As mentioned above, guinea pigs are especially well suited to study atherosclerosis because guinea pigs are unable to make their own vitamin C, and in addition, they develop atherosclerotic plaques similar to those found in humans. This enzyme catalyses the final known enzymic step required for collagen and elastin cross-linking in the biosynthesis of normal mature extracellular . 1997 September 15; 100(6): 1493–1500. [PDF] Reducing the Risk for Cardiovascular Disease with Nutritional Supplements  M Rath. Introduction. So be on the lookout and have Menkes syndrome as a DDx. Found inside – Page 47Action of lysyl oxidase cross-links hydroxylysines and lysines on adjacent chains to yield mature collagen fibrils. ... The hydroxylations are catalyzed by hydroxylases that require ascorbic acid/vitamin C as a cofactor. 3. 1995 Mar;113(2):179-88. Once oxidized, these lysyl side chains spontaneously engage in various reactions between collagen strands to . Animal experiments in genetically modified mice which have “knocked out” the lysine binding sites on lipoprotein (a) show a fivefold reduction in atherosclerotic plaque formation. Why is Collagen Important ? Transgenic mice expressing this mutant form of apolipoprotein(a) as well as mice expressing wild-type apolipoprotein(a) have been created in an inbred mouse strain. This is highly significant because the natural course of heart disease is progression, and any intervetion that alters the natural course of a diseae process is highly significant. White AL; Lanford RE. Time has come for the old dinosaurs to go. Whether this association is due to antioxidant vitamins or some other factors remains unclear. Evidence for the role of vitamin C-6 as a cofactor of lysyl oxidase. Vit-C prevent the oxidation of cellular components by the effect of free radicals, peroxides, superoxides etc. Found inside – Page 477In addition, vitamin C is involved in collagen crosslinking, which affects its mechanical function, through activation of lysyl oxidase and prolyl and lysyl hydroxylases (Shaw et al., 2017). Work conducted in pregnant rats has shown ... All Animals Can Make Vitamin C, but the Guinea Pig Can’t This situation may reflect in part a failure of the medical community to communicate effectively with the public regarding evidence-based medicine and the life-saving benefits of preventive strategies. Administration of vitamin C for 10 days (2 g/d) reduces adhesion of monocytes obtained from cigarette smokers to cultured endothelial cells.14 Vitamin C’s potency generally exceeds that of vitamin E as an antiinflammatory and antiatherogenic agent. ‘Optician’ Letters 9th May 2003 and later in 2004. http://en.wikipedia.org/wiki/Guinea_pig In Volume 25, leading experts present studies on the value of increased ascorbic acid intake and explore its specific contributions to human and animal health. http://www.internetwks.com/owen/ Nutr Metab (Lond). Enzyme 7-α-hydroxylase involved during cholesterol biosynthesis requires Vit.C. We examined the gene expression of the TGF-β signaling pathway and folate cycle genes that showed strong associations in our previous data. Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig. If you are facing the prospects of coronary artery bypass surgery (left image), you might ask the obvious question: Why hasn’t my cardiologist told me about this information and started me on the Linus Pauling Protocol? Heart disease would become an uncommon illness. Found insideI don't know if it's because of the acidity of vitamin C (a.k.a. ascorbic acid), or whether there is something special about vitamin ... works with vitamin C throughout the body (lysyl oxidase to cross-link collagen is but one example), ... All of them have similar catalytic activity owing to the highly conserved C-terminal region containing the copper binding domain, residues for lysine tryosylquinone (LTQ), cofactor formation, and a cytokine receptor-like (CRL) domain. Narayanan AS, Siegel RC, Martin GR. This vitamin is also quickly deformed by alkalies. Remarkable breakthrough in human health and well ness. Vitamin C is required for lysyl hydroxylase, an enzyme responsible for attaching the lysine residues together on adjacent collagen strands. Yale J Biol Med. 4) The Willis Guinea Pig Experiments in the 1950’s show that depriving the animal of vitamin C causes atherosclerosis which is quite similar to the human lesion. It is water soluble vitamin, also know as ascorbic acid. The enzyme for this reaction is lysyl oxidase, co-factors: copper, Vitamin B 6. Lysine Plus provides significant amounts of Vitamin C and L-Lysine in capsule form. In the early 1950’s, a Canadian, G. C. Willis, MD, made these same observations, and they have been confirmed by 60 years of coronary and peripheral arteriography at major medical centers. This initial study showed that Lp(a) accumulates in the arterial wall, partly in the form of lipoprotein-like particles, therefore contributing to plaque formation and coronary heart disease. The joints wear out, the small arteries begin to crack and degenerate, the skin shows easy bruising and bleeding as small vessels rupture throughout the body, and the teeth may loosen and fall out. Bone consists of high percentage of collagen and requires vitamin C for proper formation. This reaction is stereospecific and unrelated to intracellular degradation of collagen. Yet, the striking beneficial effects observed in the statin treatment arms of both the HPS and HATS20 and of the angiotensin converting enzyme inhibitor in the HOPE study21 establish the mutability of outcomes measured in these patient populations in the same trials. Carr AC, Frei B. These results indicate a correlation between lysine binding properties of Lp(a) and vascular accumulation, supporting the postulated role of apo(a) LBS in this potentially atherogenic characteristic of Lp(a). Bone. Vitamin E is a generic term that refers to a group of eight naturally occurring lipid-soluble . 1977 Nov 1; 167 (2):463-467. It is a cofactor for lysyl oxidase, which is the final enzyme necessary in collagen synthesis. Atherosclerosis. Regulation of collagen biosynthesis by ascorbic acid: a review. (Source: Brown-Goldstein Scientific American 1982, and Linus Pauling Heart Disease Video), 7) Veins, in general, do not suffer plaque deposits. http://www.ajcn.org/cgi/reprint/23/1/27.pdf www.naturalmedicine101.com Once oxidized, these lysyl side chains spontaneously engage in various reactions between collagen strands to . Additionally it was analysed whether there are differences in the apolipoprotein composition between lesion-free and diseased human arterial wall tissue. I am wondering if adding Tocotrienols to my regimen and a few other supplements would be sufficient or if it is too late for a non surgical approach. Anti-Vitamin C Articles, Failure of Vitamin C, http://jama.ama-assn.org/cgi/content/full/2008.600, Vitamins E and C in the Prevention of Cardiovascular Disease in Men This makes the guinea pig an ideal experimental model for human diseases. Cell surface assembly of lipoprotein(a) in primary cultures of baboon hepatocytes. Once oxidized, these lysyl side chains spontaneously engage in various reactions between collagen strands to . What would happen if there was a cheap and effective way to reverse and prevent heart disease, (ie. to be functionally optimally. In September, 2000, an Oxford meta-analysis of 27 large studies showed that people with elevated Lp(a) are 70% more like to suffer a heart attack or stroke. Vitamin E: 800-2400 IU per day. Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts  Paul Knekt et al. Lysine-NH 3 + ------> Allysine-C=O (b) A reaction between these aldehydes and free amino groups on other lysine residues forms a "Schiff" base , then covalent crosslink . Over 35% of this radioactivity appears in the form of [G-3H]pyridoxal and a further 30% as other vitamin B-6 compounds. to be functionally optimally. Throughout evolution, a number of animals including humans have lost the ability to synthesize ascorbic acid (ascorbate, vitamin C), an essential molecule in the physiology of animals and plants. Collagen contains unusual amino acids, hydroxyproline and hydroxylysine, formed by a vitamin C–dependent process that entails enzymatic transfer of hydroxyl groups to selected proline and lysine residues in the nascent procollagen chains. In addition to its antiscorbutic action, vitamin C has potent antioxidant properties. Pingback: How to Reverse Heart Attack? This is the same process that happens in the artery. So simple, yet so crucial. The Steam Roller is Not Joking – //////@\\\\\\\. Vitamin C catalyzes the post translational modification responsible for the hydroxylation of prolyl and lysyl residues of collagen fibres. http://www.jbc.org/cgi/content/abstract/269/18/13685 Quantification of apo[a] and apoB in human atherosclerotic lesions by Judith M. Pepin et al. Vitamin C, Collagen, and Cracks in the Plaque, by Peter Libby, MD; Masanori Aikawa, MD PhD, Most fatal acute myocardial infarctions result from a fracture of the plaque’s fibrous cap. Supplements to Promote Collagen Production What is Collagen and How is it Formed? However, few long-term trials have evaluated men at initially low risk of cardiovascular disease, and no previous trial in men has examined vitamin C alone in the prevention of cardiovascular disease. Man is among the exceptional higher animals that are unable to synthesize L-ascorbic acid because of their deficiency in L-gulono- gamma-lactone oxidase, the enzyme catalyzing the terminal step in L- ascorbic acid biosynthesis. Found inside – Page 71... oxalylamino - 1 - amine inhibits lysyl oxidase , Lysine Lysyl oxidase Cu2 + Allysine Allysine aldol Histidine Lysyl oxidase Lysine Allysine Cu2 + Aldol ... Vitamin C 5 - Hydroxylysine Histidino dehydrohydroxy merodesmosine ... These results, if extra-polated to human beings, would indicate that chronic subclinical AH2 (ascorbate) deficiency may result in progressive oxidative damage which in the long run may lead to permanent degenerative diseases in the heart. There also was no significant effect of vitamin C on major cardiovascular events (active and placebo vitamin E groups, 10.8 and 10.9 events per 1000 person-years, respectively; HR, 0.99 [95% CI, 0.89-1.11]; P = .91), as well as total myocardial infarction (HR, 1.04 [95% CI, 0.87-1.24]; P = .65), total stroke (HR, 0.89 [95% CI, 0.74-1.07]; P = .21), and cardiovascular mortality (HR, 1.02 [95% CI, 0.85-1.21]; P = .86). While copper is only needed in small amounts, it is an essential mineral and therefore cannot be made in the body, it must be obtained . Collagen is the major protein of connective tissue and arteries. Animals That Don’t Make Vitamin C, Do Get Atherosclerotic Heart Disease Steps in Collagen Synthesis (see diagram below Courtesy of Wikimedia). There are two α1 chains and one α2 chain (Goodsell, 2003). Eur Heart J 1997 Apr;18(4):603-7. Found inside – Page 443Ascorbic acid is not synthesized endogenously in humans; therefore, we are entirely dependent on the diet for this nutrient. ... The best established function of vitamin C is the activation of prolyl and lysyl hydroxylases from inactive ... Freezing has no harmful effect on this vitamin. Lysyl oxidase (LOX) is required for the formation of bone collagen cross-links. Copper is a co-factor for lysyl oxidase, so in Menkes, active lysyl oxidase is deficient.-----I had encountered two questions on Menkes syndrome during my prep year. J Clin Invest 1996 Jul 1;98(1):185-91. Compared with subjects in the lowest dietary intake quintiles for vitamins E and C, those in the highest intake quintiles had relative risks of CHD incidence of 0.84 (95% CI: 0.71, 1.00; P = 0.17) and 1.23 (1.04, 1.45; P = 0.07), respectively, and the relative risks for subjects in the highest intake quintiles for the various carotenoids varied from 0.90 to 0.99. left image: courtesy wikimedia, roadroller. Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Link to this article:http://wp.me/P3gFbV-qL, References and Links Dogs and Cats DO succumb to other common types of heart disease such as cardiomyopathy and heart worm etc.). However, although the aortic wall . 1998 May;67(5 Suppl):996S-1002S. http://www.hullcontactlensclinic.co.uk/cardior.htm The GLO deficient mice fed a vitamin C deficient diet developed atherosclerotic plaques in the aorta with characteristic deranged collagen crosslinking. Support for this explanation is provided by the observations of similar fragmentation of elastic fibers in mice with the Blotchy allele at the X-linked Mottled locus (33). Biochem. The lack of Vitamin C is a deficiency disease called Scurvy. Pauling’s later years were devoted to heart disease, and in 1989 he published “A Unified Theory of Human Cardiovascular Disease,”  in which he states that atherosclerotic plaques in heart disease are actually part of a repair process, to repair the arterial damage caused by chronic vitamin C deficiency. In vitro analysis of Lp(a) isolated from the various groups of mice confirmed that putative LBS defective apo(a) yielded Lp(a) unable to bind lysine-Sepharose. The long-term effect of eicosapentaenoic acid on serum levels of lipoprotein (a) and lipids in patients with vascular disease. http://www.jlr.org/cgi/reprint/32/2/317 These programs are huge money makers for the national hospital system. This blog contains written opinions by the author protected by the First Amendment of the United States Constitution (Freedom of Speech) . Thus, more potent or amphipathic antioxidants might interrupt oxidative stress during atherogenesis more effectively than the vitamins. (note: here I am referring to atherosclerotic vascular heart disease in animals. Dihydrofolate reductase (DHFR) requires Vitamin C for its activity. Inai Y et al. There were 14 641 US male physicians enrolled, who were initially aged 50 years or older, including 754 men (5.1%) with prevalent cardiovascular disease at randomization. The most striking pathological finding in our current study is the presence of abnormalities in the aortic walls of the vitamin C-deficient mice. Found inside – Page 271Vitamin C, a redox agent and a coflzetor in many hyalroxylation reactions, is also required for the hydroxylation of the ... and chicks can die literally of broken hearts or aortas—— because lysyl oxidase requires copper as a cofactor. J. Chakrabarty S, Nandi A, Mukhopadhyay CK, Chatterjee IB. http://www.internetwks.com/owen/TheoryPaper.htm, The Unified Theory, The Long Neglected Theory of Cardiovascular and Heart Disease By Owen Richard Fonorow 2002. JOURNAL OF APPLIED NUTRITION, VOLUME 48, NUMBER 3, 1996 ORIGINAL REPORT Copyright – International Academy of Nutrition and Preventive Medicine NUTRITIONAL SUPPLEMENT PROGRAM HALTS PROGRESSION OF EARLY CORONARY ATHEROSCLEROSIS DOCUMENTED BY ULTRAFAST COMPUTED TOMOGRAPHY  Matthias Rath, M.D.

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