovich wrote:If someone is on chemotherapy and their chemotherapy mechanism of action is oxidative stress induced cytotoxicity then if you take too much vitamin C while having your chemo you could actually raise the therapeutic threshold of the dose... and require more of the chemotherapy to do its prospective effectiveness by taking too much vitamin C.
Patrick Quillin wrote:Don't Take Your Vitamin C; Unless...
......A couple hundred thousand years ago, humans lost the ability to convert blood sugar (glucose) into vitamin C (ascorbic acid). Some scientists have called this evolutionary shift a figurative "fall from the Garden of Eden". All but a few creatures on earth produced their own vitamin C in massive quantities, with higher internal production when the creature gets sick. For instance, a 150 pound goat makes about 10,000 milligrams daily of vitamin C. Meanwhile, the Recommended Dietary Allowance for a 156 pound reference human is 60 milligrams per day.
......Vitamin C is one of the more utilitarian nutrients in the human body, by assisting in the construction of connective tissue (the glue that keeps the body together), regulating the levels of fats in the blood, assisting in iron absorption, aiding in the sythesis of various brain chemicals for thought, and protecting against the damaging effects of free radicals. In a study done at the University of California at Los Angeles, men who took supplements of 300 mg daily of vitamin C (5 times the RDA) live an average of 6 years longer than men who did not take supplements of vitamin C. Mark Levine, MD, researcher with the National Institutes of Health, finds evidence that 250 mg per day might be a more rational and healthy RDA for vitamin C.
Patrick Quillin wrote:......Meanwhile, oncologists worry about the possibility that vitamin C might inhibit the free radical activity of chemotherapy and radiation in destroying cancer cells. While it might seem logical that an antioxidant (like vitamin C) might reduce the effectiveness of a pro-oxidant (like chemo and radiation), the opposite has been found in animal and human studies: antioxidants protect the healthy tissue of the patient while allowing the cancer tissue to become more vulnerable to the damaging effects of chemo and radiation.
......In a study published in the Proceedings of the National Academy of Science, vitamin C always augmented tumor kill and never protected the cancer cells when scientists added various chemo and radiation therapies to cancer cells growing in a dish. In 2 major human cancer studies, adding vitamin C and other antioxidants to chemo and radiation improved patient survival, quality of life, and tumor kill.
......Then an unpublished research project from Sloan Kettering Cancer Hospital in New York found that cancer cells are "gluttons" for vitamin C, absorbing more than their fair share. The researchers concluded, though they never proved, that cancer patients should avoid vitamin C supplements while undergoing chemo and radiation. Dr. David Golde, author of the study even speculated: "The cancer cell wants vitamin C because it wants antioxidant protection." If cancer cells are looking for protection, then why is vitamin C the only antioxidant that they absorb? What about the 20,000 bioflavonoids (like quercetin), the 800 carotenoids (like beta carotene), vitamin E, lipoic acid, glutathione, and other antioxidants in the human body? Why do cancer cells only absorb vitamin C and not the others? The researchers admitted that vitamin C was being selectively absorbed by tumor cells because cancer cells are "sugar feeders" and think they are absorbing their preferred fuel, glucose (which is nearly identical in structure to vitamin C), when in fact they are absorbing vitamin C, an "Elvis impersonator" of sorts.
......Now let me weave all of this seemingly confusing data together to help make sense for the cancer patient. Any antioxidant can become a pro-oxidant in a given chemical soup. That is why Nature always gives us droves of different antioxidants to play "hot potato" with unpaired electrons until their destructive energy is dissipated. No food has just one antioxidant. No human cell wants just one antioxidant. Antioxidants can become pro-oxidants when in isolation, which is exactly what happens to cancer cells when they selectively absorb only vitamin C, hoping to get some fuel for growth. What really happens is the vitamin C quickly becomes a pro-oxidant, targeting its destruction exclusively for the cancer cells. Dozens of very well trained physicians have been giving high doses of intravenous vitamin C (10 to 100 grams daily) to thousands of cancer patients for decades with no side effects, and usually improved outcome. Intravenous vitamin C seems to have selective anti-cancer activity, according to an article in the Annals of Internal Medicine (Apr.6, 2004, p.533), authored by several doctors including researchers at the National Institutes of Health. Dr. Hugh Riordan has reported improved outcome in poor prognostic cancer patients who have been put in remission through use of high dose IV vitamin C.
Patrick Quillin wrote:......Vitamin C supplements can be helpful in slowing cancer, while making medical therapy more of a selective toxin against the cancer and protecting healthy host tissue. Vitamin C protects against heart disease, lengthens life span, and more...when taken in conjunction with a wide assortment of other antioxidants along with a good diet.
......A number of bright researchers have taken a tiny bit of knowledge out of context (vitamin C thickens artery walls, is selectively absorbed by tumors, can become pro-oxidant), then ASSUMED a sequence of unproven conclusions, without consulting the "prior art" in this field. Don't take your vitamin C supplements -- unless you want to live longer.
majkinetor wrote:This is interesting:
Physicians are advised to recommend that individuals increase their consumption of vitamin C rich foods as a means of reducing risk of H. pylori infection and as a possible means of mitigating the effects of infection in those with gastric disease who test positive tor H. priori. However, patients should be further advised to eliminate high-dose vitamin (intake while being treated with LAM triple therapy, to avoid any potential interference with the efficacy of the medication. It is known that low gastric pH is protective of H. pylori, which is why proton pump inhibitors to achieve neutral gastric pH are combined with antibiotics. From this preliminary research, prudent would suggest thai ascorbic acid (and perhaps other organic acids capable of lowering intragastric pH) should be avoided during and H. pylori therapy. Related research indicates that coadministration of probiotic flora to restore gut ecology can enhance clinical outcomes.
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LAM ( lansoprazole , amoxycillin and metronidazole ) are reported above. However, research with amoxicillin, metronidazole, bismuth and omeprazole here (which was out after the book was written) concludes that Vitamin C is beneficial as addition to the treatment.
You mean we're not all going to wake up tomorrow to these headlines :gofanu wrote:Of course, all this suggests that H pylori might be treated with vitamin C, as might some negative effects of smoking. That would of course require a total rethink of "their" views about vitamin C, would scuttle the drug treatment $$ of H Pylori, and shoot hell out of the anti tobacco industry.
FRM
In other words, treatment with 5gm/day can cure H Pylori, and "if you do not get the results you expect, you did not use enough or continue long enough." Dr F Klenner
Administration of vitamin C, in a 5 g/day dosage during 28 days is neither effective for H. pylori eradication nor quantitatively alters the bacteria load in the stomach of infected patient
H. pylori synthesizes large amount of urease, which is found in its cytosol. The cytosolic urease is released into the gastric juice upon spontaneous autolysis of a subpopulation of H. pylori and subsequently it is adsorbed onto the surface of intact bacteria. The urease catalyses the hydrolysis of urea present in the gastric juice, to yield carbonic acid and ammonia. Thus H. pylori makes a cloud of ammonia on its surface to neutralize the gastric acid which enables it to colonize the gastric epithelium.[15,16] Once successfully colonized, H. pylori resides below the gastric mucus layer which has a higher pH than gastric lumen.[17,18] So in chronic infection, the role played by urease, in survival of the bacteria seems less important. However, besides protecting from acid, urease also aids in colonization by providing ammonia for bacterial protein synthesis
As far as I know acidic gastric environment is detrimental to h pylori
DHAA's pharmacokinetics is nothing like reduced vitamin c which comprises 99% of all vitamin c supplements. When you talk about DHAA you're talking about something most people can't even buy. That's why DHAA should never be referred to as vitamin c, not ever.
You don't refer to FeO2 as "iron", for heaven's sake, nor do you typically call it "oxidized iron" (that's a bar of iron with a thin layer of oxide), instead you refer to FeO2 as "iron-oxide" or "rust". Similarly we should insist that DHAA *never* be called "vitamin c" at any time, neither should it ever be called "oxidized vitamin c" (which can be a tablet of AA where the outside has turned yellow).
We should insist then on the medical community using the full name for DHAA, "dehydroascrobic acid", or "vitamin-c-oxide", or something entirely different preferably that sounds nothing like "vitamin c" (I have my own opinions what to call it, but they wouldn't be helpful).
ofonorow wrote:Bravo! You are so right, and I personally have never focused on this important distinction. (perhaps because unlike rust, DHAA can be reduced back to vitamin C, correct?) Anyway, if you want to turn this post into a short article, I would like to try to help get this published in the Townsend Letter as a letter to the editor. What do you think?DHAA's pharmacokinetics is nothing like reduced vitamin c which comprises 99% of all vitamin c supplements. When you talk about DHAA you're talking about something most people can't even buy. That's why DHAA should never be referred to as vitamin c, not ever.
You don't refer to FeO2 as "iron", for heaven's sake, nor do you typically call it "oxidized iron" (that's a bar of iron with a thin layer of oxide), instead you refer to FeO2 as "iron-oxide" or "rust". Similarly we should insist that DHAA *never* be called "vitamin c" at any time, neither should it ever be called "oxidized vitamin c" (which can be a tablet of AA where the outside has turned yellow).
We should insist then on the medical community using the full name for DHAA, "dehydroascrobic acid", or "vitamin-c-oxide", or something entirely different preferably that sounds nothing like "vitamin c" (I have my own opinions what to call it, but they wouldn't be helpful).
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